BioPAX pathway converted from "Synapsis" in the Reactome database. Synapsis Synapsis Formation of Central Elements of the Synaptonemal Complex Initiation of recombination precedes and is required for synapsis (Roig et al. 2004). The synaptonemal complex forms when transverse filaments of SYCP1 link axial/lateral elements of sister chromatids to a central element comprising SYCE1, SYCE2, and other proteins (Tarsounas et al. 1997). The order of assembly is unknown. Authored: May, B, 2010-07-02 Reviewed: Bolcun-Filas, E, 2011-02-25 Reviewed: Cohen, PE, 2011-02-04 Reviewed: Holloway, JK, 2011-02-04 Reviewed: Lyndaker, A, 2011-02-25 Reviewed: Schimenti, JC, 2011-02-04 Reviewed: Strong, E, 2011-02-25 Edited: May, B, 2010-07-02 Reactome DB_ID: 912481 1 nucleoplasm GO 0005654 UniProt:P63279 UBE2I UBE2I UBE2I UBC9 UBCE9 FUNCTION Accepts the ubiquitin-like proteins SUMO1, SUMO2, SUMO3, SUMO4 and SUMO1P1/SUMO5 from the UBLE1A-UBLE1B E1 complex and catalyzes their covalent attachment to other proteins with the help of an E3 ligase such as RANBP2, CBX4 and ZNF451. Can catalyze the formation of poly-SUMO chains. Necessary for sumoylation of FOXL2 and KAT5. Essential for nuclear architecture and chromosome segregation. Sumoylates p53/TP53 at 'Lys-386'. Mediates sumoylation of ERCC6 which is essential for its transcription-coupled nucleotide excision repair activity (PubMed:26620705).PATHWAY Protein modification; protein sumoylation.SUBUNIT Forms a complex with SENP6 and UBE2I in response to UV irradiation (PubMed:17704809). Forms a tight complex with RANGAP1 and RANBP2 (PubMed:15378033, PubMed:15608651, PubMed:11853669, PubMed:15931224, PubMed:16732283). Identified in a complex with SUMO2 and UBE2I, where one ZNF451 interacts with one UBE2I and two SUMO2 chains, one bound to the UBE2I active site and the other to another region of the same UBE2I molecule (PubMed:12924945, PubMed:26524494). Interacts with SETX (PubMed:24105744). Interacts with HIPK1 and HIPK2 (By similarity). Interacts with PPM1J (By similarity). Interacts with RASD2 (By similarity). Interacts with TCF3 (By similarity). Interacts with NR2C1; the interaction promotes its sumoylation (By similarity). Interacts with SIAH1 (PubMed:9334332). Interacts with PARP (PubMed:9197546). Interacts with various transcription factors such as TFAP2A, TFAP2B, and TFAP2C (PubMed:12072434). Interacts with AR (PubMed:10383460). Interacts with ETS1 (PubMed:9333025). Interacts with SOX4 (PubMed:16631117). Interacts with RWDD3; the interaction enhances the sumoylation of a number of proteins such as HIF1A and I-kappa-B (PubMed:17956732, PubMed:23469069). Interacts with FOXL2 (PubMed:19744555). Interacts with DNM1l (via its GTPase and B domains); the interaction promotes sumoylation of DNM1L, mainly in its B domain (PubMed:19638400). Interacts with NFATC2IP; this inhibits formation of poly-SUMO chains (PubMed:20077568). Interacts with FHIT (PubMed:11085938). Interacts with PRKRA and p53/TP53 (By similarity). Interacts with UHRF2 (PubMed:23404503). Interacts with NR3C1 and this interaction is enhanced in the presence of RWDD3 (PubMed:23508108, PubMed:25918163). Interacts with MTA1 (PubMed:21965678). Interacts with ZNF451 (PubMed:26524494). Interacts with CPEB3 (By similarity). Interacts with SUMO1, SUMO2 and SUMO3 (PubMed:17466333). Interacts with IPO13 (PubMed:21139563). Interacts with DNMT1 (PubMed:19450230). Interacts with SUMO1P1/SUMO5 (PubMed:27211601). Interacts with PML-RARA oncoprotein (via the coiled-colied domain); the interaction is required for sumoylation of the PML-RARA oncoprotein (PubMed:15809060). Interacts with ZBED1/hDREF (PubMed:27068747).SUBUNIT (Microbial infection) Interacts with human herpesvirus 6 IE2.SUBUNIT (Microbial infection) Interacts with human adenovirus early E1A protein; this interaction interferes with polysumoylation.SUBUNIT (Microbial infection) Interacts with Epstein-barr virus protein LMP1.SUBUNIT (Microbial infection) Interacts with ebolavirus VP35; this interaction mediates the sumoylation of IRF7 and contributes to the viral inhibition of IFN-type I production.SUBUNIT (Microbial infection) Interacts with Hantaan hantavirus nucleoprotein.SUBUNIT (Microbial infection) Interacts with human cytomegalovirus protein UL44.TISSUE SPECIFICITY Expressed in heart, skeletal muscle, pancreas, kidney, liver, lung, placenta and brain. Also expressed in testis and thymus.PTM Phosphorylation at Ser-71 significantly enhances SUMOylation activity.SIMILARITY Belongs to the ubiquitin-conjugating enzyme family. Reactome http://www.reactome.org Homo sapiens NCBI Taxonomy 9606 UniProt P63279 Chain Coordinates 1 EQUAL 158 EQUAL Reactome DB_ID: 912451 1 UniProt:Q6PIF2 SYCE2 SYCE2 SYCE2 CESC1 FUNCTION Major component of the transverse central element of synaptonemal complexes (SCS), formed between homologous chromosomes during meiotic prophase. Requires SYCP1 in order to be incorporated into the central element. May have a role in the synaptonemal complex assembly, stabilization and recombination (By similarity).SUBUNIT Homodimer. Found in a complex with SYCP1 and SYCE1. Interacts with SYCP1, SYCE1 and SYCE3 (By similarity). Interacts with TEX12 (By similarity).SIMILARITY Belongs to the SYCE family. UniProt Q6PIF2 1 EQUAL 218 EQUAL Reactome DB_ID: 914230 1 UniProt:Q9BTC0-1 DIDO1 DIDO1 DIDO1 KIAA0333 C20orf158 DATF1 FUNCTION Putative transcription factor, weakly pro-apoptotic when overexpressed (By similarity). Tumor suppressor. Required for early embryonic stem cell development.SUBUNIT Interacts specifically (via PHD-type zinc finger) with histone H3 that is trimethylated at 'Lys-4' (H3K4me3), histone phosphorylation at 'Thr-3' or 'Thr-6' disrupts this binding and promotes translocation of DIDO1 from chromatin to the mitotic spindle during mitosis.TISSUE SPECIFICITY Ubiquitous.DOMAIN The PHD-type zinc finger forms an aromatic cage around H3K4me3.MISCELLANEOUS Defects in DIDO1 may be a cause of myeloid neoplasms. UniProt Q9BTC0-1 1 EQUAL 2240 EQUAL Reactome DB_ID: 912338 1 Axial-Lateral Element of Synaptonemal Complex [nucleoplasm] Axial-Lateral Element of Synaptonemal Complex Reactome DB_ID: 912384 1 Meiotic Cohesin complex [nucleoplasm] Meiotic Cohesin complex Reactome DB_ID: 163016 1 UniProt:Q8WVM7 STAG1 STAG1 STAG1 SA1 SCC3 FUNCTION Component of cohesin complex, a complex required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. The cohesin complex may also play a role in spindle pole assembly during mitosis.SUBUNIT Cohesin complexes are composed of a heterodimer between a SMC1 protein (SMC1A or SMC1B) and SMC3, which are attached via their hinge domain, and RAD21 which link them at their heads, and one STAG protein (STAG1, STAG2 or STAG3). In cohesin complexes, STAG1 is mutually exclusive with STAG2 and STAG3 (PubMed:11076961). Interacts directly with RAD21 in cohesin complex (By similarity). Found in a cohesin complex with SMC1A, SMC3 and RAD21 (PubMed:22628566).PTM Phosphorylated by PLK1. The large dissociation of cohesin from chromosome arms during prophase is partly due to its phosphorylation (By similarity).SIMILARITY Belongs to the SCC3 family. UniProt Q8WVM7 1 EQUAL 1258 EQUAL Reactome DB_ID: 163028 1 UniProt:O95072 REC8 REC8 REC8L1 REC8 FUNCTION Required during meiosis for separation of sister chromatids and homologous chromosomes. Proteolytic cleavage of REC8 on chromosome arms by separin during anaphase I allows for homologous chromosome separation in meiosis I and cleavage of REC8 on centromeres during anaphase II allows for sister chromatid separation in meiosis II (By similarity).SUBUNIT Interacts (phosphorylated and unphosphorylated form) with SMC3. Interacts with SYCP3. Interacts (phosphorylated and unphosphorylated form) with SMC1B. Does not interact with SMC1A. Interacts with RAD51 (By similarity). Forms a complex with EWSR1, PRDM9, SYCP3 and SYCP1; complex formation is dependent of phosphorylated form of REC8 and requires PRDM9 bound to hotspot DNA; EWSR1 joins PRDM9 with the chromosomal axis through REC8 (By similarity).TISSUE SPECIFICITY Expressed in testis and thymus. Expressed in the B-cell lines WI-L2-NS and Namalwa (at protein level).PTM Phosphorylated.SIMILARITY Belongs to the rad21 family. UniProt O95072 1 EQUAL 547 EQUAL Reactome DB_ID: 64561 1 UniProt:Q14683 SMC1A SMC1A DXS423E SMC1L1 KIAA0178 SMC1A SB1.8 SMC1 FUNCTION Involved in chromosome cohesion during cell cycle and in DNA repair. Central component of cohesin complex. The cohesin complex is required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. The cohesin complex may also play a role in spindle pole assembly during mitosis. Involved in DNA repair via its interaction with BRCA1 and its related phosphorylation by ATM, or via its phosphorylation by ATR. Works as a downstream effector both in the ATM/NBS1 branch and in the ATR/MSH2 branch of S-phase checkpoint.SUBUNIT Forms a heterodimer with SMC3 in cohesin complexes (PubMed:22628566). Cohesin complexes are composed of the SMC1 (SMC1A or SMC1B) and SMC3 heterodimer attached via their SMC hinge domain, RAD21 which link them, and one STAG protein (STAG1, STAG2 or STAG3), which interacts with RAD21 (PubMed:11076961). In germ cell cohesin complexes, SMC1A is mutually exclusive with SMC1B (By similarity). Interacts with BRCA1 (PubMed:11877377). Found in a complex with CDCA5, SMC3 and RAD21, PDS5A/SCC-112 and PDS5B/APRIN (PubMed:15837422). Interacts with NDC80 (PubMed:9295362, PubMed:10409732,). Interacts with BRAT1 (PubMed:22977523). Found in a complex containing POLE and SMC3. Interacts with RPGR, STAG3 and SYCP2 (By similarity). Found in a cohesin complex with SMC3, STAG1 and RAD21 (PubMed:22628566). The SMC1A-SMC3 heterodimer interacts with the NIPBL-MAU2 heterodimer (PubMed:22628566).DOMAIN The flexible SMC hinge domain, which separates the large intramolecular coiled coil regions, allows the heterotypic interaction with the corresponding domain of SMC3, forming a V-shaped heterodimer. The two heads of the heterodimer are then connected by different ends of the cleavable RAD21 protein, forming a ring structure (By similarity).PTM Ubiquitinated by the DCX(DCAF15) complex, leading to its degradation.PTM Phosphorylated by ATM upon ionizing radiation in a NBS1-dependent manner. Phosphorylated by ATR upon DNA methylation in a MSH2/MSH6-dependent manner. Phosphorylation of Ser-957 and Ser-966 activates it and is required for S-phase checkpoint activation.MISCELLANEOUS Mutated Cornelia de Lange cell lines display genomic instability and sensitivity to ionizing radiation and interstrand cross-linking agents.SIMILARITY Belongs to the SMC family. SMC1 subfamily. UniProt Q14683 1 EQUAL 1233 EQUAL Reactome DB_ID: 163009 1 UniProt:Q9UQE7 SMC3 SMC3 SMC3L1 CSPG6 SMC3 BMH BAM FUNCTION Central component of cohesin, a complex required for chromosome cohesion during the cell cycle. The cohesin complex may form a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. Cohesion is coupled to DNA replication and is involved in DNA repair. The cohesin complex also plays an important role in spindle pole assembly during mitosis and in chromosomes movement.SUBUNIT Forms a heterodimer with SMC1A or SMC1B in cohesin complexes (PubMed:22628566). Cohesin complexes are composed of the SMC1 (SMC1A or SMC1B) and SMC3 heterodimer attached via their SMC hinge domain, RAD21 which link them, and one STAG protein (STAG1, STAG2 or STAG3), which interacts with RAD21. Also found in meiosis-specific cohesin complexes (PubMed:11076961). Found in a complex with SMC1A, CDCA5 and RAD21, PDS5A/SCC-112 and PDS5B/APRIN (PubMed:15837422). Interacts with NUMA1, and forms a ternary complex with KIF3B and KIFAP3, suggesting a function in tethering the chromosomes to the spindle pole and in chromosome movement (PubMed:9506951, PubMed:11590136). Interacts with PDS5A and WAPL; regulated by SMC3 acetylation (PubMed:19907496). Interacts (via SMC hinge domain) with KIAA1328 (via N- and C-terminal domains) (PubMed:15656913). Interacts with DDX11 (PubMed:17105772). Found in a cohesin complex with SMC1A, STAG1 and RAD21 (PubMed:22628566). The SMC1A-SMC3 heterodimer interacts with the NIPBL-MAU2 heterodimer (PubMed:22628566). Interacts with MXI1, MXD3, MXD4, SYCP2, RPGR and STAG3 (By similarity). Interacts with the NuRD complex component HDAC2; the interaction is direct (PubMed:12198550).DOMAIN The flexible SMC hinge domain, which separates the large intramolecular coiled coil regions, allows the heterotypic interaction with the corresponding domain of SMC1A or SMC1B, forming a V-shaped heterodimer. The two heads of the heterodimer are then connected by different ends of the cleavable RAD21 protein, forming a ring structure (By similarity).PTM Ubiquitinated by the DCX(DCAF15) complex, leading to its degradation.PTM Phosphorylated at Ser-1083 in a SPO11-dependent manner.PTM Acetylation at Lys-105 and Lys-106 by ESCO1 is important for genome stability and S phase sister chromatid cohesion. Regulated by DSCC1, it is required for processive DNA synthesis, coupling sister chromatid cohesion establishment during S phase to DNA replication. Deacetylation by HDAC8, regulates release of the cohesin complex from chromatin.MISCELLANEOUS Mutated Cornelia de Lange cell lines display genomic instability and sensitivity to ionizing radiation and interstrand cross-linking agents.SIMILARITY Belongs to the SMC family. SMC3 subfamily.CAUTION Was originally isolated as a proteoglycan protein (explaining its name). Although not excluded, such secreted function is not clear. UniProt Q9UQE7 1 EQUAL 1217 EQUAL Reactome DB_ID: 912342 1 UniProt:Q9UJ98 STAG3 STAG3 STAG3 FUNCTION Meiosis specific component of cohesin complex. The cohesin complex is required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. The meiosis-specific cohesin complex probably replaces mitosis specific cohesin complex when it dissociates from chromatin during prophase I.SUBUNIT Component of the meiosis-specific cohesin complex, which also contains the SMC1 (SMC1A or SMC1B) and SMC3 heterodimer. Such complex likely contains RAD21, or the meiosis-specific related protein REC8. Interacts with CCDC79/TERB1; recruiting cohesin to telomeres to develop structural rigidity (By similarity).TISSUE SPECIFICITY Testis specific.PTM Phosphorylated.SIMILARITY Belongs to the SCC3 family. UniProt Q9UJ98 1 EQUAL 1225 EQUAL Reactome DB_ID: 163046 1 UniProt:Q8N3U4 STAG2 STAG2 STAG2 SA2 FUNCTION Component of cohesin complex, a complex required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. The cohesin complex may also play a role in spindle pole assembly during mitosis.SUBUNIT Interacts directly with RAD21 in cohesin complex. Cohesin complexes are composed of a heterodimer between a SMC1 protein (SMC1A or SMC1B) and SMC3, which are attached via their hinge domain, and RAD21 which link them at their heads, and one STAG protein (STAG1, STAG2 or STAG3). In cohesin complexes, STAG2 is mutually exclusive with STAG1 and STAG3.PTM Phosphorylated by PLK1. The large dissociation of cohesin from chromosome arms during prophase is partly due to its phosphorylation (By similarity).SIMILARITY Belongs to the SCC3 family.CAUTION Variants MKMS 743-TRP--PHE-1231 DEL and HPE13 1033-ARG--PHE-1231 DEL were previously described; however, the corresponding paper has been retracted as Case 1's sex was incorrectly reported invalidating the conclusions. UniProt Q8N3U4 1 EQUAL 1231 EQUAL Reactome DB_ID: 163042 1 UniProt:O60216 RAD21 RAD21 RAD21 HR21 SCC1 KIAA0078 NXP1 SUBUNIT Component of the cohesin complex, which consists of an SMC1A/B and SMC3 heterodimer core and 2 non-Smc subunits RAD21 and STAG1/SA1, STAG2/SA2 or STAG3/SA3 (PubMed:10931856, PubMed:11590136, PubMed:22628566, PubMed:25575569). Interacts (via N-terminus) with SMC1A; the interaction is direct (PubMed:12198550). The cohesin complex interacts with NUMA1 (PubMed:11590136). The cohesin complex also interacts with CDCA5, PDS5A and PDS5B; this interaction might regulate the ability of the cohesin complex to mediate sister chromatid cohesion (PubMed:15837422). The interaction with PDS5B is direct and is stimulated by STAG1/SA1 (PubMed:19696148). The cohesin complex interacts with the cohesin loading complex subunits NIPBL/Scc2 (via HEAT repeats) and MAU2/Scc4 (PubMed:22628566). The cohesin complex interacts with DDX11/ChIR1 (PubMed:17105772). Directly interacts with WAPL; this interaction is stimulated by STAG1/SA1 (PubMed:19696148). Interacts with the ISWI chromatin remodeling complex component SMARCA5; the interaction is direct (PubMed:12198550). Interacts with the NuRD complex component CHD4; the interaction is direct (PubMed:12198550).TISSUE SPECIFICITY Expressed in the gut (at protein level).DEVELOPMENTAL STAGE Regulated in a cell cycle-dependent manner: expression increases in late S phase and reaches maximum in G2 at the nucleotide level (PubMed:8812457). Not regulated during the cell cycle (at protein level) (PubMed:11073952).DOMAIN The C-terminal part associates with the head of SMC1A, while the N-terminal part binds to the head of SMC3.PTM Cleaved by separase/ESPL1 at the onset of anaphase; this cleavage is required for sister chromatid separation and cytokinesis (PubMed:11509732). Cleaved by caspase-3/CASP3 or caspase-7/CASP7 at the beginning of apoptosis (PubMed:12417729, PubMed:11875078).PTM Phosphorylated; becomes hyperphosphorylated in M phase of cell cycle. The large dissociation of cohesin from chromosome arms during prophase may be partly due to its phosphorylation by PLK1.SIMILARITY Belongs to the rad21 family. UniProt O60216 1 EQUAL 631 EQUAL Reactome DB_ID: 912340 1 UniProt:Q8NDV3 SMC1B SMC1B SMC1L2 SMC1B FUNCTION Meiosis-specific component of cohesin complex. Required for the maintenance of meiotic cohesion, but not, or only to a minor extent, for its establishment. Contributes to axial element (AE) formation and the organization of chromatin loops along the AE. Plays a key role in synapsis, recombination and chromosome movements. The cohesin complex is required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. The meiosis-specific cohesin complex probably replaces mitosis specific cohesin complex when it dissociates from chromatin during prophase I (By similarity).SUBUNIT Forms a heterodimer with SMC3. Component of a meiosis-specific cohesin complex, probably composed of the SMC1B and SMC3 heterodimer attached via their SMC hinge domain, RAD21 (or its meiosis-specific related protein REC8), which link them, and STAG3, which interacts with RAD21 or REC8 (By similarity).DOMAIN The flexible SMC hinge domain, which separates the large intramolecular coiled coil regions, allows the heterotypic interaction with the corresponding domain of SMC3, forming a V-shaped heterodimer. The two heads of the heterodimer are then connected by different ends of the cleavable RAD21 or REC8 protein, forming a ring structure (By similarity).SIMILARITY Belongs to the SMC family. SMC1 subfamily. UniProt Q8NDV3 1 EQUAL 1235 EQUAL Reactome Database ID Release 82 912384 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=912384 Reactome R-HSA-912384 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-912384.1 Reactome DB_ID: 912329 1 UniProt:Q8IZU3 SYCP3 SYCP3 SCP3 SYCP3 FUNCTION Component of the synaptonemal complexes (SCS), formed between homologous chromosomes during meiotic prophase. Required for centromere pairing during meiosis in male germ cells (By similarity). Required for normal meiosis during spermatogenesis and male fertility (PubMed:14643120). Plays a lesser role in female fertility. Required for efficient phosphorylation of HORMAD1 and HORMAD2 (By similarity).SUBUNIT Component of the lateral elements of synaptonemal complexes (By similarity). Homotetramer; the tetrameric helix bundles assemble end to end into long homopolimeric fibers that exhibit a transversal striation with a periodicity of about 20 nm (in vitro) (PubMed:24950965). Interacts with SYCP2 (By similarity). Forms a complex with EWSR1, PRDM9, REC8 and SYCP1; complex formation is dependent of phosphorylated form of REC8 and requires PRDM9 bound to hotspot DNA; EWSR1 joins PRDM9 with the chromosomal axis through REC8 (By similarity).TISSUE SPECIFICITY Testis-specific.DOMAIN Composed of a long central coiled coil domain. The N-terminal and C-terminal regions interact with DNA.PTM Phosphorylated.SIMILARITY Belongs to the XLR/SYCP3 family. UniProt Q8IZU3 1 EQUAL 236 EQUAL Reactome DB_ID: 912407 1 UniProt:Q9BX26 SYCP2 SYCP2 SYCP2 SCP2 FUNCTION Major component of the axial/lateral elements of synaptonemal complexes (SCS) during meiotic prophase. Plays a role in the assembly of synaptonemal complexes. Required for normal meiotic chromosome synapsis during oocyte and spermatocyte development and for normal male and female fertility. Required for insertion of SYCP3 into synaptonemal complexes. May be involved in the organization of chromatin by temporarily binding to DNA scaffold attachment regions. Requires SYCP3, but not SYCP1, in order to be incorporated into the axial/lateral elements.SUBUNIT Component of the lateral elements of synaptonemal complexes. Heterodimer with SYCP3 (By similarity). Interacts with SMC1A and SMC3 (By similarity). Interacts with TEX11 (By similarity).PTM Phosphorylated.SIMILARITY Belongs to the SYCP2 family. UniProt Q9BX26 1 EQUAL 1530 EQUAL Reactome Database ID Release 82 912338 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=912338 Reactome R-HSA-912338 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-912338.1 Reactome DB_ID: 912480 1 UniProt:P54652 HSPA2 HSPA2 HSPA2 FUNCTION Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation. This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones. The affinity for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. It goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release (PubMed:26865365). Plays a role in spermatogenesis. In association with SHCBP1L may participate in the maintenance of spindle integrity during meiosis in male germ cells (By similarity).SUBUNIT Interacts with FKBP6 (PubMed:18529014). Interacts with ZNF541. Component of the CatSper complex. Interacts with RABL2/RABL2A; binds preferentially to GTP-bound RABL2. Interacts with SHCBP1L; this interaction may promote the recruitment of HSPA2 to the spindle (By similarity). Interacts with FKBP6 (PubMed:18529014).DOMAIN The N-terminal nucleotide binding domain (NBD) (also known as the ATPase domain) is responsible for binding and hydrolyzing ATP. The C-terminal substrate-binding domain (SBD) (also known as peptide-binding domain) binds to the client/substrate proteins. The two domains are allosterically coupled so that, when ATP is bound to the NBD, the SBD binds relatively weakly to clients. When ADP is bound in the NBD, a conformational change enhances the affinity of the SBD for client proteins.SIMILARITY Belongs to the heat shock protein 70 family. UniProt P54652 1 EQUAL 639 EQUAL Reactome DB_ID: 8867779 1 UniProt:A1L190 SYCE3 SYCE3 SYCE3 C22orf41 THEG2 FUNCTION Major component of the transverse central element of synaptonemal complexes (SCS), formed between homologous chromosomes during meiotic prophase. Required for chromosome loading of the central element-specific SCS proteins, and for initiating synapsis between homologous chromosomes. Chromosome loading appears to require SYCP1. Required for fertility.SUBUNIT Homodimer. Interacts with SYCE1. Interacts with SYCE2. Interacts with proteasome subunit PSMA8; to participate in meiosis progression during spermatogenesis (By similarity). Interacts with SPO16 (By similarity). UniProt A1L190 1 EQUAL 88 EQUAL Reactome DB_ID: 912456 1 UniProt:Q8N0S2 SYCE1 SYCE1 SYCE1 C10orf94 FUNCTION Major component of the transverse central element of synaptonemal complexes (SCS), formed between homologous chromosomes during meiotic prophase. Requires SYCP1 in order to be incorporated into the central element. May have a role in the synaptonemal complex assembly, stabilization and recombination.SUBUNIT Homodimer. Found in a complex with SYCP1 and SYCE2. Interacts with SYCP1, SYCE2 and SYCE3. Interacts with SIX6OS1.SIMILARITY Belongs to the SYCE family. UniProt Q8N0S2 1 EQUAL 351 EQUAL Reactome DB_ID: 912441 1 UniProt:Q9BXU0 TEX12 TEX12 TEX12 FUNCTION Component of the transverse central element of synaptonemal complexes (SCS), formed between homologous chromosomes during meiotic prophase (By similarity). Requires SYCP1 in order to be incorporated into the central element (By similarity).SUBUNIT Interacts with SYCE2.TISSUE SPECIFICITY Testis specific. UniProt Q9BXU0 1 EQUAL 123 EQUAL Reactome DB_ID: 912512 1 UniProt:O75344 FKBP6 FKBP6 FKBP36 FKBP6 FUNCTION Co-chaperone required during spermatogenesis to repress transposable elements and prevent their mobilization, which is essential for the germline integrity. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and govern the methylation and subsequent repression of transposons. Acts as a co-chaperone via its interaction with HSP90 and is required for the piRNA amplification process, the secondary piRNA biogenesis. May be required together with HSP90 in removal of 16 nucleotide ping-pong by-products from Piwi complexes, possibly facilitating turnover of Piwi complexes (By similarity).SUBUNIT Interacts (via TPR repeats) with HSP90 (By similarity). Interacts with HSP72/HSPA2 and CLTC. Interacts with GAPDH; leading to inhibit GAPDH catalytic activity.TISSUE SPECIFICITY Detected in all tissues examined, with higher expression in testis, heart, skeletal muscle, liver, and kidney.DISEASE FKBP6 is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region. Haploinsufficiency of FKBP6 may be the cause of certain cardiovascular and musculo-skeletal abnormalities observed in the disease (PubMed:9782077). A father and son with Williams-Beuren syndrome appear to have a common heterozygous deletion that includes FKBP6 gene. However, the haploinsufficiency for FKBP6 does not appear to preclude male fertility (PubMed:15770126).DISEASE Defects in FKBP6 may be a cause of azoospermia. A study based on 323 patients with azoospermia or severe oligozoospermia suggested an association between FKBP6 variants and azoospermia (PubMed:17307919). However, other studies suggest that defects in FKBP6 are not a common cause of non-obstructive azoospermia (PubMed:16227348).SIMILARITY Belongs to the FKBP6 family.CAUTION Although it contains a PPIase FKBP-type domain, does not show peptidyl-prolyl cis-trans isomerase activity. UniProt O75344 1 EQUAL 327 EQUAL Reactome DB_ID: 912494 1 UniProt:Q15431 SYCP1 SYCP1 SYCP1 SCP1 FUNCTION Major component of the transverse filaments of synaptonemal complexes, formed between homologous chromosomes during meiotic prophase. Required for normal assembly of the central element of the synaptonemal complexes. Required for normal centromere pairing during meiosis. Required for normal meiotic chromosome synapsis during oocyte and spermatocyte development and for normal male and female fertility.SUBUNIT Structural component of synaptonemal complexes (By similarity). Homotetramer that consists of an N-terminal four-helical bundle that bifurcates into two elongated C-terminal dimeric coiled coils (PubMed:29915389, PubMed:26323297). This tetrameric building block potentially self-assembles into a supramolecular zipper-like lattice to mediate meiotic chromosome synapsis. Self-assembly is likely initiated by local proton density at chromosome axis, which is predicted to trigger antiparallel back to back assembly of adjacent C-terminal ends into tetrameric structures that anchor to chromosomal DNA. Then the N-terminal ends are predicted to undergo cooperative antiparallel head to head assembly at the midline of synaptonemal complexes central element to form a zipper-like lattice between properly aligned homologous chromosomes (PubMed:29915389). The nascent synapsis generated by SYCP1 is stabilized through interaction with central element proteins SYCE1 and SYCE2 (By similarity). Forms a complex with EWSR1, PRDM9, SYCP3 and REC8; complex formation is dependent of phosphorylated form of REC8 and requires PRDM9 bound to hotspot DNA; EWSR1 joins PRDM9 with the chromosomal axis through REC8 (By similarity). Interacts with SPO16 (By similarity).TISSUE SPECIFICITY Testis.DOMAIN The molecule is in a coiled coil structure that is formed by 4 polypeptide chains. The N-terminal and C-terminal regions exhibit a prominent seven-residues periodicity. UniProt Q15431 1 EQUAL 976 EQUAL Reactome DB_ID: 912422 1 Synaptonemal Complex [nucleoplasm] Synaptonemal Complex Reactome DB_ID: 912481 1 1 EQUAL 158 EQUAL Reactome DB_ID: 912437 1 Transverse Filament of Synaptonemal Complex [nucleoplasm] Transverse Filament of Synaptonemal Complex Reactome DB_ID: 912494 2 1 EQUAL 976 EQUAL Reactome Database ID Release 82 912437 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=912437 Reactome R-HSA-912437 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-912437.2 Reactome DB_ID: 914230 1 1 EQUAL 2240 EQUAL Reactome DB_ID: 912338 1 Reactome DB_ID: 912480 1 1 EQUAL 639 EQUAL Reactome DB_ID: 912489 1 Central Element of Synaptonemal Complex [nucleoplasm] Central Element of Synaptonemal Complex Reactome DB_ID: 912451 1 1 EQUAL 218 EQUAL Reactome DB_ID: 8867779 1 1 EQUAL 88 EQUAL Reactome DB_ID: 912456 1 1 EQUAL 351 EQUAL Reactome DB_ID: 912441 1 1 EQUAL 123 EQUAL Reactome Database ID Release 82 912489 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=912489 Reactome R-HSA-912489 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-912489.2 Reactome DB_ID: 912512 1 1 EQUAL 327 EQUAL Reactome Database ID Release 82 912422 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=912422 Reactome R-HSA-912422 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-912422.1 Reactome Database ID Release 82 912505 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=912505 Reactome R-HSA-912505 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-912505.2 9285814 Pubmed 1997 Protein-protein interactions in the synaptonemal complex Tarsounas, M Pearlman, RE Gasser, PJ Park, MS Moens, PB Mol Biol Cell 8:1405-14 15235794 Pubmed 2004 Female-specific features of recombinational double-stranded DNA repair in relation to synapsis and telomere dynamics in human oocytes Roig, I Liebe, B Egozcue, J Cabero, L Garcia, M Scherthan, H Chromosoma 113:22-33