Reviewed, UniProtKB/Swiss-Prot Q9UQE7 (SMC3_HUMAN)

Names and origin

Protein names

Recommended name:
    Structural maintenance of chromosomes protein 3
Alternative name(s):
    Chondroitin sulfate proteoglycan 6
    Chromosome-associated polypeptide
      Short name=hCAP
    Basement membrane-associated chondroitin proteoglycan
      Short name=Bamacan

Gene names

Name:	SMC3
Synonyms:	BAM, BMH, CSPG6, SMC3L1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1217 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Involved in chromosome cohesion during cell cycle and in DNA repair. Central component of cohesin complex. The cohesin complex is required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. The cohesin complex may also play a role in spindle pole assembly during mitosis and in chromosome movement. Ref.5
Subunit structure	Interacts with MXI1, MXD3 and MXD4. Interacts with SYCP2. Found in a complex with SMC1A, CDCA5 and RAD21, PDS5A/APRIN and PDS5B/SCC-112 By similarity. Forms a heterodimer with SMC1A or SMC1B in cohesin complexes. Cohesin complexes are composed of the SMC1 (SMC1A or SMC1B) and SMC3 heterodimer attached via their hinge domain, RAD21 which link them, and one STAG protein (STAG1, STAG2 or STAG3), which interacts with RAD21. Also found in meiosis-specific cohesin complexes. Interacts with NUMA1, and forms a ternary complex with KIF3B and KIFAP3, suggesting a function in tethering the chromosomes to the spindle pole and in chromosome movement.
Subcellular location	Nucleus. Note: 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.
Domain	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 By similarity.
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.7 Ref.10 Ref.11 Ref.12
Involvement in disease	Defects in SMC3 are the cause of Cornelia de Lange syndrome type 3 (CDLS3) [MIM:610759]. CDLS is a dominantly inherited multisystem developmental disorder characterized by growth and cognitive retardation, abnormalities of the upper limbs, gastroesophageal dysfunction, cardiac, ophthalmologic and genitourinary anomalies, hirsutism, and characteristic facial features. CDSL3 is a mild form with absence of major structural anomalies typically associated with CDLS. The phenotype in some instances approaches that of apparently non-syndromic mental retardation. Ref.14
Sequence similarities	Belongs to the SMC family. SMC3 subfamily.
Caution	Was originally isolated as a proteoglycan protein (explaining its name). Although not excluded, such secreted function is not clear.
Sequence caution	The sequence AAD32447.1 differs from that shown. Reason: Frameshift at positions 457, 488 and 523.

Ontologies

Keywords
Biological process	Cell cycle Cell division DNA damage DNA repair Meiosis Mitosis
Cellular component	Nucleus
Disease	Disease mutation
Domain	Coiled coil
Ligand	ATP-binding Nucleotide-binding
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	DNA mediated transformation Traceable author statement. Source: ProtInc DNA repair Inferred from electronic annotation. Source: UniProtKB-KW cell division Inferred from electronic annotation. Source: UniProtKB-KW meiosis Inferred from direct assay. Source: UniProtKB mitosis Ref.1 Traceable author statement. Source: ProtInc mitotic spindle organization Ref.6 Inferred from expression pattern. Source: UniProtKB signal transduction Inferred from direct assay. Source: UniProtKB sister chromatid cohesion Ref.6 Non-traceable author statement. Source: UniProtKB
Cellular component	basement membrane Traceable author statement. Source: ProtInc cohesin complex Ref.1 Non-traceable author statement. Source: UniProtKB cytoplasm Ref.6 Inferred from direct assay. Source: UniProtKB nuclear matrix Ref.6 Inferred from direct assay. Source: UniProtKB spindle pole Ref.6 Inferred from direct assay. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW dynein binding Ref.6 Inferred from direct assay. Source: UniProtKB microtubule motor activity Ref.6 Non-traceable author statement. Source: UniProtKB protein heterodimerization activity Ref.6 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CASP4	P49662	1	EBI-80718,EBI-1057327
CDK4	P11802	1	EBI-80718,EBI-295644
MAGED1	Q9Y5V3	1	EBI-80718,EBI-716006
NEK6	Q9HC98	1	EBI-80718,EBI-740364
PDS5A	Q29RF7	1	EBI-80718,EBI-1175454
PDS5B	Q9NTI5	1	EBI-80718,EBI-1175604
RAD21	O60216	2	EBI-80718,EBI-80739
STAG1	Q8WVM7	1	EBI-80718,EBI-1175097
STAG2	Q8N3U4	1	EBI-80718,EBI-1057252

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1217	1217	Structural maintenance of chromosomes protein 3		PRO_0000119001
Regions
	Nucleotide binding	32 – 39	8	ATP Potential
	Region	505 – 667	163	Flexible hinge
	Coiled coil	179 – 350	172	Potential
	Coiled coil	393 – 503	111	Potential
	Coiled coil	669 – 916	248	Potential
	Coiled coil	958 – 989	32	Potential
	Compositional bias	1115 – 1150	36	Ala/Asp-rich (DA-box)
Amino acid modifications
	Modified residue	787	1	Phosphoserine Ref.10
	Modified residue	1013	1	Phosphoserine By similarity
	Modified residue	1065	1	Phosphoserine Ref.7 Ref.10 Ref.12
	Modified residue	1067	1	Phosphoserine Ref.7 Ref.10 Ref.12
	Modified residue	1074	1	Phosphoserine Ref.7
	Modified residue	1081	1	Phosphoserine Ref.11
	Modified residue	1083	1	Phosphoserine Ref.7 Ref.10
Natural variations
	Natural variant	491	1	Missing in CDLS3. Ref.14		VAR_032845
Experimental info
	Sequence conflict	462	1	K → T Ref.3
	Sequence conflict	509	1	I → V Ref.3
	Sequence conflict	526	1	Q → P Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q9UQE7-1 [UniParc]. Last modified March 25, 2003. Version 2. Checksum: 21EF9A08A5D8096A	FASTA	1,217	141,542
	10 20 30 40 50 60 MYIKQVIIQG FRSYRDQTIV DPFSSKHNVI VGRNGSGKSN FFYAIQFVLS DEFSHLRPEQ 70 80 90 100 110 120 RLALLHEGTG PRVISAFVEI IFDNSDNRLP IDKEEVSLRR VIGAKKDQYF LDKKMVTKND 130 140 150 160 170 180 VMNLLESAGF SRSNPYYIVK QGKINQMATA PDSQRLKLLR EVAGTRVYDE RKEESISLMK 190 200 210 220 230 240 ETEGKREKIN ELLKYIEERL HTLEEEKEEL AQYQKWDKMR RALEYTIYNQ ELNETRAKLD 250 260 270 280 290 300 ELSAKRETSG EKSRQLRDAQ QDARDKMEDI ERQVRELKTK ISAMKEEKEQ LSAERQEQIK 310 320 330 340 350 360 QRTKLELKAK DLQDELAGNS EQRKRLLKER QKLLEKIEEK QKELAETEPK FNSVKEKEER 370 380 390 400 410 420 GIARLAQATQ ERTDLYAKQG RGSQFTSKEE RDKWIKKELK SLDQAINDKK RQIAAIHKDL 430 440 450 460 470 480 EDTEANKEKN LEQYNKLDQD LNEVKARVEE LDRKYYEVKN KKDELQSERN YLWREENAEQ 490 500 510 520 530 540 QALAAKREDL EKKQQLLRAA TGKAILNGID SINKVLDHFR RKGINQHVQN GYHGIVMNNF 550 560 570 580 590 600 ECEPAFYTCV EVTAGNRLFY HIVDSDEVST KILMEFNKMN LPGEVTFLPL NKLDVRDTAY 610 620 630 640 650 660 PETNDAIPMI SKLRYNPRFD KAFKHVFGKT LICRSMEVST QLARAFTMDC ITLEGDQVSH 670 680 690 700 710 720 RGALTGGYYD TRKSRLELQK DVRKAEEELG ELEAKLNENL RRNIERINNE IDQLMNQMQQ 730 740 750 760 770 780 IETQQRKFKA SRDSILSEMK MLKEKRQQSE KTFMPKQRSL QSLEASLHAM ESTRESLKAE 790 800 810 820 830 840 LGTDLLSQLS LEDQKRVDAL NDEIRQLQQE NRQLLNERIK LEGIITRVET YLNENLRKRL 850 860 870 880 890 900 DQVEQELNEL RETEGGTVLT ATTSELEAIN KRVKDTMARS EDLDNSIDKT EAGIKELQKS 910 920 930 940 950 960 MERWKNMEKE HMDAINHDTK ELEKMTNRQG MLLKKKEECM KKIRELGSLP QEAFEKYQTL 970 980 990 1000 1010 1020 SLKQLFRKLE QCNTELKKYS HVNKKALDQF VNFSEQKEKL IKRQEELDRG YKSIMELMNV 1030 1040 1050 1060 1070 1080 LELRKYEAIQ LTFKQVSKNF SEVFQKLVPG GKATLVMKKG DVEGSQSQDE GEGSGESERG 1090 1100 1110 1120 1130 1140 SGSQSSVPSV DQFTGVGIRV SFTGKQGEMR EMQQLSGGQK SLVALALIFA IQKCDPAPFY 1150 1160 1170 1180 1190 1200 LFDEIDQALD AQHRKAVSDM IMELAVHAQF ITTTFRPELL ESADKFYGVK FRNKVSHIDV 1210 ITAEMAKDFV EDDTTHG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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. 273:6591-6594(1998) [PubMed: 9506951] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH KIFAP3, IDENTIFICATION IN A COMPLEX WITH KIFAP3 AND KIF3B. Tissue: B-cell.
[2]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed: 15164054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells." Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., Tao J., Huang Q.-H., Zhou J., Hu G.-X. , Gu J., Chen S.-J., Chen Z. Genome Res. 10:1546-1560(2000) [PubMed: 11042152] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 410-1217. Tissue: Umbilical cord blood.
[4]	Stanchi F., Bertocco E., Simionati B., Zimbello R., Lanfranchi G., Valle G. Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 827-1217. Tissue: Neuron.
[5]	"Characterization of vertebrate cohesin complexes and their regulation in prophase." Sumara I., Vorlaufer E., Gieffers C., Peters B.H., Peters J.-M. J. Cell Biol. 151:749-762(2000) [PubMed: 11076961] [Abstract] Cited for: CHARACTERIZATION, FUNCTION, IDENTIFICATION IN A COHESIN COMPLEX WITH SMC1A; STAG1 OR STAG2.
[6]	"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. 276:47575-47582(2001) [PubMed: 11590136] [Abstract] Cited for: INTERACTION WITH NUMA1.
[7]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1065; SER-1067; SER-1074 AND SER-1083, MASS SPECTROMETRY. Tissue: Epithelium.
[8]	"Sororin, a substrate of the anaphase-promoting complex, is required for sister chromatid cohesion in vertebrates." Rankin S., Ayad N.G., Kirschner M.W. Mol. Cell 18:185-200(2005) [PubMed: 15837422] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH CDCA5; SMC1A; RAD21; PDS5A AND PDS5B.
[9]	Erratum Rankin S., Ayad N.G., Kirschner M.W. Mol. Cell 18:609-609(2005)
[10]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-787; SER-1065; SER-1067 AND SER-1083, MASS SPECTROMETRY.
[11]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1081, MASS SPECTROMETRY.
[12]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1065 AND SER-1067, MASS SPECTROMETRY.
[13]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[14]	"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. 80:485-494(2007) [PubMed: 17273969] [Abstract] Cited for: VARIANT CDLS3 GLU-491 DEL.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF020043 mRNA. Translation: AAC14893.1. AL359260 Genomic DNA. Translation: CAI16576.1. AF067163 mRNA. Translation: AAD32447.1. Frameshift. AJ005015 mRNA. Translation: CAA06289.1.
IPI	IPI00219420.
RefSeq	NP_005436.1.
UniGene	Hs.24485
3D structure databases
ModBase	Search...
Protein-protein interaction databases
DIP	DIP:29200N.
IntAct	Q9UQE7. 20 interactions.
PTM databases
PhosphoSite	Q9UQE7.
Proteomic databases
PRIDE	Q9UQE7.
Genome annotation databases
Ensembl	ENSG00000108055. Homo sapiens. [Contig view]
GeneID	9126.
KEGG	hsa:9126.
UCSC	uc001kze.1. human.
Organism-specific databases
GeneCards	GC10P112318.
H-InvDB	HIX0009197.
HGNC	HGNC:2468. SMC3.
MIM	606062. gene. 610759. phenotype.
Orphanet	199. Cornelia de Lange syndrome.
PharmGKB	PA33894.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q9UQE7.
OMA	Q9UQE7. IQGFKSY.
Enzyme and pathway databases
Reactome	REACT_152. Cell Cycle, Mitotic.
Gene expression databases
ArrayExpress	Q9UQE7.
Bgee	Q9UQE7.
CleanEx	HS_SMC3.
GermOnline	ENSG00000108055. Homo sapiens.
Family and domain databases
InterPro	IPR003395. RecF/RecN/SMC_N. IPR010935. SMC_hinge. [Graphical view]
Pfam	PF06470. SMC_hinge. 1 hit. PF02463. SMC_N. 1 hit. [Graphical view]
ProDom	PD000006. ABC_transporter. 1 hit. [Graphical view] [Entries sharing at least one domain]
ProtoNet	Search...
Other Resources
NextBio	34209.
SOURCE	Search...

Entry information

Entry name

SMC3_HUMAN

Accession

Primary (citable) accession number: Q9UQE7
Secondary accession number(s): O60464, Q5T482

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 25, 2003
Last sequence update:	March 25, 2003
Last modified:	July 7, 2009
This is version 85 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)