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SMC4 structural maintenance of chromosomes 4 [ Homo sapiens (human) ]

Gene ID: 10051, updated on 10-Dec-2024

Summary

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Official Symbol
SMC4provided by HGNC
Official Full Name
structural maintenance of chromosomes 4provided by HGNC
Primary source
HGNC:HGNC:14013
See related
Ensembl:ENSG00000113810 MIM:605575; AllianceGenome:HGNC:14013
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
CAPC; CAP-C; SMC-4; SMC4L1
Summary
This gene belongs to the 'structural maintenance of chromosomes' (SMC) gene family. Members of this gene family play a role in two changes in chromosome structure during mitotic segregation of chromosomes- chromosome condensation and sister chromatid cohesion. The protein encoded by this gene is likely a subunit of the 13S condensin complex, which is involved in chromosome condensation. A pseudogene related to this gene is located on chromosome 2. [provided by RefSeq, Jun 2016]
Expression
Broad expression in testis (RPKM 22.9), bone marrow (RPKM 22.6) and 24 other tissues See more
Orthologs
mouse all
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Genomic context

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See SMC4 in Genome Data Viewer
Location:
3q25.33
Exon count:
24
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (160399650..160434953)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (163174262..163209567)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (160117438..160152741)

Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14854 Neighboring gene TRIM59-IFT80 readthrough (NMD candidate) Neighboring gene chromosome 3 open reading frame 80 Neighboring gene intraflagellar transport 80 Neighboring gene ribosomal protein L35a pseudogene 10 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:160117119-160117481 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14855 Neighboring gene microRNA 16-2 Neighboring gene microRNA 15b Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr3:160149190-160150389 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:160166710-160167230 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20758 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:160167750-160168269 Neighboring gene tripartite motif containing 59 Neighboring gene beta-1,3-glucuronyltransferase 3 pseudogene 1

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Low expression levels of microRNA-124-5p correlated with poor prognosis in colorectal cancer via targeting of SMC4. Jinushi T, et al. Cancer Med, 2014 Dec. PMID 25081869, Free PMC Article
  2. Overexpression of the structural maintenance of chromosome 4 protein is associated with tumor de-differentiation, advanced stage and vascular invasion of primary liver cancer. Zhou B, et al. Oncol Rep, 2012 Oct. PMID 22842912
  3. A novel miR-219-SMC4-JAK2/Stat3 regulatory pathway in human hepatocellular carcinoma. Zhou B, et al. J Exp Clin Cancer Res, 2014 Jun 30. PMID 24980149, Free PMC Article
  4. The structural maintenance of chromosomes (SMC) family of proteins in mammals. Ball AR Jr, et al. Chromosome Res, 2001. PMID 11321372
  5. SMC4 knockdown inhibits malignant biological behaviors of endometrial cancer cells by regulation of FoxO1 activity. Yan Y, et al. Arch Biochem Biophys, 2021 Nov 15. PMID 34506757

See all (187) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Screening Differential CircRNAs Expression Profiles Reveals the Regulatory Role of the has_circTPT1_003-has-miR-218-5p-CCNE2/SMC4 Signaling Axis in Bladder Carcinoma Progression.
    Title: Screening Differential CircRNAs Expression Profiles Reveals the Regulatory Role of the has_circTPT1_003-has-miR-218-5p-CCNE2/SMC4 Signaling Axis in Bladder Carcinoma Progression.
  2. Structural Maintenance of Chromosome Protein 4 Promotes the Progression of Cardia Adenocarcinoma via Regulation of the Wnt/beta-catenin Signaling Pathway.
    Title: Structural Maintenance of Chromosome Protein 4 Promotes the Progression of Cardia Adenocarcinoma via Regulation of the Wnt/β-catenin Signaling Pathway.
  3. FoxO1 promotes ovarian cancer by increasing transcription and METTL14-mediated m[6]A modification of SMC4.
    Title: FoxO1 promotes ovarian cancer by increasing transcription and METTL14-mediated m(6)A modification of SMC4.
  4. TREM-1 induces pyroptosis in cardiomyocytes by activating NLRP3 inflammasome through the SMC4/NEMO pathway.
    Title: TREM-1 induces pyroptosis in cardiomyocytes by activating NLRP3 inflammasome through the SMC4/NEMO pathway.
  5. MiR-433-3p restrains the proliferation, migration and invasion of glioma cells via targeting SMC4.
    Title: MiR-433-3p restrains the proliferation, migration and invasion of glioma cells via targeting SMC4.
  6. SMC4 knockdown inhibits malignant biological behaviors of endometrial cancer cells by regulation of FoxO1 activity.
    Title: SMC4 knockdown inhibits malignant biological behaviors of endometrial cancer cells by regulation of FoxO1 activity.
  7. Study found that mRNA expression of SMC4 was upregulated in invasive breast cancer cells. Patients with high mRNA level of SMC4 suffered different survival with triple negative breast cancer (TNBC) and non-TNBC. These results suggest that SMC4 could be a good biomarker for predicting the prognosis.
    Title: The Prognostic Value of the Expression of SMC4 mRNA in Breast Cancer.
  8. study demonstrated a novel HIF-1-miR-219-SMC4 regulatory pathway under hypoxic condition in hepatocellular carcinoma cells.
    Title: HIF-1-miR-219-SMC4 Regulatory Pathway Promoting Proliferation and Migration of HCC under Hypoxic Condition.
  9. this paper shows that condensin Smc4 promotes inflammatory innate immune response by epigenetically enhancing NEMO transcription
    Title: Condensin Smc4 promotes inflammatory innate immune response by epigenetically enhancing NEMO transcription.
  10. Study examined the expression of SMC4 in acute myeloid leukemia (AML) pediatric patients cells and normal cells and revealed that SMC4 was significantly higher than control. Utilizing SMC4 gene knockdown in the established MLL-AF9 AML mouse model study found that SMC4 knockdown inhibited AML progression by maintaining leukemia stem cells.
    Title: Structural maintenance of chromosomes 4 is required for leukemia stem cell maintenance in MLL-AF9 induced acute myeloid leukemia.
Submit: New GeneRIF Correction See all GeneRIFs (16)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Tat tat Interaction of HIV-1 Tat with SMC4 in T-cells is identified by a proteomic strategy based on affinity chromatography coupled with mass spectrometry PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding TAS
Traceable Author Statement
more info
 PubMed 
enables ATP hydrolysis activity IEA
Inferred from Electronic Annotation
more info
  
enables chromatin binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables single-stranded DNA binding IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in cell division IEA
Inferred from Electronic Annotation
more info
  
involved_in kinetochore organization IEA
Inferred from Electronic Annotation
more info
  
involved_in meiotic chromosome condensation IEA
Inferred from Electronic Annotation
more info
  
involved_in meiotic chromosome segregation IEA
Inferred from Electronic Annotation
more info
  
involved_in mitotic chromosome condensation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in mitotic sister chromatid segregation TAS
Traceable Author Statement
more info
 PubMed 
involved_in positive regulation of chromosome condensation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of chromosome condensation ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of chromosome segregation ISO
Inferred from Sequence Orthology
more info
  
involved_in positive regulation of chromosome separation ISO
Inferred from Sequence Orthology
more info
  
Component Evidence Code Pubs
located_in chromosome, centromeric region IEA
Inferred from Electronic Annotation
more info
  
located_in condensed nuclear chromosome ISO
Inferred from Sequence Orthology
more info
  
part_of condensin complex IDA
Inferred from Direct Assay
more info
 PubMed 
part_of condensin complex NAS
Non-traceable Author Statement
more info
 PubMed 
part_of condensin complex TAS
Traceable Author Statement
more info
 PubMed 
located_in cytosol IDA
Inferred from Direct Assay
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in nuclear speck IDA
Inferred from Direct Assay
more info
  
located_in nucleoplasm TAS
Traceable Author Statement
more info
  
located_in nucleus TAS
Traceable Author Statement
more info
 PubMed 

General protein information

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Preferred Names
structural maintenance of chromosomes protein 4
Names
SMC protein 4
SMC4 structural maintenance of chromosomes 4-like 1
chromosome-associated polypeptide C

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_050987.1 RefSeqGene

    Range
    5347..40650
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001002800.3 → NP_001002800.1  structural maintenance of chromosomes protein 4 isoform 1

    See identical proteins and their annotated locations for NP_001002800.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) is the longest transcript and encodes the longer isoform (1).
    Source sequence(s)
    AB019987, AL136877, BC106033
    Consensus CDS
    CCDS3189.1
    UniProtKB/Swiss-Prot
    A6NLT9, D3DNL8, O95752, Q8NDL4, Q9NTJ3, Q9UNT9
    UniProtKB/TrEMBL
    B3KXX5
    Related
    ENSP00000349961.3, ENST00000357388.8
    Conserved Domains (4) summary
    cd03274
    Location:82 → 241
    ABC_SMC4_euk; ATP-binding cassette domain of eukaryotic SMC4 proteins
    smart00968
    Location:613 → 727
    SMC_hinge; SMC proteins Flexible Hinge Domain
    pfam02463
    Location:83 → 1274
    SMC_N; RecF/RecN/SMC N terminal domain
    cl23887
    Location:327 → 427
    DUF4349; Domain of unknown function (DUF4349)

  2. NM_001288753.2 → NP_001275682.1  structural maintenance of chromosomes protein 4 isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) has an alternate splice site in the 5' coding region, compared to variant 2. The resulting isoform (2) lacks an internal segment, compared to isoform 1.
    Source sequence(s)
    AK128143, AL136877
    Consensus CDS
    CCDS75046.1
    UniProtKB/TrEMBL
    B3KXX5, E9PD53
    Related
    ENSP00000417964.1, ENST00000469762.5
    Conserved Domains (4) summary
    cd03274
    Location:57 → 216
    ABC_SMC4_euk; ATP-binding cassette domain of eukaryotic SMC4 proteins
    smart00968
    Location:588 → 702
    SMC_hinge; SMC proteins Flexible Hinge Domain
    pfam02463
    Location:58 → 1249
    SMC_N; RecF/RecN/SMC N terminal domain
    cl23887
    Location:302 → 402
    DUF4349; Domain of unknown function (DUF4349)

  3. NM_005496.3 → NP_005487.3  structural maintenance of chromosomes protein 4 isoform 1

    See identical proteins and their annotated locations for NP_005487.3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) differs in the 5' UTR, compared to variant 2. Both variants 1 and 2 encode the same isoform (1).
    Source sequence(s)
    AL136877, AL833949
    Consensus CDS
    CCDS3189.1
    UniProtKB/Swiss-Prot
    A6NLT9, D3DNL8, O95752, Q8NDL4, Q9NTJ3, Q9UNT9
    UniProtKB/TrEMBL
    B3KXX5
    Related
    ENSP00000341382.5, ENST00000344722.5
    Conserved Domains (4) summary
    cd03274
    Location:82 → 241
    ABC_SMC4_euk; ATP-binding cassette domain of eukaryotic SMC4 proteins
    smart00968
    Location:613 → 727
    SMC_hinge; SMC proteins Flexible Hinge Domain
    pfam02463
    Location:83 → 1274
    SMC_N; RecF/RecN/SMC N terminal domain
    cl23887
    Location:327 → 427
    DUF4349; Domain of unknown function (DUF4349)

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000003.12 Reference GRCh38.p14 Primary Assembly

    Range
    160399650..160434953
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011512311.3 → XP_011510613.1  structural maintenance of chromosomes protein 4 isoform X1

    See identical proteins and their annotated locations for XP_011510613.1

    UniProtKB/Swiss-Prot
    A6NLT9, D3DNL8, O95752, Q8NDL4, Q9NTJ3, Q9UNT9
    UniProtKB/TrEMBL
    B3KXX5
    Conserved Domains (4) summary
    cd03274
    Location:82 → 241
    ABC_SMC4_euk; ATP-binding cassette domain of eukaryotic SMC4 proteins
    smart00968
    Location:613 → 727
    SMC_hinge; SMC proteins Flexible Hinge Domain
    pfam02463
    Location:83 → 1274
    SMC_N; RecF/RecN/SMC N terminal domain
    cl23887
    Location:327 → 427
    DUF4349; Domain of unknown function (DUF4349)

  2. XM_006713459.5 → XP_006713522.1  structural maintenance of chromosomes protein 4 isoform X3

    UniProtKB/TrEMBL
    B3KXX5
    Conserved Domains (4) summary
    cd03274
    Location:82 → 241
    ABC_SMC4_euk; ATP-binding cassette domain of eukaryotic SMC4 proteins
    smart00968
    Location:535 → 649
    SMC_hinge; SMC proteins Flexible Hinge Domain
    pfam02463
    Location:83 → 1196
    SMC_N; RecF/RecN/SMC N terminal domain
    cl23887
    Location:327 → 427
    DUF4349; Domain of unknown function (DUF4349)

  3. XM_011512312.3 → XP_011510614.1  structural maintenance of chromosomes protein 4 isoform X2

    UniProtKB/TrEMBL
    B3KXX5
    Conserved Domains (3) summary
    cd03274
    Location:10 → 169
    ABC_SMC4_euk; ATP-binding cassette domain of eukaryotic SMC4 proteins
    smart00968
    Location:541 → 655
    SMC_hinge; SMC proteins Flexible Hinge Domain
    pfam02463
    Location:11 → 1202
    SMC_N; RecF/RecN/SMC N terminal domain

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060927.1 Alternate T2T-CHM13v2.0

    Range
    163174262..163209567
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054344823.1 → XP_054200798.1  structural maintenance of chromosomes protein 4 isoform X1

    UniProtKB/Swiss-Prot
    A6NLT9, D3DNL8, O95752, Q8NDL4, Q9NTJ3, Q9UNT9
    UniProtKB/TrEMBL
    B3KXX5

  2. XM_054344825.1 → XP_054200800.1  structural maintenance of chromosomes protein 4 isoform X3

    UniProtKB/TrEMBL
    B3KXX5

  3. XM_054344824.1 → XP_054200799.1  structural maintenance of chromosomes protein 4 isoform X2

    UniProtKB/TrEMBL
    B3KXX5

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_001002799.1: Suppressed sequence

    Description
    NM_001002799.1: This RefSeq was permanently suppressed because it contains an unsupported deletion in the CDS that causes a frameshift resulting in premature translation termination. NM_001002799.1 is therefore a nonsense-mediated m
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9NTJ3.2 GenPept UniProtKB/Swiss-Prot:Q9NTJ3

Gene LinkOut

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