MGP Database

New search | Record Overview | Ontology/Pathway Information | Domain Information | UniProt Annotations | Related Proteins
MGP003805

UniProt Annotations

Entry Information
Gene Namestructural maintenance of chromosomes 3
Protein EntrySMC3_HUMAN
UniProt IDQ9UQE7
SpeciesHuman
Comments
Comment typeDescription
CautionWas originally isolated as a proteoglycan protein (explaining its name). Although not excluded, such secreted function is not clear. {ECO:0000305}.
DiseaseCornelia de Lange syndrome 3 (CDLS3) [MIM:610759]: A form of Cornelia de Lange syndrome, a clinically heterogeneous developmental disorder associated with malformations affecting multiple systems. Characterized by facial dysmorphisms, abnormal hands and feet, growth delay, cognitive retardation, hirsutism, gastroesophageal dysfunction and cardiac, ophthalmologic and genitourinary anomalies. Cornelia de Lange syndrome type 3 is a mild form with absence of major structural anomalies. The phenotype in some instances approaches that of apparently non- syndromic mental retardation. {ECO:0000269|PubMed:17273969}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DomainThe flexible 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). {ECO:0000250}.
FunctionCentral 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. {ECO:0000269|PubMed:11076961, ECO:0000269|PubMed:19907496}.
InteractionQ9BTE3:MCMBP; NbExp=6; IntAct=EBI-80718, EBI-749378; Q29RF7:PDS5A; NbExp=4; IntAct=EBI-80718, EBI-1175454; Q9NTI5:PDS5B; NbExp=7; IntAct=EBI-80718, EBI-1175604; O60216:RAD21; NbExp=10; IntAct=EBI-80718, EBI-80739; P32908:SMC1 (xeno); NbExp=4; IntAct=EBI-80718, EBI-17402; Q8WVM7:STAG1; NbExp=10; IntAct=EBI-80718, EBI-1175097; Q8N3U4:STAG2; NbExp=9; IntAct=EBI-80718, EBI-1057252;
MiscellaneousMutated Cornelia de Lange cell lines display genomic instability and sensitivity to ionizing radiation and interstrand cross-linking agents.
PtmAcetylation 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. {ECO:0000269|PubMed:18614053, ECO:0000269|PubMed:19608861, ECO:0000269|PubMed:19907496, ECO:0000269|PubMed:22885700}.
PtmPhosphorylated at Ser-1083 in a SPO11-dependent manner. {ECO:0000250}.
Sequence CautionSequence=AAD32447.1; Type=Frameshift; Positions=457, 488, 523; Evidence={ECO:0000305};
SimilarityBelongs to the SMC family. SMC3 subfamily. {ECO:0000305}.
Subcellular LocationNucleus. Chromosome. Chromosome, centromere. Note=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). {ECO:0000250}.
SubunitInteracts with MXI1, MXD3 and MXD4. Interacts with SYCP2. Found in a complex with SMC1A, CDCA5 and RAD21, PDS5A/APRIN and PDS5B/SCC-112 (By similarity). Forms a heterodimer with SMC1A or SMC1B in cohesin complexes. Cohesin complexes are composed of the SMC1 (SMC1A or SMC1B) and SMC3 heterodimer attached via their 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. 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. Interacts with PDS5A and WAPAL; regulated by SMC3 acetylation. Interacts with RPGR (By similarity). {ECO:0000250}.
  logo