TMEFF2

TMEFF2
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2FMW
Identifiers
Aliases	TMEFF2 , CT120.2, HPP1, TENB2, TPEF, TR, TR-2, transmembrane protein with EGF like and two follistatin like domains 2
External IDs	OMIM: 605734; MGI: 1861735; HomoloGene: 9417; GeneCards: TMEFF2; OMA:TMEFF2 - orthologs
Gene location (Human)
Chr.	Chromosome 2 (human)
End	192,194,933 bp
Gene location (Mouse)
Chr.	Chromosome 1 (mouse)
End	51,226,429 bp
RNA expression pattern
	Top expressed in
	middle temporal gyrus; ; Brodmann area 46; ; spinal ganglia; ; Brodmann area 23; ; thalamus; ; pars reticulata; ; entorhinal cortex; ; corpus callosum; ; subthalamic nucleus; ; endothelial cell;
	Top expressed in
	anterior horn of spinal cord; ; facial motor nucleus; ; anterior amygdaloid area; ; supraoptic nucleus; ; optic nerve; ; habenula; ; lateral hypothalamus; ; ventral tegmental area; ; globus pallidus; ; deep cerebellar nuclei;
	More reference expression data
	n/a
Gene ontology
Molecular function	molecular function ;
Cellular component	integral component of membrane ; extracellular region ; membrane ; plasma membrane ;
Biological process	negative regulation of integrin biosynthetic process ; negative regulation of cell migration ; negative regulation of stress fiber assembly ; wound healing, spreading of cells ; animal organ morphogenesis ; tissue development ;
	Sources:Amigo / QuickGO
Orthologs
	23671
	56363
	ENSG00000144339
	ENSMUSG00000026109
	Q9UIK5
	Q9QYM9
	NM_001305134 ; NM_001305145 ; NM_016192
	NM_019790
	NP_001292063 ; NP_001292074 ; NP_057276
	NP_062764
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated October 16, 2024

The Transmembrane protein with an EGF-like and two follistatin-like domains 2 (TMEFF2) gene is located on chromosome 2q32-q33 and encodes a 374-residue long single polypeptide, type-I transmembrane proteoglycan.^[5] According to the HUGO gene nomenclature committee, the aliases of TMEFF2 include, HPP1, Tomoregulin (TR), Transmembrane protein TENB2 (TENB2), Cancer/testis antigen family 120, member 2 (CT120.2) and Transmembrane protein containing EGF and follistatin domains (TPEF). TMEFF2 was identified and characterized by at least five independent groups within the time span of approximately a year.

TMEFF2 is proteolytically shed from the cell surface.^[6] The reported functions of TMEFF2 span across a wide range of physiological and pathological spectra including metabolism, neuroprotection, apoptosis, embryonic development, onco-suppression and endocrine function. TMEFF2 promoter and its 5′-upstream CpG island are methylated in a number of cancers. An inverse correlation between TMEFF2 methylation and the stage, response to therapy and survival outcome has been observed.^[5] The detection of methylated free-circulating TMEFF2 DNA has been suggested as a potential diagnostic tool for colorectal cancer. The TMEFF2 downregulation signature equals and sometimes outperforms the Gleason and pathological scores in prostate cancer. TMEFF2 is downregulated in glioma and cotricotropinomas, and it impairs the production of adrenocorticotropic hormone in glioma cells. Through binding the amyloid β protein, its precursor and derivatives, TMEFF2 provides neuroprotection in Alzheimer's disease.^[6]

TMEFF2 is a multidomain protein with its N-terminus harbouring a signal peptide followed by two follistatin-like domains, an EGF (epidermal growth factor)-like domain, a transmembrane portion and a short intracellular domain.^[5] The EGF-like domain of TMEFF2 appears to be functionally ineffective because of the substitution of a crucial arginine residue (Arg39) with histidine, whereas the follistatin-like domains are reported to be crucial for the relevant functions of TMEFF2 .^[7]^[8]

Related Research Articles

Versican is a large extracellular matrix proteoglycan that is present in a variety of human tissues. It is encoded by the VCAN gene.

Mothers against decapentaplegic homolog 7 or SMAD7 is a protein that in humans is encoded by the SMAD7 gene.

Methyl-CpG-binding domain protein 1 is a protein that in humans is encoded by the MBD1 gene. The protein encoded by MBD1 binds to methylated sequences in DNA, and thereby influences transcription. It binds to a variety of methylated sequences, and appears to mediate repression of gene expression. It has been shown to play a role in chromatin modification through interaction with the histone H3K9 methyltransferase SETDB1. H3K9me3 is a repressive modification.

Heparin-binding EGF-like growth factor (HB-EGF) is a member of the EGF family of proteins that in humans is encoded by the HBEGF gene.

Receptor tyrosine-protein kinase erbB-4 is an enzyme that in humans is encoded by the ERBB4 gene. Alternatively spliced variants that encode different protein isoforms have been described; however, not all variants have been fully characterized.

Cluster of differentiation 97 is a protein also known as BL-Ac[F2] encoded by the ADGRE5 gene. CD97 is a member of the adhesion G protein-coupled receptor (GPCR) family. Adhesion GPCRs are characterized by an extended extracellular region often possessing N-terminal protein modules that is linked to a TM7 region via a domain known as the GPCR-Autoproteolysis INducing (GAIN) domain.

Adhesion G protein-coupled receptor L4 is a latrophilin-like orphan receptor of the adhesion G protein-coupled receptor family. In humans this protein is encoded by the ADGRL4 gene. ADGRL4 appears to have a role in angiogenesis, both physiological and pathological in cancer.

CD82, or KAI1, is a human protein encoded by the CD82 gene.

Lysine-specific demethylase 4A is an enzyme that in humans is encoded by the KDM4A gene.

EGF-containing fibulin-like extracellular matrix protein 2 is a protein that in humans is encoded by the EFEMP2 gene.

Protein kinase C-binding protein NELL1 also known as NEL-like protein 1 (NELL1) or Nel-related protein 1 (NRP1) is a protein that in humans is encoded by the NELL1 gene.

Cysteine-rich with EGF-like domain protein 1 is a protein that in humans is encoded by the CRELD1 gene.

Tetraspanin-8 is a protein that in humans is encoded by the TSPAN8 gene.

Delta and Notch-like epidermal growth factor-related receptor is a protein that in humans is encoded by the DNER gene.

Testican-2 is a protein that in humans is encoded by the SPOCK2 gene.

SH2 domain-containing protein 3A is a protein that in humans is encoded by the SH2D3A gene. The protein may be useful in Western Blots and ELISAs.

Chondroitin sulfate proteoglycan 5 is a protein that in humans is encoded by the CSPG5 gene.

Transmembrane protein 8B is a protein that in humans is encoded by the TMEM8B gene. It encodes for a transmembrane protein that is 338 amino acids long, and is located on human chromosome 9. Aliases associated with this gene include C9orf127, NAG-5, and NGX61.

Transmembrane protein 8A is a protein that in humans is encoded by the TMEM8A gene (16p13.3.). Evolutionarily, TMEM8A orthologs are found in primates and mammals and in a few more distantly related species. TMEM8A contains five transmembrane domains and one EGF-like domain which are all highly conserved in the ortholog space. Although there is no confirmed function of TMEM8A, through analyzing expression and experimental data, it is predicted that TMEM8A is an adhesion protein that plays a role in keeping T-cells in their resting state.

CKLF-like MARVEL transmembrane domain-containing 5 (CMTM5), previously termed chemokine-like factor superfamily 5, designates any one of the six protein isoforms encoded by six different alternative splices of its gene, CMTM5; CMTM5-v1 is the most studied of these isoforms. The CMTM5 gene is located in band 11.2 on the long arm of chromosome 14.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000144339 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000026109 – Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
1 2 3 Masood M, Grimm S, El-Bahrawy M, Yagüe E (December 2020). "TMEFF2: A Transmembrane Proteoglycan with Multifaceted Actions in Cancer and Disease". Cancers. 12 (12): 3862. doi: 10.3390/cancers12123862 . PMC 7766544 . PMID 33371267.
1 2 "TMEFF2 Encyclopedia MDPI".
↑ Horie M, Mitsumoto Y, Kyushiki H, Kanemoto N, Watanabe A, Taniguchi Y, Nishino N, Okamoto T, Kondo M, Mori T, Noguchi K, Nakamura Y, Takahashi EI, Tanigami A (July 2000). "Identification and characterization of TMEFF2, a novel survival factor for hippocampal and mesencephalic neurons". Genomics. 67 (2): 146–52. doi:10.1006/geno.2000.6228. PMID 10903839.
↑ "Entrez Gene: TMEFF2 transmembrane protein with EGF-like and two follistatin-like domains 2".

Masood M, Grimm S, El-Bahrawy M, Yagüe E (December 2020). "TMEFF2: A Transmembrane Proteoglycan with Multifaceted Actions in Cancer and Disease". Cancers. 12 (12): 3862. doi: 10.3390/cancers12123862 . PMC 7766544 . PMID 33371267.
Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
Uchida T, Wada K, Akamatsu T, Yonezawa M, Noguchi H, Mizoguchi A, Kasuga M, Sakamoto C (December 1999). "A novel epidermal growth factor-like molecule containing two follistatin modules stimulates tyrosine phosphorylation of erbB-4 in MKN28 gastric cancer cells". Biochemical and Biophysical Research Communications. 266 (2): 593–602. doi:10.1006/bbrc.1999.1873. PMID 10600548.
Liang G, Robertson KD, Talmadge C, Sumegi J, Jones PA (September 2000). "The gene for a novel transmembrane protein containing epidermal growth factor and follistatin domains is frequently hypermethylated in human tumor cells". Cancer Research. 60 (17): 4907–12. PMID 10987305.
Young J, Biden KG, Simms LA, Huggard P, Karamatic R, Eyre HJ, Sutherland GR, Herath N, Barker M, Anderson GJ, Fitzpatrick DR, Ramm GA, Jass JR, Leggett BA (January 2001). "HPP1: a transmembrane protein-encoding gene commonly methylated in colorectal polyps and cancers". Proceedings of the National Academy of Sciences of the United States of America. 98 (1): 265–70. doi: 10.1073/pnas.011415298 . PMC 14579 . PMID 11120884.
Glynne-Jones E, Harper ME, Seery LT, James R, Anglin I, Morgan HE, Taylor KM, Gee JM, Nicholson RI (October 2001). "TENB2, a proteoglycan identified in prostate cancer that is associated with disease progression and androgen independence". International Journal of Cancer. 94 (2): 178–84. doi: 10.1002/ijc.1450 . PMID 11668495. S2CID 22411392.
Shibata DM, Sato F, Mori Y, Perry K, Yin J, Wang S, Xu Y, Olaru A, Selaru F, Spring K, Young J, Abraham JM, Meltzer SJ (October 2002). "Hypermethylation of HPP1 is associated with hMLH1 hypermethylation in gastric adenocarcinomas". Cancer Research. 62 (20): 5637–40. PMID 12384516.
Sato F, Shibata D, Harpaz N, Xu Y, Yin J, Mori Y, Wang S, Olaru A, Deacu E, Selaru FM, Kimos MC, Hytiroglou P, Young J, Leggett B, Gazdar AF, Toyooka S, Abraham JM, Meltzer SJ (December 2002). "Aberrant methylation of the HPP1 gene in ulcerative colitis-associated colorectal carcinoma". Cancer Research. 62 (23): 6820–2. PMID 12460892.
Gery S, Koeffler HP (May 2003). "Repression of the TMEFF2 promoter by c-Myc". Journal of Molecular Biology. 328 (5): 977–83. doi:10.1016/S0022-2836(03)00404-2. PMID 12729735.
Sabbioni S, Miotto E, Veronese A, Sattin E, Gramantieri L, Bolondi L, Calin GA, Gafà R, Lanza G, Carli G, Ferrazzi E, Feo C, Liboni A, Gullini S, Negrini M (2004). "Multigene methylation analysis of gastrointestinal tumors: TPEF emerges as a frequent tumor-specific aberrantly methylated marker that can be detected in peripheral blood". Molecular Diagnosis. 7 (3–4): 201–7. doi:10.2165/00066982-200307030-00010. PMID 15068392.
Zhang Z, Henzel WJ (October 2004). "Signal peptide prediction based on analysis of experimentally verified cleavage sites". Protein Science. 13 (10): 2819–24. doi:10.1110/ps.04682504. PMC 2286551 . PMID 15340161.
Schulmann K, Sterian A, Berki A, Yin J, Sato F, Xu Y, Olaru A, Wang S, Mori Y, Deacu E, Hamilton J, Kan T, Krasna MJ, Beer DG, Pepe MS, Abraham JM, Feng Z, Schmiegel W, Greenwald BD, Meltzer SJ (June 2005). "Inactivation of p16, RUNX3, and HPP1 occurs early in Barrett's-associated neoplastic progression and predicts progression risk". Oncogene. 24 (25): 4138–48. doi: 10.1038/sj.onc.1208598 . PMID 15824739.
Otsuki T, Ota T, Nishikawa T, Hayashi K, Suzuki Y, Yamamoto J, Wakamatsu A, Kimura K, Sakamoto K, Hatano N, Kawai Y, Ishii S, Saito K, Kojima S, Sugiyama T, Ono T, Okano K, Yoshikawa Y, Aotsuka S, Sasaki N, Hattori A, Okumura K, Nagai K, Sugano S, Isogai T (2007). "Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries". DNA Research. 12 (2): 117–26. doi: 10.1093/dnares/12.2.117 . PMID 16303743.

This article on a gene on human chromosome 2 is a stub. You can help Wikipedia by expanding it.

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000144339 – Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000026109 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[Masood_et_al.-5] 1 2 3 Masood M, Grimm S, El-Bahrawy M, Yagüe E (December 2020). "TMEFF2: A Transmembrane Proteoglycan with Multifaceted Actions in Cancer and Disease". Cancers. 12 (12): 3862. doi: 10.3390/cancers12123862 . PMC 7766544 . PMID 33371267.

[Encyclopedia-6] 1 2 "TMEFF2 Encyclopedia MDPI".

[pmid10903839-7] Horie M, Mitsumoto Y, Kyushiki H, Kanemoto N, Watanabe A, Taniguchi Y, Nishino N, Okamoto T, Kondo M, Mori T, Noguchi K, Nakamura Y, Takahashi EI, Tanigami A (July 2000). "Identification and characterization of TMEFF2, a novel survival factor for hippocampal and mesencephalic neurons". Genomics. 67 (2): 146–52. doi:10.1006/geno.2000.6228. PMID 10903839.

[entrez-8] "Entrez Gene: TMEFF2 transmembrane protein with EGF-like and two follistatin-like domains 2".

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

TMEFF2

Related Research Articles

References

Further reading