BioPAX pathway converted from "Recruitment of NuMA to mitotic centrosomes" in the Reactome database. Recruitment of NuMA to mitotic centrosomes The NuMA protein, which functions as a nuclear matrix protein in interphase (Merdes and Cleveland 1998), redistributes to the cytoplasm following nuclear envelope breakdown where it plays an essential role in formation and maintenance of the spindle poles (Gaglio, et al., 1995; Gaglio, et al., 1996; Merdes et al, 1996). The mitotic activation of NuMA involves Ran-GTP-dependent dissociation from importin (Nachury et al, 2001, Wiese et al, 2001). NuMA is transported to the mitotic poles where it forms an insoluble crescent around centrosomes tethering microtubules into the bipolar configuration of the mitotic apparatus (Merdes et al., 2000; Kisurina-Evgenieva et al, 2004). Although NuMA is not a bona fide constituent of the mitotic centrosome but rather a protein associated with microtubules at the spindle pole, specific splice variants of NuMA have been identified that associate with the centrosome during interphase (Tang et al, 1994). Authored: Matthews, L, 2008-11-11 14:53:40 Reviewed: Merdes, A, 2008-11-17 13:55:29 Edited: Matthews, L, 2008-11-09 05:12:41 LEFT-TO-RIGHT Translocation of NuMA to the centrosomes After the nuclear envelope breakdown, phosphorylated NuMA rapidly moves to the centrosomal region (Compton and Luo 1995, Hsu and Yeh 1996, Kotak et al. 2013). Authored: Matthews, L, 2008-11-11 14:53:40 Reviewed: Merdes, A, 2008-11-17 13:55:29 Edited: Matthews, L, 2008-11-12 17:55:26 Edited: Orlic-Milacic, Marija, 2017-03-17 p-T2055-NUMA1 homodimer Reactome DB_ID: 380486 cytosol GENE ONTOLOGY GO:0005829 p-NUMA1 phosphorylated NuMA Reactome DB_ID: 380484 UniProt:Q14980 NUMA1 NUMA1 NMP22 NUMA FUNCTION Microtubule (MT)-binding protein that plays a role in the formation and maintenance of the spindle poles and the alignement and the segregation of chromosomes during mitotic cell division (PubMed:7769006, PubMed:17172455, PubMed:19255246, PubMed:24996901, PubMed:26195665, PubMed:27462074). Functions to tether the minus ends of MTs at the spindle poles, which is critical for the establishment and maintenance of the spindle poles (PubMed:12445386, PubMed:11956313). Plays a role in the establishment of the mitotic spindle orientation during metaphase and elongation during anaphase in a dynein-dynactin-dependent manner (PubMed:23870127, PubMed:24109598, PubMed:24996901, PubMed:26765568). In metaphase, part of a ternary complex composed of GPSM2 and G(i) alpha proteins, that regulates the recruitment and anchorage of the dynein-dynactin complex in the mitotic cell cortex regions situated above the two spindle poles, and hence regulates the correct oritentation of the mitotic spindle (PubMed:23027904, PubMed:22327364, PubMed:23921553). During anaphase, mediates the recruitment and accumulation of the dynein-dynactin complex at the cell membrane of the polar cortical region through direct association with phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), and hence participates in the regulation of the spindle elongation and chromosome segregation (PubMed:22327364, PubMed:23921553, PubMed:24996901, PubMed:24371089). Binds also to other polyanionic phosphoinositides, such as phosphatidylinositol 3-phosphate (PIP), lysophosphatidic acid (LPA) and phosphatidylinositol triphosphate (PIP3), in vitro (PubMed:24996901, PubMed:24371089). Also required for proper orientation of the mitotic spindle during asymmetric cell divisions (PubMed:21816348). Plays a role in mitotic MT aster assembly (PubMed:11163243, PubMed:11229403, PubMed:12445386). Involved in anastral spindle assembly (PubMed:25657325). Positively regulates TNKS protein localization to spindle poles in mitosis (PubMed:16076287). Highly abundant component of the nuclear matrix where it may serve a non-mitotic structural role, occupies the majority of the nuclear volume (PubMed:10075938). Required for epidermal differentiation and hair follicle morphogenesis (By similarity).SUBUNIT Homodimer (PubMed:10075938). Also forms multiarm oligomers by association of C-terminal tail domains, oligomers may further assemble to form a hexagonal nuclear lattice-like network (PubMed:10075938). Associates with the dynein-dynactin complex; this association promotes the transport and accumulation of NUMA1 at the mitotic spindle poles that is inhibited by the BRISC complex in a PLK1-dependent manner (PubMed:10811826, PubMed:17172455, PubMed:23027904, PubMed:22327364, PubMed:26195665). Part of a spindle orientation complex at least composed of GNAI1, GPSM2 and NUMA1 (PubMed:26766442). Interacts (via C-terminus) with microtubules (MTs); this interaction is direct and promotes both MT bundle formation and stability in a dynein-dynactin complex- and CDK1-independent manner (PubMed:12445386, PubMed:11956313, PubMed:26765568). Interacts with EPB41 and EPB41L2; these interactions are negatively regulated by CDK1 during metaphase and are important for anaphase-specific localization of NUMA1 in symmetrically dividing cells (PubMed:23870127, PubMed:24996901). Interacts (via C-terminus) with GPSM2 (via TPR repeats); this interaction is direct, prevented by competitive binding of INSC, is inhibited in a PLK1-dependent manner, blocks the association of NUMA1 with MTs and inhibits NUMA1-induced MT bundle formation, prevents the association of NUMA1 with SPAG5, induces mitotic spindle pole localization of GPSM2, both metaphase cell cortex localization of NUMA1 and mitotic spindle organization (PubMed:11781568, PubMed:12445386, PubMed:22327364, PubMed:24109598, PubMed:27462074, PubMed:21816348). Does not interact with GPSM2 during anaphase (PubMed:23870127). Interacts (via C-terminus) with the nuclear importin alpha/importin beta receptor; this interaction is inhibited by RanGTP (PubMed:11163243). Interacts (via C-terminus) with KPNB1; this interaction is inhibited by RanGTP and the BRISC complex (PubMed:11229403, PubMed:26195665). Interacts with ABRAXAS2 and the BRISC complex; these interactions regulate mitotic spindle assembly (PubMed:26195665). Interacts (via N-terminal end of the coiled-coil domain) with RAE1; this interaction promotes mitotic spindle formation (PubMed:17172455). Interacts (via C-terminus) with SPAG5 (via C-terminus); this interaction promotes the recruitment of SPAG5 to the MTs at spindle poles in a dynein-dynactin-dependent manner and regulates mitotic spindle organization and proper chromosome alignment during mitosis (PubMed:27462074). Interacts with TNKS; this interaction occurs at the onset of mitosis (PubMed:12080061, PubMed:16076287). Interacts with TNKS2 (PubMed:12080061). Interacts with tubulin (PubMed:11956313). Interacts with KHDC3L (via C-terminus) (By similarity).DOMAIN The C-terminal tubulin-binding domain mediates direct binding to microtubules, independently of dynein-dynactin complex, and induces their bundling and stabilization (PubMed:11956313). The 4.1-binding domain is necessary for its cortical stability and spindle orientation (PubMed:24109598).PTM Phosphorylation and dephosphorylation on Thr-2055 regulates the extent of cortical NUMA1 and the dynein-dynactin complex localization during mitotic metaphase and anaphase (PubMed:23921553). In metaphase, phosphorylation on Thr-2055 occurs in a kinase CDK1-dependent manner; this phosphorylation maintains low levels of cortical dynein-dynactin complex at metaphase, and hence proper spindle positioning (PubMed:7769006, PubMed:23921553, PubMed:24371089). In anaphase, dephosphorylated on Thr-2055 by phosphatase PPP2CA; this dephosphorylation stimulates its membrane association and with the dynein-dynactin complex its enrichment at the cell cortex, and hence robust spindle elongation (PubMed:23921553, PubMed:24371089). Probably also phosphorylated on Thr-2015 and Ser-2087 by CDK1; these phosphorylations may regulate its cell cortex recruitment during metaphase and anaphase (PubMed:23870127). Phosphorylated on Thr-1047, Ser-1769, Ser-1772, Ser-1789 and Ser-1834 by PLK1; these phosphorylations induce cortical dynein-dynactin complex dissociation from the NUMA1-GPSM2 complex and negatively regulates cortical dynein-dynactin complex localization (PubMed:22327364).PTM ADP-ribosylated by TNKS at the onset of mitosis; ADP-ribosylation is not required for its localization to spindle poles (PubMed:16076287).PTM O-glycosylated during cytokinesis at sites identical or close to phosphorylation sites, this interferes with the phosphorylation status (PubMed:20068230).PTM Ubiquitinated with 'Lys-63'-linked polyubiquitin chains. Deubiquitination by the BRISC complex is important for the incorporation of NUMA1 into mitotic spindle poles and normal spindle pole function, probably by modulating interactions between NUMA1, dynein-dynactin complex and importin-beta.MISCELLANEOUS Also known as nuclear matrix protein-22/NMP-22/NMP22, an antigen used in diagnostic tests of bladder cancer. Homo sapiens NCBI Taxonomy 9606 UniProt Q14980 2055 EQUAL O-phospho-L-threonine MOD MOD:00047 1 EQUAL 2115 EQUAL Reactome Database ID Release 81 380484 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380484 Reactome R-HSA-380484 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380484.1 Reactome http://www.reactome.org 2 Reactome Database ID Release 81 380486 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380486 Reactome R-HSA-380486 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380486.2 Mature centrosomes enriched in gamma-TURC complexes Reactome DB_ID: 380440 gamma-TuRC gamma-tubulin complex Reactome DB_ID: 379277 GCP-4 TUBGCP4 Reactome DB_ID: 379268 UniProt:Q9UGJ1 TUBGCP4 TUBGCP4 76P GCP4 FUNCTION Gamma-tubulin complex is necessary for microtubule nucleation at the centrosome.SUBUNIT Gamma-tubulin complex is composed of gamma-tubulin, TUBGCP2, TUBGCP3, TUBGCP4, TUBGCP5 and TUBGCP6. Interacts with NINL. Interacts with ATF5; the ATF5:PCNT:polyglutamylated tubulin (PGT) tripartite unites the mother centriole and the pericentriolar material (PCM) in the centrosome (PubMed:26213385).TISSUE SPECIFICITY Ubiquitously expressed.SIMILARITY Belongs to the TUBGCP family. UniProt Q9UGJ1 1 EQUAL 667 EQUAL Reactome Database ID Release 81 379268 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379268 Reactome R-HSA-379268 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-379268.1 1 GCP-5 TUBGCP5 Reactome DB_ID: 379271 UniProt:Q96RT8 TUBGCP5 TUBGCP5 GCP5 KIAA1899 FUNCTION Gamma-tubulin complex is necessary for microtubule nucleation at the centrosome.SUBUNIT Gamma-tubulin complex is composed of gamma-tubulin, TUBGCP2, TUBGCP3, TUBGCP4, TUBGCP5 and TUBGCP6.TISSUE SPECIFICITY Widely expressed, with highest levels in heart and skeletal muscle and moderate levels in brain.SIMILARITY Belongs to the TUBGCP family. UniProt Q96RT8 1 EQUAL 1024 EQUAL Reactome Database ID Release 81 379271 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379271 Reactome R-HSA-379271 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-379271.1 1 GCP-6 TUBGCP6 Reactome DB_ID: 379274 UniProt:Q96RT7 TUBGCP6 TUBGCP6 GCP6 KIAA1669 FUNCTION Gamma-tubulin complex is necessary for microtubule nucleation at the centrosome.SUBUNIT Gamma-tubulin complex is composed of gamma-tubulin, TUBGCP2, TUBGCP3, TUBGCP4, TUBGCP5 and TUBGCP6.SIMILARITY Belongs to the TUBGCP family. UniProt Q96RT7 1 EQUAL 1819 EQUAL Reactome Database ID Release 81 379274 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379274 Reactome R-HSA-379274 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-379274.1 1 MZT2A Mitotic-spindle organizing protein 2A MOZART2A FAM128A GCP8A MZT2A_HUMAN Reactome DB_ID: 8955056 UniProt:Q6P582 MZT2A MZT2A FAM128A MOZART2A SUBUNIT Part of the gamma-tubulin complex.SIMILARITY Belongs to the MOZART2 family. UniProt Q6P582 1 EQUAL 158 EQUAL Reactome Database ID Release 81 8955056 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8955056 Reactome R-HSA-8955056 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8955056.1 1 MZT2B Mitotic-spindle organizing protein 2B MOZART2B FAM128B GCP8B MZT2B_HUMAN Reactome DB_ID: 8955057 UniProt:Q6NZ67 MZT2B MZT2B FAM128B MOZART2B SUBUNIT Part of the gamma-tubulin complex. Interacts with TUBG1.SIMILARITY Belongs to the MOZART2 family. UniProt Q6NZ67 1 EQUAL 158 EQUAL Reactome Database ID Release 81 8955057 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8955057 Reactome R-HSA-8955057 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8955057.1 1 gamma-TuSC Reactome DB_ID: 380447 TUBG2 gamma-2- tubulin Reactome DB_ID: 379272 UniProt:Q9NRH3 TUBG2 TUBG2 FUNCTION Tubulin is the major constituent of microtubules. The gamma chain is found at microtubule organizing centers (MTOC) such as the spindle poles or the centrosome. Pericentriolar matrix component that regulates alpha/beta chain minus-end nucleation, centrosome duplication and spindle formation (By similarity).PTM Phosphorylation at Ser-131 by BRSK1 regulates centrosome duplication, possibly by mediating relocation of gamma-tubulin and its associated proteins from the cytoplasm to the centrosome.SIMILARITY Belongs to the tubulin family. UniProt Q9NRH3 1 EQUAL 451 EQUAL Reactome Database ID Release 81 379272 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379272 Reactome R-HSA-379272 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-379272.1 1 GCP-3 TUBGCP3 Reactome DB_ID: 379276 UniProt:Q96CW5 TUBGCP3 TUBGCP3 GCP3 FUNCTION Gamma-tubulin complex is necessary for microtubule nucleation at the centrosome.SUBUNIT Gamma-tubulin complex is composed of gamma-tubulin, TUBGCP2, TUBGCP3, TUBGCP4, TUBGCP5 and TUBGCP6. Interacts with CDK5RAP2; the interaction is leading to centrosomal localization of TUBGCP3 and CDK5RAP2. Interacts with NIN (via N-terminus); the interaction may promote recruitment of the gamma-tubulin ring complex to the centrosome (By similarity).TISSUE SPECIFICITY Ubiquitously expressed.SIMILARITY Belongs to the TUBGCP family. UniProt Q96CW5 1 EQUAL 907 EQUAL Reactome Database ID Release 81 379276 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379276 Reactome R-HSA-379276 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-379276.1 1 TUBG1 gamma-1- tubulin Reactome DB_ID: 379269 UniProt:P23258 TUBG1 TUBG1 TUBG FUNCTION Tubulin is the major constituent of microtubules. The gamma chain is found at microtubule organizing centers (MTOC) such as the spindle poles or the centrosome. Pericentriolar matrix component that regulates alpha/beta chain minus-end nucleation, centrosome duplication and spindle formation.SUBUNIT Interacts with TUBGCP2 and TUBGCP3 (PubMed:9566969, PubMed:9566969). Interacts with B9D2 (By similarity). Interacts with CDK5RAP2; the interaction is leading to centrosomal localization of TUBG1 and CDK5RAP2 (PubMed:17959831). Interacts with PIFO (PubMed:20643351). Interacts with SAS6 and NUP62 at the centrosome (PubMed:24107630). Interacts with EML3 (phosphorylated at 'Thr-881') and HAUS8 (PubMed:30723163).PTM Phosphorylation at Ser-131 by BRSK1 regulates centrosome duplication, possibly by mediating relocation of gamma-tubulin and its associated proteins from the cytoplasm to the centrosome.SIMILARITY Belongs to the tubulin family. UniProt P23258 1 EQUAL 451 EQUAL Reactome Database ID Release 81 379269 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379269 Reactome R-HSA-379269 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-379269.1 1 GCP-2 TUBGCP2 Reactome DB_ID: 379275 UniProt:Q9BSJ2 TUBGCP2 TUBGCP2 GCP2 FUNCTION Gamma-tubulin complex is necessary for microtubule nucleation at the centrosome. Plays a role in neuronal migration.SUBUNIT Gamma-tubulin complex is composed of gamma-tubulin, TUBGCP2, TUBGCP3, TUBGCP4, TUBGCP5 and TUBGCP6. Interacts with ATF5; the ATF5:PCNT:polyglutamylated tubulin (PGT) tripartite unites the mother centriole and the pericentriolar material (PCM) in the centrosome (PubMed:26213385).TISSUE SPECIFICITY Ubiquitously expressed.SIMILARITY Belongs to the TUBGCP family. UniProt Q9BSJ2 1 EQUAL 902 EQUAL Reactome Database ID Release 81 379275 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379275 Reactome R-HSA-379275 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-379275.1 1 Reactome Database ID Release 81 380447 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380447 Reactome R-HSA-380447 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380447.1 6 MZT1 MOZART1 Mitotic-spindle organizing protein 1 C13orf37 MZT1_HUMAN Reactome DB_ID: 8955055 UniProt:Q08AG7 MZT1 MZT1 C13orf37 MOZART1 FUNCTION Required for gamma-tubulin complex recruitment to the centrosome.SUBUNIT Part of the gamma-tubulin complex. Interacts with TUBG1.SIMILARITY Belongs to the MOZART1 family. UniProt Q08AG7 2 EQUAL 82 EQUAL Reactome Database ID Release 81 8955055 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8955055 Reactome R-HSA-8955055 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8955055.1 1 NME7 Nucleoside diphosphate kinase 7 NDK7_HUMAN Reactome DB_ID: 6806880 UniProt:Q9Y5B8 NME7 NME7 FUNCTION Major role in the synthesis of nucleoside triphosphates other than ATP. The ATP gamma phosphate is transferred to the NDP beta phosphate via a ping-pong mechanism, using a phosphorylated active-site intermediate.SIMILARITY Belongs to the NDK family. UniProt Q9Y5B8 1 EQUAL 376 EQUAL Reactome Database ID Release 81 6806880 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=6806880 Reactome R-HSA-6806880 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-6806880.2 1 NEDD1 Reactome DB_ID: 379267 UniProt:Q8NHV4 NEDD1 NEDD1 FUNCTION Required for mitosis progression. Promotes the nucleation of microtubules from the spindle.SUBUNIT Interacts with FAM29A (PubMed:19029337). Interacts with HSPA1A and HSPA1B. Interacts with gamma-tubulin in a HSPA1A/B-dependent manner (PubMed:27137183).PTM During mitosis, prior phosphorylation on Thr-550 by CDK1 promotes subsequent phosphorylation by PLK1 on Thr-382, Ser-397, Ser-426 and Ser-637. Phosphorylated NEDD1 can interact with gamma-tubulin for targeting the gamma-tubulin ring complex (gTuRC) to the centrosome, an important step for spindle formation. UniProt Q8NHV4 1 EQUAL 660 EQUAL Reactome Database ID Release 81 379267 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379267 Reactome R-HSA-379267 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-379267.1 1 Reactome Database ID Release 81 379277 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379277 Reactome R-HSA-379277 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-379277.3 1 centrosome Reactome DB_ID: 380268 CEP250 Cep250/C-Nap1 Reactome DB_ID: 380263 UniProt:Q9BV73 CEP250 CEP250 CEP2 CNAP1 FUNCTION May be involved in ciliogenesis (PubMed:28005958). Probably plays an important role in centrosome cohesion during interphase.SUBUNIT Monomer and homodimer (Probable). Forms a complex in vitro with both NEK2 kinase and the PPP1CC catalytic subunit of protein phosphatase 1 (PP1) (PubMed:9647649, PubMed:10880350). Interacts with CEP135 (PubMed:18851962). Interacts with CROCC/rootletin (By similarity). Interacts with CNTLN (PubMed:24554434). Interacts with NIN (via C-terminus) (By similarity).TISSUE SPECIFICITY Ubiquitously and weakly expressed.PTM Differentially phosphorylated during cell cycle. Phosphorylation may regulate association/dissociation from centrosome. During M phase of mitosis, C-terminal part is phosphorylated by NEK2, suggesting that it may trigger the dissociation from the mitotic centrosome. Dephosphorylated in vitro by the PP1 phosphatase.MISCELLANEOUS Antibodies against CEP2 are present in sera from patients with autoimmune diseases that developed autoantibodies against centrosomal proteins. UniProt Q9BV73 1 EQUAL 2442 EQUAL Reactome Database ID Release 81 380263 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380263 Reactome R-HSA-380263 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380263.1 1 YWHAG 14-3-3 protein gamma 14-3-3 gamma Reactome DB_ID: 380312 UniProt:P61981 YWHAG YWHAG FUNCTION Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner.SUBUNIT Homodimer. Interacts with SAMSN1 (By similarity). Interacts with RAF1, SSH1 and CRTC2/TORC2. Interacts with ABL1 (phosphorylated form); the interaction retains it in the cytoplasm. Interacts with GAB2. Interacts with MDM4 (phosphorylated); negatively regulates MDM4 activity toward TP53. Interacts with PKA-phosphorylated AANAT and SIRT2.Interacts with the 'Thr-369' phosphorylated form of DAPK2 (PubMed:26047703). Interacts with PI4KB, TBC1D22A and TBC1D22B (PubMed:23572552). Interacts with SLITRK1 (PubMed:19640509). Interacts with LRRK2; this interaction is dependent on LRRK2 phosphorylation (PubMed:28202711). Interacts with MARK2 and MARK3 (PubMed:16959763). Interacts with MEFV (PubMed:27030597). Interacts with ENDOG, TSC2 and PIK3C3; interaction with ENDOG weakens its interaction with TSC2 and PIK3C3 (PubMed:33473107).TISSUE SPECIFICITY Highly expressed in brain, skeletal muscle, and heart.PTM Phosphorylated by various PKC isozymes.SIMILARITY Belongs to the 14-3-3 family. UniProt P61981 1 EQUAL 247 EQUAL Reactome Database ID Release 81 380312 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380312 Reactome R-HSA-380312 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380312.1 1 CEP70 Cep70 Reactome DB_ID: 380257 UniProt:Q8NHQ1 CEP70 CEP70 BITE FUNCTION Plays a role in the organization of both preexisting and nascent microtubules in interphase cells. During mitosis, required for the organization and orientation of the mitotic spindle.SUBUNIT Directly interacts with tubulin-gamma; this interaction determines centrosomal localization.DOMAIN The coiled-coil domains may be important for tubulin-gamma-binding and hence for centrosomal localization. UniProt Q8NHQ1 1 EQUAL 597 EQUAL Reactome Database ID Release 81 380257 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380257 Reactome R-HSA-380257 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380257.1 1 CEP57 Cep57 Reactome DB_ID: 380271 UniProt:Q86XR8 CEP57 CEP57 KIAA0092 TSP57 FUNCTION Centrosomal protein which may be required for microtubule attachment to centrosomes. May act by forming ring-like structures around microtubules. Mediates nuclear translocation and mitogenic activity of the internalized growth factor FGF2, but that of FGF1.SUBUNIT Homodimer and homooligomer. Interacts with microtubules. Interacts with FGF2 and RAP80. Does not interact with FGF1 or FGF2 isoform 24 kDa.TISSUE SPECIFICITY Ubiquitous.DOMAIN The C-terminal region mediates the interaction with microtubules and is able to nucleate and bundles microtubules in vitro.DOMAIN The centrosome localization domain (CLD) region mediates the localization to centrosomes and homooligomerization.SIMILARITY Belongs to the translokin family. UniProt Q86XR8 1 EQUAL 500 EQUAL Reactome Database ID Release 81 380271 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380271 Reactome R-HSA-380271 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380271.1 1 DCTN3 Dynactin 3 p24/p22 Reactome DB_ID: 380264 UniProt:O75935 DCTN3 DCTN3 DCTN22 FUNCTION Together with dynein may be involved in spindle assembly and cytokinesis.SUBUNIT Subunit of dynactin, a multiprotein complex associated with dynein.TISSUE SPECIFICITY Ubiquitously expressed. Highly expressed in muscle and pancreas and detected at lower levels in brain.SIMILARITY Belongs to the dynactin subunit 3 family. UniProt O75935 1 EQUAL 186 EQUAL Reactome Database ID Release 81 380264 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380264 Reactome R-HSA-380264 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380264.2 1 EB1 MAPRE1 Reactome DB_ID: 376240 UniProt:Q15691 MAPRE1 MAPRE1 FUNCTION Plus-end tracking protein (+TIP) that binds to the plus-end of microtubules and regulates the dynamics of the microtubule cytoskeleton (PubMed:12388762, PubMed:16109370, PubMed:19632184, PubMed:21646404, PubMed:23001180, PubMed:28726242, PubMed:28814570, PubMed:34608293). Promotes cytoplasmic microtubule nucleation and elongation (PubMed:12388762, PubMed:16109370, PubMed:19632184, PubMed:21646404, PubMed:28726242, PubMed:28814570). Involved in mitotic spindle positioning by stabilizing microtubules and promoting dynamic connection between astral microtubules and the cortex during mitotic chromosome segregation (PubMed:12388762, PubMed:34608293). Also acts as a regulator of minus-end microtubule organization: interacts with the complex formed by AKAP9 and PDE4DIP, leading to recruit CAMSAP2 to the Golgi apparatus, thereby tethering non-centrosomal minus-end microtubules to the Golgi, an important step for polarized cell movement (PubMed:28814570). Promotes elongation of CAMSAP2-decorated microtubule stretches on the minus-end of microtubules (PubMed:28814570). Acts as a regulator of autophagosome transport via interaction with CAMSAP2 (PubMed:28726242). May play a role in cell migration (By similarity).SUBUNIT Homodimer (PubMed:15616574). Heterodimer with MAPRE3 (PubMed:19255245). Interacts with DCTN1, DCTN2, TERF1 and dynein intermediate chain (PubMed:10226031, PubMed:11943150, PubMed:12388762, PubMed:14514668, PubMed:23874158, PubMed:16109370, PubMed:16949363). Interaction with DIAPH1 and DIAPH2 (By similarity). Interacts with APC (via C-terminal domain), CLASP2, DST, KIF2C and STIM1; probably required for their targeting to the growing microtubule plus ends (PubMed:7606712, PubMed:12388762, PubMed:14514668, PubMed:15631994, PubMed:19543227, PubMed:15616574, PubMed:19632184). Interacts with MTUS2; interaction is direct and probably targets MTUS2 to microtubules (PubMed:19543227). Interacts with APC2 (PubMed:10644998). Interacts with CLASP1 (PubMed:15631994). Interacts with CDK5RAP2 (PubMed:19553473). Interacts with MACF1 (By similarity). Interacts with RABL2/RABL2A; binds preferentially to GTP-bound RABL2 (By similarity). Interacts with KCNAB2 (By similarity). Interacts (via C-terminus) with CLIP1 (PubMed:17563362, PubMed:21646404). Interacts with SLAIN2 and SLAIN1 (PubMed:21646404). Interacts with KIF18B; this interaction is required for efficient accumulation of KIF18B at microtubule plus ends (PubMed:21820309). Interacts with MISP (PubMed:23509069). Interacts with KNSTRN (PubMed:23035123). Interacts with NCKAP5L (PubMed:26485573). Interacts with CAMSAP2 (PubMed:28726242). Interacts with PDE4DIP isoform 13/MMG8/SMYLE; this interaction is required for its recruitment to the Golgi apparatus (PubMed:25217626, PubMed:28814570). Forms a pericentrosomal complex with AKAP9, CDK5RAP2 and PDE4DIP isoform 13/MMG8/SMYLE; within this complex, MAPRE1 binding to CDK5RAP2 may be mediated by PDE4DIP (PubMed:29162697). Interacts with AKNA (By similarity). Interacts with GAS2L1, GAS2L2, and GAS2L3 (PubMed:24706950). Interacts with RARRES1 and AGBL2 (PubMed:21303978).TISSUE SPECIFICITY Ubiquitously expressed.DOMAIN Composed of two functionally independent domains. The N-terminal domain forms a hydrophobic cleft involved in microtubule binding and the C-terminal is involved in the formation of mutually exclusive complexes with APC and DCTN1.PTM Acetylation at Lys-220 by KAT2B/PCAF promotes dynamic kinetochore-microtubule interactions in early mitosis.PTM Crotonylated by KAT5 during mitosis, promoting astral microtubule plasticity and dynamic connection between astral microtubules and the cortex during mitotic chromosome segregation, thereby ensuring accurate spindle positioning in mitosis (PubMed:34608293). Decrotonylated by HDAC3 (PubMed:34608293).SIMILARITY Belongs to the MAPRE family. UniProt Q15691 2 EQUAL 268 EQUAL Reactome Database ID Release 81 376240 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=376240 Reactome R-HSA-376240 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-376240.1 1 Nlp NINL Reactome DB_ID: 380706 UniProt:Q9Y2I6 NINL NINL KIAA0980 NLP FUNCTION Involved in the microtubule organization in interphase cells. Overexpression induces the fragmentation of the Golgi, and causes lysosomes to disperse toward the cell periphery; it also interferes with mitotic spindle assembly. May play a role in ovarian carcinogenesis.SUBUNIT Interacts with gamma-tubulin and TUBGCP4. Interacts with anaphase promoting complex/cyclosome (APC/C). Interacts with CDC20 and FZR1. Isoform 2 interacts with LCA5 and USH2A.TISSUE SPECIFICITY Expressed in KYSE-150 esophageal carcinoma, HeLa cervical carcinoma and U2OS osteosarcoma cells. Expression is regulated in a cell cycle-dependent manner and peaks during G2/M phase (at protein level). Expressed in fetal heart, skeletal muscle, liver, lung and cochlea, and in adult brain, testis, kidney and retina.DOMAIN The KEN and D (destructive) boxes are required for the cell cycle-controlled NINL degradation by the APC/C pathway.PTM Phosphorylated by PLK1 which disrupts its centrosome association and interaction with gamma-tubulin.PTM Ubiquitinated by the APC/C complex leading to its degradation. UniProt Q9Y2I6 1 EQUAL 1382 EQUAL Reactome Database ID Release 81 380706 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380706 Reactome R-HSA-380706 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380706.1 1 AZI1 Cep131 Reactome DB_ID: 380295 UniProt:Q9UPN4 CEP131 CEP131 AZI1 KIAA1118 FUNCTION Component of centriolar satellites contributing to the building of a complex and dynamic network required to regulate cilia/flagellum formation (PubMed:17954613, PubMed:24185901). In proliferating cells, MIB1-mediated ubiquitination induces its sequestration within centriolar satellites, precluding untimely cilia formation initiation (PubMed:24121310). In contrast, during normal and ultraviolet or heat shock cellular stress-induced ciliogenesis, its non-ubiquitinated form is rapidly displaced from centriolar satellites and recruited to centrosome/basal bodies in a microtubule- and p38 MAPK-dependent manner (PubMed:24121310, PubMed:26616734). Acts also as a negative regulator of BBSome ciliary trafficking (PubMed:24550735). Plays a role in sperm flagellar formation; may be involved in the regulation of intraflagellar transport (IFT) and/or intramanchette (IMT) trafficking, which are important for axoneme extension and/or cargo delivery to the nascent sperm tail (By similarity). Required for optimal cell proliferation and cell cycle progression; may play a role in the regulation of genome stability in non-ciliogenic cells (PubMed:22797915, PubMed:26297806). Involved in centriole duplication (By similarity). Required for CEP152, WDR62 and CEP63 centrosomal localization and promotes the centrosomal localization of CDK2 (PubMed:26297806). Essential for maintaining proper centriolar satellite integrity (PubMed:30804208).SUBUNIT Self-associates. Associates with the centriolar satellite BBSome protein complex. Interacts with BBS4; the interaction limits BBS4 availability for association with the BBSome complex, and hence negatively regulates ciliary localization of the BBSome complex (PubMed:24550735). Interacts with MIB1 (PubMed:24121310). Interacts with PCM1; the interaction increases in response to ultraviolet light (UV) radiation (PubMed:22797915, PubMed:24121310). Associates with microtubules; association with microtubules is reduced in response to cellular stress, such as UV stimulation, in a process that requires p38 MAP kinase signaling (PubMed:24121310). Interacts with CEP290, DCTN1, PCNT, PCM1 and CEP152. Interacts with 14-3-3 proteins following UV-induced phosphorylation by MAPKAPK2; this inhibits formation of novel centriolar satellites (PubMed:26616734). Interacts with SDCCAG8 (PubMed:27224062). Interacts with CCDC61 (PubMed:31789463). Interacts with PLK4 (PubMed:30804208).INDUCTION Up-regulated by the transcription factor SP1.PTM Ubiquitinated. Undergoes monoubiquitination catalyzed by the E3 ubiquitin-protein ligase MIB1 in proliferating cells, preventing cilia formation. Monoubiquitination by MIB1 is inhibited in response to cellular stress, such as ultraviolet light (UV) radiation or heat shock, resulting in cilia formation initiation.PTM MAPKAPK2-dependent phosphorylation at Ser-47 and Ser-78 occurs in response to cellular stress such as exposure to ultraviolet irradiation and promotes binding to 14-3-3 proteins which leads to cytoplasmic sequestration of CEP131 and blocks formation of new centriolar satellites (PubMed:26616734). Phosphorylation at Ser-78 mediated by PLK4 is essential for proper organization and integrity of centriolar satellites but is dispensable for its localization to centrioles and its function in ciliogenesis (PubMed:30804208).MISCELLANEOUS Transient cell cultured-based knock-down (by RNAi) of CEP131 leads to a reduction in ciliogenesis (PubMed:17954613, PubMed:24121310). However, analysis of mice with chronic absence of CEP131 following genetic deletion (knockout) shows that cilia develop and function normally in vivo. This suggests that CEP131 is not essential for ciliogenesis, except for the modified cilia of the developing sperm flagella, and that there is an alternative mechanism to compensate for the lack of CEP131.SIMILARITY Belongs to the CEP131 family. UniProt Q9UPN4 1 EQUAL 1083 EQUAL Reactome Database ID Release 81 380295 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380295 Reactome R-HSA-380295 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380295.1 1 CNTRL Centriolin Reactome DB_ID: 380256 UniProt:Q7Z7A1 CNTRL CNTRL CEP1 CEP110 FUNCTION Involved in cell cycle progression and cytokinesis. During the late steps of cytokinesis, anchors exocyst and SNARE complexes at the midbody, thereby allowing secretory vesicle-mediated abscission.SUBUNIT Interacts with HOOK2. Interacts with EXOC6 and SNAPIN. Associates with the exocyst complex.TISSUE SPECIFICITY Widely expressed with highest levels in testis and trachea.DISEASE A chromosomal aberration involving CEP110 may be a cause of stem cell myeloproliferative disorder (MPD). Translocation t(8;9)(p12;q33) with FGFR1. MPD is characterized by myeloid hyperplasia, eosinophilia and T-cell or B-cell lymphoblastic lymphoma. In general it progresses to acute myeloid leukemia. The fusion protein CEP110-FGFR1 is found in the cytoplasm, exhibits constitutive kinase activity and may be responsible for the transforming activity. UniProt Q7Z7A1 1 EQUAL 2325 EQUAL Reactome Database ID Release 81 380256 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380256 Reactome R-HSA-380256 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380256.1 1 Lis1 PAFAH1B1 Reactome DB_ID: 376249 UniProt:P43034 PAFAH1B1 PAFAH1B1 LIS1 MDCR MDS PAFAHA FUNCTION Regulatory subunit (beta subunit) of the cytosolic type I platelet-activating factor (PAF) acetylhydrolase (PAF-AH (I)), an enzyme that catalyzes the hydrolyze of the acetyl group at the sn-2 position of PAF and its analogs and participates in PAF inactivation. Regulates the PAF-AH (I) activity in a catalytic dimer composition-dependent manner (By similarity). Required for proper activation of Rho GTPases and actin polymerization at the leading edge of locomoting cerebellar neurons and postmigratory hippocampal neurons in response to calcium influx triggered via NMDA receptors (By similarity). Positively regulates the activity of the minus-end directed microtubule motor protein dynein. May enhance dynein-mediated microtubule sliding by targeting dynein to the microtubule plus end. Required for several dynein- and microtubule-dependent processes such as the maintenance of Golgi integrity, the peripheral transport of microtubule fragments and the coupling of the nucleus and centrosome. Required during brain development for the proliferation of neuronal precursors and the migration of newly formed neurons from the ventricular/subventricular zone toward the cortical plate. Neuronal migration involves a process called nucleokinesis, whereby migrating cells extend an anterior process into which the nucleus subsequently translocates. During nucleokinesis dynein at the nuclear surface may translocate the nucleus towards the centrosome by exerting force on centrosomal microtubules. May also play a role in other forms of cell locomotion including the migration of fibroblasts during wound healing. Required for dynein recruitment to microtubule plus ends and BICD2-bound cargos (PubMed:22956769). May modulate the Reelin pathway through interaction of the PAF-AH (I) catalytic dimer with VLDLR (By similarity).SUBUNIT Component of the cytosolic PAF-AH (I) heterotetrameric enzyme, which is composed of PAFAH1B1 (beta), PAFAH1B2 (alpha2) and PAFAH1B3 (alpha1) subunits. The catalytic activity of the enzyme resides in the alpha1 (PAFAH1B3) and alpha2 (PAFAH1B2) subunits, whereas the beta subunit (PAFAH1B1) has regulatory activity. Trimer formation is not essential for the catalytic activity. Interacts with the catalytic dimer of PAF-AH (I) heterotetrameric enzyme: interacts with PAFAH1B2 homodimer (alpha2/alpha2 homodimer), PAFAH1B3 homodimer (alpha1/alpha1 homodimer) and PAFAH1B2-PAFAH1B3 heterodimer (alpha2/alpha1 heterodimer) (By similarity). Interacts with IQGAP1, KATNB1 and NUDC. Interacts with DAB1 when DAB1 is phosphorylated in response to RELN/reelin signaling (By similarity). Can self-associate. Interacts with DCX, dynein, dynactin, NDE1, NDEL1 and RSN. Interacts with DISC1, and this interaction is enhanced by NDEL1. Interacts with INTS13. Interacts with DCDC1 (PubMed:22159412).TISSUE SPECIFICITY Fairly ubiquitous expression in both the frontal and occipital areas of the brain.DOMAIN Dimerization mediated by the LisH domain may be required to activate dynein.MISCELLANEOUS Originally the subunits of the type I platelet-activating factor (PAF) acetylhydrolase was named alpha (PAFAH1B1), beta (PAFAH1B2) and gamma (PAFAH1B3) (By similarity) (Ref.4). Now these subunits have been renamed beta (PAFAH1B1), alpha2 (PAFAH1B2) and alpha1 (PAFAH1B3) respectively (By similarity).SIMILARITY Belongs to the WD repeat LIS1/nudF family. UniProt P43034 1 EQUAL 410 EQUAL Reactome Database ID Release 81 376249 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=376249 Reactome R-HSA-376249 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-376249.1 1 AKAP9 GC-NAP A kinase Anchor protein (Yotiao) A4D1E4_HUMAN Reactome DB_ID: 380260 UniProt:Q99996 AKAP9 AKAP9 AKAP350 AKAP450 KIAA0803 FUNCTION Scaffolding protein that assembles several protein kinases and phosphatases on the centrosome and Golgi apparatus. Required to maintain the integrity of the Golgi apparatus (PubMed:10202149, PubMed:15047863). Required for microtubule nucleation at the cis-side of the Golgi apparatus (PubMed:15047863, PubMed:19242490). Required for association of the centrosomes with the poles of the bipolar mitotic spindle during metaphase (PubMed:25657325). In complex with PDE4DIP isoform 13/MMG8/SMYLE, recruits CAMSAP2 to the Golgi apparatus and tethers non-centrosomal minus-end microtubules to the Golgi, an important step for polarized cell movement (PubMed:27666745, PubMed:28814570). In complex with PDE4DIP isoform 13/MMG8/SMYLE, EB1/MAPRE1 and CDK5RAP2, contributes to microtubules nucleation and extension also from the centrosome to the cell periphery (PubMed:29162697).SUBUNIT Interacts with the regulatory region of protein kinase N (PKN), protein phosphatase 2A (PP2A), protein phosphatase 1 (PP1) and the immature non-phosphorylated form of PKC epsilon. Interacts with CIP4 and FNBP1 (PubMed:15047863). Interacts with chloride intracellular channel proteins CLIC1, CLIC4 and CLIC5 (PubMed:12163479). CSNK1D binding promotes its centrosomal subcellular location (PubMed:12270714). Interacts with GM130/GOLGA2; leading to recruitment to the Golgi apparatus (PubMed:19242490). Interacts with KCNQ1; targets protein kinase A (PKA) catalytic and regulatory subunits and protein phosphatase 1 (PP1), to the heterodimer KCNQ1-KCNE1 (PubMed:11799244). Interacts with PDE4DIP isoform 13/MMG8/SMYLE; this interaction stabilizes both proteins (PubMed:25217626, PubMed:27666745, PubMed:28814570). In complex with PDE4DIP isoform 13, recruits CAMSAP2 to the Golgi apparatus (PubMed:27666745, PubMed:28814570). Forms a pericentrosomal complex with CDK5RAP2, EB1/MAPRE1 and PDE4DIP isoform 13; within this complex, MAPRE1 binding to CDK5RAP2 may be mediated by PDE4DIP (PubMed:29162697). Interacts with MAPRE1 and MAPRE3 (PubMed:28814570). Interacts (via C-terminus) with CAMSAP2; this interaction is much stronger in the presence of PDE4DIP isoform 13/MMG8/SMYLE (PubMed:27666745). Interacts with CAMSAP3 (PubMed:28089391). Interacts (via C-terminus) with the gamma-tubulin ring complex (gamma-TuRC), composed of gamma-tubulin, TUBGCP2, TUBGCP3, TUBGCP4, TUBGCP5 and TUBGCP6 (PubMed:27666745).TISSUE SPECIFICITY Widely expressed (PubMed:10202149). Isoform 4: Highly expressed in skeletal muscle and in pancreas (PubMed:9482789).DOMAIN RII-binding site, predicted to form an amphipathic helix, could participate in protein-protein interactions with a complementary surface on the R-subunit dimer. UniProt Q99996 1 EQUAL 3911 EQUAL Reactome Database ID Release 81 380260 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380260 Reactome R-HSA-380260 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380260.1 1 CEP152 Cep152 Reactome DB_ID: 380277 UniProt:O94986 CEP152 CEP152 KIAA0912 FUNCTION Necessary for centrosome duplication; the function seems also to involve CEP63, CDK5RAP2 and WDR62 through a stepwise assembled complex at the centrosome that recruits CDK2 required for centriole duplication (PubMed:26297806). Acts as a molecular scaffold facilitating the interaction of PLK4 and CENPJ, 2 molecules involved in centriole formation (PubMed:21059844, PubMed:20852615). Proposed to snatch PLK4 away from PLK4:CEP92 complexes in early G1 daughter centriole and to reposition PLK4 at the outer boundary of a newly forming CEP152 ring structure (PubMed:24997597). Also plays a key role in deuterosome-mediated centriole amplification in multiciliated that can generate more than 100 centrioles (By similarity). Overexpression of CEP152 can drive amplification of centrioles (PubMed:20852615).SUBUNIT Interacts (via N-terminus) with PLK4; the interaction is mutally exclusive with a PLK4:CEP192 interaction (PubMed:21059844, PubMed:20852615, PubMed:24997597). Interacts (via C-terminus) with CENPJ (via-N-terminus) (PubMed:20852615). Interacts with CINP (PubMed:21131973). Interacts with CDK5RAP2, WDR62, CEP63 and CEP131 (PubMed:21983783, PubMed:24613305, PubMed:26297806). CEP63, CDK5RAP2, CEP152, WDR62 are proposed to form a stepwise assembled complex at the centrosome forming a ring near parental centrioles (PubMed:26297806). Interacts with DEUP1; this interaction recruits CEP152 to the deuterosome. The interactions with CEP63 and DEUP1 are mutually exclusive (By similarity).SIMILARITY Belongs to the CEP152 family. UniProt O94986 1 EQUAL 1654 EQUAL Reactome Database ID Release 81 380277 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380277 Reactome R-HSA-380277 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380277.1 1 CCCAP SDCCAG8 Reactome DB_ID: 380273 UniProt:Q86SQ7 SDCCAG8 SDCCAG8 CCCAP NPHP10 HSPC085 FUNCTION Plays a role in the establishment of cell polarity and epithelial lumen formation (By similarity). Plays also an essential role in ciliogenesis and subsequent Hedgehog signaling pathway that requires the presence of intact primary cilia for pathway activation. Mechanistically, interacts with and mediates RABEP2 centrosomal localization which is critical for ciliogenesis (PubMed:27224062).SUBUNIT Homodimer (By similarity). Interacts with OFD1; the interaction is direct (PubMed:20835237). Interacts with FAM161A (PubMed:22940612). Interacts with RABEP2, ERC1 and CEP131 (PubMed:27224062).TISSUE SPECIFICITY Expressed in thymus, prostate, testis, ovary, small intestine, colon, mucosa, colon and renal cancer tumors. UniProt Q86SQ7 1 EQUAL 713 EQUAL Reactome Database ID Release 81 380273 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380273 Reactome R-HSA-380273 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380273.1 1 CSNK1E CKIepsilon Casein kinase I isoform epsilon Reactome DB_ID: 205877 UniProt:P49674 CSNK1E CSNK1E FUNCTION Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. Can phosphorylate a large number of proteins. Participates in Wnt signaling. Phosphorylates DVL1 and DVL2. Central component of the circadian clock. In balance with PP1, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation. Controls PER1 and PER2 nuclear transport and degradation. Inhibits cytokine-induced granuloytic differentiation.ACTIVITY REGULATION Phosphorylation leads to a decrease of the catalytic activity.SUBUNIT Monomer (PubMed:23106386). Component of the circadian core oscillator, which includes the CRY proteins, CLOCK, or NPAS2, ARTNL/BMAL1 or ARTNL2/BMAL2, CSNK1D and/or CSNK1E, TIMELESS and the PER proteins (By similarity). Interacts with PER1 (PubMed:10790862). Interacts with ANKRD6 (By similarity). Interacts with DBNDD2 (PubMed:16618118). Interacts with LRP5 and LRP6 (PubMed:16513652). Interacts with SOCS3 (PubMed:15070676). Interacts with SNAI1 (via zinc fingers) (PubMed:20305697). Interacts with DDX3X; this interaction greatly enhances CSNK1E affinity for ATP and DVL2 phosphorylation, but inhibits DDX3X ATPase/helicase activity. In the presence of RNA, the interaction is decreased (PubMed:23413191, PubMed:29222110).TISSUE SPECIFICITY Expressed in all tissues examined, including brain, heart, lung, liver, pancreas, kidney, placenta and skeletal muscle. Expressed in monocytes and lymphocytes but not in granulocytes.INDUCTION Down-regulated during granulocytic differentiation.PTM Autophosphorylated. Partially dephosphorylated by PPP5C. May be dephosphorylated by PP1.SIMILARITY Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family. Casein kinase I subfamily. UniProt P49674 1 EQUAL 416 EQUAL Reactome Database ID Release 81 205877 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=205877 Reactome R-HSA-205877 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-205877.1 1 CEP290 Cep290 Reactome DB_ID: 380275 UniProt:O15078 CEP290 CEP290 BBS14 KIAA0373 NPHP6 FUNCTION Involved in early and late steps in cilia formation. Its association with CCP110 is required for inhibition of primary cilia formation by CCP110 (PubMed:18694559). May play a role in early ciliogenesis in the disappearance of centriolar satellites and in the transition of primary ciliar vesicles (PCVs) to capped ciliary vesicles (CCVs). Required for the centrosomal recruitment of RAB8A and for the targeting of centriole satellite proteins to centrosomes such as of PCM1 (PubMed:24421332). Required for the correct localization of ciliary and phototransduction proteins in retinal photoreceptor cells; may play a role in ciliary transport processes (By similarity). Required for efficient recruitment of RAB8A to primary cilium (PubMed:17705300). In the ciliary transition zone is part of the tectonic-like complex which is required for tissue-specific ciliogenesis and may regulate ciliary membrane composition (By similarity). Involved in regulation of the BBSome complex integrity, specifically for presence of BBS2, BBS5 and BBS8/TTC8 in the complex, and in ciliary targeting of selected BBSome cargos. May play a role in controlling entry of the BBSome complex to cilia possibly implicating IQCB1/NPHP5 (PubMed:25552655). Activates ATF4-mediated transcription (PubMed:16682973).SUBUNIT Part of the tectonic-like complex (also named B9 complex) (By similarity). Interacts with ATF4 via its N-terminal region (PubMed:16682973). Associates with the BBSome complex (PubMed:25552655, PubMed:23943788), interacting (via N-terminus) with BBS4 (PubMed:23943788). Interacts with IQCB1/NPHP5; IQCB1 and CEP290/NPHP6 are proposed to form a functional NPHP5-6 module localized to the centrosome. Interacts with NPHP4; the interaction likely requires additional interactors. Interacts with ZNF423, FAM161A, CEP162, CEP162, CEP131, TALPID3, CCDC13, CC2D2A, RPGRIP1 (PubMed:18950740, PubMed:18723859, PubMed:21565611, PubMed:22863007, PubMed:22940612, PubMed:22797915, PubMed:23446637, PubMed:23644468, PubMed:24421332, PubMed:24816561, PubMed:20200501). Can self-associate (homo- or heteromeric) (PubMed:18723859). Interacts with CCP110; required for suppressing cilia formation (PubMed:18694559). Interacts with RPGR (By similarity). Associates (via C-terminus) with microtubules (PubMed:24121310, PubMed:24051377); association to microtubule is reduced in response to cellular stress, such as ultraviolet light (UV) radiation or heat shock, in a process that requires p38 MAP kinase signaling (PubMed:24121310). Interacts with FAM161A (By similarity). Interacts with PCM1 (By similarity). Interacts with CCDC66 (PubMed:28235840). Interacts with ARMC9 and CSPP1 (PubMed:32453716).TISSUE SPECIFICITY Ubiquitous. Expressed strongly in placenta and weakly in brain.PTM Ubiquitinated. May undergo monoubiquitination; monoubiquitination is inhibited in response to cellular stress, such as ultraviolet light (UV) radiation or heat shock, but does not cause it displacement from centriolar satellites.DISEASE Antibodies against CEP290 are present in sera from patients with cutaneous T-cell lymphomas, but not in the healthy control population. UniProt O15078 1 EQUAL 2479 EQUAL Reactome Database ID Release 81 380275 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380275 Reactome R-HSA-380275 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380275.1 1 CSNK1D Casein kinase I, delta Reactome DB_ID: 380315 UniProt:P48730 CSNK1D CSNK1D HCKID FUNCTION Essential serine/threonine-protein kinase that regulates diverse cellular growth and survival processes including Wnt signaling, DNA repair and circadian rhythms. It can phosphorylate a large number of proteins. Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. Phosphorylates connexin-43/GJA1, MAP1A, SNAPIN, MAPT/TAU, TOP2A, DCK, HIF1A, EIF6, p53/TP53, DVL2, DVL3, ESR1, AIB1/NCOA3, DNMT1, PKD2, YAP1, PER1 and PER2. Central component of the circadian clock. In balance with PP1, determines the circadian period length through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation. Controls PER1 and PER2 nuclear transport and degradation. YAP1 phosphorylation promotes its SCF(beta-TRCP) E3 ubiquitin ligase-mediated ubiquitination and subsequent degradation. DNMT1 phosphorylation reduces its DNA-binding activity. Phosphorylation of ESR1 and AIB1/NCOA3 stimulates their activity and coactivation. Phosphorylation of DVL2 and DVL3 regulates WNT3A signaling pathway that controls neurite outgrowth. EIF6 phosphorylation promotes its nuclear export. Triggers down-regulation of dopamine receptors in the forebrain. Activates DCK in vitro by phosphorylation. TOP2A phosphorylation favors DNA cleavable complex formation. May regulate the formation of the mitotic spindle apparatus in extravillous trophoblast. Modulates connexin-43/GJA1 gap junction assembly by phosphorylation. Probably involved in lymphocyte physiology. Regulates fast synaptic transmission mediated by glutamate.ACTIVITY REGULATION Exhibits substrate-dependent heparin activation. Drug-mediated inhibition leads to a delay of the oscillations with the magnitude of this effect dependent upon the timing of drug administration. Inhibited by phosphorylation. Repressed by 3-[(2,4,6-trimethoxyphenyl)methylidenyl]-indolin-2-one (IC261), N-(2-aminoethyl)-5-chloroisoquinoline-8-sulfonamide (CKI-7), 4-[4-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-5-pyridin-2-yl-1H-imidazol-2-yl]benzamide (D4476), 3,4-diaryl-isoxazoles and -imidazoles, and 4-(3-cyclohexyl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl) pyrimidin-2-ylamine (PF670462, PF670).SUBUNIT Monomer (PubMed:22168824, PubMed:23106386). Component of the circadian core oscillator, which includes the CRY proteins, CLOCK, or NPAS2, ARTNL/BMAL1 or ARTNL2/BMAL2, CSNK1D and/or CSNK1E, TIMELESS and the PER proteins (By similarity). Interacts with DNMT1 and MAP1A (By similarity). Interacts directly with PER1 and PER2 which may lead to their degradation (PubMed:11165242). Interacts with MAPT/TAU (PubMed:14761950). Interacts with SNAPIN (By similarity). Interacts with DBNDD2 (PubMed:16618118). Interacts with AIB1/NCOA3 and ESR1 (PubMed:19339517). Interacts with AKAP9/AKAP450; this interaction promotes centrosomal subcellular location (PubMed:12270714). Binds to tubulins in mitotic cells upon DNA damage (PubMed:10826492). Interacts with GJA1 (PubMed:12270943). Interacts with DDX3X; this interaction enhances CSNK1D kinase activity in vitro, but it is unclear whether this interaction is physiologically relevant (PubMed:29222110).TISSUE SPECIFICITY Expressed in all tissues examined, including brain, heart, lung, liver, pancreas, kidney, placenta and skeletal muscle. However, kinase activity is not uniform, with highest kinase activity in splenocytes. In blood, highly expressed in hemopoietic cells and mature granulocytes. Also found in monocytes and lymphocytes.DEVELOPMENTAL STAGE Highly present in extravillous trophoblast cells, which are present at the placenta implantation site and invade the decidua and decidual vessels.PTM Autophosphorylated on serine and threonine residues; this autophosphorylation represses activity. Reactivated by phosphatase-mediated dephosphorylation. May be dephosphorylated by PP1.MISCELLANEOUS May be involved in Alzheimer disease by phosphorylating MAPT/TAU.SIMILARITY Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family. Casein kinase I subfamily.CAUTION Was shown to phosphorylate and activate DCK in vitro but probably not in vivo. UniProt P48730 1 EQUAL 415 EQUAL Reactome Database ID Release 81 380315 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380315 Reactome R-HSA-380315 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380315.1 1 DYNC1I2 Dynein intermediate chain 2 Reactome DB_ID: 201607 UniProt:Q13409 DYNC1I2 DYNC1I2 DNCI2 DNCIC2 FUNCTION Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function (PubMed:31079899). Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules (PubMed:31079899). The intermediate chains mediate the binding of dynein to dynactin via its 150 kDa component (p150-glued) DCTN1 (By similarity). Involved in membrane-transport, such as Golgi apparatus, late endosomes and lysosomes (By similarity).SUBUNIT Homodimer (By similarity). The cytoplasmic dynein 1 complex consists of two catalytic heavy chains (HCs) and a number of non-catalytic subunits presented by intermediate chains (ICs), light intermediate chains (LICs) and light chains (LCs); the composition seems to vary in respect to the IC, LIC and LC composition (By similarity). The heavy chain homodimer serves as a scaffold for the probable homodimeric assembly of the respective non-catalytic subunits (By similarity). The ICs and LICs bind directly to the HC dimer and the LCs assemble on the IC dimer (By similarity). Interacts with DYNLT3 (By similarity). Interacts with DYNLT1 (PubMed:27502274). Interacts (dephosphorylated at Ser-90) with DCTN1 (By similarity). Interacts with BICD2. Interacts with SPEF2 (By similarity).SUBUNIT (Microbial infection) Interacts with human adenovirus 5 hexon protein; this interaction probably allows virus intracellular transport.PTM The phosphorylation status of Ser-90 appears to be involved in dynactin-dependent target binding.PTM Pyrophosphorylation by 5-diphosphoinositol pentakisphosphate (5-IP7) promotes interaction with DCTN1. Serine pyrophosphorylation is achieved by Mg(2+)-dependent, but enzyme independent transfer of a beta-phosphate from a inositol pyrophosphate to a pre-phosphorylated serine residue.SIMILARITY Belongs to the dynein intermediate chain family. UniProt Q13409 1 EQUAL 638 EQUAL Reactome Database ID Release 81 201607 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=201607 Reactome R-HSA-201607 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-201607.1 1 CEP192 Cep192 Reactome DB_ID: 380319 UniProt:Q8TEP8 CEP192 CEP192 KIAA1569 PP8407 FUNCTION Required for mitotic centrosome maturation and bipolar spindle assembly (PubMed:25042804, PubMed:17980596, PubMed:18207742). Appears to be a major regulator of pericentriolar material (PCM) recruitment, centrosome maturation, and centriole duplication (PubMed:25042804, PubMed:17980596, PubMed:18207742). Centrosome-specific activating scaffold for AURKA and PLK1 (PubMed:25042804).SUBUNIT Interacts with SHBG (PubMed:15862967). Interacts with PLK4; this interaction mediates the formation of a ternary complex composed by PLK4, TENT5C and CEP192 (PubMed:32433990).PTM Hydroxylation by PHD1/EGLN2 at Pro-2313 promotes ubiquitination.PTM Ubiquitinated by a SCF(SKP2) complex following proline hydroxylation. UniProt Q8TEP8 1 EQUAL 1941 EQUAL Reactome Database ID Release 81 380319 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380319 Reactome R-HSA-380319 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380319.1 1 PRKAR2B cAMP-dependent protein kinase type II-beta regulatory chain Reactome DB_ID: 57842 UniProt:P31323 PRKAR2B PRKAR2B FUNCTION Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. Type II regulatory chains mediate membrane association by binding to anchoring proteins, including the MAP2 kinase.SUBUNIT The inactive form of the enzyme is composed of two regulatory chains and two catalytic chains. Activation by cAMP produces two active catalytic monomers and a regulatory dimer that binds four cAMP molecules. Interacts with PRKACA and PRKACB (PubMed:33058759). Interacts with the phosphorylated form of PJA2. Forms a complex composed of PRKAR2B, GSK3B and GSKIP through GSKIP interaction; facilitates PKA-induced phosphorylation and regulates GSK3B activity (PubMed:25920809).TISSUE SPECIFICITY Four types of regulatory chains are found: I-alpha, I-beta, II-alpha, and II-beta. Their expression varies among tissues and is in some cases constitutive and in others inducible.PTM Phosphorylated by the activated catalytic chain.SIMILARITY Belongs to the cAMP-dependent kinase regulatory chain family. UniProt P31323 2 EQUAL 418 EQUAL Reactome Database ID Release 81 57842 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=57842 Reactome R-HSA-57842 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-57842.1 1 CDK1 Cdc2 Reactome DB_ID: 170075 UniProt:P06493 CDK1 CDK1 CDC2 CDC28A CDKN1 P34CDC2 FUNCTION Plays a key role in the control of the eukaryotic cell cycle by modulating the centrosome cycle as well as mitotic onset; promotes G2-M transition, and regulates G1 progress and G1-S transition via association with multiple interphase cyclins (PubMed:16407259, PubMed:17459720, PubMed:16933150, PubMed:18356527, PubMed:19509060, PubMed:20171170, PubMed:19917720, PubMed:20937773, PubMed:20935635, PubMed:21063390, PubMed:23355470, PubMed:23601106, PubMed:23602554, PubMed:25556658, PubMed:26829474, PubMed:30704899). Required in higher cells for entry into S-phase and mitosis (PubMed:16407259, PubMed:17459720, PubMed:16933150, PubMed:18356527, PubMed:19509060, PubMed:20171170, PubMed:19917720, PubMed:20937773, PubMed:20935635, PubMed:21063390, PubMed:23355470, PubMed:23601106, PubMed:23602554, PubMed:25556658). Phosphorylates PARVA/actopaxin, APC, AMPH, APC, BARD1, Bcl-xL/BCL2L1, BRCA2, CALD1, CASP8, CDC7, CDC20, CDC25A, CDC25C, CC2D1A, CENPA, CSNK2 proteins/CKII, FZR1/CDH1, CDK7, CEBPB, CHAMP1, DMD/dystrophin, EEF1 proteins/EF-1, EZH2, KIF11/EG5, EGFR, FANCG, FOS, GFAP, GOLGA2/GM130, GRASP1, UBE2A/hHR6A, HIST1H1 proteins/histone H1, HMGA1, HIVEP3/KRC, KAT5, LMNA, LMNB, LMNC, LBR, LATS1, MAP1B, MAP4, MARCKS, MCM2, MCM4, MKLP1, MYB, NEFH, NFIC, NPC/nuclear pore complex, PITPNM1/NIR2, NPM1, NCL, NUCKS1, NPM1/numatrin, ORC1, PRKAR2A, EEF1E1/p18, EIF3F/p47, p53/TP53, NONO/p54NRB, PAPOLA, PLEC/plectin, RB1, TPPP, UL40/R2, RAB4A, RAP1GAP, RCC1, RPS6KB1/S6K1, KHDRBS1/SAM68, ESPL1, SKI, BIRC5/survivin, STIP1, TEX14, beta-tubulins, MAPT/TAU, NEDD1, VIM/vimentin, TK1, FOXO1, RUNX1/AML1, SAMHD1, SIRT2, CGAS and RUNX2 (PubMed:16407259, PubMed:17459720, PubMed:16933150, PubMed:18356527, PubMed:19509060, PubMed:20171170, PubMed:19917720, PubMed:20937773, PubMed:20935635, PubMed:21063390, PubMed:23355470, PubMed:23601106, PubMed:23602554, PubMed:25556658, PubMed:32351706, PubMed:26829474, PubMed:30704899). CDK1/CDC2-cyclin-B controls pronuclear union in interphase fertilized eggs (PubMed:18480403, PubMed:20360007). Essential for early stages of embryonic development (PubMed:18480403, PubMed:20360007). During G2 and early mitosis, CDC25A/B/C-mediated dephosphorylation activates CDK1/cyclin complexes which phosphorylate several substrates that trigger at least centrosome separation, Golgi dynamics, nuclear envelope breakdown and chromosome condensation (PubMed:18480403, PubMed:20360007). Once chromosomes are condensed and aligned at the metaphase plate, CDK1 activity is switched off by WEE1- and PKMYT1-mediated phosphorylation to allow sister chromatid separation, chromosome decondensation, reformation of the nuclear envelope and cytokinesis (PubMed:18480403, PubMed:20360007). Inactivated by PKR/EIF2AK2- and WEE1-mediated phosphorylation upon DNA damage to stop cell cycle and genome replication at the G2 checkpoint thus facilitating DNA repair (PubMed:20360007). Reactivated after successful DNA repair through WIP1-dependent signaling leading to CDC25A/B/C-mediated dephosphorylation and restoring cell cycle progression (PubMed:20395957). In proliferating cells, CDK1-mediated FOXO1 phosphorylation at the G2-M phase represses FOXO1 interaction with 14-3-3 proteins and thereby promotes FOXO1 nuclear accumulation and transcription factor activity, leading to cell death of postmitotic neurons (PubMed:18356527). The phosphorylation of beta-tubulins regulates microtubule dynamics during mitosis (PubMed:16371510). NEDD1 phosphorylation promotes PLK1-mediated NEDD1 phosphorylation and subsequent targeting of the gamma-tubulin ring complex (gTuRC) to the centrosome, an important step for spindle formation (PubMed:19509060). In addition, CC2D1A phosphorylation regulates CC2D1A spindle pole localization and association with SCC1/RAD21 and centriole cohesion during mitosis (PubMed:20171170). The phosphorylation of Bcl-xL/BCL2L1 after prolongated G2 arrest upon DNA damage triggers apoptosis (PubMed:19917720). In contrast, CASP8 phosphorylation during mitosis prevents its activation by proteolysis and subsequent apoptosis (PubMed:20937773). This phosphorylation occurs in cancer cell lines, as well as in primary breast tissues and lymphocytes (PubMed:20937773). EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing (PubMed:20935635). CALD1 phosphorylation promotes Schwann cell migration during peripheral nerve regeneration (By similarity). CDK1-cyclin-B complex phosphorylates NCKAP5L and mediates its dissociation from centrosomes during mitosis (PubMed:26549230). Regulates the amplitude of the cyclic expression of the core clock gene ARNTL/BMAL1 by phosphorylating its transcriptional repressor NR1D1, and this phosphorylation is necessary for SCF(FBXW7)-mediated ubiquitination and proteasomal degradation of NR1D1 (PubMed:27238018). Phosphorylates EML3 at 'Thr-881' which is essential for its interaction with HAUS augmin-like complex and TUBG1 (PubMed:30723163). Phosphorylates CGAS during mitosis, leading to its inhibition, thereby preventing CGAS activation by self DNA during mitosis (PubMed:32351706).FUNCTION (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry.ACTIVITY REGULATION Phosphorylation at Thr-14 or Tyr-15 inactivates the enzyme, while phosphorylation at Thr-161 activates it. Activated through a multistep process; binding to cyclin-B is required for relocation of cyclin-kinase complexes to the nucleus, activated by CAK/CDK7-mediated phosphorylation on Thr-161, and CDC25-mediated dephosphorylation of inhibitory phosphorylation on Thr-14 and Tyr-15. Inhibited by flavopiridol and derivatives, pyrimidine derivatives, pyridine derivatives, purine derivatives, staurosporine, paullones, oxoindoles, indazole analogs, indolin-2-ones, pyrazolo[3,4-b]pyridines, imidazo[1,2-a]pyridine (AZ703), thiazolinone analogs(RO-3306), thiazol urea, macrocyclic quinoxalin-2-one, pyrrolo[2,3-a]carbazole, pyrazolo[1,5-a]-1,3,5-triazine, pyrazolo[1,5-a]pyrimidine (Dinaciclib, SCH 727965), 2-(1-ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine (roscovitine), olomoucine, AG-024322, AT-7519, P276-00, R547/Ro-4584820 and SNS-032/BMS-387032. Repressed by the CDK inhibitors CDKN1A/p21 and CDKN1B/p27 during the G1 phase and by CDKN1A/p21 at the G1-S checkpoint upon DNA damage. Transient activation by rapid and transient dephosphorylation at Tyr-15 triggered by TGFB1.SUBUNIT Forms a stable but non-covalent complex with a regulatory subunit and with a cyclin. Interacts with cyclins-B (CCNB1, CCNB2 and CCNB3) to form a serine/threonine kinase holoenzyme complex also known as maturation promoting factor (MPF). The cyclin subunit imparts substrate specificity to the complex. Can also form CDK1-cylin-D and CDK1-cyclin-E complexes that phosphorylate RB1 in vitro. Binds to RB1 and other transcription factors such as FOXO1 and RUNX2. Promotes G2-M transition when in complex with a cyclin-B. Interacts with DLGAP5. Binds to the CDK inhibitors CDKN1A/p21 and CDKN1B/p27. Isoform 2 is unable to complex with cyclin-B1 and also fails to bind to CDKN1A/p21. Interacts with catalytically active CCNB1 and RALBP1 during mitosis to form an endocytotic complex during interphase. Associates with cyclins-A and B1 during S-phase in regenerating hepatocytes. Interacts with FANCC. Interacts with CEP63; this interaction recruits CDK1 to centrosomes. Interacts with CENPA (PubMed:25556658). Interacts with NR1D1 (PubMed:27238018). Interacts with proteasome subunit PSMA8; to participate in meiosis progression during spermatogenesis (By similarity).TISSUE SPECIFICITY Isoform 2 is found in breast cancer tissues.INDUCTION Follows a cyclic expression; during interphase, accumulates gradually following G1, S to reach a critical threshold at the end of G2, which promotes self-activation and triggers onset of mitosis. Induced transiently by TGFB1 at an early phase of TGFB1-mediated apoptosis, but later repressed. Triggered by CKS1B during mitotic entry in breast cancer cells. Down-regulated under genotoxic stresses triggered by PKR/EIF2AK2-mediated phosphorylation.PTM Phosphorylation at Thr-161 by CAK/CDK7 activates kinase activity. Phosphorylation at Thr-14 and Tyr-15 by PKMYT1 prevents nuclear translocation. Phosphorylation at Tyr-15 by WEE1 and WEE2 inhibits the protein kinase activity and acts as a negative regulator of entry into mitosis (G2 to M transition). Phosphorylation by PKMYT1 and WEE1 takes place during mitosis to keep CDK1-cyclin-B complexes inactive until the end of G2. By the end of G2, PKMYT1 and WEE1 are inactivated, but CDC25A and CDC25B are activated. Dephosphorylation by active CDC25A and CDC25B at Thr-14 and Tyr-15, leads to CDK1 activation at the G2-M transition. Phosphorylation at Tyr-15 by WEE2 during oogenesis is required to maintain meiotic arrest in oocytes during the germinal vesicle (GV) stage, a long period of quiescence at dictyate prophase I, leading to prevent meiotic reentry. Phosphorylation by WEE2 is also required for metaphase II exit during egg activation to ensure exit from meiosis in oocytes and promote pronuclear formation. Phosphorylated at Tyr-4 by PKR/EIF2AK2 upon genotoxic stress. This phosphorylation triggers CDK1 polyubiquitination and subsequent proteolysis, thus leading to G2 arrest. In response to UV irradiation, phosphorylation at Tyr-15 by PRKCD activates the G2/M DNA damage checkpoint.PTM Polyubiquitinated upon genotoxic stress.MISCELLANEOUS As a key regulator of the cell cycle, CDK1 is a potent therapeutic target for inhibitors in cancer treatment.SIMILARITY Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily. UniProt P06493 1 EQUAL 297 EQUAL Reactome Database ID Release 81 170075 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=170075 Reactome R-HSA-170075 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-170075.1 1 DCTN1-2 Dynactin 1 isoform 2 Reactome DB_ID: 380301 UniProt:Q14203-2 DCTN1 DCTN1 FUNCTION Plays a key role in dynein-mediated retrograde transport of vesicles and organelles along microtubules by recruiting and tethering dynein to microtubules. Binds to both dynein and microtubules providing a link between specific cargos, microtubules and dynein. Essential for targeting dynein to microtubule plus ends, recruiting dynein to membranous cargos and enhancing dynein processivity (the ability to move along a microtubule for a long distance without falling off the track). Can also act as a brake to slow the dynein motor during motility along the microtubule (PubMed:25185702). Can regulate microtubule stability by promoting microtubule formation, nucleation and polymerization and by inhibiting microtubule catastrophe in neurons. Inhibits microtubule catastrophe by binding both to microtubules and to tubulin, leading to enhanced microtubule stability along the axon (PubMed:23874158). Plays a role in metaphase spindle orientation (PubMed:22327364). Plays a role in centriole cohesion and subdistal appendage organization and function. Its recruitment to the centriole in a KIF3A-dependent manner is essential for the maintenance of centriole cohesion and the formation of subdistal appendage. Also required for microtubule anchoring at the mother centriole (PubMed:23386061). Plays a role in primary cilia formation (PubMed:25774020).SUBUNIT Monomer and homodimer (PubMed:23874158). Dynactin is a large macromolecular complex of at least 10 components; p150(glued) binds directly to microtubules and to cytoplasmic dynein. Interacts with the C-terminus of MAPRE1, MAPRE2 and MAPRE3. Interacts (via C-terminus) with SNX6. Interacts with CLN3, DYNAP, ECPAS and FBXL5. Interacts with MISP; this interaction regulates its distribution at the cell cortex. Interacts with CEP131. Interacts with CEP126 (PubMed:24867236). Interacts with CLIP1 (PubMed:17828275, PubMed:17828277, PubMed:26972003, PubMed:20679239). Interacts with dynein intermediate chain and dynein heavy chain (PubMed:25185702). Interacts with PLK1 (via POLO-box domain) (PubMed:20679239). Interacts with TBCB (PubMed:22777741). Binds preferentially to tyrosinated microtubules than to detyrosinated microtubules (PubMed:26972003, PubMed:26968983). Interacts with PARD6A (PubMed:20719959). Interacts with HPS6 (PubMed:25189619). Interacts with KIF3A. Interacts with BICD2 (By similarity). Interacts with DST (isoform 9) (By similarity). Interacts with DST (isoform 1) (By similarity). Identified in a complex with MREG and RILP (By similarity). Interacts with BCCIP (isoform 2/alpha) (PubMed:28394342). Interacts with DCDC1 (PubMed:22159412). Interacts with AKNA (By similarity). Interacts with DYNC1I2 (By similarity).TISSUE SPECIFICITY Brain.DOMAIN The CAP-Gly domain is essential for interactions with microtubules and its binding partners and for its motion along the microtubules. Essential for its preferential binding to tyrosinated microtubules and for promoting the sustained interaction of the dynein motor with microtubules.PTM Ubiquitinated by a SCF complex containing FBXL5, leading to its degradation by the proteasome.PTM Phosphorylation by SLK at Thr-145, Thr-146 and Thr-147 targets DCTN1 to the centrosome. It is uncertain if SLK phosphorylates all three threonines or one or two of them. PLK1-mediated phosphorylation at Ser-179 is essential for its localization in the nuclear envelope, promotes its dissociation from microtubules during early mitosis and positively regulates nuclear envelope breakdown during prophase.SIMILARITY Belongs to the dynactin 150 kDa subunit family. UniProt Isoform Q14203-2 1 EQUAL 1278 EQUAL Reactome Database ID Release 81 380301 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380301 Reactome R-HSA-380301 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380301.1 1 FOP FGFR1OP Reactome DB_ID: 380309 UniProt:O95684 CEP43 CEP43 FGFR1OP FOP FUNCTION Required for anchoring microtubules to the centrosomes (PubMed:16314388, PubMed:28659385). Required for ciliation (PubMed:28625565, PubMed:28659385).SUBUNIT Homodimer (PubMed:16690081). Part of a ternary complex that contains CEP350, CEP43 and MAPRE1. Interacts directly with CEP350 and MAPRE1 (PubMed:16314388). Interacts with CEP19 (PubMed:28625565, PubMed:28428259, PubMed:28659385). Interacts (via N-terminus) with CEP350 (via C-terminus) (PubMed:28625565, PubMed:28428259).TISSUE SPECIFICITY Ubiquitous. Highly expressed in heart, liver, muscle, kidney, intestine, colon, adrenal gland, prostate, testis, and pancreas.DISEASE A chromosomal aberration involving CEP43 may be a cause of stem cell myeloproliferative disorder (MPD). Translocation t(6;8)(q27;p11) with FGFR1. MPD is characterized by myeloid hyperplasia, eosinophilia and T-cell or B-cell lymphoblastic lymphoma. In general it progresses to acute myeloid leukemia. The fusion proteins CEP43-FGFR1 or FGFR1-CEP43 may exhibit constitutive kinase activity and be responsible for the transforming activity (PubMed:9949182).SIMILARITY Belongs to the CEP43 family.CAUTION Interacting region of CEP19 is conflicting: According to a report, interacts via N-terminus (PubMed:28428259). According to another report, interacts via C-terminus (PubMed:28659385). UniProt O95684 1 EQUAL 399 EQUAL Reactome Database ID Release 81 380309 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380309 Reactome R-HSA-380309 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380309.1 1 TOG CKAP5 Reactome DB_ID: 377729 UniProt:Q14008 CKAP5 CKAP5 KIAA0097 FUNCTION Binds to the plus end of microtubules and regulates microtubule dynamics and microtubule organization. Acts as processive microtubule polymerase. Promotes cytoplasmic microtubule nucleation and elongation. Plays a major role in organizing spindle poles. In spindle formation protects kinetochore microtubules from depolymerization by KIF2C and has an essential role in centrosomal microtubule assembly independently of KIF2C activity. Contributes to centrosome integrity. Acts as component of the TACC3/ch-TOG/clathrin complex proposed to contribute to stabilization of kinetochore fibers of the mitotic spindle by acting as inter-microtubule bridge. The TACC3/ch-TOG/clathrin complex is required for the maintenance of kinetochore fiber tension (PubMed:23532825). Enhances the strength of NDC80 complex-mediated kinetochore-tip microtubule attachments (PubMed:27156448).SUBUNIT Interacts with TACC1 (PubMed:11903063). Interacts with SLAIN2 and SLAIN1 (PubMed:21646404). Interacts with HNRNPA2B1 (PubMed:15703215). Interacts with TACC3 independently of clathrin (PubMed:25596274). Interacts with TACC3 and clathrin forming the TACC3/ch-TOG/clathrin complex located at spindle inter-microtubules bridges (PubMed:21297582, PubMed:23532825). Interacts with NDC80; indicative for an association with the NDC80 complex (PubMed:27156448).TISSUE SPECIFICITY Overexpressed in hepatomas and colonic tumors. Also expressed in skeletal muscle, brain, heart, placenta, lung, liver, kidney and pancreas. Expression is elevated in the brain; highly expressed in the Purkinje cell bodies of the cerebellum.DOMAIN The TOG (tumor overexpressed gene) domains are arranged in a N-terminal pentameric array with each domain composed of six (for the most part non-canonical) HEAT repeats forming a oblong paddle-like structure. Intra-HEAT loops are positioned along a face of the TOG domain and bind to a single alpha/beta-tubulin heterodimer. The TOG domains in the array seem to be structurally and functionally polarized. Differential functions may range from microtubule (MT) lattice binding and/or free tubulin heterodimer binding to potentiating stable incorporation of tubulin into the MT lattice.SIMILARITY Belongs to the TOG/XMAP215 family. UniProt Q14008 1 EQUAL 2032 EQUAL Reactome Database ID Release 81 377729 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=377729 Reactome R-HSA-377729 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-377729.1 1 HSP90 HSP90AA1 Reactome DB_ID: 192864 UniProt:P07900 HSP90AA1 HSP90AA1 HSP90A HSPC1 HSPCA FUNCTION Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity which is essential for its chaperone activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function (PubMed:11274138, PubMed:15577939, PubMed:15937123, PubMed:27353360, PubMed:29127155, PubMed:12526792). Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself (PubMed:29127155). Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle (PubMed:27295069, PubMed:26991466). Plays a critical role in mitochondrial import, delivers preproteins to the mitochondrial import receptor TOMM70 (PubMed:12526792). Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels (PubMed:25973397). In the first place, they alter the steady-state levels of certain transcription factors in response to various physiological cues(PubMed:25973397). Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment (PubMed:25973397). Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression (PubMed:25973397). Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:11276205). Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation (PubMed:24613385). Mediates the association of TOMM70 with IRF3 or TBK1 in mitochondrial outer membrane which promotes host antiviral response (PubMed:20628368, PubMed:25609812).ACTIVITY REGULATION In the resting state, through the dimerization of its C-terminal domain, HSP90 forms a homodimer which is defined as the open conformation (PubMed:18400751). Upon ATP-binding, the N-terminal domain undergoes significant conformational changes and comes in contact to form an active closed conformation (PubMed:18400751). After HSP90 finishes its chaperoning tasks of assisting the proper folding, stabilization and activation of client proteins under the active state, ATP molecule is hydrolyzed to ADP which then dissociates from HSP90 and directs the protein back to the resting state (PubMed:18400751). Co-chaperone TSC1 promotes ATP binding and inhibits HSP90AA1 ATPase activity (PubMed:29127155). Binding to phosphorylated AHSA1 promotes HSP90AA1 ATPase activity (PubMed:29127155). Inhibited by geldanamycin, Ganetespib (STA-9090) and SNX-2112 (PubMed:29127155, PubMed:12526792).SUBUNIT Homodimer (PubMed:7588731, PubMed:8289821, PubMed:18400751, PubMed:29127155). Identified in NR3C1/GCR steroid receptor-chaperone complexes formed at least by NR3C1, HSP90AA1 and a variety of proteins containing TPR repeats such as FKBP4, FKBP5, PPID, PPP5C or STIP1 (PubMed:15383005, PubMed:9195923). Forms a complex containing HSP90AA1, TSC1 and TSC2; TSC1 is required to recruit TCS2 to the complex (PubMed:29127155). The closed form interacts (via the middle domain and TPR repeat-binding motif) with co-chaperone TSC1 (via C-terminus) (PubMed:29127155). Interacts with TOM34 (PubMed:9660753). Interacts with TERT; the interaction, together with PTGES3, is required for correct assembly and stabilization of the TERT holoenzyme complex (PubMed:11274138, PubMed:9817749). Interacts with CHORDC1 and DNAJC7 (PubMed:12853476, PubMed:19875381). Interacts with STUB1 and UBE2N; may couple the chaperone and ubiquitination systems (PubMed:16307917, PubMed:27353360). Interacts (via TPR repeat-binding motif) with PPP5C (via TPR repeats); the interaction is direct and activates PPP5C phosphatase activity (PubMed:15383005, PubMed:15577939, PubMed:16531226, PubMed:27353360). Following LPS binding, may form a complex with CXCR4, GDF5 and HSPA8 (PubMed:11276205). Interacts with KSR1 (PubMed:10409742). Interacts with co-chaperone CDC37 (via C-terminus); the interaction inhibits HSP90AA1 ATPase activity (PubMed:23569206, PubMed:27353360). May interact with NWD1 (PubMed:24681825). Interacts with FNIP1 and FNIP2; the interaction inhibits HSP90AA1 ATPase activity (PubMed:17028174, PubMed:27353360). Interacts with co-chaperone AHSA1 (phosphorylated on 'Tyr-223'); the interaction activates HSP90AA1 ATPase activity and results in the dissociation of TSC1 from HSP90AA1 (PubMed:12604615, PubMed:27353360, PubMed:29127155). Interacts with FLCN in the presence of FNIP1 (PubMed:27353360). Interacts with HSP70, STIP1 and PTGES3 (PubMed:27353360). Interacts with SMYD3; this interaction enhances SMYD3 histone-lysine N-methyltransferase (PubMed:15235609, PubMed:25738358). Interacts with SGTA (via TPR repeats) (PubMed:15708368). Interacts with TTC1 (via TPR repeats) (PubMed:15708368). Interacts with HSF1 in an ATP-dependent manner (PubMed:11583998. PubMed:26517842). Interacts with MET; the interaction suppresses MET kinase activity (PubMed:26517842). Interacts with ERBB2 in an ATP-dependent manner; the interaction suppresses ERBB2 kinase activity (PubMed:26517842). Interacts with HIF1A, KEAP1 and RHOBTB2 (PubMed:26517842). Interacts with HSF1; this interaction is decreased in a IER5-dependent manner, promoting HSF1 accumulation in the nucleus, homotrimerization and DNA-binding activities (PubMed:26754925). Interacts with STUB1 and SMAD3 (PubMed:24613385). Interacts with HSP90AB1; interaction is constitutive (PubMed:20353823). Interacts with HECTD1 (via N-terminus) (By similarity). Interacts with NR3C1 (via domain NR LBD) and NR1D1 (via domain NR LBD) (By similarity). Interacts with NLPR12 (PubMed:30559449, PubMed:17947705). Interacts with PDCL3 (By similarity). Interacts with TOMM70; the interaction is required for preprotein mitochondrial import (PubMed:12526792). Interacts with TOMM70, IRF3 and TBK1; the interactions are direct and mediate the association of TOMM70 with IRF3 and TBK1 (PubMed:20628368).SUBUNIT (Microbial infection) Interacts with herpes simplex virus 1 protein US11; this interaction inhibits TBK1-induced interferon production.DOMAIN The TPR repeat-binding motif mediates interaction with TPR repeat-containing proteins like the co-chaperone STUB1.PTM ISGylated.PTM S-nitrosylated; negatively regulates the ATPase activity and the activation of eNOS by HSP90AA1.PTM Ubiquitinated via 'Lys-63'-linked polyubiquitination by HECTD1. Ubiquitination promotes translocation into the cytoplasm away from the membrane and secretory pathways.SIMILARITY Belongs to the heat shock protein 90 family. UniProt P07900 2 EQUAL 732 EQUAL Reactome Database ID Release 81 192864 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=192864 Reactome R-HSA-192864 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-192864.1 1 CEP63 Cep63 Reactome DB_ID: 380267 UniProt:Q96MT8 CEP63 CEP63 FUNCTION Required for normal spindle assembly. Plays a key role in mother-centriole-dependent centriole duplication; the function seems also to involve CEP152, CDK5RAP2 and WDR62 through a stepwise assembled complex at the centrosome that recruits CDK2 required for centriole duplication. Reported to be required for centrosomal recruitment of CEP152; however, this function has been questioned (PubMed:21983783, PubMed:26297806). Also recruits CDK1 to centrosomes (PubMed:21406398). Plays a role in DNA damage response. Following DNA damage, such as double-strand breaks (DSBs), is removed from centrosomes; this leads to the inactivation of spindle assembly and delay in mitotic progression (PubMed:21406398).SUBUNIT Interacts with CEP152 and CDK1; these interactions recruit both ligands to centrosomes (PubMed:21406398). Interacts with CDK2, CDK5RAP2, WDR62, CEP90, KIAA0753/moonraker and CCDC14. CEP63, CDK5RAP2, CEP152, WDR62 are proposed to form a stepwise assembled complex at the centrosome forming a ring near parental centrioles (PubMed:21406398, PubMed:26297806). Interacts with CCDC57; the interaction is required for their location to proximal end of centrioles (PubMed:32402286).MISCELLANEOUS CEP63 and DEUP1 paralogs are both involved in centriole amplification: while CEP63 mediates mother-centriole-dependent centriole duplication, DEUP1 mediates de novo centriole amplification in multiciliated cells.SIMILARITY Belongs to the CEP63 family. UniProt Q96MT8 1 EQUAL 703 EQUAL Reactome Database ID Release 81 380267 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380267 Reactome R-HSA-380267 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380267.1 1 CEP76 Cep76 Reactome DB_ID: 380281 UniProt:Q8TAP6 CEP76 CEP76 C18orf9 FUNCTION Centrosomal protein involved in regulation of centriole duplication. Required to limit centriole duplication to once per cell cycle by preventing centriole reduplication.SUBUNIT Interacts with CCP110 and CEP97.DEVELOPMENTAL STAGE Expressed at low level in G1 and is induced in S and G2 phase, during which point centrioles have already commenced duplication (at protein level).SIMILARITY Belongs to the CEP76 family. UniProt Q8TAP6 1 EQUAL 659 EQUAL Reactome Database ID Release 81 380281 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380281 Reactome R-HSA-380281 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380281.1 1 NEK2 Nek2A Reactome DB_ID: 177329 UniProt:P51955 NEK2 NEK2 NEK2A NLK1 FUNCTION Protein kinase which is involved in the control of centrosome separation and bipolar spindle formation in mitotic cells and chromatin condensation in meiotic cells. Regulates centrosome separation (essential for the formation of bipolar spindles and high-fidelity chromosome separation) by phosphorylating centrosomal proteins such as CROCC, CEP250 and NINL, resulting in their displacement from the centrosomes. Regulates kinetochore microtubule attachment stability in mitosis via phosphorylation of NDC80. Involved in regulation of mitotic checkpoint protein complex via phosphorylation of CDC20 and MAD2L1. Plays an active role in chromatin condensation during the first meiotic division through phosphorylation of HMGA2. Phosphorylates: PPP1CC; SGO1; NECAB3 and NPM1. Essential for localization of MAD2L1 to kinetochore and MAPK1 and NPM1 to the centrosome. Phosphorylates CEP68 and CNTLN directly or indirectly (PubMed:24554434). NEK2-mediated phosphorylation of CEP68 promotes CEP68 dissociation from the centrosome and its degradation at the onset of mitosis (PubMed:25704143). Involved in the regulation of centrosome disjunction (PubMed:26220856).ACTIVITY REGULATION Isoform 1 is inhibited by ionizing radiation in the presence of PPP1CA. Its catalytic activity is inhibited by the inhibitor CCT241950. In the presence of this inhibitor, displays an autoinhibited conformation: Tyr-70 side chain points into the active site, interacts with the activation loop, and blocks the alphaC helix.SUBUNIT Isoform 1, isoform 2 and isoform 4 form homo- and heterodimers. Interacts with NECAB3 and HMGA2 (By similarity). Isoform 1 interacts with CDC20, CTNB1, MAD1L1, MAPK, NEK11, NPM1, NDC80, PCNT and SGO1 (PubMed:14978040, PubMed:15358203, PubMed:15388344, PubMed:15161910, PubMed:17621308, PubMed:18086858, PubMed:18297113, PubMed:20599736, PubMed:20034488). Isoform 1 interacts with STK3/MST2 (via SARAH domain) and SAV1 (via SARAH domain) (PubMed:21076410). Isoform 1 and isoform 2 interact with MAD2L1 (PubMed:20034488). Isoform 1 and isoform 4 interact with PPP1CA and PPP1CC (PubMed:15659832, PubMed:17283141). Interacts with CEP68; the interaction leads to phosphorylation of CEP68. Interacts with CNTLN; the interaction leads to phosphorylation of CNTLN (PubMed:24554434). Isoform 1 interacts with CEP85 (PubMed:26220856).TISSUE SPECIFICITY Isoform 1 and isoform 2 are expressed in peripheral blood T-cells and a wide variety of transformed cell types. Isoform 1 and isoform 4 are expressed in the testis. Up-regulated in various cancer cell lines, as well as primary breast tumors.INDUCTION Expression and activity peak in the G2 phase of the mitotic cycle and decrease once the cells have entered mitosis due to degradation by the anaphase promoting complex APC/C-CDC20. In G1 phase, both isoform 1 and isoform 2 are almost undetectable. However, at the G1/S transition, there is an increase in expression of both isoforms which then remain at this increased level throughout S and G2. At the onset of mitosis, isoform 1 undergoes a rapid disappearance whereas isoform 2 continues to be present at about the same level as in G2. During the rest of mitosis, isoform 1 remains absent, while isoform 2 only begins to decline upon re-entry into the next G1 phase.DOMAIN The leucine-zipper domain is required for its dimerization and activation.PTM Activated by autophosphorylation. Protein phosphatase 1 represses autophosphorylation and activation of isoform 1 by dephosphorylation. Phosphorylation by STK3/MST2 is necessary for its localization to the centrosome.SIMILARITY Belongs to the protein kinase superfamily. NEK Ser/Thr protein kinase family. NIMA subfamily. UniProt P51955 1 EQUAL 445 EQUAL Reactome Database ID Release 81 177329 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=177329 Reactome R-HSA-177329 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-177329.1 1 YWHAE 14-3-3 protein epsilon 143E_HUMAN 14-3-3 epsilon Reactome DB_ID: 194368 UniProt:P62258 YWHAE YWHAE FUNCTION Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner (By similarity). Positively regulates phosphorylated protein HSF1 nuclear export to the cytoplasm (PubMed:12917326).SUBUNIT Homodimer (PubMed:17085597). Heterodimerizes with YWHAZ (PubMed:16376338). Interacts with PKA-phosphorylated AANAT (PubMed:11427721). Interacts with ABL1 (phosphorylated form); the interaction retains it in the cytoplasm (PubMed:15696159). Interacts with ARHGEF28 (By similarity). Interacts with BEX3 (By similarity). Weakly interacts with CDKN1B (PubMed:12042314). Interacts with the 'Thr-369' phosphorylated form of DAPK2 (PubMed:26047703). Interacts with DENND1A (PubMed:26055712). Interacts with GAB2 (PubMed:19172738). Interacts with phosphorylated GRB10 (PubMed:15722337). Interacts with KSR1 (PubMed:10409742). Interacts with NDEL1 (By similarity). Interacts with PI4KB, TBC1D22A and TBC1D22B (PubMed:23572552). Interacts with the phosphorylated (by AKT1) form of SRPK2 (PubMed:19592491). Interacts with TIAM2. Interacts with the 'Ser-1134' and 'Ser-1161' phosphorylated form of SOS1 (By similarity). Interacts with ZFP36 (via phosphorylated form) (By similarity). Interacts with SLITRK1 (PubMed:19640509). Interacts with HSF1 (via phosphorylated form); this interaction promotes HSF1 sequestration in the cytoplasm in a ERK-dependent manner (PubMed:12917326). Interacts with RIPOR2 isoform 2 (PubMed:25588844). Interacts with KLHL22; required for the nuclear localization of KLHL22 upon amino acid starvation (PubMed:29769719). Interacts with CRTC1 (PubMed:30611118). Interacts with CRTC2 (probably when phosphorylated at 'Ser-171') (PubMed:30611118). Interacts with CRTC3 (probably when phosphorylated at 'Ser-162' and/or 'Ser-273') (PubMed:30611118). Interacts with ATP2B1 and ATP2B3; this interaction inhibits calcium-transporting ATPase activity (PubMed:18029012). Interacts with MEFV (PubMed:27030597).SUBUNIT (Microbial infection) Interacts with HCV core protein.SIMILARITY Belongs to the 14-3-3 family. UniProt P62258 1 EQUAL 255 EQUAL Reactome Database ID Release 81 194368 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=194368 Reactome R-HSA-194368 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-194368.1 1 TUBB4A beta tubulin 5 Reactome DB_ID: 190588 UniProt:P04350 TUBB4A TUBB4A TUBB4 TUBB5 FUNCTION Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.SUBUNIT Dimer of alpha and beta chains. A typical microtubule is a hollow water-filled tube with an outer diameter of 25 nm and an inner diameter of 15 nM. Alpha-beta heterodimers associate head-to-tail to form protofilaments running lengthwise along the microtubule wall with the beta-tubulin subunit facing the microtubule plus end conferring a structural polarity. Microtubules usually have 13 protofilaments but different protofilament numbers can be found in some organisms and specialized cells.TISSUE SPECIFICITY Major isotype in brain, where it represents 46% of all beta-tubulins. In the brain, highest expression levels in the cerebellum, followed by putamen and white matter. Moderate levels in testis. Very low levels, if any, in other tissues.DOMAIN The highly acidic C-terminal region may bind cations such as calcium.DOMAIN The MREI motif is common among all beta-tubulin isoforms and may be critical for tubulin autoregulation.PTM Some glutamate residues at the C-terminus are polyglutamylated, resulting in polyglutamate chains on the gamma-carboxyl group (PubMed:26875866). Polyglutamylation plays a key role in microtubule severing by spastin (SPAST). SPAST preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity by SPAST increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold (PubMed:26875866). Glutamylation is also involved in cilia motility (By similarity).PTM Some glutamate residues at the C-terminus are monoglycylated but not polyglycylated due to the absence of functional TTLL10 in human. Monoglycylation is mainly limited to tubulin incorporated into cilia and flagella axonemes, which is required for their stability and maintenance. Flagella glycylation controls sperm motility. Both polyglutamylation and monoglycylation can coexist on the same protein on adjacent residues, and lowering glycylation levels increases polyglutamylation, and reciprocally.PTM Phosphorylated on Ser-172 by CDK1 during the cell cycle, from metaphase to telophase, but not in interphase. This phosphorylation inhibits tubulin incorporation into microtubules.SIMILARITY Belongs to the tubulin family. UniProt P04350 1 EQUAL 444 EQUAL Reactome Database ID Release 81 190588 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=190588 Reactome R-HSA-190588 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-190588.1 1 ODF2 Reactome DB_ID: 380293 UniProt:Q5BJF6 ODF2 ODF2 FUNCTION Seems to be a major component of sperm tail outer dense fibers (ODF). ODFs are filamentous structures located on the outside of the axoneme in the midpiece and principal piece of the mammalian sperm tail and may help to maintain the passive elastic structures and elastic recoil of the sperm tail. May have a modulating influence on sperm motility. Functions as a general scaffold protein that is specifically localized at the distal/subdistal appendages of mother centrioles. Component of the centrosome matrix required for the localization of PLK1 and NIN to the centrosomes. Required for the formation and/or maintenance of normal CETN1 assembly.SUBUNIT Self-associates. Associates with microtubules and forms a fibrillar structure partially linked to the microtubule network. Interacts via its C-terminus with PLK1 (PubMed:16966375). Interacts with ODF1 (By similarity). Interacts with MARK4; the interaction is required for localization of ODF2 to centrioles (PubMed:23400999). Interacts with TSSK4 (By similarity). Interacts with AKNA (By similarity). Interacts with QRICH2 (PubMed:30683861). Interacts with CFAP58 (By similarity).TISSUE SPECIFICITY Testis-specific (at protein level). Highly expressed in cytoplasm of step 2 round spermatids. Detected in the middle piece and extends to about half the principal piece of the sperm tails.PTM Tyrosine phosphorylated. Phosphorylated by TSSK4 on Ser-95.SIMILARITY Belongs to the ODF2 family. UniProt Q5BJF6 1 EQUAL 829 EQUAL Reactome Database ID Release 81 380293 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380293 Reactome R-HSA-380293 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380293.1 1 OFD1 Reactome DB_ID: 380318 UniProt:O75665 OFD1 OFD1 CXorf5 FUNCTION Component of the centrioles controlling mother and daughter centrioles length. Recruits to the centriole IFT88 and centriole distal appendage-specific proteins including CEP164. Involved in the biogenesis of the cilium, a centriole-associated function. The cilium is a cell surface projection found in many vertebrate cells required to transduce signals important for development and tissue homeostasis. Plays an important role in development by regulating Wnt signaling and the specification of the left-right axis. Only OFD1 localized at the centriolar satellites is removed by autophagy, which is an important step in the ciliogenesis regulation (By similarity).SUBUNIT Homooligomer. Interacts with LCA5. Interacts with RUVBL1; the interaction is direct and may mediate interaction with the NuA4 histone acetyltransferase complex. Interacts with SDCCAG8; the interaction is direct. Interacts with MAP1LC3B. Interacts with C2CD3; OFD1 may act as a negative regulator of C2CD3. Forms a complex with KIAA0753/OFIP and CEP20/FOR20; the interaction with CEP20 is detected only in the presence of KIAA0753. Interacts with PCM1; this interaction may be mediated by KIAA0753/OFIP (PubMed:26643951).TISSUE SPECIFICITY Widely expressed. Expressed in 9 and 14 weeks old embryos in metanephric mesenchyme, oral mucosa, lung, heart, nasal and cranial cartilage, and brain. Expressed in metanephros, brain, tongue, and limb.SIMILARITY Belongs to the OFD1 family. UniProt O75665 1 EQUAL 1012 EQUAL Reactome Database ID Release 81 380318 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380318 Reactome R-HSA-380318 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380318.1 1 CEP72 Cep72 Reactome DB_ID: 380321 UniProt:Q9P209 CEP72 CEP72 KIAA1519 FUNCTION Involved in the recruitment of key centrosomal proteins to the centrosome. Provides centrosomal microtubule-nucleation activity on the gamma-tubulin ring complexes (gamma-TuRCs) and has critical roles in forming a focused bipolar spindle, which is needed for proper tension generation between sister chromatids. Required for localization of KIZ, AKAP9 and gamma-tubulin ring complexes (gamma-TuRCs) (PubMed:19536135). Involved in centriole duplication. Required for CDK5RAP22, CEP152, WDR62 and CEP63 centrosomal localization and promotes the centrosomal localization of CDK2 (PubMed:26297806).SUBUNIT Interacts with KIZ, PCM1 and CDK5RAP2.SIMILARITY Belongs to the CEP72 family. UniProt Q9P209 1 EQUAL 647 EQUAL Reactome Database ID Release 81 380321 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380321 Reactome R-HSA-380321 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380321.1 1 CEP41 Cep41 Reactome DB_ID: 380269 UniProt:Q9BYV8 CEP41 CEP41 TSGA14 FUNCTION Required during ciliogenesis for tubulin glutamylation in cilium. Probably acts by participating in the transport of TTLL6, a tubulin polyglutamylase, between the basal body and the cilium.SUBUNIT Found in a complex with TTLL6.DOMAIN Although it contains a rhodanese domain, does not display phosphatase activity, suggesting that the protein is enzymatically inactive.DISEASE Genetic variations in CEP41 may be associated with susceptibility to autism (PubMed:21438139).SIMILARITY Belongs to the CEP41 family. UniProt Q9BYV8 1 EQUAL 373 EQUAL Reactome Database ID Release 81 380269 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380269 Reactome R-HSA-380269 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380269.1 1 ALMS1 Reactome DB_ID: 380289 UniProt:Q8TCU4 ALMS1 ALMS1 KIAA0328 FUNCTION Involved in PCM1-dependent intracellular transport. Required, directly or indirectly, for the localization of NCAPD2 to the proximal ends of centrioles. Required for proper formation and/or maintenance of primary cilia (PC), microtubule-based structures that protrude from the surface of epithelial cells.TISSUE SPECIFICITY Expressed in all tissues tested including adipose and pancreas. Expressed by beta-cells of the islets in the pancreas (at protein level).DEVELOPMENTAL STAGE Widely expressed in fetal tissues. Detected in fetal pancreas, skeletal muscle, liver, kidney and brain (at protein level). Expressed in fetal aorta and brain.SIMILARITY Belongs to the ALMS1 family. UniProt Q8TCU4 1 EQUAL 4167 EQUAL Reactome Database ID Release 81 380289 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380289 Reactome R-HSA-380289 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380289.1 1 1 PCM1 PCM-1 Reactome DB_ID: 380308 UniProt:Q15154 PCM1 PCM1 FUNCTION Required for centrosome assembly and function (PubMed:12403812, PubMed:15659651, PubMed:16943179). Essential for the correct localization of several centrosomal proteins including CEP250, CETN3, PCNT and NEK2 (PubMed:12403812, PubMed:15659651). Required to anchor microtubules to the centrosome (PubMed:12403812, PubMed:15659651). Also involved in cilium biogenesis by recruiting the BBSome, a ciliary protein complex involved in cilium biogenesis, to the centriolar satellites (PubMed:20551181, PubMed:24121310, PubMed:27979967).SUBUNIT Self-associates. Interacts with C2CD3 (By similarity). Interacts with BBS4, BBS8, CETN3, HAP1, NDE1, NDEL1, MAP1LC3B, GABARAPAL2, and GABARAP (PubMed:12403812, PubMed:14520415, PubMed:15107855, PubMed:16291865, PubMed:24089205, PubMed:9361024). Interacts with CEP131; the interaction increases in response to ultraviolet light (UV) radiation (PubMed:24121310). Associates with microtubule; association to microtubule is reduced in response to cellular stress, such as ultraviolet light (UV) radiation or heat shock, in a process that requires p38 MAP kinase signaling (PubMed:24121310). Interacts with CCDC113 (PubMed:25074808). Interacts with SSX2IP (By similarity). Interacts with CCDC13 (PubMed:24816561). Interacts with CEP290 (By similarity). Interacts with PARD6A (PubMed:20719959). Interacts with KIAA0753/OFIP, CEP20/FOR20 and OFD1; the interaction with CEP20/FOR20 and OFD1 may be mediated by KIAA0753/OFIP (PubMed:26643951). Interacts with CCDC66 (PubMed:28235840). Interacts with CCDC61 (PubMed:31789463). Interacts with DZIP1; localizes DZIP1 and the associated BBSome to centriolar satellite (PubMed:27979967).TISSUE SPECIFICITY Expressed in blood, bone marrow, breast, lymph node, ovary and thyroid.INDUCTION Expression is reduced in breast and ovarian cancer.PTM Ubiquitinated. Undergoes monoubiquitination catalyzed by the E3 ubiquitin-protein ligase MIB1 in proliferating cells, preventing cilia formation (PubMed:24121310). Monoubiquitination by MIB1 is inhibited in response to cellular stress, such as ultraviolet light (UV) radiation or heat shock, resulting in cilia formation initiation (PubMed:24121310).PTM Variant Ser-159 is phosphorylated.PTM Phosphorylated on multiple serine and threonine residues by DYRK3 during the G2-to-M transition, after the nuclear-envelope breakdown (PubMed:29973724). Phosphorylation by DYRK3 promotes disassembly of pericentriolar material (PubMed:29973724). Phosphorylation at Ser-372 mediated by PLK4 is required to maintain the integrity of centriolar satellites (PubMed:30804208).DISEASE A chromosomal aberration involving PCM1 is found in papillary thyroid carcinomas (PTCs) (PubMed:10980597). Translocation t(8;10)(p21.3;q11.2) with RET links the protein kinase domain of RET to the major portion of PCM1 (PubMed:10980597).DISEASE A chromosomal aberration involving PCM1 is found in a variety of hematological malignancies including atypical chronic myeloid leukemia (atypical CML) and T-cell lymphoma (PubMed:15805263, PubMed:16034466, PubMed:16091753, PubMed:16769584, PubMed:16424865). Translocation t(8;9)(p22;p24) with JAK2 links the protein kinase domain of JAK2 to the major portion of PCM1 (PubMed:15805263, PubMed:16034466, PubMed:16091753, PubMed:16769584, PubMed:16424865).SIMILARITY Belongs to the PCM1 family. UniProt Q15154 1 EQUAL 2024 EQUAL Reactome Database ID Release 81 380308 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380308 Reactome R-HSA-380308 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380308.1 1 CCP110 Cep110 Reactome DB_ID: 380261 UniProt:O43303 CCP110 CCP110 CEP110 CP110 KIAA0419 FUNCTION Necessary for centrosome duplication at different stages of procentriole formation. Acts as a key negative regulator of ciliogenesis in collaboration with CEP97 by capping the mother centriole thereby preventing cilia formation (PubMed:17719545, PubMed:17681131, PubMed:23486064, PubMed:30375385). Also involved in promoting ciliogenesis. May play a role in the assembly of the mother centriole subdistal appendages (SDA) thereby effecting the fusion of recycling endosomes to basal bodies during cilia formation (By similarity). Required for correct spindle formation and has a role in regulating cytokinesis and genome stability via cooperation with CALM1 and CETN2 (PubMed:16760425).SUBUNIT Interacts with CALM1, CETN2, CEP76, CEP97, CEP104, CEP290, TALPID3. Seems to associate with discrete CETN2, CEP97 and CEP290-containing complexes. Interacts with NEURL4 and CCNF; these interactions are not mutually exclusive and both lead to CCP110 ubiquitination and proteasome-dependent degradation. Via its interaction with NEURL4, may indirectly interact with HERC2. Interacts with KIF24, leading to its recruitment to centrioles. Interacts with USP20 and USP33 (PubMed:23486064). Interacts with MPHOSPH9 (PubMed:30375385).TISSUE SPECIFICITY Highly expressed in testis. Detected at intermediate levels in spleen, thymus, prostate, small intestine, colon and peripheral blood leukocytes.INDUCTION Up-regulated during the transition from G1 to S phase of the cell cycle. The highest levels are observed in S phase, after which the levels decrease markedly.PTM Phosphorylated by CDKs.PTM Ubiquitinated by the SCF(CCNF) during G2 phase, leading to its degradation by the proteasome and preventing centrosome reduplication. Deubiquitinated by USP33 in S and G2/M phase, leading to stabilize CCP110 during the period which centrioles duplicate and elongate. UniProt O43303 1 EQUAL 1012 EQUAL Reactome Database ID Release 81 380261 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380261 Reactome R-HSA-380261 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380261.1 1 CEP164 Cep164 Reactome DB_ID: 380305 UniProt:Q9UPV0 CEP164 CEP164 KIAA1052 NPHP15 FUNCTION Plays a role in microtubule organization and/or maintenance for the formation of primary cilia (PC), a microtubule-based structure that protrudes from the surface of epithelial cells. Plays a critical role in G2/M checkpoint and nuclear divisions. A key player in the DNA damage-activated ATR/ATM signaling cascade since it is required for the proper phosphorylation of H2AX, RPA, CHEK2 and CHEK1. Plays a critical role in chromosome segregation, acting as a mediator required for the maintenance of genomic stability through modulation of MDC1, RPA and CHEK1.SUBUNIT Interacts (via N-terminus) with ATRIP. Interacts with ATM, ATR and MDC1. Interacts with XPA (via N-terminus) upon UV irradiation. Interacts with CEP83, CCDC92, TTBK2, DVL3, NPHP3 and weakly with NPHP4. Interacts with DZIP1 (By similarity).TISSUE SPECIFICITY Expressed in several cell lines.PTM Phosphorylation at Ser-186 is induced upon DNA-damage caused by treatment with IR irradiation, UV irradiation, hydroxyurea or amphidicolin. Also MDC1-mediated chromatin remodeling is critical for DNA damage-induced phosphorylation. UniProt Q9UPV0 1 EQUAL 1460 EQUAL Reactome Database ID Release 81 380305 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380305 Reactome R-HSA-380305 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380305.1 1 TUBB4B beta tubulin 2C Reactome DB_ID: 191702 UniProt:P68371 TUBB4B TUBB4B TUBB2C FUNCTION Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.SUBUNIT Dimer of alpha and beta chains. A typical microtubule is a hollow water-filled tube with an outer diameter of 25 nm and an inner diameter of 15 nM. Alpha-beta heterodimers associate head-to-tail to form protofilaments running lengthwise along the microtubule wall with the beta-tubulin subunit facing the microtubule plus end conferring a structural polarity. Microtubules usually have 13 protofilaments but different protofilament numbers can be found in some organisms and specialized cells.TISSUE SPECIFICITY Ubiquitous.DOMAIN The highly acidic C-terminal region may bind cations such as calcium.DOMAIN The MREI motif is common among all beta-tubulin isoforms and may be critical for tubulin autoregulation.PTM Some glutamate residues at the C-terminus are polyglutamylated, resulting in polyglutamate chains on the gamma-carboxyl group (PubMed:26875866). Polyglutamylation plays a key role in microtubule severing by spastin (SPAST). SPAST preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity by SPAST increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold (PubMed:26875866). Glutamylation is also involved in cilia motility (By similarity).PTM Some glutamate residues at the C-terminus are monoglycylated but not polyglycylated due to the absence of functional TTLL10 in human. Monoglycylation is mainly limited to tubulin incorporated into cilia and flagella axonemes, which is required for their stability and maintenance. Flagella glycylation controls sperm motility. Both polyglutamylation and monoglycylation can coexist on the same protein on adjacent residues, and lowering glycylation levels increases polyglutamylation, and reciprocally.PTM Phosphorylated on Ser-172 by CDK1 during the cell cycle, from metaphase to telophase, but not in interphase. This phosphorylation inhibits tubulin incorporation into microtubules.SIMILARITY Belongs to the tubulin family. UniProt P68371 1 EQUAL 445 EQUAL Reactome Database ID Release 81 191702 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=191702 Reactome R-HSA-191702 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-191702.1 1 DCTN2 Dynactin subunit 2 Dynamitin Reactome DB_ID: 380302 UniProt:Q13561 DCTN2 DCTN2 DCTN50 FUNCTION Modulates cytoplasmic dynein binding to an organelle, and plays a role in prometaphase chromosome alignment and spindle organization during mitosis. Involved in anchoring microtubules to centrosomes. May play a role in synapse formation during brain development.SUBUNIT Subunit of dynactin, a multiprotein complex associated with dynein. Interacts with BICD2 and CEP135 (By similarity). Interacts with DYNAP (PubMed:20978158). Interacts with ECPAS (PubMed:20682791). Interacts with MAPRE1 (PubMed:10226031).SIMILARITY Belongs to the dynactin subunit 2 family. UniProt Q13561 2 EQUAL 401 EQUAL Reactome Database ID Release 81 380302 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380302 Reactome R-HSA-380302 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380302.2 1 SFI1 Reactome DB_ID: 380265 UniProt:A8K8P3 SFI1 SFI1 KIAA0542 FUNCTION Plays a role in the dynamic structure of centrosome-associated contractile fibers via its interaction with CETN2.SUBUNIT Interacts with CETN2 (via C-terminus).DOMAIN CETN2-binding regions contains a conserved Trp residue in their C-terminal ends, which seems critical for interaction with CETN2.SIMILARITY Belongs to the SFI1 family.CAUTION It is uncertain whether Met-1 or Met-24 is the initiator. UniProt A8K8P3 1 EQUAL 1242 EQUAL Reactome Database ID Release 81 380265 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380265 Reactome R-HSA-380265 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380265.1 1 HAUS complex HAUS1:HAUS2:HAUS3:HAUS4:HAUS5:HAUS6:HAUS7:HAUS8 Reactome DB_ID: 8855211 HAUS3 HAUS augmin-like complex subunit 3 C4orf15 HAUS3_HUMAN Reactome DB_ID: 8855201 UniProt:Q68CZ6 HAUS3 HAUS3 C4orf15 FUNCTION Contributes to mitotic spindle assembly, maintenance of centrosome integrity and completion of cytokinesis as part of the HAUS augmin-like complex.SUBUNIT Component of the HAUS augmin-like complex. The complex interacts with the gamma-tubulin ring complex and this interaction is required for spindle assembly. Interacts with EML3 (phosphorylated at 'Thr-881') (PubMed:30723163).SIMILARITY Belongs to the HAUS3 family. UniProt Q68CZ6 2 EQUAL 603 EQUAL Reactome Database ID Release 81 8855201 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8855201 Reactome R-HSA-8855201 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8855201.1 1 HAUS5 HAUS augmin-like complex subunit 5 KIAA0841 HAUS5_HUMAN Reactome DB_ID: 8855197 UniProt:O94927 HAUS5 HAUS5 KIAA0841 FUNCTION Contributes to mitotic spindle assembly, maintenance of centrosome integrity and completion of cytokinesis as part of the HAUS augmin-like complex.SUBUNIT Component of the HAUS augmin-like complex. The complex interacts with the gamma-tubulin ring complex and this interaction is required for spindle assembly. Interacts with EML3 (phosphorylated at 'Thr-881') (PubMed:30723163).SIMILARITY Belongs to the HAUS5 family. UniProt O94927 1 EQUAL 633 EQUAL Reactome Database ID Release 81 8855197 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8855197 Reactome R-HSA-8855197 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8855197.1 1 HAUS8 HAUS augmin-like complex subunit 8 HEC1/NDC80-interacting centrosome-associated protein 1 Sarcoma antigen NY-SAR-48 HICE1 HAUS8_HUMAN Reactome DB_ID: 8855198 UniProt:Q9BT25 HAUS8 HAUS8 HICE1 FUNCTION Contributes to mitotic spindle assembly, maintenance of centrosome integrity and completion of cytokinesis as part of the HAUS augmin-like complex.SUBUNIT Component of the HAUS augmin-like complex. The complex interacts with the gamma-tubulin ring complex and this interaction is required for spindle assembly. Associates with microtubules. The interaction with microtubules is strong during mitosis, while it is weak or absent during interphase. It is unclear whether this interaction is direct or indirect. Interacts with EML3 (phosphorylated at 'Thr-881') and TUBG1 (PubMed:30723163).SIMILARITY Belongs to the HAUS8 family. UniProt Q9BT25 2 EQUAL 410 EQUAL Reactome Database ID Release 81 8855198 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8855198 Reactome R-HSA-8855198 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8855198.1 1 DGT6 HAUS6 HAUS augmin-like complex subunit 6 FAM29A KIAA1574 HAUS6_HUMAN Reactome DB_ID: 8855196 UniProt:Q7Z4H7 HAUS6 HAUS6 DGT6 FAM29A KIAA1574 FUNCTION Contributes to mitotic spindle assembly, maintenance of centrosome integrity and completion of cytokinesis as part of the HAUS augmin-like complex. Promotes the nucleation of microtubules from the spindle through recruitment of NEDD1 and gamma-tubulin.SUBUNIT Component of the HAUS augmin-like complex. The complex interacts with the gamma-tubulin ring complex and this interaction is required for spindle assembly (PubMed:19369198, PubMed:19427217). Interacts with PLK1, NEDD1 and gamma-tubulin (PubMed:19029337). Interacts with EML3 (phosphorylated at 'Thr-881') (PubMed:30723163).PTM Phosphorylated during mitosis.SIMILARITY Belongs to the HAUS6 family. UniProt Q7Z4H7 1 EQUAL 955 EQUAL Reactome Database ID Release 81 8855196 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8855196 Reactome R-HSA-8855196 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8855196.1 1 HAUS4 HAUS augmin-like complex subunit 4 C14orf94 HAUS4_HUMAN Reactome DB_ID: 8855202 UniProt:Q9H6D7 HAUS4 HAUS4 C14orf94 FUNCTION Contributes to mitotic spindle assembly, maintenance of centrosome integrity and completion of cytokinesis as part of the HAUS augmin-like complex.SUBUNIT Component of the HAUS augmin-like complex. The complex interacts with the gamma-tubulin ring complex and this interaction is required for spindle assembly. Interacts with EML3 (phosphorylated at 'Thr-881') (PubMed:30723163).SIMILARITY Belongs to the HAUS4 family. UniProt Q9H6D7 1 EQUAL 363 EQUAL Reactome Database ID Release 81 8855202 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8855202 Reactome R-HSA-8855202 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8855202.1 1 HAUS2 Cep27 HAUS2_HUMAN Reactome DB_ID: 380274 UniProt:Q9NVX0 HAUS2 HAUS2 C15orf25 CEP27 FUNCTION Contributes to mitotic spindle assembly, maintenance of centrosome integrity and completion of cytokinesis as part of the HAUS augmin-like complex.SUBUNIT Component of the HAUS augmin-like complex. The complex interacts with the gamma-tubulin ring complex and this interaction is required for spindle assembly. Interacts with EML3 (phosphorylated at 'Thr-881') (PubMed:30723163).SIMILARITY Belongs to the HAUS2 family. UniProt Q9NVX0 1 EQUAL 235 EQUAL Reactome Database ID Release 81 380274 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380274 Reactome R-HSA-380274 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380274.2 1 UIP1 HAUS7 HAUS augmin-like complex subunit 7 26S proteasome-associated UCH37-interacting protein 1 UCHL5-interacting protein UCHL5IP X-linked protein STS1769 HAUS7_HUMAN Reactome DB_ID: 8855200 UniProt:Q99871 HAUS7 HAUS7 UCHL5IP UIP1 FUNCTION Contributes to mitotic spindle assembly, maintenance of centrosome integrity and completion of cytokinesis as part of the HAUS augmin-like complex.SUBUNIT Component of the HAUS augmin-like complex. The complex interacts with the gamma-tubulin ring complex and this interaction is required for spindle assembly. Interacts with UCHL5 (PubMed:11163772). Interacts with EML3 (phosphorylated at 'Thr-881') (PubMed:30723163).TISSUE SPECIFICITY Detected in spleen, thymus, testis, ovary, small intestine and colon, with highest levels of expression in testis and ovary.SIMILARITY Belongs to the HAUS7 family. UniProt Q99871 1 EQUAL 368 EQUAL Reactome Database ID Release 81 8855200 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8855200 Reactome R-HSA-8855200 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8855200.1 1 HEIC HAUS1 HAUS augmin-like complex subunit 1 Coiled-coil domain-containing protein 5 Enhancer of invasion-cluster HEI-C CCDC5 HAUS1_HUMAN Reactome DB_ID: 8855199 UniProt:Q96CS2 HAUS1 HAUS1 CCDC5 HEIC FUNCTION Contributes to mitotic spindle assembly, maintenance of centrosome integrity and completion of cytokinesis as part of the HAUS augmin-like complex.SUBUNIT Component of the HAUS augmin-like complex. The complex interacts with the gamma-tubulin ring complex and this interaction is required for spindle assembly. Associates with microtubules. The interaction with microtubules is strong during mitosis, while it is weak or absent during interphase. It is unclear whether this interaction is direct or indirect. Interacts with EML3 (phosphorylated at 'Thr-881') (PubMed:30723163).TISSUE SPECIFICITY Widely expressed. Expressed in pancreas, kidney, skeletal muscle, liver and heart. Weakly expressed in lung, brain and placenta.MISCELLANEOUS HAUS1-depleted cells retain functional cell cycle checkpoints, but the depletion decreases the G2/M cell cycle compartment and induces apoptosis. The protein level remains constant through the cell cycle.SIMILARITY Belongs to the HAUS1 family. UniProt Q96CS2 1 EQUAL 278 EQUAL Reactome Database ID Release 81 8855199 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8855199 Reactome R-HSA-8855199 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8855199.1 1 Reactome Database ID Release 81 8855211 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8855211 Reactome R-HSA-8855211 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8855211.1 ComplexPortal CPX-1847 additional information MI MI:0361 1 CEP78 Cep78 Reactome DB_ID: 380304 UniProt:Q5JTW2 CEP78 CEP78 C9orf81 FUNCTION May be required for efficient PLK4 centrosomal localization and PLK4-induced overduplication of centrioles (PubMed:27246242). May play a role in cilium biogenesis (PubMed:27588451).SUBUNIT Interacts with PLK4 (PubMed:27246242). Interacts with FAM161A (PubMed:27588451).TISSUE SPECIFICITY Widely expressed (PubMed:27588451, PubMed:27588452). Expressed in different retinal cell types with higher expression in cone compared to rod cells (at protein level) (PubMed:27588452).DEVELOPMENTAL STAGE Expression is cell cycle-dependent, with low levels in mitosis. The expression starts to increase during late G1 until the S/G2 transition (at protein level).SIMILARITY Belongs to the CEP78 family. UniProt Q5JTW2 1 EQUAL 689 EQUAL Reactome Database ID Release 81 380304 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380304 Reactome R-HSA-380304 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380304.1 1 Cep215 CDK5RAP2 Reactome DB_ID: 380282 UniProt:Q96SN8 CDK5RAP2 CDK5RAP2 CEP215 KIAA1633 FUNCTION Potential regulator of CDK5 activity via its interaction with CDK5R1. Negative regulator of centriole disengagement (licensing) which maintains centriole engagement and cohesion. Involved in regulation of mitotic spindle orientation (By similarity). Plays a role in the spindle checkpoint activation by acting as a transcriptional regulator of both BUBR1 and MAD2 promoter. Together with EB1/MAPRE1, may promote microtubule polymerization, bundle formation, growth and dynamics at the plus ends. Regulates centrosomal maturation by recruitment of the gamma-tubulin ring complex (gamma-TuRC) onto centrosomes (PubMed:26485573). In complex with PDE4DIP isoform 13/MMG8/SMYLE, MAPRE1 and AKAP9, contributes to microtubules nucleation and extension from the centrosome to the cell periphery (PubMed:29162697). Required for the recruitment of AKAP9 to centrosomes (PubMed:29162697). Plays a role in neurogenesis (By similarity).SUBUNIT Interacts with CDK5R1 (p35 form) (By similarity). CDK5RAP1, CDK5RAP2 and CDK5RAP3 show competitive binding to CDK5R1. May form a complex with CDK5R1 and CDK5 (By similarity). Interacts with pericentrin/PCNT; the interaction is leading to centrosomal and Golgi localization of CDK5RAP2 and PCNT (PubMed:20466722). Interacts with AKAP9; the interaction targets CDK5RAP2 and AKAP9 to Golgi apparatus (PubMed:20466722). Interacts with MAPRE1; the interaction is direct and targets CDK5RAP2 and EB1/MAPRE1 to microtubule plus ends (PubMed:19553473). Interacts with TUBG1; the interaction is leading to the centrosomal localization of CDK5RAP2 and TUBG1 (PubMed:17959831). Interacts with TUBGCP3 (PubMed:17959831). Interacts with CALM1 (PubMed:20466722). Interacts with CDC20 (PubMed:19282672). Interacts with CEP68; degradation of CEP68 in early mitosis leads to removal of CDK5RAP2 from the centrosome which promotes centriole disengagement and subsequent centriole separation (PubMed:25503564). Interacts with NCKAP5L (PubMed:26485573). Forms a pericentrosomal complex with AKAP9, MAPRE1 and PDE4DIP isoform 13/MMG8/SMYLE; within this complex, MAPRE1 binding to CDK5RAP2 may be mediated by PDE4DIP (PubMed:29162697). Interacts with LGALS3BP; this interaction may connect the pericentrosomal complex to the gamma-tubulin ring complex (gamma-TuRC) to promote microtubule assembly and acetylation (PubMed:29162697).TISSUE SPECIFICITY Widely expressed. Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.PTM Phosphorylated in vitro by CDK5. UniProt Q96SN8 1 EQUAL 1893 EQUAL Reactome Database ID Release 81 380282 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380282 Reactome R-HSA-380282 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380282.1 1 PCNT Pericentrin B Reactome DB_ID: 380290 UniProt:O95613 PCNT PCNT KIAA0402 PCNT2 FUNCTION Integral component of the filamentous matrix of the centrosome involved in the initial establishment of organized microtubule arrays in both mitosis and meiosis. Plays a role, together with DISC1, in the microtubule network formation. Is an integral component of the pericentriolar material (PCM). May play an important role in preventing premature centrosome splitting during interphase by inhibiting NEK2 kinase activity at the centrosome.SUBUNIT Interacts with CHD3. Interacts with CHD4; the interaction regulates centrosome integrity (By similarity). Interacts with DISC1 and PCM1. Binds calmodulin. Interacts with CDK5RAP2; the interaction is leading to centrosomal localization of PCNT and CDK5RAP2. Interacts with isoform 1 of NEK2. Interacts with CEP131. Interacts with CCDC13 (PubMed:24816561). Interacts with CEP68 (PubMed:25503564). Interacts with ATF5; the ATF5:PCNT:polyglutamylated tubulin (PGT) tripartite unites the mother centriole and the pericentriolar material (PCM) in the centrosome (PubMed:26213385).TISSUE SPECIFICITY Expressed in all tissues tested, including placenta, liver, kidney and thymus.DOMAIN Composed of a coiled-coil central region flanked by non-helical N- and C-terminals.PTM Cleaved during mitotis which leads to removal of CDK5RAP2 from the centrosome and promotes centriole disengagement and subsequent centriole separation (PubMed:22722493, PubMed:25503564). The C-terminal fragment is rapidly degraded following cleavage (PubMed:22722493). UniProt O95613 1 EQUAL 3336 EQUAL Reactome Database ID Release 81 380290 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380290 Reactome R-HSA-380290 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380290.1 1 Arp1 ACTR1A alpha centractin Reactome DB_ID: 380258 UniProt:P61163 ACTR1A ACTR1A CTRN1 FUNCTION Component of a multi-subunit complex involved in microtubule based vesicle motility. It is associated with the centrosome.SUBUNIT Interacts with BCCIP (isoform 2/alpha).SIMILARITY Belongs to the actin family. ARP1 subfamily. UniProt P61163 1 EQUAL 376 EQUAL Reactome Database ID Release 81 380258 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380258 Reactome R-HSA-380258 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380258.2 1 TUBA4A Tubulin alpha-4A chain alpha tubulin -1 Alpha-tubulin 1 Reactome DB_ID: 191694 UniProt:P68366 TUBA4A TUBA4A TUBA1 FUNCTION Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.SUBUNIT Dimer of alpha and beta chains. A typical microtubule is a hollow water-filled tube with an outer diameter of 25 nm and an inner diameter of 15 nM. Alpha-beta heterodimers associate head-to-tail to form protofilaments running lengthwise along the microtubule wall with the beta-tubulin subunit facing the microtubule plus end conferring a structural polarity. Microtubules usually have 13 protofilaments but different protofilament numbers can be found in some organisms and specialized cells. Interacts with CFAP157 (By similarity).DOMAIN The MREC motif may be critical for tubulin autoregulation.PTM Some glutamate residues at the C-terminus are polyglutamylated, resulting in polyglutamate chains on the gamma-carboxyl group (PubMed:26875866). Polyglutamylation plays a key role in microtubule severing by spastin (SPAST). SPAST preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity by SPAST increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold (PubMed:26875866). Glutamylation is also involved in cilia motility (By similarity).PTM Some glutamate residues at the C-terminus are monoglycylated but not polyglycylated due to the absence of functional TTLL10 in human. Monoglycylation is mainly limited to tubulin incorporated into cilia and flagella axonemes, which is required for their stability and maintenance. Flagella glycylation controls sperm motility. Both polyglutamylation and monoglycylation can coexist on the same protein on adjacent residues, and lowering glycylation levels increases polyglutamylation, and reciprocally.PTM Acetylation of alpha chains at Lys-40 is located inside the microtubule lumen. This modification has been correlated with increased microtubule stability, intracellular transport and ciliary assembly.PTM Methylation of alpha chains at Lys-40 is found in mitotic microtubules and is required for normal mitosis and cytokinesis contributing to genomic stability.MISCELLANEOUS This tubulin does not have a C-terminal tyrosine.SIMILARITY Belongs to the tubulin family. UniProt P68366 1 EQUAL 448 EQUAL Reactome Database ID Release 81 191694 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=191694 Reactome R-HSA-191694 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-191694.1 1 CPAP CENPJ Centromere protein J CENP-J Reactome DB_ID: 380291 UniProt:Q9HC77 CENPJ CENPJ CPAP LAP LIP1 FUNCTION Plays an important role in cell division and centrosome function by participating in centriole duplication (PubMed:17681131, PubMed:20531387). Inhibits microtubule nucleation from the centrosome. Involved in the regulation of slow processive growth of centriolar microtubules. Acts as microtubule plus-end tracking protein that stabilizes centriolar microtubules and inhibits microtubule polymerization and extension from the distal ends of centrioles (PubMed:15047868, PubMed:27219064, PubMed:27306797). Required for centriole elongation and for STIL-mediated centriole amplification (PubMed:22020124). Required for the recruitment of CEP295 to the proximal end of new-born centrioles at the centriolar microtubule wall during early S phase in a PLK4-dependent manner (PubMed:27185865). May be involved in the control of centriolar-microtubule growth by acting as a regulator of tubulin release (PubMed:27306797).SUBUNIT Forms homodimers (PubMed:27219064). Associates with microtubules plus ends; binds to beta-tublin subunits exposed on microtubule outer surface at its distal tip; also associates with microtubule lattice (PubMed:19131341, PubMed:27219064, PubMed:27306797). Associated with the gamma-tubulin complex. Interacts with the head domain of EPB41 (PubMed:11003675). Interacts with LYST (PubMed:11984006). Interacts with CEP152 (via C-terminus) (PubMed:20852615). Interacts with STIL (PubMed:22020124, PubMed:25385835). Forms a complex with STIL and SASS6 (PubMed:22020124).PTM Phosphorylation at Ser-589 and Ser-595 by PLK2 is required for procentriole formation and centriole elongation. Phosphorylation by PLK2 oscillates during the cell cycle: it increases at G1/S transition and decreases during the exit from mitosis. Phosphorylation at Ser-595 is also mediated by PLK4 but is not a critical step in PLK4 function in procentriole assembly.SIMILARITY Belongs to the TCP10 family. UniProt Q9HC77 1 EQUAL 1338 EQUAL Reactome Database ID Release 81 380291 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380291 Reactome R-HSA-380291 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380291.2 1 CLASP1 Clasp1 Reactome DB_ID: 376230 UniProt:Q7Z460 CLASP1 CLASP1 KIAA0622 MAST1 FUNCTION Microtubule plus-end tracking protein that promotes the stabilization of dynamic microtubules. Involved in the nucleation of noncentrosomal microtubules originating from the trans-Golgi network (TGN). Required for the polarization of the cytoplasmic microtubule arrays in migrating cells towards the leading edge of the cell. May act at the cell cortex to enhance the frequency of rescue of depolymerizing microtubules by attaching their plus-ends to cortical platforms composed of ERC1 and PHLDB2. This cortical microtubule stabilizing activity is regulated at least in part by phosphatidylinositol 3-kinase signaling. Also performs a similar stabilizing function at the kinetochore which is essential for the bipolar alignment of chromosomes on the mitotic spindle.SUBUNIT Interacts with CLIP2, ERC1, MAPRE1, MAPRE3, microtubules, PHLDB2 and RSN. The interaction with ERC1 may be mediated by PHLDB2. Interacts with GCC2; recruits CLASP1 to Golgi membranes. Interacts with MACF1 (By similarity).SIMILARITY Belongs to the CLASP family. UniProt Q7Z460 1 EQUAL 1538 EQUAL Reactome Database ID Release 81 376230 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=376230 Reactome R-HSA-376230 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-376230.1 1 CEP135 Cep135 Reactome DB_ID: 380266 UniProt:Q66GS9 CEP135 CEP135 CEP4 KIAA0635 FUNCTION Centrosomal protein involved in centriole biogenesis. Acts as a scaffolding protein during early centriole biogenesis. Required for the targeting of centriole satellite proteins to centrosomes such as of PCM1, SSX2IP and CEP290 and recruitment of WRAP73 to centrioles. Also required for centriole-centriole cohesion during interphase by acting as a platform protein for CEP250 at the centriole. Required for the recruitment of CEP295 to the proximal end of new-born centrioles at the centriolar microtubule wall during early S phase in a PLK4-dependent manner (PubMed:27185865).SUBUNIT Interacts with DCTN2 (By similarity). Interacts with CEP250 (PubMed:18851962).SIMILARITY Belongs to the CEP135/TSGA10 family. UniProt Q66GS9 1 EQUAL 1140 EQUAL Reactome Database ID Release 81 380266 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380266 Reactome R-HSA-380266 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380266.1 1 PRKACA PKA C-alpha cAMP-dependent protein kinase, alpha-catalytic subunit Reactome DB_ID: 57844 UniProt:P17612 PRKACA PRKACA PKACA FUNCTION Phosphorylates a large number of substrates in the cytoplasm and the nucleus (PubMed:15642694, PubMed:15905176, PubMed:16387847, PubMed:17333334, PubMed:17565987, PubMed:17693412, PubMed:18836454, PubMed:19949837, PubMed:20356841, PubMed:21085490, PubMed:21514275, PubMed:21812984). Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA, SOX9 and VASP (PubMed:15642694, PubMed:15905176, PubMed:16387847, PubMed:17333334, PubMed:17565987, PubMed:17693412, PubMed:18836454, PubMed:19949837, PubMed:20356841, PubMed:21085490, PubMed:21514275, PubMed:21812984). Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis (PubMed:21423175). RORA is activated by phosphorylation (PubMed:21514275). Required for glucose-mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts (PubMed:19949837). Involved in chondrogenesis by mediating phosphorylation of SOX9 (By similarity). Involved in the regulation of platelets in response to thrombin and collagen; maintains circulating platelets in a resting state by phosphorylating proteins in numerous platelet inhibitory pathways when in complex with NF-kappa-B (NFKB1 and NFKB2) and I-kappa-B-alpha (NFKBIA), but thrombin and collagen disrupt these complexes and free active PRKACA stimulates platelets and leads to platelet aggregation by phosphorylating VASP (PubMed:15642694, PubMed:20356841). Prevents the antiproliferative and anti-invasive effects of alpha-difluoromethylornithine in breast cancer cells when activated (PubMed:17333334). RYR2 channel activity is potentiated by phosphorylation in presence of luminal Ca(2+), leading to reduced amplitude and increased frequency of store overload-induced Ca(2+) release (SOICR) characterized by an increased rate of Ca(2+) release and propagation velocity of spontaneous Ca(2+) waves, despite reduced wave amplitude and resting cytosolic Ca(2+) (PubMed:17693412). PSMC5/RPT6 activation by phosphorylation stimulates proteasome (PubMed:17565987). Negatively regulates tight junctions (TJs) in ovarian cancer cells via CLDN3 phosphorylation (PubMed:15905176). NFKB1 phosphorylation promotes NF-kappa-B p50-p50 DNA binding (PubMed:15642694). Involved in embryonic development by down-regulating the Hedgehog (Hh) signaling pathway that determines embryo pattern formation and morphogenesis. Prevents meiosis resumption in prophase-arrested oocytes via CDC25B inactivation by phosphorylation (By similarity). May also regulate rapid eye movement (REM) sleep in the pedunculopontine tegmental (PPT) (By similarity). Phosphorylates APOBEC3G and AICDA (PubMed:16387847, PubMed:18836454). Phosphorylates HSF1; this phosphorylation promotes HSF1 nuclear localization and transcriptional activity upon heat shock (PubMed:21085490).ACTIVITY REGULATION Allosterically activated by various compounds, including ATP. Activated by cAMP; the nucleotide acts as a dynamic and allosteric activator by coupling the two lobes of apo PKA, enhancing the enzyme dynamics synchronously and priming it for catalysis. Inhibited by H89 (N-[2-[[3-(4-Bromophenyl)-2-propenyl]amino]ethyl]-5-isoquinolinesulfonamide), spiroindoline, azole-based inhibitors, (3s)-amino-aminomethylbenzamide analogs, ARC-1032 (6-{[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]formamido}-N-[(1R)-4-carbamimidamido-1-carbamoylbutyl]hexanamide), ARC-1034 (6-{[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]formamido}-N-[(1R)-4-carbamimidamido-1-{[(1R)-4-carbamimidamido-1-carbamoylbutyl]carbamoyl}butyl]hexanamide), ARC-582, ARC-902 (Adc-6-aminohexanoic acid-(D-Arg)(6)-NH(2)), ARC-1012 ((2R)-6-amino-2-(6-{[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]formamido}hexanamido)-N-(5-{[(1R)-4-carbamimidamido-1-{[(1R)-4-carbamimidamido-1-carbamoylbutyl]carbamoyl}butyl]carbamoyl}pentyl)hexanamide) and ARC-1039 (6-{[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]formamido}-N-[(1R)-1-[(5-{[(1R)-4-carbamimidamido-1-{[(1R)-4-carbamimidamido-1-carbamoylbutyl]carbamoyl}butyl]carbamoyl}pentyl)carbamoyl]ethyl]he xanamide).SUBUNIT A number of inactive tetrameric holoenzymes are produced by the combination of homo- or heterodimers of the different regulatory subunits associated with two catalytic subunits. cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP and two free monomeric catalytic subunits. The cAMP-dependent protein kinase catalytic subunit binds PJA2. Both isoforms 1 and 2 forms activate cAMP-sensitive PKAI and PKAII holoenzymes by interacting with regulatory subunit (R) of PKA, PRKAR1A/PKR1 and PRKAR2A/PKR2, respectively. Interacts with PRKAR1A and PRKAR2B (PubMed:33058759). Interacts with NFKB1, NFKB2 and NFKBIA in platelets; these interactions are disrupted by thrombin and collagen. Binds to ABL1 in spermatozoa and with CDC25B in oocytes. Interacts with APOBEC3G and AICDA. Interacts with RAB13; downstream effector of RAB13 involved in tight junction assembly. Found in a complex at least composed of MROH2B, PRKACA isoform 2 and TCP11 (By similarity). Interacts with MROH2B (By similarity). Isoform 2 interacts with TCP11 (By similarity). Interacts with HSF1 (PubMed:21085490).TISSUE SPECIFICITY Isoform 1 is ubiquitous. Isoform 2 is sperm-specific and is enriched in pachytene spermatocytes but is not detected in round spermatids.PTM Asn-3 is partially deaminated to Asp giving rise to 2 major isoelectric variants, called CB and CA respectively.PTM Autophosphorylated. Phosphorylation is enhanced by vitamin K(2). Phosphorylated on threonine and serine residues. Phosphorylation on Thr-198 is required for full activity.PTM Phosphorylated at Tyr-331 by activated receptor tyrosine kinases EGFR and PDGFR; this increases catalytic efficiency.SIMILARITY Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. cAMP subfamily. UniProt P17612 2 EQUAL 351 EQUAL Reactome Database ID Release 81 57844 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=57844 Reactome R-HSA-57844 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-57844.1 1 SSNA1 NA-14 Reactome DB_ID: 380255 UniProt:O43805 SSNA1 SSNA1 NA14 TISSUE SPECIFICITY Widely expressed.SIMILARITY Belongs to the SSNA1 family. UniProt O43805 1 EQUAL 119 EQUAL Reactome Database ID Release 81 380255 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380255 Reactome R-HSA-380255 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380255.1 1 PLK1 Reactome DB_ID: 164603 UniProt:P53350 PLK1 PLK1 PLK FUNCTION Serine/threonine-protein kinase that performs several important functions throughout M phase of the cell cycle, including the regulation of centrosome maturation and spindle assembly, the removal of cohesins from chromosome arms, the inactivation of anaphase-promoting complex/cyclosome (APC/C) inhibitors, and the regulation of mitotic exit and cytokinesis. Polo-like kinase proteins acts by binding and phosphorylating proteins are that already phosphorylated on a specific motif recognized by the POLO box domains. Phosphorylates BORA, BUB1B/BUBR1, CCNB1, CDC25C, CEP55, ECT2, ERCC6L, FBXO5/EMI1, FOXM1, KIF20A/MKLP2, CENPU, NEDD1, NINL, NPM1, NUDC, PKMYT1/MYT1, KIZ, PPP1R12A/MYPT1, PRC1, RACGAP1/CYK4, SGO1, STAG2/SA2, TEX14, TOPORS, p73/TP73, TPT1, WEE1 and HNRNPU. Plays a key role in centrosome functions and the assembly of bipolar spindles by phosphorylating KIZ, NEDD1 and NINL. NEDD1 phosphorylation promotes subsequent targeting of the gamma-tubulin ring complex (gTuRC) to the centrosome, an important step for spindle formation. Phosphorylation of NINL component of the centrosome leads to NINL dissociation from other centrosomal proteins. Involved in mitosis exit and cytokinesis by phosphorylating CEP55, ECT2, KIF20A/MKLP2, CENPU, PRC1 and RACGAP1. Recruited at the central spindle by phosphorylating and docking PRC1 and KIF20A/MKLP2; creates its own docking sites on PRC1 and KIF20A/MKLP2 by mediating phosphorylation of sites subsequently recognized by the POLO box domains. Phosphorylates RACGAP1, thereby creating a docking site for the Rho GTP exchange factor ECT2 that is essential for the cleavage furrow formation. Promotes the central spindle recruitment of ECT2. Plays a central role in G2/M transition of mitotic cell cycle by phosphorylating CCNB1, CDC25C, FOXM1, CENPU, PKMYT1/MYT1, PPP1R12A/MYPT1 and WEE1. Part of a regulatory circuit that promotes the activation of CDK1 by phosphorylating the positive regulator CDC25C and inhibiting the negative regulators WEE1 and PKMYT1/MYT1. Also acts by mediating phosphorylation of cyclin-B1 (CCNB1) on centrosomes in prophase. Phosphorylates FOXM1, a key mitotic transcription regulator, leading to enhance FOXM1 transcriptional activity. Involved in kinetochore functions and sister chromatid cohesion by phosphorylating BUB1B/BUBR1, FBXO5/EMI1 and STAG2/SA2. PLK1 is high on non-attached kinetochores suggesting a role of PLK1 in kinetochore attachment or in spindle assembly checkpoint (SAC) regulation. Required for kinetochore localization of BUB1B. Regulates the dissociation of cohesin from chromosomes by phosphorylating cohesin subunits such as STAG2/SA2. Phosphorylates SGO1: required for spindle pole localization of isoform 3 of SGO1 and plays a role in regulating its centriole cohesion function. Mediates phosphorylation of FBXO5/EMI1, a negative regulator of the APC/C complex during prophase, leading to FBXO5/EMI1 ubiquitination and degradation by the proteasome. Acts as a negative regulator of p53 family members: phosphorylates TOPORS, leading to inhibit the sumoylation of p53/TP53 and simultaneously enhance the ubiquitination and subsequent degradation of p53/TP53. Phosphorylates the transactivation domain of the transcription factor p73/TP73, leading to inhibit p73/TP73-mediated transcriptional activation and pro-apoptotic functions. Phosphorylates BORA, and thereby promotes the degradation of BORA. Contributes to the regulation of AURKA function. Also required for recovery after DNA damage checkpoint and entry into mitosis. Phosphorylates MISP, leading to stabilization of cortical and astral microtubule attachments required for proper spindle positioning (PubMed:8991084, PubMed:11202906, PubMed:12207013, PubMed:12447691, PubMed:12524548, PubMed:12738781, PubMed:12852856, PubMed:12939256, PubMed:14532005, PubMed:14734534, PubMed:15070733, PubMed:15148369, PubMed:15469984, PubMed:16198290, PubMed:16247472, PubMed:16980960, PubMed:17081991, PubMed:17351640, PubMed:17376779, PubMed:17617734, PubMed:18174154, PubMed:18331714, PubMed:18418051, PubMed:18477460, PubMed:18521620, PubMed:18615013, PubMed:19160488, PubMed:19351716, PubMed:19468300, PubMed:19468302, PubMed:19473992, PubMed:19509060, PubMed:19597481, PubMed:23455478, PubMed:23509069). Together with MEIKIN, acts as a regulator of kinetochore function during meiosis I: required both for mono-orientation of kinetochores on sister chromosomes and protection of centromeric cohesin from separase-mediated cleavage (By similarity). Phosphorylates CEP68 and is required for its degradation (PubMed:25503564). Regulates nuclear envelope breakdown during prophase by phosphorylating DCTN1 resulting in its localization in the nuclear envelope (PubMed:20679239). Phosphorylates the heat shock transcription factor HSF1, promoting HSF1 nuclear translocation upon heat shock (PubMed:15661742). Phosphorylates HSF1 also in the early mitotic period; this phosphorylation regulates HSF1 localization to the spindle pole, the recruitment of the SCF(BTRC) ubiquitin ligase complex induicing HSF1 degradation, and hence mitotic progression (PubMed:18794143). Regulates mitotic progression by phosphorylating RIOK2 (PubMed:21880710). Through the phosphorylation of DZIP1 regulates the localization during mitosis of the BBSome, a ciliary protein complex involved in cilium biogenesis (PubMed:27979967).ACTIVITY REGULATION Activated by phosphorylation of Thr-210 by AURKA; phosphorylation by AURKA is enhanced by BORA. Once activated, activity is stimulated by binding target proteins. Binding of target proteins has no effect on the non-activated kinase. Several inhibitors targeting PLKs are currently in development and are under investigation in a growing number of clinical trials, such as BI 2536, an ATP-competitive PLK1 inhibitor or BI 6727, a dihydropteridinone that specifically inhibits the catalytic activity of PLK1.SUBUNIT Interacts with CEP170 and EVI5. Interacts and phosphorylates ERCC6L. Interacts with FAM29A. Interacts with SLX4/BTBD12 and TTDN1. Interacts with BUB1B. Interacts (via POLO-box domain) with the phosphorylated form of BUB1, CENPU and CDC25C. Interacts with isoform 3 of SGO1. Interacts with BORA, KIF2A and AURKA. Interacts with TOPORS and CYLD. Interacts with ECT2; the interaction is stimulated upon phosphorylation of ECT2 on 'Thr-444'. Interacts with PRC1. Interacts with KIF20A/MKLP2 (when phosphorylated), leading to the recruitment at the central spindle. Interacts (via POLO box domains) with PPP1R12A/MYPT1 (when previously phosphorylated by CDK1). Part of an astrin (SPAG5)-kinastrin (SKAP) complex containing KNSTRN, SPAG5, PLK1, DYNLL1 and SGO2. Interacts with BIRC6/bruce. Interacts with CDK1-phosphorylated FRY; this interaction occurs in mitotic cells, but not in interphase cells. FRY interaction facilitates AURKA-mediated PLK1 phosphorylation. Interacts with CDK1-phosphorylated DCTN6 during mitotic prometaphase; the interaction facilitates recruitment to kinetochores. Interacts with CEP68; the interaction phosphorylates CEP68 (PubMed:25503564). Interacts (via POLO-box domain) with DCTN1 (PubMed:20679239). Interacts with CEP20 in later G1, S, G2 and M phases of the cell cycle; this interaction recruits PLK1 to centrosomes, a step required for S phase progression (PubMed:24018379). Interacts with HSF1; this interaction increases upon heat shock but does not modulate neither HSF1 homotrimerization nor DNA-binding activities (PubMed:15661742, PubMed:18794143). Interacts with HNRNPU; this interaction induces phosphorylation of HNRNPU in mitosis (PubMed:25986610). Interacts (via its N-terminus) to RIOK2 (PubMed:21880710). Interacts with KLHL22 (PubMed:24067371, PubMed:23455478).TISSUE SPECIFICITY Placenta and colon.DEVELOPMENTAL STAGE Accumulates to a maximum during the G2 and M phases, declines to a nearly undetectable level following mitosis and throughout G1 phase, and then begins to accumulate again during S phase.INDUCTION By growth-stimulating agents.DOMAIN The POLO box domains act as phosphopeptide-binding module that recognize and bind serine-[phosphothreonine/phosphoserine]-(proline/X) motifs. PLK1 recognizes and binds docking proteins that are already phosphorylated on these motifs, and then phosphorylates them. PLK1 can also create its own docking sites by mediating phosphorylation of serine-[phosphothreonine/phosphoserine]-(proline/X) motifs subsequently recognized by the POLO box domains.PTM Catalytic activity is enhanced by phosphorylation of Thr-210. Phosphorylation at Thr-210 is first detected on centrosomes in the G2 phase of the cell cycle, peaks in prometaphase and gradually disappears from centrosomes during anaphase. Dephosphorylation at Thr-210 at centrosomes is probably mediated by protein phosphatase 1C (PP1C), via interaction with PPP1R12A/MYPT1. Autophosphorylation and phosphorylation of Ser-137 may not be significant for the activation of PLK1 during mitosis, but may enhance catalytic activity during recovery after DNA damage checkpoint. Phosphorylated in vitro by STK10.PTM Ubiquitinated by the anaphase promoting complex/cyclosome (APC/C) in anaphase and following DNA damage, leading to its degradation by the proteasome. Ubiquitination is mediated via its interaction with FZR1/CDH1. Ubiquitination and subsequent degradation prevents entry into mitosis and is essential to maintain an efficient G2 DNA damage checkpoint. Monoubiquitination at Lys-492 by the BCR(KLHL22) ubiquitin ligase complex does not lead to degradation: it promotes PLK1 dissociation from phosphoreceptor proteins and subsequent removal from kinetochores, allowing silencing of the spindle assembly checkpoint (SAC) and chromosome segregation.DISEASE Defects in PLK1 are associated with some cancers, such as gastric, thyroid or B-cell lymphomas. Expression is cancer increased in tumor tissues with a poor prognosis, suggesting a role in malignant transformations and carcinogenesis.SIMILARITY Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. CDC5/Polo subfamily. UniProt P53350 1 EQUAL 603 EQUAL Reactome Database ID Release 81 164603 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=164603 Reactome R-HSA-164603 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-164603.1 1 PPP2R1A PP2A-subunit A alpha isoform Reactome DB_ID: 165982 UniProt:P30153 PPP2R1A PPP2R1A FUNCTION The PR65 subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. Upon interaction with GNA12 promotes dephosphorylation of microtubule associated protein TAU/MAPT (PubMed:15525651). Required for proper chromosome segregation and for centromeric localization of SGO1 in mitosis (PubMed:16580887).SUBUNIT PP2A consists of a common heterodimeric core enzyme, composed of PPP2CA a 36 kDa catalytic subunit (subunit C) and PPP2R1A a 65 kDa constant regulatory subunit (PR65 or subunit A), that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules. Found in a complex with at least ARL2, PPP2CB, PPP2R1A, PPP2R2A, PPP2R5E and TBCD (By similarity). Interacts with FOXO1; the interaction dephosphorylates FOXO1 on AKT-mediated phosphorylation sites (By similarity). Interacts with IPO9 (PubMed:12670497). Interacts with TP53 and SGO1 (PubMed:17245430, PubMed:16580887). Interacts with PLA2G16; this interaction might decrease PP2A activity (PubMed:17374643). Interacts with CTTNBP2NL (PubMed:18782753). Interacts with GNA12; the interaction promotes protein phosphatase 2A activation causing dephosphorylation of MAPT (PubMed:15525651). Interacts with CIP2A; this interaction stabilizes CIP2A (PubMed:28174209). Interacts with PABIR1/FAM122A (PubMed:27588481). Interacts with ADCY8; antagonizes interaction between ADCY8 and calmodulin (By similarity). Interacts with CRTC3 (when phosphorylated at 'Ser-391') (PubMed:30611118). Interacts with SPRY2 (PubMed:17974561).SUBUNIT (Microbial infection) Interacts with JC virus small t antigen; this interaction inhibits PPP2R1A activity.DOMAIN Each HEAT repeat appears to consist of two alpha helices joined by a hydrophilic region, the intrarepeat loop. The repeat units may be arranged laterally to form a rod-like structure.SIMILARITY Belongs to the phosphatase 2A regulatory subunit A family. UniProt P30153 2 EQUAL 589 EQUAL Reactome Database ID Release 81 165982 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=165982 Reactome R-HSA-165982 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-165982.1 1 CETN2 Centrin-2 Reactome DB_ID: 380298 UniProt:P41208 CETN2 CETN2 CALT CEN2 FUNCTION Plays a fundamental role in microtubule organizing center structure and function. Required for centriole duplication and correct spindle formation. Has a role in regulating cytokinesis and genome stability via cooperation with CALM1 and CCP110.FUNCTION Involved in global genome nucleotide excision repair (GG-NER) by acting as component of the XPC complex. Cooperatively with RAD23B appears to stabilize XPC. In vitro, stimulates DNA binding of the XPC:RAD23B dimer.FUNCTION The XPC complex is proposed to represent the first factor bound at the sites of DNA damage and together with other core recognition factors, XPA, RPA and the TFIIH complex, is part of the pre-incision (or initial recognition) complex. The XPC complex recognizes a wide spectrum of damaged DNA characterized by distortions of the DNA helix such as single-stranded loops, mismatched bubbles or single-stranded overhangs. The orientation of XPC complex binding appears to be crucial for inducing a productive NER. XPC complex is proposed to recognize and to interact with unpaired bases on the undamaged DNA strand which is followed by recruitment of the TFIIH complex and subsequent scanning for lesions in the opposite strand in a 5'-to-3' direction by the NER machinery. Cyclobutane pyrimidine dimers (CPDs) which are formed upon UV-induced DNA damage esacpe detection by the XPC complex due to a low degree of structural perurbation. Instead they are detected by the UV-DDB complex which in turn recruits and cooperates with the XPC complex in the respective DNA repair.FUNCTION As a component of the TREX-2 complex, involved in the export of mRNAs to the cytoplasm through the nuclear pores.SUBUNIT Monomer. Homooligomer (PubMed:15356003). Interacts with SFI1 (PubMed:16956364). Interacts with CCP110 (PubMed:16760425). Component of the XPC complex composed of XPC, RAD23B and CETN2 (PubMed:11279143, PubMed:15964821, PubMed:16533048, PubMed:16627479). Component of the nuclear pore complex (NPC)-associated TREX-2 complex (transcription and export complex 2), composed of at least GANP, 2 copies of ENY2, PCID2, SEM1/DSS1, and either centrin CETN2 or centrin CETN3. The TREX-2 complex also associates with ALYREF/ALY and with the nucleoporin NUP153 (PubMed:22307388, PubMed:23591820).MISCELLANEOUS Binds two moles of calcium per mole of protein.SIMILARITY Belongs to the centrin family. UniProt P41208 1 EQUAL 172 EQUAL Reactome Database ID Release 81 380298 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380298 Reactome R-HSA-380298 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380298.1 1 TUBA1A alpha tubulin 3 Reactome DB_ID: 191689 UniProt:Q71U36 TUBA1A TUBA1A TUBA3 FUNCTION Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.SUBUNIT Dimer of alpha and beta chains. A typical microtubule is a hollow water-filled tube with an outer diameter of 25 nm and an inner diameter of 15 nM. Alpha-beta heterodimers associate head-to-tail to form protofilaments running lengthwise along the microtubule wall with the beta-tubulin subunit facing the microtubule plus end conferring a structural polarity. Microtubules usually have 13 protofilaments but different protofilament numbers can be found in some organisms and specialized cells. Interacts with SETD2; the interaction is independent on alpha-tubulin acetylation on Lys-40.TISSUE SPECIFICITY Expressed at a high level in fetal brain.PTM Some glutamate residues at the C-terminus are polyglutamylated, resulting in polyglutamate chains on the gamma-carboxyl group (PubMed:26875866). Polyglutamylation plays a key role in microtubule severing by spastin (SPAST). SPAST preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity by SPAST increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold (PubMed:26875866). Glutamylation is also involved in cilia motility (By similarity).PTM Some glutamate residues at the C-terminus are monoglycylated but not polyglycylated due to the absence of functional TTLL10 in human. Monoglycylation is mainly limited to tubulin incorporated into cilia and flagella axonemes, which is required for their stability and maintenance. Flagella glycylation controls sperm motility. Both polyglutamylation and monoglycylation can coexist on the same protein on adjacent residues, and lowering glycylation levels increases polyglutamylation, and reciprocally.PTM Acetylation of alpha chains at Lys-40 is located inside the microtubule lumen. This modification has been correlated with increased microtubule stability, intracellular transport and ciliary assembly.PTM Methylation of alpha chains at Lys-40 is found in mitotic microtubules and is required for normal mitosis and cytokinesis contributing to genomic stability.PTM Nitration of Tyr-451 is irreversible and interferes with normal dynein intracellular distribution.PTM Undergoes a tyrosination/detyrosination cycle, the cyclic removal and re-addition of a C-terminal tyrosine residue by the enzymes tubulin tyrosine carboxypeptidase (VASH1 or VASH2) and tubulin tyrosine ligase (TTL), respectively.SIMILARITY Belongs to the tubulin family. UniProt Q71U36 1 EQUAL 451 EQUAL Reactome Database ID Release 81 191689 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=191689 Reactome R-HSA-191689 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-191689.1 1 PLK4 Reactome DB_ID: 380286 UniProt:O00444 PLK4 PLK4 SAK STK18 FUNCTION Serine/threonine-protein kinase that plays a central role in centriole duplication. Able to trigger procentriole formation on the surface of the parental centriole cylinder, leading to the recruitment of centriole biogenesis proteins such as SASS6, CENPJ/CPAP, CCP110, CEP135 and gamma-tubulin. When overexpressed, it is able to induce centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole during S phase. Phosphorylates 'Ser-151' of FBXW5 during the G1/S transition, leading to inhibit FBXW5 ability to ubiquitinate SASS6. Its central role in centriole replication suggests a possible role in tumorigenesis, centrosome aberrations being frequently observed in tumors. Also involved in deuterosome-mediated centriole amplification in multiciliated that can generate more than 100 centrioles. Also involved in trophoblast differentiation by phosphorylating HAND1, leading to disrupt the interaction between HAND1 and MDFIC and activate HAND1. Phosphorylates CDC25C and CHEK2. Required for the recruitment of STIL to the centriole and for STIL-mediated centriole amplification (PubMed:22020124). Phosphorylates CEP131 at 'Ser-78' and PCM1 at 'Ser-372' which is essential for proper organization and integrity of centriolar satellites (PubMed:30804208).SUBUNIT Homodimer (By similarity). Interacts with CEP152 (via N-terminus). Interacts with CEP78; this interaction may be important for proper PLK4 localization to the centriole and PLK4-induced overduplication of centrioles (PubMed:27246242). Interacts with CEP131 (PubMed:30804208). Interacts simultaneously with TENT5C and CEP192 (PubMed:32433990). Interacts with TENT5C; this interaction leads to the TENT5C recruitment in the centrosome (PubMed:32433990).INDUCTION Down-regulated in HCT 116 colorectal cancer cells, leading to aberrant centrioles composed of disorganized cylindrical microtubules and displaced appendages. Down-regulated by p53/TP53.DOMAIN Cryptic POLO box 1 (CPB1) and Cryptic POLO box 2 (CPB2) domains can simultaneously bind to both TENT5C and CEP192.PTM Acetylation by KAT2A and KAT2B impairs kinase activity by shifting the kinase to an inactive conformation.PTM Ubiquitinated; leading to its degradation by the proteasome.PTM Tyrosine-phosphorylated by TEC.SIMILARITY Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. CDC5/Polo subfamily. UniProt O00444 1 EQUAL 970 EQUAL Reactome Database ID Release 81 380286 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380286 Reactome R-HSA-380286 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380286.1 1 PIN DYNLL1 DLC1 Dynein light chain 1, cytoplasmic 8 kDa dynein light chain DLC8 Protein inhibitor of neuronal nitric oxide synthase Reactome DB_ID: 387105 UniProt:P63167 DYNLL1 DYNLL1 DLC1 DNCL1 DNCLC1 HDLC1 FUNCTION Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. May play a role in changing or maintaining the spatial distribution of cytoskeletal structures.FUNCTION Binds and inhibits the catalytic activity of neuronal nitric oxide synthase.FUNCTION Promotes transactivation functions of ESR1 and plays a role in the nuclear localization of ESR1.FUNCTION Regulates apoptotic activities of BCL2L11 by sequestering it to microtubules. Upon apoptotic stimuli the BCL2L11-DYNLL1 complex dissociates from cytoplasmic dynein and translocates to mitochondria and sequesters BCL2 thus neutralizing its antiapoptotic activity.SUBUNIT Homodimer. Monomer; the monomeric form is incapable of binding to target proteins. The cytoplasmic dynein 1 complex consists of two catalytic heavy chains (HCs) and a number of non-catalytic subunits presented by intermediate chains (ICs), light intermediate chains (LICs) and light chains (LCs); the composition seems to vary in respect to the IC, LIC and LC composition. The heavy chain homodimer serves as a scaffold for the probable homodimeric assembly of the respective non-catalytic subunits. The ICs and LICs bind directly to the HC dimer and the LCs assemble on the IC dimer. Interacts with TXNDC17. Interacts with WWC1 and ESR1. The WWC1-DYNLL1 interaction is mandatory for the recruitment and transactivation functions of ESR1 or DYNLL1 to the target chromatin. Interacts with BCL2L11 isoform 1 and isoform 2. Interacts with BCL2; the interaction is greatly enhanced in the nucleus and in mitochondria upon induction of apoptosis. Interacts with PAK1; the interaction requires dimeric DYNLL1. Interacts with MYZAP. Part of an astrin (SPAG5)-kinastrin (SKAP) complex containing KNSTRN, SPAG5, PLK1, DYNLL1 and SGO2. Interacts with ATMIN; this interaction inhibits ATMIN transcriptional activity and hence may play a role in a feedback loop whereby DYNLL1 inhibits transactivation of its own promoter by ATMIN. Interacts with NEK9 (not phosphorylated at 'Ser-944'). Interacts with BICD2 (By similarity). Interacts with BCAS1 (By similarity). Interacts with Basson/BSN. Interacts with HDAC6 (PubMed:31505170). Interacts with TPPP (PubMed:31505170). Interacts with AMBRA1 (via TQT motifs); tethering AMBRA1 to the cytoskeleton (PubMed:20921139). Interacts with FAM83D/CHICA (via C-terminus) (PubMed:22965910). Interacts with HMMR, SPAG5/Astrin and KNSTRN/Kinastrin (PubMed:22965910).SUBUNIT (Microbial infection) Interacts with human spumaretrovirus Gag protein; this interaction is critical for intracellular microtubule-dependent viral genome transport toward the centrosome.SUBUNIT (Microbial infection) Interacts with ebolavirus protein VP35; this interaction stabilizes VP35 N-terminal oligomerization domain and enhances viral RNA synthesis.TISSUE SPECIFICITY Ubiquitous (PubMed:8628263). Expressed in testis (PubMed:22965910).INDUCTION Up-regulated by ATMIN, PAK1 and estrogen.PTM Phosphorylation at Ser-88 appears to control the dimer-monomer transition. According to PubMed:15193260, it is phosphorylated at Ser-88 by PAK1, however, according to PubMed:18650427, the DYNLL1 dimer is not accessible for PAK1 and the phosphorylation could not be demonstrated in vitro.SIMILARITY Belongs to the dynein light chain family. UniProt P63167 1 EQUAL 89 EQUAL Reactome Database ID Release 81 387105 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=387105 Reactome R-HSA-387105 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-387105.1 1 1 TUBB Tubulin beta-5 chain Reactome DB_ID: 380317 extracellular region GENE ONTOLOGY GO:0005576 UniProt:P07437 TUBB TUBB TUBB5 OK/SW-cl.56 FUNCTION Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.SUBUNIT Heterodimer of alpha and beta chains (PubMed:26637975). A typical microtubule is a hollow water-filled tube with an outer diameter of 25 nm and an inner diameter of 15 nM. Alpha-beta heterodimers associate head-to-tail to form protofilaments running lengthwise along the microtubule wall with the beta-tubulin subunit facing the microtubule plus end conferring a structural polarity. Microtubules usually have 13 protofilaments but different protofilament numbers can be found in some organisms and specialized cells. Interacts with PIFO (PubMed:20643351). Interacts with DIAPH1 (PubMed:23325789). Interacts with MX1 (By similarity). May interact with RNABP10 (By similarity). Interacts with CFAP157 (By similarity). Nascent tubulin polypeptide interacts (via beta-tubulin MREI motif) with TTC5/STRAP; this interaction results in tubulin mRNA-targeted degradation (PubMed:31727855).TISSUE SPECIFICITY Ubiquitously expressed with highest levels in spleen, thymus and immature brain.INDUCTION Autoregulated by feedback control of mRNA degradation (PubMed:31727855). In excess of soluble tubulin, nascent beta-tubulin chain binds TTC5/STRAP cofactor through the MREI motif which triggers cotranslation degradation of tubulin mRNA (PubMed:31727855).DOMAIN The highly acidic C-terminal region may bind cations such as calcium.DOMAIN The MREI motif is common among all beta-tubulin isoforms and may be critical for tubulin autoregulation.PTM Some glutamate residues at the C-terminus are polyglutamylated, resulting in polyglutamate chains on the gamma-carboxyl group (PubMed:26875866, PubMed:28576883). Polyglutamylation plays a key role in microtubule severing by spastin (SPAST). SPAST preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity by SPAST increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold (PubMed:26875866). Glutamylation is also involved in cilia motility (By similarity).PTM Some glutamate residues at the C-terminus are monoglycylated but not polyglycylated due to the absence of functional TTLL10 in human. Monoglycylation is mainly limited to tubulin incorporated into cilia and flagella axonemes, which is required for their stability and maintenance. Flagella glycylation controls sperm motility (Probable) (PubMed:28576883). Both polyglutamylation and monoglycylation can coexist on the same protein on adjacent residues, and lowering glycylation levels increases polyglutamylation, and reciprocally (Probable) (PubMed:28576883).PTM Phosphorylated on Ser-172 by CDK1 during the cell cycle, from metaphase to telophase, but not in interphase. This phosphorylation inhibits tubulin incorporation into microtubules.SIMILARITY Belongs to the tubulin family. UniProt P07437 1 EQUAL 444 EQUAL Reactome Database ID Release 81 380317 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380317 Reactome R-HSA-380317 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380317.2 1 NDE1 Reactome DB_ID: 376257 UniProt:Q9NXR1 NDE1 NDE1 NUDE FUNCTION Required for centrosome duplication and formation and function of the mitotic spindle. Essential for the development of the cerebral cortex. May regulate the production of neurons by controlling the orientation of the mitotic spindle during division of cortical neuronal progenitors of the proliferative ventricular zone of the brain. Orientation of the division plane perpendicular to the layers of the cortex gives rise to two proliferative neuronal progenitors whereas parallel orientation of the division plane yields one proliferative neuronal progenitor and a post-mitotic neuron. A premature shift towards a neuronal fate within the progenitor population may result in an overall reduction in the final number of neurons and an increase in the number of neurons in the deeper layers of the cortex.SUBUNIT Self-associates. Interacts with CNTRL, LIS1, dynein, SLMAP and TCP1 (By similarity). Interacts with CENPF, dynactin, tubulin gamma, PAFAH1B1, PCM1 and PCNT. Interacts with ZNF365.TISSUE SPECIFICITY Expressed in the neuroepithelium throughout the developing brain, including the cerebral cortex and cerebellum.PTM Phosphorylated in mitosis. Phosphorylated in vitro by CDC2. Phosphorylation at Thr-246 is essential for the G2/M transition (By similarity).SIMILARITY Belongs to the nudE family. UniProt Q9NXR1 1 EQUAL 346 EQUAL Reactome Database ID Release 81 376257 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=376257 Reactome R-HSA-376257 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-376257.1 1 DYNC1H1 cytoplasmic dynein 1 heavy chain 1 Reactome DB_ID: 380285 UniProt:Q14204 DYNC1H1 DYNC1H1 DHC1 DNCH1 DNCL DNECL DYHC KIAA0325 FUNCTION Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. Dynein has ATPase activity; the force-producing power stroke is thought to occur on release of ADP. Plays a role in mitotic spindle assembly and metaphase plate congression (PubMed:27462074).SUBUNIT Homodimer. The cytoplasmic dynein 1 complex consists of two catalytic heavy chains (HCs) and a number of non-catalytic subunits presented by intermediate chains (ICs), light intermediate chains (LICs) and light chains (LCs); the composition seems to vary in respect to the IC, LIC and LC composition. The heavy chain homodimer serves as a scaffold for the probable homodimeric assembly of the respective non-catalytic subunits. The ICs and LICs bind directly to the HC dimer and dynein LCs assemble on the IC dimer. Interacts with DYNC1LI1; DYNC1LI1 and DYNC1LI2 bind mutually exclusive to DYNC1H1. Interacts with DYNC1LI2; DYNC1LI1 and DYNC1LI2 bind mutually exclusive to DYNC1H1. Interacts with DYNC1I2 (By similarity). Interacts with BICD2 (PubMed:25512093). Interacts with isoform 2 of CRACR2A (PubMed:31092558). Interacts with DNALI1 (By similarity).DOMAIN Dynein heavy chains probably consist of an N-terminal stem (which binds cargo and interacts with other dynein components), and the head or motor domain. The motor contains six tandemly-linked AAA domains in the head, which form a ring. A stalk-like structure (formed by two of the coiled coil domains) protrudes between AAA 4 and AAA 5 and terminates in a microtubule-binding site. A seventh domain may also contribute to this ring; it is not clear whether the N-terminus or the C-terminus forms this extra domain. There are four well-conserved and two non-conserved ATPase sites, one per AAA domain. Probably only one of these (within AAA 1) actually hydrolyzes ATP, the others may serve a regulatory function.SIMILARITY Belongs to the dynein heavy chain family. UniProt Q14204 1 EQUAL 4646 EQUAL Reactome Database ID Release 81 380285 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380285 Reactome R-HSA-380285 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380285.1 1 Reactome Database ID Release 81 380268 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380268 Reactome R-HSA-380268 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380268.2 1 Reactome Database ID Release 81 380440 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380440 Reactome R-HSA-380440 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380440.1 Mature centrosome enriched in gamma-TURC:p-T2055-NUMA1 homodimer Reactome DB_ID: 380503 1 1 Reactome Database ID Release 81 380503 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380503 Reactome R-HSA-380503 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380503.2 Reactome Database ID Release 81 380508 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380508 Reactome R-HSA-380508 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380508.2 23921553 Pubmed 2013 NuMA phosphorylation by CDK1 couples mitotic progression with cortical dynein function Kotak, Sachin Busso, Coralie Gönczy, Pierre EMBO J. 32:2517-29 7769006 Pubmed 1995 Mutation of the predicted p34cdc2 phosphorylation sites in NuMA impair the assembly of the mitotic spindle and block mitosis Compton, DA Luo, C J Cell Sci 108:621-33 8838651 Pubmed 1996 Dynamic changes of NuMA during the cell cycle and possible appearance of a truncated form of NuMA during apoptosis Hsu, HL Yeh, NH J Cell Sci 109:277-88 LEFT-TO-RIGHT Association of NuMA with microtubules NuMA can interact with microtubules by direct binding to tubulin. Binding occurs through amino acids 1868-1967 of human NuMA (tail IIA) and appears to play a role in the organization of the spindle poles by stably crosslinking microtubule fibers (Haren and Merdes 2002). While the exact mechanism of microtubule bundling is not known, NuMA has been shown to form large fibrous networks (Saredi et al. 1996, Gueth-Hallonet et al.1998, Harborth et al.1999) apparently as a result of dimerization of the NuMA rod domains followed by association of multiple NuMA dimers through their tail domains. Authored: Matthews, L, 2008-11-11 14:53:40 Reviewed: Merdes, A, 2008-11-17 13:55:29 Edited: Matthews, L, 2008-11-09 05:12:41 Edited: Matthews, L, 2008-11-24 13:58:10 Edited: Orlic-Milacic, Marija, 2017-03-17 Microtubule Reactome DB_ID: 190599 Microtubule protofilament Reactome DB_ID: 8982424 Reactome Database ID Release 81 8982424 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8982424 Reactome R-HSA-8982424 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8982424.2 ChEBI 36080 13 Reactome Database ID Release 81 190599 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=190599 Reactome R-HSA-190599 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-190599.2 p-T2055-NUMA1 homodimer:Mature centrosome:nucleated microtubules Reactome DB_ID: 380495 1 Mature centrosome:nucleated microtubules Reactome DB_ID: 379273 1 1 Reactome Database ID Release 81 379273 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379273 Reactome R-HSA-379273 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-379273.2 1 Reactome Database ID Release 81 380495 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380495 Reactome R-HSA-380495 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380495.2 Reactome Database ID Release 81 380316 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380316 Reactome R-HSA-380316 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380316.3 9743603 Pubmed 1998 Induction of a regular nuclear lattice by overexpression of NuMA Gueth-Hallonet, C Wang, J Harborth, J Weber, K Osborn, M Exp Cell Res 243:434-52 8907707 Pubmed 1996 NuMA assembles into an extensive filamentous structure when expressed in the cell cytoplasm Saredi, A Howard, L Compton, DA J Cell Sci 109:619-30 11956313 Pubmed 2002 Direct binding of NuMA to tubulin is mediated by a novel sequence motif in the tail domain that bundles and stabilizes microtubules Haren, L Merdes, Andeas J Cell Sci 115:1815-24 10075938 Pubmed 1999 Self assembly of NuMA: multiarm oligomers as structural units of a nuclear lattice Harborth, J Wang, J Gueth-Hallonet, C Weber, K Osborn, M EMBO J 18:1689-700 Reactome Database ID Release 81 380320 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380320 Reactome R-HSA-380320 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-380320.2 11163243 Pubmed 2001 Importin beta is a mitotic target of the small GTPase Ran in spindle assembly Nachury, MV Maresca, TJ Salmon, WC Waterman-Storer, CM Heald, R Weis, K Cell 104:95-106 15561764 Pubmed 2004 Multiple mechanisms regulate NuMA dynamics at spindle poles Kisurina-Evgenieva, O Mack, G Du, Q Macara, I Khodjakov, A Compton, DA J Cell Sci 117:6391-400 10811826 Pubmed 2000 Formation of spindle poles by dynein/dynactin-dependent transport of NuMA Merdes, Andeas Heald, R Samejima, K Earnshaw, WC Cleveland, DW J Cell Biol 149:851-62 8896597 Pubmed 1996 Opposing motor activities are required for the organization of the mammalian mitotic spindle pole Gaglio, T Saredi, A Bingham, JB Hasbani, MJ Gill, SR Schroer, TA Compton, DA J Cell Biol 135:399-414 11229403 Pubmed 2001 Role of importin-beta in coupling Ran to downstream targets in microtubule assembly Wiese, C Wilde, A Moore, MS Adam, SA Merdes, Andeas Zheng, Y Science 291:653-6 7962183 Pubmed 1994 Nuclear mitotic apparatus protein (NuMA): spindle association, nuclear targeting and differential subcellular localization of various NuMA isoforms Tang, TK Tang, CJ Chao, YJ Wu, CW J Cell Sci 107:1389-402 7593190 Pubmed 1995 NuMA is required for the organization of microtubules into aster-like mitotic arrays Gaglio, T Saredi, A Compton, DA J Cell Biol 131:693-708 8898198 Pubmed 1996 A complex of NuMA and cytoplasmic dynein is essential for mitotic spindle assembly Merdes, Andeas Ramyar, K Vechio, JD Cleveland, DW Cell 87:447-58 9394013 Pubmed 1998 The role of NuMA in the interphase nucleus Merdes, Andeas Cleveland, DW J Cell Sci 111:71-9