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

    Gene ID: 10051, updated on 24-Apr-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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    Location:
    3q25.33
    Exon count:
    24
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (160399650..160434953)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (163174262..163209567)
    105.20220307 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. 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
    2. The Prognostic Value of the Expression of SMC4 mRNA in Breast Cancer. Ma RM, et al. Dis Markers, 2019. PMID 31871499, Free PMC Article
    3. Structural maintenance of chromosomes 4 is a predictor of survival and a novel therapeutic target in colorectal cancer. Feng XD, et al. Asian Pac J Cancer Prev, 2014. PMID 25422241
    4. 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
    5. 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

    See all (152) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. 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.
    2. 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.
    3. 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.
    4. 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.
    5. 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.
    6. 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.
    7. 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.
    8. 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.
    9. analysis of functional differences of SMC2 and SMC4 hinge domain between condensins and cohesin in DNA recognition
      Title: Structural Basis for Dimer Formation of Human Condensin Structural Maintenance of Chromosome Proteins and Its Implications for Single-stranded DNA Recognition.
    10. Results indicate that miR-124-5p may target the tumorigenesis gene, SMC4, which suggests that expression levels of miR-124-5p in plasma and FFPE samples.
      Title: Low expression levels of microRNA-124-5p correlated with poor prognosis in colorectal cancer via targeting of SMC4.
    Submit: New GeneRIF Correction See all GeneRIFs (14)

    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)

    Genotypes

    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_2023_10

    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

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

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

    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

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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