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    TIMD4 T cell immunoglobulin and mucin domain containing 4 [ Homo sapiens (human) ]

    Gene ID: 91937, updated on 10-Dec-2024

    Summary

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    Official Symbol
    TIMD4provided by HGNC
    Official Full Name
    T cell immunoglobulin and mucin domain containing 4provided by HGNC
    Primary source
    HGNC:HGNC:25132
    See related
    Ensembl:ENSG00000145850 MIM:610096; AllianceGenome:HGNC:25132
    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
    TIM4; SMUCKLER
    Summary
    Predicted to enable phosphatidylserine binding activity. Predicted to be involved in apoptotic cell clearance and cytoskeletal rearrangement involved in phagocytosis, engulfment. Predicted to be located in extracellular region and plasma membrane. [provided by Alliance of Genome Resources, Dec 2024]
    Expression
    Biased expression in lymph node (RPKM 8.4), testis (RPKM 2.6) and 5 other tissues See more
    Orthologs
    all
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    Genomic context

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    See TIMD4 in Genome Data Viewer
    Location:
    5q33.3
    Exon count:
    10
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (156919292..156963226, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (157438332..157482246, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (156346303..156390237, complement)

    Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene RNA, U6 small nuclear 556, pseudogene Neighboring gene PPP1R2 family member B Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr5:156339619-156340818 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:156340819-156341764 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23495 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23496 Neighboring gene apolipoprotein O pseudogene 1 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr5:156441149-156441653 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr5:156441654-156442157 Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:156477155-156477714 Neighboring gene hepatitis A virus cellular receptor 1 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr5:156499176-156500375 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23497 Neighboring gene hepatitis A virus cellular receptor 2

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

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    Related articles in PubMed

    1. TIM-4 promotes the growth of non-small-cell lung cancer in a RGD motif-dependent manner. Zhang Q, et al. Br J Cancer, 2015 Nov 17. PMID 26512878, Free PMC Article
    2. Distribution characteristics and linkage disequilibrium of TIM4 promoter polymorphisms in asthma patients of Chinese Han population. Cai P, et al. J Huazhong Univ Sci Technolog Med Sci, 2008 Aug. PMID 18704309
    3. The phosphatidylserine receptor TIM-4 does not mediate direct signaling. Park D, et al. Curr Biol, 2009 Feb 24. PMID 19217291
    4. Tim-4 expression increases in ischemic stroke patients and is associated with poor outcome. Xu L, et al. J Neuroimmunol, 2018 Mar 15. PMID 29233585
    5. Role of TIM-4 in exosome-dependent entry of HIV-1 into human immune cells. Sims B, et al. Int J Nanomedicine, 2017. PMID 28740388, Free PMC Article

    See all (65) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. TIM-4 orchestrates mitochondrial homeostasis to promote lung cancer progression via ANXA2/PI3K/AKT/OPA1 axis.
      Title: TIM-4 orchestrates mitochondrial homeostasis to promote lung cancer progression via ANXA2/PI3K/AKT/OPA1 axis.
    2. Overexpression of Nuclear Enriched Autosomal Transcript 1 Facilitates Cell Proliferation, Migration Invasion, and Suppresses Apoptosis in Endometrial Cancer by Targeting MicroRNA-202-3p/T Cell Immunoglobulin and Mucin Domain 4 Axis.
      Title: Overexpression of Nuclear Enriched Autosomal Transcript 1 Facilitates Cell Proliferation, Migration Invasion, and Suppresses Apoptosis in Endometrial Cancer by Targeting MicroRNA-202-3p/T Cell Immunoglobulin and Mucin Domain 4 Axis.
    3. TIM-4 in macrophages contributes to nasal polyp formation through the TGF-beta1-mediated epithelial to mesenchymal transition in nasal epithelial cells.
      Title: TIM-4 in macrophages contributes to nasal polyp formation through the TGF-β1-mediated epithelial to mesenchymal transition in nasal epithelial cells.
    4. Tim4 recognizes carbon nanotubes and mediates phagocytosis leading to granuloma formation.
      Title: Tim4 recognizes carbon nanotubes and mediates phagocytosis leading to granuloma formation.
    5. Platelet-derived extracellular vesicles are increased in sera of Alzheimer's disease patients, as revealed by Tim4-based assays.
      Title: Platelet-derived extracellular vesicles are increased in sera of Alzheimer's disease patients, as revealed by Tim4-based assays.
    6. Tim-4(+) cavity-resident macrophages impair anti-tumor CD8(+) T cell immunity.
      Title: Tim-4(+) cavity-resident macrophages impair anti-tumor CD8(+) T cell immunity.
    7. EphA2 Interacts with Tim-4 through Association between Its FN3 Domain and the IgV Domain of Tim-4.
      Title: EphA2 Interacts with Tim-4 through Association between Its FN3 Domain and the IgV Domain of Tim-4.
    8. TIMD4 exhibits regulatory capability on the proliferation and apoptosis of diffuse large B-cell lymphoma cells via the Wnt/beta-catenin pathway.
      Title: TIMD4 exhibits regulatory capability on the proliferation and apoptosis of diffuse large B-cell lymphoma cells via the Wnt/β-catenin pathway.
    9. The expression of Tim-1 and Tim-4 molecules in regulatory T cells in type 1 diabetes.
      Title: The expression of Tim-1 and Tim-4 molecules in regulatory T cells in type 1 diabetes.
    10. Tim4 regulates NALP3 inflammasome expression and activity during monocyte/macrophage dysfunction in septic shock patients.
      Title: Tim4 regulates NALP3 inflammasome expression and activity during monocyte/macrophage dysfunction in septic shock patients.
    Submit: New GeneRIF Correction See all GeneRIFs (49)

    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

    EBI GWAS Catalog

    Description
    Biological, clinical and population relevance of 95 loci for blood lipids.
    EBI GWAS Catalog
    Common variants at 30 loci contribute to polygenic dyslipidemia.
    EBI GWAS Catalog
    Discovery and refinement of loci associated with lipid levels.
    EBI GWAS Catalog
    Genomic study in Mexicans identifies a new locus for triglycerides and refines European lipid loci.
    EBI GWAS Catalog

    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
    capsid gag TIM-4 inhibits the release of HIV-1 in terms of reduced levels of CA and RT activity in virus particles, and induces the accumulation of cell-associated CA PubMed
    reverse transcriptase gag-pol TIM-4 inhibits the release of HIV-1 in terms of reduced levels of CA and RT activity in virus particles, and induces the accumulation of cell-associated CA 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

    Clone Names

    • FLJ27515

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables phosphatidylserine binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in apoptotic cell clearance IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in cytoskeletal rearrangement involved in phagocytosis, engulfment IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    located_in extracellular region IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in plasma membrane IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    T-cell immunoglobulin and mucin domain-containing protein 4
    Names
    T-cell immunoglobulin mucin receptor 4
    T-cell membrane protein 4
    TIM-4
    TIMD-4

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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_001146726.2 → NP_001140198.1  T-cell immunoglobulin and mucin domain-containing protein 4 isoform 2 precursor

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) lacks an exon in the coding region compared to variant 1. The encoded isoform (2) is shorter compared to isoform 1.
      Source sequence(s)
      AA843555, AC008491, AC026777, BC008988
      Consensus CDS
      CCDS54943.1
      UniProtKB/Swiss-Prot
      Q96H15
      Related
      ENSP00000385973.3, ENST00000407087.4
      Conserved Domains (2) summary
      cd00096
      Location:36 → 40
      Ig; Ig strand B [structural motif]
      cl11960
      Location:28 → 129
      Ig; Immunoglobulin domain

    2. NM_138379.3 → NP_612388.2  T-cell immunoglobulin and mucin domain-containing protein 4 isoform 1 precursor

      See identical proteins and their annotated locations for NP_612388.2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AA843555, AC008491, BC008988
      Consensus CDS
      CCDS4332.1
      UniProtKB/Swiss-Prot
      B5MCL9, Q96H15
      Related
      ENSP00000274532.2, ENST00000274532.7
      Conserved Domains (2) summary
      smart00410
      Location:27 → 115
      IG_like; Immunoglobulin like
      pfam07686
      Location:23 → 128
      V-set; Immunoglobulin V-set domain

    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_000005.10 Reference GRCh38.p14 Primary Assembly

      Range
      156919292..156963226 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017010021.2 → XP_016865510.1  T-cell immunoglobulin and mucin domain-containing protein 4 isoform X1

    2. XM_011534694.3 → XP_011532996.1  T-cell immunoglobulin and mucin domain-containing protein 4 isoform X2

      Conserved Domains (1) summary
      pfam07686
      Location:23 → 128
      V-set; Immunoglobulin V-set domain

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060929.1 Alternate T2T-CHM13v2.0

      Range
      157438332..157482246 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054353790.1 → XP_054209765.1  T-cell immunoglobulin and mucin domain-containing protein 4 isoform X1

    2. XM_054353791.1 → XP_054209766.1  T-cell immunoglobulin and mucin domain-containing protein 4 isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q96H15.2 GenPept UniProtKB/Swiss-Prot:Q96H15

    Gene LinkOut

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

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