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    SEMA4C semaphorin 4C [ Homo sapiens (human) ]

    Gene ID: 54910, updated on 3-May-2024

    Summary

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    Official Symbol
    SEMA4Cprovided by HGNC
    Official Full Name
    semaphorin 4Cprovided by HGNC
    Primary source
    HGNC:HGNC:10731
    See related
    Ensembl:ENSG00000168758 MIM:604462; AllianceGenome:HGNC:10731
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    SEMAF; SEMAI; SEMACL1; M-SEMA-F
    Summary
    Predicted to enable chemorepellent activity and semaphorin receptor binding activity. Involved in muscle cell differentiation and positive regulation of stress-activated MAPK cascade. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]
    Expression
    Ubiquitous expression in placenta (RPKM 20.2), endometrium (RPKM 13.1) and 24 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    2q11.2
    Exon count:
    19
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (96859718..96870830, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (97366349..97377098, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (97525455..97535817, complement)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:97503619-97504173 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11779 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11780 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:97507205-97507810 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:97510949-97511138 Neighboring gene ankyrin repeat domain 23 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11781 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11782 Neighboring gene ankyrin repeat domain 39 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:97531745-97532406 Neighboring gene collagen alpha-1(I) chain-like Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11783 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11784 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11785 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11786 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11787 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11788 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:97538976-97539476 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16235 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16234 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:97540777-97541537 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:97541538-97542298 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:97547779-97548334 Neighboring gene family with sequence similarity 178 member B Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:97553339-97553894 Neighboring gene Sharpr-MPRA regulatory region 12522 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:97564470-97564614 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:97569425-97569924 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:97572409-97573004 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:97578973-97579660 Neighboring gene uncharacterized LOC101927053 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:97592729-97593442 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:97615759-97616400 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:97616401-97617040 Neighboring gene RNA, 5S ribosomal pseudogene 101

    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. Serum semaphorin4C as an auxiliary diagnostic biomarker for breast cancer. Wang Y, et al. Clin Transl Med, 2021 Aug. PMID 34459126, Free PMC Article
    2. High SEMA4C expression promotes the epithelial-mesenchymal transition and predicts poor prognosis in colorectal carcinoma. Hou Y, et al. Aging (Albany NY), 2020 Nov 7. PMID 33177246, Free PMC Article
    3. SEMA4C is a novel target to limit osteosarcoma growth, progression, and metastasis. Smeester BA, et al. Oncogene, 2020 Jan. PMID 31582836
    4. Semaphorin 4C Promotes Macrophage Recruitment and Angiogenesis in Breast Cancer. Yang J, et al. Mol Cancer Res, 2019 Oct. PMID 31308149
    5. Tumor-associated Lymphatic Endothelial Cells Promote Lymphatic Metastasis By Highly Expressing and Secreting SEMA4C. Wei JC, et al. Clin Cancer Res, 2017 Jan 1. PMID 27401250

    See all (57) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Serum semaphorin4C as an auxiliary diagnostic biomarker for breast cancer.
      Title: Serum semaphorin4C as an auxiliary diagnostic biomarker for breast cancer.
    2. Effect of microrna-138 on epithelial-Mesenchymal transition and invasion of breast cancer cells by targeting semaphorin 4C.
      Title: Effect of microrna-138 on epithelial-Mesenchymal transition and invasion of breast cancer cells by targeting semaphorin 4C.
    3. High SEMA4C expression promotes the epithelial-mesenchymal transition and predicts poor prognosis in colorectal carcinoma.
      Title: High SEMA4C expression promotes the epithelial-mesenchymal transition and predicts poor prognosis in colorectal carcinoma.
    4. SEMA4C is a novel target to limit osteosarcoma growth, progression, and metastasis.
      Title: SEMA4C is a novel target to limit osteosarcoma growth, progression, and metastasis.
    5. Sema4C mediates EMT inducing chemotherapeutic resistance of miR-31-3p in cervical cancer cells.
      Title: Sema4C mediates EMT inducing chemotherapeutic resistance of miR-31-3p in cervical cancer cells.
    6. Downregulation of SEMA4C Inhibit Epithelial-Mesenchymal Transition (EMT) and the Invasion and Metastasis of Cervical Cancer Cells via Inhibiting Transforming Growth Factor-beta 1 (TGF-beta1)-Induced Hela cells p38 Mitogen-Activated Protein Kinase (MAPK) Activation.
      Title: Downregulation of SEMA4C Inhibit Epithelial-Mesenchymal Transition (EMT) and the Invasion and Metastasis of Cervical Cancer Cells via Inhibiting Transforming Growth Factor-beta 1 (TGF-β1)-Induced Hela cells p38 Mitogen-Activated Protein Kinase (MAPK) Activation.
    7. SEMA4C expression in breast cancer cells promotes cancer cell proliferation, macrophage recruitment, and angiogenesis.
      Title: Semaphorin 4C Promotes Macrophage Recruitment and Angiogenesis in Breast Cancer.
    8. Sema4D and 4C can contribute to tumor progression in human patients or experimental models, while the role of Sema4A has not yet been fully understood
      Title: Semaphorin 4A, 4C, and 4D: Function comparison in the autoimmunity, allergy, and cancer.
    9. data indicate that Sema4C/PlexinB2 signaling is essential for the growth of breast carcinoma cells, featuring a novel potential therapeutic target. In addition, elevated Sema4C expression enables indolent luminal-type tumors to become resistant to estrogen deprivation, invasive and metastatic in vivo
      Title: Sema4C/PlexinB2 signaling controls breast cancer cell growth, hormonal dependence and tumorigenic potential.
    10. Tumor-associated LECs produce sSEMA4C to promote lymphatic metastasis of tumors.
      Title: Tumor-associated Lymphatic Endothelial Cells Promote Lymphatic Metastasis By Highly Expressing and Secreting SEMA4C.
    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)

    Genotypes

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ20369, KIAA1739, MGC126382, MGC126383

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables chemorepellent activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables semaphorin receptor binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in axon guidance IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in cell migration in hindbrain ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in cerebellum development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in muscle cell differentiation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative chemotaxis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in neural crest cell migration IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in neural tube closure ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of cell migration IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of stress-activated MAPK cascade IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in semaphorin-plexin signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in semaphorin-plexin signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Component Evidence Code Pubs
    located_in extracellular space HDA PubMed 
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in postsynaptic density ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in postsynaptic density membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in synaptic vesicle membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in synaptic vesicle membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  

    General protein information

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    Preferred Names
    semaphorin-4C
    Names
    M-Sema F
    sema domain, immunoglobulin domain (Ig), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 4C

    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.

    mRNA and Protein(s)

    1. NM_017789.5 → NP_060259.4  semaphorin-4C precursor

      See identical proteins and their annotated locations for NP_060259.4

      Status: VALIDATED

      Source sequence(s)
      AC092636, BC017476, BC109104, BI518922
      Consensus CDS
      CCDS2029.1
      UniProtKB/Swiss-Prot
      Q32MJ3, Q7Z5X0, Q9C0C4
      Related
      ENSP00000306844.5, ENST00000305476.10
      Conserved Domains (3) summary
      cd11258
      Location:42 → 498
      Sema_4C; The Sema domain, a protein interacting module, of semaphorin 4C (Sema4C)
      smart00423
      Location:499 → 528
      PSI; domain found in Plexins, Semaphorins and Integrins
      cl11960
      Location:560 → 647
      Ig; Immunoglobulin domain

    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_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      96859718..96870830 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047444831.1 → XP_047300787.1  semaphorin-4C isoform X1

      UniProtKB/Swiss-Prot
      Q32MJ3, Q7Z5X0, Q9C0C4

    2. XM_011511380.2 → XP_011509682.1  semaphorin-4C isoform X1

      See identical proteins and their annotated locations for XP_011509682.1

      UniProtKB/Swiss-Prot
      Q32MJ3, Q7Z5X0, Q9C0C4
      Conserved Domains (3) summary
      cd11258
      Location:42 → 498
      Sema_4C; The Sema domain, a protein interacting module, of semaphorin 4C (Sema4C)
      smart00423
      Location:499 → 528
      PSI; domain found in Plexins, Semaphorins and Integrins
      cl11960
      Location:560 → 647
      Ig; Immunoglobulin domain

    3. XM_011511381.2 → XP_011509683.1  semaphorin-4C isoform X1

      See identical proteins and their annotated locations for XP_011509683.1

      UniProtKB/Swiss-Prot
      Q32MJ3, Q7Z5X0, Q9C0C4
      Conserved Domains (3) summary
      cd11258
      Location:42 → 498
      Sema_4C; The Sema domain, a protein interacting module, of semaphorin 4C (Sema4C)
      smart00423
      Location:499 → 528
      PSI; domain found in Plexins, Semaphorins and Integrins
      cl11960
      Location:560 → 647
      Ig; Immunoglobulin domain

    4. XM_011511379.3 → XP_011509681.1  semaphorin-4C isoform X1

      See identical proteins and their annotated locations for XP_011509681.1

      UniProtKB/Swiss-Prot
      Q32MJ3, Q7Z5X0, Q9C0C4
      Conserved Domains (3) summary
      cd11258
      Location:42 → 498
      Sema_4C; The Sema domain, a protein interacting module, of semaphorin 4C (Sema4C)
      smart00423
      Location:499 → 528
      PSI; domain found in Plexins, Semaphorins and Integrins
      cl11960
      Location:560 → 647
      Ig; Immunoglobulin domain

    5. XM_011511378.3 → XP_011509680.1  semaphorin-4C isoform X1

      See identical proteins and their annotated locations for XP_011509680.1

      UniProtKB/Swiss-Prot
      Q32MJ3, Q7Z5X0, Q9C0C4
      Conserved Domains (3) summary
      cd11258
      Location:42 → 498
      Sema_4C; The Sema domain, a protein interacting module, of semaphorin 4C (Sema4C)
      smart00423
      Location:499 → 528
      PSI; domain found in Plexins, Semaphorins and Integrins
      cl11960
      Location:560 → 647
      Ig; Immunoglobulin domain

    6. XM_011511382.4 → XP_011509684.1  semaphorin-4C isoform X1

      See identical proteins and their annotated locations for XP_011509684.1

      UniProtKB/Swiss-Prot
      Q32MJ3, Q7Z5X0, Q9C0C4
      Conserved Domains (3) summary
      cd11258
      Location:42 → 498
      Sema_4C; The Sema domain, a protein interacting module, of semaphorin 4C (Sema4C)
      smart00423
      Location:499 → 528
      PSI; domain found in Plexins, Semaphorins and Integrins
      cl11960
      Location:560 → 647
      Ig; Immunoglobulin domain

    7. XM_011511383.2 → XP_011509685.1  semaphorin-4C isoform X1

      See identical proteins and their annotated locations for XP_011509685.1

      UniProtKB/Swiss-Prot
      Q32MJ3, Q7Z5X0, Q9C0C4
      Conserved Domains (3) summary
      cd11258
      Location:42 → 498
      Sema_4C; The Sema domain, a protein interacting module, of semaphorin 4C (Sema4C)
      smart00423
      Location:499 → 528
      PSI; domain found in Plexins, Semaphorins and Integrins
      cl11960
      Location:560 → 647
      Ig; Immunoglobulin domain

    8. XM_017004393.3 → XP_016859882.1  semaphorin-4C isoform X2

    9. XM_017004394.3 → XP_016859883.1  semaphorin-4C isoform X3

      Related
      ENST00000482925.5

    10. XM_047444832.1 → XP_047300788.1  semaphorin-4C isoform X4

    11. XM_047444834.1 → XP_047300790.1  semaphorin-4C isoform X4

    12. XM_006712606.4 → XP_006712669.2  semaphorin-4C isoform X4

      Conserved Domains (1) summary
      cd11258
      Location:42 → 480
      Sema_4C; The Sema domain, a protein interacting module, of semaphorin 4C (Sema4C)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      97366349..97377098 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054342672.1 → XP_054198647.1  semaphorin-4C isoform X1

      UniProtKB/Swiss-Prot
      Q32MJ3, Q7Z5X0, Q9C0C4

    2. XM_054342676.1 → XP_054198651.1  semaphorin-4C isoform X1

      UniProtKB/Swiss-Prot
      Q32MJ3, Q7Z5X0, Q9C0C4

    3. XM_054342674.1 → XP_054198649.1  semaphorin-4C isoform X1

      UniProtKB/Swiss-Prot
      Q32MJ3, Q7Z5X0, Q9C0C4

    4. XM_054342671.1 → XP_054198646.1  semaphorin-4C isoform X6

    5. XM_054342670.1 → XP_054198645.1  semaphorin-4C isoform X5

    6. XM_054342675.1 → XP_054198650.1  semaphorin-4C isoform X1

      UniProtKB/Swiss-Prot
      Q32MJ3, Q7Z5X0, Q9C0C4

    7. XM_054342673.1 → XP_054198648.1  semaphorin-4C isoform X1

      UniProtKB/Swiss-Prot
      Q32MJ3, Q7Z5X0, Q9C0C4

    8. XM_054342677.1 → XP_054198652.1  semaphorin-4C isoform X3

    9. XM_054342679.1 → XP_054198654.1  semaphorin-4C isoform X4

    10. XM_054342680.1 → XP_054198655.1  semaphorin-4C isoform X4

    11. XM_054342678.1 → XP_054198653.1  semaphorin-4C isoform X4

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9C0C4.2 GenPept UniProtKB/Swiss-Prot:Q9C0C4

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