en TSPAN12

TSPAN12
Identifiers
Aliases	TSPAN12, EVR5, NET-2, NET2, TM4SF12, tetraspanin 12
External IDs	OMIM: 613138; MGI: 1889818; HomoloGene: 8212; GeneCards: TSPAN12; OMA:TSPAN12 - orthologs
Gene location (Human)
Chr.	Chromosome 7 (human)
End	120,858,402 bp
Gene location (Mouse)
Chr.	Chromosome 6 (mouse)
End	21,852,514 bp
RNA expression pattern
	Top expressed in
	oocyte; ; kidney tubule; ; secondary oocyte; ; right adrenal gland; ; right ventricle; ; lower lobe of lung; ; jejunal mucosa; ; glomerulus; ; metanephric glomerulus; ; left adrenal gland;
	Top expressed in
	brown adipose tissue; ; parotid gland; ; submandibular gland; ; tunica adventitia of aorta; ; white adipose tissue; ; intercostal muscle; ; female external genitalia; ; liver; ; adrenal gland; ; mucosa of urinary bladder;
	More reference expression data
	n/a
Gene ontology
Molecular function	protein binding; Wnt-activated receptor activity;
Cellular component	membrane; plasma membrane; integral component of membrane; integral component of plasma membrane;
Biological process	angiogenesis; retina layer formation; regulation of angiogenesis; cell surface receptor signaling pathway; Wnt signaling pathway;
	Sources:Amigo / QuickGO
Orthologs
	23554
	269831
	ENSG00000106025
	ENSMUSG00000029669
	O95859
	Q8BKT6
	NM_012338
	NM_173007; NM_001363814
	NP_036470
	NP_766595; NP_001350743
	Wikidata
View/Edit Human	View/Edit Mouse

Tetraspanin-12 (Tspan-12) also known as tetraspan NET-2 (NET2) or transmembrane 4 superfamily member 12 (TM4SF12) is a tetraspanin protein that in humans is encoded by the TSPAN12 gene. Tetraspanin-12 is found in the membrane of a variety of cells. It has an unusually long C-terminal intracellular tail of approximately 60 amino acids.

Function

Its main binding partner is the ADAM10 protein,^[5] a sheddase that interacts with a variety of adhesion molecules that are found on the cell membrane including L1-CAM, E-Cadherin, N-Cadherin and CD44.^[6]^[7] It also binds to the MT1-MMP metalloprotease protein that is closely related to ADAM10 but has a minimal effect on promotion of expression and function.^[8] TSPAN12 also seems to regulate vascular development, as shown by a study involving TSPAN12 knockout mice.^[9] TSPAN12 is a significant contributor to primary and metastatic cancer and is responsible for protecting β-catenin from degradation.^[10]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000106025 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000029669 – 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.
^ Xu D, Sharma C, Hemler ME (November 2009). "Tetraspanin12 regulates ADAM10-dependent cleavage of amyloid precursor protein". FASEB J. 23 (11): 3674–81. doi:10.1096/fj.09-133462. PMC 2775005. PMID 19587294.
^ Lee SB, Schramme A, Doberstein K, Dummer R, Abdel-Bakky MS, Keller S, Altevogt P, Oh ST, Reichrath J, Oxmann D, Pfeilschifter J, Mihic-Probst D, Gutwein P (March 2010). "ADAM10 is upregulated in melanoma metastasis compared with primary melanoma". J. Invest. Dermatol. 130 (3): 763–73. doi:10.1038/jid.2009.335. PMID 19865098.
^ Anderegg U, Eichenberg T, Parthaune T, Haiduk C, Saalbach A, Milkova L, Ludwig A, Grosche J, Averbeck M, Gebhardt C, Voelcker V, Sleeman JP, Simon JC (June 2009). "ADAM10 is the constitutive functional sheddase of CD44 in human melanoma cells". J. Invest. Dermatol. 129 (6): 1471–82. doi:10.1038/jid.2008.323. PMID 18971959.
^ Lafleur MA, Xu D, Hemler ME (April 2009). "Tetraspanin proteins regulate membrane type-1 matrix metalloproteinase-dependent pericellular proteolysis". Mol. Biol. Cell. 20 (7): 2030–40. doi:10.1091/mbc.E08-11-1149. PMC 2663921. PMID 19211836.
^ Junge HJ, Yang S, Burton JB, Paes K, Shu X, French DM, Costa M, Rice DS, Ye W (October 2009). "TSPAN12 regulates retinal vascular development by promoting Norrin- but not Wnt-induced FZD4/beta-catenin signaling". Cell. 139 (2): 299–311. doi:10.1016/j.cell.2009.07.048. PMID 19837033. S2CID 2276711.
^ Knoblich K, Wang HX, Sharma C, Fletcher AL, Turley SJ, Hemler ME (April 2014). "Tetraspanin TSPAN12 regulates tumor growth and metastasis and inhibits β-catenin degradation". Cell Mol Life Sci. 71 (7): 1305–14. doi:10.1007/s00018-013-1444-8. PMC 11113286. PMID 23955570. S2CID 16135992.

External links

GeneReviews/NCBI/NIH/UW entry on Familial Exudative Vitreoretinopathy, Autosomal Dominant

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[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000106025 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000029669 – 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.

[pmid19587294-5] Xu D, Sharma C, Hemler ME (November 2009). "Tetraspanin12 regulates ADAM10-dependent cleavage of amyloid precursor protein". FASEB J. 23 (11): 3674–81. doi:10.1096/fj.09-133462. PMC 2775005. PMID 19587294.

[pmid19865098-6] Lee SB, Schramme A, Doberstein K, Dummer R, Abdel-Bakky MS, Keller S, Altevogt P, Oh ST, Reichrath J, Oxmann D, Pfeilschifter J, Mihic-Probst D, Gutwein P (March 2010). "ADAM10 is upregulated in melanoma metastasis compared with primary melanoma". J. Invest. Dermatol. 130 (3): 763–73. doi:10.1038/jid.2009.335. PMID 19865098.

[pmid18971959-7] Anderegg U, Eichenberg T, Parthaune T, Haiduk C, Saalbach A, Milkova L, Ludwig A, Grosche J, Averbeck M, Gebhardt C, Voelcker V, Sleeman JP, Simon JC (June 2009). "ADAM10 is the constitutive functional sheddase of CD44 in human melanoma cells". J. Invest. Dermatol. 129 (6): 1471–82. doi:10.1038/jid.2008.323. PMID 18971959.

[pmid19211836-8] Lafleur MA, Xu D, Hemler ME (April 2009). "Tetraspanin proteins regulate membrane type-1 matrix metalloproteinase-dependent pericellular proteolysis". Mol. Biol. Cell. 20 (7): 2030–40. doi:10.1091/mbc.E08-11-1149. PMC 2663921. PMID 19211836.

[pmid19837033-9] Junge HJ, Yang S, Burton JB, Paes K, Shu X, French DM, Costa M, Rice DS, Ye W (October 2009). "TSPAN12 regulates retinal vascular development by promoting Norrin- but not Wnt-induced FZD4/beta-catenin signaling". Cell. 139 (2): 299–311. doi:10.1016/j.cell.2009.07.048. PMID 19837033. S2CID 2276711.

[pmid23955570-10] Knoblich K, Wang HX, Sharma C, Fletcher AL, Turley SJ, Hemler ME (April 2014). "Tetraspanin TSPAN12 regulates tumor growth and metastasis and inhibits β-catenin degradation". Cell Mol Life Sci. 71 (7): 1305–14. doi:10.1007/s00018-013-1444-8. PMC 11113286. PMID 23955570. S2CID 16135992.

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