BioPAX pathway converted from "Synapsis" in the Reactome database.LEFT-TO-RIGHTSynapsisFormation of Central Elements of the Synaptonemal ComplexInitiation 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, 2010-07-02Reviewed: Bolcun-Filas, E, 2011-02-25Reviewed: Cohen, PE, 2011-02-04Reviewed: Holloway, JK, 2011-02-04Reviewed: Lyndaker, A, 2011-02-25Reviewed: Schimenti, JC, 2011-02-04Reviewed: Strong, E, 2011-02-25Edited: May, B, 2010-07-02FKBP6Peptidyl-prolyl cis-trans isomerase FKBP6FKBP6_HUMANReactome DB_ID: 912512nucleoplasmGENE ONTOLOGYGO:0005654UniProt:O75344 FKBP6FKBP6FKBP36FUNCTION 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.Homo sapiensNCBI Taxonomy9606UniProtO753441EQUAL327EQUALReactome Database ID Release 75912512Database 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=912512ReactomeR-HSA-9125121Reactome 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-912512.1Reactomehttp://www.reactome.orgDIDO3DIDO1-1Death-inducer obliterator 1 isoform 1DIDO1_HUMANReactome DB_ID: 914230UniProt:Q9BTC0-1 DIDO1DIDO1C20orf158DATF1KIAA0333FUNCTION 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 IsoformQ9BTC0-11EQUAL2240EQUALReactome Database ID Release 75914230Database 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=914230ReactomeR-HSA-9142301Reactome 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-914230.1SYCE3Synaptonemal complex central element protein 3SYCE3_HUMANReactome DB_ID: 8867779UniProt:A1L190 SYCE3SYCE3C22orf41THEG2FUNCTION 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).UniProtA1L1901EQUAL88EQUALReactome Database ID Release 758867779Database 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=8867779ReactomeR-HSA-88677792Reactome 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-8867779.2SYCP1Synaptonemal complex protein 1SYCP1_HUMANReactome DB_ID: 912494UniProt:Q15431 SYCP1SYCP1SCP1FUNCTION 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).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.UniProtQ154311EQUAL976EQUALReactome Database ID Release 75912494Database 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=912494ReactomeR-HSA-9124941Reactome 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-912494.1UBE2IUBE2I (UBC9)SUMO-conjugating enzyme UBC9UBC9_HUMANReactome DB_ID: 912481UniProt:P63279 UBE2IUBE2IUBC9UBCE9FUNCTION 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.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.UniProtP632791EQUAL158EQUALReactome Database ID Release 75912481Database 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=912481ReactomeR-HSA-9124811Reactome 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-912481.1TEX12Testis-expressed sequence 12 proteinTEX12_HUMANReactome DB_ID: 912441UniProt:Q9BXU0 TEX12TEX12TISSUE SPECIFICITY Testis specific.UniProtQ9BXU01EQUAL123EQUALReactome Database ID Release 75912441Database 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=912441ReactomeR-HSA-9124411Reactome 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-912441.1SYCE1Synaptonemal complex central element protein 1SYCE1_HUMANReactome DB_ID: 912456UniProt:Q8N0S2 SYCE1SYCE1C10orf94FUNCTION 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.UniProtQ8N0S21EQUAL351EQUALReactome Database ID Release 75912456Database 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=912456ReactomeR-HSA-9124561Reactome 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-912456.1Axial-Lateral Element of Synaptonemal ComplexReactome DB_ID: 912338SYCP3Synaptonemal complex protein 3SYCP3_HUMANReactome DB_ID: 912329UniProt:Q8IZU3 SYCP3SYCP3SCP3FUNCTION 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.UniProtQ8IZU31EQUAL236EQUALReactome Database ID Release 75912329Database 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=912329ReactomeR-HSA-9123291Reactome 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-912329.11SYCP2Synaptonemal complex protein 2SYCP2_HUMANReactome DB_ID: 912407UniProt:Q9BX26 SYCP2SYCP2SCP2FUNCTION 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.UniProtQ9BX261EQUAL1530EQUALReactome Database ID Release 75912407Database 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=912407ReactomeR-HSA-9124071Reactome 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-912407.11Meiotic Cohesin complexReactome DB_ID: 912384REC8Rec8Reactome DB_ID: 163028UniProt:O95072 REC8REC8REC8L1FUNCTION 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.UniProtO950721EQUAL547EQUALReactome Database ID Release 75163028Database 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=163028ReactomeR-HSA-1630281Reactome 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-163028.11SMC3Structural maintenance of chromosomes protein 3Reactome DB_ID: 163009UniProt:Q9UQE7 SMC3SMC3BAMBMHCSPG6SMC3L1FUNCTION 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 plays also 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).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.UniProtQ9UQE71EQUAL1217EQUALReactome Database ID Release 75163009Database 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=163009ReactomeR-HSA-1630091Reactome 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-163009.11STAG3Cohesin subunit SA-3STAG3_HUMANReactome DB_ID: 912342UniProt:Q9UJ98 STAG3STAG3FUNCTION 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.UniProtQ9UJ981EQUAL1225EQUALReactome Database ID Release 75912342Database 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=912342ReactomeR-HSA-9123421Reactome 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-912342.11SA2STAG2Cohesin subunit SA-2SCC3 homolog 2Reactome DB_ID: 163046UniProt:Q8N3U4 STAG2STAG2SA2FUNCTION 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.UniProtQ8N3U41EQUAL1231EQUALReactome Database ID Release 75163046Database 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=163046ReactomeR-HSA-1630461Reactome 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-163046.11SA1STAG1Cohesin subunit SA-1SCC3 homolog 1Reactome DB_ID: 163016UniProt:Q8WVM7 STAG1STAG1SA1SCC3FUNCTION 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.UniProtQ8WVM71EQUAL1258EQUALReactome Database ID Release 75163016Database 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=163016ReactomeR-HSA-1630161Reactome 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-163016.11SMC1BStructural maintenance of chromosomes protein 1BSMC1B_HUMANReactome DB_ID: 912340UniProt:Q8NDV3 SMC1BSMC1BSMC1L2FUNCTION 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.UniProtQ8NDV31EQUAL1235EQUALReactome Database ID Release 75912340Database 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=912340ReactomeR-HSA-9123401Reactome 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-912340.11RAD21Reactome DB_ID: 163042UniProt:O60216 RAD21RAD21HR21KIAA0078NXP1SCC1SUBUNIT 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). 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).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.UniProtO602161EQUAL631EQUALReactome Database ID Release 75163042Database 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=163042ReactomeR-HSA-1630421Reactome 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-163042.11SMC1ASMC1 (BAA11495)Structural maintenance of chromosome 1-like 1 protein (SMC1alpha protein) (SB1.8/DXS423E protein) (Sb1.8)Structural maintenance of chromosome 1-like 1 proteinSMC1alpha proteinSB1.8/DXS423E proteinSb1.8Reactome DB_ID: 64561UniProt:Q14683 SMC1ASMC1ADXS423EKIAA0178SB1.8SMC1SMC1L1FUNCTION 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.UniProtQ146831EQUAL1233EQUALReactome Database ID Release 7564561Database 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=64561ReactomeR-HSA-645611Reactome 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-64561.11Reactome Database ID Release 75912384Database 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=912384ReactomeR-HSA-9123841Reactome 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-912384.11Reactome Database ID Release 75912338Database 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=912338ReactomeR-HSA-9123381Reactome 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-912338.1SYCE2Synaptonemal complex central element protein 2SYCE2_HUMANReactome DB_ID: 912451UniProt:Q6PIF2 SYCE2SYCE2CESC1FUNCTION 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).SIMILARITY Belongs to the SYCE family.UniProtQ6PIF21EQUAL218EQUALReactome Database ID Release 75912451Database 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=912451ReactomeR-HSA-9124511Reactome 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-912451.1HSPA2Heat shock-related 70 kDa protein 2HSP72_HUMANReactome DB_ID: 912480UniProt:P54652 HSPA2HSPA2FUNCTION 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.UniProtP546521EQUAL639EQUALReactome Database ID Release 75912480Database 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=912480ReactomeR-HSA-9124801Reactome 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-912480.1Synaptonemal ComplexReactome DB_ID: 91242211Central Element of Synaptonemal ComplexReactome DB_ID: 9124891111Reactome Database ID Release 75912489Database 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=912489ReactomeR-HSA-9124892Reactome 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-912489.21Transverse Filament of Synaptonemal ComplexReactome DB_ID: 9124372Reactome Database ID Release 75912437Database 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=912437ReactomeR-HSA-9124372Reactome 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-912437.21111Reactome Database ID Release 75912422Database 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=912422ReactomeR-HSA-9124221Reactome 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-912422.1Reactome Database ID Release 75912505Database 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=912505ReactomeR-HSA-9125052Reactome 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-912505.29285814Pubmed1997Protein-protein interactions in the synaptonemal complexTarsounas, MPearlman, REGasser, PJPark, MSMoens, PBMol Biol Cell 8:1405-1415235794Pubmed2004Female-specific features of recombinational double-stranded DNA repair in relation to synapsis and telomere dynamics in human oocytesRoig, ILiebe, BEgozcue, JCabero, LGarcia, MScherthan, HChromosoma 113:22-33