Programmed cell death protein 6

Details

Name
Programmed cell death protein 6
Synonyms
  • ALG2
  • Apoptosis-linked gene 2 protein
  • Probable calcium-binding protein ALG-2
Gene Name
PDCD6
Organism
Humans
Amino acid sequence
>lcl|BSEQ0009841|Programmed cell death protein 6
MAAYSYRPGPGAGPGPAAGAALPDQSFLWNVFQRVDKDRSGVISDTELQQALSNGTWTPF
NPVTVRSIISMFDRENKAGVNFSEFTGVWKYITDWQNVFRTYDRDNSGMIDKNELKQALS
GFGYRLSDQFHDILIRKFDRQGRGQIAFDDFIQGCIVLQRLTDIFRRYDTDQDGWIQVSY
EQYLSMVFSIV
Number of residues
191
Molecular Weight
21868.32
Theoretical pI
Not Available
GO Classification
Functions
binding, bridging / calcium ion binding / calcium-dependent cysteine-type endopeptidase activity / calcium-dependent protein binding / identical protein binding / protein anchor / protein dimerization activity
Processes
activation of cysteine-type endopeptidase activity involved in apoptotic process / angiogenesis / apoptotic signaling pathway / cellular response to heat / intracellular protein transport / negative regulation of protein kinase B signaling / negative regulation of TOR signaling / negative regulation of vascular endothelial growth factor receptor signaling pathway / positive regulation of angiogenesis / positive regulation of cysteine-type endopeptidase activity involved in apoptotic process / positive regulation of endothelial cell migration / positive regulation of endothelial cell proliferation / proteolysis / response to calcium ion / vascular endothelial growth factor receptor-2 signaling pathway
Components
cytoplasm / cytoplasmic vesicle / endoplasmic reticulum / endoplasmic reticulum exit site / endoplasmic reticulum membrane / endosome / extracellular exosome / nuclear membrane / nucleus
General Function
Protein dimerization activity
Specific Function
Calcium-binding protein required for T-cell receptor-, Fas-, and glucocorticoid-induced cell death. May mediate Ca(2+)-regulated signals along the death pathway (By similarity). Calcium-dependent adapter necessary for the association between PDCD6IP and TSG101. Interaction with DAPK1 can accelerate apoptotic cell death by increasing caspase-3 activity. May inhibit KDR/VEGFR2-dependent angiogenesis; the function involves inhibition of VEGF-induced phosphoprylation of the Akt signaling pathway. Seems to play a role in the regulation of the distribution and function of MCOLN1 in the endosomal pathway. Isoform 2 has a lower Ca(2+) affinity than isoform 1. Isoform 1 and, to a lesser extend, isoform 2, can stabilize SHISA5.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Nucleus membrane
Gene sequence
>lcl|BSEQ0017845|Programmed cell death protein 6 (PDCD6)
ATGGCCGCCTACTCTTACCGCCCCGGCCCTGGGGCCGGCCCTGGGCCTGCTGCAGGCGCG
GCGCTGCCGGACCAGAGCTTCCTGTGGAACGTTTTCCAGAGGGTCGATAAAGACAGGAGT
GGAGTGATATCAGACACCGAGCTTCAGCAAGCTCTCTCCAACGGCACGTGGACTCCCTTT
AATCCAGTGACTGTCAGGTCGATCATATCCATGTTTGACCGTGAGAACAAGGCCGGCGTG
AACTTCAGCGAGTTCACGGGTGTGTGGAAGTACATCACGGACTGGCAGAACGTCTTCCGC
ACGTACGACCGGGACAACTCCGGGATGATCGATAAGAACGAGCTGAAGCAGGCCCTCTCA
GGCTACCGGCTCTCTGACCAGTTCCACGACATCCTCATTCGAAAGTTTGACAGGCAGGGA
CGGGGGCAGATTGCCTTCGACGACTTCATCCAGGGCTGCATCGTCCTGCAGAGGTTGACG
GATATATTCAGACGTTACGACACGGATCAGGACGGCTGGATTCAGGTGTCGTACGAACAG
TACCTGTCCATGGTCTTCAGTATCGTATGA
Chromosome Location
5
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDO75340
UniProtKB Entry NamePDCD6_HUMAN
HGNC IDHGNC:8765
General References
  1. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
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  4. Kitaura Y, Matsumoto S, Satoh H, Hitomi K, Maki M: Peflin and ALG-2, members of the penta-EF-hand protein family, form a heterodimer that dissociates in a Ca2+-dependent manner. J Biol Chem. 2001 Apr 27;276(17):14053-8. Epub 2001 Feb 1. [Article]
  5. Kitaura Y, Satoh H, Takahashi H, Shibata H, Maki M: Both ALG-2 and peflin, penta-EF-hand (PEF) proteins, are stabilized by dimerization through their fifth EF-hand regions. Arch Biochem Biophys. 2002 Mar 1;399(1):12-8. [Article]
  6. Satoh H, Shibata H, Nakano Y, Kitaura Y, Maki M: ALG-2 interacts with the amino-terminal domain of annexin XI in a Ca(2+)-dependent manner. Biochem Biophys Res Commun. 2002 Mar 15;291(5):1166-72. [Article]
  7. Lee JH, Rho SB, Chun T: Programmed cell death 6 (PDCD6) protein interacts with death-associated protein kinase 1 (DAPk1): additive effect on apoptosis via caspase-3 dependent pathway. Biotechnol Lett. 2005 Jul;27(14):1011-5. [Article]
  8. Montaville P, Dai Y, Cheung CY, Giller K, Becker S, Michalak M, Webb SE, Miller AL, Krebs J: Nuclear translocation of the calcium-binding protein ALG-2 induced by the RNA-binding protein RBM22. Biochim Biophys Acta. 2006 Nov;1763(11):1335-43. Epub 2006 Sep 14. [Article]
  9. Yamasaki A, Tani K, Yamamoto A, Kitamura N, Komada M: The Ca2+-binding protein ALG-2 is recruited to endoplasmic reticulum exit sites by Sec31A and stabilizes the localization of Sec31A. Mol Biol Cell. 2006 Nov;17(11):4876-87. Epub 2006 Sep 6. [Article]
  10. Draeby I, Woods YL, la Cour JM, Mollerup J, Bourdon JC, Berchtold MW: The calcium binding protein ALG-2 binds and stabilizes Scotin, a p53-inducible gene product localized at the endoplasmic reticulum membrane. Arch Biochem Biophys. 2007 Nov 1;467(1):87-94. Epub 2007 Aug 21. [Article]
  11. Shibata H, Suzuki H, Kakiuchi T, Inuzuka T, Yoshida H, Mizuno T, Maki M: Identification of Alix-type and Non-Alix-type ALG-2-binding sites in human phospholipid scramblase 3: differential binding to an alternatively spliced isoform and amino acid-substituted mutants. J Biol Chem. 2008 Apr 11;283(15):9623-32. doi: 10.1074/jbc.M800717200. Epub 2008 Feb 6. [Article]
  12. Okumura M, Ichioka F, Kobayashi R, Suzuki H, Yoshida H, Shibata H, Maki M: Penta-EF-hand protein ALG-2 functions as a Ca2+-dependent adaptor that bridges Alix and TSG101. Biochem Biophys Res Commun. 2009 Aug 14;386(1):237-41. doi: 10.1016/j.bbrc.2009.06.015. Epub 2009 Jun 9. [Article]
  13. Vergarajauregui S, Martina JA, Puertollano R: Identification of the penta-EF-hand protein ALG-2 as a Ca2+-dependent interactor of mucolipin-1. J Biol Chem. 2009 Dec 25;284(52):36357-66. doi: 10.1074/jbc.M109.047241. Epub 2009 Oct 28. [Article]
  14. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  15. Janowicz A, Michalak M, Krebs J: Stress induced subcellular distribution of ALG-2, RBM22 and hSlu7. Biochim Biophys Acta. 2011 May;1813(5):1045-9. doi: 10.1016/j.bbamcr.2010.11.010. Epub 2010 Nov 29. [Article]
  16. Rho SB, Song YJ, Lim MC, Lee SH, Kim BR, Park SY: Programmed cell death 6 (PDCD6) inhibits angiogenesis through PI3K/mTOR/p70S6K pathway by interacting of VEGFR-2. Cell Signal. 2012 Jan;24(1):131-9. doi: 10.1016/j.cellsig.2011.08.013. Epub 2011 Aug 26. [Article]
  17. Bienvenut WV, Sumpton D, Martinez A, Lilla S, Espagne C, Meinnel T, Giglione C: Comparative large scale characterization of plant versus mammal proteins reveals similar and idiosyncratic N-alpha-acetylation features. Mol Cell Proteomics. 2012 Jun;11(6):M111.015131. doi: 10.1074/mcp.M111.015131. Epub 2012 Jan 5. [Article]
  18. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. [Article]
  19. Suzuki H, Kawasaki M, Inuzuka T, Okumura M, Kakiuchi T, Shibata H, Wakatsuki S, Maki M: Structural basis for Ca2+ -dependent formation of ALG-2/Alix peptide complex: Ca2+/EF3-driven arginine switch mechanism. Structure. 2008 Oct 8;16(10):1562-73. doi: 10.1016/j.str.2008.07.012. [Article]
  20. Inuzuka T, Suzuki H, Kawasaki M, Shibata H, Wakatsuki S, Maki M: Molecular basis for defect in Alix-binding by alternatively spliced isoform of ALG-2 (ALG-2DeltaGF122) and structural roles of F122 in target recognition. BMC Struct Biol. 2010 Aug 6;10:25. doi: 10.1186/1472-6807-10-25. [Article]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB11093Calcium citrateapproved, investigationalunknownagonistDetails
DB11348Calcium PhosphateapprovedunknownagonistDetails
DB01373CalciumnutraceuticalunknownDetails
DB01593Zincapproved, investigationalunknownDetails
DB14481Calcium phosphate dihydrateapprovedunknownDetails
DB14487Zinc acetateapproved, investigationalunknownDetails