Human Gene SMC3 (ENST00000361804.5) from GENCODE V44
  Description: Homo sapiens structural maintenance of chromosomes 3 (SMC3), mRNA. (from RefSeq NM_005445)
RefSeq Summary (NM_005445): 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. [provided by RefSeq, Jul 2008].
Gencode Transcript: ENST00000361804.5
Gencode Gene: ENSG00000108055.11
Transcript (Including UTRs)
   Position: hg38 chr10:110,567,695-110,606,048 Size: 38,354 Total Exon Count: 29 Strand: +
Coding Region
   Position: hg38 chr10:110,567,817-110,604,302 Size: 36,486 Coding Exon Count: 29 

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RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesGeneReviewsMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr10:110,567,695-110,606,048)mRNA (may differ from genome)Protein (1217 aa)
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-  Comments and Description Text from UniProtKB
  ID: SMC3_HUMAN
DESCRIPTION: RecName: Full=Structural maintenance of chromosomes protein 3; Short=SMC protein 3; Short=SMC-3; AltName: Full=Basement membrane-associated chondroitin proteoglycan; Short=Bamacan; AltName: Full=Chondroitin sulfate proteoglycan 6; AltName: Full=Chromosome-associated polypeptide; Short=hCAP;
FUNCTION: 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.
SUBUNIT: 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. Interacts with PDS5A and WAPAL; regulated by SMC3 acetylation.
INTERACTION: Q29RF7:PDS5A; NbExp=4; IntAct=EBI-80718, EBI-1175454; Q9NTI5:PDS5B; NbExp=6; IntAct=EBI-80718, EBI-1175604; O60216:RAD21; NbExp=8; IntAct=EBI-80718, EBI-80739; P32908:SMC1 (xeno); NbExp=4; IntAct=EBI-80718, EBI-17402; Q8WVM7:STAG1; NbExp=7; IntAct=EBI-80718, EBI-1175097; Q8N3U4:STAG2; NbExp=6; IntAct=EBI-80718, EBI-1057252;
SUBCELLULAR LOCATION: 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.
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).
PTM: Phosphorylated upon DNA damage, probably by ATM or ATR.
PTM: 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.
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.
MISCELLANEOUS: Mutated Cornelia de Lange cell lines display genomic instability and sensitivity to ionizing radiation and interstrand cross-linking agents.
SIMILARITY: 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: Sequence=AAD32447.1; Type=Frameshift; Positions=457, 488, 523;

-  Primer design for this transcript
 

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-  MalaCards Disease Associations
  MalaCards Gene Search: SMC3
Diseases sorted by gene-association score: cornelia de lange syndrome 3* (919), smc3-related cornelia de lange syndrome* (500), cornelia de lange syndrome* (490), wiedemann-steiner syndrome* (231), sc phocomelia syndrome (12), roberts syndrome (8), kbg syndrome (7), retinitis pigmentosa (0)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 38.83 RPKM in Testis
Total median expression: 656.45 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
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-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -57.40122-0.470 Picture PostScript Text
3' UTR -344.201746-0.197 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR003395 - RecF/RecN/SMC
IPR010935 - SMC_hinge

Pfam Domains:
PF06470 - SMC proteins Flexible Hinge Domain
PF02463 - RecF/RecN/SMC N terminal domain

ModBase Predicted Comparative 3D Structure on Q9UQE7
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
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-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0003682 chromatin binding
GO:0003777 microtubule motor activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0036033 mediator complex binding
GO:0044877 macromolecular complex binding
GO:0046982 protein heterodimerization activity
GO:0048487 beta-tubulin binding
GO:0070840 dynein complex binding

Biological Process:
GO:0000278 mitotic cell cycle
GO:0006275 regulation of DNA replication
GO:0006281 DNA repair
GO:0006974 cellular response to DNA damage stimulus
GO:0007049 cell cycle
GO:0007062 sister chromatid cohesion
GO:0019827 stem cell population maintenance
GO:0032876 negative regulation of DNA endoreduplication
GO:0044791 positive regulation by host of viral release from host cell
GO:0051276 chromosome organization
GO:0051301 cell division
GO:0051321 meiotic cell cycle
GO:0051702 interaction with symbiont
GO:1901673 regulation of mitotic spindle assembly

Cellular Component:
GO:0000775 chromosome, centromeric region
GO:0000785 chromatin
GO:0000800 lateral element
GO:0005604 basement membrane
GO:0005622 intracellular
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005694 chromosome
GO:0005829 cytosol
GO:0008278 cohesin complex
GO:0016363 nuclear matrix
GO:0030893 meiotic cohesin complex
GO:0034991 nuclear meiotic cohesin complex
GO:0097431 mitotic spindle pole


-  Descriptions from all associated GenBank mRNAs
  AK315845 - Homo sapiens cDNA, FLJ79494 complete cds, highly similar to Structural maintenance of chromosome 3.
AK289771 - Homo sapiens cDNA FLJ75104 complete cds, highly similar to Homo sapiens chondroitin sulfate proteoglycan 6 (bamacan) (CSPG6),mRNA.
AF020043 - Homo sapiens chromosome-associated polypeptide (HCAP) mRNA, complete cds.
JD395922 - Sequence 376946 from Patent EP1572962.
BC047324 - Homo sapiens structural maintenance of chromosomes 3, mRNA (cDNA clone MGC:54230 IMAGE:5493263), complete cds.
AB587343 - Synthetic construct DNA, clone: pF1KE1028, Homo sapiens SMC3 gene for structural maintenance of chromosomes 3, without stop codon, in Flexi system.
AF067163 - Homo sapiens bamacan homolog mRNA, complete cds.
AL360194 - Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 432401.
AJ005015 - Homo sapiens mRNA for putative SMC-like protein, partial.
JD449218 - Sequence 430242 from Patent EP1572962.
JD363848 - Sequence 344872 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04110 - Cell cycle
hsa04114 - Oocyte meiosis

Reactome (by CSHL, EBI, and GO)

Protein Q9UQE7 (Reactome details) participates in the following event(s):

R-HSA-2468040 Cohesin binds PDS5 and WAPAL
R-HSA-3108212 SMC5-SMC6 Complex SUMOylates Cohesin with SUMO1
R-HSA-9011997 ESR1:ESTG, JUND:FOSB and Cohesin Complex bind distal enhancer elements in MYC gene promoter
R-HSA-2545203 Deacetylation of cleaved cohesin
R-HSA-2470935 Cohesin binding to decondensed chromatin is facilitated by NIPBL:MAU2
R-HSA-1638803 Phosphorylation of cohesin by PLK1 at centromeres
R-HSA-2468287 CDK1 phosphorylates CDCA5 (Sororin) at centromeres
R-HSA-2467811 Separation of sister chromatids
R-HSA-2467809 ESPL1 (Separase) cleaves centromeric cohesin
R-HSA-1638821 PP2A-B56 dephosphorylates centromeric cohesin
R-HSA-2545253 Deacetylation of cohesin
R-HSA-2467794 Resolution of sister chromatids
R-HSA-912467 BRCA1 is recruited to unsynapsed regions
R-HSA-912470 ATR phosphorylates Histone H2A.X at unsynapsed regions
R-HSA-2473152 Acetylation of SMC3 subunit of centromeric chromatin associated cohesin by ESCO1 or ESCO2
R-HSA-2468039 Acetylation of SMC3 subunit of chromosomal arm associated cohesin by ESCO1 or ESCO2
R-HSA-2473151 CDCA5 (Sororin) enables cohesion of sister centromeres
R-HSA-2468041 CDCA5 (Sororin) enables cohesion of sister chromosomal arms
R-HSA-2468293 CDK1 phosphorylates CDCA5 (Sororin) at chromosomal arms
R-HSA-2466068 Phosphorylation of cohesin by PLK1 at chromosomal arms
R-HSA-912450 ATR Kinase is recruited to unsynapsed regions
R-HSA-1221632 Meiotic synapsis
R-HSA-2470946 Cohesin Loading onto Chromatin
R-HSA-3108214 SUMOylation of DNA damage response and repair proteins
R-HSA-9018519 Estrogen-dependent gene expression
R-HSA-2467813 Separation of Sister Chromatids
R-HSA-1500620 Meiosis
R-HSA-68884 Mitotic Telophase/Cytokinesis
R-HSA-3108232 SUMO E3 ligases SUMOylate target proteins
R-HSA-8939211 ESR-mediated signaling
R-HSA-2500257 Resolution of Sister Chromatid Cohesion
R-HSA-68882 Mitotic Anaphase
R-HSA-1474165 Reproduction
R-HSA-1640170 Cell Cycle
R-HSA-2468052 Establishment of Sister Chromatid Cohesion
R-HSA-68886 M Phase
R-HSA-2990846 SUMOylation
R-HSA-9006931 Signaling by Nuclear Receptors
R-HSA-68877 Mitotic Prometaphase
R-HSA-2555396 Mitotic Metaphase and Anaphase
R-HSA-69242 S Phase
R-HSA-69278 Cell Cycle (Mitotic)
R-HSA-597592 Post-translational protein modification
R-HSA-162582 Signal Transduction
R-HSA-392499 Metabolism of proteins

-  Other Names for This Gene
  Alternate Gene Symbols: A8K156, BAM, BMH, CSPG6, ENST00000361804.1, ENST00000361804.2, ENST00000361804.3, ENST00000361804.4, NM_005445, O60464, Q5T482, Q9UQE7, SMC3L1, SMC3_HUMAN, uc001kze.1, uc001kze.2, uc001kze.3, uc001kze.4, uc001kze.5
UCSC ID: ENST00000361804.5
RefSeq Accession: NM_005445
Protein: Q9UQE7 (aka SMC3_HUMAN)
CCDS: CCDS31285.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene SMC3:
hpe-overview (Holoprosencephaly Overview)
cdh-ov (Congenital Diaphragmatic Hernia Overview)
cdls (Cornelia de Lange Syndrome)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.