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UniProtKB - Q9UQE7 (SMC3_HUMAN)

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Protein

Structural maintenance of chromosomes protein 3

Gene

SMC3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Central component of cohesin, a complex required for chromosome cohesion during the cell cycle. The cohesin complex may form 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. Cohesion is coupled to DNA replication and is involved in DNA repair. The cohesin complex plays also an important role in spindle pole assembly during mitosis and in chromosomes movement.2 Publications

Miscellaneous

Mutated Cornelia de Lange cell lines display genomic instability and sensitivity to ionizing radiation and interstrand cross-linking agents.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi32 – 39ATPSequence analysis8

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • chromatin binding Source: Ensembl
  • dynein complex binding Source: UniProtKB
  • mediator complex binding Source: Ensembl
  • microtubule motor activity Source: UniProtKB
  • protein heterodimerization activity Source: UniProtKB
Complete GO annotation...

GO - Biological processi

  • cell division Source: UniProtKB-KW
  • DNA repair Source: UniProtKB-KW
  • interaction with symbiont Source: CAFA
  • meiotic cell cycle Source: UniProtKB
  • mitotic cell cycle Source: ProtInc
  • mitotic sister chromatid cohesion Source: InterPro
  • negative regulation of DNA endoreduplication Source: BHF-UCL
  • positive regulation by host of viral release from host cell Source: CAFA
  • regulation of DNA replication Source: UniProtKB
  • sister chromatid cohesion Source: BHF-UCL
  • stem cell population maintenance Source: Ensembl
Complete GO annotation...

Keywordsi

Biological processCell cycle, Cell division, DNA damage, DNA repair, Meiosis, Mitosis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-1221632. Meiotic synapsis.
R-HSA-2467813. Separation of Sister Chromatids.
R-HSA-2468052. Establishment of Sister Chromatid Cohesion.
R-HSA-2470946. Cohesin Loading onto Chromatin.
R-HSA-2500257. Resolution of Sister Chromatid Cohesion.
R-HSA-3108214. SUMOylation of DNA damage response and repair proteins.
SIGNORiQ9UQE7.

Names & Taxonomyi

Protein namesi
Recommended name:
Structural maintenance of chromosomes protein 3
Short name:
SMC protein 3
Short name:
SMC-3
Alternative name(s):
Basement membrane-associated chondroitin proteoglycan
Short name:
Bamacan
Chondroitin sulfate proteoglycan 6
Chromosome-associated polypeptide
Short name:
hCAP
Gene namesi
Name:SMC3
Synonyms:BAM, BMH, CSPG6, SMC3L1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:2468. SMC3.

Subcellular locationi

  • Nucleus
  • Chromosome
  • Chromosome › centromere

    • 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. The phosphorylated form at Ser-1083 is preferentially associated with unsynapsed chromosomal regions (By similarity).By similarity

GO - Cellular componenti

  • basement membrane Source: CAFA
  • chromatin Source: UniProtKB
  • chromosome Source: Reactome
  • chromosome, centromeric region Source: Reactome
  • cohesin complex Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • intracellular Source: UniProtKB
  • lateral element Source: Ensembl
  • meiotic cohesin complex Source: UniProtKB
  • nuclear matrix Source: UniProtKB
  • nuclear meiotic cohesin complex Source: Ensembl
  • nucleoplasm Source: HPA
  • nucleus Source: ProtInc
  • spindle pole Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Centromere, Chromosome, Nucleus

Pathology & Biotechi

Involvement in diseasei

Cornelia de Lange syndrome 3 (CDLS3)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of Cornelia de Lange syndrome, a clinically heterogeneous developmental disorder associated with malformations affecting multiple systems. Characterized by facial dysmorphisms, abnormal hands and feet, growth delay, cognitive retardation, hirsutism, gastroesophageal dysfunction and cardiac, ophthalmologic and genitourinary anomalies. Cornelia de Lange syndrome type 3 is a mild form with absence of major structural anomalies. The phenotype in some instances approaches that of apparently non-syndromic mental retardation.
See also OMIM:610759
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_032845491Missing in CDLS3; affects the affinity of SMC hinge dimers for DNA; mutated hinge dimers bind DNA with higher affinity than wild-type proteins. 2 Publications1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi105K → A: 20% loss of sister chromatid cohesion; when associated with A-106. 2 Publications1
Mutagenesisi105K → R: Stabilizes interaction with PDS5A and WAPL; when associated with R-106. 2 Publications1
Mutagenesisi106K → A: 20% loss of sister chromatid cohesion; when associated with A-105. 2 Publications1
Mutagenesisi106K → R: Stabilizes interaction with PDS5A and WAPL; when associated with R-105. 2 Publications1

Keywords - Diseasei

Disease mutation, Mental retardation

Organism-specific databases

DisGeNETi9126.
MalaCardsiSMC3.
MIMi610759. phenotype.
OpenTargetsiENSG00000108055.
Orphaneti199. Cornelia de Lange syndrome.
PharmGKBiPA26966.

Polymorphism and mutation databases

BioMutaiSMC3.
DMDMi29337005.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001190011 – 1217Structural maintenance of chromosomes protein 3Add BLAST1217

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei105N6-acetyllysineCombined sources2 Publications1
Modified residuei106N6-acetyllysineCombined sources2 Publications1
Modified residuei140N6-acetyllysineCombined sources1
Modified residuei783PhosphothreonineCombined sources1
Modified residuei787PhosphoserineCombined sources1
Modified residuei886PhosphoserineCombined sources1
Modified residuei1013PhosphoserineBy similarity1
Modified residuei1065PhosphoserineCombined sources1
Modified residuei1067PhosphoserineCombined sources1
Modified residuei1074PhosphoserineBy similarity1
Modified residuei1083PhosphoserineCombined sources1
Modified residuei1190N6-acetyllysineCombined sources1

Post-translational modificationi

Phosphorylated at Ser-1083 in a SPO11-dependent manner.By similarity
Acetylation at Lys-105 and Lys-106 by ESCO1 is important for genome stability and S phase sister chromatid cohesion. Regulated by DSCC1, it is required for processive DNA synthesis, coupling sister chromatid cohesion establishment during S phase to DNA replication. Deacetylation by HDAC8, regulates release of the cohesin complex from chromatin.3 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9UQE7.
MaxQBiQ9UQE7.
PaxDbiQ9UQE7.
PeptideAtlasiQ9UQE7.
PRIDEiQ9UQE7.

PTM databases

iPTMnetiQ9UQE7.
PhosphoSitePlusiQ9UQE7.
SwissPalmiQ9UQE7.

Expressioni

Gene expression databases

BgeeiENSG00000108055.
CleanExiHS_SMC3.
GenevisibleiQ9UQE7. HS.

Organism-specific databases

HPAiHPA037411.
HPA043206.

Interactioni

Subunit structurei

Interacts with MXI1, MXD3 and MXD4. Interacts with SYCP2. Found in a complex with SMC1A, CDCA5 and RAD21, PDS5A/SCC-112 and PDS5B/APRIN (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. Interacts with PDS5A and WAPL; regulated by SMC3 acetylation. Interacts with RPGR (By similarity). Interacts (via central hinge region) with KIAA1328 (via N- and C-terminal domains) (PubMed:15656913). Interacts with DDX11 (PubMed:17105772).By similarity2 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • dynein complex binding Source: UniProtKB
  • mediator complex binding Source: Ensembl
  • protein heterodimerization activity Source: UniProtKB
Complete GO annotation...

Protein-protein interaction databases

BioGridi114574. 133 interactors.
DIPiDIP-29200N.
IntActiQ9UQE7. 72 interactors.
MINTiMINT-3083875.
STRINGi9606.ENSP00000354720.

Structurei

3D structure databases

ProteinModelPortaliQ9UQE7.
SMRiQ9UQE7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni505 – 667Flexible hingeAdd BLAST163

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili179 – 350Sequence analysisAdd BLAST172
Coiled coili393 – 503Sequence analysisAdd BLAST111
Coiled coili669 – 916Sequence analysisAdd BLAST248
Coiled coili958 – 989Sequence analysisAdd BLAST32

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi1115 – 1150Ala/Asp-rich (DA-box)Add BLAST36

Domaini

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).By similarity

Sequence similaritiesi

Belongs to the SMC family. SMC3 subfamily.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG0964. Eukaryota.
COG1196. LUCA.
GeneTreeiENSGT00580000081628.
HOGENOMiHOG000166512.
HOVERGENiHBG039849.
InParanoidiQ9UQE7.
KOiK06669.
OMAiSEMQKTE.
OrthoDBiEOG091G011B.
PhylomeDBiQ9UQE7.
TreeFamiTF105602.

Family and domain databases

InterProiView protein in InterPro
IPR027417. P-loop_NTPase.
IPR003395. RecF/RecN/SMC_N.
IPR024704. SMC.
IPR029685. SMC3.
IPR010935. SMC_hinge.
PANTHERiPTHR18937:SF288. PTHR18937:SF288. 1 hit.
PfamiView protein in Pfam
PF06470. SMC_hinge. 1 hit.
PF02463. SMC_N. 1 hit.
PIRSFiPIRSF005719. SMC. 2 hits.
SMARTiView protein in SMART
SM00968. SMC_hinge. 1 hit.
SUPFAMiSSF52540. SSF52540. 2 hits.
SSF75553. SSF75553. 2 hits.

Sequencei

Sequence statusi: Complete.

Q9UQE7-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MYIKQVIIQG FRSYRDQTIV DPFSSKHNVI VGRNGSGKSN FFYAIQFVLS 
        60         70         80         90        100
DEFSHLRPEQ RLALLHEGTG PRVISAFVEI IFDNSDNRLP IDKEEVSLRR 
       110        120        130        140        150
VIGAKKDQYF LDKKMVTKND VMNLLESAGF SRSNPYYIVK QGKINQMATA 
       160        170        180        190        200
PDSQRLKLLR EVAGTRVYDE RKEESISLMK ETEGKREKIN ELLKYIEERL 
       210        220        230        240        250
HTLEEEKEEL AQYQKWDKMR RALEYTIYNQ ELNETRAKLD ELSAKRETSG 
       260        270        280        290        300
EKSRQLRDAQ QDARDKMEDI ERQVRELKTK ISAMKEEKEQ LSAERQEQIK 
       310        320        330        340        350
QRTKLELKAK DLQDELAGNS EQRKRLLKER QKLLEKIEEK QKELAETEPK 
       360        370        380        390        400
FNSVKEKEER GIARLAQATQ ERTDLYAKQG RGSQFTSKEE RDKWIKKELK 
       410        420        430        440        450
SLDQAINDKK RQIAAIHKDL EDTEANKEKN LEQYNKLDQD LNEVKARVEE 
       460        470        480        490        500
LDRKYYEVKN KKDELQSERN YLWREENAEQ QALAAKREDL EKKQQLLRAA 
       510        520        530        540        550
TGKAILNGID SINKVLDHFR RKGINQHVQN GYHGIVMNNF ECEPAFYTCV 
       560        570        580        590        600
EVTAGNRLFY HIVDSDEVST KILMEFNKMN LPGEVTFLPL NKLDVRDTAY 
       610        620        630        640        650
PETNDAIPMI SKLRYNPRFD KAFKHVFGKT LICRSMEVST QLARAFTMDC 
       660        670        680        690        700
ITLEGDQVSH RGALTGGYYD TRKSRLELQK DVRKAEEELG ELEAKLNENL 
       710        720        730        740        750
RRNIERINNE IDQLMNQMQQ IETQQRKFKA SRDSILSEMK MLKEKRQQSE 
       760        770        780        790        800
KTFMPKQRSL QSLEASLHAM ESTRESLKAE LGTDLLSQLS LEDQKRVDAL 
       810        820        830        840        850
NDEIRQLQQE NRQLLNERIK LEGIITRVET YLNENLRKRL DQVEQELNEL 
       860        870        880        890        900
RETEGGTVLT ATTSELEAIN KRVKDTMARS EDLDNSIDKT EAGIKELQKS 
       910        920        930        940        950
MERWKNMEKE HMDAINHDTK ELEKMTNRQG MLLKKKEECM KKIRELGSLP 
       960        970        980        990       1000
QEAFEKYQTL SLKQLFRKLE QCNTELKKYS HVNKKALDQF VNFSEQKEKL 
      1010       1020       1030       1040       1050
IKRQEELDRG YKSIMELMNV LELRKYEAIQ LTFKQVSKNF SEVFQKLVPG 
      1060       1070       1080       1090       1100
GKATLVMKKG DVEGSQSQDE GEGSGESERG SGSQSSVPSV DQFTGVGIRV 
      1110       1120       1130       1140       1150
SFTGKQGEMR EMQQLSGGQK SLVALALIFA IQKCDPAPFY LFDEIDQALD 
      1160       1170       1180       1190       1200
AQHRKAVSDM IMELAVHAQF ITTTFRPELL ESADKFYGVK FRNKVSHIDV 
      1210 
ITAEMAKDFV EDDTTHG
Length:1,217
Mass (Da):141,542
Last modified:March 25, 2003 - v2
Checksum:i21EF9A08A5D8096A
GO

Sequence cautioni

The sequence AAD32447 differs from that shown. Reason: Frameshift at positions 457, 488 and 523.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti462K → T in AAD32447 (PubMed:11042152).Curated1
Sequence conflicti509I → V in AAD32447 (PubMed:11042152).Curated1
Sequence conflicti526Q → P in AAD32447 (PubMed:11042152).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_032845491Missing in CDLS3; affects the affinity of SMC hinge dimers for DNA; mutated hinge dimers bind DNA with higher affinity than wild-type proteins. 2 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF020043 mRNA. Translation: AAC14893.1.
AK289771 mRNA. Translation: BAF82460.1.
AL359260 Genomic DNA. No translation available.
CH471066 Genomic DNA. Translation: EAW49557.1.
AF067163 mRNA. Translation: AAD32447.1. Frameshift.
AJ005015 mRNA. Translation: CAA06289.1.
CCDSiCCDS31285.1.
RefSeqiNP_005436.1. NM_005445.3.
UniGeneiHs.24485.

Genome annotation databases

EnsembliENST00000361804; ENSP00000354720; ENSG00000108055.
GeneIDi9126.
KEGGihsa:9126.
UCSCiuc001kze.4. human.

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiSMC3_HUMAN
AccessioniPrimary (citable) accession number: Q9UQE7
Secondary accession number(s): A8K156, O60464, Q5T482
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 25, 2003
Last sequence update: March 25, 2003
Last modified: July 5, 2017
This is version 173 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Caution

Was originally isolated as a proteoglycan protein (explaining its name). Although not excluded, such secreted function is not clear.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. SIMILARITY comments
    Index of protein domains and families