ID:SMC3_HUMAN DESCRIPTION: RecName: Full=Structural maintenance of chromosomes protein 3; Short=SMC protein 3; Short=SMC-3; AltName: Full=Basement membrane-associated chondroitin proteoglycan; Short=Bamacan; AltName: Full=Chondroitin sulfate proteoglycan 6; AltName: Full=Chromosome-associated polypeptide; Short=hCAP; 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 plays also an important role in spindle pole assembly during mitosis and in chromosomes movement. SUBUNIT: Interacts 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. INTERACTION: Q29RF7:PDS5A; NbExp=4; IntAct=EBI-80718, EBI-1175454; Q9NTI5:PDS5B; NbExp=6; IntAct=EBI-80718, EBI-1175604; O60216:RAD21; NbExp=8; IntAct=EBI-80718, EBI-80739; P32908:SMC1 (xeno); NbExp=4; IntAct=EBI-80718, EBI-17402; Q8WVM7:STAG1; NbExp=7; IntAct=EBI-80718, EBI-1175097; Q8N3U4:STAG2; NbExp=6; IntAct=EBI-80718, EBI-1057252; SUBCELLULAR LOCATION: Nucleus. 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. DOMAIN: The 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). PTM: Phosphorylated upon DNA damage, probably by ATM or ATR. 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. DISEASE: Defects in SMC3 are the cause of Cornelia de Lange syndrome type 3 (CDLS3) [MIM:610759]. CDLS is a dominantly inherited multisystem developmental disorder characterized by growth and cognitive retardation, abnormalities of the upper limbs, gastroesophageal dysfunction, cardiac, ophthalmologic and genitourinary anomalies, hirsutism, and characteristic facial features. CDSL3 is a mild form with absence of major structural anomalies typically associated with CDLS. The phenotype in some instances approaches that of apparently non-syndromic mental retardation. 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. SEQUENCE CAUTION: Sequence=AAD32447.1; Type=Frameshift; Positions=457, 488, 523;
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.
SCOP Domains: 52540 - P-loop containing nucleoside triphosphate hydrolases 53795 - PEP carboxykinase-like 75553 - Smc hinge domain 58104 - Methyl-accepting chemotaxis protein (MCP) signaling domain
ModBase Predicted Comparative 3D Structure on Q9UQE7
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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 SMC3: cdh-ov (Congenital Diaphragmatic Hernia Overview) cdls (Cornelia de Lange Syndrome) hpe-overview (Holoprosencephaly Overview)
Gene Model Information
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
