checksum
21EF9A08A5D8096A
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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 (PubMed:32409525). 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:11590136, PubMed:9506951). 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 cohesin complex interacts with the cohesin loading complex subunits NIPBL/Scc2 (via HEAT repeats) and MAU2/Scc4 (PubMed:22628566). NIPBL directly contacts all members of the complex, RAD21, SMC1A/B, SMC3 and STAG1 (PubMed:22628566, PubMed:32409525). Interacts with MXI1, MXD3, MXD4, SYCP2, RPGR and STAG3 (By similarity). Interacts with the NuRD complex component HDAC2; the interaction is direct (PubMed:12198550).INTERACTION Associates with chromatin. Before prophase it is scattered along chromosome arms. During prophase, most of cohesin complexes dissociate from chromatin probably because of phosphorylation by PLK, except at centromeres, where cohesin complexes remain. At anaphase, the RAD21 subunit of the cohesin complex is cleaved, leading to the dissociation of the complex from chromosomes, allowing chromosome separation. The phosphorylated form at Ser-1083 is preferentially associated with unsynapsed chromosomal regions (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.DISEASE The disease is caused by variants affecting the gene represented in this entry.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.
databaseName
UniProt
dbId
64642
description
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recommendedName: Structural maintenance of chromosomes protein 3 shortName: SMC protein 3 shortName: SMC-3 alternativeName: Basement membrane-associated chondroitin proteoglycan shortName: Bamacan alternativeName: Chondroitin sulfate proteoglycan 6 alternativeName: Chromosome-associated polypeptide shortName: hCAP
displayName
UniProt:Q9UQE7 SMC3
geneName
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SMC3
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BAM
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BMH
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CSPG6
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SMC3L1
identifier
Q9UQE7
isSequenceChanged
false
keyword
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3D-structure
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Acetylation
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ATP-binding
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Cell cycle
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Cell division
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Centromere
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Chromosome
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Coiled coil
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Direct protein sequencing
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Disease variant
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DNA damage
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DNA repair
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Intellectual disability
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Meiosis
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Mitosis
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Nucleotide-binding
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Nucleus
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Phosphoprotein
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Proteomics identification
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Reference proteome
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Ubl conjugation
moleculeType
Protein
schemaClass
ReferenceGeneProduct
secondaryIdentifier
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SMC3_HUMAN
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A8K156
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O60464
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Q5T482
sequenceLength
1217
stId
uniprot:Q9UQE7