Full text data of PDCD6IP
PDCD6IP
(AIP1, ALIX, KIAA1375)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Programmed cell death 6-interacting protein; PDCD6-interacting protein (ALG-2-interacting protein 1; ALG-2-interacting protein X; Hp95)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Programmed cell death 6-interacting protein; PDCD6-interacting protein (ALG-2-interacting protein 1; ALG-2-interacting protein X; Hp95)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00246058
IPI00246058 PDCD6IP protein Programmed cell death 6-interacting protein, signal transducer activity soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
IPI00246058 PDCD6IP protein Programmed cell death 6-interacting protein, signal transducer activity soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
UniProt
Q8WUM4
ID PDC6I_HUMAN Reviewed; 868 AA.
AC Q8WUM4; E9PFU1; Q6NUS1; Q9BX86; Q9NUN0; Q9P2H2; Q9UKL5;
DT 23-MAY-2003, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAR-2002, sequence version 1.
DT 22-JAN-2014, entry version 126.
DE RecName: Full=Programmed cell death 6-interacting protein;
DE Short=PDCD6-interacting protein;
DE AltName: Full=ALG-2-interacting protein 1;
DE AltName: Full=ALG-2-interacting protein X;
DE AltName: Full=Hp95;
GN Name=PDCD6IP; Synonyms=AIP1, ALIX, KIAA1375;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT SER-550.
RX PubMed=11683497; DOI=10.1046/j.1432-0436.2001.670406.x;
RA Wu Y., Pan S., Che S., He G., Nelman-Gonzalez M., Weil M.M., Kuang J.;
RT "Overexpression of Hp95 induces G1 phase arrest in confluent HeLa
RT cells.";
RL Differentiation 67:139-153(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS THR-309 AND
RP LEU-730.
RA Li H., Shioda T., Isselbacher K.J.;
RT "Molecular cloning of human ALG-2 interacting protein 1 (AIP1).";
RL Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R.,
RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J.,
RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND
RP VARIANTS MET-7 AND ILE-378.
RC TISSUE=Lymph, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PROTEIN SEQUENCE OF 2-23; 111-120; 216-229; 439-446; 457-469 AND
RP 542-553, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, AND
RP MASS SPECTROMETRY.
RC TISSUE=Osteosarcoma;
RA Bienvenut W.V., Glen H., Frame M.C.;
RL Submitted (MAR-2008) to UniProtKB.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 209-868 (ISOFORM 1), AND
RP VARIANT ILE-378.
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 323-868 (ISOFORM 1), AND
RP VARIANT SER-550.
RC TISSUE=Brain;
RX PubMed=10718198; DOI=10.1093/dnares/7.1.65;
RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVI.
RT The complete sequences of 150 new cDNA clones from brain which code
RT for large proteins in vitro.";
RL DNA Res. 7:65-73(2000).
RN [9]
RP INTERACTION WITH CHMP4A AND CHMP4B.
RX PubMed=12860994; DOI=10.1074/jbc.M301604200;
RA Katoh K., Shibata H., Suzuki H., Narai A., Ishidoh K., Kominami E.,
RA Yoshimori T., Maki M.;
RT "The ALG-2-interacting protein Alix associates with CHMP4b, a human
RT homologue of yeast Snf7 that is involved in multivesicular body
RT sorting.";
RL J. Biol. Chem. 278:39104-39113(2003).
RN [10]
RP FUNCTION IN HIV-1 BUDDING, AND INTERACTION WITH CHMP4A; CHMP4B;
RP CHMP4C; HIV-1 P6 AND EIAV P9.
RX PubMed=14505569; DOI=10.1016/S0092-8674(03)00653-6;
RA Strack B., Calistri A., Craig S., Popova E., Goettlinger H.G.;
RT "AIP1/ALIX is a binding partner for HIV-1 p6 and EIAV p9 functioning
RT in virus budding.";
RL Cell 114:689-699(2003).
RN [11]
RP FUNCTION IN HIV-1 BUDDING, SELF-ASSOCIATION, INTERACTION WITH TSG101;
RP CHMP4A; CHMP4B CHMP4C, AND SUBCELLULAR LOCATION.
RX PubMed=14505570; DOI=10.1016/S0092-8674(03)00714-1;
RA von Schwedler U.K., Stuchell M., Mueller B., Ward D.M., Chung H.-Y.,
RA Morita E., Wang H.E., Davis T., He G.P., Cimbora D.M., Scott A.,
RA Kraeusslich H.-G., Kaplan J., Morham S.G., Sundquist W.I.;
RT "The protein network of HIV budding.";
RL Cell 114:701-713(2003).
RN [12]
RP SELF-ASSOCIATION, AND INTERACTION WITH TSG101; CHMP4A; CHMP4B; CHMP4C
RP AND EIAV P9.
RX PubMed=14519844; DOI=10.1073/pnas.2133846100;
RA Martin-Serrano J., Yarovoy A., Perez-Caballero D., Bieniasz P.D.;
RT "Divergent retroviral late-budding domains recruit vacuolar protein
RT sorting factors by using alternative adaptor proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:12414-12419(2003).
RN [13]
RP ERRATUM.
RA Martin-Serrano J., Yarovoy A., Perez-Caballero D., Bieniasz P.D.;
RL Proc. Natl. Acad. Sci. U.S.A. 100:152845-152845(2003).
RN [14]
RP INTERACTION WITH CHMP4A; CHMP4B AND CHMP4C.
RX PubMed=14678797; DOI=10.1016/j.abb.2003.09.038;
RA Katoh K., Shibata H., Hatta K., Maki M.;
RT "CHMP4b is a major binding partner of the ALG-2-interacting protein
RT Alix among the three CHMP4 isoforms.";
RL Arch. Biochem. Biophys. 421:159-165(2004).
RN [15]
RP INTERACTION WITH CHMP4A; CHMP4B AND CHMP4C.
RX PubMed=14583093; DOI=10.1042/BJ20031347;
RA Peck J.W., Bowden E.T., Burbelo P.D.;
RT "Structure and function of human Vps20 and Snf7 proteins.";
RL Biochem. J. 377:693-700(2004).
RN [16]
RP FUNCTION IN ENDOSOME ORGANIZATION.
RX PubMed=14739459; DOI=10.1126/science.1092425;
RA Matsuo H., Chevallier J., Mayran N., Le Blanc I., Ferguson C.,
RA Faure J., Blanc N.S., Matile S., Dubochet J., Sadoul R., Parton R.G.,
RA Vilbois F., Gruenberg J.;
RT "Role of LBPA and Alix in multivesicular liposome formation and
RT endosome organization.";
RL Science 303:531-534(2004).
RN [17]
RP INTERACTION WITH SGSM3, AND SUBCELLULAR LOCATION.
RX PubMed=15849434; DOI=10.1271/bbb.69.861;
RA Ichioka F., Horii M., Katoh K., Terasawa Y., Shibata H., Maki M.;
RT "Identification of Rab GTPase-activating protein-like protein
RT (RabGAPLP) as a novel Alix/AIP1-interacting protein.";
RL Biosci. Biotechnol. Biochem. 69:861-865(2005).
RN [18]
RP INTERACTION WITH MURINE LEUKEMIA VIRUS GAG POLYPROTEIN.
RX PubMed=15908698; DOI=10.1074/jbc.M413735200;
RA Segura-Morales C., Pescia C., Chatellard-Causse C., Sadoul R.,
RA Bertrand E., Basyuk E.;
RT "Tsg101 and Alix interact with murine leukemia virus Gag and cooperate
RT with Nedd4 ubiquitin ligases during budding.";
RL J. Biol. Chem. 280:27004-27012(2005).
RN [19]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H.,
RA Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R.,
RA Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E.,
RA Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND INTERACTION WITH PDCD6.
RX PubMed=16957052; DOI=10.1091/mbc.E06-05-0444;
RA Yamasaki A., Tani K., Yamamoto A., Kitamura N., Komada M.;
RT "The Ca2+-binding protein ALG-2 is recruited to endoplasmic reticulum
RT exit sites by Sec31A and stabilizes the localization of Sec31A.";
RL Mol. Biol. Cell 17:4876-4887(2006).
RN [21]
RP FUNCTION IN CYTOKINESIS, SUBCELLULAR LOCATION, INTERACTION WITH CEP55
RP AND CD2AP, AND MUTAGENESIS OF ILE-212; PHE-676 AND 800-GLY--PRO-802.
RX PubMed=17853893; DOI=10.1038/sj.emboj.7601850;
RA Morita E., Sandrin V., Chung H.Y., Morham S.G., Gygi S.P.,
RA Rodesch C.K., Sundquist W.I.;
RT "Human ESCRT and ALIX proteins interact with proteins of the midbody
RT and function in cytokinesis.";
RL EMBO J. 26:4215-4227(2007).
RN [22]
RP FUNCTION IN HIV-1 BUDDING, INTERACTION WITH CHMP4B, AND MUTAGENESIS OF
RP PHE-199; LEU-216; PHE-317; ILE-318 AND TYR-319.
RX PubMed=17428861; DOI=10.1128/JVI.00314-07;
RA Usami Y., Popov S., Goettlinger H.G.;
RT "Potent rescue of human immunodeficiency virus type 1 late domain
RT mutants by ALIX/AIP1 depends on its CHMP4 binding site.";
RL J. Virol. 81:6614-6622(2007).
RN [23]
RP FUNCTION IN CYTOKINESIS, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP CEP55.
RX PubMed=17556548; DOI=10.1126/science.1143422;
RA Carlton J.G., Martin-Serrano J.;
RT "Parallels between cytokinesis and retroviral budding: a role for the
RT ESCRT machinery.";
RL Science 316:1908-1912(2007).
RN [24]
RP INTERACTION WITH PDCD6.
RX PubMed=18256029; DOI=10.1074/jbc.M800717200;
RA Shibata H., Suzuki H., Kakiuchi T., Inuzuka T., Yoshida H., Mizuno T.,
RA Maki M.;
RT "Identification of Alix-type and non-Alix-type ALG-2-binding sites in
RT human phospholipid scramblase 3: differential binding to an
RT alternatively spliced isoform and amino acid-substituted mutants.";
RL J. Biol. Chem. 283:9623-9632(2008).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-730; THR-738 AND
RP THR-741, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [26]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [27]
RP INTERACTION WITH TSG101.
RX PubMed=19520058; DOI=10.1016/j.bbrc.2009.06.015;
RA Okumura M., Ichioka F., Kobayashi R., Suzuki H., Yoshida H.,
RA Shibata H., Maki M.;
RT "Penta-EF-hand protein ALG-2 functions as a Ca2+-dependent adaptor
RT that bridges Alix and TSG101.";
RL Biochem. Biophys. Res. Commun. 386:237-241(2009).
RN [28]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-215, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [29]
RP PHOSPHORYLATION, AND INTERACTION WITH PDGFRB.
RX PubMed=20494825; DOI=10.1016/j.cellsig.2010.05.004;
RA Wardega P., Heldin C.H., Lennartsson J.;
RT "Mutation of tyrosine residue 857 in the PDGF beta-receptor affects
RT cell proliferation but not migration.";
RL Cell. Signal. 22:1363-1368(2010).
RN [30]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-738 AND THR-741, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [31]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [32]
RP X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) OF 1-698, INTERACTION WITH
RP CHMP4A; HIV-1 P6; EIAV P9; TSG101; SH3GL1 AND SH3GL2, AND MUTAGENESIS
RP OF ILE-212; TYR-319; PHE-495; VAL-498; VAL-509; PHE-676; LEU-680;
RP ILE-683; PRO-720 AND 757-ARG-PRO-758.
RX PubMed=17350572; DOI=10.1016/j.cell.2007.01.035;
RA Fisher R.D., Chung H.Y., Zhai Q., Robinson H., Sundquist W.I.,
RA Hill C.P.;
RT "Structural and biochemical studies of ALIX/AIP1 and its role in
RT retrovirus budding.";
RL Cell 128:841-852(2007).
RN [33]
RP X-RAY CRYSTALLOGRAPHY (2.87 ANGSTROMS) OF 360-702, INTERACTION WITH
RP HIV-1 P6, AND MUTAGENESIS OF VAL-498; VAL-509; CYS-512; PHE-676 AND
RP ILE-683.
RX PubMed=17277784; DOI=10.1038/nsmb1203;
RA Lee S., Joshi A., Nagashima K., Freed E.O., Hurley J.H.;
RT "Structural basis for viral late-domain binding to Alix.";
RL Nat. Struct. Mol. Biol. 14:194-199(2007).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (2.59 ANGSTROMS) OF 2-698 IN COMPLEX WITH HIV-1
RP P6, X-RAY CRYSTALLOGRAPHY (2.59 ANGSTROMS) OF 2-698 IN COMPLEX WITH
RP HIV-1 P9, AND INTERACTION WITH EIAV P9.
RX PubMed=18066081; DOI=10.1038/nsmb1319;
RA Zhai Q., Fisher R.D., Chung H.Y., Myszka D.G., Sundquist W.I.,
RA Hill C.P.;
RT "Structural and functional studies of ALIX interactions with YPX(n)L
RT late domains of HIV-1 and EIAV.";
RL Nat. Struct. Mol. Biol. 15:43-49(2008).
RN [35]
RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 1-359 IN COMPLEX WITH
RP CHMP4A, X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1-359 IN COMPLEX WITH
RP CHMP4B, AND X-RAY CRYSTALLOGRAPHY (2.02 ANGSTROMS) OF 1-359 IN COMPLEX
RP WITH CHMP4C.
RX PubMed=18511562; DOI=10.1073/pnas.0801567105;
RA McCullough J., Fisher R.D., Whitby F.G., Sundquist W.I., Hill C.P.;
RT "ALIX-CHMP4 interactions in the human ESCRT pathway.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:7687-7691(2008).
RN [36]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 797-809 IN COMPLEX WITH
RP CEP55, AND MUTAGENESIS OF PRO-801; PRO-802 AND TYR-806.
RX PubMed=18948538; DOI=10.1126/science.1162042;
RA Lee H.H., Elia N., Ghirlando R., Lippincott-Schwartz J., Hurley J.H.;
RT "Midbody targeting of the ESCRT machinery by a noncanonical coiled
RT coil in CEP55.";
RL Science 322:576-580(2008).
RN [37]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 799-812 IN COMPLEX WITH
RP PDCD6.
RX PubMed=18940611; DOI=10.1016/j.str.2008.07.012;
RA Suzuki H., Kawasaki M., Inuzuka T., Okumura M., Kakiuchi T.,
RA Shibata H., Wakatsuki S., Maki M.;
RT "Structural basis for Ca2+ -dependent formation of ALG-2/Alix peptide
RT complex: Ca2+/EF3-driven arginine switch mechanism.";
RL Structure 16:1562-1573(2008).
RN [38]
RP VARIANT SER-429.
RX PubMed=22073189; DOI=10.1371/journal.pone.0026741;
RA Benitez B.A., Alvarado D., Cai Y., Mayo K., Chakraverty S., Norton J.,
RA Morris J.C., Sands M.S., Goate A., Cruchaga C.;
RT "Exome-sequencing confirms DNAJC5 mutations as cause of adult neuronal
RT ceroid-lipofuscinosis.";
RL PLoS ONE 6:E26741-E26741(2011).
CC -!- FUNCTION: Class E VPS protein involved in concentration and
CC sorting of cargo proteins of the multivesicular body (MVB) for
CC incorporation into intralumenal vesicles (ILVs) that are generated
CC by invagination and scission from the limiting membrane of the
CC endosome. Binds to the phospholipid lysobisphosphatidic acid
CC (LBPA) which is abundant in MVBs internal membranes. The MVB
CC pathway appears to require the sequential function of ESCRT-O,
CC -I,-II and -III complexes. The ESCRT machinery also functions in
CC topologically equivalent membrane fission events, such as the
CC terminal stages of cytokinesis and enveloped virus budding (HIV-1
CC and other lentiviruses). Appears to be an adapter for a subset of
CC ESCRT-III proteins, such as CHMP4, to function at distinct
CC membranes. Required for completion of cytokinesis. Involved in
CC HIV-1 virus budding. Can replace TSG101 it its role of supporting
CC HIV-1 release; this function implies the interaction with CHMP4B.
CC May play a role in the regulation of both apoptosis and cell
CC proliferation.
CC -!- SUBUNIT: Interacts with SH3KBP1. Interacts with PDCD6 and TSG101
CC in a calcium-dependent manner. Interacts with and SGSM3. Self-
CC associates. Interacts with CHMP4A; the interaction is direct.
CC Interacts with CHMP4B; the interaction is direct. Interacts with
CC CHMP4C; the interaction is direct. Interacts with HIV-1 p6.
CC Interacts with EIAV p9; the interaction has been shown in vitro.
CC Interacts with CEP55; the interaction is direct; CEP55 binds
CC PDCD6IP in a 2:1 stoechiometry. May interact with PDGFRB.
CC Interacts with SH3GL1 and SH3GL2. Interacts with murine leukemia
CC virus Gag polyprotein (via LYPX(n)L motif). Interacts with murine
CC leukemia virus Gag polyprotein (via LYPX(n)L motif).
CC -!- INTERACTION:
CC P29991:- (xeno); NbExp=3; IntAct=EBI-310624, EBI-8826747;
CC Q9Y5K6:CD2AP; NbExp=2; IntAct=EBI-310624, EBI-298152;
CC Q53EZ4:CEP55; NbExp=9; IntAct=EBI-7603917, EBI-747776;
CC P06241:FYN; NbExp=6; IntAct=EBI-310624, EBI-515315;
CC P03347:gag (xeno); NbExp=2; IntAct=EBI-310624, EBI-1220741;
CC P69730:gag (xeno); NbExp=2; IntAct=EBI-310624, EBI-1220941;
CC P08631:HCK; NbExp=4; IntAct=EBI-310624, EBI-346340;
CC P09022:Hoxa1 (xeno); NbExp=3; IntAct=EBI-310624, EBI-3957603;
CC O75340:PDCD6; NbExp=5; IntAct=EBI-310624, EBI-352915;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol. Melanosome. Cytoplasm,
CC cytoskeleton, microtubule organizing center, centrosome.
CC Note=Identified by mass spectrometry in melanosome fractions from
CC stage I to stage IV. Colocalized with CEP55 in the midbody during
CC cytokinesis. Colocalized with CEP55 at centrosomes of non-dividing
CC cells.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8WUM4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8WUM4-2; Sequence=VSP_044860;
CC Note=No experimental confirmation available;
CC -!- PTM: May be phosphorylated on tyrosine residues by activated
CC PDGFRB.
CC -!- SIMILARITY: Contains 1 BRO1 domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA92092.1; Type=Erroneous initiation;
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DR EMBL; AF349951; AAK20398.1; -; mRNA.
DR EMBL; AF151793; AAF08220.1; -; mRNA.
DR EMBL; BT007367; AAP36031.1; -; mRNA.
DR EMBL; AC112220; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC123901; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC020066; AAH20066.1; -; mRNA.
DR EMBL; BC068454; AAH68454.1; -; mRNA.
DR EMBL; AK002122; BAA92092.1; ALT_INIT; mRNA.
DR EMBL; AB037796; BAA92613.1; -; mRNA.
DR RefSeq; NP_001155901.1; NM_001162429.2.
DR RefSeq; NP_037506.2; NM_013374.5.
DR UniGene; Hs.475896; -.
DR PDB; 2OEV; X-ray; 3.30 A; A=1-698.
DR PDB; 2OEW; X-ray; 2.55 A; A=1-359.
DR PDB; 2OEX; X-ray; 2.58 A; A/B=360-702.
DR PDB; 2OJQ; X-ray; 2.87 A; A=360-702.
DR PDB; 2R02; X-ray; 2.60 A; A=2-698.
DR PDB; 2R03; X-ray; 2.59 A; A=2-698.
DR PDB; 2R05; X-ray; 2.55 A; A=2-698.
DR PDB; 2XS1; X-ray; 2.30 A; A=1-698.
DR PDB; 2XS8; X-ray; 2.50 A; A=1-698.
DR PDB; 2ZNE; X-ray; 2.20 A; C/D=799-812.
DR PDB; 3C3O; X-ray; 2.15 A; A=1-359.
DR PDB; 3C3Q; X-ray; 2.10 A; A=1-359.
DR PDB; 3C3R; X-ray; 2.02 A; A=1-359.
DR PDB; 3E1R; X-ray; 2.00 A; C=797-809.
DR PDB; 4JJY; X-ray; 6.50 A; A/B=355-702.
DR PDBsum; 2OEV; -.
DR PDBsum; 2OEW; -.
DR PDBsum; 2OEX; -.
DR PDBsum; 2OJQ; -.
DR PDBsum; 2R02; -.
DR PDBsum; 2R03; -.
DR PDBsum; 2R05; -.
DR PDBsum; 2XS1; -.
DR PDBsum; 2XS8; -.
DR PDBsum; 2ZNE; -.
DR PDBsum; 3C3O; -.
DR PDBsum; 3C3Q; -.
DR PDBsum; 3C3R; -.
DR PDBsum; 3E1R; -.
DR PDBsum; 4JJY; -.
DR ProteinModelPortal; Q8WUM4; -.
DR SMR; Q8WUM4; 2-702.
DR DIP; DIP-29327N; -.
DR IntAct; Q8WUM4; 39.
DR MINT; MINT-4999333; -.
DR STRING; 9606.ENSP00000307387; -.
DR PhosphoSite; Q8WUM4; -.
DR DMDM; 31076831; -.
DR UCD-2DPAGE; Q8WUM4; -.
DR PaxDb; Q8WUM4; -.
DR PRIDE; Q8WUM4; -.
DR DNASU; 10015; -.
DR Ensembl; ENST00000307296; ENSP00000307387; ENSG00000170248.
DR Ensembl; ENST00000457054; ENSP00000411825; ENSG00000170248.
DR GeneID; 10015; -.
DR KEGG; hsa:10015; -.
DR UCSC; uc003cfy.4; human.
DR CTD; 10015; -.
DR GeneCards; GC03P033839; -.
DR H-InvDB; HIX0163463; -.
DR HGNC; HGNC:8766; PDCD6IP.
DR HPA; CAB016212; -.
DR HPA; HPA011905; -.
DR MIM; 608074; gene.
DR neXtProt; NX_Q8WUM4; -.
DR PharmGKB; PA33116; -.
DR eggNOG; NOG325528; -.
DR HOGENOM; HOG000006938; -.
DR HOVERGEN; HBG053533; -.
DR InParanoid; Q8WUM4; -.
DR KO; K12200; -.
DR OMA; CYQSHRD; -.
DR OrthoDB; EOG7V49XV; -.
DR PhylomeDB; Q8WUM4; -.
DR Reactome; REACT_116125; Disease.
DR ChiTaRS; PDCD6IP; human.
DR EvolutionaryTrace; Q8WUM4; -.
DR GeneWiki; PDCD6IP; -.
DR GenomeRNAi; 10015; -.
DR NextBio; 37837; -.
DR PRO; PR:Q8WUM4; -.
DR ArrayExpress; Q8WUM4; -.
DR Bgee; Q8WUM4; -.
DR CleanEx; HS_PDCD6IP; -.
DR Genevestigator; Q8WUM4; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0016032; P:viral process; TAS:Reactome.
DR Gene3D; 1.25.40.280; -; 1.
DR InterPro; IPR025304; ALIX_V_dom.
DR InterPro; IPR004328; BRO1_dom.
DR Pfam; PF13949; ALIX_LYPXL_bnd; 1.
DR Pfam; PF03097; BRO1; 1.
DR SMART; SM01041; BRO1; 1.
DR PROSITE; PS51180; BRO1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Apoptosis;
KW Cell cycle; Cell division; Complete proteome; Cytoplasm; Cytoskeleton;
KW Direct protein sequencing; Host-virus interaction; Phosphoprotein;
KW Polymorphism; Protein transport; Reference proteome; Transport.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 868 Programmed cell death 6-interacting
FT protein.
FT /FTId=PRO_0000218891.
FT DOMAIN 3 392 BRO1.
FT REGION 176 868 Interaction with EIAV p9.
FT REGION 176 503 Interaction with CHMP4A, CHMP4B and
FT CHMP4C.
FT REGION 503 868 Self-association.
FT REGION 717 720 Interaction with TSG101.
FT REGION 797 806 Interaction with CEP55.
FT REGION 864 868 Essential to promote virus budding.
FT COMPBIAS 717 860 Pro-rich.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 215 215 N6-acetyllysine.
FT MOD_RES 730 730 Phosphoserine.
FT MOD_RES 738 738 Phosphothreonine.
FT MOD_RES 741 741 Phosphothreonine.
FT VAR_SEQ 239 239 K -> KYFYFQ (in isoform 2).
FT /FTId=VSP_044860.
FT VARIANT 7 7 V -> M (in dbSNP:rs11554560).
FT /FTId=VAR_068975.
FT VARIANT 309 309 A -> T (in dbSNP:rs3792594).
FT /FTId=VAR_053017.
FT VARIANT 378 378 V -> I (in dbSNP:rs3203777).
FT /FTId=VAR_053018.
FT VARIANT 429 429 G -> S (in dbSNP:rs148256302).
FT /FTId=VAR_069765.
FT VARIANT 550 550 N -> S (in dbSNP:rs9813017).
FT /FTId=VAR_053019.
FT VARIANT 638 638 K -> E (in dbSNP:rs3183982).
FT /FTId=VAR_053020.
FT VARIANT 730 730 S -> L (in dbSNP:rs1127732).
FT /FTId=VAR_024381.
FT MUTAGEN 199 199 F->D: Abolishes interaction with CHMP4B
FT and abolishes rescue of PTAP-type L
FT domain-deficient HIV-1 p6.
FT MUTAGEN 212 212 I->D: Abolishes interaction with CHMP4A;
FT impairs rescue of PTAP-type L domain-
FT deficient HIV-1 p6; inhibits support of
FT cytokinesis.
FT MUTAGEN 216 216 L->D: Abolishes interaction with CHMP4B
FT and abolishes rescue of PTAP-type L
FT domain-deficient HIV-1 p6.
FT MUTAGEN 317 317 F->A: Diminishes rescue of PTAP-type L
FT domain-deficient HIV-1 p6.
FT MUTAGEN 318 318 I->A: Greatly diminishes rescue of PTAP-
FT type L domain--deficient HIV-1 p6.
FT MUTAGEN 319 319 Y->A: Greatly diminishes rescue of PTAP-
FT type L domain-deficient HIV-1 p6.
FT MUTAGEN 319 319 Y->F: No effect on rescue of PTAP-type L
FT domain-deficient HIV-1 p6.
FT MUTAGEN 495 495 F->D: Impairs rescue of PTAP-type L
FT domain-deficient HIV-1 p6.
FT MUTAGEN 498 498 V->D: Reduces interaction with HIV-1 p6
FT and EIAV p9; abolishes rescue of PTAP-
FT type L domain-deficient HIV-1 p6.
FT MUTAGEN 509 509 V->D: Abolishes interaction with HIV-1
FT p6; impairs rescue of PTAP-type L domain-
FT deficient HIV-1 p6.
FT MUTAGEN 512 512 C->A: No effect on interaction with HIV-1
FT p6; impairs rescue of PTAP-type L domain-
FT deficient HIV-1 p6.
FT MUTAGEN 676 676 F->D: Abolishes interaction with HIV-1 p6
FT and EIAV p9; abolishes rescue of PTAP-
FT type L domain-deficient HIV-1 p6; no
FT effect on cytokinesis.
FT MUTAGEN 680 680 L->D: Impairs rescue of PTAP-type L
FT domain-deficient HIV-1 p6.
FT MUTAGEN 683 683 I->A: No effect on interaction with HIV-1
FT p6.
FT MUTAGEN 683 683 I->D: Reduces interaction with HIV-1 p6
FT and EIAV p9; abolishes rescue of PTAP-
FT type L domain-deficient HIV-1 p6.
FT MUTAGEN 720 720 P->L: Abolishes interaction with TSG101;
FT no effect on rescue of PTAP-type L
FT domain-deficient HIV-1 p6.
FT MUTAGEN 757 758 RP->AA: Abolishes interaction with SH3GL1
FT and SH3GL2; no effect on rescue of PTAP-
FT type L domain-deficient HIV-1 p6.
FT MUTAGEN 800 802 GPP->AAA: Abolishes interaction with
FT CEP55; inhibits support of cytokinesis.
FT MUTAGEN 801 801 P->A: Diminishes interaction with CEP55.
FT MUTAGEN 802 802 P->A: Diminishes interaction with CEP55.
FT MUTAGEN 806 806 Y->A: Abolishes interaction with CEP55.
FT CONFLICT 580 580 M -> T (in Ref. 7; BAA92092).
FT HELIX 18 28
FT STRAND 33 35
FT HELIX 39 55
FT HELIX 62 78
FT TURN 79 83
FT TURN 84 86
FT STRAND 93 96
FT STRAND 98 100
FT STRAND 104 106
FT STRAND 110 114
FT HELIX 116 136
FT STRAND 140 142
FT HELIX 143 170
FT STRAND 171 173
FT TURN 177 179
FT HELIX 181 205
FT HELIX 210 231
FT HELIX 241 266
FT HELIX 270 290
FT TURN 292 294
FT HELIX 298 317
FT HELIX 326 328
FT STRAND 348 350
FT TURN 354 357
FT HELIX 361 398
FT TURN 399 402
FT HELIX 403 406
FT STRAND 408 412
FT HELIX 415 426
FT TURN 427 429
FT HELIX 430 471
FT TURN 473 475
FT HELIX 481 514
FT HELIX 517 523
FT HELIX 527 532
FT HELIX 541 543
FT HELIX 547 575
FT HELIX 581 590
FT STRAND 591 593
FT HELIX 596 639
FT HELIX 644 697
FT STRAND 802 805
FT TURN 810 812
SQ SEQUENCE 868 AA; 96023 MW; 573588D1F612EC93 CRC64;
MATFISVQLK KTSEVDLAKP LVKFIQQTYP SGGEEQAQYC RAAEELSKLR RAAVGRPLDK
HEGALETLLR YYDQICSIEP KFPFSENQIC LTFTWKDAFD KGSLFGGSVK LALASLGYEK
SCVLFNCAAL ASQIAAEQNL DNDEGLKIAA KHYQFASGAF LHIKETVLSA LSREPTVDIS
PDTVGTLSLI MLAQAQEVFF LKATRDKMKD AIIAKLANQA ADYFGDAFKQ CQYKDTLPKE
VFPVLAAKHC IMQANAEYHQ SILAKQQKKF GEEIARLQHA AELIKTVASR YDEYVNVKDF
SDKINRALAA AKKDNDFIYH DRVPDLKDLD PIGKATLVKS TPVNVPISQK FTDLFEKMVP
VSVQQSLAAY NQRKADLVNR SIAQMREATT LANGVLASLN LPAAIEDVSG DTVPQSILTK
SRSVIEQGGI QTVDQLIKEL PELLQRNREI LDESLRLLDE EEATDNDLRA KFKERWQRTP
SNELYKPLRA EGTNFRTVLD KAVQADGQVK ECYQSHRDTI VLLCKPEPEL NAAIPSANPA
KTMQGSEVVN VLKSLLSNLD EVKKEREGLE NDLKSVNFDM TSKFLTALAQ DGVINEEALS
VTELDRVYGG LTTKVQESLK KQEGLLKNIQ VSHQEFSKMK QSNNEANLRE EVLKNLATAY
DNFVELVANL KEGTKFYNEL TEILVRFQNK CSDIVFARKT ERDELLKDLQ QSIAREPSAP
SIPTPAYQSS PAGGHAPTPP TPAPRTMPPT KPQPPARPPP PVLPANRAPS ATAPSPVGAG
TAAPAPSQTP GSAPPPQAQG PPYPTYPGYP GYCQMPMPMG YNPYAYGQYN MPYPPVYHQS
PGQAPYPGPQ QPSYPFPQPP QQSYYPQQ
//
ID PDC6I_HUMAN Reviewed; 868 AA.
AC Q8WUM4; E9PFU1; Q6NUS1; Q9BX86; Q9NUN0; Q9P2H2; Q9UKL5;
DT 23-MAY-2003, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAR-2002, sequence version 1.
DT 22-JAN-2014, entry version 126.
DE RecName: Full=Programmed cell death 6-interacting protein;
DE Short=PDCD6-interacting protein;
DE AltName: Full=ALG-2-interacting protein 1;
DE AltName: Full=ALG-2-interacting protein X;
DE AltName: Full=Hp95;
GN Name=PDCD6IP; Synonyms=AIP1, ALIX, KIAA1375;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT SER-550.
RX PubMed=11683497; DOI=10.1046/j.1432-0436.2001.670406.x;
RA Wu Y., Pan S., Che S., He G., Nelman-Gonzalez M., Weil M.M., Kuang J.;
RT "Overexpression of Hp95 induces G1 phase arrest in confluent HeLa
RT cells.";
RL Differentiation 67:139-153(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS THR-309 AND
RP LEU-730.
RA Li H., Shioda T., Isselbacher K.J.;
RT "Molecular cloning of human ALG-2 interacting protein 1 (AIP1).";
RL Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R.,
RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J.,
RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND
RP VARIANTS MET-7 AND ILE-378.
RC TISSUE=Lymph, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PROTEIN SEQUENCE OF 2-23; 111-120; 216-229; 439-446; 457-469 AND
RP 542-553, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, AND
RP MASS SPECTROMETRY.
RC TISSUE=Osteosarcoma;
RA Bienvenut W.V., Glen H., Frame M.C.;
RL Submitted (MAR-2008) to UniProtKB.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 209-868 (ISOFORM 1), AND
RP VARIANT ILE-378.
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 323-868 (ISOFORM 1), AND
RP VARIANT SER-550.
RC TISSUE=Brain;
RX PubMed=10718198; DOI=10.1093/dnares/7.1.65;
RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVI.
RT The complete sequences of 150 new cDNA clones from brain which code
RT for large proteins in vitro.";
RL DNA Res. 7:65-73(2000).
RN [9]
RP INTERACTION WITH CHMP4A AND CHMP4B.
RX PubMed=12860994; DOI=10.1074/jbc.M301604200;
RA Katoh K., Shibata H., Suzuki H., Narai A., Ishidoh K., Kominami E.,
RA Yoshimori T., Maki M.;
RT "The ALG-2-interacting protein Alix associates with CHMP4b, a human
RT homologue of yeast Snf7 that is involved in multivesicular body
RT sorting.";
RL J. Biol. Chem. 278:39104-39113(2003).
RN [10]
RP FUNCTION IN HIV-1 BUDDING, AND INTERACTION WITH CHMP4A; CHMP4B;
RP CHMP4C; HIV-1 P6 AND EIAV P9.
RX PubMed=14505569; DOI=10.1016/S0092-8674(03)00653-6;
RA Strack B., Calistri A., Craig S., Popova E., Goettlinger H.G.;
RT "AIP1/ALIX is a binding partner for HIV-1 p6 and EIAV p9 functioning
RT in virus budding.";
RL Cell 114:689-699(2003).
RN [11]
RP FUNCTION IN HIV-1 BUDDING, SELF-ASSOCIATION, INTERACTION WITH TSG101;
RP CHMP4A; CHMP4B CHMP4C, AND SUBCELLULAR LOCATION.
RX PubMed=14505570; DOI=10.1016/S0092-8674(03)00714-1;
RA von Schwedler U.K., Stuchell M., Mueller B., Ward D.M., Chung H.-Y.,
RA Morita E., Wang H.E., Davis T., He G.P., Cimbora D.M., Scott A.,
RA Kraeusslich H.-G., Kaplan J., Morham S.G., Sundquist W.I.;
RT "The protein network of HIV budding.";
RL Cell 114:701-713(2003).
RN [12]
RP SELF-ASSOCIATION, AND INTERACTION WITH TSG101; CHMP4A; CHMP4B; CHMP4C
RP AND EIAV P9.
RX PubMed=14519844; DOI=10.1073/pnas.2133846100;
RA Martin-Serrano J., Yarovoy A., Perez-Caballero D., Bieniasz P.D.;
RT "Divergent retroviral late-budding domains recruit vacuolar protein
RT sorting factors by using alternative adaptor proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:12414-12419(2003).
RN [13]
RP ERRATUM.
RA Martin-Serrano J., Yarovoy A., Perez-Caballero D., Bieniasz P.D.;
RL Proc. Natl. Acad. Sci. U.S.A. 100:152845-152845(2003).
RN [14]
RP INTERACTION WITH CHMP4A; CHMP4B AND CHMP4C.
RX PubMed=14678797; DOI=10.1016/j.abb.2003.09.038;
RA Katoh K., Shibata H., Hatta K., Maki M.;
RT "CHMP4b is a major binding partner of the ALG-2-interacting protein
RT Alix among the three CHMP4 isoforms.";
RL Arch. Biochem. Biophys. 421:159-165(2004).
RN [15]
RP INTERACTION WITH CHMP4A; CHMP4B AND CHMP4C.
RX PubMed=14583093; DOI=10.1042/BJ20031347;
RA Peck J.W., Bowden E.T., Burbelo P.D.;
RT "Structure and function of human Vps20 and Snf7 proteins.";
RL Biochem. J. 377:693-700(2004).
RN [16]
RP FUNCTION IN ENDOSOME ORGANIZATION.
RX PubMed=14739459; DOI=10.1126/science.1092425;
RA Matsuo H., Chevallier J., Mayran N., Le Blanc I., Ferguson C.,
RA Faure J., Blanc N.S., Matile S., Dubochet J., Sadoul R., Parton R.G.,
RA Vilbois F., Gruenberg J.;
RT "Role of LBPA and Alix in multivesicular liposome formation and
RT endosome organization.";
RL Science 303:531-534(2004).
RN [17]
RP INTERACTION WITH SGSM3, AND SUBCELLULAR LOCATION.
RX PubMed=15849434; DOI=10.1271/bbb.69.861;
RA Ichioka F., Horii M., Katoh K., Terasawa Y., Shibata H., Maki M.;
RT "Identification of Rab GTPase-activating protein-like protein
RT (RabGAPLP) as a novel Alix/AIP1-interacting protein.";
RL Biosci. Biotechnol. Biochem. 69:861-865(2005).
RN [18]
RP INTERACTION WITH MURINE LEUKEMIA VIRUS GAG POLYPROTEIN.
RX PubMed=15908698; DOI=10.1074/jbc.M413735200;
RA Segura-Morales C., Pescia C., Chatellard-Causse C., Sadoul R.,
RA Bertrand E., Basyuk E.;
RT "Tsg101 and Alix interact with murine leukemia virus Gag and cooperate
RT with Nedd4 ubiquitin ligases during budding.";
RL J. Biol. Chem. 280:27004-27012(2005).
RN [19]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H.,
RA Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R.,
RA Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E.,
RA Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND INTERACTION WITH PDCD6.
RX PubMed=16957052; DOI=10.1091/mbc.E06-05-0444;
RA Yamasaki A., Tani K., Yamamoto A., Kitamura N., Komada M.;
RT "The Ca2+-binding protein ALG-2 is recruited to endoplasmic reticulum
RT exit sites by Sec31A and stabilizes the localization of Sec31A.";
RL Mol. Biol. Cell 17:4876-4887(2006).
RN [21]
RP FUNCTION IN CYTOKINESIS, SUBCELLULAR LOCATION, INTERACTION WITH CEP55
RP AND CD2AP, AND MUTAGENESIS OF ILE-212; PHE-676 AND 800-GLY--PRO-802.
RX PubMed=17853893; DOI=10.1038/sj.emboj.7601850;
RA Morita E., Sandrin V., Chung H.Y., Morham S.G., Gygi S.P.,
RA Rodesch C.K., Sundquist W.I.;
RT "Human ESCRT and ALIX proteins interact with proteins of the midbody
RT and function in cytokinesis.";
RL EMBO J. 26:4215-4227(2007).
RN [22]
RP FUNCTION IN HIV-1 BUDDING, INTERACTION WITH CHMP4B, AND MUTAGENESIS OF
RP PHE-199; LEU-216; PHE-317; ILE-318 AND TYR-319.
RX PubMed=17428861; DOI=10.1128/JVI.00314-07;
RA Usami Y., Popov S., Goettlinger H.G.;
RT "Potent rescue of human immunodeficiency virus type 1 late domain
RT mutants by ALIX/AIP1 depends on its CHMP4 binding site.";
RL J. Virol. 81:6614-6622(2007).
RN [23]
RP FUNCTION IN CYTOKINESIS, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP CEP55.
RX PubMed=17556548; DOI=10.1126/science.1143422;
RA Carlton J.G., Martin-Serrano J.;
RT "Parallels between cytokinesis and retroviral budding: a role for the
RT ESCRT machinery.";
RL Science 316:1908-1912(2007).
RN [24]
RP INTERACTION WITH PDCD6.
RX PubMed=18256029; DOI=10.1074/jbc.M800717200;
RA Shibata H., Suzuki H., Kakiuchi T., Inuzuka T., Yoshida H., Mizuno T.,
RA Maki M.;
RT "Identification of Alix-type and non-Alix-type ALG-2-binding sites in
RT human phospholipid scramblase 3: differential binding to an
RT alternatively spliced isoform and amino acid-substituted mutants.";
RL J. Biol. Chem. 283:9623-9632(2008).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-730; THR-738 AND
RP THR-741, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [26]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [27]
RP INTERACTION WITH TSG101.
RX PubMed=19520058; DOI=10.1016/j.bbrc.2009.06.015;
RA Okumura M., Ichioka F., Kobayashi R., Suzuki H., Yoshida H.,
RA Shibata H., Maki M.;
RT "Penta-EF-hand protein ALG-2 functions as a Ca2+-dependent adaptor
RT that bridges Alix and TSG101.";
RL Biochem. Biophys. Res. Commun. 386:237-241(2009).
RN [28]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-215, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [29]
RP PHOSPHORYLATION, AND INTERACTION WITH PDGFRB.
RX PubMed=20494825; DOI=10.1016/j.cellsig.2010.05.004;
RA Wardega P., Heldin C.H., Lennartsson J.;
RT "Mutation of tyrosine residue 857 in the PDGF beta-receptor affects
RT cell proliferation but not migration.";
RL Cell. Signal. 22:1363-1368(2010).
RN [30]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-738 AND THR-741, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [31]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [32]
RP X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) OF 1-698, INTERACTION WITH
RP CHMP4A; HIV-1 P6; EIAV P9; TSG101; SH3GL1 AND SH3GL2, AND MUTAGENESIS
RP OF ILE-212; TYR-319; PHE-495; VAL-498; VAL-509; PHE-676; LEU-680;
RP ILE-683; PRO-720 AND 757-ARG-PRO-758.
RX PubMed=17350572; DOI=10.1016/j.cell.2007.01.035;
RA Fisher R.D., Chung H.Y., Zhai Q., Robinson H., Sundquist W.I.,
RA Hill C.P.;
RT "Structural and biochemical studies of ALIX/AIP1 and its role in
RT retrovirus budding.";
RL Cell 128:841-852(2007).
RN [33]
RP X-RAY CRYSTALLOGRAPHY (2.87 ANGSTROMS) OF 360-702, INTERACTION WITH
RP HIV-1 P6, AND MUTAGENESIS OF VAL-498; VAL-509; CYS-512; PHE-676 AND
RP ILE-683.
RX PubMed=17277784; DOI=10.1038/nsmb1203;
RA Lee S., Joshi A., Nagashima K., Freed E.O., Hurley J.H.;
RT "Structural basis for viral late-domain binding to Alix.";
RL Nat. Struct. Mol. Biol. 14:194-199(2007).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (2.59 ANGSTROMS) OF 2-698 IN COMPLEX WITH HIV-1
RP P6, X-RAY CRYSTALLOGRAPHY (2.59 ANGSTROMS) OF 2-698 IN COMPLEX WITH
RP HIV-1 P9, AND INTERACTION WITH EIAV P9.
RX PubMed=18066081; DOI=10.1038/nsmb1319;
RA Zhai Q., Fisher R.D., Chung H.Y., Myszka D.G., Sundquist W.I.,
RA Hill C.P.;
RT "Structural and functional studies of ALIX interactions with YPX(n)L
RT late domains of HIV-1 and EIAV.";
RL Nat. Struct. Mol. Biol. 15:43-49(2008).
RN [35]
RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 1-359 IN COMPLEX WITH
RP CHMP4A, X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1-359 IN COMPLEX WITH
RP CHMP4B, AND X-RAY CRYSTALLOGRAPHY (2.02 ANGSTROMS) OF 1-359 IN COMPLEX
RP WITH CHMP4C.
RX PubMed=18511562; DOI=10.1073/pnas.0801567105;
RA McCullough J., Fisher R.D., Whitby F.G., Sundquist W.I., Hill C.P.;
RT "ALIX-CHMP4 interactions in the human ESCRT pathway.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:7687-7691(2008).
RN [36]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 797-809 IN COMPLEX WITH
RP CEP55, AND MUTAGENESIS OF PRO-801; PRO-802 AND TYR-806.
RX PubMed=18948538; DOI=10.1126/science.1162042;
RA Lee H.H., Elia N., Ghirlando R., Lippincott-Schwartz J., Hurley J.H.;
RT "Midbody targeting of the ESCRT machinery by a noncanonical coiled
RT coil in CEP55.";
RL Science 322:576-580(2008).
RN [37]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 799-812 IN COMPLEX WITH
RP PDCD6.
RX PubMed=18940611; DOI=10.1016/j.str.2008.07.012;
RA Suzuki H., Kawasaki M., Inuzuka T., Okumura M., Kakiuchi T.,
RA Shibata H., Wakatsuki S., Maki M.;
RT "Structural basis for Ca2+ -dependent formation of ALG-2/Alix peptide
RT complex: Ca2+/EF3-driven arginine switch mechanism.";
RL Structure 16:1562-1573(2008).
RN [38]
RP VARIANT SER-429.
RX PubMed=22073189; DOI=10.1371/journal.pone.0026741;
RA Benitez B.A., Alvarado D., Cai Y., Mayo K., Chakraverty S., Norton J.,
RA Morris J.C., Sands M.S., Goate A., Cruchaga C.;
RT "Exome-sequencing confirms DNAJC5 mutations as cause of adult neuronal
RT ceroid-lipofuscinosis.";
RL PLoS ONE 6:E26741-E26741(2011).
CC -!- FUNCTION: Class E VPS protein involved in concentration and
CC sorting of cargo proteins of the multivesicular body (MVB) for
CC incorporation into intralumenal vesicles (ILVs) that are generated
CC by invagination and scission from the limiting membrane of the
CC endosome. Binds to the phospholipid lysobisphosphatidic acid
CC (LBPA) which is abundant in MVBs internal membranes. The MVB
CC pathway appears to require the sequential function of ESCRT-O,
CC -I,-II and -III complexes. The ESCRT machinery also functions in
CC topologically equivalent membrane fission events, such as the
CC terminal stages of cytokinesis and enveloped virus budding (HIV-1
CC and other lentiviruses). Appears to be an adapter for a subset of
CC ESCRT-III proteins, such as CHMP4, to function at distinct
CC membranes. Required for completion of cytokinesis. Involved in
CC HIV-1 virus budding. Can replace TSG101 it its role of supporting
CC HIV-1 release; this function implies the interaction with CHMP4B.
CC May play a role in the regulation of both apoptosis and cell
CC proliferation.
CC -!- SUBUNIT: Interacts with SH3KBP1. Interacts with PDCD6 and TSG101
CC in a calcium-dependent manner. Interacts with and SGSM3. Self-
CC associates. Interacts with CHMP4A; the interaction is direct.
CC Interacts with CHMP4B; the interaction is direct. Interacts with
CC CHMP4C; the interaction is direct. Interacts with HIV-1 p6.
CC Interacts with EIAV p9; the interaction has been shown in vitro.
CC Interacts with CEP55; the interaction is direct; CEP55 binds
CC PDCD6IP in a 2:1 stoechiometry. May interact with PDGFRB.
CC Interacts with SH3GL1 and SH3GL2. Interacts with murine leukemia
CC virus Gag polyprotein (via LYPX(n)L motif). Interacts with murine
CC leukemia virus Gag polyprotein (via LYPX(n)L motif).
CC -!- INTERACTION:
CC P29991:- (xeno); NbExp=3; IntAct=EBI-310624, EBI-8826747;
CC Q9Y5K6:CD2AP; NbExp=2; IntAct=EBI-310624, EBI-298152;
CC Q53EZ4:CEP55; NbExp=9; IntAct=EBI-7603917, EBI-747776;
CC P06241:FYN; NbExp=6; IntAct=EBI-310624, EBI-515315;
CC P03347:gag (xeno); NbExp=2; IntAct=EBI-310624, EBI-1220741;
CC P69730:gag (xeno); NbExp=2; IntAct=EBI-310624, EBI-1220941;
CC P08631:HCK; NbExp=4; IntAct=EBI-310624, EBI-346340;
CC P09022:Hoxa1 (xeno); NbExp=3; IntAct=EBI-310624, EBI-3957603;
CC O75340:PDCD6; NbExp=5; IntAct=EBI-310624, EBI-352915;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol. Melanosome. Cytoplasm,
CC cytoskeleton, microtubule organizing center, centrosome.
CC Note=Identified by mass spectrometry in melanosome fractions from
CC stage I to stage IV. Colocalized with CEP55 in the midbody during
CC cytokinesis. Colocalized with CEP55 at centrosomes of non-dividing
CC cells.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8WUM4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8WUM4-2; Sequence=VSP_044860;
CC Note=No experimental confirmation available;
CC -!- PTM: May be phosphorylated on tyrosine residues by activated
CC PDGFRB.
CC -!- SIMILARITY: Contains 1 BRO1 domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA92092.1; Type=Erroneous initiation;
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DR EMBL; AF349951; AAK20398.1; -; mRNA.
DR EMBL; AF151793; AAF08220.1; -; mRNA.
DR EMBL; BT007367; AAP36031.1; -; mRNA.
DR EMBL; AC112220; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC123901; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC020066; AAH20066.1; -; mRNA.
DR EMBL; BC068454; AAH68454.1; -; mRNA.
DR EMBL; AK002122; BAA92092.1; ALT_INIT; mRNA.
DR EMBL; AB037796; BAA92613.1; -; mRNA.
DR RefSeq; NP_001155901.1; NM_001162429.2.
DR RefSeq; NP_037506.2; NM_013374.5.
DR UniGene; Hs.475896; -.
DR PDB; 2OEV; X-ray; 3.30 A; A=1-698.
DR PDB; 2OEW; X-ray; 2.55 A; A=1-359.
DR PDB; 2OEX; X-ray; 2.58 A; A/B=360-702.
DR PDB; 2OJQ; X-ray; 2.87 A; A=360-702.
DR PDB; 2R02; X-ray; 2.60 A; A=2-698.
DR PDB; 2R03; X-ray; 2.59 A; A=2-698.
DR PDB; 2R05; X-ray; 2.55 A; A=2-698.
DR PDB; 2XS1; X-ray; 2.30 A; A=1-698.
DR PDB; 2XS8; X-ray; 2.50 A; A=1-698.
DR PDB; 2ZNE; X-ray; 2.20 A; C/D=799-812.
DR PDB; 3C3O; X-ray; 2.15 A; A=1-359.
DR PDB; 3C3Q; X-ray; 2.10 A; A=1-359.
DR PDB; 3C3R; X-ray; 2.02 A; A=1-359.
DR PDB; 3E1R; X-ray; 2.00 A; C=797-809.
DR PDB; 4JJY; X-ray; 6.50 A; A/B=355-702.
DR PDBsum; 2OEV; -.
DR PDBsum; 2OEW; -.
DR PDBsum; 2OEX; -.
DR PDBsum; 2OJQ; -.
DR PDBsum; 2R02; -.
DR PDBsum; 2R03; -.
DR PDBsum; 2R05; -.
DR PDBsum; 2XS1; -.
DR PDBsum; 2XS8; -.
DR PDBsum; 2ZNE; -.
DR PDBsum; 3C3O; -.
DR PDBsum; 3C3Q; -.
DR PDBsum; 3C3R; -.
DR PDBsum; 3E1R; -.
DR PDBsum; 4JJY; -.
DR ProteinModelPortal; Q8WUM4; -.
DR SMR; Q8WUM4; 2-702.
DR DIP; DIP-29327N; -.
DR IntAct; Q8WUM4; 39.
DR MINT; MINT-4999333; -.
DR STRING; 9606.ENSP00000307387; -.
DR PhosphoSite; Q8WUM4; -.
DR DMDM; 31076831; -.
DR UCD-2DPAGE; Q8WUM4; -.
DR PaxDb; Q8WUM4; -.
DR PRIDE; Q8WUM4; -.
DR DNASU; 10015; -.
DR Ensembl; ENST00000307296; ENSP00000307387; ENSG00000170248.
DR Ensembl; ENST00000457054; ENSP00000411825; ENSG00000170248.
DR GeneID; 10015; -.
DR KEGG; hsa:10015; -.
DR UCSC; uc003cfy.4; human.
DR CTD; 10015; -.
DR GeneCards; GC03P033839; -.
DR H-InvDB; HIX0163463; -.
DR HGNC; HGNC:8766; PDCD6IP.
DR HPA; CAB016212; -.
DR HPA; HPA011905; -.
DR MIM; 608074; gene.
DR neXtProt; NX_Q8WUM4; -.
DR PharmGKB; PA33116; -.
DR eggNOG; NOG325528; -.
DR HOGENOM; HOG000006938; -.
DR HOVERGEN; HBG053533; -.
DR InParanoid; Q8WUM4; -.
DR KO; K12200; -.
DR OMA; CYQSHRD; -.
DR OrthoDB; EOG7V49XV; -.
DR PhylomeDB; Q8WUM4; -.
DR Reactome; REACT_116125; Disease.
DR ChiTaRS; PDCD6IP; human.
DR EvolutionaryTrace; Q8WUM4; -.
DR GeneWiki; PDCD6IP; -.
DR GenomeRNAi; 10015; -.
DR NextBio; 37837; -.
DR PRO; PR:Q8WUM4; -.
DR ArrayExpress; Q8WUM4; -.
DR Bgee; Q8WUM4; -.
DR CleanEx; HS_PDCD6IP; -.
DR Genevestigator; Q8WUM4; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0016032; P:viral process; TAS:Reactome.
DR Gene3D; 1.25.40.280; -; 1.
DR InterPro; IPR025304; ALIX_V_dom.
DR InterPro; IPR004328; BRO1_dom.
DR Pfam; PF13949; ALIX_LYPXL_bnd; 1.
DR Pfam; PF03097; BRO1; 1.
DR SMART; SM01041; BRO1; 1.
DR PROSITE; PS51180; BRO1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Apoptosis;
KW Cell cycle; Cell division; Complete proteome; Cytoplasm; Cytoskeleton;
KW Direct protein sequencing; Host-virus interaction; Phosphoprotein;
KW Polymorphism; Protein transport; Reference proteome; Transport.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 868 Programmed cell death 6-interacting
FT protein.
FT /FTId=PRO_0000218891.
FT DOMAIN 3 392 BRO1.
FT REGION 176 868 Interaction with EIAV p9.
FT REGION 176 503 Interaction with CHMP4A, CHMP4B and
FT CHMP4C.
FT REGION 503 868 Self-association.
FT REGION 717 720 Interaction with TSG101.
FT REGION 797 806 Interaction with CEP55.
FT REGION 864 868 Essential to promote virus budding.
FT COMPBIAS 717 860 Pro-rich.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 215 215 N6-acetyllysine.
FT MOD_RES 730 730 Phosphoserine.
FT MOD_RES 738 738 Phosphothreonine.
FT MOD_RES 741 741 Phosphothreonine.
FT VAR_SEQ 239 239 K -> KYFYFQ (in isoform 2).
FT /FTId=VSP_044860.
FT VARIANT 7 7 V -> M (in dbSNP:rs11554560).
FT /FTId=VAR_068975.
FT VARIANT 309 309 A -> T (in dbSNP:rs3792594).
FT /FTId=VAR_053017.
FT VARIANT 378 378 V -> I (in dbSNP:rs3203777).
FT /FTId=VAR_053018.
FT VARIANT 429 429 G -> S (in dbSNP:rs148256302).
FT /FTId=VAR_069765.
FT VARIANT 550 550 N -> S (in dbSNP:rs9813017).
FT /FTId=VAR_053019.
FT VARIANT 638 638 K -> E (in dbSNP:rs3183982).
FT /FTId=VAR_053020.
FT VARIANT 730 730 S -> L (in dbSNP:rs1127732).
FT /FTId=VAR_024381.
FT MUTAGEN 199 199 F->D: Abolishes interaction with CHMP4B
FT and abolishes rescue of PTAP-type L
FT domain-deficient HIV-1 p6.
FT MUTAGEN 212 212 I->D: Abolishes interaction with CHMP4A;
FT impairs rescue of PTAP-type L domain-
FT deficient HIV-1 p6; inhibits support of
FT cytokinesis.
FT MUTAGEN 216 216 L->D: Abolishes interaction with CHMP4B
FT and abolishes rescue of PTAP-type L
FT domain-deficient HIV-1 p6.
FT MUTAGEN 317 317 F->A: Diminishes rescue of PTAP-type L
FT domain-deficient HIV-1 p6.
FT MUTAGEN 318 318 I->A: Greatly diminishes rescue of PTAP-
FT type L domain--deficient HIV-1 p6.
FT MUTAGEN 319 319 Y->A: Greatly diminishes rescue of PTAP-
FT type L domain-deficient HIV-1 p6.
FT MUTAGEN 319 319 Y->F: No effect on rescue of PTAP-type L
FT domain-deficient HIV-1 p6.
FT MUTAGEN 495 495 F->D: Impairs rescue of PTAP-type L
FT domain-deficient HIV-1 p6.
FT MUTAGEN 498 498 V->D: Reduces interaction with HIV-1 p6
FT and EIAV p9; abolishes rescue of PTAP-
FT type L domain-deficient HIV-1 p6.
FT MUTAGEN 509 509 V->D: Abolishes interaction with HIV-1
FT p6; impairs rescue of PTAP-type L domain-
FT deficient HIV-1 p6.
FT MUTAGEN 512 512 C->A: No effect on interaction with HIV-1
FT p6; impairs rescue of PTAP-type L domain-
FT deficient HIV-1 p6.
FT MUTAGEN 676 676 F->D: Abolishes interaction with HIV-1 p6
FT and EIAV p9; abolishes rescue of PTAP-
FT type L domain-deficient HIV-1 p6; no
FT effect on cytokinesis.
FT MUTAGEN 680 680 L->D: Impairs rescue of PTAP-type L
FT domain-deficient HIV-1 p6.
FT MUTAGEN 683 683 I->A: No effect on interaction with HIV-1
FT p6.
FT MUTAGEN 683 683 I->D: Reduces interaction with HIV-1 p6
FT and EIAV p9; abolishes rescue of PTAP-
FT type L domain-deficient HIV-1 p6.
FT MUTAGEN 720 720 P->L: Abolishes interaction with TSG101;
FT no effect on rescue of PTAP-type L
FT domain-deficient HIV-1 p6.
FT MUTAGEN 757 758 RP->AA: Abolishes interaction with SH3GL1
FT and SH3GL2; no effect on rescue of PTAP-
FT type L domain-deficient HIV-1 p6.
FT MUTAGEN 800 802 GPP->AAA: Abolishes interaction with
FT CEP55; inhibits support of cytokinesis.
FT MUTAGEN 801 801 P->A: Diminishes interaction with CEP55.
FT MUTAGEN 802 802 P->A: Diminishes interaction with CEP55.
FT MUTAGEN 806 806 Y->A: Abolishes interaction with CEP55.
FT CONFLICT 580 580 M -> T (in Ref. 7; BAA92092).
FT HELIX 18 28
FT STRAND 33 35
FT HELIX 39 55
FT HELIX 62 78
FT TURN 79 83
FT TURN 84 86
FT STRAND 93 96
FT STRAND 98 100
FT STRAND 104 106
FT STRAND 110 114
FT HELIX 116 136
FT STRAND 140 142
FT HELIX 143 170
FT STRAND 171 173
FT TURN 177 179
FT HELIX 181 205
FT HELIX 210 231
FT HELIX 241 266
FT HELIX 270 290
FT TURN 292 294
FT HELIX 298 317
FT HELIX 326 328
FT STRAND 348 350
FT TURN 354 357
FT HELIX 361 398
FT TURN 399 402
FT HELIX 403 406
FT STRAND 408 412
FT HELIX 415 426
FT TURN 427 429
FT HELIX 430 471
FT TURN 473 475
FT HELIX 481 514
FT HELIX 517 523
FT HELIX 527 532
FT HELIX 541 543
FT HELIX 547 575
FT HELIX 581 590
FT STRAND 591 593
FT HELIX 596 639
FT HELIX 644 697
FT STRAND 802 805
FT TURN 810 812
SQ SEQUENCE 868 AA; 96023 MW; 573588D1F612EC93 CRC64;
MATFISVQLK KTSEVDLAKP LVKFIQQTYP SGGEEQAQYC RAAEELSKLR RAAVGRPLDK
HEGALETLLR YYDQICSIEP KFPFSENQIC LTFTWKDAFD KGSLFGGSVK LALASLGYEK
SCVLFNCAAL ASQIAAEQNL DNDEGLKIAA KHYQFASGAF LHIKETVLSA LSREPTVDIS
PDTVGTLSLI MLAQAQEVFF LKATRDKMKD AIIAKLANQA ADYFGDAFKQ CQYKDTLPKE
VFPVLAAKHC IMQANAEYHQ SILAKQQKKF GEEIARLQHA AELIKTVASR YDEYVNVKDF
SDKINRALAA AKKDNDFIYH DRVPDLKDLD PIGKATLVKS TPVNVPISQK FTDLFEKMVP
VSVQQSLAAY NQRKADLVNR SIAQMREATT LANGVLASLN LPAAIEDVSG DTVPQSILTK
SRSVIEQGGI QTVDQLIKEL PELLQRNREI LDESLRLLDE EEATDNDLRA KFKERWQRTP
SNELYKPLRA EGTNFRTVLD KAVQADGQVK ECYQSHRDTI VLLCKPEPEL NAAIPSANPA
KTMQGSEVVN VLKSLLSNLD EVKKEREGLE NDLKSVNFDM TSKFLTALAQ DGVINEEALS
VTELDRVYGG LTTKVQESLK KQEGLLKNIQ VSHQEFSKMK QSNNEANLRE EVLKNLATAY
DNFVELVANL KEGTKFYNEL TEILVRFQNK CSDIVFARKT ERDELLKDLQ QSIAREPSAP
SIPTPAYQSS PAGGHAPTPP TPAPRTMPPT KPQPPARPPP PVLPANRAPS ATAPSPVGAG
TAAPAPSQTP GSAPPPQAQG PPYPTYPGYP GYCQMPMPMG YNPYAYGQYN MPYPPVYHQS
PGQAPYPGPQ QPSYPFPQPP QQSYYPQQ
//
MIM
608074
*RECORD*
*FIELD* NO
608074
*FIELD* TI
*608074 PROGRAMMED CELL DEATH 6-INTERACTING PROTEIN; PDCD6IP
;;PDCD6-INTERACTING PROTEIN;;
read moreALG2-INTERACTING PROTEIN 1; AIP1;;
ALG2-INTERACTING PROTEIN X; ALIX;;
KIAA1375
*FIELD* TX
DESCRIPTION
PDCD6IP interacts with proteins associated with apoptosis, including
PDCD6 (601057), and with endophilins, which regulate membrane shape
(Chatellard-Causse et al., 2002).
CLONING
By sequencing clones obtained from a size-fractionated fetal brain cDNA
library, Nagase et al. (2000) cloned PDCD6IP, which they designated
KIAA1375. RT-PCR ELISA detected moderate expression in all adult and
fetal tissues tested except adult lung, spleen, and pancreas and fetal
brain, which all showed low expression. Moderate expression was detected
in all individual brain regions examined.
Wu et al. (2001) cloned full-length PDCD6IP, which they designated p95,
by searching databases for sequences similar to YNK1, the C. elegans
PDCD6IP homolog, followed by 5-prime and 3-prime RACE of a placenta cDNA
library. The deduced 868-amino acid PDCD6IP protein has a calculated
molecular mass of 96 kD. It has a proline-rich C terminus containing
several PxxP motifs, which are SRC (190090) homology domain-3
(SH3)-binding domains. PDCD6IP also contains a tyrosine
autophosphorylation consensus sequence that is conserved with SRC family
members, as well as several additional conserved tyrosines. PDCD6IP
shares significant homology with proteins from mouse, Xenopus,
Drosophila, several yeast species, and Arabidopsis. Northern blot
analysis detected an endogenous 3.5-kb transcript in HeLa cell RNA.
Western blot analysis of HeLa cell lysates determined that the PDCD6IP
protein has an apparent molecular mass of 95 kD.
Missotten et al. (1999) cloned mouse Pdcd6ip, which they called Alix, in
a yeast 2-hybrid screen of a brain cDNA library using Alg2 (PDCD6) as
bait. The deduced 869-amino acid protein has a calculated molecular mass
of about 96 kD. The authors noted that, in addition to several
SH3-binding domains, the C terminus of Alix contains a WW-binding
domain. Northern blot analysis detected 3.5- and 6.5-kb transcripts in
all adult mouse tissues tested.
GENE FUNCTION
Normal epithelial cells stop proliferating in culture following
cell-cell contact due to induction of G1 phase arrest in the cell cycle.
However, malignant HeLa cells do not inhibit proliferation upon
cell-cell contact and proceed toward multilayer growth. Wu et al. (2001)
determined that overexpression of PDCD6IP restored the ability of HeLa
cells to undergo G1 phase arrest and form a monolayer culture after
confluence. Overexpression of PDCD6IP did not inhibit HeLa cell growth
in sparse cultures.
Wu et al. (2002) found that overexpression of PDCD6IP in HeLa cells
promoted detachment-induced apoptosis, inhibited detachment of viable
cells from the substratum, and reduced tumorigenicity following
injection into nude mice. Overexpression in mouse fibroblasts promoted
flat cell morphology and slowed cell proliferation. Transfection of
antisense PDCD6IP had the opposite effects, with more rounded fibroblast
morphology and dense growth.
Missotten et al. (1999) determined that interaction between mouse Alix
and Alg2 is calcium-dependent.
Vito et al. (1999) determined that mouse Alix and Alg2 colocalized in
the cytosol of fibroblasts and required calcium for their association.
Overexpression of the C terminus of Alix protected HeLa and COS cells
from apoptosis induced by withdrawal of trophic factors.
By yeast 2-hybrid analysis, Chatellard-Causse et al. (2002) determined
that mouse Alix binds to the endophilins Sh3p4 (604465), Sh3p8 (601768),
and Sh3p13 (603362). Coimmunoprecipitation and overlay experiments with
truncation mutants demonstrated that the SH3 domains of endophilins bind
to the C terminus of Alix, specifically within a 14-amino acid region
containing a PxRPPPP consensus sequence. Upon overexpression in human
embryonic kidney cells, full-length Alix and the N terminus of Alix
concentrated in the perinuclear region and at the cell periphery in
lamellipodia and filopodia. Overexpression of the C terminus of Alix in
several cell lines led to concentration around perinuclear vesicles and
to cytoplasmic vacuolization into tubulovesicular structures.
Immunolocalization revealed that the structures were lined by Alix and
endoplasmic reticulum resident proteins. Vacuolization was enhanced upon
coexpression of with Sh3p4, and Alix lacking the proline-rich domain did
not cause vacuolization when overexpressed alone or with Sh3p4.
Matsuo et al. (2004) found that the unconventional phospholipid
lysobisphosphatidic acid (LBPA) could induce the formation of
multivesicular liposomes that resembled the multivesicular endosomes
that exist where this lipid is found in vivo. This process depended on
the same pH gradient that exists across endosome membranes in vivo and
was selectively controlled by Alix. In turn, Alix regulated the
organization of LBPA-containing endosomes in vivo.
By yeast 2-hybrid analysis, coimmunoprecipitation analysis, and in vitro
protein pull-down assays, Katoh et al. (2003) showed that CHMP4B
(610897) interacted with ALIX. Overexpression of CHMP4B in HeLa cells
caused redistribution of ALIX from the cytoplasm to the perinuclear
area, where the 2 proteins colocalized. Transient overexpression of the
ALIX N-terminal region in HEK293 cells stably expressing CHMP4B induced
formation of vesicle-like structures in which CHMP4B and truncated ALIX
colocalized. A dominant-negative form of the AAA-type ATPase SKD1
(VPS4B; 609983), which plays critical roles in the endocytic pathway,
coimmunoprecipitated with CHMP4B. Furthermore, both CHMP4B and ALIX
colocalized with dominant-negative SKD1 in perinuclear dot-like
distributions in transfected HeLa cells, suggesting that the 3 proteins
are involved in formation of multivesicular bodies.
Using coimmunoprecipitation analysis and in vitro pull-down assays,
Katoh et al. (2004) showed that ALIX interacted with all 3 CHMP4
proteins, although the interaction was stronger between ALIX and CHMP4B
than between ALIX and CHMP4A (610051) or CHMP4C (610899).
Carlton and Martin-Serrano (2007) found that 2 proteins involved in
HIV-1 budding--tumor susceptibility gene 101 (TSG101; 601387), a subunit
of the endosomal sorting complex required for transport 1 (ESCRT-1), and
ALIX, an ESCRT-associated protein--were recruited to the midbody during
cytokinesis by interaction with centrosome protein 55 (CEP55; 610000), a
centrosome and midbody protein essential for abscission. TSG101, ALIX,
and possibly other components of ESCRT-1 were required for the
completion of cytokinesis. Carlton and Martin-Serrano (2007) concluded
that thus, HIV-1 budding and cytokinesis use a similar subset of
cellular components to carry out topologically similar membrane fission
events.
By yeast 2-hybrid analysis of a human T-cell cDNA library, followed by
coimmunoprecipitation and immunofluorescence analyses, Chen et al.
(2009) identified ALIX as a binding partner for GAL3 (LGALS3; 153619)
and showed that ALIX translocated to the immunologic synapse in
activated T cells. Chen et al. (2009) concluded that GAL3 is an
inhibitory regulator of T-cell activation and that it functions
intracellularly by promoting T-cell receptor downregulation, possibly
through modulation of ALIX function at the immunologic synapse.
Feng et al. (2013) showed that hepatitis A virus (HAV) released from
cells is cloaked in host-derived membranes, thereby protecting the
virion from antibody-mediated neutralization. The enveloped viruses
(eHAV) resemble exosomes, small vesicles that are important in
intercellular communications. They are fully infectious, sensitive to
extraction with chloroform, and circulate in the blood of infected
humans. Their biogenesis is dependent on host proteins associated with
endosomal-sorting complexes required for transport, namely VPS4B and
ALIX. Feng et al. (2013) concluded that while the hijacking of membranes
by HAV facilitates escape from neutralizing antibodies and probably
promotes virus spread within the liver, anti-capsid antibodies restrict
replication after infection with eHAV, suggesting a possible explanation
for prophylaxis after exposure.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the PDCD6IP
gene to chromosome 3 (TMAP sts-R60314).
*FIELD* RF
1. Carlton, J. G.; Martin-Serrano, J.: Parallels between cytokinesis
and retroviral budding: a role for the ESCRT machinery. Science 316:
1908-1912, 2007.
2. Chatellard-Causse, C.; Blot, B.; Cristina, N.; Torch, S.; Missotten,
M.; Sadoul, R.: Alix (ALG2-interacting protein X), a protein involved
in apoptosis, binds to endophilins and induces cytoplasmic vacuolization. J.
Biol. Chem. 277: 29108-29115, 2002.
3. Chen, H.-Y.; Fermin, A.; Vardhana, S.; Weng, I.-C.; Lo, K. F. R.;
Chang, E.-Y.; Maverakis, E.; Yang, R.-Y.; Hsu, D. K.; Dustin, M. L.;
Liu, F.-T.: Galectin-3 negatively regulates TCR-mediated CD4+ T-cell
activation at the immunological synapse. Proc. Nat. Acad. Sci. 106:
14496-14501, 2009.
4. Feng, Z.; Hensley, L.; McKnight, K. L.; Hu, F.; Madden, V.; Ping,
L.; Jeong, S.-H.; Walker, C.; Lanford, R. E.; Lemon, S. M.: A pathogenic
picornavirus acquires an envelope by hijacking cellular membranes. Nature 496:
367-371, 2013.
5. Katoh, K.; Shibata, H.; Hatta, K.; Maki, M.: CHMP4b is a major
binding partner of the ALG-2-interacting protein Alix among the three
CHMP4 isoforms. Arch. Biochem. Biophys. 421: 159-165, 2004.
6. Katoh, K.; Shibata, H.; Suzuki, H.; Nara, A.; Ishidoh, K.; Kominami,
E.; Yoshimori, T.; Maki, M.: The ALG-2-interacting protein Alix associates
with CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular
body sorting. J. Biol. Chem. 278: 39104-39113, 2003.
7. Matsuo, H.; Chevallier, J.; Mayran, N.; Le Blanc, I.; Ferguson,
C.; Faure, J.; Blanc, N. S.; Matile, S.; Dubochet, J.; Sadoul, R.;
Parton, R. G.; Vilbois, F.; Gruenberg, J.: Role of LBPA and Alix
in multivesicular liposome formation and endosome organization. Science 303:
531-534, 2004.
8. Missotten, M.; Nichols, A.; Rieger, K.; Sadoul, R.: Alix, a novel
mouse protein undergoing calcium-dependent interaction with the apoptosis-linked-gene
2 (ALG-2) protein. Cell Death Differ. 6: 124-129, 1999.
9. Nagase, T.; Kikuno, R.; Ishikawa, K.; Hirosawa, M.; Ohara, O.:
Prediction of the coding sequences of unidentified human genes. XVI.
The complete sequences of 150 new cDNA clones from brain which code
for large proteins in vitro. DNA Res. 7: 65-73, 2000.
10. Vito, P.; Pellegrini, L.; Guiet, C.; D'Adamio, L.: Cloning of
AIP1, a novel protein that associates with the apoptosis-linked gene
ALG-2 in a Ca(2+)-dependent reaction. J. Biol. Chem. 274: 1533-1540,
1999.
11. Wu, Y.; Pan, S.; Che, S.; He, G.; Nelman-Gonzalez, M.; Weil, M.
M.; Kuang, J.: Overexpression of Hp95 induces G1 phase arrest in
confluent HeLa cells. Differentiation 67: 139-153, 2001.
12. Wu, Y.; Pan, S.; Luo, W.; Lin, S.-H.; Kuang, J.: Hp95 promotes
anoikis and inhibits tumorigenicity of HeLa cells. Oncogene 21:
6801-6808, 2002.
*FIELD* CN
Ada Hamosh - updated: 05/01/2013
Paul J. Converse - updated: 10/17/2011
Ada Hamosh - updated: 7/24/2007
Patricia A. Hartz - updated: 3/29/2007
Ada Hamosh - updated: 2/2/2004
*FIELD* CD
Patricia A. Hartz: 9/4/2003
*FIELD* ED
alopez: 05/01/2013
terry: 11/4/2011
mgross: 11/3/2011
terry: 10/17/2011
alopez: 7/25/2007
terry: 7/24/2007
mgross: 3/29/2007
alopez: 2/2/2004
mgross: 9/5/2003
mgross: 9/4/2003
*RECORD*
*FIELD* NO
608074
*FIELD* TI
*608074 PROGRAMMED CELL DEATH 6-INTERACTING PROTEIN; PDCD6IP
;;PDCD6-INTERACTING PROTEIN;;
read moreALG2-INTERACTING PROTEIN 1; AIP1;;
ALG2-INTERACTING PROTEIN X; ALIX;;
KIAA1375
*FIELD* TX
DESCRIPTION
PDCD6IP interacts with proteins associated with apoptosis, including
PDCD6 (601057), and with endophilins, which regulate membrane shape
(Chatellard-Causse et al., 2002).
CLONING
By sequencing clones obtained from a size-fractionated fetal brain cDNA
library, Nagase et al. (2000) cloned PDCD6IP, which they designated
KIAA1375. RT-PCR ELISA detected moderate expression in all adult and
fetal tissues tested except adult lung, spleen, and pancreas and fetal
brain, which all showed low expression. Moderate expression was detected
in all individual brain regions examined.
Wu et al. (2001) cloned full-length PDCD6IP, which they designated p95,
by searching databases for sequences similar to YNK1, the C. elegans
PDCD6IP homolog, followed by 5-prime and 3-prime RACE of a placenta cDNA
library. The deduced 868-amino acid PDCD6IP protein has a calculated
molecular mass of 96 kD. It has a proline-rich C terminus containing
several PxxP motifs, which are SRC (190090) homology domain-3
(SH3)-binding domains. PDCD6IP also contains a tyrosine
autophosphorylation consensus sequence that is conserved with SRC family
members, as well as several additional conserved tyrosines. PDCD6IP
shares significant homology with proteins from mouse, Xenopus,
Drosophila, several yeast species, and Arabidopsis. Northern blot
analysis detected an endogenous 3.5-kb transcript in HeLa cell RNA.
Western blot analysis of HeLa cell lysates determined that the PDCD6IP
protein has an apparent molecular mass of 95 kD.
Missotten et al. (1999) cloned mouse Pdcd6ip, which they called Alix, in
a yeast 2-hybrid screen of a brain cDNA library using Alg2 (PDCD6) as
bait. The deduced 869-amino acid protein has a calculated molecular mass
of about 96 kD. The authors noted that, in addition to several
SH3-binding domains, the C terminus of Alix contains a WW-binding
domain. Northern blot analysis detected 3.5- and 6.5-kb transcripts in
all adult mouse tissues tested.
GENE FUNCTION
Normal epithelial cells stop proliferating in culture following
cell-cell contact due to induction of G1 phase arrest in the cell cycle.
However, malignant HeLa cells do not inhibit proliferation upon
cell-cell contact and proceed toward multilayer growth. Wu et al. (2001)
determined that overexpression of PDCD6IP restored the ability of HeLa
cells to undergo G1 phase arrest and form a monolayer culture after
confluence. Overexpression of PDCD6IP did not inhibit HeLa cell growth
in sparse cultures.
Wu et al. (2002) found that overexpression of PDCD6IP in HeLa cells
promoted detachment-induced apoptosis, inhibited detachment of viable
cells from the substratum, and reduced tumorigenicity following
injection into nude mice. Overexpression in mouse fibroblasts promoted
flat cell morphology and slowed cell proliferation. Transfection of
antisense PDCD6IP had the opposite effects, with more rounded fibroblast
morphology and dense growth.
Missotten et al. (1999) determined that interaction between mouse Alix
and Alg2 is calcium-dependent.
Vito et al. (1999) determined that mouse Alix and Alg2 colocalized in
the cytosol of fibroblasts and required calcium for their association.
Overexpression of the C terminus of Alix protected HeLa and COS cells
from apoptosis induced by withdrawal of trophic factors.
By yeast 2-hybrid analysis, Chatellard-Causse et al. (2002) determined
that mouse Alix binds to the endophilins Sh3p4 (604465), Sh3p8 (601768),
and Sh3p13 (603362). Coimmunoprecipitation and overlay experiments with
truncation mutants demonstrated that the SH3 domains of endophilins bind
to the C terminus of Alix, specifically within a 14-amino acid region
containing a PxRPPPP consensus sequence. Upon overexpression in human
embryonic kidney cells, full-length Alix and the N terminus of Alix
concentrated in the perinuclear region and at the cell periphery in
lamellipodia and filopodia. Overexpression of the C terminus of Alix in
several cell lines led to concentration around perinuclear vesicles and
to cytoplasmic vacuolization into tubulovesicular structures.
Immunolocalization revealed that the structures were lined by Alix and
endoplasmic reticulum resident proteins. Vacuolization was enhanced upon
coexpression of with Sh3p4, and Alix lacking the proline-rich domain did
not cause vacuolization when overexpressed alone or with Sh3p4.
Matsuo et al. (2004) found that the unconventional phospholipid
lysobisphosphatidic acid (LBPA) could induce the formation of
multivesicular liposomes that resembled the multivesicular endosomes
that exist where this lipid is found in vivo. This process depended on
the same pH gradient that exists across endosome membranes in vivo and
was selectively controlled by Alix. In turn, Alix regulated the
organization of LBPA-containing endosomes in vivo.
By yeast 2-hybrid analysis, coimmunoprecipitation analysis, and in vitro
protein pull-down assays, Katoh et al. (2003) showed that CHMP4B
(610897) interacted with ALIX. Overexpression of CHMP4B in HeLa cells
caused redistribution of ALIX from the cytoplasm to the perinuclear
area, where the 2 proteins colocalized. Transient overexpression of the
ALIX N-terminal region in HEK293 cells stably expressing CHMP4B induced
formation of vesicle-like structures in which CHMP4B and truncated ALIX
colocalized. A dominant-negative form of the AAA-type ATPase SKD1
(VPS4B; 609983), which plays critical roles in the endocytic pathway,
coimmunoprecipitated with CHMP4B. Furthermore, both CHMP4B and ALIX
colocalized with dominant-negative SKD1 in perinuclear dot-like
distributions in transfected HeLa cells, suggesting that the 3 proteins
are involved in formation of multivesicular bodies.
Using coimmunoprecipitation analysis and in vitro pull-down assays,
Katoh et al. (2004) showed that ALIX interacted with all 3 CHMP4
proteins, although the interaction was stronger between ALIX and CHMP4B
than between ALIX and CHMP4A (610051) or CHMP4C (610899).
Carlton and Martin-Serrano (2007) found that 2 proteins involved in
HIV-1 budding--tumor susceptibility gene 101 (TSG101; 601387), a subunit
of the endosomal sorting complex required for transport 1 (ESCRT-1), and
ALIX, an ESCRT-associated protein--were recruited to the midbody during
cytokinesis by interaction with centrosome protein 55 (CEP55; 610000), a
centrosome and midbody protein essential for abscission. TSG101, ALIX,
and possibly other components of ESCRT-1 were required for the
completion of cytokinesis. Carlton and Martin-Serrano (2007) concluded
that thus, HIV-1 budding and cytokinesis use a similar subset of
cellular components to carry out topologically similar membrane fission
events.
By yeast 2-hybrid analysis of a human T-cell cDNA library, followed by
coimmunoprecipitation and immunofluorescence analyses, Chen et al.
(2009) identified ALIX as a binding partner for GAL3 (LGALS3; 153619)
and showed that ALIX translocated to the immunologic synapse in
activated T cells. Chen et al. (2009) concluded that GAL3 is an
inhibitory regulator of T-cell activation and that it functions
intracellularly by promoting T-cell receptor downregulation, possibly
through modulation of ALIX function at the immunologic synapse.
Feng et al. (2013) showed that hepatitis A virus (HAV) released from
cells is cloaked in host-derived membranes, thereby protecting the
virion from antibody-mediated neutralization. The enveloped viruses
(eHAV) resemble exosomes, small vesicles that are important in
intercellular communications. They are fully infectious, sensitive to
extraction with chloroform, and circulate in the blood of infected
humans. Their biogenesis is dependent on host proteins associated with
endosomal-sorting complexes required for transport, namely VPS4B and
ALIX. Feng et al. (2013) concluded that while the hijacking of membranes
by HAV facilitates escape from neutralizing antibodies and probably
promotes virus spread within the liver, anti-capsid antibodies restrict
replication after infection with eHAV, suggesting a possible explanation
for prophylaxis after exposure.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the PDCD6IP
gene to chromosome 3 (TMAP sts-R60314).
*FIELD* RF
1. Carlton, J. G.; Martin-Serrano, J.: Parallels between cytokinesis
and retroviral budding: a role for the ESCRT machinery. Science 316:
1908-1912, 2007.
2. Chatellard-Causse, C.; Blot, B.; Cristina, N.; Torch, S.; Missotten,
M.; Sadoul, R.: Alix (ALG2-interacting protein X), a protein involved
in apoptosis, binds to endophilins and induces cytoplasmic vacuolization. J.
Biol. Chem. 277: 29108-29115, 2002.
3. Chen, H.-Y.; Fermin, A.; Vardhana, S.; Weng, I.-C.; Lo, K. F. R.;
Chang, E.-Y.; Maverakis, E.; Yang, R.-Y.; Hsu, D. K.; Dustin, M. L.;
Liu, F.-T.: Galectin-3 negatively regulates TCR-mediated CD4+ T-cell
activation at the immunological synapse. Proc. Nat. Acad. Sci. 106:
14496-14501, 2009.
4. Feng, Z.; Hensley, L.; McKnight, K. L.; Hu, F.; Madden, V.; Ping,
L.; Jeong, S.-H.; Walker, C.; Lanford, R. E.; Lemon, S. M.: A pathogenic
picornavirus acquires an envelope by hijacking cellular membranes. Nature 496:
367-371, 2013.
5. Katoh, K.; Shibata, H.; Hatta, K.; Maki, M.: CHMP4b is a major
binding partner of the ALG-2-interacting protein Alix among the three
CHMP4 isoforms. Arch. Biochem. Biophys. 421: 159-165, 2004.
6. Katoh, K.; Shibata, H.; Suzuki, H.; Nara, A.; Ishidoh, K.; Kominami,
E.; Yoshimori, T.; Maki, M.: The ALG-2-interacting protein Alix associates
with CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular
body sorting. J. Biol. Chem. 278: 39104-39113, 2003.
7. Matsuo, H.; Chevallier, J.; Mayran, N.; Le Blanc, I.; Ferguson,
C.; Faure, J.; Blanc, N. S.; Matile, S.; Dubochet, J.; Sadoul, R.;
Parton, R. G.; Vilbois, F.; Gruenberg, J.: Role of LBPA and Alix
in multivesicular liposome formation and endosome organization. Science 303:
531-534, 2004.
8. Missotten, M.; Nichols, A.; Rieger, K.; Sadoul, R.: Alix, a novel
mouse protein undergoing calcium-dependent interaction with the apoptosis-linked-gene
2 (ALG-2) protein. Cell Death Differ. 6: 124-129, 1999.
9. Nagase, T.; Kikuno, R.; Ishikawa, K.; Hirosawa, M.; Ohara, O.:
Prediction of the coding sequences of unidentified human genes. XVI.
The complete sequences of 150 new cDNA clones from brain which code
for large proteins in vitro. DNA Res. 7: 65-73, 2000.
10. Vito, P.; Pellegrini, L.; Guiet, C.; D'Adamio, L.: Cloning of
AIP1, a novel protein that associates with the apoptosis-linked gene
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*FIELD* CN
Ada Hamosh - updated: 05/01/2013
Paul J. Converse - updated: 10/17/2011
Ada Hamosh - updated: 7/24/2007
Patricia A. Hartz - updated: 3/29/2007
Ada Hamosh - updated: 2/2/2004
*FIELD* CD
Patricia A. Hartz: 9/4/2003
*FIELD* ED
alopez: 05/01/2013
terry: 11/4/2011
mgross: 11/3/2011
terry: 10/17/2011
alopez: 7/25/2007
terry: 7/24/2007
mgross: 3/29/2007
alopez: 2/2/2004
mgross: 9/5/2003
mgross: 9/4/2003