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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
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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

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