TMBIM4

Transmembrane BAX inhibitor motif-containing protein 4 is a protein that in humans is encoded by the TMBIM4 gene.[4][5][6] It is also known as human Golgi anti-apoptotic protein (hGAAP) due to its function and sub-cellular localization.

TMBIM4
Identifiers
Aliases	TMBIM4, GAAP, LFG4, S1R, ZPRO, CGI-119, transmembrane BAX inhibitor motif containing 4
External IDs	OMIM: 616874 MGI: 1915462 HomoloGene: 56740 GeneCards: TMBIM4
Gene location (Human) Chr. Chromosome 12 (human)[1] Band 12q14.3 Start 66,135,846 bp[1] End 66,170,072 bp[1]
RNA expression pattern More reference expression data
Gene ontology Molecular function • GO:0001948 protein binding Cellular component • integral component of membrane • Golgi apparatus • Golgi membrane • Golgi stack • membrane Biological process • regulation of calcium-mediated signaling • negative regulation of apoptotic process • apoptotic process Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	51643	68212
Ensembl	ENSG00000155957	ENSMUSG00000020225
UniProt	Q9HC24	Q9DA39
RefSeq (mRNA)	NM_016056 NM_001282606 NM_001282609 NM_001282610	NM_026617
RefSeq (protein)	NP_001269535 NP_001269538 NP_001269539 NP_057140 NP_001269535.1	NP_080893
Location (UCSC)	Chr 12: 66.14 – 66.17 Mb	n/a
PubMed search	[2]	[3]
Wikidata
View/Edit Human View/Edit Mouse

Function

Human GAAP [7] is a protein present in the Golgi that helps regulate apoptosis, a form of programmed cell death. By regulating the fluxes of Ca⁺², an increase of GAAP can help prevent apoptosis.[8][9] GAAP is also involved in promoting cell migration[10] [11] and has been identified as a novel Golgi cation channel.[12] Other GAAPs can be found in all eucaryotes analyzed and in some bacteria. A viral GAAP (vGAAP) can also be found in some strains of vaccinia virus, the live vaccine used to eradicate smallpox.

See also

• Golgi
• Apoptosis
• Ion channel
• Cell migration

References

1. GRCh38: Ensembl release 89: ENSG00000155957 - Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. Zhang QH, Ye M, Wu XY, Ren SX, Zhao M, Zhao CJ, Fu G, Shen Y, Fan HY, Lu G, Zhong M, Xu XR, Han ZG, Zhang JW, Tao J, Huang QH, Zhou J, Hu GX, Gu J, Chen SJ, Chen Z (October 2000). "Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells". Genome Research. 10 (10): 1546–60. doi:10.1101/gr.140200. PMC 310934. PMID 11042152.
5. Lai CH, Chou CY, Ch'ang LY, Liu CS, Lin W (May 2000). "Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics". Genome Research. 10 (5): 703–13. doi:10.1101/gr.10.5.703. PMC 310876. PMID 10810093.
6. "Entrez Gene: TMBIM4 transmembrane BAX inhibitor motif containing 4".
7. Saraiva, Nuno; Carrara, Guia; Smith, Geoffrey L (2017). "Golgi anti-apoptotic protein: a tale of camels, calcium, channels and cancer". Open Biology. 7(5):170045. doi:10.1098/rsob.170045. PMID 28469007.
8. de Mattia F, Gubser C, van Dommelen MM, Visch HJ, Distelmaier F, Postigo A, Luyten T, Parys JB, de Smedt H, Smith GL, Willems PH, van Kuppeveld FJ (August 2009). "Human Golgi antiapoptotic protein modulates intracellular calcium fluxes". Molecular Biology of the Cell. 20 (16): 3638–45. doi:10.1091/mbc.E09-05-0385. PMC 2777924. PMID 19553469.
9. Saraiva N, Prole DL, Carrara G, Maluquer de Motes C, Johnson BF, Byrne B, Taylor CW, Smith GL (May 2013). "Human and viral Golgi anti-apoptotic proteins (GAAPs) oligomerize via different mechanisms and monomeric GAAP inhibits apoptosis and modulates calcium". The Journal of Biological Chemistry. 288 (18): 13057–67. doi:10.1074/jbc.M112.414367. PMC 3642348. PMID 23508950.
10. Saraiva, Nuno; Prole, David L.; Carrara, Guia; Johnson, Benjamin F.; Taylor, Colin W.; Parsons, Maddy; Smith, Geoffrey L. (2013-08-19). "hGAAP promotes cell adhesion and migration via the stimulation of store-operated Ca2+ entry and calpain 2". J Cell Biol. 202 (4): 699–713. doi:10.1083/jcb.201301016. ISSN 0021-9525. PMC 3747308. PMID 23940116.
11. Almeida, Nuno; Saraiva, Nuno (2020). "Stimulation of cell invasion by the Golgi Ion Channel GAAP/TMBIM4 via an H2O2-Dependent Mechanism". Redox Biology. 28:101361. doi:10.1016/j.redox.2019.101361. PMID 31693977.
12. Carrara, Guia; Saraiva, Nuno; Parsons, Maddy; Byrne, Bernadette; Prole, David L.; Taylor, Colin W.; Smith, Geoffrey L. (2015-05-01). "Golgi Anti-apoptotic Proteins Are Highly Conserved Ion Channels That Affect Apoptosis and Cell Migration". Journal of Biological Chemistry. 290 (18): 11785–11801. doi:10.1074/jbc.M115.637306. ISSN 0021-9258. PMC 4416878. PMID 25713081.

Further reading

• 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.
• Hu RM, Han ZG, Song HD, Peng YD, Huang QH, Ren SX, Gu YJ, Huang CH, Li YB, Jiang CL, Fu G, Zhang QH, Gu BW, Dai M, Mao YF, Gao GF, Rong R, Ye M, Zhou J, Xu SH, Gu J, Shi JX, Jin WR, Zhang CK, Wu TM, Huang GY, Chen Z, Chen MD, Chen JL (August 2000). "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning". Proceedings of the National Academy of Sciences of the United States of America. 97 (17): 9543–8. doi:10.1073/pnas.160270997. PMC 16901. PMID 10931946.
• 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.
• Gubser C, Bergamaschi D, Hollinshead M, Lu X, van Kuppeveld FJ, Smith GL (February 2007). "A new inhibitor of apoptosis from vaccinia virus and eukaryotes". PLOS Pathogens. 3 (2): e17. doi:10.1371/journal.ppat.0030017. PMC 1803007. PMID 17319741.
• Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.