ID   RBP1_HUMAN              Reviewed;         655 AA.
AC   Q15311;
DT   15-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   09-FEB-2010, entry version 84.
DE   RecName: Full=RalA-binding protein 1;
DE            Short=RalBP1;
DE   AltName: Full=Ral-interacting protein 1;
DE   AltName: Full=76 kDa Ral-interacting protein;
DE   AltName: Full=Dinitrophenyl S-glutathione ATPase;
DE            Short=DNP-SG ATPase;
GN   Name=RALBP1; Synonyms=RLIP1, RLIP76;
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], FUNCTION, AND INTERACTION WITH RALA.
RX   MEDLINE=95403450; PubMed=7673236; DOI=10.1074/jbc.270.38.22473;
RA   Jullien-Flores V., Dorseuil O., Romero F., Letourneur F.,
RA   Saragosti S., Berger R., Tavitian A., Gacon G., Camonis J.H.;
RT   "Bridging Ral GTPase to Rho pathways. RLIP76, a Ral effector with
RT   CDC42/Rac GTPase-activating protein activity.";
RL   J. Biol. Chem. 270:22473-22477(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION, AND PROTEIN SEQUENCE OF
RP   2-15; 409-438 AND 472-486.
RC   TISSUE=Bone marrow;
RX   MEDLINE=20384219; PubMed=10924126; DOI=10.1021/bi992964c;
RA   Awasthi S., Cheng J., Singhal S.S., Saini M.K., Pandya U., Pikula S.,
RA   Bandorowicz-Pikula J., Singh S.V., Zimniak P., Awasthi Y.C.;
RT   "Novel function of human RLIP76: ATP-dependent transport of
RT   glutathione conjugates and doxorubicin.";
RL   Biochemistry 39:9327-9334(2000).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Placenta;
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   [4]
RP   INTERACTION WITH REPS2.
RC   TISSUE=Brain;
RX   MEDLINE=98086250; PubMed=9422736; DOI=10.1074/jbc.273.2.814;
RA   Ikeda M., Ishida O., Hinoi T., Kishida S., Kikuchi A.;
RT   "Identification and characterization of a novel protein interacting
RT   with Ral-binding protein 1, a putative effector protein of Ral.";
RL   J. Biol. Chem. 273:814-821(1998).
RN   [5]
RP   FUNCTION, AND INTERACTION WITH CCNB1; CDC2; EPN1; NUMB AND TFAP2A.
RX   PubMed=12775724; DOI=10.1074/jbc.M302191200;
RA   Rosse C., L'Hoste S., Offner N., Picard A., Camonis J.;
RT   "RLIP, an effector of the Ral GTPases, is a platform for Cdk1 to
RT   phosphorylate epsin during the switch off of endocytosis in mitosis.";
RL   J. Biol. Chem. 278:30597-30604(2003).
RN   [6]
RP   FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   MEDLINE=21331153; PubMed=11437348; DOI=10.1006/abbi.2001.2395;
RA   Sharma R., Singhal S.S., Cheng J., Yang Y., Sharma A., Zimniak P.,
RA   Awasthi S., Awasthi Y.C.;
RT   "RLIP76 is the major ATP-dependent transporter of glutathione-
RT   conjugates and doxorubicin in human erythrocytes.";
RL   Arch. Biochem. Biophys. 391:171-179(2001).
RN   [7]
RP   INTERACTION WITH DAB2IP.
RX   PubMed=15310755; DOI=10.1074/jbc.M407617200;
RA   Zhang H., Zhang R., Luo Y., D'Alessio A., Pober J.S., Min W.;
RT   "AIP1/DAB2IP, a novel member of the Ras-GAP family, transduces TRAF2-
RT   induced ASK1-JNK activation.";
RL   J. Biol. Chem. 279:44955-44965(2004).
RN   [8]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-92 AND SER-93, AND MASS
RP   SPECTROMETRY.
RC   TISSUE=Epithelium;
RX   PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA   Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA   Mann M.;
RT   "Global, in vivo, and site-specific phosphorylation dynamics in
RT   signaling networks.";
RL   Cell 127:635-648(2006).
RN   [9]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-27 AND SER-29, AND MASS
RP   SPECTROMETRY.
RC   TISSUE=Platelet;
RX   PubMed=18088087; DOI=10.1021/pr0704130;
RA   Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA   Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT   "Phosphoproteome of resting human platelets.";
RL   J. Proteome Res. 7:526-534(2008).
RN   [10]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-34 AND SER-62, AND MASS
RP   SPECTROMETRY.
RX   PubMed=18220336; DOI=10.1021/pr0705441;
RA   Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D.,
RA   Yates J.R. III;
RT   "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT   efficient phosphoproteomic analysis.";
RL   J. Proteome Res. 7:1346-1351(2008).
RN   [11]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-92 AND SER-93, AND MASS
RP   SPECTROMETRY.
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   [12]
RP   IDENTIFICATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RA   Colinge J., Superti-Furga G., Bennett K.L.;
RL   Submitted (OCT-2008) to UniProtKB.
RN   [13]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-11; SER-29; SER-30;
RP   SER-34; SER-92; SER-93; TYR-270; THR-280 AND SER-463, AND MASS
RP   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   [14]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-29; SER-92; SER-93 AND
RP   SER-645, AND MASS SPECTROMETRY.
RX   PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA   Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA   Mann M., Daub H.;
RT   "Large-scale proteomics analysis of the human kinome.";
RL   Mol. Cell. Proteomics 8:1751-1764(2009).
RN   [15]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-92 AND SER-93, AND MASS
RP   SPECTROMETRY.
RC   TISSUE=T-cell;
RX   PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA   Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA   Rodionov V., Han D.K.;
RT   "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT   reveals system-wide modulation of protein-protein interactions.";
RL   Sci. Signal. 2:RA46-RA46(2009).
CC   -!- FUNCTION: Can activate specifically hydrolysis of GTP bound to
CC       RAC1 and CDC42, but not RALA. Mediates ATP-dependent transport of
CC       S-(2,4-dinitrophenyl)-glutathione (DNP-SG) and doxorubicin (DOX)
CC       and is the major ATP-dependent transporter of glutathione
CC       conjugates of electrophiles (GS-E) and DOX in erythrocytes. Can
CC       catalyze transport of glutathione conjugates and xenobiotics, and
CC       may contribute to the multidrug resistance phenomenon. Serves as a
CC       scaffold protein that brings together proteins forming an
CC       endocytotic complex during interphase and also with CDC2 to switch
CC       off endocytosis, One of its substrates would be EPN1/Epsin.
CC   -!- SUBUNIT: Interacts with the GTP-bound form of RALA, RALB, CDC42
CC       and RAC1. Interacts with REPS1 and REPS2 and this does not affect
CC       the Ral-binding activity. Interacts with DAB2IP. Interacts with
CC       catalytically active CCNB1 and CDC2 during mitosis. Interacts with
CC       EPN1, NUMB and TFAP2A during interphase and mitosis.
CC   -!- SUBCELLULAR LOCATION: Membrane; Peripheral membrane protein.
CC   -!- TISSUE SPECIFICITY: Expressed ubiquitously but at low levels.
CC       Shows a strong expression in the erythrocytes.
CC   -!- SIMILARITY: Contains 1 Rho-GAP domain.
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DR   EMBL; L42542; AAB00103.1; -; mRNA.
DR   EMBL; BC013126; AAH13126.1; -; mRNA.
DR   IPI; IPI00009544; -.
DR   PIR; F59435; F59435.
DR   RefSeq; NP_006779.1; -.
DR   UniGene; Hs.528993; -.
DR   UniGene; Hs.719181; -.
DR   SMR; Q15311; 184-352.
DR   IntAct; Q15311; 3.
DR   STRING; Q15311; -.
DR   TCDB; 9.A.1.1.1; non ABC multidrug exporter (N-MDE) family.
DR   PhosphoSite; Q15311; -.
DR   PeptideAtlas; Q15311; -.
DR   PRIDE; Q15311; -.
DR   Ensembl; ENST00000019317; ENSP00000019317; ENSG00000017797; Homo sapiens.
DR   Ensembl; ENST00000383432; ENSP00000372924; ENSG00000017797; Homo sapiens.
DR   GeneID; 10928; -.
DR   KEGG; hsa:10928; -.
DR   UCSC; uc002kob.1; human.
DR   CTD; 10928; -.
DR   GeneCards; GC18P009465; -.
DR   H-InvDB; HIX0014325; -.
DR   HGNC; HGNC:9841; RALBP1.
DR   MIM; 605801; gene.
DR   PharmGKB; PA34199; -.
DR   eggNOG; prNOG10919; -.
DR   HOGENOM; HBG713891; -.
DR   HOVERGEN; Q15311; -.
DR   InParanoid; Q15311; -.
DR   OMA; TQAGIKE; -.
DR   OrthoDB; EOG94BDMF; -.
DR   PhylomeDB; Q15311; -.
DR   Reactome; REACT_11044; Signaling by Rho GTPases.
DR   NextBio; 41515; -.
DR   ArrayExpress; Q15311; -.
DR   Bgee; Q15311; -.
DR   CleanEx; HS_RALBP1; -.
DR   Genevestigator; Q15311; -.
DR   GermOnline; ENSG00000017797; Homo sapiens.
DR   GO; GO:0019898; C:extrinsic to membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005622; C:intracellular; IEA:InterPro.
DR   GO; GO:0043492; F:ATPase activity, coupled to movement of sub...; IDA:UniProtKB.
DR   GO; GO:0030675; F:Rac GTPase activator activity; IDA:UniProtKB.
DR   GO; GO:0048365; F:Rac GTPase binding; IPI:UniProtKB.
DR   GO; GO:0017160; F:Ral GTPase binding; IPI:UniProtKB.
DR   GO; GO:0006935; P:chemotaxis; TAS:ProtInc.
DR   GO; GO:0043089; P:positive regulation of Cdc42 GTPase activity; IDA:UniProtKB.
DR   GO; GO:0007264; P:small GTPase mediated signal transduction; IPI:UniProtKB.
DR   GO; GO:0006810; P:transport; IDA:UniProtKB.
DR   InterPro; IPR008936; Rho_GTPase_activation_prot.
DR   InterPro; IPR000198; RhoGAP.
DR   Gene3D; G3DSA:1.10.555.10; RhoGAP; 1.
DR   Pfam; PF00620; RhoGAP; 1.
DR   SMART; SM00324; RhoGAP; 1.
DR   PROSITE; PS50238; RHOGAP; 1.
PE   1: Evidence at protein level;
KW   Complete proteome; Direct protein sequencing; GTPase activation;
KW   Membrane; Phosphoprotein; Polymorphism; Transport.
FT   INIT_MET      1      1       Removed.
FT   CHAIN         2    655       RalA-binding protein 1.
FT                                /FTId=PRO_0000056733.
FT   DOMAIN      192    380       Rho-GAP.
FT   REGION      403    499       Interacts with RalA.
FT   COMPBIAS    164    171       Poly-Lys.
FT   MOD_RES      11     11       Phosphoserine.
FT   MOD_RES      27     27       Phosphothreonine.
FT   MOD_RES      29     29       Phosphoserine.
FT   MOD_RES      30     30       Phosphoserine.
FT   MOD_RES      34     34       Phosphoserine.
FT   MOD_RES      62     62       Phosphoserine.
FT   MOD_RES      92     92       Phosphoserine.
FT   MOD_RES      93     93       Phosphoserine.
FT   MOD_RES     270    270       Phosphotyrosine.
FT   MOD_RES     280    280       Phosphothreonine.
FT   MOD_RES     463    463       Phosphoserine.
FT   MOD_RES     645    645       Phosphoserine.
FT   VARIANT     617    617       A -> V (in dbSNP:rs35867116).
FT                                /FTId=VAR_049147.
SQ   SEQUENCE   655 AA;  76063 MW;  EC6F75329FD8D062 CRC64;
     MTECFLPPTS SPSEHRRVEH GSGLTRTPSS EEISPTKFPG LYRTGEPSPP HDILHEPPDV
     VSDDEKDHGK KKGKFKKKEK RTEGYAAFQE DSSGDEAESP SKMKRSKGIH VFKKPSFSKK
     KEKDFKIKEK PKEEKHKEEK HKEEKHKEKK SKDLTAADVV KQWKEKKKKK KPIQEPEVPQ
     IDVPNLKPIF GIPLADAVER TMMYDGIRLP AVFRECIDYV EKYGMKCEGI YRVSGIKSKV
     DELKAAYDRE ESTNLEDYEP NTVASLLKQY LRDLPENLLT KELMPRFEEA CGRTTETEKV
     QEFQRLLKEL PECNYLLISW LIVHMDHVIA KELETKMNIQ NISIVLSPTV QISNRVLYVF
     FTHVQELFGN VVLKQVMKPL RWSNMATMPT LPETQAGIKE EIRRQEFLLN CLHRDLQGGI
     KDLSKEERLW EVQRILTALK RKLREAKRQE CETKIAQEIA SLSKEDVSKE EMNENEEVIN
     ILLAQENEIL TEQEELLAME QFLRRQIASE KEEIERLRAE IAEIQSRQQH GRSETEEYSS
     ESESESEDEE ELQIILEDLQ RQNEELEIKN NHLNQAIHEE REAIIELRVQ LRLLQMQRAK
     AEQQAQEDEE PEWRGGAVQP PRDGVLEPKA AKEQPKAGKE PAKPSPSRDR KETSI
//