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
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; ; substantia nigra; ; spinal ganglia; ; Brodmann area 23; ; dorsolateral prefrontal cortex; ; corpus callosum; ; globus pallidus;
	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

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]

References[]

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000144339 - Ensembl, May 2017
^ ^a ^b ^c 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.
^ ^a ^b ^c 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. PMID 33371267.
^ ^a ^b "TMEFF2 Encyclopdia".
^ 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".

Further reading[]

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. 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.
Suzuki M, Shigematsu H, Shames DS, Sunaga N, Takahashi T, Shivapurkar N, Iizasa T, Frenkel EP, Minna JD, Fujisawa T, Gazdar AF (October 2005). "DNA methylation-associated inactivation of TGFbeta-related genes DRM/Gremlin, RUNX3, and HPP1 in human cancers". British Journal of Cancer. 93 (9): 1029–37. doi:10.1038/sj.bjc.6602837. PMC 2361683. PMID 16234815.
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 .

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

[refGRCm38Ensembl-2] 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] 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. PMID 33371267.

[Encycopedia-6] "TMEFF2 Encyclopdia".

[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".

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