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TM4SF4 Gene

protein-coding   GIFtS: 49
GCID: GC03P149191

Transmembrane 4 L Six Family Member 4

(Previous name: transmembrane 4 superfamily member 4)
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(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Transmembrane 4 L Six Family Member 41 2     il-TMP2
ILTMP2 3 5     Intestinal And Liver (Il) Tetraspan Membrane Protein2
Transmembrane 4 Superfamily Member 41 2     Transmembrane 4 L6 Family Member 42
Intestine And Liver Tetraspan Membrane Protein2 3     IL-TMP3

External Ids:    HGNC: 118561   Entrez Gene: 71042   Ensembl: ENSG000001699037   OMIM: 6065675   UniProtKB: P482303   

Export aliases for TM4SF4 gene to outside databases

Previous GC identifers: GC03P146120 GC03P150076 GC03P150473 GC03P150512 GC03P150674 GC03P146564


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for TM4SF4 Gene:
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 that can
regulate cell proliferation.(provided by RefSeq, Mar 2011)

GeneCards Summary for TM4SF4 Gene:
TM4SF4 (transmembrane 4 L six family member 4) is a protein-coding gene. An important paralog of this gene is ENSG00000273331.

UniProtKB/Swiss-Prot: T4S4_HUMAN, P48230
Function: Regulates the adhesive and proliferative status of intestinal epithelial cells. Can mediate
density-dependent cell proliferation




(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000003.11  NC_018914.2  NT_005612.17  
Regulatory elements:
   Regulatory transcription factor binding sites in the TM4SF4 gene promoter:
         C/EBPbeta   AML1a   FOXO3   Evi-1   E47   FOXO3b   Nkx6-1   HFH-1   FOXO3a   ATF6   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidTM4SF4 promoter sequence
   Search Chromatin IP Primers for TM4SF4

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat TM4SF4


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 3q25   Ensembl cytogenetic band:  3q25.1   HGNC cytogenetic band: 3q25

TM4SF4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
TM4SF4 gene location

GeneLoc information about chromosome 3         GeneLoc Exon Structure

GeneLoc location for GC03P149191:  view genomic region     (about GC identifiers)

Start:
149,191,761 bp from pter      End:
149,221,181 bp from pter
Size:
29,421 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: T4S4_HUMAN, P48230 (See protein sequence)
Recommended Name: Transmembrane 4 L6 family member 4  
Size: 202 amino acids; 21396 Da
Secondary accessions: B2RDA4

Explore the universe of human proteins at neXtProt for TM4SF4: NX_P48230

Post-translational modifications: 

  • N-glycosylated. Glycosylation is required for the growth inhibitory effect1
  • Glycosylation2 at Asn124, Asn156
  • REFSEQ proteins: NP_004608.1  
    ENSEMBL proteins: 
     ENSP00000305852   ENSP00000419367  

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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    1 InterPro protein domain:
     IPR008661 L6_membrane

    Graphical View of Domain Structure for InterPro Entry P48230

    ProtoNet protein and cluster: P48230

    1 Blocks protein domain: IPB008661 L6 membrane

    UniProtKB/Swiss-Prot: T4S4_HUMAN, P48230
    Similarity: Belongs to the L6 tetraspanin family


    Find genes that share domains with TM4SF4           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: T4S4_HUMAN, P48230
    Function: Regulates the adhesive and proliferative status of intestinal epithelial cells. Can mediate
    density-dependent cell proliferation

    Phenotypes:
         1 MGI phenotypic allele for Tm4sf4 (no phenotypes)


    Find genes that share phenotypes with TM4SF4           About GenesLikeMe

    Animal Models:
       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for TM4SF4
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    miRNA
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    4 qRT-PCR Assays for microRNAs that regulate TM4SF4:
    hsa-miR-520d-5p hsa-miR-3674 hsa-miR-524-5p hsa-miR-664
    SwitchGear 3'UTR luciferase reporter plasmidTM4SF4 3' UTR sequence
    Inhib. RNA
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    Browse Sino Biological Human cDNA Clones
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    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    T4S4_HUMAN, P48230: Membrane; Multi-pass membrane protein
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    plasma membrane3

    Gene Ontology (GO): 1 cellular component term:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0016021integral component of membrane IEA--

    Find genes that share ontologies with TM4SF4           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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        Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for TM4SF4
    Interactions:

        Search GeneGlobe Interaction Network for TM4SF4

    STRING Interaction Network Preview (showing 1 interactants - click image to see more details)

    2 Interacting proteins for TM4SF4 (P482303 ENSP000003058524) via UniProtKB, MINT, STRING, and/or I2D
    InteractantInteraction Details
    GeneCardExternal ID(s)
    CREB3O438893I2D: score=1 
    SIRT1ENSP000002120154STRING: ENSP00000212015
    About this table

    Gene Ontology (GO): 1 biological process term:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0042246tissue regeneration IEA--

    Find genes that share ontologies with TM4SF4           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for TM4SF4 (T4S4)



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for TM4SF4 gene: 
    NM_004617.3  

    Unigene Cluster for TM4SF4:

    Transmembrane 4 L six family member 4
    Hs.133527  [show with all ESTs]
    Unigene Representative Sequence: AK055577
    3 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000305354(uc003exd.2) ENST00000465758 ENST00000463068
    miRNA
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    4 qRT-PCR Assays for microRNAs that regulate TM4SF4:
    hsa-miR-520d-5p hsa-miR-3674 hsa-miR-524-5p hsa-miR-664
    SwitchGear 3'UTR luciferase reporter plasmidTM4SF4 3' UTR sequence
    Inhib. RNA
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    Primer
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    OriGene qPCR primer pairs and template standards for TM4SF4
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    Pre-validated RT2 qPCR Primer Assay in human, mouse, rat TM4SF4
      QuantiTect SYBR Green Assays in human, mouse, rat TM4SF4
      QuantiFast Probe-based Assays in human, mouse, rat TM4SF4

    Additional mRNA sequence: 

    AK055577.1 AK315464.1 BC001386.2 BT007430.1 U31449.1 

    7 DOTS entries:

    DT.456083  DT.92432504  DT.95272341  DT.100783606  DT.100029904  DT.92432501  DT.95272340 

    Selected AceView cDNA sequences (see all 198):

    AI572072 BI253205 AW339205 NM_004617 AI566443 CA778155 BC001386 BE872624 
    U31449 BX423709 AI584060 AA452917 BM264034 BE868856 CA943651 BM825250 
    BM310834 AW013983 T80802 BG656336 AW338459 BQ287802 AK055577 AI337361 

    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    TM4SF4 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: GCTAGGGTTC
    TM4SF4 Expression
    About this image


    TM4SF4 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 2) fully expand
     
     Pancreas (Endocrine System)
             Endocrine Progenitor Cells Ventral Pancreatic Bud
     
     Gall Bladder (Hepatobiliary System)
    TM4SF4 Protein expression data from MOPED1, PaxDb2 and MaxQB3 --

    SOURCE GeneReport for Unigene cluster: Hs.133527

    UniProtKB/Swiss-Prot: T4S4_HUMAN, P48230
    Tissue specificity: Jejunum and liver

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    In Situ
    Assay Products:
     

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for TM4SF4

    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of chordates.

    Orthologs for TM4SF4 gene from Selected species (see all 12)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Tm4sf41 , 5 transmembrane 4 superfamily member 41, 5 86.8(n)1
    87.62(a)1
      3 (27.72 cM)5
    2293021  NM_145539.21  NP_663514.21 
     574253145 
    chicken
    (Gallus gallus)
    Aves TM4SF41 transmembrane 4 L six family member 4 68.65(n)
    70.81(a)
      771806  XM_001234022.3  XP_001234023.1 
    lizard
    (Anolis carolinensis)
    Reptilia TM4SF46
    transmembrane 4 L six family member 4
    67(a)
    1 ↔ 1
    3(18949094-18968156)
    African clawed frog
    (Xenopus laevis)
    Amphibia tm4sf4-prov2 transmembrane 4 superfamily member 4 77.52(n)    BC054239.1 
    zebrafish
    (Danio rerio)
    Actinopterygii Dr.35632 Transcribed sequence with weak similarity to protein more 77.27(n)    CD015290.1 


    ENSEMBL Gene Tree for TM4SF4 (if available)
    TreeFam Gene Tree for TM4SF4 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for TM4SF4 gene
    ENSG000002733312  TM4SF52  TM4SF192  TM4SF182  TM4SF12  
    4 SIMAP similar genes for TM4SF4 using alignment to 2 protein entries:     T4S4_HUMAN (see all proteins):
    TM4SF1    TM4SF5    TM4SF18    TM4SF19

    Find genes that share paralogs with TM4SF4           About GenesLikeMe



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for TM4SF4 (see all 799)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 3 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs799481011,2
    C,F--149190447(+) GTGTTG/AGAAAA 1 -- us2k12Minor allele frequency- A:0.07NA EA 240
    rs767806731,2
    C,F--149190449(+) GTTGGA/GAAACA 1 -- us2k13Minor allele frequency- G:0.04CSA WA EA 240
    rs1412232271,2
    --149190493(+) TTCTGG/TTGGAA 1 -- us2k10--------
    rs1890064581,2
    --149190538(+) TCTGTA/GTATCC 1 -- us2k10--------
    rs1163588171,2
    F--149190619(+) GAAGGG/ATCTCC 1 -- us2k11Minor allele frequency- A:0.02NA 120
    rs769920481,2
    C,F--149190625(+) TCTCCT/CACTGT 1 -- us2k12Minor allele frequency- C:0.07NA EA 240
    rs1507395941,2
    --149190637(+) TGCATA/TTACCT 1 -- us2k10--------
    rs1808014401,2
    --149190706(+) TTTTCA/TAAAAG 1 -- us2k10--------
    rs753257321,2
    C,F--149190713(+) AAAGGA/GAAATC 1 -- us2k11Minor allele frequency- G:0.03NA 120
    rs1852491021,2
    --149190722(+) TCTATA/GAGAGA 1 -- us2k10--------

    HapMap Linkage Disequilibrium report for TM4SF4 (149191761 - 149221181 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 2 variations for TM4SF4:    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv4056CNV Loss18451855
    esv29983CNV Gain17803354

    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing TM4SF4
    DNA2.0 Custom Variant and Variant Library Synthesis for TM4SF4

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 606567    OMIM disorders: --


    Find genes that share disorders with TM4SF4           About GenesLikeMe

    Genetic Association Database (GAD): TM4SF4

    Export disorders for TM4SF4 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for TM4SF4 gene, integrated from 10 sources (see all 12):
    (articles sorted by number of sources associating them with TM4SF4)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. A tetraspan membrane glycoprotein produced in the human intestinal epithelium and liver that can regulate cell density-dependent proliferation. (PubMed id 7665614)1, 2, 3 Wice B.M. and Gordon J.I. (J. Biol. Chem. 1995)
    2. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)1, 2 Gerhard D.S.... Malek J. (Genome Res. 2004)
    3. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PubMed id 14702039)1, 2 Ota T.... Sugano S. (Nat. Genet. 2004)
    4. Adenovirus-mediated delivery of siRNA targeting TM4SF4 attenuated liver cancer cell growth in vitro and in vivo. (PubMed id 23296076)1 Wang L....Zhao M. (Acta Biochim. Biophys. Sin. (Shanghai) 2013)
    5. Overexpression of S100B, TM4SF4, and OLFM4 genes is correlated with liver metastasis in Taiwanese colorectal cancer patients. (PubMed id 22011044)1 Huang M.Y....Lin S.R. (DNA Cell Biol. 2012)
    6. Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry. (PubMed id 19159218)2 Chen R.... Zou H. (J. Proteome Res. 2009)
    7. Microarray evaluation of endometrial receptivity in Chinese women with polycystic ovary syndrome. (PubMed id 18765015)1 Qiao J....Zhang X. (Reprod. Biomed. Online 2008)
    8. Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions. (PubMed id 15342556)1 Suzuki Y.... Sugano S. (Genome Res. 2004)
    9. Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. (PubMed id 12477932)1 Strausberg R.L....Marra M.A. (Proc. Natl. Acad. Sci. U.S.A. 2002)
    10. Complexes of tetraspanins with integrins: more than meets the eye. (PubMed id 11739647)1 Berditchevski F. (J. Cell. Sci. 2001)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 7104 HGNC: 11856 AceView: TM4SF4 Ensembl:ENSG00000169903 euGenes: HUgn7104
    ECgene: TM4SF4 H-InvDB: TM4SF4

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for TM4SF4 Pharmacogenomics, SNPs, Pathways

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for TM4SF4 gene:
    Search GeneIP for patents involving TM4SF4

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, eBioscience, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
    Advanced Cell Diagnostics, Animal models from inGenious Targeting Laboratory, genOway)
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