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

Summary

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

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_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.
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.
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 EBI GWAS CatalogPubMed
GWAS for discovery and replication of genetic loci associated with sudden cardiac arrest in patients with coronary artery disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
The Genetics of Hemoglobin A2 Regulation in Sickle Cell Anemia. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D2S280 (e-PCR), detects polymorphism
- UniSTS:77659

D2S280 (e-PCR), detects polymorphism
- UniSTS:52572

A006V48 (e-PCR)
- UniSTS:50843

PMC14579P1 (e-PCR)
- UniSTS:271005

PMC31832P1 (e-PCR)
- UniSTS:273091

RH104195 (e-PCR)
- UniSTS:98520

SHGC-148409 (e-PCR)
- UniSTS:176379

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)

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
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 ...
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

NC_000002.12 Reference GRCh38.p14 Primary Assembly

Range

191949046..192194933 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

UniProtKB/TrEMBL

B2RD22
XM_017003740.3 → XP_016859229.1 tomoregulin-2 isoform X3