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Gene Review

SMC3  -  structural maintenance of chromosomes 3

Homo sapiens

Synonyms: BAM, BMH, Bamacan, Basement membrane-associated chondroitin proteoglycan, CDLS3, ...
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Disease relevance of SMC3

  • The immunohistochemical analysis of colon adenocarcinomas from clinical specimens revealed that beta-catenin and SMC3 antigens co-localize with maximal stain intensity within the transformed areas [1].
  • We have found previously that SMC3 expression is elevated in a large fraction of human colon carcinomas [1].
  • Mutations in Cohesin Complex Members SMC3 and SMC1A Cause a Mild Variant of Cornelia de Lange Syndrome with Predominant Mental Retardation [2].
  • Deletion of one or both BMH genes caused hypersensitivity to rapamycin in a manner that was dependent on gene dosage [3].
  • HCAP protein was detected in 9 of 14 CaP metastases but not in normal prostate tissues from cadaveric donors or patients with organ-confined tumors [4].

Psychiatry related information on SMC3

  • Our data indicate that SMC3 and SMC1A mutations (1) contribute to ~5% of cases of CdLS, (2) result in a consistently mild phenotype with absence of major structural anomalies typically associated with CdLS, and (3) in some instances, result in a phenotype that approaches that of apparently nonsyndromic mental retardation [2].

High impact information on SMC3

  • Structural maintenance of chromosomes (SMC) proteins (SMC1, SMC3) are evolutionarily conserved chromosomal proteins that are components of the cohesin complex, necessary for sister chromatid cohesion [5].
  • We have previously proposed a similar stabilizing role for bamacan in the basement membrane matrix [6].
  • Structural analysis of the mutant SMC3 and SMC1A proteins indicate that all are likely to produce functional cohesin complexes, but we posit that they may alter their chromosome binding dynamics [2].
  • SMC1beta is specifically expressed in testes and coimmunoprecipitates with SMC3 from testis nuclear extracts, but not from a variety of somatic cells [7].
  • RESULTS: Characterization of cohesin's ATPase activity suggests that hydrolysis depends on the binding of ATP to both Smc1 and Smc3 heads [8].

Biological context of SMC3

  • Mass spectrometric analysis of proteins that were immunoprecipitated from the retinal axoneme-enriched fraction using an anti-ORF15 antibody identified two chromosome-associated proteins, structural maintenance of chromosomes (SMC) 1 and SMC3 [9].
  • We found that a second complex, hSMC1/hSMC3, is required for metaphase progression in mitotic cells [10].
  • The cohesin multiprotein complex containing SMC1, SMC3, Scc3 (SA), and Scc1 (Rad21) is required for sister chromatid cohesion in eukaryotes [11].
  • The amino acid sequences of the long, anti-parallel coiled coils of the cohesin subunits SMC1 and SMC3 are almost totally conserved in mammals [12].
  • In contrast, mutations predicted to prevent hydrolysis of ATP bound to either head abolished cohesin's association with chromatin but not Scc1's ability to connect Smc1's head with that of Smc3 [13].

Anatomical context of SMC3

  • Both SMC1 and SMC3 localized to the cilia of retinal photoreceptors and Madin-Darby canine kidney cells, suggesting a broader physiological relevance of this interaction [9].
  • To assess the role of this protein in tumorigenesis, we investigated whether induced overexpression of bamacan/SMC3 could transform normal fibroblasts [14].
  • Bamacan is differentially expressed in mouse tissues with the highest levels in testes and brain [15].
  • SMC1alpha and SMC3 were also found to localize along meiotic chromosome cores of Spo11 null spermatocytes, in which double-strand break formation required for DNA recombination and homologous pairing were disrupted [16].
  • HCAP mRNA was detected in CaP cell lines, in primary CaP tissues and in its osseous metastases [4].

Associations of SMC3 with chemical compounds


Physical interactions of SMC3

  • SMAP was extracted as a ternary complex with HCAP and KIF3B from the nuclear fraction in the presence of Mg-ATP [20].

Other interactions of SMC3

  • We isolated here a SMAP-interacting protein from a human brain cDNA library, identified it to be a human homolog of Xenopus XCAP-E (Xenopus chromosome-associated polypeptide), a subunit of condensins that regulate the assembly and structural maintenance of mitotic chromosomes, and named it HCAP (Human chromosome-associated polypeptide) [20].
  • Tissue and subcellular distribution analyses indicated that HCAP was ubiquitously expressed and highly concentrated in the nuclear fraction, where SMAP and KIF3B were also present [20].
  • In preretinal membranes, perlecan, bamacan, and Types VI, VIII, XII, and XIV collagen were newly identified [21].

Analytical, diagnostic and therapeutic context of SMC3


  1. The cohesin SMC3 is a target the for beta-catenin/TCF4 transactivation pathway. Ghiselli, G., Coffee, N., Munnery, C.E., Koratkar, R., Siracusa, L.D. J. Biol. Chem. (2003) [Pubmed]
  2. Mutations in Cohesin Complex Members SMC3 and SMC1A Cause a Mild Variant of Cornelia de Lange Syndrome with Predominant Mental Retardation. Deardorff, M.A., Kaur, M., Yaeger, D., Rampuria, A., Korolev, S., Pie, J., Gil-Rodriguez, C., Arnedo, M., Loeys, B., Kline, A.D., Wilson, M., Lillquist, K., Siu, V., Ramos, F.J., Musio, A., Jackson, L.S., Dorsett, D., Krantz, I.D. Am. J. Hum. Genet. (2007) [Pubmed]
  3. The 14-3-3 proteins positively regulate rapamycin-sensitive signaling. Bertram, P.G., Zeng, C., Thorson, J., Shaw, A.S., Zheng, X.F. Curr. Biol. (1998) [Pubmed]
  4. Expression of the human cachexia-associated protein (HCAP) in prostate cancer and in a prostate cancer animal model of cachexia. Wang, Z., Corey, E., Hass, G.M., Higano, C.S., True, L.D., Wallace, D., Tisdale, M.J., Vessella, R.L. Int. J. Cancer (2003) [Pubmed]
  5. SMC1 is a downstream effector in the ATM/NBS1 branch of the human S-phase checkpoint. Yazdi, P.T., Wang, Y., Zhao, S., Patel, N., Lee, E.Y., Qin, J. Genes Dev. (2002) [Pubmed]
  6. cDNA cloning of the basement membrane chondroitin sulfate proteoglycan core protein, bamacan: a five domain structure including coiled-coil motifs. Wu, R.R., Couchman, J.R. J. Cell Biol. (1997) [Pubmed]
  7. Novel meiosis-specific isoform of mammalian SMC1. Revenkova, E., Eijpe, M., Heyting, C., Gross, B., Jessberger, R. Mol. Cell. Biol. (2001) [Pubmed]
  8. Cohesin's ATPase Activity Is Stimulated by the C-Terminal Winged-Helix Domain of Its Kleisin Subunit. Arumugam, P., Nishino, T., Haering, C.H., Gruber, S., Nasmyth, K. Curr. Biol. (2006) [Pubmed]
  9. RPGR-ORF15, which is mutated in retinitis pigmentosa, associates with SMC1, SMC3, and microtubule transport proteins. Khanna, H., Hurd, T.W., Lillo, C., Shu, X., Parapuram, S.K., He, S., Akimoto, M., Wright, A.F., Margolis, B., Williams, D.S., Swaroop, A. J. Biol. Chem. (2005) [Pubmed]
  10. Identification of two distinct human SMC protein complexes involved in mitotic chromosome dynamics. Schmiesing, J.A., Ball, A.R., Gregson, H.C., Alderton, J.M., Zhou, S., Yokomori, K. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  11. A potential role for human cohesin in mitotic spindle aster assembly. Gregson, H.C., Schmiesing, J.A., Kim, J.S., Kobayashi, T., Zhou, S., Yokomori, K. J. Biol. Chem. (2001) [Pubmed]
  12. Sequence divergence of coiled coils-structural rods, myosin filament packing, and the extraordinary conservation of cohesins. White, G.E., Erickson, H.P. J. Struct. Biol. (2006) [Pubmed]
  13. ATP hydrolysis is required for cohesin's association with chromosomes. Arumugam, P., Gruber, S., Tanaka, K., Haering, C.H., Mechtler, K., Nasmyth, K. Curr. Biol. (2003) [Pubmed]
  14. Overexpression of bamacan/SMC3 causes transformation. Ghiselli, G., Iozzo, R.V. J. Biol. Chem. (2000) [Pubmed]
  15. Complete cDNA cloning, genomic organization, chromosomal assignment, functional characterization of the promoter, and expression of the murine Bamacan gene. Ghiselli, G., Siracusa, L.D., Iozzo, R.V. J. Biol. Chem. (1999) [Pubmed]
  16. Differential association of SMC1alpha and SMC3 proteins with meiotic chromosomes in wild-type and SPO11-deficient male mice. James, R.D., Schmiesing, J.A., Peters, A.H., Yokomori, K., Disteche, C.M. Chromosome Res. (2002) [Pubmed]
  17. Perlecan and basement membrane-chondroitin sulfate proteoglycan (bamacan) are two basement membrane chondroitin/dermatan sulfate proteoglycans in the Engelbreth-Holm-Swarm tumor matrix. Couchman, J.R., Kapoor, R., Sthanam, M., Wu, R.R. J. Biol. Chem. (1996) [Pubmed]
  18. Malignant mixed mesodermal tumors of the uterus and ovary treated with cisplatin-based combination chemotherapy. Grosh, W.W., Jones, H.W., Burnett, L.S., Greco, F.A. Gynecol. Oncol. (1986) [Pubmed]
  19. Comparison of cyclophosphamide plus cisplatin versus hexamethylmelamine, cyclophosphamide, doxorubicin, and cisplatin in combination as initial chemotherapy for stage III and IV ovarian carcinomas. Edmonson, J.H., McCormack, G.W., Fleming, T.R., Cullinan, S.A., Krook, J.E., Malkasian, G.D., Podratz, K.C., Mailliard, J.A., Jefferies, J.A., Barlow, J.F. Cancer treatment reports. (1985) [Pubmed]
  20. Complex formation of SMAP/KAP3, a KIF3A/B ATPase motor-associated protein, with a human chromosome-associated polypeptide. Shimizu, K., Shirataki, H., Honda, T., Minami, S., Takai, Y. J. Biol. Chem. (1998) [Pubmed]
  21. Basement membrane abnormalities in human eyes with diabetic retinopathy. Ljubimov, A.V., Burgeson, R.E., Butkowski, R.J., Couchman, J.R., Zardi, L., Ninomiya, Y., Sado, Y., Huang, Z.S., Nesburn, A.B., Kenney, M.C. J. Histochem. Cytochem. (1996) [Pubmed]
  22. Hinderin, a five-domains protein including coiled-coil motifs that binds to SMC3. Patel, C.A., Ghiselli, G. BMC Cell Biol. (2005) [Pubmed]
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