Structural maintenance of chromosome 3 (chondroitin sulfate proteoglycan 6, chromosome-associated polypeptide, hCAP, bamacan, basement membrane-associated chondroitin proteoglycan, CSPG6, BAM, BMH, SMC3, SMC3L1)
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Function
- role in chromosome cohesion during cell cycle & in DNA repair
- component of cohesin complex
- interacts with MXI1, MXD3 & MXD4
- interacts with SYCP2
- found in a complex with SMC1A, CDCA5 & RAD21, PDS5A/APRIN & PDS5B/SCC-112 (putative)
- forms a heterodimer with SMC1A or SMC1B in cohesin complexes
- also found in meiosis-specific cohesin complexes
- interacts with NUMA1, & forms a ternary complex with KIF3B & KIFAP3, suggesting a function in tethering the chromosomes to the spindle pole & in chromosome movement
- phosphorylated upon DNA damage, probably by ATM or ATR
Structure
- 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 (putative)
- belongs to the SMC family, SMC3 subfamily
Compartment
- nucleus
- 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
Pathology
- defects in SMC3 are the cause of Cornelia de Lange syndrome type 3
Notes
- originally isolated as a proteoglycan protein (explaining its name); secreted function is uncertain