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{{Short description|Protein-coding gene in humans}}
{{PBB|geneid=9126}} __NOTOC__
'''Structural maintenance of chromosomes 3''', also known as '''SMC3''', is a [[human genetics|human gene]].<ref name="entrez">{{cite web | title = Entrez Gene: SMC3 structural maintenance of chromosomes 3| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9126| accessdate = }}</ref>


{{Infobox_gene}}
== Function ==
'''Structural maintenance of chromosomes protein 3''' (SMC3) is a [[protein]] that in humans is encoded by the '''SMC3''' [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: SMC3 structural maintenance of chromosomes 3| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9126}}</ref> SMC3 is a subunit of the [[Cohesin]] complex which mediates [[Establishment of sister chromatid cohesion|sister chromatid cohesion]], homologous recombination and [[Topologically associating domain|DNA looping]]. Cohesin is formed of SMC3, [[SMC1A|SMC1]], [[RAD21]] and either [[STAG1|SA1]] or [[STAG2|SA2]]. In humans, SMC3 is present in all cohesin complexes whereas there are multiple [[Sequence homology|paralogs]] for the other subunits.


SMC3 is a member of the [[SMC protein|SMC protein family]]. Members of this family are key regulators of DNA repair, chromosome condensation and chromosome segregation.
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.<ref name="entrez" />


== Structure and interactions ==
==Model organisms==
[[File:Structure of the interface between SMC3 (blue) and SMC1 (green) (PDB 2WD5) from mice (Kurze et al. 2009).png|thumb|left|Structure of the interface between SMC3 (blue) and SMC1 (green) (PDB 2WD5) from mice (Kurze et al., 2009)]]
{| class="wikitable sortable collapsible collapsed" border="1" cellpadding="2" style="float: right;" |
[[File:Structure of the SMC3 (blue)-RAD21 (green) interface (PDB 4UX3).png|thumb|left|Structure of the interface between SMC3 (blue) and RAD21 (green) (PDB 4UX3) from budding yeast (Gligoris et al., 2014)]]
|+ ''Smc3'' knockout mouse phenotype
The domain organisation of SMC proteins is evolutionarily conserved and is composed of an N-terminal [[Walker motifs|Walker A motif]], coiled-coil, "hinge", coiled-coil and a C-terminal [[Walker motifs|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 [[ATP-binding cassette transporter|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
|-
! Characteristic!! Phenotype


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.
|-
| [[Homozygote]] viability || bgcolor="#C40000"|Abnormal
|-
| [[Recessive]] lethal study || bgcolor="#C40000"|Abnormal
|-
| Homozygous Fertility || bgcolor="#C40000"|Abnormal
|-
| Body weight || bgcolor="#C40000"|Abnormal<ref name="Body weight">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBBZ/weight-curves/ |title=Body weight data for Smc3 |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| [[Open Field (animal test)|Anxiety]] || bgcolor="#488ED3"|Normal
|-
| Neurological assessment || bgcolor="#488ED3"|Normal
|-
| Grip strength || bgcolor="#488ED3"|Normal
|-
| [[Hot plate test|Hot plate]] || bgcolor="#488ED3"|Normal
|-
| [[Dysmorphology]] || bgcolor="#C40000"|Abnormal<ref name="Dysmorphology">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBBZ/dysmorphology/ |title=Dysmorphology data for Smc3 |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| [[Indirect calorimetry]] || bgcolor="#488ED3"|Normal
|-
| [[Glucose tolerance test]] || bgcolor="#488ED3"|Normal
|-
| [[Auditory brainstem response]] || bgcolor="#488ED3"|Normal
|-
| [[Dual-energy X-ray absorptiometry|DEXA]] || bgcolor="#C40000"|Abnormal<ref name="DEXA">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBBZ/body-composition-dexa/ |title=DEXA data for Smc3 |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| [[Radiography]] || bgcolor="#488ED3"|Normal
|-
| Body temperature || bgcolor="#488ED3"|Normal
|-
| Eye morphology || bgcolor="#488ED3"|Normal
|-
| [[Clinical chemistry]] || bgcolor="#488ED3"|Normal
|-
| [[Haematology]] || bgcolor="#488ED3"|Normal
|-
| [[Peripheral blood lymphocyte]]s || bgcolor="#488ED3"|Normal
|-
| Heart weight || bgcolor="#488ED3"|Normal
|-
| Eye Histopathology || bgcolor="#488ED3"|Normal
|-
| ''[[Salmonella]]'' infection || bgcolor="#488ED3"|Normal<ref name="''Salmonella'' infection">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBBZ/salmonella-challenge/ |title=''Salmonella'' infection data for Smc3 |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| ''[[Citrobacter]]'' infection || bgcolor="#488ED3"|Normal<ref name="''Citrobacter'' infection">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBBZ/citrobacter-challenge/ |title=''Citrobacter'' infection data for Smc3 |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| colspan=2; style="text-align: center;" | All tests and analysis from<ref name="mgp_reference">{{cite journal | doi = 10.1111/j.1755-3768.2010.4142.x | title = The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice | year = 2010 | author = Gerdin AK | journal = Acta Ophthalmologica | volume = 88 | pages = 925–7 }}</ref><ref>[http://www.sanger.ac.uk/mouseportal/ Mouse Resources Portal], Wellcome Trust Sanger Institute.</ref>
|}
[[Model organism]]s have been used in the study of SMC3 function. A conditional [[knockout mouse]] line, called ''Smc3<sup>tm1a(EUCOMM)Wtsi</sup>''<ref name="allele_ref">{{cite web |url=http://www.knockoutmouse.org/martsearch/search?query=Smc3 |title=International Knockout Mouse Consortium}}</ref><ref name="mgi_allele_ref">{{cite web |url=http://www.informatics.jax.org/searchtool/Search.do?query=MGI:4434007 |title=Mouse Genome Informatics}}</ref> 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.<ref name="pmid21677750">{{cite journal | vauthors = 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 | title = A conditional knockout resource for the genome-wide study of mouse gene function | journal = Nature | volume = 474 | issue = 7351 | pages = 337–42 | year = 2011 | pmid = 21677750 | pmc = 3572410 | doi = 10.1038/nature10163 }}</ref><ref name="mouse_library">{{cite journal | vauthors = Dolgin E | title = Mouse library set to be knockout | journal = Nature | volume = 474 | issue = 7351 | pages = 262–3 | year = 2011 | pmid = 21677718 | doi = 10.1038/474262a }}</ref><ref name="mouse_for_all_reasons">{{cite journal | vauthors = Collins FS, Rossant J, Wurst W | title = A mouse for all reasons | journal = Cell | volume = 128 | issue = 1 | pages = 9–13 | year = 2007 | pmid = 17218247 | doi = 10.1016/j.cell.2006.12.018 }}</ref>


During [[meiosis]], SMC3 forms cohesin complexes with [[SMC1B|SMC1ß]], [[STAG3 (gene)|STAG3]] and [[REC8]] which generate cohesion between homologous chromosomes and sister chromatids.<ref name="pmid20634189">{{cite journal |vauthors=Garcia-Cruz R, Brieño MA, Roig I, Grossmann M, Velilla E, Pujol A, Cabero L, Pessarrodona A, Barbero JL, Garcia Caldés M |title=Dynamics of cohesin proteins REC8, STAG3, SMC1 beta and SMC3 are consistent with a role in sister chromatid cohesion during meiosis in human oocytes |journal=Hum. Reprod. |volume=25 |issue=9 |pages=2316–27 |year=2010 |pmid=20634189 |doi=10.1093/humrep/deq180 |doi-access=free }}</ref>
Male and female animals underwent a standardized [[phenotypic screen]] to determine the effects of deletion.<ref name="mgp_reference" /><ref name="pmid21722353">{{cite journal | vauthors = van der Weyden L, White JK, Adams DJ, Logan DW | title = The mouse genetics toolkit: revealing function and mechanism | journal = Genome Biol. | volume = 12 | issue = 6 | pages = 224 | year = 2011 | pmid = 21722353 | pmc = 3218837 | doi = 10.1186/gb-2011-12-6-224 }}</ref> Twenty two tests were carried out on [[mutant]] mice and six significant abnormalities were observed.<ref name="mgp_reference" /> 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]].<ref name="mgp_reference" /><ref name="pmid21722353"/>


== Cornelia de Lange syndrome ==
== Interactions ==


[[Cornelia de Lange syndrome|Cornelia de Lange syndrome (CdLS)]] is a rare genetic disorder that presents with variable clinical abnormalities including [[dysmorphic feature]]s, severe growth retardation, [[global developmental delay]], and [[intellectual disability]]. SMC3 is one of five genes that have been implicated in CdLS.<ref name="pmid28781842">{{cite journal |vauthors=Infante E, Alkorta-Aranburu G, El-Gharbawy A |title=Rare form of autosomal dominant familial Cornelia de Lange syndrome due to a novel duplication in SMC3 |journal=Clinical Case Reports |volume=5 |issue=8 |pages=1277–1283 |year=2017 |pmid=28781842 |pmc=5538066 |doi=10.1002/ccr3.1010 }}</ref> In one case report, a novel SMC3 gene duplication was detected in a child with [[failure to thrive]], [[hypotonia]] and facial [[dysmorphic feature]]s of CdLS.<ref name="pmid28781842" /> The same duplication was also observed in the mother, who had milder dysmorphic facies.
SMC3 (gene) has been shown to [[Protein-protein interaction|interact]] with:
{{div col|colwidth=20em}}
* [[KIFAP3]],<ref name = pmid9506951>{{cite journal | vauthors = Shimizu K, Shirataki H, Honda T, Minami S, Takai Y | title = Complex formation of SMAP/KAP3, a KIF3A/B ATPase motor-associated protein, with a human chromosome-associated polypeptide | journal = J. Biol. Chem. | volume = 273 | issue = 12 | pages = 6591–4 | date = March 1998 | pmid = 9506951 | doi = 10.1074/jbc.273.12.6591}}</ref>
* [[MXD1]],<ref name = pmid9528857>{{cite journal | vauthors = Gupta K, Anand G, Yin X, Grove L, Prochownik EV | title = Mmip1: a novel leucine zipper protein that reverses the suppressive effects of Mad family members on c-myc | journal = Oncogene | volume = 16 | issue = 9 | pages = 1149–59 | date = March 1998 | pmid = 9528857 | doi = 10.1038/sj.onc.1201634 }}</ref>
* [[MXI1]],<ref name = pmid9528857/>
* [[REC8]],<ref name = pmid12759374>{{cite journal | vauthors = Lee J, Iwai T, Yokota T, Yamashita M | title = Temporally and spatially selective loss of Rec8 protein from meiotic chromosomes during mammalian meiosis | journal = J. Cell. Sci. | volume = 116 | issue = Pt 13 | pages = 2781–90 | date = July 2003 | pmid = 12759374 | doi = 10.1242/jcs.00495 }}</ref> and
* [[SMC1A]].<ref name = pmid12759374/><ref name = pmid11877376>{{cite journal | vauthors = Kim ST, Xu B, Kastan MB | title = Involvement of the cohesin protein, Smc1, in Atm-dependent and independent responses to DNA damage | journal = Genes Dev. | volume = 16 | issue = 5 | pages = 560–70 | date = March 2002 | pmid = 11877376 | pmc = 155347 | doi = 10.1101/gad.970602 }}</ref><ref name = pmid9789013>{{cite journal | vauthors = Schmiesing JA, Ball AR, Gregson HC, Alderton JM, Zhou S, Yokomori K | title = Identification of two distinct human SMC protein complexes involved in mitotic chromosome dynamics | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 95 | issue = 22 | pages = 12906–11 | date = October 1998 | pmid = 9789013 | pmc = 23650 | doi = 10.1073/pnas.95.22.12906}}</ref><ref name = pmid11590136>{{cite journal | vauthors = Gregson HC, Schmiesing JA, Kim JS, Kobayashi T, Zhou S, Yokomori K | title = A potential role for human cohesin in mitotic spindle aster assembly | journal = J. Biol. Chem. | volume = 276 | issue = 50 | pages = 47575–82 | date = Dec 2001 | pmid = 11590136 | doi = 10.1074/jbc.M103364200 }}</ref>
{{Div col end}}


== See also ==
== Role in Basement Membrane ==
* [[Cornelia de Lange Syndrome]]


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.<ref name="entrez" />
== References ==
== References ==
{{Reflist}}
{{Reflist}}

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


== External links ==
== External links ==
* [http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=cdls GeneReviews/NCBI/UW/NIH entry on Cornelia de Lange syndrome]
* [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=cdls GeneReviews/NCBI/UW/NIH entry on Cornelia de Lange syndrome]
* {{FactorBook|SMC3}}
* {{FactorBook|SMC3}}


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[[Category:Human proteins]]
[[Category:Human proteins]]
[[Category:Genes mutated in mice]]
[[Category:Genes mutated in mice]]


{{Gene-10-stub}}

Latest revision as of 06:20, 18 December 2023

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; OMA:SMC3 - orthologs
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 – 110.61 MbChr 19: 53.59 – 53.63 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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 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

[edit]
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

[edit]

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.

Role in Basement Membrane

[edit]

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]

References

[edit]
  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000108055 – Ensembl, May 2017
  2. ^ a b c 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. ^ a b "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. ^ a b 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". Clinical Case Reports. 5 (8): 1277–1283. doi:10.1002/ccr3.1010. PMC 5538066. PMID 28781842.
[edit]
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