Description: Homo sapiens structural maintenance of chromosomes 1A (SMC1A), mRNA. RefSeq Summary (NM_006306): 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]. Transcript (Including UTRs) Position: hg19 chrX:53,401,070-53,449,618 Size: 48,549 Total Exon Count: 25 Strand: - Coding Region Position: hg19 chrX:53,407,024-53,449,549 Size: 42,526 Coding Exon Count: 25
ID:SMC1A_HUMAN DESCRIPTION: RecName: Full=Structural maintenance of chromosomes protein 1A; Short=SMC protein 1A; Short=SMC-1-alpha; Short=SMC-1A; AltName: Full=Sb1.8; 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. SUBUNIT: Interacts 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. INTERACTION: P33993:MCM7; NbExp=8; IntAct=EBI-80690, EBI-355924; SUBCELLULAR LOCATION: Nucleus. Chromosome. Chromosome, centromere, kinetochore. 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. DOMAIN: The 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). 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. DISEASE: Defects in SMC1A are the cause of Cornelia de Lange syndrome type 2 (CDLS2) [MIM:300590]; also known as Cornelia de Lange syndrome X-linked. CDLS is a clinically heterogeneous developmental disorder associated with malformations affecting multiple systems. CDLS is characterized by facial dysmorphisms, abnormal hands and feet, growth delay, cognitive retardation and various other malformations including gastroesophageal dysfunction and cardiac, ophthalmologic and genitourinary anomalies. 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. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/SMC1A";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Pfam Domains: PF02463 - RecF/RecN/SMC N terminal domain PF06470 - SMC proteins Flexible Hinge Domain PF13175 - AAA ATPase domain PF13304 - AAA domain, putative AbiEii toxin, Type IV TA system PF13476 - AAA domain PF13555 - P-loop containing region of AAA domain
SCOP Domains: 52540 - P-loop containing nucleoside triphosphate hydrolases 53795 - PEP carboxykinase-like 75553 - Smc hinge domain
ModBase Predicted Comparative 3D Structure on Q14683
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
GeneReviews article(s) related to gene SMC1A: cdh-ov (Congenital Diaphragmatic Hernia Overview) cdls (Cornelia de Lange Syndrome) hpe-overview (Holoprosencephaly Overview)
Gene Model Information
category:
coding
nonsense-mediated-decay:
no
RNA accession:
NM_006306.2
exon count:
25
CDS single in 3' UTR:
no
RNA size:
9725
ORF size:
3702
CDS single in intron:
no
Alignment % ID:
100.00
txCdsPredict score:
7493.00
frame shift in genome:
no
% Coverage:
100.00
has start codon:
yes
stop codon in genome:
no
# of Alignments:
1
has end codon:
yes
retained intron:
no
# AT/AC introns
0
selenocysteine:
no
end bleed into intron:
0
# strange splices:
0
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