SMC1A
Proper cohesion of sister chromatids is a prerequisite for the correct segregation of chromosomes during cell division. The cohesin multiprotein complex is required for sister chromatid cohesion. This complex is composed partly of two structural maintenance of chromosomes (SMC) proteins, SMC3 and either SMC1B or the protein encoded by this gene. Most of the cohesin complexes dissociate from the chromosomes before mitosis, although those complexes at the kinetochore remain. Therefore, the encoded protein is thought to be an important part of functional kinetochores. In addition, this protein interacts with BRCA1 and is phosphorylated by ATM, indicating a potential role for this protein in DNA repair. This gene, which belongs to the SMC gene family, is located in an area of the X-chromosome that escapes X inactivation. Mutations in this gene result in Cornelia de Lange syndrome. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]
Full Name
Structural Maintenance Of Chromosomes 1A
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.
Biological Process
Biological Process cell divisionIEA:UniProtKB-KW
Biological Process DNA repairManual Assertion Based On ExperimentTAS:UniProtKB
Biological Process establishment of meiotic sister chromatid cohesion1 PublicationIC:ComplexPortal
Biological Process meiotic cell cycleISS:UniProtKB
Biological Process mitotic sister chromatid cohesionManual Assertion Based On ExperimentTAS:UniProtKB
Biological Process mitotic sister chromatid segregationManual Assertion Based On ExperimentTAS:UniProtKB
Biological Process mitotic spindle assemblyManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process response to DNA damage checkpoint signalingManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process response to radiationManual Assertion Based On ExperimentIEP:UniProtKB
Biological Process sister chromatid cohesionManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process somatic stem cell population maintenanceIEA:Ensembl
Cellular Location
Nucleus
Chromosome
Chromosome, centromere, kinetochore
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.
Involvement in disease
Cornelia de Lange syndrome 2 (CDLS2):
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.
Developmental and epileptic encephalopathy 85 with or without midline brain defects (DEE85):
An X-linked form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE85 is characterized by onset of severe refractory seizures in the first year of life, global developmental delay with impaired intellectual development and poor or absent speech, and dysmorphic facial features. Many patients have midline brain defects on brain imaging.
PTM
Ubiquitinated by the DCX(DCAF15) complex, leading to its degradation.
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.
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