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    TMEFF2 transmembrane protein with EGF like and two follistatin like domains 2 [ Homo sapiens (human) ]

    Gene ID: 23671, updated on 14-Nov-2024

    Summary

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    Official Symbol
    TMEFF2provided by HGNC
    Official Full Name
    transmembrane protein with EGF like and two follistatin like domains 2provided by HGNC
    Primary source
    HGNC:HGNC:11867
    See related
    Ensembl:ENSG00000144339 MIM:605734; AllianceGenome:HGNC:11867
    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
    TR; HPP1; TPEF; TR-2; TENB2; CT120.2
    Summary
    This gene encodes a member of the tomoregulin family of transmembrane proteins. This protein has been shown to function as both an oncogene and a tumor suppressor depending on the cellular context and may regulate prostate cancer cell invasion. Multiple soluble forms of this protein have been identified that arise from both an alternative splice variant and ectodomain shedding. Additionally, this gene has been found to be hypermethylated in multiple cancer types. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]
    Expression
    Biased expression in prostate (RPKM 5.9), brain (RPKM 4.8) and 3 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See TMEFF2 in Genome Data Viewer
    Location:
    2q32.3
    Exon count:
    11
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (191949046..192194933, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (192437261..192683624, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (192813772..193059659, complement)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:192711519-192712027 Neighboring gene Sharpr-MPRA regulatory region 6341 Neighboring gene Sharpr-MPRA regulatory region 2977 Neighboring gene CAVIN2 and TMEFF2 antisense RNA 1 Neighboring gene Sharpr-MPRA regulatory region 5853 Neighboring gene caveolae associated protein 2 Neighboring gene DNAJB1 pseudogene 1 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:192867249-192867501 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16884 Neighboring gene NANOG hESC enhancer GRCh37_chr2:192976090-192976700 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:192995676-192996367 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:192994983-192995675 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:193059605-193060180 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:193372281-193372872 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:193372873-193373463 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr2:193406886-193407706 Neighboring gene NANOG hESC enhancer GRCh37_chr2:193600042-193600633 Neighboring gene Sharpr-MPRA regulatory region 3165 Neighboring gene PCGEM1 prostate-specific transcript Neighboring gene ribosomal protein S17 pseudogene 8 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:193795141-193795642 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:193795643-193796142 Neighboring gene uncharacterized LOC107985969 Neighboring gene MPRA-validated peak3996 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 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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    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Prognostic and clinicopathological significance of TMEFF2, SMOC-2, and SOX17 expression in endometrial carcinoma.
      Title: Prognostic and clinicopathological significance of TMEFF2, SMOC-2, and SOX17 expression in endometrial carcinoma.
    2. Long non-coding RNA LINC01963 inhibits progression of pancreatic carcinoma by targeting miR-641/TMEFF2.
      Title: Long non-coding RNA LINC01963 inhibits progression of pancreatic carcinoma by targeting miR-641/TMEFF2.
    3. MiR-323-3p Targeting Transmembrane Protein with EGF-Like and 2 Follistatin Domain (TMEFF2) Inhibits Human Lung Cancer A549 Cell Apoptosis by Regulation of AKT and ERK Signaling Pathways.
      Title: MiR-323-3p Targeting Transmembrane Protein with EGF-Like and 2 Follistatin Domain (TMEFF2) Inhibits Human Lung Cancer A549 Cell Apoptosis by Regulation of AKT and ERK Signaling Pathways.
    4. HPP1 Ectodomain Shedding is Mediated by ADAM17 and is Necessary for Tumor Suppression in Colon Cancer.
      Title: HPP1 Ectodomain Shedding is Mediated by ADAM17 and is Necessary for Tumor Suppression in Colon Cancer.
    5. Roles of a TMPO-AS1/microRNA-200c/TMEFF2 ceRNA network in the malignant behaviors and 5-FU resistance of ovarian cancer cells.
      Title: Roles of a TMPO-AS1/microRNA-200c/TMEFF2 ceRNA network in the malignant behaviors and 5-FU resistance of ovarian cancer cells.
    6. TMEFF2 plays an important role in the initiation, development, and malignant behavior of endometrial carcinoma (EC) and can be a potential target for early diagnosis and treatment in EC
      Title: TMEFF2 is a novel prognosis signature and target for endometrial carcinoma.
    7. TMEFF2 expression was down-regulated in pancreatic cancer tissue compared with normal pancreas. In human pancreatic cancer cell lines, overexpression of TMEFF2 suppressed cell proliferation and enhanced apoptosis, suppressed the expression of p-STAT3, MCL1, VEGF and increased the expression of the tyrosine-specific protein phosphatase, SHP-1.
      Title: Expression of TMEFF2 in Human Pancreatic Cancer Tissue and the Effects of TMEFF2 Knockdown on Cell, Proliferation, and Apoptosis in Human Pancreatic Cell Lines.
    8. Study identifies a panel of 11 TMEFF2 regulated cell cycle related genes (TMCC11), provides evidence that the TMCC11 gene signature is a robust independent prognostic marker for prostate cancer (PCa), and suggests the possibility that low TMEFF2 expression marks a distinct subclass of PCa.
      Title: A TMEFF2-regulated cell cycle derived gene signature is prognostic of recurrence risk in prostate cancer.
    9. Our data show that candidate TSG genes QKI and TMEFF2 harbor mutational ITH as well as the frameshift mutations in GC and CRC with MSI-H. From this observation, frameshift mutations of QKI and TMEFF2 may play a role in tumorigenesis through their TSG inactivation in GC and CRC.
      Title: Frameshift mutation of candidate tumor suppressor genes QK1 and TMEFF2 in gastric and colorectal cancers.
    10. Differential TMEFF2 processing from a single transmembrane protein may be a general mechanism to modulate transmembrane protein levels and domains, dependent on the repertoire of ADAMs or TTSPs expressed by the target cell.
      Title: TMEFF2 shedding is regulated by oxidative stress and mediated by ADAMs and transmembrane serine proteases implicated in prostate cancer.
    Submit: New GeneRIF Correction See all GeneRIFs (39)

    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
    Genome-wide association with diabetes-related traits in the Framingham Heart Study.
    EBI GWAS Catalog
    GWAS for discovery and replication of genetic loci associated with sudden cardiac arrest in patients with coronary artery disease.
    EBI GWAS Catalog
    The Genetics of Hemoglobin A2 Regulation in Sickle Cell Anemia.
    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)

    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

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in cell differentiation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    acts_upstream_of_or_within negative regulation of cell migration IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    acts_upstream_of_or_within negative regulation of integrin biosynthetic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within negative regulation of stress fiber assembly IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    acts_upstream_of_or_within wound healing, spreading of cells IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in extracellular region IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in membrane NAS
    Non-traceable Author Statement
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    tomoregulin-2
    Names
    cancer/testis antigen family 120, member 2
    hyperplastic polyposis protein 1
    transmembrane protein TENB2
    transmembrane protein with EGF-like and two follistatin-like domains

    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_001305134.2 → NP_001292063.1  tomoregulin-2 isoform 2 precursor

      See identical proteins and their annotated locations for NP_001292063.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate splice site in the 3' terminal exon and therefore differs in the 3' coding region and 3' UTR compared to variant 1. The encoded isoform (2) is shorter and has a distinct C-terminus compared to isoform 1.
      Source sequence(s)
      AC098617, AF242222, AL157430
      Consensus CDS
      CCDS82548.1
      UniProtKB/TrEMBL
      B2RD22
      Related
      ENSP00000376128.1, ENST00000392314.5
      Conserved Domains (3) summary
      smart00280
      Location:181 → 227
      KAZAL; Kazal type serine protease inhibitors
      cd00104
      Location:95 → 135
      KAZAL_FS; Kazal type serine protease inhibitors and follistatin-like domains. Kazal inhibitors inhibit serine proteases, such as, trypsin, chyomotrypsin, avian ovomucoids, and elastases. The inhibitory domain has one reactive site peptide bond, which serves the ...
      cl28647
      Location:236 → 301
      PHA02887; EGF-like protein; Provisional

    2. NM_001305145.1 → NP_001292074.1  tomoregulin-2 isoform 3 precursor

      See identical proteins and their annotated locations for NP_001292074.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks several exons and its 3' terminal exon extends past a splice site that is used in variant 1. This results in a novel 3' coding region and 3' UTR, compared to variant 1. The encoded isoform (3, also known as TMEFF2-S) is shorter and has a distinct C-terminus compared to isoform 1.
      Source sequence(s)
      AC092644, AF242222, DQ133599
      Consensus CDS
      CCDS82547.1
      UniProtKB/Swiss-Prot
      Q9UIK5
      Related
      ENSP00000386871.3, ENST00000409056.3
      Conserved Domains (1) summary
      cd00104
      Location:95 → 135
      KAZAL_FS; Kazal type serine protease inhibitors and follistatin-like domains. Kazal inhibitors inhibit serine proteases, such as, trypsin, chyomotrypsin, avian ovomucoids, and elastases. The inhibitory domain has one reactive site peptide bond, which serves the ...

    3. NM_016192.4 → NP_057276.2  tomoregulin-2 isoform 1 precursor

      See identical proteins and their annotated locations for NP_057276.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1).
      Source sequence(s)
      AC098617, AF179274, AF242222, AL157430
      Consensus CDS
      CCDS2314.1
      UniProtKB/Swiss-Prot
      Q2FA44, Q4ZFW4, Q53H90, Q53RE1, Q8N2R5, Q9NR15, Q9NSS5, Q9P2Y9, Q9UIK5, Q9UK65
      UniProtKB/TrEMBL
      B2RD22, B3KQB7
      Related
      ENSP00000272771.5, ENST00000272771.10
      Conserved Domains (3) summary
      PHA02887
      Location:236 → 301
      PHA02887; EGF-like protein; Provisional
      smart00280
      Location:181 → 227
      KAZAL; Kazal type serine protease inhibitors
      cd00104
      Location:95 → 135
      KAZAL_FS; Kazal type serine protease inhibitors and follistatin-like domains. Kazal inhibitors inhibit serine proteases, such as, trypsin, chyomotrypsin, avian ovomucoids, and elastases. The inhibitory domain has one reactive site peptide bond, which serves the ...

    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_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      191949046..192194933 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011510890.4 → XP_011509192.1  tomoregulin-2 isoform X1

      See identical proteins and their annotated locations for XP_011509192.1

      UniProtKB/TrEMBL
      B2RD22, B3KQB7
      Conserved Domains (3) summary
      PHA02887
      Location:227 → 292
      PHA02887; EGF-like protein; Provisional
      smart00280
      Location:172 → 218
      KAZAL; Kazal type serine protease inhibitors
      cd00104
      Location:95 → 135
      KAZAL_FS; Kazal type serine protease inhibitors and follistatin-like domains. Kazal inhibitors inhibit serine proteases, such as, trypsin, chyomotrypsin, avian ovomucoids, and elastases. The inhibitory domain has one reactive site peptide bond, which serves the ...

    2. XM_017003739.3 → XP_016859228.1  tomoregulin-2 isoform X2

      UniProtKB/TrEMBL
      B2RD22

    3. XM_017003740.3 → XP_016859229.1  tomoregulin-2 isoform X3

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      192437261..192683624 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054341229.1 → XP_054197204.1  tomoregulin-2 isoform X1

    2. XM_054341230.1 → XP_054197205.1  tomoregulin-2 isoform X2

    3. XM_054341231.1 → XP_054197206.1  tomoregulin-2 isoform X3

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9UIK5.1 GenPept UniProtKB/Swiss-Prot:Q9UIK5

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