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    TPBG trophoblast glycoprotein [ Homo sapiens (human) ]

    Gene ID: 7162, updated on 5-Mar-2024

    Summary

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    Official Symbol
    TPBGprovided by HGNC
    Official Full Name
    trophoblast glycoproteinprovided by HGNC
    Primary source
    HGNC:HGNC:12004
    See related
    Ensembl:ENSG00000146242 MIM:190920; AllianceGenome:HGNC:12004
    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
    5T4; M6P1; 5T4AG; WAIF1
    Summary
    This gene encodes a leucine-rich transmembrane glycoprotein that may be involved in cell adhesion. The encoded protein is an oncofetal antigen that is specific to trophoblast cells. In adults this protein is highly expressed in many tumor cells and is associated with poor clinical outcome in numerous cancers. Alternate splicing in the 5' UTR results in multiple transcript variants that encode the same protein. [provided by RefSeq, Oct 2009]
    Expression
    Ubiquitous expression in esophagus (RPKM 8.0), endometrium (RPKM 5.0) and 22 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    6q14.1
    Exon count:
    4
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (82362983..82367420)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (83582429..83586866)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (83072700..83077137)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene single stranded DNA binding protein 2 pseudogene Neighboring gene Sharpr-MPRA regulatory region 1235 Neighboring gene uncharacterized LOC105377874 Neighboring gene MPRA-validated peak5923 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24777 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24778 Neighboring gene ReSE screen-validated silencer GRCh37_chr6:82999144-82999335 Neighboring gene uncharacterized LOC105377875 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:83073481-83073992 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:83072967-83073480 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:83074144-83075046 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:83075047-83075948 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24779 Neighboring gene uncharacterized LOC124901352 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:83260993-83261494 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:83267770-83268402 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:83268403-83269035 Neighboring gene uncharacterized LOC105377876 Neighboring gene MPRA-validated peak5925 silencer

    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. Role of TPBG (Trophoblast Glycoprotein) Antigen in Human Pericyte Migratory and Angiogenic Activity. Spencer HL, et al. Arterioscler Thromb Vasc Biol, 2019 Jun. PMID 31018661
    2. Trophoblast Glycoprotein (TPGB/5T4) in Human Placenta: Expression, Regulation, and Presence in Extracellular Microvesicles and Exosomes. Alam SMK, et al. Reprod Sci, 2018 Feb. PMID 28481180, Free PMC Article
    3. 5T4-Targeted Therapy Ablates Cancer Stem Cells and Prevents Recurrence of Head and Neck Squamous Cell Carcinoma. Kerk SA, et al. Clin Cancer Res, 2017 May 15. PMID 27780858, Free PMC Article
    4. Trophoblast glycoprotein promotes pancreatic ductal adenocarcinoma cell metastasis through Wnt/planar cell polarity signaling. He P, et al. Mol Med Rep, 2015 Jul. PMID 25738465
    5. Understanding and exploiting 5T4 oncofoetal glycoprotein expression. Stern PL, et al. Semin Cancer Biol, 2014 Dec. PMID 25066861

    See all (36) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. LINC00342 induces metastasis of lung adenocarcinoma by targeting miR-15b/TPBG.
      Title: LINC00342 induces metastasis of lung adenocarcinoma by targeting miR-15b/TPBG.
    2. TPBG orchestrates the migratory and angiogenic activities of pericytes through the activation of the CXCL12/CXCR7/pERK axis.
      Title: Role of TPBG (Trophoblast Glycoprotein) Antigen in Human Pericyte Migratory and Angiogenic Activity.
    3. In extravillous trophoblasts, 5T4 may function in epithelial-to-mesenchymal transition during placentation. The role of syncytiotrophoblast 5T4 is unknown, but its abundance in shed syncytial vesicles may signify route of sensitization of the maternal immune system.
      Title: Trophoblast Glycoprotein (TPGB/5T4) in Human Placenta: Expression, Regulation, and Presence in Extracellular Microvesicles and Exosomes.
    4. Collectively, these findings demonstrate that an anti-5T4 antibody-drug conjugate reduces the fraction of cancer stem cells (CSC), and prevents local recurrence and suggest a novel therapeutic approach for patients with head and neck squamous cell carcinoma.
      Title: 5T4-Targeted Therapy Ablates Cancer Stem Cells and Prevents Recurrence of Head and Neck Squamous Cell Carcinoma.
    5. We obtained GWS evidence (P < 2.7 x 10(-6)) for gene-based association in the total sample with a novel locus, TPBG (P = 1.8 x 10(-6)).
      Title: Transethnic genome-wide scan identifies novel Alzheimer's disease loci.
    6. In conclusion, the present study provided evidence that TPBG is involved in PDAC metastasis, and that TPBG and its associated signaling pathways may be a suitable target for pancreatic ductal adenocarcinoma therapy.
      Title: Trophoblast glycoprotein promotes pancreatic ductal adenocarcinoma cell metastasis through Wnt/planar cell polarity signaling.
    7. 5T4 expression is mechanistically associated with the directional movement of cells through epithelial mesenchymal transition, facilitation of CXCL12/CXCR4 chemotaxis, blocking of canonical Wnt/beta-catenin while favouring non-canonical pathway signalling
      Title: Understanding and exploiting 5T4 oncofoetal glycoprotein expression.
    8. Tyrosine 325 plus the leucine-rich repeat 1 surface centered on a second exposed aromatic residue, phenylalanine 97, are essential for inhibition of Wnt/beta-catenin signaling.
      Title: Structural insights into the inhibition of Wnt signaling by cancer antigen 5T4/Wnt-activated inhibitory factor 1.
    9. The surface expression of 5T4 marks the use of the CXCR4 rather than the CXCR7 receptor, with distinct consequences for CXCL12 exposure.
      Title: CXCL12 receptor preference, signal transduction, biological response and the expression of 5T4 oncofoetal glycoprotein.
    10. 5T4 is a potential new antigen for targeted therapies such as immunotherapy in MPM, as it is overexpressed on mesothelioma cells and recognised by 5T4-specific cytotoxic T-cells.
      Title: Overexpression and potential targeting of the oncofoetal antigen 5T4 in malignant pleural mesothelioma.
    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

    Gene Ontology Provided by GOA

    Process Evidence Code Pubs
    involved_in cell adhesion NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in cell chemotaxis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in dendrite arborization IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in mesenchymal cell migration IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of canonical Wnt signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of cell population proliferation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in olfactory learning IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of ERK1 and ERK2 cascade IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of chemotaxis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of synapse assembly IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in protein localization to plasma membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in synaptic transmission, GABAergic IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in axon terminus IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in cell surface HDA PubMed 
    located_in dendrite IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in endoplasmic reticulum IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    trophoblast glycoprotein
    Names
    5T4 oncofetal antigen
    5T4 oncofetal trophoblast glycoprotein
    5T4 oncotrophoblast glycoprotein
    wnt-activated inhibitory factor 1

    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_033981.1 RefSeqGene

      Range
      5612..9215
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001166392.2 → NP_001159864.1  trophoblast glycoprotein precursor

      See identical proteins and their annotated locations for NP_001159864.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Both variants 1 and 2 encode the same protein.
      Source sequence(s)
      AL121977
      Consensus CDS
      CCDS4995.1
      UniProtKB/Swiss-Prot
      A8K555, Q13641
      Related
      ENSP00000440049.1, ENST00000543496.3
      Conserved Domains (4) summary
      smart00013
      Location:61 → 95
      LRRNT; Leucine rich repeat N-terminal domain
      smart00082
      Location:294 → 345
      LRRCT; Leucine rich repeat C-terminal domain
      sd00033
      Location:73 → 95
      LRR_RI; leucine-rich repeat [structural motif]
      pfam13855
      Location:211 → 270
      LRR_8; Leucine rich repeat

    2. NM_001376922.1 → NP_001363851.1  trophoblast glycoprotein precursor

      Status: VALIDATED

      Source sequence(s)
      AL121977
      Consensus CDS
      CCDS4995.1
      UniProtKB/Swiss-Prot
      A8K555, Q13641
      Related
      ENSP00000358765.4, ENST00000369750.4
      Conserved Domains (4) summary
      smart00013
      Location:61 → 95
      LRRNT; Leucine rich repeat N-terminal domain
      smart00082
      Location:294 → 345
      LRRCT; Leucine rich repeat C-terminal domain
      sd00033
      Location:73 → 95
      LRR_RI; leucine-rich repeat [structural motif]
      pfam13855
      Location:211 → 270
      LRR_8; Leucine rich repeat

    3. NM_006670.5 → NP_006661.1  trophoblast glycoprotein precursor

      See identical proteins and their annotated locations for NP_006661.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longer transcript. Both variants 1 and 2 encode the same protein.
      Source sequence(s)
      AL121977
      Consensus CDS
      CCDS4995.1
      UniProtKB/Swiss-Prot
      A8K555, Q13641
      Related
      ENSP00000441219.1, ENST00000535040.4
      Conserved Domains (4) summary
      smart00013
      Location:61 → 95
      LRRNT; Leucine rich repeat N-terminal domain
      smart00082
      Location:294 → 345
      LRRCT; Leucine rich repeat C-terminal domain
      sd00033
      Location:73 → 95
      LRR_RI; leucine-rich repeat [structural motif]
      pfam13855
      Location:211 → 270
      LRR_8; Leucine rich repeat

    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_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      82362983..82367420
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_013171802.1 Reference GRCh38.p14 PATCHES

      Range
      232798..237235
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      83582429..83586866
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q13641.1 GenPept UniProtKB/Swiss-Prot:Q13641

    Gene LinkOut

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

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