Full text data of RABEP1
RABEP1
(RAB5EP, RABPT5, RABPT5A)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Rab GTPase-binding effector protein 1 (Rabaptin-4; Rabaptin-5; Rabaptin-5alpha; Renal carcinoma antigen NY-REN-17)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Rab GTPase-binding effector protein 1 (Rabaptin-4; Rabaptin-5; Rabaptin-5alpha; Renal carcinoma antigen NY-REN-17)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q15276
ID RABE1_HUMAN Reviewed; 862 AA.
AC Q15276; B2RAG7; O95369; Q8IVX3;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 17-OCT-2006, sequence version 2.
DT 22-JAN-2014, entry version 130.
DE RecName: Full=Rab GTPase-binding effector protein 1;
DE AltName: Full=Rabaptin-4;
DE AltName: Full=Rabaptin-5;
DE AltName: Full=Rabaptin-5alpha;
DE AltName: Full=Renal carcinoma antigen NY-REN-17;
GN Name=RABEP1; Synonyms=RAB5EP, RABPT5, RABPT5A;
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), FUNCTION, SUBCELLULAR
RP LOCATION, AND INTERACTION WITH RAB5A.
RC TISSUE=Cervix carcinoma;
RX PubMed=8521472; DOI=10.1016/0092-8674(95)90120-5;
RA Stenmark H., Vitale G., Ulrich O., Zerial M.;
RT "Rabaptin-5 is a direct effector of the small GTPase Rab5 in endocytic
RT membrane fusion.";
RL Cell 83:423-432(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, SUBCELLULAR
RP LOCATION, AND INTERACTION WITH RAB4A AND RAB5A.
RC TISSUE=Cervix carcinoma;
RX PubMed=10698684; DOI=10.1042/0264-6021:3460593;
RA Nagelkerken B., van Anken E., van Raak M., Gerez L., Mohrmann K.,
RA van Uden N., Holthuizen J., Pelkmans L., van der Sluijs P.;
RT "Rabaptin4, a novel effector of the small GTPase rab4a, is recruited
RT to perinuclear recycling vesicles.";
RL Biochem. J. 346:593-601(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=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 [5]
RP PROTEIN SEQUENCE OF 807-819, AND MASS SPECTROMETRY.
RC TISSUE=Fetal brain cortex;
RA Lubec G., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [6]
RP INTERACTION WITH RABGEF1.
RX PubMed=9323142; DOI=10.1016/S0092-8674(00)80380-3;
RA Horiuchi H., Lippe R., McBride H.M., Rubino M., Woodman P.,
RA Stenmark H., Rybin V., Wilm M., Ashman K., Mann M., Zerial M.;
RT "A novel Rab5 GDP/GTP exchange factor complexed to Rabaptin-5 links
RT nucleotide exchange to effector recruitment and function.";
RL Cell 90:1149-1159(1997).
RN [7]
RP PROTEOLYTIC CLEAVAGE BY CASPASES IN APOPTOTIC CELLS.
RX PubMed=9321397; DOI=10.1093/emboj/16.20.6182;
RA Cosulich S.C., Horiuchi H., Zerial M., Clarke P.R., Woodman P.G.;
RT "Cleavage of rabaptin-5 blocks endosome fusion during apoptosis.";
RL EMBO J. 16:6182-6191(1997).
RN [8]
RP INTERACTION WITH TSC2.
RX PubMed=9045618; DOI=10.1074/jbc.272.10.6097;
RA Xiao G.-H., Shoarinejad F., Jin F., Golemis E.A., Yeung R.S.;
RT "The tuberous sclerosis 2 gene product, tuberin, functions as a Rab5
RT GTPase activating protein (GAP) in modulating endocytosis.";
RL J. Biol. Chem. 272:6097-6100(1997).
RN [9]
RP IDENTIFICATION AS A RENAL CANCER ANTIGEN.
RC TISSUE=Renal cell carcinoma;
RX PubMed=10508479;
RX DOI=10.1002/(SICI)1097-0215(19991112)83:4<456::AID-IJC4>3.0.CO;2-5;
RA Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H.,
RA Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T.,
RA Old L.J.;
RT "Antigens recognized by autologous antibody in patients with renal-
RT cell carcinoma.";
RL Int. J. Cancer 83:456-464(1999).
RN [10]
RP FUNCTION, AND INTERACTION WITH RABGEF1.
RX PubMed=11452015; DOI=10.1091/mbc.12.7.2219;
RA Lippe R., Miaczynska M., Rybin V., Runge A., Zerial M.;
RT "Functional synergy between Rab5 effector Rabaptin-5 and exchange
RT factor Rabex-5 when physically associated in a complex.";
RL Mol. Biol. Cell 12:2219-2228(2001).
RN [11]
RP INTERACTION WITH GGA1; GGA2; GGA3; AP1G1 AND AP1G2, AND SUBCELLULAR
RP LOCATION.
RX PubMed=12505986; DOI=10.1093/emboj/cdg015;
RA Mattera R., Arighi C.N., Lodge R., Zerial M., Bonifacino J.S.;
RT "Divalent interaction of the GGAs with the Rabaptin-5-Rabex-5
RT complex.";
RL EMBO J. 22:78-88(2003).
RN [12]
RP FUNCTION, INTERACTION WITH RAB4A AND AP1G1, AND SUBCELLULAR LOCATION.
RX PubMed=12773381; DOI=10.1093/emboj/cdg257;
RA Deneka M., Neeft M., Popa I., van Oort M., Sprong H., Oorschot V.,
RA Klumperman J., Schu P., van der Sluijs P.;
RT "Rabaptin-5alpha/rabaptin-4 serves as a linker between rab4 and
RT gamma(1)-adaptin in membrane recycling from endosomes.";
RL EMBO J. 22:2645-2657(2003).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-407, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-407 AND SER-410, AND
RP 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 [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
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 [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-407, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic 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).
RN [18]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-282, 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 [19]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH ECM29.
RX PubMed=20682791; DOI=10.1074/jbc.M110.154120;
RA Gorbea C., Pratt G., Ustrell V., Bell R., Sahasrabudhe S.,
RA Hughes R.E., Rechsteiner M.;
RT "A protein interaction network for Ecm29 links the 26 S proteasome to
RT molecular motors and endosomal components.";
RL J. Biol. Chem. 285:31616-31633(2010).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-407 AND SER-410, 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 [21]
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 [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-407 AND SER-410, AND
RP MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [23]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (2.31 ANGSTROMS) OF 789-862 IN COMPLEX WITH
RP RAB5A, SUBUNIT, AND MUTAGENESIS OF ASP-812; GLU-815; GLN-818; ASO-820;
RP PHE-821; VAL-822; GLN-826 AND GLN-829.
RX PubMed=15378032; DOI=10.1038/nsmb832;
RA Zhu G., Zhai P., Liu J., Terzyan S., Li G., Zhang X.C.;
RT "Structural basis of Rab5-Rabaptin5 interaction in endocytosis.";
RL Nat. Struct. Mol. Biol. 11:975-983(2004).
CC -!- FUNCTION: Rab effector protein acting as linker between gamma-
CC adaptin, RAB4A and RAB5A. Involved in endocytic membrane fusion
CC and membrane trafficking of recycling endosomes. Stimulates
CC RABGEF1 mediated nucleotide exchange on RAB5A.
CC -!- SUBUNIT: Homodimer when bound to RAB5A. Heterodimer with RABGEF1.
CC The heterodimer binds RAB4A and RAB5A that have been activated by
CC GTP-binding. Binds TSC2, GGA1, GGA2, GGA3, AP1G1 and AP1G2.
CC Interacts with ECM29.
CC -!- INTERACTION:
CC O43747:AP1G1; NbExp=2; IntAct=EBI-447043, EBI-447609;
CC O75843:AP1G2; NbExp=2; IntAct=EBI-447043, EBI-373637;
CC Q9UJY5:GGA1; NbExp=8; IntAct=EBI-447043, EBI-447141;
CC Q9UJY4:GGA2; NbExp=6; IntAct=EBI-447043, EBI-447646;
CC Q9NZ52:GGA3; NbExp=4; IntAct=EBI-447043, EBI-447404;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Early endosome. Recycling
CC endosome. Cytoplasmic vesicle.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Rabaptin-5;
CC IsoId=Q15276-1; Sequence=Displayed;
CC Name=2; Synonyms=Rabaptin-4;
CC IsoId=Q15276-2; Sequence=VSP_010451;
CC -!- PTM: Proteolytic cleavage by caspases in apoptotic cells causes
CC loss of endosome fusion activity.
CC -!- SIMILARITY: Belongs to the rabaptin family.
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DR EMBL; X91141; CAA62580.1; -; mRNA.
DR EMBL; AF098638; AAC70781.1; -; mRNA.
DR EMBL; AK314183; BAG36864.1; -; mRNA.
DR EMBL; BC041700; AAH41700.1; -; mRNA.
DR RefSeq; NP_001077054.1; NM_001083585.1.
DR RefSeq; NP_004694.2; NM_004703.4.
DR UniGene; Hs.592121; -.
DR PDB; 1P4U; X-ray; 2.20 A; B=435-447.
DR PDB; 1TU3; X-ray; 2.31 A; F/G/H/I/J=789-862.
DR PDB; 1X79; X-ray; 2.41 A; B/C=551-661.
DR PDBsum; 1P4U; -.
DR PDBsum; 1TU3; -.
DR PDBsum; 1X79; -.
DR ProteinModelPortal; Q15276; -.
DR SMR; Q15276; 553-640, 802-854.
DR DIP; DIP-29350N; -.
DR IntAct; Q15276; 17.
DR MINT; MINT-126137; -.
DR STRING; 9606.ENSP00000262477; -.
DR PhosphoSite; Q15276; -.
DR DMDM; 116242743; -.
DR PaxDb; Q15276; -.
DR PRIDE; Q15276; -.
DR Ensembl; ENST00000262477; ENSP00000262477; ENSG00000029725.
DR Ensembl; ENST00000341923; ENSP00000339569; ENSG00000029725.
DR Ensembl; ENST00000408982; ENSP00000386150; ENSG00000029725.
DR Ensembl; ENST00000546142; ENSP00000437701; ENSG00000029725.
DR GeneID; 9135; -.
DR KEGG; hsa:9135; -.
DR UCSC; uc002gbm.4; human.
DR CTD; 9135; -.
DR GeneCards; GC17P005185; -.
DR HGNC; HGNC:17677; RABEP1.
DR HPA; CAB004549; -.
DR HPA; HPA019669; -.
DR HPA; HPA024235; -.
DR HPA; HPA024691; -.
DR MIM; 603616; gene.
DR neXtProt; NX_Q15276; -.
DR PharmGKB; PA134884097; -.
DR eggNOG; NOG237924; -.
DR HOGENOM; HOG000234329; -.
DR HOVERGEN; HBG055335; -.
DR InParanoid; Q15276; -.
DR KO; K12480; -.
DR OMA; QKEVHNA; -.
DR OrthoDB; EOG7WHH8T; -.
DR PhylomeDB; Q15276; -.
DR ChiTaRS; RABEP1; human.
DR EvolutionaryTrace; Q15276; -.
DR GeneWiki; RABEP1; -.
DR GenomeRNAi; 9135; -.
DR NextBio; 34253; -.
DR PMAP-CutDB; Q15276; -.
DR PRO; PR:Q15276; -.
DR ArrayExpress; Q15276; -.
DR Bgee; Q15276; -.
DR CleanEx; HS_RABEP1; -.
DR Genevestigator; Q15276; -.
DR GO; GO:0005769; C:early endosome; TAS:ProtInc.
DR GO; GO:0030139; C:endocytic vesicle; IDA:UniProtKB.
DR GO; GO:0055037; C:recycling endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005096; F:GTPase activator activity; IEA:InterPro.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0006897; P:endocytosis; TAS:ProtInc.
DR GO; GO:0061025; P:membrane fusion; TAS:ProtInc.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IEA:GOC.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR InterPro; IPR003914; Rabaptin.
DR InterPro; IPR018514; Rabaptin_coiled-coil.
DR InterPro; IPR015390; Rabaptin_Rab5-bd_dom.
DR Pfam; PF09311; Rab5-bind; 1.
DR Pfam; PF03528; Rabaptin; 2.
DR PRINTS; PR01432; RABAPTIN.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Apoptosis;
KW Coiled coil; Complete proteome; Cytoplasm; Cytoplasmic vesicle;
KW Direct protein sequencing; Endocytosis; Endosome; Phosphoprotein;
KW Polymorphism; Protein transport; Reference proteome; Transport.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 862 Rab GTPase-binding effector protein 1.
FT /FTId=PRO_0000187556.
FT COILED 11 345 Potential.
FT COILED 534 816 Potential.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 282 282 N6-acetyllysine.
FT MOD_RES 407 407 Phosphoserine.
FT MOD_RES 410 410 Phosphoserine.
FT VAR_SEQ 758 790 Missing (in isoform 2).
FT /FTId=VSP_010451.
FT VARIANT 640 640 E -> G (in dbSNP:rs3026099).
FT /FTId=VAR_028106.
FT MUTAGEN 812 812 D->K: No effect on RAB5A binding
FT affinity.
FT MUTAGEN 815 815 E->K: No effect on RAB5A binding
FT affinity.
FT MUTAGEN 818 818 Q->W: Strongly decreases RAB5A binding
FT affinity.
FT MUTAGEN 820 820 D->K: Strongly decreases RAB5A binding
FT affinity.
FT MUTAGEN 821 821 F->R: Strongly decreases RAB5A binding
FT affinity.
FT MUTAGEN 822 822 V->D: Strongly decreases RAB5A binding
FT affinity.
FT MUTAGEN 826 826 Q->A: Strongly decreases RAB5A binding
FT affinity.
FT MUTAGEN 829 829 Q->A: Strongly decreases RAB5A binding
FT affinity.
FT CONFLICT 149 149 S -> Y (in Ref. 1; CAA62580 and 2;
FT AAC70781).
FT CONFLICT 628 628 M -> I (in Ref. 3; BAG36864).
FT HELIX 553 639
FT HELIX 805 836
FT HELIX 841 847
SQ SEQUENCE 862 AA; 99290 MW; CAAF91638B8ED516 CRC64;
MAQPGPASQP DVSLQQRVAE LEKINAEFLR AQQQLEQEFN QKRAKFKELY LAKEEDLKRQ
NAVLQAAQDD LGHLRTQLWE AQAEMENIKA IATVSENTKQ EAIDEVKRQW REEVASLQAV
MKETVRDYEH QFHLRLEQER TQWAQYRESA EREIADLRRR LSEGQEEENL ENEMKKAQED
AEKLRSVVMP MEKEIAALKD KLTEAEDKIK ELEASKVKEL NHYLEAEKSC RTDLEMYVAV
LNTQKSVLQE DAEKLRKELH EVCHLLEQER QQHNQLKHTW QKANDQFLES QRLLMRDMQR
MEIVLTSEQL RQVEELKKKD QEDDEQQRLN KRKDHKKADV EEEIKIPVVC ALTQEESSAQ
LSNEEEHLDS TRGSVHSLDA GLLLPSGDPF SKSDNDMFKD GLRRAQSTDS LGTSGSLQSK
ALGYNYKAKS AGNLDESDFG PLVGADSVSE NFDTASLGSL QMPSGFMLTK DQERAIKAMT
PEQEETASLL SSVTQGMESA YVSPSGYRLV SETEWNLLQK EVHNAGNKLG RRCDMCSNYE
KQLQGIQIQE AETRDQVKKL QLMLRQANDQ LEKTMKDKQE LEDFIKQSSE DSSHQISALV
LRAQASEILL EELQQGLSQA KRDVQEQMAV LMQSREQVSE ELVRLQKDND SLQGKHSLHV
SLQQAEDFIL PDTTEALREL VLKYREDIIN VRTAADHVEE KLKAEILFLK EQIQAEQCLK
ENLEETLQLE IENCKEEIAS ISSLKAELER IKVEKGQLES TLREKSQQLE SLQEIKISLE
EQLKKETAAK ATVEQLMFEE KNKAQRLQTE LDVSEQVQRD FVKLSQTLQV QLERIRQADS
LERIRAILND TKLTDINQLP ET
//
ID RABE1_HUMAN Reviewed; 862 AA.
AC Q15276; B2RAG7; O95369; Q8IVX3;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 17-OCT-2006, sequence version 2.
DT 22-JAN-2014, entry version 130.
DE RecName: Full=Rab GTPase-binding effector protein 1;
DE AltName: Full=Rabaptin-4;
DE AltName: Full=Rabaptin-5;
DE AltName: Full=Rabaptin-5alpha;
DE AltName: Full=Renal carcinoma antigen NY-REN-17;
GN Name=RABEP1; Synonyms=RAB5EP, RABPT5, RABPT5A;
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), FUNCTION, SUBCELLULAR
RP LOCATION, AND INTERACTION WITH RAB5A.
RC TISSUE=Cervix carcinoma;
RX PubMed=8521472; DOI=10.1016/0092-8674(95)90120-5;
RA Stenmark H., Vitale G., Ulrich O., Zerial M.;
RT "Rabaptin-5 is a direct effector of the small GTPase Rab5 in endocytic
RT membrane fusion.";
RL Cell 83:423-432(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, SUBCELLULAR
RP LOCATION, AND INTERACTION WITH RAB4A AND RAB5A.
RC TISSUE=Cervix carcinoma;
RX PubMed=10698684; DOI=10.1042/0264-6021:3460593;
RA Nagelkerken B., van Anken E., van Raak M., Gerez L., Mohrmann K.,
RA van Uden N., Holthuizen J., Pelkmans L., van der Sluijs P.;
RT "Rabaptin4, a novel effector of the small GTPase rab4a, is recruited
RT to perinuclear recycling vesicles.";
RL Biochem. J. 346:593-601(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=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 [5]
RP PROTEIN SEQUENCE OF 807-819, AND MASS SPECTROMETRY.
RC TISSUE=Fetal brain cortex;
RA Lubec G., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [6]
RP INTERACTION WITH RABGEF1.
RX PubMed=9323142; DOI=10.1016/S0092-8674(00)80380-3;
RA Horiuchi H., Lippe R., McBride H.M., Rubino M., Woodman P.,
RA Stenmark H., Rybin V., Wilm M., Ashman K., Mann M., Zerial M.;
RT "A novel Rab5 GDP/GTP exchange factor complexed to Rabaptin-5 links
RT nucleotide exchange to effector recruitment and function.";
RL Cell 90:1149-1159(1997).
RN [7]
RP PROTEOLYTIC CLEAVAGE BY CASPASES IN APOPTOTIC CELLS.
RX PubMed=9321397; DOI=10.1093/emboj/16.20.6182;
RA Cosulich S.C., Horiuchi H., Zerial M., Clarke P.R., Woodman P.G.;
RT "Cleavage of rabaptin-5 blocks endosome fusion during apoptosis.";
RL EMBO J. 16:6182-6191(1997).
RN [8]
RP INTERACTION WITH TSC2.
RX PubMed=9045618; DOI=10.1074/jbc.272.10.6097;
RA Xiao G.-H., Shoarinejad F., Jin F., Golemis E.A., Yeung R.S.;
RT "The tuberous sclerosis 2 gene product, tuberin, functions as a Rab5
RT GTPase activating protein (GAP) in modulating endocytosis.";
RL J. Biol. Chem. 272:6097-6100(1997).
RN [9]
RP IDENTIFICATION AS A RENAL CANCER ANTIGEN.
RC TISSUE=Renal cell carcinoma;
RX PubMed=10508479;
RX DOI=10.1002/(SICI)1097-0215(19991112)83:4<456::AID-IJC4>3.0.CO;2-5;
RA Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H.,
RA Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T.,
RA Old L.J.;
RT "Antigens recognized by autologous antibody in patients with renal-
RT cell carcinoma.";
RL Int. J. Cancer 83:456-464(1999).
RN [10]
RP FUNCTION, AND INTERACTION WITH RABGEF1.
RX PubMed=11452015; DOI=10.1091/mbc.12.7.2219;
RA Lippe R., Miaczynska M., Rybin V., Runge A., Zerial M.;
RT "Functional synergy between Rab5 effector Rabaptin-5 and exchange
RT factor Rabex-5 when physically associated in a complex.";
RL Mol. Biol. Cell 12:2219-2228(2001).
RN [11]
RP INTERACTION WITH GGA1; GGA2; GGA3; AP1G1 AND AP1G2, AND SUBCELLULAR
RP LOCATION.
RX PubMed=12505986; DOI=10.1093/emboj/cdg015;
RA Mattera R., Arighi C.N., Lodge R., Zerial M., Bonifacino J.S.;
RT "Divalent interaction of the GGAs with the Rabaptin-5-Rabex-5
RT complex.";
RL EMBO J. 22:78-88(2003).
RN [12]
RP FUNCTION, INTERACTION WITH RAB4A AND AP1G1, AND SUBCELLULAR LOCATION.
RX PubMed=12773381; DOI=10.1093/emboj/cdg257;
RA Deneka M., Neeft M., Popa I., van Oort M., Sprong H., Oorschot V.,
RA Klumperman J., Schu P., van der Sluijs P.;
RT "Rabaptin-5alpha/rabaptin-4 serves as a linker between rab4 and
RT gamma(1)-adaptin in membrane recycling from endosomes.";
RL EMBO J. 22:2645-2657(2003).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-407, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-407 AND SER-410, AND
RP 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 [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
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 [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-407, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic 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).
RN [18]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-282, 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 [19]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH ECM29.
RX PubMed=20682791; DOI=10.1074/jbc.M110.154120;
RA Gorbea C., Pratt G., Ustrell V., Bell R., Sahasrabudhe S.,
RA Hughes R.E., Rechsteiner M.;
RT "A protein interaction network for Ecm29 links the 26 S proteasome to
RT molecular motors and endosomal components.";
RL J. Biol. Chem. 285:31616-31633(2010).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-407 AND SER-410, 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 [21]
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 [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-407 AND SER-410, AND
RP MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [23]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (2.31 ANGSTROMS) OF 789-862 IN COMPLEX WITH
RP RAB5A, SUBUNIT, AND MUTAGENESIS OF ASP-812; GLU-815; GLN-818; ASO-820;
RP PHE-821; VAL-822; GLN-826 AND GLN-829.
RX PubMed=15378032; DOI=10.1038/nsmb832;
RA Zhu G., Zhai P., Liu J., Terzyan S., Li G., Zhang X.C.;
RT "Structural basis of Rab5-Rabaptin5 interaction in endocytosis.";
RL Nat. Struct. Mol. Biol. 11:975-983(2004).
CC -!- FUNCTION: Rab effector protein acting as linker between gamma-
CC adaptin, RAB4A and RAB5A. Involved in endocytic membrane fusion
CC and membrane trafficking of recycling endosomes. Stimulates
CC RABGEF1 mediated nucleotide exchange on RAB5A.
CC -!- SUBUNIT: Homodimer when bound to RAB5A. Heterodimer with RABGEF1.
CC The heterodimer binds RAB4A and RAB5A that have been activated by
CC GTP-binding. Binds TSC2, GGA1, GGA2, GGA3, AP1G1 and AP1G2.
CC Interacts with ECM29.
CC -!- INTERACTION:
CC O43747:AP1G1; NbExp=2; IntAct=EBI-447043, EBI-447609;
CC O75843:AP1G2; NbExp=2; IntAct=EBI-447043, EBI-373637;
CC Q9UJY5:GGA1; NbExp=8; IntAct=EBI-447043, EBI-447141;
CC Q9UJY4:GGA2; NbExp=6; IntAct=EBI-447043, EBI-447646;
CC Q9NZ52:GGA3; NbExp=4; IntAct=EBI-447043, EBI-447404;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Early endosome. Recycling
CC endosome. Cytoplasmic vesicle.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Rabaptin-5;
CC IsoId=Q15276-1; Sequence=Displayed;
CC Name=2; Synonyms=Rabaptin-4;
CC IsoId=Q15276-2; Sequence=VSP_010451;
CC -!- PTM: Proteolytic cleavage by caspases in apoptotic cells causes
CC loss of endosome fusion activity.
CC -!- SIMILARITY: Belongs to the rabaptin family.
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DR EMBL; X91141; CAA62580.1; -; mRNA.
DR EMBL; AF098638; AAC70781.1; -; mRNA.
DR EMBL; AK314183; BAG36864.1; -; mRNA.
DR EMBL; BC041700; AAH41700.1; -; mRNA.
DR RefSeq; NP_001077054.1; NM_001083585.1.
DR RefSeq; NP_004694.2; NM_004703.4.
DR UniGene; Hs.592121; -.
DR PDB; 1P4U; X-ray; 2.20 A; B=435-447.
DR PDB; 1TU3; X-ray; 2.31 A; F/G/H/I/J=789-862.
DR PDB; 1X79; X-ray; 2.41 A; B/C=551-661.
DR PDBsum; 1P4U; -.
DR PDBsum; 1TU3; -.
DR PDBsum; 1X79; -.
DR ProteinModelPortal; Q15276; -.
DR SMR; Q15276; 553-640, 802-854.
DR DIP; DIP-29350N; -.
DR IntAct; Q15276; 17.
DR MINT; MINT-126137; -.
DR STRING; 9606.ENSP00000262477; -.
DR PhosphoSite; Q15276; -.
DR DMDM; 116242743; -.
DR PaxDb; Q15276; -.
DR PRIDE; Q15276; -.
DR Ensembl; ENST00000262477; ENSP00000262477; ENSG00000029725.
DR Ensembl; ENST00000341923; ENSP00000339569; ENSG00000029725.
DR Ensembl; ENST00000408982; ENSP00000386150; ENSG00000029725.
DR Ensembl; ENST00000546142; ENSP00000437701; ENSG00000029725.
DR GeneID; 9135; -.
DR KEGG; hsa:9135; -.
DR UCSC; uc002gbm.4; human.
DR CTD; 9135; -.
DR GeneCards; GC17P005185; -.
DR HGNC; HGNC:17677; RABEP1.
DR HPA; CAB004549; -.
DR HPA; HPA019669; -.
DR HPA; HPA024235; -.
DR HPA; HPA024691; -.
DR MIM; 603616; gene.
DR neXtProt; NX_Q15276; -.
DR PharmGKB; PA134884097; -.
DR eggNOG; NOG237924; -.
DR HOGENOM; HOG000234329; -.
DR HOVERGEN; HBG055335; -.
DR InParanoid; Q15276; -.
DR KO; K12480; -.
DR OMA; QKEVHNA; -.
DR OrthoDB; EOG7WHH8T; -.
DR PhylomeDB; Q15276; -.
DR ChiTaRS; RABEP1; human.
DR EvolutionaryTrace; Q15276; -.
DR GeneWiki; RABEP1; -.
DR GenomeRNAi; 9135; -.
DR NextBio; 34253; -.
DR PMAP-CutDB; Q15276; -.
DR PRO; PR:Q15276; -.
DR ArrayExpress; Q15276; -.
DR Bgee; Q15276; -.
DR CleanEx; HS_RABEP1; -.
DR Genevestigator; Q15276; -.
DR GO; GO:0005769; C:early endosome; TAS:ProtInc.
DR GO; GO:0030139; C:endocytic vesicle; IDA:UniProtKB.
DR GO; GO:0055037; C:recycling endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005096; F:GTPase activator activity; IEA:InterPro.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0006897; P:endocytosis; TAS:ProtInc.
DR GO; GO:0061025; P:membrane fusion; TAS:ProtInc.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IEA:GOC.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR InterPro; IPR003914; Rabaptin.
DR InterPro; IPR018514; Rabaptin_coiled-coil.
DR InterPro; IPR015390; Rabaptin_Rab5-bd_dom.
DR Pfam; PF09311; Rab5-bind; 1.
DR Pfam; PF03528; Rabaptin; 2.
DR PRINTS; PR01432; RABAPTIN.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Apoptosis;
KW Coiled coil; Complete proteome; Cytoplasm; Cytoplasmic vesicle;
KW Direct protein sequencing; Endocytosis; Endosome; Phosphoprotein;
KW Polymorphism; Protein transport; Reference proteome; Transport.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 862 Rab GTPase-binding effector protein 1.
FT /FTId=PRO_0000187556.
FT COILED 11 345 Potential.
FT COILED 534 816 Potential.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 282 282 N6-acetyllysine.
FT MOD_RES 407 407 Phosphoserine.
FT MOD_RES 410 410 Phosphoserine.
FT VAR_SEQ 758 790 Missing (in isoform 2).
FT /FTId=VSP_010451.
FT VARIANT 640 640 E -> G (in dbSNP:rs3026099).
FT /FTId=VAR_028106.
FT MUTAGEN 812 812 D->K: No effect on RAB5A binding
FT affinity.
FT MUTAGEN 815 815 E->K: No effect on RAB5A binding
FT affinity.
FT MUTAGEN 818 818 Q->W: Strongly decreases RAB5A binding
FT affinity.
FT MUTAGEN 820 820 D->K: Strongly decreases RAB5A binding
FT affinity.
FT MUTAGEN 821 821 F->R: Strongly decreases RAB5A binding
FT affinity.
FT MUTAGEN 822 822 V->D: Strongly decreases RAB5A binding
FT affinity.
FT MUTAGEN 826 826 Q->A: Strongly decreases RAB5A binding
FT affinity.
FT MUTAGEN 829 829 Q->A: Strongly decreases RAB5A binding
FT affinity.
FT CONFLICT 149 149 S -> Y (in Ref. 1; CAA62580 and 2;
FT AAC70781).
FT CONFLICT 628 628 M -> I (in Ref. 3; BAG36864).
FT HELIX 553 639
FT HELIX 805 836
FT HELIX 841 847
SQ SEQUENCE 862 AA; 99290 MW; CAAF91638B8ED516 CRC64;
MAQPGPASQP DVSLQQRVAE LEKINAEFLR AQQQLEQEFN QKRAKFKELY LAKEEDLKRQ
NAVLQAAQDD LGHLRTQLWE AQAEMENIKA IATVSENTKQ EAIDEVKRQW REEVASLQAV
MKETVRDYEH QFHLRLEQER TQWAQYRESA EREIADLRRR LSEGQEEENL ENEMKKAQED
AEKLRSVVMP MEKEIAALKD KLTEAEDKIK ELEASKVKEL NHYLEAEKSC RTDLEMYVAV
LNTQKSVLQE DAEKLRKELH EVCHLLEQER QQHNQLKHTW QKANDQFLES QRLLMRDMQR
MEIVLTSEQL RQVEELKKKD QEDDEQQRLN KRKDHKKADV EEEIKIPVVC ALTQEESSAQ
LSNEEEHLDS TRGSVHSLDA GLLLPSGDPF SKSDNDMFKD GLRRAQSTDS LGTSGSLQSK
ALGYNYKAKS AGNLDESDFG PLVGADSVSE NFDTASLGSL QMPSGFMLTK DQERAIKAMT
PEQEETASLL SSVTQGMESA YVSPSGYRLV SETEWNLLQK EVHNAGNKLG RRCDMCSNYE
KQLQGIQIQE AETRDQVKKL QLMLRQANDQ LEKTMKDKQE LEDFIKQSSE DSSHQISALV
LRAQASEILL EELQQGLSQA KRDVQEQMAV LMQSREQVSE ELVRLQKDND SLQGKHSLHV
SLQQAEDFIL PDTTEALREL VLKYREDIIN VRTAADHVEE KLKAEILFLK EQIQAEQCLK
ENLEETLQLE IENCKEEIAS ISSLKAELER IKVEKGQLES TLREKSQQLE SLQEIKISLE
EQLKKETAAK ATVEQLMFEE KNKAQRLQTE LDVSEQVQRD FVKLSQTLQV QLERIRQADS
LERIRAILND TKLTDINQLP ET
//
MIM
603616
*RECORD*
*FIELD* NO
603616
*FIELD* TI
*603616 RAB GTPase-BINDING EFFECTOR PROTEIN 1; RABEP1
;;RABAPTIN 5; RABPT5
RABEP1/PDGFRB FUSION GENE, INCLUDED
read more*FIELD* TX
CLONING
The small GTPase RAB5 (179512) is a rate-limiting component in membrane
docking or fusion in the early endocytic pathway. The GTP-bound form of
RAB5 is the active conformation. Using a yeast 2-hybrid screen, Stenmark
et al. (1995) identified HeLa cell cDNAs encoding a protein that
interacted with the GTP-bound form of RAB5. The predicted 862-amino acid
protein was designated rabaptin-5, a name combining the Greek word
'apto,' meaning 'touch', with RAB5. Both the N- and C-terminal regions
of rabaptin-5 are predicted to be mainly alpha-helical and contain
heptad repeats characteristic of coiled-coil domains. Western blot
analysis of mammalian cell extracts indicated that the 115-kD protein is
ubiquitously expressed and is present in a major cytosolic and minor
endosome-bound pool.
GENE FUNCTION
Stenmark et al. (1995) demonstrated that rabaptin-5 binds directly to
RAB5 and preferentially to its GTP-bound form. RAB5 recruits rabaptin-5
to early endosomes in a GTP-dependent manner. Overexpression of
rabaptin-5 leads to morphologic alterations of the early endosome
compartment similar to those induced by overexpression of RAB5. The
authors concluded that rabaptin-5 is an effector of RAB5 that transmits
the signal of the active GTP-bound RAB5 conformation to the membrane
docking and/or fusion apparatus. They proposed a model in which RAB5-GDP
is converted by a membrane-bound GDP/GTP exchange factor into the active
GTP-bound conformation. Once activated, GTP-bound RAB5 then recruits
rabaptin-5 from the cytosol, thereby positioning rabaptin-5 to exert its
function in membrane docking or fusion.
Xiao et al. (1997) reported that tuberin (191092) exhibits substantial
GTPase-activating protein activity towards RAB5, and that rabaptin-5
mediates the tuberin association with RAB5.
Using immunodepletion experiments, Horiuchi et al. (1997) found that the
RABGEF1 (609700)-RABPT5 complex was essential for both homotypic and
heterotypic endosome fusions. Both RABGEF1 and RABPT5 bound RAB5
preferentially in the presence of GTP rather than GDP. RABGEF1 displayed
specific GDP/GTP exchange activity on RAB5 upon delivery of RAB5 to the
membrane.
Mattera et al. (2003) found that the GGAs (e.g., GGA1; 606004), a family
of ARF (see 103180)-dependent clathrin adaptors involved in selection of
trans-Golgi network cargo, interacted with the RABGEF1-RABPT5 complex in
vitro and in vivo.
Omori et al. (2008) identified elipsa, the zebrafish ortholog of
TRAF3IP1 (607380), as a component of intraflagellar transport particles,
which are involved in the formation and function of cilia. Elipsa
interacted with rabaptin-5, which in turn interacted with Rab8 (RAB8A;
165040), a small GTPase localized to cilia. Omori et al. (2008)
concluded that elipsa, rabaptin-5, and Rab8 provide a bridge between the
intraflagellar transport particle and protein complexes that assemble at
the ciliary membrane.
Endocytosis plays a major role in the deactivation of receptors
localized to the plasma membrane. Wang et al. (2009) found that hypoxia,
via the VHL (608537)-HIF2A (EPAS1; 603349) signaling pathway,
downregulated rabaptin-5 expression, leading to decelerated endocytosis
and prolonged activation of ligand-bound EGFR (131550). Primary kidney
and breast tumors with strong hypoxic signatures showed significantly
lower expression of rabaptin-5 RNA and protein. Wang et al. (2009)
identified a conserved hypoxia-responsive element (HRE) in the
rabaptin-5 promoter that bound in vitro-translated HIF1A (603348) and
HIF2A, leading to displacement of RNA polymerase II and attenuating
rabaptin-5 transcription.
MAPPING
The RABEP1 gene maps to chromosome 17p13 (Magnusson et al., 2001).
CYTOGENETICS
In a patient with chronic myelomonocytic leukemia (CMML; see 607785) and
an acquired t(5;17)(q33;p13), Magnusson et al. (2001) demonstrated
rabaptin-5 as a novel partner fused in-frame to the 5-prime portion of
the PDGFBR gene (173410). The fusion protein included more than 85% of
the native rabaptin-5 fused to the transmembrane and intracellular
tyrosine kinase domains of PDGFRB. Rabaptin-5 is an essential and
rate-limiting component of early endosomal fusion. The RABEP1/PDGFRB
fusion protein links 2 important pathways of growth regulation.
*FIELD* RF
1. Horiuchi, H.; Lippe, R.; McBride, H. M.; Rubino, M.; Woodman, P.;
Stenmark, H.; Rybin, V.; Wilm, M.; Ashman, K.; Mann, M.; Zerial, M.
: A novel Rab5 GDP/GTP exchange factor complexed to rabaptin-5 links
nucleotide exchange to effector recruitment and function. Cell 90:
1149-1159, 1997.
2. Magnusson, M. K.; Meade, K. E.; Brown, K. E.; Arthur, D. C.; Krueger,
L. A.; Barrett, A. J.; Dunbar, C. E.: Rabaptin-5 is a novel fusion
partner to platelet-derived growth factor beta receptor in chronic
myelomonocytic leukemia. Blood 98: 2518-2525, 2001.
3. Mattera, R.; Arighi, C. N.; Lodge, R.; Zerial, M.; Bonifacino,
J. S.: Divalent interaction of the GGAs with the Rabaptin-5-Rabex-5
complex. EMBO J. 22: 78-88, 2003.
4. Omori, Y.; Zhao, C.; Saras, A.; Mukhopadhyay, S.; Kim, W.; Furukawa,
T.; Sengupta, P.; Veraksa, A.; Malicki, J.: elipsa is an early determinant
of ciliogenesis that links the IFT particle to membrane-associated
small GTPase Rab8. Nature Cell Biol. 10: 437-444, 2008.
5. Stenmark, H.; Vitale, G.; Ullrich, O.; Zerial, M.: Rabaptin-5
is a direct effector of the small GTPase Rab5 in endocytic membrane
fusion. Cell 83: 423-432, 1995.
6. Wang, Y.; Roche, O.; Yan, M. S.; Finak, G.; Evans, A. J.; Metcalf,
J. L.; Hast, B. E.; Hanna, S. C.; Wondergem, B.; Furge, K. A.; Irwin,
M. S.; Kim, W. Y.; Teh, B. T.; Grinstein, S.; Park, M.; Marsden, P.
A.; Ohh, M.: Regulation of endocytosis via the oxygen-sensing pathway. Nature
Med. 15: 319-324, 2009.
7. Xiao, G.-H.; Shoarinejad, F.; Jin, F.; Golemis, E. A.; Yeung, R.
S.: The tuberous sclerosis 2 gene product, tuberin, functions as
a Rab5 GTPase activating protein (GAP) in modulating endocytosis. J.
Biol. Chem. 272: 6097-6100, 1997.
*FIELD* CN
Patricia A. Hartz - updated: 6/8/2009
Patricia A. Hartz - updated: 6/4/2009
Paul J. Converse - updated: 11/7/2005
Victor A. McKusick - updated: 9/27/2002
Victor A. McKusick - updated: 9/16/2002
*FIELD* CD
Rebekah S. Rasooly: 3/9/1999
*FIELD* ED
wwang: 05/18/2011
ckniffin: 5/3/2011
ckniffin: 5/2/2011
wwang: 6/11/2009
terry: 6/8/2009
mgross: 6/4/2009
terry: 6/4/2009
carol: 2/29/2008
mgross: 11/7/2005
cwells: 11/5/2003
alopez: 9/27/2002
tkritzer: 9/25/2002
tkritzer: 9/16/2002
mgross: 3/10/1999
mgross: 3/9/1999
*RECORD*
*FIELD* NO
603616
*FIELD* TI
*603616 RAB GTPase-BINDING EFFECTOR PROTEIN 1; RABEP1
;;RABAPTIN 5; RABPT5
RABEP1/PDGFRB FUSION GENE, INCLUDED
read more*FIELD* TX
CLONING
The small GTPase RAB5 (179512) is a rate-limiting component in membrane
docking or fusion in the early endocytic pathway. The GTP-bound form of
RAB5 is the active conformation. Using a yeast 2-hybrid screen, Stenmark
et al. (1995) identified HeLa cell cDNAs encoding a protein that
interacted with the GTP-bound form of RAB5. The predicted 862-amino acid
protein was designated rabaptin-5, a name combining the Greek word
'apto,' meaning 'touch', with RAB5. Both the N- and C-terminal regions
of rabaptin-5 are predicted to be mainly alpha-helical and contain
heptad repeats characteristic of coiled-coil domains. Western blot
analysis of mammalian cell extracts indicated that the 115-kD protein is
ubiquitously expressed and is present in a major cytosolic and minor
endosome-bound pool.
GENE FUNCTION
Stenmark et al. (1995) demonstrated that rabaptin-5 binds directly to
RAB5 and preferentially to its GTP-bound form. RAB5 recruits rabaptin-5
to early endosomes in a GTP-dependent manner. Overexpression of
rabaptin-5 leads to morphologic alterations of the early endosome
compartment similar to those induced by overexpression of RAB5. The
authors concluded that rabaptin-5 is an effector of RAB5 that transmits
the signal of the active GTP-bound RAB5 conformation to the membrane
docking and/or fusion apparatus. They proposed a model in which RAB5-GDP
is converted by a membrane-bound GDP/GTP exchange factor into the active
GTP-bound conformation. Once activated, GTP-bound RAB5 then recruits
rabaptin-5 from the cytosol, thereby positioning rabaptin-5 to exert its
function in membrane docking or fusion.
Xiao et al. (1997) reported that tuberin (191092) exhibits substantial
GTPase-activating protein activity towards RAB5, and that rabaptin-5
mediates the tuberin association with RAB5.
Using immunodepletion experiments, Horiuchi et al. (1997) found that the
RABGEF1 (609700)-RABPT5 complex was essential for both homotypic and
heterotypic endosome fusions. Both RABGEF1 and RABPT5 bound RAB5
preferentially in the presence of GTP rather than GDP. RABGEF1 displayed
specific GDP/GTP exchange activity on RAB5 upon delivery of RAB5 to the
membrane.
Mattera et al. (2003) found that the GGAs (e.g., GGA1; 606004), a family
of ARF (see 103180)-dependent clathrin adaptors involved in selection of
trans-Golgi network cargo, interacted with the RABGEF1-RABPT5 complex in
vitro and in vivo.
Omori et al. (2008) identified elipsa, the zebrafish ortholog of
TRAF3IP1 (607380), as a component of intraflagellar transport particles,
which are involved in the formation and function of cilia. Elipsa
interacted with rabaptin-5, which in turn interacted with Rab8 (RAB8A;
165040), a small GTPase localized to cilia. Omori et al. (2008)
concluded that elipsa, rabaptin-5, and Rab8 provide a bridge between the
intraflagellar transport particle and protein complexes that assemble at
the ciliary membrane.
Endocytosis plays a major role in the deactivation of receptors
localized to the plasma membrane. Wang et al. (2009) found that hypoxia,
via the VHL (608537)-HIF2A (EPAS1; 603349) signaling pathway,
downregulated rabaptin-5 expression, leading to decelerated endocytosis
and prolonged activation of ligand-bound EGFR (131550). Primary kidney
and breast tumors with strong hypoxic signatures showed significantly
lower expression of rabaptin-5 RNA and protein. Wang et al. (2009)
identified a conserved hypoxia-responsive element (HRE) in the
rabaptin-5 promoter that bound in vitro-translated HIF1A (603348) and
HIF2A, leading to displacement of RNA polymerase II and attenuating
rabaptin-5 transcription.
MAPPING
The RABEP1 gene maps to chromosome 17p13 (Magnusson et al., 2001).
CYTOGENETICS
In a patient with chronic myelomonocytic leukemia (CMML; see 607785) and
an acquired t(5;17)(q33;p13), Magnusson et al. (2001) demonstrated
rabaptin-5 as a novel partner fused in-frame to the 5-prime portion of
the PDGFBR gene (173410). The fusion protein included more than 85% of
the native rabaptin-5 fused to the transmembrane and intracellular
tyrosine kinase domains of PDGFRB. Rabaptin-5 is an essential and
rate-limiting component of early endosomal fusion. The RABEP1/PDGFRB
fusion protein links 2 important pathways of growth regulation.
*FIELD* RF
1. Horiuchi, H.; Lippe, R.; McBride, H. M.; Rubino, M.; Woodman, P.;
Stenmark, H.; Rybin, V.; Wilm, M.; Ashman, K.; Mann, M.; Zerial, M.
: A novel Rab5 GDP/GTP exchange factor complexed to rabaptin-5 links
nucleotide exchange to effector recruitment and function. Cell 90:
1149-1159, 1997.
2. Magnusson, M. K.; Meade, K. E.; Brown, K. E.; Arthur, D. C.; Krueger,
L. A.; Barrett, A. J.; Dunbar, C. E.: Rabaptin-5 is a novel fusion
partner to platelet-derived growth factor beta receptor in chronic
myelomonocytic leukemia. Blood 98: 2518-2525, 2001.
3. Mattera, R.; Arighi, C. N.; Lodge, R.; Zerial, M.; Bonifacino,
J. S.: Divalent interaction of the GGAs with the Rabaptin-5-Rabex-5
complex. EMBO J. 22: 78-88, 2003.
4. Omori, Y.; Zhao, C.; Saras, A.; Mukhopadhyay, S.; Kim, W.; Furukawa,
T.; Sengupta, P.; Veraksa, A.; Malicki, J.: elipsa is an early determinant
of ciliogenesis that links the IFT particle to membrane-associated
small GTPase Rab8. Nature Cell Biol. 10: 437-444, 2008.
5. Stenmark, H.; Vitale, G.; Ullrich, O.; Zerial, M.: Rabaptin-5
is a direct effector of the small GTPase Rab5 in endocytic membrane
fusion. Cell 83: 423-432, 1995.
6. Wang, Y.; Roche, O.; Yan, M. S.; Finak, G.; Evans, A. J.; Metcalf,
J. L.; Hast, B. E.; Hanna, S. C.; Wondergem, B.; Furge, K. A.; Irwin,
M. S.; Kim, W. Y.; Teh, B. T.; Grinstein, S.; Park, M.; Marsden, P.
A.; Ohh, M.: Regulation of endocytosis via the oxygen-sensing pathway. Nature
Med. 15: 319-324, 2009.
7. Xiao, G.-H.; Shoarinejad, F.; Jin, F.; Golemis, E. A.; Yeung, R.
S.: The tuberous sclerosis 2 gene product, tuberin, functions as
a Rab5 GTPase activating protein (GAP) in modulating endocytosis. J.
Biol. Chem. 272: 6097-6100, 1997.
*FIELD* CN
Patricia A. Hartz - updated: 6/8/2009
Patricia A. Hartz - updated: 6/4/2009
Paul J. Converse - updated: 11/7/2005
Victor A. McKusick - updated: 9/27/2002
Victor A. McKusick - updated: 9/16/2002
*FIELD* CD
Rebekah S. Rasooly: 3/9/1999
*FIELD* ED
wwang: 05/18/2011
ckniffin: 5/3/2011
ckniffin: 5/2/2011
wwang: 6/11/2009
terry: 6/8/2009
mgross: 6/4/2009
terry: 6/4/2009
carol: 2/29/2008
mgross: 11/7/2005
cwells: 11/5/2003
alopez: 9/27/2002
tkritzer: 9/25/2002
tkritzer: 9/16/2002
mgross: 3/10/1999
mgross: 3/9/1999