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NameProgrammed cell death protein 6
Synonyms
  • ALG2
  • Apoptosis-linked gene 2 protein
  • Probable calcium-binding protein ALG-2
Gene NamePDCD6
OrganismHuman
Amino acid sequence
>lcl|BSEQ0009841|Programmed cell death protein 6
MAAYSYRPGPGAGPGPAAGAALPDQSFLWNVFQRVDKDRSGVISDTELQQALSNGTWTPF
NPVTVRSIISMFDRENKAGVNFSEFTGVWKYITDWQNVFRTYDRDNSGMIDKNELKQALS
GFGYRLSDQFHDILIRKFDRQGRGQIAFDDFIQGCIVLQRLTDIFRRYDTDQDGWIQVSY
EQYLSMVFSIV
Number of residues191
Molecular Weight21868.32
Theoretical pINot Available
GO Classification
Functions
  • calcium-dependent cysteine-type endopeptidase activity
  • identical protein binding
  • binding, bridging
  • protein anchor
  • calcium ion binding
  • calcium-dependent protein binding
  • protein dimerization activity
Processes
  • negative regulation of protein kinase B signaling
  • response to calcium ion
  • negative regulation of vascular endothelial growth factor receptor signaling pathway
  • angiogenesis
  • vascular endothelial growth factor receptor-2 signaling pathway
  • positive regulation of endothelial cell migration
  • positive regulation of angiogenesis
  • apoptotic signaling pathway
  • positive regulation of endothelial cell proliferation
  • proteolysis
  • activation of cysteine-type endopeptidase activity involved in apoptotic process
  • intracellular protein transport
  • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
  • negative regulation of TOR signaling
  • cellular response to heat
Components
  • cytoplasmic vesicle
  • extracellular exosome
  • nuclear membrane
  • endoplasmic reticulum exit site
  • endosome
  • cytoplasm
  • nucleus
  • endoplasmic reticulum
  • endoplasmic reticulum membrane
General FunctionProtein dimerization activity
Specific FunctionCalcium-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 RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDO75340
UniProtKB Entry NamePDCD6_HUMAN
Cellular LocationNucleus membrane
Gene sequence
>lcl|BSEQ0017845|Programmed cell death protein 6 (PDCD6)
ATGGCCGCCTACTCTTACCGCCCCGGCCCTGGGGCCGGCCCTGGGCCTGCTGCAGGCGCG
GCGCTGCCGGACCAGAGCTTCCTGTGGAACGTTTTCCAGAGGGTCGATAAAGACAGGAGT
GGAGTGATATCAGACACCGAGCTTCAGCAAGCTCTCTCCAACGGCACGTGGACTCCCTTT
AATCCAGTGACTGTCAGGTCGATCATATCCATGTTTGACCGTGAGAACAAGGCCGGCGTG
AACTTCAGCGAGTTCACGGGTGTGTGGAAGTACATCACGGACTGGCAGAACGTCTTCCGC
ACGTACGACCGGGACAACTCCGGGATGATCGATAAGAACGAGCTGAAGCAGGCCCTCTCA
GGCTACCGGCTCTCTGACCAGTTCCACGACATCCTCATTCGAAAGTTTGACAGGCAGGGA
CGGGGGCAGATTGCCTTCGACGACTTCATCCAGGGCTGCATCGTCCTGCAGAGGTTGACG
GATATATTCAGACGTTACGACACGGATCAGGACGGCTGGATTCAGGTGTCGTACGAACAG
TACCTGTCCATGGTCTTCAGTATCGTATGA
GenBank Gene IDNot Available
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:8765
Chromosome Location5
LocusNot Available
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. 14702039
  2. Schmutz J, Martin J, Terry A, Couronne O, Grimwood J, Lowry S, Gordon LA, Scott D, Xie G, Huang W, Hellsten U, Tran-Gyamfi M, She X, Prabhakar S, Aerts A, Altherr M, Bajorek E, Black S, Branscomb E, Caoile C, Challacombe JF, Chan YM, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Glavina T, Gomez M, Gonzales E, Goodstein D, Grigoriev I, Groza M, Hammon N, Hawkins T, Haydu L, Israni S, Jett J, Kadner K, Kimball H, Kobayashi A, Lopez F, Lou Y, Martinez D, Medina C, Morgan J, Nandkeshwar R, Noonan JP, Pitluck S, Pollard M, Predki P, Priest J, Ramirez L, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wheeler J, Wu K, Yang J, Dickson M, Cheng JF, Eichler EE, Olsen A, Pennacchio LA, Rokhsar DS, Richardson P, Lucas SM, Myers RM, Rubin EM: The DNA sequence and comparative analysis of human chromosome 5. Nature. 2004 Sep 16;431(7006):268-74. 15372022
  3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  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. 11278427
  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. 11883899
  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. 11883939
  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. 16132846
  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. 17045351
  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. 16957052
  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. 17889823
  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. 18256029
  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. 19520058
  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. 19864416
  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. 21269460
  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. 21122810
  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. 21893193
  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. 22223895
  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. 25944712
  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. 18940611
  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. 20691033
  21. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE: The consensus coding sequences of human breast and colorectal cancers. Science. 2006 Oct 13;314(5797):268-74. Epub 2006 Sep 7. 16959974