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    TSPAN4 tetraspanin 4 [ Homo sapiens (human) ]

    Gene ID: 7106, updated on 2-Nov-2024

    Summary

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    Official Symbol
    TSPAN4provided by HGNC
    Official Full Name
    tetraspanin 4provided by HGNC
    Primary source
    HGNC:HGNC:11859
    See related
    Ensembl:ENSG00000214063 MIM:602644; AllianceGenome:HGNC:11859
    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
    NAG2; NAG-2; TM4SF7; TSPAN-4; TETRASPAN
    Summary
    The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is a cell surface glycoprotein and is similar in sequence to its family member CD53 antigen. It is known to complex with integrins and other transmembrane 4 superfamily proteins. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in fat (RPKM 26.0), spleen (RPKM 24.1) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See TSPAN4 in Genome Data Viewer
    Location:
    11p15.5
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (842852..867111)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (894229..918529)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (842852..867111)

    Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3040 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3041 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:834349-834888 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:837986-838960 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3042 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:840788-841532 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:841533-842278 Neighboring gene H3K27ac hESC enhancer GRCh37_chr11:842279-843022 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3044 Neighboring gene ReSE screen-validated silencer GRCh37_chr11:843356-843524 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3045 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3046 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3047 Neighboring gene CD151 molecule (Raph blood group) Neighboring gene RNA polymerase II, I and III subunit L Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:854507-855020 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:858925-859458 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:859459-859992 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:859993-860525 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:860526-861060 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:863729-864262 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:865863-866396 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:870607-871369 Neighboring gene extensin-like Neighboring gene chitinase domain containing 1 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:889730-890249 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:891289-891806 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:891807-892326 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:893960-894462 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:897610-898120 Neighboring gene ReSE screen-validated silencer GRCh37_chr11:903420-903590 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3048 Neighboring gene Sharpr-MPRA regulatory region 4982 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:920183-920682 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3049 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:937789-938701 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:940609-941519 Neighboring gene adaptor related protein complex 2 subunit alpha 2 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:942997-943671 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:944346-945020 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:945021-945694 Neighboring gene Sharpr-MPRA regulatory region 620 Neighboring gene RNA, U6 small nuclear 1025, pseudogene

    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 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. Human tetraspanin transmembrane 4 superfamily member 4 or intestinal and liver tetraspan membrane protein is overexpressed in hepatocellular carcinoma and accelerates tumor cell growth. Li Y, et al. Acta Biochim Biophys Sin (Shanghai), 2012 Mar. PMID 22236579
    2. Identification of TSPAN4 as Novel Histamine H(4) Receptor Interactor. Ma X, et al. Biomolecules, 2021 Jul 30. PMID 34439793, Free PMC Article
    3. Exome sequencing of child-parent trios with bladder exstrophy: Findings in 26 children. Pitsava G, et al. Am J Med Genet A, 2021 Oct. PMID 34355505, Free PMC Article
    4. TSPAN4 and migrasomes in atherosclerosis regression correlated to myocardial infarction and pan-cancer progression. Zheng Y, et al. Cell Adh Migr, 2023 Dec. PMID 36513632, Free PMC Article
    5. Direct extracellular contact between integrin alpha(3)beta(1) and TM4SF protein CD151. Yauch RL, et al. J Biol Chem, 2000 Mar 31. PMID 10734060

    See all (29) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. TSPAN4 and migrasomes in atherosclerosis regression correlated to myocardial infarction and pan-cancer progression.
      Title: TSPAN4 and migrasomes in atherosclerosis regression correlated to myocardial infarction and pan-cancer progression.
    2. Exome sequencing of child-parent trios with bladder exstrophy: Findings in 26 children.
      Title: Exome sequencing of child-parent trios with bladder exstrophy: Findings in 26 children.
    3. Identification of TSPAN4 as Novel Histamine H4 Receptor Interactor.
      Title: Identification of TSPAN4 as Novel Histamine H(4) Receptor Interactor.
    4. TM4SF4/il-TMP has the potential to be biomarker in a hepatocellular carcinoma and plays a crucial role in promotion of cancer cell proliferation
      Title: Human tetraspanin transmembrane 4 superfamily member 4 or intestinal and liver tetraspan membrane protein is overexpressed in hepatocellular carcinoma and accelerates tumor cell growth.
    5. Observational study of gene-disease association. (HuGE Navigator)
      Title: New genetic associations detected in a host response study to hepatitis B vaccine.
    Submit: New GeneRIF Correction

    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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    Replication interactions

    Interaction Pubs
    HIV-1 infection (VSV-G pseudotyped) of CEMT4 T cells downregulates plasma membrane expression of TSPAN4 PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope transmembrane glycoprotein gp41 env A synthetic peptide corresponding to the immunosuppressive domain (amino acids 574-592) of HIV-1 gp41 downregulates the expression of tetraspanin 4 (TSPAN4) in peptide-treated PBMCs PubMed

    Go to the HIV-1, Human Interaction Database

    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 antigen binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables integrin binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in protein-containing complex assembly IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in focal adhesion HDA PubMed 
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in vesicle IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    tetraspanin-4
    Names
    novel antigen 2
    tetraspan TM4SF
    transmembrane 4 superfamily member 7

    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_001025234.2 → NP_001020405.1  tetraspanin-4 isoform a

      See identical proteins and their annotated locations for NP_001020405.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR, compared to variant 1. Variants 1, 2, 3, 4, 5 and 6 encode the same isoform (a).
      Source sequence(s)
      BC000389, BM555783, BM755435, BQ679002
      Consensus CDS
      CCDS7721.1
      UniProtKB/Swiss-Prot
      O14817, Q6IAP6
      UniProtKB/TrEMBL
      J3KQ42
      Related
      ENSP00000380554.1, ENST00000397406.5
      Conserved Domains (2) summary
      cd03165
      Location:105 → 202
      NET-5_like_LEL; Tetraspanin, extracellular domain or large extracellular loop (LEL), NET-5_like family. Tetraspanins are trans-membrane proteins with 4 trans-membrane segments. Both the N- and C-termini lie on the intracellular side of the membrane. This alignment model ...
      pfam00335
      Location:9 → 226
      Tetraspannin; Tetraspanin family

    2. NM_001025235.2 → NP_001020406.1  tetraspanin-4 isoform a

      See identical proteins and their annotated locations for NP_001020406.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR, compared to variant 1. Variants 1, 2, 3, 4, 5 and 6 encode the same isoform (a).
      Source sequence(s)
      AL543667, BC000389, BM555783, BM755435
      Consensus CDS
      CCDS7721.1
      UniProtKB/Swiss-Prot
      O14817, Q6IAP6
      UniProtKB/TrEMBL
      J3KQ42
      Conserved Domains (2) summary
      cd03165
      Location:105 → 202
      NET-5_like_LEL; Tetraspanin, extracellular domain or large extracellular loop (LEL), NET-5_like family. Tetraspanins are trans-membrane proteins with 4 trans-membrane segments. Both the N- and C-termini lie on the intracellular side of the membrane. This alignment model ...
      pfam00335
      Location:9 → 226
      Tetraspannin; Tetraspanin family

    3. NM_001025236.2 → NP_001020407.1  tetraspanin-4 isoform a

      See identical proteins and their annotated locations for NP_001020407.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 5' UTR, compared to variant 1. Variants 1, 2, 3, 4, 5 and 6 encode the same isoform (a).
      Source sequence(s)
      AL543667, BC000389, BG752017, BM555783, BM755435
      Consensus CDS
      CCDS7721.1
      UniProtKB/Swiss-Prot
      O14817, Q6IAP6
      UniProtKB/TrEMBL
      J3KQ42
      Related
      ENSP00000380555.1, ENST00000397408.5
      Conserved Domains (2) summary
      cd03165
      Location:105 → 202
      NET-5_like_LEL; Tetraspanin, extracellular domain or large extracellular loop (LEL), NET-5_like family. Tetraspanins are trans-membrane proteins with 4 trans-membrane segments. Both the N- and C-termini lie on the intracellular side of the membrane. This alignment model ...
      pfam00335
      Location:9 → 226
      Tetraspannin; Tetraspanin family

    4. NM_001025237.2 → NP_001020408.1  tetraspanin-4 isoform a

      See identical proteins and their annotated locations for NP_001020408.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript. Variants 1, 2, 3, 4, 5 and 6 encode the same isoform (a).
      Source sequence(s)
      AP006623, BC000389, BI820547, BM555783, BM755435
      Consensus CDS
      CCDS7721.1
      UniProtKB/Swiss-Prot
      O14817, Q6IAP6
      UniProtKB/TrEMBL
      J3KQ42
      Related
      ENSP00000380553.1, ENST00000397404.5
      Conserved Domains (2) summary
      cd03165
      Location:105 → 202
      NET-5_like_LEL; Tetraspanin, extracellular domain or large extracellular loop (LEL), NET-5_like family. Tetraspanins are trans-membrane proteins with 4 trans-membrane segments. Both the N- and C-termini lie on the intracellular side of the membrane. This alignment model ...
      pfam00335
      Location:9 → 226
      Tetraspannin; Tetraspanin family

    5. NM_001025238.2 → NP_001020409.1  tetraspanin-4 isoform a

      See identical proteins and their annotated locations for NP_001020409.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) differs in the 5' UTR, compared to variant 1. Variants 1, 2, 3, 4, 5 and 6 encode the same isoform (a).
      Source sequence(s)
      BC000389, BM555783, BM755435
      Consensus CDS
      CCDS7721.1
      UniProtKB/Swiss-Prot
      O14817, Q6IAP6
      UniProtKB/TrEMBL
      J3KQ42
      Related
      ENSP00000380558.2, ENST00000397411.6
      Conserved Domains (2) summary
      cd03165
      Location:105 → 202
      NET-5_like_LEL; Tetraspanin, extracellular domain or large extracellular loop (LEL), NET-5_like family. Tetraspanins are trans-membrane proteins with 4 trans-membrane segments. Both the N- and C-termini lie on the intracellular side of the membrane. This alignment model ...
      pfam00335
      Location:9 → 226
      Tetraspannin; Tetraspanin family

    6. NM_001025239.2 → NP_001020410.1  tetraspanin-4 isoform b

      See identical proteins and their annotated locations for NP_001020410.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (7) lacks an in-frame portion of the 5' coding region, compared to variant 1. The resulting isoform (b) has a shorter N-terminus when compared to isoform a.
      Source sequence(s)
      BC000389, BM555783, BM755435
      Consensus CDS
      CCDS41589.1
      UniProtKB/TrEMBL
      A8MVV6, B7WPM8
      Related
      ENSP00000380551.1, ENST00000397396.5
      Conserved Domains (2) summary
      cd03165
      Location:41 → 138
      NET-5_like_LEL; Tetraspanin, extracellular domain or large extracellular loop (LEL), NET-5_like family. Tetraspanins are trans-membrane proteins with 4 trans-membrane segments. Both the N- and C-termini lie on the intracellular side of the membrane. This alignment model ...
      pfam00335
      Location:1 → 166
      Tetraspannin; Tetraspanin family

    7. NM_003271.5 → NP_003262.1  tetraspanin-4 isoform a

      See identical proteins and their annotated locations for NP_003262.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) differs in the 5' UTR, compared to variant 1. Variants 1, 2, 3, 4, 5 and 6 encode the same isoform (a).
      Source sequence(s)
      BC000389, BM555783, BM755435
      Consensus CDS
      CCDS7721.1
      UniProtKB/Swiss-Prot
      O14817, Q6IAP6
      UniProtKB/TrEMBL
      J3KQ42
      Related
      ENSP00000380552.2, ENST00000397397.7
      Conserved Domains (2) summary
      cd03165
      Location:105 → 202
      NET-5_like_LEL; Tetraspanin, extracellular domain or large extracellular loop (LEL), NET-5_like family. Tetraspanins are trans-membrane proteins with 4 trans-membrane segments. Both the N- and C-termini lie on the intracellular side of the membrane. This alignment model ...
      pfam00335
      Location:9 → 226
      Tetraspannin; Tetraspanin family

    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_000011.10 Reference GRCh38.p14 Primary Assembly

      Range
      842852..867111
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011520341.3 → XP_011518643.1  tetraspanin-4 isoform X2

      See identical proteins and their annotated locations for XP_011518643.1

      UniProtKB/TrEMBL
      A8MVV6, B7WPM8
      Conserved Domains (2) summary
      cd03165
      Location:41 → 138
      NET-5_like_LEL; Tetraspanin, extracellular domain or large extracellular loop (LEL), NET-5_like family. Tetraspanins are trans-membrane proteins with 4 trans-membrane segments. Both the N- and C-termini lie on the intracellular side of the membrane. This alignment model ...
      pfam00335
      Location:1 → 166
      Tetraspannin; Tetraspanin family

    2. XM_011520338.2 → XP_011518640.1  tetraspanin-4 isoform X2

      See identical proteins and their annotated locations for XP_011518640.1

      UniProtKB/TrEMBL
      A8MVV6, B7WPM8
      Conserved Domains (2) summary
      cd03165
      Location:41 → 138
      NET-5_like_LEL; Tetraspanin, extracellular domain or large extracellular loop (LEL), NET-5_like family. Tetraspanins are trans-membrane proteins with 4 trans-membrane segments. Both the N- and C-termini lie on the intracellular side of the membrane. This alignment model ...
      pfam00335
      Location:1 → 166
      Tetraspannin; Tetraspanin family

    3. XM_011520339.3 → XP_011518641.1  tetraspanin-4 isoform X3

      See identical proteins and their annotated locations for XP_011518641.1

      Conserved Domains (2) summary
      cd03165
      Location:41 → 138
      NET-5_like_LEL; Tetraspanin, extracellular domain or large extracellular loop (LEL), NET-5_like family. Tetraspanins are trans-membrane proteins with 4 trans-membrane segments. Both the N- and C-termini lie on the intracellular side of the membrane. This alignment model ...
      pfam00335
      Location:33 → 166
      Tetraspannin; Tetraspanin family

    4. XM_011520337.3 → XP_011518639.1  tetraspanin-4 isoform X2

      See identical proteins and their annotated locations for XP_011518639.1

      UniProtKB/TrEMBL
      A8MVV6, B7WPM8
      Related
      ENSP00000431943.1, ENST00000525201.5
      Conserved Domains (2) summary
      cd03165
      Location:41 → 138
      NET-5_like_LEL; Tetraspanin, extracellular domain or large extracellular loop (LEL), NET-5_like family. Tetraspanins are trans-membrane proteins with 4 trans-membrane segments. Both the N- and C-termini lie on the intracellular side of the membrane. This alignment model ...
      pfam00335
      Location:1 → 166
      Tetraspannin; Tetraspanin family

    5. XM_005253102.2 → XP_005253159.1  tetraspanin-4 isoform X1

      See identical proteins and their annotated locations for XP_005253159.1

      UniProtKB/Swiss-Prot
      O14817, Q6IAP6
      UniProtKB/TrEMBL
      J3KQ42
      Related
      ENSP00000386513.2, ENST00000409543.6
      Conserved Domains (2) summary
      cd03165
      Location:105 → 202
      NET-5_like_LEL; Tetraspanin, extracellular domain or large extracellular loop (LEL), NET-5_like family. Tetraspanins are trans-membrane proteins with 4 trans-membrane segments. Both the N- and C-termini lie on the intracellular side of the membrane. This alignment model ...
      pfam00335
      Location:9 → 226
      Tetraspannin; Tetraspanin family

    6. XM_011520340.3 → XP_011518642.1  tetraspanin-4 isoform X2

      See identical proteins and their annotated locations for XP_011518642.1

      UniProtKB/TrEMBL
      A8MVV6, B7WPM8
      Conserved Domains (2) summary
      cd03165
      Location:41 → 138
      NET-5_like_LEL; Tetraspanin, extracellular domain or large extracellular loop (LEL), NET-5_like family. Tetraspanins are trans-membrane proteins with 4 trans-membrane segments. Both the N- and C-termini lie on the intracellular side of the membrane. This alignment model ...
      pfam00335
      Location:1 → 166
      Tetraspannin; Tetraspanin family

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060935.1 Alternate T2T-CHM13v2.0

      Range
      894229..918529
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054369774.1 → XP_054225749.1  tetraspanin-4 isoform X2

      UniProtKB/TrEMBL
      A8MVV6, B7WPM8

    2. XM_054369773.1 → XP_054225748.1  tetraspanin-4 isoform X2

      UniProtKB/TrEMBL
      A8MVV6, B7WPM8

    3. XM_054369771.1 → XP_054225746.1  tetraspanin-4 isoform X4

    4. XM_054369776.1 → XP_054225751.1  tetraspanin-4 isoform X3

    5. XM_054369777.1 → XP_054225752.1  tetraspanin-4 isoform X2

      UniProtKB/TrEMBL
      A8MVV6, B7WPM8

    6. XM_054369772.1 → XP_054225747.1  tetraspanin-4 isoform X1

      UniProtKB/Swiss-Prot
      O14817, Q6IAP6

    7. XM_054369775.1 → XP_054225750.1  tetraspanin-4 isoform X2

      UniProtKB/TrEMBL
      A8MVV6, B7WPM8
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O14817.1 GenPept UniProtKB/Swiss-Prot:O14817

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