MGP Database

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MGP003473

UniProt Annotations

Entry Information
Gene Namestructural maintenance of chromosomes 1A
Protein EntrySMC1A_HUMAN
UniProt IDQ14683
SpeciesHuman
Comments
Comment typeDescription
DiseaseCornelia de Lange syndrome 2 (CDLS2) [MIM:300590]: 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. {ECO:0000269|PubMed:16604071, ECO:0000269|PubMed:17221863, ECO:0000269|PubMed:17273969, ECO:0000269|PubMed:19701948, ECO:0000269|PubMed:20358602, ECO:0000269|PubMed:20635401}. 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 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). {ECO:0000250}.
FunctionInvolved 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. {ECO:0000269|PubMed:11877377}.
InteractionQ99IB8:- (xeno); NbExp=3; IntAct=EBI-80690, EBI-6927928; P33993:MCM7; NbExp=8; IntAct=EBI-80690, EBI-355924;
MiscellaneousMutated Cornelia de Lange cell lines display genomic instability and sensitivity to ionizing radiation and interstrand cross-linking agents.
PtmPhosphorylated 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. {ECO:0000269|PubMed:11877377, ECO:0000269|PubMed:14657349, ECO:0000269|PubMed:17525332, ECO:0000269|PubMed:18669648, ECO:0000269|PubMed:19690332, ECO:0000269|PubMed:20068231}.
SimilarityBelongs to the SMC family. SMC1 subfamily. {ECO:0000305}.
Subcellular LocationNucleus {ECO:0000269|PubMed:12199140}. Chromosome {ECO:0000269|PubMed:12199140}. Chromosome, centromere, kinetochore {ECO:0000269|PubMed:12199140}. 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. In germ cells, cohesin complex dissociates from chromatin at prophase I, and may be replaced by a meiosis-specific cohesin complex. The phosphorylated form on Ser-957 and Ser-966 associates with chromatin during G1/S/G2 phases but not during M phase, suggesting that phosphorylation does not regulate cohesin function. Integral component of the functional centromere- kinetochore complex at the kinetochore region during mitosis.
SubunitInteracts with POLE. Interacts with SYCP2. Interacts with BRCA1. Found in a complex with CDCA5, SMC3 and RAD21, PDS5A/APRIN and PDS5B/SCC-112 (By similarity). Forms a heterodimer with SMC3 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. In germ cell cohesin complexes, SMC1A is mutually exclusive with SMC1B. Interacts with BRCA1. Interacts with NDC80. Interacts with RPGR (By similarity). {ECO:0000250}.
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