SMC3

Structural maintenance of chromosomes protein 3 (SMC3) is a protein that in humans is encoded by the SMC3 gene.[5] SMC3 is a subunit of the Cohesin complex which mediates sister chromatid cohesion, homologous recombination and DNA looping. Cohesin is formed of SMC3, SMC1, RAD21 and either SA1 or SA2. In humans, SMC3 is present in all cohesin complexes whereas there are multiple paralogs for the other subunits.

SMC3
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesSMC3, BAM, BMH, CDLS3, CSPG6, HCAP, SMC3L1, structural maintenance of chromosomes 3
External IDsOMIM: 606062 MGI: 1339795 HomoloGene: 3974 GeneCards: SMC3
Gene location (Human)
Chr.Chromosome 10 (human)[1]
Band10q25.2Start110,567,691 bp[1]
End110,604,636 bp[1]
RNA expression pattern




More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

9126

13006

Ensembl

ENSG00000108055

ENSMUSG00000024974

UniProt

Q9UQE7

Q9CW03

RefSeq (mRNA)

NM_005445

NM_007790

RefSeq (protein)

NP_005436

NP_031816

Location (UCSC)Chr 10: 110.57 – 110.6 MbChr 19: 53.6 – 53.65 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

SMC3 is a member of the SMC protein family. Members of this family are key regulators of DNA repair, chromosome condensation and chromosome segregation.

Structure and interactions
Structure of the interface between SMC3 (blue) and SMC1 (green) (PDB 2WD5) from mice (Kurze et al., 2009)
Structure of the interface between SMC3 (blue) and RAD21 (green) (PDB 4UX3) from budding yeast (Gligoris et al., 2014)

The domain organisation of SMC proteins is evolutionarily conserved and is composed of an N-terminal Walker A motif, coiled-coil, "hinge", coiled-coil and a C-terminal Walker B motif. The protein folds back on itself to form a rod-shaped molecule with a heterodimerisation "hinge" domain at one end and an ABC-type ATPase "head" at the other. These globular domains are separated by a ~50 nm anti-parallel coiled-coil. SMC3 and SMC1 bind via their hinge domains creating V-shaped heterodimers. The N-terminal domain of RAD21 binds to the coiled coil of SMC3 just above the head domain while the C-terminal domain of RAD21 binds the head domain of SMC1. This end to end binding of the SMC3-SMC1-RAD21 trimer creates a closed ring within which DNA can be entrapped. SA1 or

When DNA is replicated and sister chromatid cohesion is established SMC3 is acetylated on a pair of highly conserved lysines by ESCO1 and ESCO2. In budding yeast this modification is sufficient to stabilise cohesin on the DNA until mitosis but in animals, binding of sororin is also required.

During meiosis, SMC3 forms cohesin complexes with SMC1ß, STAG3 and REC8 which generate cohesion between homologous chromosomes and sister chromatids.[6]

Cornelia de Lange syndrome

Cornelia de Lange syndrome (CdLS) is a rare genetic disorder that presents with variable clinical abnormalities including dysmorphic features, severe growth retardation, global developmental delay, and intellectual disability. SMC3 is one of five genes that have been implicated in CdLS.[7] In one case report, a novel SMC3 gene duplication was detected in a child with failure to thrive, hypotonia and facial dysmorphic features of CdLS.[7] The same duplication was also observed in the mother, who had milder dysmorphic facies.

Mouse Model

Model organisms have been used in the study of SMC3 function. A conditional knockout mouse line, called Smc3tm1a(EUCOMM)Wtsi[15][16] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[17][18][19]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[13][20] Twenty two tests were carried out on mutant mice and six significant abnormalities were observed.[13] No homozygous mutant embryos were identified during gestation, and thus none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice. Females had a higher than normal incidence of pre-wean death in their offspring, and also had a decreased body weight. Males heterozygotes displayed a shortened, upturned snout.[13][20]

Role in Basement Membrane

SMC3 occurs in certain cell types as a secreted protein and post-translational addition of chondroitin sulfate chains gives rise to the secreted proteoglycan bamacan, an abundant basement membrane protein.[5]

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gollark: ```python>>> memmove(id(7), id(8), sys.getsizeof(7))140001623574848>>> 78```YES!
gollark: Sadly, no, I assume I must move all 28 bytes.
gollark: ```pythoncast(id(7), POINTER(c_int64)).contents = cast(id(8), POINTER(c_int64)).contents```It's weirdly fine with this.
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References
  1. GRCh38: Ensembl release 89: ENSG00000108055 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000024974 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: SMC3 structural maintenance of chromosomes 3".
  6. Garcia-Cruz R, Brieño MA, Roig I, Grossmann M, Velilla E, Pujol A, Cabero L, Pessarrodona A, Barbero JL, Garcia Caldés M (2010). "Dynamics of cohesin proteins REC8, STAG3, SMC1 beta and SMC3 are consistent with a role in sister chromatid cohesion during meiosis in human oocytes". Hum. Reprod. 25 (9): 2316–27. doi:10.1093/humrep/deq180. PMID 20634189.
  7. Infante E, Alkorta-Aranburu G, El-Gharbawy A (2017). "Rare form of autosomal dominant familial Cornelia de Lange syndrome due to a novel duplication in SMC3". Clin Case Rep. 5 (8): 1277–1283. doi:10.1002/ccr3.1010. PMC 5538066. PMID 28781842.
  8. "Body weight data for Smc3". Wellcome Trust Sanger Institute.
  9. "Dysmorphology data for Smc3". Wellcome Trust Sanger Institute.
  10. "DEXA data for Smc3". Wellcome Trust Sanger Institute.
  11. "Salmonella infection data for Smc3". Wellcome Trust Sanger Institute.
  12. "Citrobacter infection data for Smc3". Wellcome Trust Sanger Institute.
  13. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
  14. Mouse Resources Portal, Wellcome Trust Sanger Institute.
  15. "International Knockout Mouse Consortium".
  16. "Mouse Genome Informatics".
  17. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  18. Dolgin E (2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  19. Collins FS, Rossant J, Wurst W (2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
  20. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biol. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
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