PDC6I_HUMAN
ID PDC6I_HUMAN Reviewed; 868 AA.
AC Q8WUM4; C5MQH7; E9PFU1; Q6NUS1; Q9BX86; Q9NUN0; Q9P2H2; Q9UKL5;
DT 23-MAY-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 201.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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 cells.";
RL Differentiation 67:139-153(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RX PubMed=19906316; DOI=10.1186/1471-2164-10-518;
RA Wang P., Yu P., Gao P., Shi T., Ma D.;
RT "Discovery of novel human transcript variants by analysis of intronic
RT single-block EST with polyadenylation site.";
RL BMC Genomics 10:518-518(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS THR-309 AND 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 [4]
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 vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
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., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., 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., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANTS
RP 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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 2-23; 111-120; 216-229; 439-446; 457-469 AND 542-553,
RP CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, AND IDENTIFICATION
RP BY MASS SPECTROMETRY.
RC TISSUE=Osteosarcoma;
RA Bienvenut W.V., Glen H., Frame M.C.;
RL Submitted (MAR-2008) to UniProtKB.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 209-868 (ISOFORM 1), AND VARIANT
RP 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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 323-868 (ISOFORM 1), AND VARIANT
RP 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. The
RT complete sequences of 150 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:65-73(2000).
RN [10]
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 sorting.";
RL J. Biol. Chem. 278:39104-39113(2003).
RN [11]
RP FUNCTION IN HIV-1 BUDDING (MICROBIAL INFECTION), INTERACTION WITH CHMP4A;
RP CHMP4B AND CHMP4C, AND INTERACTION WITH HIV-1 P6 AND EIAV P9 (MICROBIAL
RP INFECTION).
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 in
RT virus budding.";
RL Cell 114:689-699(2003).
RN [12]
RP FUNCTION IN HIV-1 BUDDING (MICROBIAL INFECTION), SELF-ASSOCIATION,
RP INTERACTION WITH TSG101; 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 [13]
RP SELF-ASSOCIATION, INTERACTION WITH TSG101; CHMP4A; CHMP4B AND CHMP4C, AND
RP INTERACTION WITH EIAV P9 (MICROBIAL INFECTION).
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 sorting
RT factors by using alternative adaptor proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:12414-12419(2003).
RN [14]
RP ERRATUM OF PUBMED:14519844.
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 [15]
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 Alix
RT among the three CHMP4 isoforms.";
RL Arch. Biochem. Biophys. 421:159-165(2004).
RN [16]
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 [17]
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., Faure J.,
RA Blanc N.S., Matile S., Dubochet J., Sadoul R., Parton R.G., Vilbois F.,
RA Gruenberg J.;
RT "Role of LBPA and Alix in multivesicular liposome formation and endosome
RT organization.";
RL Science 303:531-534(2004).
RN [18]
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 (RabGAPLP) as
RT a novel Alix/AIP1-interacting protein.";
RL Biosci. Biotechnol. Biochem. 69:861-865(2005).
RN [19]
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., Bertrand E.,
RA Basyuk E.;
RT "Tsg101 and Alix interact with murine leukemia virus Gag and cooperate with
RT Nedd4 ubiquitin ligases during budding.";
RL J. Biol. Chem. 280:27004-27012(2005).
RN [20]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J.,
RA Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S.,
RA Shabanowitz J., Hearing V.J., Wu C., Appella E., 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 [21]
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 exit
RT sites by Sec31A and stabilizes the localization of Sec31A.";
RL Mol. Biol. Cell 17:4876-4887(2006).
RN [22]
RP FUNCTION IN CYTOKINESIS, SUBCELLULAR LOCATION, INTERACTION WITH CEP55 AND
RP 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., Rodesch C.K.,
RA Sundquist W.I.;
RT "Human ESCRT and ALIX proteins interact with proteins of the midbody and
RT function in cytokinesis.";
RL EMBO J. 26:4215-4227(2007).
RN [23]
RP FUNCTION IN HIV-1 BUDDING (MICROBIAL INFECTION), INTERACTION WITH CHMP4B,
RP AND MUTAGENESIS OF 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 mutants
RT by ALIX/AIP1 depends on its CHMP4 binding site.";
RL J. Virol. 81:6614-6622(2007).
RN [24]
RP FUNCTION IN CYTOKINESIS AND HIV1 RELEASE, SUBCELLULAR LOCATION, AND
RP INTERACTION WITH 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 ESCRT
RT machinery.";
RL Science 316:1908-1912(2007).
RN [25]
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 human
RT phospholipid scramblase 3: differential binding to an alternatively spliced
RT isoform and amino acid-substituted mutants.";
RL J. Biol. Chem. 283:9623-9632(2008).
RN [26]
RP FUNCTION IN CYTOKINESIS AND HIV1 RELEASE, INTERACTION WITH CEP55 AND
RP TSG101, SUBCELLULAR LOCATION, AND MUTAGENESIS OF PHE-199; ILE-212; PHE-676;
RP 717-PRO--PRO-720; 744-PRO-ARG-745; 757-ARG--PRO-759; 794-PRO--CYS-813;
RP 801-PRO-PRO-802; 803-TYR-PRO-804; 805-THR-TYR-806; 852-PRO--PRO-855 AND
RP 864-TYR-TYR-865.
RX PubMed=18641129; DOI=10.1073/pnas.0802008105;
RA Carlton J.G., Agromayor M., Martin-Serrano J.;
RT "Differential requirements for Alix and ESCRT-III in cytokinesis and HIV-1
RT release.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10541-10546(2008).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-730; THR-738 AND THR-741, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [28]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [29]
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., Shibata H.,
RA Maki M.;
RT "Penta-EF-hand protein ALG-2 functions as a Ca2+-dependent adaptor that
RT bridges Alix and TSG101.";
RL Biochem. Biophys. Res. Commun. 386:237-241(2009).
RN [30]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-215, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA 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 [31]
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 cell
RT proliferation but not migration.";
RL Cell. Signal. 22:1363-1368(2010).
RN [32]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-738 AND THR-741, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [33]
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., Buerckstuemmer T.,
RA 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 [34]
RP INTERACTION WITH ARRDC1.
RX PubMed=21191027; DOI=10.1128/jvi.02045-10;
RA Rauch S., Martin-Serrano J.;
RT "Multiple interactions between the ESCRT machinery and arrestin-related
RT proteins: implications for PPXY-dependent budding.";
RL J. Virol. 85:3546-3556(2011).
RN [35]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [36]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SDCBP AND SDC2, AND
RP MUTAGENESIS OF PHE-676.
RX PubMed=22660413; DOI=10.1038/ncb2502;
RA Baietti M.F., Zhang Z., Mortier E., Melchior A., Degeest G., Geeraerts A.,
RA Ivarsson Y., Depoortere F., Coomans C., Vermeiren E., Zimmermann P.,
RA David G.;
RT "Syndecan-syntenin-ALIX regulates the biogenesis of exosomes.";
RL Nat. Cell Biol. 14:677-685(2012).
RN [37]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-479 AND SER-481, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [38]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [39]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-745, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [40]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [41]
RP INTERACTION WITH EBOLA VIRUS PROTEIN VP40 (MICROBIAL INFECTION).
RX PubMed=25786915; DOI=10.1093/infdis/jiu838;
RA Han Z., Madara J.J., Liu Y., Liu W., Ruthel G., Freedman B.D., Harty R.N.;
RT "ALIX Rescues Budding of a Double PTAP/PPEY L-Domain Deletion Mutant of
RT Ebola VP40: A Role for ALIX in Ebola Virus Egress.";
RL J. Infect. Dis. 212:S138-S145(2015).
RN [42]
RP X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) OF 1-698, INTERACTION WITH CHMP4A;
RP HIV-1 P6; EIAV P9; TSG101; SH3GL1 AND SH3GL2, AND MUTAGENESIS OF ILE-212;
RP TYR-319; PHE-495; VAL-498; VAL-509; PHE-676; LEU-680; ILE-683; PRO-720 AND
RP 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., Hill C.P.;
RT "Structural and biochemical studies of ALIX/AIP1 and its role in retrovirus
RT budding.";
RL Cell 128:841-852(2007).
RN [43]
RP X-RAY CRYSTALLOGRAPHY (2.87 ANGSTROMS) OF 360-702, INTERACTION WITH HIV-1
RP P6, AND MUTAGENESIS OF VAL-498; VAL-509; CYS-512; PHE-676 AND 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 [44]
RP X-RAY CRYSTALLOGRAPHY (2.59 ANGSTROMS) OF 2-698 IN COMPLEX WITH HIV-1 P6,
RP X-RAY CRYSTALLOGRAPHY (2.59 ANGSTROMS) OF 2-698 IN COMPLEX WITH HIV-1 P9,
RP 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., Hill C.P.;
RT "Structural and functional studies of ALIX interactions with YPX(n)L late
RT domains of HIV-1 and EIAV.";
RL Nat. Struct. Mol. Biol. 15:43-49(2008).
RN [45]
RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 1-359 IN COMPLEX WITH CHMP4A,
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1-359 IN COMPLEX WITH CHMP4B, AND
RP X-RAY CRYSTALLOGRAPHY (2.02 ANGSTROMS) OF 1-359 IN COMPLEX 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 [46]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 797-809 IN COMPLEX WITH CEP55,
RP 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 coil in
RT CEP55.";
RL Science 322:576-580(2008).
RN [47]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 799-812 IN COMPLEX WITH PDCD6.
RX PubMed=18940611; DOI=10.1016/j.str.2008.07.012;
RA Suzuki H., Kawasaki M., Inuzuka T., Okumura M., Kakiuchi T., Shibata H.,
RA 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 [48]
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: Multifunctional protein involved in endocytosis,
CC multivesicular body biogenesis, membrane repair, cytokinesis, apoptosis
CC and maintenance of tight junction integrity. Class E VPS protein
CC involved in concentration and sorting of cargo proteins of the
CC multivesicular body (MVB) for incorporation into intralumenal vesicles
CC (ILVs) that are generated by invagination and scission from the
CC limiting membrane of the endosome. Binds to the phospholipid
CC lysobisphosphatidic acid (LBPA) which is abundant in MVBs internal
CC membranes. The MVB pathway requires the sequential function of ESCRT-O,
CC -I,-II and -III complexes (PubMed:14739459). The ESCRT machinery also
CC functions in topologically equivalent membrane fission events, such as
CC the terminal stages of cytokinesis (PubMed:17853893, PubMed:17556548).
CC Adapter for a subset of ESCRT-III proteins, such as CHMP4, to function
CC at distinct membranes. Required for completion of cytokinesis
CC (PubMed:17853893, PubMed:17556548, PubMed:18641129). May play a role in
CC the regulation of both apoptosis and cell proliferation. Regulates
CC exosome biogenesis in concert with SDC1/4 and SDCBP (PubMed:22660413).
CC By interacting with F-actin, PARD3 and TJP1 secures the proper assembly
CC and positioning of actomyosin-tight junction complex at the apical
CC sides of adjacent epithelial cells that defines a spatial membrane
CC domain essential for the maintenance of epithelial cell polarity and
CC barrier (By similarity). {ECO:0000250|UniProtKB:Q9WU78,
CC ECO:0000269|PubMed:14739459, ECO:0000269|PubMed:17556548,
CC ECO:0000269|PubMed:17853893, ECO:0000269|PubMed:18641129,
CC ECO:0000269|PubMed:22660413}.
CC -!- FUNCTION: (Microbial infection) Involved in HIV-1 virus budding. Can
CC replace TSG101 it its role of supporting HIV-1 release; this function
CC requires the interaction with CHMP4B. The ESCRT machinery also
CC functions in topologically equivalent membrane fission events, such as
CC enveloped virus budding (HIV-1 and other lentiviruses).
CC {ECO:0000269|PubMed:14505569, ECO:0000269|PubMed:14505570,
CC ECO:0000269|PubMed:14519844, ECO:0000269|PubMed:17556548,
CC ECO:0000269|PubMed:18641129}.
CC -!- SUBUNIT: Self-associates (PubMed:14505570, PubMed:14519844). Interacts
CC with SH3KBP1/CIN85 (By similarity). Interacts with PDCD6 in a calcium
CC -dependent manner (PubMed:16957052, PubMed:18256029, PubMed:18940611).
CC Interacts with TSG101 in a calcium-dependent manner; PDCD6IP
CC homooligomerization may be required for TSG101-binding
CC (PubMed:14505570, PubMed:14519844, PubMed:18641129, PubMed:19520058,
CC PubMed:17350572). Interacts with SGSM3 (PubMed:15849434). Directly
CC interacts with CHMP4A, CHMP4B and CHMP4C (PubMed:12860994,
CC PubMed:14505569, PubMed:14505570, PubMed:14519844, PubMed:14678797,
CC PubMed:14583093, PubMed:17428861, PubMed:17350572, PubMed:18511562).
CC Directly interacts with CEP55 in a 1:2 stoechiometry (PubMed:17853893,
CC PubMed:17556548, PubMed:18641129, PubMed:18948538). The interaction
CC with CEP55 is required for PDCD6IP targeting to the midbody
CC (PubMed:18641129). May interact with PDGFRB (PubMed:20494825).
CC Interacts with SH3GL1 and SH3GL2/endophilin-1 (PubMed:17350572). Forms
CC a complex with SDCBP and SDC2 (PubMed:22660413). Found in a complex
CC with F-actin, TJP1/ZO-1 and PARD3 (By similarity). Interacts with CD2AP
CC (PubMed:17853893). Interacts with ARRDC1 (PubMed:21191027).
CC {ECO:0000250|UniProtKB:Q9QZA2, ECO:0000250|UniProtKB:Q9WU78,
CC ECO:0000269|PubMed:12860994, ECO:0000269|PubMed:14505569,
CC ECO:0000269|PubMed:14505570, ECO:0000269|PubMed:14519844,
CC ECO:0000269|PubMed:14583093, ECO:0000269|PubMed:14678797,
CC ECO:0000269|PubMed:15849434, ECO:0000269|PubMed:16957052,
CC ECO:0000269|PubMed:17350572, ECO:0000269|PubMed:17428861,
CC ECO:0000269|PubMed:17556548, ECO:0000269|PubMed:17853893,
CC ECO:0000269|PubMed:18256029, ECO:0000269|PubMed:18511562,
CC ECO:0000269|PubMed:18641129, ECO:0000269|PubMed:18940611,
CC ECO:0000269|PubMed:18948538, ECO:0000269|PubMed:19520058,
CC ECO:0000269|PubMed:20494825, ECO:0000269|PubMed:21191027,
CC ECO:0000269|PubMed:22660413}.
CC -!- SUBUNIT: (Microbial infection) Interacts with HIV-1 p6
CC (PubMed:14505569, PubMed:17350572, PubMed:17277784, PubMed:18066081).
CC Interacts with HIV-1 p9 (PubMed:18066081).
CC {ECO:0000269|PubMed:14505569, ECO:0000269|PubMed:14519844,
CC ECO:0000269|PubMed:17277784, ECO:0000269|PubMed:17350572,
CC ECO:0000269|PubMed:18066081}.
CC -!- SUBUNIT: (Microbial infection) Interacts with EIAV p9.
CC {ECO:0000269|PubMed:14505569, ECO:0000269|PubMed:14519844,
CC ECO:0000269|PubMed:17350572, ECO:0000269|PubMed:18066081}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Murine leukemia virus Gag
CC polyprotein (via LYPX(n)L motif). {ECO:0000269|PubMed:15908698}.
CC -!- SUBUNIT: (Microbial infection) Interacts with ebola virus protein VP40
CC (via YPx(n)L/I motif). {ECO:0000269|PubMed:15908698}.
CC -!- INTERACTION:
CC Q8WUM4; Q9Y5K6: CD2AP; NbExp=3; IntAct=EBI-310624, EBI-298152;
CC Q8WUM4; Q53EZ4: CEP55; NbExp=16; IntAct=EBI-310624, EBI-747776;
CC Q8WUM4; Q9BY43: CHMP4A; NbExp=3; IntAct=EBI-310624, EBI-747981;
CC Q8WUM4; Q9H444: CHMP4B; NbExp=6; IntAct=EBI-310624, EBI-749627;
CC Q8WUM4; Q96CF2: CHMP4C; NbExp=3; IntAct=EBI-310624, EBI-1221015;
CC Q8WUM4; P06241: FYN; NbExp=6; IntAct=EBI-310624, EBI-515315;
CC Q8WUM4; P08631: HCK; NbExp=4; IntAct=EBI-310624, EBI-346340;
CC Q8WUM4; P17931: LGALS3; NbExp=2; IntAct=EBI-310624, EBI-1170392;
CC Q8WUM4; O75340: PDCD6; NbExp=12; IntAct=EBI-310624, EBI-352915;
CC Q8WUM4; Q9D8B3: Chmp4b; Xeno; NbExp=2; IntAct=EBI-310624, EBI-8322817;
CC Q8WUM4; P03347: gag; Xeno; NbExp=2; IntAct=EBI-310624, EBI-1220741;
CC Q8WUM4; P69730: gag; Xeno; NbExp=2; IntAct=EBI-310624, EBI-1220941;
CC Q8WUM4; P09022: Hoxa1; Xeno; NbExp=3; IntAct=EBI-310624, EBI-3957603;
CC Q8WUM4; Q90VU7: nef; Xeno; NbExp=4; IntAct=EBI-310624, EBI-7460704;
CC Q8WUM4; PRO_0000308465 [P29991]; Xeno; NbExp=3; IntAct=EBI-310624, EBI-8826747;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q9QZA2}. Melanosome
CC {ECO:0000269|PubMed:17081065}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000269|PubMed:17556548,
CC ECO:0000269|PubMed:17853893}. Secreted, extracellular exosome
CC {ECO:0000269|PubMed:22660413}. Cell junction, tight junction
CC {ECO:0000250|UniProtKB:Q9WU78}. Midbody, Midbody ring
CC {ECO:0000269|PubMed:17853893, ECO:0000269|PubMed:18641129}.
CC Note=Identified by mass spectrometry in melanosome fractions from stage
CC I to stage IV. Colocalized with CEP55 at centrosomes of non-dividing
CC cells. Component of the actomyosin-tight junction complex (By
CC similarity). PDCD6IP targeting to the midbody requires the interaction
CC with CEP55 (PubMed:18641129). {ECO:0000250|UniProtKB:Q9QZA2,
CC ECO:0000250|UniProtKB:Q9WU78, ECO:0000269|PubMed:17081065,
CC ECO:0000269|PubMed:17556548, ECO:0000269|PubMed:17853893,
CC ECO:0000269|PubMed:18641129}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8WUM4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8WUM4-2; Sequence=VSP_044860;
CC Name=3;
CC IsoId=Q8WUM4-3; Sequence=VSP_057190, VSP_057191;
CC -!- PTM: May be phosphorylated on tyrosine residues by activated PDGFRB.
CC {ECO:0000269|PubMed:20494825}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA92092.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF349951; AAK20398.1; -; mRNA.
DR EMBL; GQ131806; ACS12984.1; -; 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 CCDS; CCDS2660.1; -. [Q8WUM4-1]
DR CCDS; CCDS54561.1; -. [Q8WUM4-2]
DR RefSeq; NP_001155901.1; NM_001162429.2. [Q8WUM4-2]
DR RefSeq; NP_001243121.1; NM_001256192.1. [Q8WUM4-3]
DR RefSeq; NP_037506.2; NM_013374.5. [Q8WUM4-1]
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; 3WUV; X-ray; 2.79 A; C/F/I/L/O/R=796-810.
DR PDB; 4JJY; X-ray; 6.50 A; A/B=355-708.
DR PDB; 5V3R; X-ray; 1.91 A; A=1-359.
DR PDB; 5WA1; X-ray; 1.87 A; A=1-358.
DR PDB; 6KP3; X-ray; 2.20 A; A=1-359.
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; 3WUV; -.
DR PDBsum; 4JJY; -.
DR PDBsum; 5V3R; -.
DR PDBsum; 5WA1; -.
DR PDBsum; 6KP3; -.
DR AlphaFoldDB; Q8WUM4; -.
DR SMR; Q8WUM4; -.
DR BioGRID; 115332; 182.
DR ComplexPortal; CPX-3282; Syndecan-1-syntenin-1-ALIX complex.
DR DIP; DIP-29327N; -.
DR IntAct; Q8WUM4; 95.
DR MINT; Q8WUM4; -.
DR STRING; 9606.ENSP00000411825; -.
DR MoonDB; Q8WUM4; Predicted.
DR GlyGen; Q8WUM4; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q8WUM4; -.
DR MetOSite; Q8WUM4; -.
DR PhosphoSitePlus; Q8WUM4; -.
DR SwissPalm; Q8WUM4; -.
DR BioMuta; PDCD6IP; -.
DR DMDM; 31076831; -.
DR UCD-2DPAGE; Q8WUM4; -.
DR CPTAC; CPTAC-419; -.
DR CPTAC; CPTAC-420; -.
DR EPD; Q8WUM4; -.
DR jPOST; Q8WUM4; -.
DR MassIVE; Q8WUM4; -.
DR MaxQB; Q8WUM4; -.
DR PaxDb; Q8WUM4; -.
DR PeptideAtlas; Q8WUM4; -.
DR PRIDE; Q8WUM4; -.
DR ProteomicsDB; 20178; -.
DR ProteomicsDB; 74695; -. [Q8WUM4-1]
DR Antibodypedia; 2777; 391 antibodies from 39 providers.
DR DNASU; 10015; -.
DR Ensembl; ENST00000307296.8; ENSP00000307387.3; ENSG00000170248.15. [Q8WUM4-1]
DR Ensembl; ENST00000457054.6; ENSP00000411825.2; ENSG00000170248.15. [Q8WUM4-2]
DR GeneID; 10015; -.
DR KEGG; hsa:10015; -.
DR MANE-Select; ENST00000307296.8; ENSP00000307387.3; NM_013374.6; NP_037506.2.
DR UCSC; uc003cfx.5; human. [Q8WUM4-1]
DR CTD; 10015; -.
DR DisGeNET; 10015; -.
DR GeneCards; PDCD6IP; -.
DR HGNC; HGNC:8766; PDCD6IP.
DR HPA; ENSG00000170248; Low tissue specificity.
DR MIM; 608074; gene.
DR neXtProt; NX_Q8WUM4; -.
DR OpenTargets; ENSG00000170248; -.
DR PharmGKB; PA33116; -.
DR VEuPathDB; HostDB:ENSG00000170248; -.
DR eggNOG; KOG2220; Eukaryota.
DR GeneTree; ENSGT01050000245038; -.
DR HOGENOM; CLU_007181_2_0_1; -.
DR InParanoid; Q8WUM4; -.
DR OMA; SEWIHHM; -.
DR OrthoDB; 550620at2759; -.
DR PhylomeDB; Q8WUM4; -.
DR TreeFam; TF323502; -.
DR PathwayCommons; Q8WUM4; -.
DR Reactome; R-HSA-162588; Budding and maturation of HIV virion.
DR Reactome; R-HSA-5210891; Uptake and function of anthrax toxins.
DR Reactome; R-HSA-5213460; RIPK1-mediated regulated necrosis.
DR Reactome; R-HSA-5675482; Regulation of necroptotic cell death.
DR SignaLink; Q8WUM4; -.
DR SIGNOR; Q8WUM4; -.
DR BioGRID-ORCS; 10015; 228 hits in 1086 CRISPR screens.
DR ChiTaRS; PDCD6IP; human.
DR EvolutionaryTrace; Q8WUM4; -.
DR GeneWiki; PDCD6IP; -.
DR GenomeRNAi; 10015; -.
DR Pharos; Q8WUM4; Tbio.
DR PRO; PR:Q8WUM4; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q8WUM4; protein.
DR Bgee; ENSG00000170248; Expressed in calcaneal tendon and 209 other tissues.
DR ExpressionAtlas; Q8WUM4; baseline and differential.
DR Genevisible; Q8WUM4; HS.
DR GO; GO:0042641; C:actomyosin; ISS:UniProtKB.
DR GO; GO:0005923; C:bicellular tight junction; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070971; C:endoplasmic reticulum exit site; IMP:UniProtKB.
DR GO; GO:0005768; C:endosome; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB.
DR GO; GO:1903561; C:extracellular vesicle; HDA:UniProtKB.
DR GO; GO:0090543; C:Flemming body; IDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0001772; C:immunological synapse; IDA:BHF-UCL.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
DR GO; GO:0048306; F:calcium-dependent protein binding; IPI:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR GO; GO:0031871; F:proteinase activated receptor binding; IPI:UniProtKB.
DR GO; GO:0000915; P:actomyosin contractile ring assembly; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0070830; P:bicellular tight junction assembly; ISS:UniProtKB.
DR GO; GO:0045199; P:maintenance of epithelial cell apical/basal polarity; ISS:UniProtKB.
DR GO; GO:0061952; P:midbody abscission; IMP:UniProtKB.
DR GO; GO:0000281; P:mitotic cytokinesis; IDA:UniProtKB.
DR GO; GO:0036258; P:multivesicular body assembly; NAS:ParkinsonsUK-UCL.
DR GO; GO:0071985; P:multivesicular body sorting pathway; IEA:InterPro.
DR GO; GO:1903543; P:positive regulation of exosomal secretion; IMP:UniProtKB.
DR GO; GO:1903553; P:positive regulation of extracellular exosome assembly; IMP:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; IDA:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0010824; P:regulation of centrosome duplication; IMP:UniProtKB.
DR GO; GO:1903551; P:regulation of extracellular exosome assembly; IMP:UniProtKB.
DR GO; GO:0090559; P:regulation of membrane permeability; ISS:UniProtKB.
DR GO; GO:0090611; P:ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway; IMP:UniProtKB.
DR GO; GO:0046755; P:viral budding; IDA:UniProtKB.
DR GO; GO:0039702; P:viral budding via host ESCRT complex; IGI:UniProtKB.
DR Gene3D; 1.25.40.280; -; 1.
DR InterPro; IPR025304; ALIX_V_dom.
DR InterPro; IPR045251; BRO1-like.
DR InterPro; IPR004328; BRO1_dom.
DR InterPro; IPR038499; BRO1_sf.
DR PANTHER; PTHR23030; PTHR23030; 1.
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; Cell cycle;
KW Cell division; Cell junction; Cytoplasm; Cytoskeleton;
KW Direct protein sequencing; Host-virus interaction; Methylation;
KW Phosphoprotein; Protein transport; Reference proteome; Secreted;
KW Tight junction; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.7, ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:25944712"
FT CHAIN 2..868
FT /note="Programmed cell death 6-interacting protein"
FT /id="PRO_0000218891"
FT DOMAIN 3..392
FT /note="BRO1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00526"
FT REGION 176..868
FT /note="Interaction with EIAV p9"
FT REGION 176..503
FT /note="Interaction with CHMP4A, CHMP4B and CHMP4C"
FT REGION 418..868
FT /note="Interaction with SDCBP"
FT /evidence="ECO:0000269|PubMed:22660413"
FT REGION 503..868
FT /note="Self-association"
FT REGION 713..809
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 717..720
FT /note="Interaction with TSG101"
FT REGION 801..806
FT /note="Interaction with CEP55"
FT /evidence="ECO:0000269|PubMed:18641129"
FT REGION 832..868
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 864..868
FT /note="Essential to promote virus budding"
FT COMPBIAS 714..728
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 735..767
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 788..809
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 838..868
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|Ref.7, ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:25944712"
FT MOD_RES 215
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 479
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 481
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 730
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 738
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 741
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 745
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT VAR_SEQ 239
FT /note="K -> KYFYFQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_044860"
FT VAR_SEQ 240..271
FT /note="EVFPVLAAKHCIMQANAEYHQSILAKQQKKFG -> VSYCFYKHLLTLHVKY
FT LDFFVYKKQVETYKEI (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:19906316"
FT /id="VSP_057190"
FT VAR_SEQ 272..868
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:19906316"
FT /id="VSP_057191"
FT VARIANT 7
FT /note="V -> M (in dbSNP:rs11554560)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_068975"
FT VARIANT 309
FT /note="A -> T (in dbSNP:rs3792594)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_053017"
FT VARIANT 378
FT /note="V -> I (in dbSNP:rs3203777)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_053018"
FT VARIANT 429
FT /note="G -> S (in dbSNP:rs76608858)"
FT /evidence="ECO:0000269|PubMed:22073189"
FT /id="VAR_069765"
FT VARIANT 550
FT /note="N -> S (in dbSNP:rs9813017)"
FT /evidence="ECO:0000269|PubMed:10718198,
FT ECO:0000269|PubMed:11683497"
FT /id="VAR_053019"
FT VARIANT 638
FT /note="K -> E (in dbSNP:rs3183982)"
FT /id="VAR_053020"
FT VARIANT 730
FT /note="S -> L (in dbSNP:rs1127732)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_024381"
FT MUTAGEN 199
FT /note="F->D: Does not support cytokinesis; loss of normal
FT midbody formation; loss of CHMP4A-, CHMP4B- and CHMP4C-
FT binding in a yeast two-hybrid assay; no effect on
FT localization to the midbody; abolishes rescue of PTAP-type
FT L domain-deficient HIV-1 p6."
FT /evidence="ECO:0000269|PubMed:17428861,
FT ECO:0000269|PubMed:18641129"
FT MUTAGEN 212
FT /note="I->D: Does not support cytokinesis; loss of normal
FT midbody formation; loss of CHMP4A-, CHMP4B- and CHMP4C-
FT binding in a yeast two-hybrid assay; impairs rescue of
FT PTAP-type L domain-deficient HIV-1 p6; no effect on
FT localization to the midbody."
FT /evidence="ECO:0000269|PubMed:17350572,
FT ECO:0000269|PubMed:17853893, ECO:0000269|PubMed:18641129"
FT MUTAGEN 216
FT /note="L->D: Abolishes interaction with CHMP4B and
FT abolishes rescue of PTAP-type L domain-deficient HIV-1 p6."
FT /evidence="ECO:0000269|PubMed:17428861"
FT MUTAGEN 317
FT /note="F->A: Diminishes rescue of PTAP-type L domain-
FT deficient HIV-1 p6."
FT /evidence="ECO:0000269|PubMed:17428861"
FT MUTAGEN 318
FT /note="I->A: Greatly diminishes rescue of PTAP-type L
FT domain--deficient HIV-1 p6."
FT /evidence="ECO:0000269|PubMed:17428861"
FT MUTAGEN 319
FT /note="Y->A: Greatly diminishes rescue of PTAP-type L
FT domain-deficient HIV-1 p6."
FT /evidence="ECO:0000269|PubMed:17350572,
FT ECO:0000269|PubMed:17428861"
FT MUTAGEN 319
FT /note="Y->F: No effect on rescue of PTAP-type L domain-
FT deficient HIV-1 p6."
FT /evidence="ECO:0000269|PubMed:17350572,
FT ECO:0000269|PubMed:17428861"
FT MUTAGEN 495
FT /note="F->D: Impairs rescue of PTAP-type L domain-deficient
FT HIV-1 p6."
FT /evidence="ECO:0000269|PubMed:17350572"
FT MUTAGEN 498
FT /note="V->D: Reduces interaction with HIV-1 p6 and EIAV p9;
FT abolishes rescue of PTAP-type L domain-deficient HIV-1 p6."
FT /evidence="ECO:0000269|PubMed:17277784,
FT ECO:0000269|PubMed:17350572"
FT MUTAGEN 509
FT /note="V->D: Abolishes interaction with HIV-1 p6; impairs
FT rescue of PTAP-type L domain-deficient HIV-1 p6."
FT /evidence="ECO:0000269|PubMed:17277784,
FT ECO:0000269|PubMed:17350572"
FT MUTAGEN 512
FT /note="C->A: No effect on interaction with HIV-1 p6;
FT impairs rescue of PTAP-type L domain-deficient HIV-1 p6."
FT /evidence="ECO:0000269|PubMed:17277784"
FT MUTAGEN 676
FT /note="F->A: Loss of interaction with SDCBP."
FT /evidence="ECO:0000269|PubMed:22660413"
FT MUTAGEN 676
FT /note="F->D: Abolishes interaction with HIV-1 p6 and EIAV
FT p9; abolishes rescue of PTAP-type L domain-deficient HIV-1
FT p6; no effect on cytokinesis, nor on midbody formation."
FT /evidence="ECO:0000269|PubMed:17277784,
FT ECO:0000269|PubMed:17350572, ECO:0000269|PubMed:17853893,
FT ECO:0000269|PubMed:18641129"
FT MUTAGEN 680
FT /note="L->D: Impairs rescue of PTAP-type L domain-deficient
FT HIV-1 p6."
FT /evidence="ECO:0000269|PubMed:17350572"
FT MUTAGEN 683
FT /note="I->A: No effect on interaction with HIV-1 p6."
FT /evidence="ECO:0000269|PubMed:17277784,
FT ECO:0000269|PubMed:17350572"
FT MUTAGEN 683
FT /note="I->D: Reduces interaction with HIV-1 p6 and EIAV p9;
FT abolishes rescue of PTAP-type L domain-deficient HIV-1 p6."
FT /evidence="ECO:0000269|PubMed:17277784,
FT ECO:0000269|PubMed:17350572"
FT MUTAGEN 717..720
FT /note="PSAP->AAAA: No effect on midbody formation, nor on
FT cytokinesis; reduced TSG101-binding; no effect on HIV-1
FT release. Almost complete loss of TSG101-binding and
FT impaired cytokinesis; when associated with 852-A--A-855."
FT /evidence="ECO:0000269|PubMed:18641129"
FT MUTAGEN 720
FT /note="P->L: Abolishes interaction with TSG101; no effect
FT on rescue of PTAP-type L domain-deficient HIV-1 p6."
FT /evidence="ECO:0000269|PubMed:17350572"
FT MUTAGEN 744..745
FT /note="PR->VD: No effect on midbody formation; loss of
FT CD2AP- and SH3KBP1-binding in a yeast two-hybrid assay; no
FT effect on HIV-1 release."
FT /evidence="ECO:0000269|PubMed:18641129"
FT MUTAGEN 757..759
FT /note="RPP->GAA: No effect on midbody formation; loss of
FT SH3GL2-binding in a yeast two-hybrid assay."
FT /evidence="ECO:0000269|PubMed:18641129"
FT MUTAGEN 757..758
FT /note="RP->AA: Abolishes interaction with SH3GL1 and
FT SH3GL2; no effect on rescue of PTAP-type L domain-deficient
FT HIV-1 p6."
FT /evidence="ECO:0000269|PubMed:17350572"
FT MUTAGEN 794..813
FT /note="Missing: Does not support the formation of normal
FT midbodies; loss of localization to the midbody; loss of
FT CD2AP-, CEP55-, SH3GL2-, SH3KBP1-, TSG101-binding in a
FT yeast two-hybrid assay."
FT /evidence="ECO:0000269|PubMed:18641129"
FT MUTAGEN 800..802
FT /note="GPP->AAA: Abolishes interaction with CEP55; inhibits
FT support of cytokinesis."
FT /evidence="ECO:0000269|PubMed:17853893"
FT MUTAGEN 801..802
FT /note="PP->VD: Loss of midbody localization; does not
FT support cytokinesis; loss of CEP55-binding in a yeast two-
FT hybrid assay; no effect on HIV-1 release."
FT /evidence="ECO:0000269|PubMed:18641129"
FT MUTAGEN 801
FT /note="P->A: Decreased interaction with CEP55."
FT /evidence="ECO:0000269|PubMed:18948538"
FT MUTAGEN 802
FT /note="P->A: Decreased interaction with CEP55."
FT /evidence="ECO:0000269|PubMed:18948538"
FT MUTAGEN 803..804
FT /note="YP->VD: No effect on CEP55-binding in a yeast two-
FT hybrid assay."
FT /evidence="ECO:0000269|PubMed:18641129"
FT MUTAGEN 805..806
FT /note="TY->VD: Loss of CEP55-binding in a yeast two-hybrid
FT assay."
FT /evidence="ECO:0000269|PubMed:18641129"
FT MUTAGEN 806
FT /note="Y->A: Abolishes interaction with CEP55."
FT /evidence="ECO:0000269|PubMed:18948538"
FT MUTAGEN 852..855
FT /note="PSYP->ASAA: Loss of homoologimerization and reduced
FT TSG101-binding; decreased HIV-1 release; no effect on
FT cytokinesis. Almost complete loss of TSG101-binding and
FT impaired cytokinesis; when associated with 717-A--A-720."
FT /evidence="ECO:0000269|PubMed:18641129"
FT MUTAGEN 864..865
FT /note="YY->AA: Loss of homooligomerization; reduced TSG101-
FT binding; impaired HIV-1 release."
FT /evidence="ECO:0000269|PubMed:18641129"
FT CONFLICT 580
FT /note="M -> T (in Ref. 8; BAA92092)"
FT /evidence="ECO:0000305"
FT HELIX 18..28
FT /evidence="ECO:0007829|PDB:5WA1"
FT STRAND 29..31
FT /evidence="ECO:0007829|PDB:6KP3"
FT STRAND 32..34
FT /evidence="ECO:0007829|PDB:2OEV"
FT HELIX 35..54
FT /evidence="ECO:0007829|PDB:5WA1"
FT HELIX 62..76
FT /evidence="ECO:0007829|PDB:5WA1"
FT TURN 77..88
FT /evidence="ECO:0007829|PDB:5WA1"
FT STRAND 93..96
FT /evidence="ECO:0007829|PDB:5WA1"
FT STRAND 98..100
FT /evidence="ECO:0007829|PDB:2R05"
FT TURN 104..106
FT /evidence="ECO:0007829|PDB:5V3R"
FT STRAND 110..114
FT /evidence="ECO:0007829|PDB:5WA1"
FT HELIX 116..136
FT /evidence="ECO:0007829|PDB:5WA1"
FT STRAND 140..142
FT /evidence="ECO:0007829|PDB:2OEV"
FT HELIX 143..170
FT /evidence="ECO:0007829|PDB:5WA1"
FT STRAND 171..173
FT /evidence="ECO:0007829|PDB:2OEV"
FT HELIX 177..179
FT /evidence="ECO:0007829|PDB:5WA1"
FT HELIX 181..205
FT /evidence="ECO:0007829|PDB:5WA1"
FT HELIX 210..231
FT /evidence="ECO:0007829|PDB:5WA1"
FT HELIX 241..266
FT /evidence="ECO:0007829|PDB:5WA1"
FT HELIX 270..290
FT /evidence="ECO:0007829|PDB:5WA1"
FT TURN 292..294
FT /evidence="ECO:0007829|PDB:5WA1"
FT HELIX 298..317
FT /evidence="ECO:0007829|PDB:5WA1"
FT HELIX 326..328
FT /evidence="ECO:0007829|PDB:5WA1"
FT STRAND 348..350
FT /evidence="ECO:0007829|PDB:3C3R"
FT TURN 354..357
FT /evidence="ECO:0007829|PDB:5V3R"
FT HELIX 361..398
FT /evidence="ECO:0007829|PDB:2XS1"
FT TURN 399..402
FT /evidence="ECO:0007829|PDB:2XS1"
FT HELIX 403..406
FT /evidence="ECO:0007829|PDB:2XS1"
FT STRAND 408..412
FT /evidence="ECO:0007829|PDB:2R05"
FT HELIX 415..426
FT /evidence="ECO:0007829|PDB:2XS1"
FT TURN 427..429
FT /evidence="ECO:0007829|PDB:2XS1"
FT HELIX 430..471
FT /evidence="ECO:0007829|PDB:2XS1"
FT TURN 473..475
FT /evidence="ECO:0007829|PDB:2XS1"
FT HELIX 481..514
FT /evidence="ECO:0007829|PDB:2XS1"
FT HELIX 517..523
FT /evidence="ECO:0007829|PDB:2XS1"
FT HELIX 527..532
FT /evidence="ECO:0007829|PDB:2XS1"
FT HELIX 541..543
FT /evidence="ECO:0007829|PDB:2XS1"
FT HELIX 547..575
FT /evidence="ECO:0007829|PDB:2XS1"
FT HELIX 581..590
FT /evidence="ECO:0007829|PDB:2XS1"
FT STRAND 591..593
FT /evidence="ECO:0007829|PDB:2R05"
FT HELIX 596..639
FT /evidence="ECO:0007829|PDB:2XS1"
FT HELIX 644..697
FT /evidence="ECO:0007829|PDB:2XS1"
FT STRAND 802..805
FT /evidence="ECO:0007829|PDB:3E1R"
FT TURN 810..813
FT /evidence="ECO:0007829|PDB:2ZNE"
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
