UniProtKB - Q9UQE7 (SMC3_HUMAN)
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Protein
Structural maintenance of chromosomes protein 3
Gene
SMC3
Organism
Homo sapiens (Human)
Status
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 32 – 39 | ATPSequence analysis | 8 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- beta-tubulin binding Source: UniProtKB
- chromatin binding Source: Ensembl
- dynein complex binding Source: UniProtKB
- mediator complex binding Source: Ensembl
- microtubule motor activity Source: UniProtKB
- protein heterodimerization activity Source: UniProtKB
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
- 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
- regulation of mitotic spindle assembly Source: UniProtKB
- sister chromatid cohesion Source: BHF-UCL
- stem cell population maintenance Source: Ensembl
Keywordsi
Biological process | Cell cycle, Cell division, DNA damage, DNA repair, Meiosis, Mitosis |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
Reactomei | R-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. |
SIGNORi | Q9UQE7. |
Names & Taxonomyi
Protein namesi | Recommended name: Structural maintenance of chromosomes protein 3Short 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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000108055.9. |
HGNCi | HGNC:2468. SMC3. |
MIMi | 606062. gene. |
neXtProti | NX_Q9UQE7. |
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:610759Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_032845 | 491 | Missing in CDLS3; affects the affinity of SMC hinge dimers for DNA; mutated hinge dimers bind DNA with higher affinity than wild-type proteins. 2 Publications | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 105 | K → A: 20% loss of sister chromatid cohesion; when associated with A-106. 2 Publications | 1 | |
Mutagenesisi | 105 | K → R: Stabilizes interaction with PDS5A and WAPL; when associated with R-106. 2 Publications | 1 | |
Mutagenesisi | 106 | K → A: 20% loss of sister chromatid cohesion; when associated with A-105. 2 Publications | 1 | |
Mutagenesisi | 106 | K → R: Stabilizes interaction with PDS5A and WAPL; when associated with R-105. 2 Publications | 1 |
Keywords - Diseasei
Disease mutation, Mental retardationOrganism-specific databases
DisGeNETi | 9126. |
GeneReviewsi | SMC3. |
MalaCardsi | SMC3. |
MIMi | 610759. phenotype. |
OpenTargetsi | ENSG00000108055. |
Orphaneti | 199. Cornelia de Lange syndrome. |
PharmGKBi | PA26966. |
Polymorphism and mutation databases
BioMutai | SMC3. |
DMDMi | 29337005. |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000119001 | 1 – 1217 | Structural maintenance of chromosomes protein 3Add BLAST | 1217 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 105 | N6-acetyllysineCombined sources2 Publications | 1 | |
Modified residuei | 106 | N6-acetyllysineCombined sources2 Publications | 1 | |
Modified residuei | 140 | N6-acetyllysineCombined sources | 1 | |
Modified residuei | 783 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 787 | PhosphoserineCombined sources | 1 | |
Modified residuei | 886 | PhosphoserineCombined sources | 1 | |
Modified residuei | 1013 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1065 | PhosphoserineCombined sources | 1 | |
Modified residuei | 1067 | PhosphoserineCombined sources | 1 | |
Modified residuei | 1074 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1083 | PhosphoserineCombined sources | 1 | |
Modified residuei | 1190 | N6-acetyllysineCombined sources | 1 |
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, PhosphoproteinProteomic databases
EPDi | Q9UQE7. |
MaxQBi | Q9UQE7. |
PaxDbi | Q9UQE7. |
PeptideAtlasi | Q9UQE7. |
PRIDEi | Q9UQE7. |
PTM databases
iPTMneti | Q9UQE7. |
PhosphoSitePlusi | Q9UQE7. |
SwissPalmi | Q9UQE7. |
Expressioni
Gene expression databases
Bgeei | ENSG00000108055. |
CleanExi | HS_SMC3. |
Genevisiblei | Q9UQE7. HS. |
Organism-specific databases
HPAi | HPA037411. HPA043206. |
Interactioni
Subunit structurei
Forms a heterodimer with SMC1A or SMC1B in cohesin complexes (PubMed:22628566). 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 (PubMed:11076961). Found in a complex with SMC1A, CDCA5 and RAD21, PDS5A/SCC-112 and PDS5B/APRIN (PubMed:15837422). 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 (PubMed:9506951, PubMed:11590136). Interacts with PDS5A and WAPL; regulated by SMC3 acetylation (PubMed:19907496). Interacts (via central hinge region) with KIAA1328 (via N- and C-terminal domains) (PubMed:15656913). Interacts with DDX11 (PubMed:17105772). Found in a cohesin complex with SMC1A, STAG1 and RAD21 (PubMed:22628566). The SMC1A-SMC3 heterodimer interacts with the NIPBL-MAU2 heterodimer (PubMed:22628566). Interacts with MXI1, MXD3, MXD4, SYCP2, RPGR and STAG3 (By similarity).By similarity8 Publications
Binary interactionsi
GO - Molecular functioni
- beta-tubulin binding Source: UniProtKB
- dynein complex binding Source: UniProtKB
- mediator complex binding Source: Ensembl
- protein heterodimerization activity Source: UniProtKB
Protein-protein interaction databases
BioGridi | 114574. 145 interactors. |
CORUMi | Q9UQE7. |
DIPi | DIP-29200N. |
IntActi | Q9UQE7. 90 interactors. |
MINTi | Q9UQE7. |
STRINGi | 9606.ENSP00000354720. |
Structurei
3D structure databases
ProteinModelPortali | Q9UQE7. |
SMRi | Q9UQE7. |
ModBasei | Search... |
MobiDBi | Search... |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 505 – 667 | Flexible hingeAdd BLAST | 163 |
Coiled coil
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Coiled coili | 179 – 350 | Sequence analysisAdd BLAST | 172 | |
Coiled coili | 393 – 503 | Sequence analysisAdd BLAST | 111 | |
Coiled coili | 669 – 916 | Sequence analysisAdd BLAST | 248 | |
Coiled coili | 958 – 989 | Sequence analysisAdd BLAST | 32 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 1115 – 1150 | Ala/Asp-rich (DA-box)Add BLAST | 36 |
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
Keywords - Domaini
Coiled coilPhylogenomic databases
eggNOGi | KOG0964. Eukaryota. COG1196. LUCA. |
GeneTreei | ENSGT00580000081628. |
HOGENOMi | HOG000166512. |
HOVERGENi | HBG039849. |
InParanoidi | Q9UQE7. |
KOi | K06669. |
OMAi | SEMQKTE. |
OrthoDBi | EOG091G011B. |
PhylomeDBi | Q9UQE7. |
TreeFami | TF105602. |
Family and domain databases
InterProi | View protein in InterPro IPR027417. P-loop_NTPase. IPR003395. RecF/RecN/SMC_N. IPR024704. SMC. IPR010935. SMC_hinge. IPR036277. SMC_hinge_sf. |
Pfami | View protein in Pfam PF06470. SMC_hinge. 1 hit. PF02463. SMC_N. 1 hit. |
PIRSFi | PIRSF005719. SMC. 1 hit. |
SMARTi | View protein in SMART SM00968. SMC_hinge. 1 hit. |
SUPFAMi | SSF52540. SSF52540. 2 hits. SSF75553. SSF75553. 2 hits. |
i Sequence
Sequence statusi: Complete.
Q9UQE7-1 [UniParc]FASTAAdd to basket
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
Sequence cautioni
The sequence AAD32447 differs from that shown. Reason: Frameshift at positions 457, 488 and 523.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 462 | K → T in AAD32447 (PubMed:11042152).Curated | 1 | |
Sequence conflicti | 509 | I → V in AAD32447 (PubMed:11042152).Curated | 1 | |
Sequence conflicti | 526 | Q → P in AAD32447 (PubMed:11042152).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_032845 | 491 | Missing in CDLS3; affects the affinity of SMC hinge dimers for DNA; mutated hinge dimers bind DNA with higher affinity than wild-type proteins. 2 Publications | 1 |
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. |
CCDSi | CCDS31285.1. |
RefSeqi | NP_005436.1. NM_005445.3. |
UniGenei | Hs.24485. |
Genome annotation databases
Ensembli | ENST00000361804; ENSP00000354720; ENSG00000108055. |
GeneIDi | 9126. |
KEGGi | hsa:9126. |
UCSCi | uc001kze.4. human. |
Similar proteinsi
Entry informationi
Entry namei | SMC3_HUMAN | |
Accessioni | Q9UQE7Primary (citable) accession number: Q9UQE7 Secondary accession number(s): A8K156, O60464, Q5T482 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | March 25, 2003 |
Last sequence update: | March 25, 2003 | |
Last modified: | March 28, 2018 | |
This is version 180 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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