SMC3

Structural maintenance of chromosomes 3
Identifiers
Symbols	SMC3 ; BAM; BMH; CDLS3; CSPG6; HCAP; SMC3L1
External IDs	OMIM: 606062 MGI: 1339795 HomoloGene: 3974 GeneCards: SMC3 Gene
Gene ontology Molecular function • chromatin binding • microtubule motor activity • protein binding • ATP binding • mediator complex binding • dynein binding • protein heterodimerization activity Cellular component • chromosome, centromeric region • chromatin • lateral element • spindle pole • basement membrane • nucleus • nucleoplasm • chromosome • cytoplasm • cytosol • cohesin complex • cohesin core heterodimer • nuclear matrix • meiotic cohesin complex • nuclear meiotic cohesin complex Biological process • mitotic cell cycle • regulation of DNA replication • DNA repair • mitotic spindle organization • sister chromatid cohesion • mitotic sister chromatid cohesion • mitotic nuclear division • meiotic nuclear division • signal transduction • protein sumoylation • stem cell maintenance • negative regulation of DNA endoreduplication • post-translational protein modification • cellular protein metabolic process • cell division Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
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 Mb	Chr 19: 53.6 – 53.65 Mb
PubMed search

Structural maintenance of chromosomes 3, also known as SMC3, is a human gene.^[1]

Function

This gene belongs to the SMC3 subfamily of SMC proteins. The encoded protein occurs in certain cell types as either an intracellular, nuclear protein or a secreted protein. The nuclear form, known as structural maintenance of chromosomes 3, is a component of the multimeric cohesin complex that holds together sister chromatids during mitosis, enabling proper chromosome segregation. Post-translational modification of the encoded protein by the addition of chondroitin sulfate chains gives rise to the secreted proteoglycan bamacan, an abundant basement membrane protein.^[1]

Model organisms

Smc3 knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Abnormal
Recessive lethal study	Abnormal
Homozygous Fertility	Abnormal
Body weight	Abnormal[2]
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Abnormal[3]
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Abnormal[4]
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology	Normal
Peripheral blood lymphocytes	Normal
Heart weight	Normal
Eye Histopathology	Normal
Salmonella infection	Normal[5]
Citrobacter infection	Normal[6]
All tests and analysis from[7][8]

Model organisms have been used in the study of SMC3 function. A conditional knockout mouse line, called Smc3^{tm1a(EUCOMM)Wtsi[9][10]} 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.^[11][12][13]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.^[7][14] Twenty two tests were carried out on mutant mice and six significant abnormalities were observed.^[7] 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.^[7][14]

Interactions

SMC3 (gene) has been shown to interact with:

• KIFAP3,^[15]
• MXD1,^[16]
• MXI1,^[16]
• REC8,^[17] and
• SMC1A.^{[17][18][19][20]}

See also

• Cornelia de Lange Syndrome

References

1. "Entrez Gene: SMC3 structural maintenance of chromosomes 3".
2. "Body weight data for Smc3". Wellcome Trust Sanger Institute.
3. "Dysmorphology data for Smc3". Wellcome Trust Sanger Institute.
4. "DEXA data for Smc3". Wellcome Trust Sanger Institute.
5. "Salmonella infection data for Smc3". Wellcome Trust Sanger Institute.
6. "Citrobacter infection data for Smc3". Wellcome Trust Sanger Institute.
7. 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.
8. Mouse Resources Portal, Wellcome Trust Sanger Institute.
9. "International Knockout Mouse Consortium".
10. "Mouse Genome Informatics".
11. 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.
12. Dolgin E (2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
13. 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.
14. 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.
15. Shimizu K, Shirataki H, Honda T, Minami S, Takai Y (March 1998). "Complex formation of SMAP/KAP3, a KIF3A/B ATPase motor-associated protein, with a human chromosome-associated polypeptide". J. Biol. Chem. 273 (12): 6591–4. doi:10.1074/jbc.273.12.6591. PMID 9506951.
16. Gupta K, Anand G, Yin X, Grove L, Prochownik EV (March 1998). "Mmip1: a novel leucine zipper protein that reverses the suppressive effects of Mad family members on c-myc". Oncogene 16 (9): 1149–59. doi:10.1038/sj.onc.1201634. PMID 9528857.
17. Lee J, Iwai T, Yokota T, Yamashita M (July 2003). "Temporally and spatially selective loss of Rec8 protein from meiotic chromosomes during mammalian meiosis". J. Cell. Sci. 116 (Pt 13): 2781–90. doi:10.1242/jcs.00495. PMID 12759374.
18. Kim ST, Xu B, Kastan MB (March 2002). "Involvement of the cohesin protein, Smc1, in Atm-dependent and independent responses to DNA damage". Genes Dev. 16 (5): 560–70. doi:10.1101/gad.970602. PMC 155347. PMID 11877376.
19. Schmiesing JA, Ball AR, Gregson HC, Alderton JM, Zhou S, Yokomori K (October 1998). "Identification of two distinct human SMC protein complexes involved in mitotic chromosome dynamics". Proc. Natl. Acad. Sci. U.S.A. 95 (22): 12906–11. doi:10.1073/pnas.95.22.12906. PMC 23650. PMID 9789013.
20. Gregson HC, Schmiesing JA, Kim JS, Kobayashi T, Zhou S, Yokomori K (Dec 2001). "A potential role for human cohesin in mitotic spindle aster assembly". J. Biol. Chem. 276 (50): 47575–82. doi:10.1074/jbc.M103364200. PMID 11590136.

Further reading

• Wu RR, Couchman JR (1997). "cDNA cloning of the basement membrane chondroitin sulfate proteoglycan core protein, bamacan: a five domain structure including coiled-coil motifs". J. Cell Biol. 136 (2): 433–44. doi:10.1083/jcb.136.2.433. PMC 2134808. PMID 9015313.
• Shimizu K, Shirataki H, Honda T, Minami S, Takai Y (1998). "Complex formation of SMAP/KAP3, a KIF3A/B ATPase motor-associated protein, with a human chromosome-associated polypeptide". J. Biol. Chem. 273 (12): 6591–4. doi:10.1074/jbc.273.12.6591. PMID 9506951.
• Gupta K, Anand G, Yin X, Grove L, Prochownik EV (1998). "Mmip1: a novel leucine zipper protein that reverses the suppressive effects of Mad family members on c-myc". Oncogene 16 (9): 1149–59. doi:10.1038/sj.onc.1201634. PMID 9528857.
• Schmiesing JA, Ball AR, Gregson HC, Alderton JM, Zhou S, Yokomori K (1998). "Identification of two distinct human SMC protein complexes involved in mitotic chromosome dynamics". Proc. Natl. Acad. Sci. U.S.A. 95 (22): 12906–11. doi:10.1073/pnas.95.22.12906. PMC 23650. PMID 9789013.
• Ghiselli G, Iozzo RV (2000). "Overexpression of bamacan/SMC3 causes transformation". J. Biol. Chem. 275 (27): 20235–8. doi:10.1074/jbc.C000213200. PMID 10801778.
• Zhang QH, Ye M, Wu XY, Ren SX, Zhao M, Zhao CJ, Fu G, Shen Y, Fan HY, Lu G, Zhong M, Xu XR, Han ZG, Zhang JW, Tao J, Huang QH, Zhou J, Hu GX, Gu J, Chen SJ, Chen Z (2000). "Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells". Genome Res. 10 (10): 1546–60. doi:10.1101/gr.140200. PMC 310934. PMID 11042152.
• Sumara I, Vorlaufer E, Gieffers C, Peters BH, Peters JM (2000). "Characterization of vertebrate cohesin complexes and their regulation in prophase". J. Cell Biol. 151 (4): 749–62. doi:10.1083/jcb.151.4.749. PMC 2169443. PMID 11076961.
• Revenkova E, Eijpe M, Heyting C, Gross B, Jessberger R (2001). "Novel meiosis-specific isoform of mammalian SMC1". Mol. Cell. Biol. 21 (20): 6984–98. doi:10.1128/MCB.21.20.6984-6998.2001. PMC 99874. PMID 11564881.
• Gregson HC, Schmiesing JA, Kim JS, Kobayashi T, Zhou S, Yokomori K (2001). "A potential role for human cohesin in mitotic spindle aster assembly". J. Biol. Chem. 276 (50): 47575–82. doi:10.1074/jbc.M103364200. PMID 11590136.
• Kim ST, Xu B, Kastan MB (2002). "Involvement of the cohesin protein, Smc1, in Atm-dependent and independent responses to DNA damage". Genes Dev. 16 (5): 560–70. doi:10.1101/gad.970602. PMC 155347. PMID 11877376.
• James RD, Schmiesing JA, Peters AH, Yokomori K, Disteche CM (2002). "Differential association of SMC1alpha and SMC3 proteins with meiotic chromosomes in wild-type and SPO11-deficient male mice". Chromosome Res. 10 (7): 549–60. doi:10.1023/A:1020910601858. PMID 12498344.
• Ghiselli G, Coffee N, Munnery CE, Koratkar R, Siracusa LD (2003). "The cohesin SMC3 is a target the for beta-catenin/TCF4 transactivation pathway". J. Biol. Chem. 278 (22): 20259–67. doi:10.1074/jbc.M209511200. PMID 12651860.
• Lee J, Iwai T, Yokota T, Yamashita M (2003). "Temporally and spatially selective loss of Rec8 protein from meiotic chromosomes during mammalian meiosis". J. Cell. Sci. 116 (Pt 13): 2781–90. doi:10.1242/jcs.00495. PMID 12759374.
• Prieto I, Tease C, Pezzi N, Buesa JM, Ortega S, Kremer L, Martínez A, Martínez-A C, Hultén MA, Barbero JL (2004). "Cohesin component dynamics during meiotic prophase I in mammalian oocytes". Chromosome Res. 12 (3): 197–213. doi:10.1023/B:CHRO.0000021945.83198.0e. PMID 15125634.
• Andersen JS, Lam YW, Leung AK, Ong SE, Lyon CE, Lamond AI, Mann M (2005). "Nucleolar proteome dynamics". Nature 433 (7021): 77–83. doi:10.1038/nature03207. PMID 15635413.
• Patel CA, Ghiselli G (2005). "Hinderin, a five-domains protein including coiled-coil motifs that binds to SMC3". BMC Cell Biol. 6 (1): 3. doi:10.1186/1471-2121-6-3. PMC 547899. PMID 15656913.
• Rankin S, Ayad NG, Kirschner MW (2005). "Sororin, a substrate of the anaphase-promoting complex, is required for sister chromatid cohesion in vertebrates". Mol. Cell 18 (2): 185–200. doi:10.1016/j.molcel.2005.03.017. PMID 15837422.
• Khanna H, Hurd TW, Lillo C, Shu X, Parapuram SK, He S, Akimoto M, Wright AF, Margolis B, Williams DS, Swaroop A (2005). "RPGR-ORF15, which is mutated in retinitis pigmentosa, associates with SMC1, SMC3, and microtubule transport proteins". J. Biol. Chem. 280 (39): 33580–7. doi:10.1074/jbc.M505827200. PMC 1249479. PMID 16043481.

External links

• GeneReviews/NCBI/UW/NIH entry on Cornelia de Lange syndrome
• FactorBook SMC3