ID RABX5_HUMAN Reviewed; 491 AA. AC Q9UJ41; B4DZM7; Q3HKR2; Q3HKR3; Q53FG0; DT 05-JUL-2004, integrated into UniProtKB/Swiss-Prot. DT 08-MAY-2019, sequence version 3. DT 27-MAR-2024, entry version 196. DE RecName: Full=Rab5 GDP/GTP exchange factor; DE AltName: Full=RAP1; DE AltName: Full=Rabaptin-5-associated exchange factor for Rab5; DE AltName: Full=Rabex-5; GN Name=RABGEF1; Synonyms=RABEX5; 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). RX PubMed=11098082; DOI=10.1016/s0304-3835(00)00553-x; RA Nimmrich I., Erdmann S., Melchers U., Finke U., Hentsch S., Moyer M.P., RA Hoffmann I., Mueller O.; RT "Seven genes that are differentially transcribed in colorectal tumor cell RT lines."; RL Cancer Lett. 160:37-43(2000). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Cervix carcinoma; RA Barbieri M.A., Hunker C.M.; RL Submitted (OCT-2005) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). RC TISSUE=Brain, and Testis; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Testis; RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., RA Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Lymph; 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 [8] RP FUNCTION, AND INTERACTION WITH RABEP1. RX PubMed=9323142; DOI=10.1016/s0092-8674(00)80380-3; RA Horiuchi H., Lippe R., McBride H.M., Rubino M., Woodman P., Stenmark H., RA 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 [9] RP FUNCTION, AND INTERACTION WITH RABEP1. 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 factor RT Rabex-5 when physically associated in a complex."; RL Mol. Biol. Cell 12:2219-2228(2001). RN [10] 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 complex."; RL EMBO J. 22:78-88(2003). RN [11] 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 [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-124, AND IDENTIFICATION BY RP 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 [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. 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 [15] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-151 AND LYS-170, AND RP IDENTIFICATION BY MASS 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 [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-373 AND SER-377, 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 [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-124 AND SER-400, 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 [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-132, AND IDENTIFICATION BY RP 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 [19] RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 134-387, FUNCTION, INTERACTION RP WITH RAB5; RAB21 AND RAB22, AND MUTAGENESIS OF ASP-313; PRO-317; TYR-354 RP AND THR-357. RX PubMed=15339665; DOI=10.1016/j.cell.2004.08.009; RA Delprato A., Merithew E., Lambright D.G.; RT "Structure, exchange determinants, and family-wide rab specificity of the RT tandem helical bundle and Vps9 domains of Rabex-5."; RL Cell 118:607-617(2004). RN [20] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 17-74 IN COMPLEX WITH UBIQUITIN, RP UBIQUITINATION, AND MUTAGENESIS OF ALA-58. RX PubMed=16499958; DOI=10.1016/j.cell.2006.02.020; RA Penengo L., Mapelli M., Murachelli A.G., Confalonieri S., Magri L., RA Musacchio A., Di Fiore P.P., Polo S., Schneider T.R.; RT "Crystal structure of the ubiquitin binding domains of rabex-5 reveals two RT modes of interaction with ubiquitin."; RL Cell 124:1183-1195(2006). RN [21] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 134-387 IN COMPLEX WITH RAB21. RX PubMed=17450153; DOI=10.1038/nsmb1232; RA Delprato A., Lambright D.G.; RT "Structural basis for Rab GTPase activation by VPS9 domain exchange RT factors."; RL Nat. Struct. Mol. Biol. 14:406-412(2007). CC -!- FUNCTION: Rab effector protein acting as linker between gamma-adaptin, CC RAB4A or RAB5A. Involved in endocytic membrane fusion and membrane CC trafficking of recycling endosomes. Stimulates nucleotide exchange on CC RAB5A. Can act as a ubiquitin ligase (By similarity). {ECO:0000250, CC ECO:0000269|PubMed:11452015, ECO:0000269|PubMed:15339665, CC ECO:0000269|PubMed:9323142}. CC -!- SUBUNIT: Interacts with RGS14; the interaction is GTP-dependent (By CC similarity). Heterodimer with RABEP1. The heterodimer binds RAB4A and CC RAB5A that have been activated by GTP-binding. Interacts with RAB21, CC and with 100-fold lower affinity also with RAB22. Binds TSC2, GGA1, CC GGA2, GGA3, AP1G1 and AP1G2. Interacts with ubiquitinated EGFR. CC {ECO:0000250, ECO:0000269|PubMed:11452015, ECO:0000269|PubMed:12505986, CC ECO:0000269|PubMed:15339665, ECO:0000269|PubMed:16499958, CC ECO:0000269|PubMed:17450153, ECO:0000269|PubMed:9323142}. CC -!- INTERACTION: CC Q9UJ41; Q9UL45: BLOC1S6; NbExp=3; IntAct=EBI-913954, EBI-465781; CC Q9UJ41; Q9C0C6: CIPC; NbExp=3; IntAct=EBI-913954, EBI-5654244; CC Q9UJ41; Q15038: DAZAP2; NbExp=3; IntAct=EBI-913954, EBI-724310; CC Q9UJ41; P00533: EGFR; NbExp=4; IntAct=EBI-913954, EBI-297353; CC Q9UJ41; Q9BQD3: KXD1; NbExp=2; IntAct=EBI-913954, EBI-739657; CC Q9UJ41; D3DUQ6: TEAD4; NbExp=3; IntAct=EBI-913954, EBI-10176734; CC Q9UJ41; Q96FV9: THOC1; NbExp=3; IntAct=EBI-913954, EBI-1765605; CC Q9UJ41; Q9C019: TRIM15; NbExp=3; IntAct=EBI-913954, EBI-2342111; CC Q9UJ41; Q9BYV2: TRIM54; NbExp=3; IntAct=EBI-913954, EBI-2130429; CC Q9UJ41; Q99757: TXN2; NbExp=3; IntAct=EBI-913954, EBI-2932492; CC Q9UJ41; P0CG47: UBB; NbExp=6; IntAct=EBI-913954, EBI-413034; CC Q9UJ41; Q96C32: UBC; NbExp=3; IntAct=EBI-913954, EBI-745483; CC Q9UJ41; Q53FD0: ZC2HC1C; NbExp=3; IntAct=EBI-913954, EBI-740767; CC Q9UJ41; P62990: UBC; Xeno; NbExp=2; IntAct=EBI-913954, EBI-413053; CC Q9UJ41-2; Q9UL25: RAB21; NbExp=2; IntAct=EBI-6448458, EBI-1056039; CC Q9UJ41-2; Q15276: RABEP1; NbExp=2; IntAct=EBI-6448458, EBI-447043; CC Q9UJ41-4; Q9NYB9-2: ABI2; NbExp=3; IntAct=EBI-14093916, EBI-11096309; CC Q9UJ41-4; Q8N6D5: ANKRD29; NbExp=3; IntAct=EBI-14093916, EBI-17439331; CC Q9UJ41-4; Q96B67: ARRDC3; NbExp=3; IntAct=EBI-14093916, EBI-2875665; CC Q9UJ41-4; Q9UL45: BLOC1S6; NbExp=6; IntAct=EBI-14093916, EBI-465781; CC Q9UJ41-4; Q8TD31-3: CCHCR1; NbExp=3; IntAct=EBI-14093916, EBI-10175300; CC Q9UJ41-4; Q16543: CDC37; NbExp=3; IntAct=EBI-14093916, EBI-295634; CC Q9UJ41-4; Q15038: DAZAP2; NbExp=6; IntAct=EBI-14093916, EBI-724310; CC Q9UJ41-4; Q14203-5: DCTN1; NbExp=3; IntAct=EBI-14093916, EBI-25840379; CC Q9UJ41-4; Q13561: DCTN2; NbExp=3; IntAct=EBI-14093916, EBI-715074; CC Q9UJ41-4; Q9Y6C2-2: EMILIN1; NbExp=3; IntAct=EBI-14093916, EBI-11748557; CC Q9UJ41-4; Q96D09: GPRASP2; NbExp=3; IntAct=EBI-14093916, EBI-473189; CC Q9UJ41-4; Q96ED9-2: HOOK2; NbExp=3; IntAct=EBI-14093916, EBI-10961706; CC Q9UJ41-4; Q8IYA8: IHO1; NbExp=3; IntAct=EBI-14093916, EBI-8638439; CC Q9UJ41-4; Q9UJV3-2: MID2; NbExp=3; IntAct=EBI-14093916, EBI-10172526; CC Q9UJ41-4; O43482: OIP5; NbExp=3; IntAct=EBI-14093916, EBI-536879; CC Q9UJ41-4; P54725: RAD23A; NbExp=3; IntAct=EBI-14093916, EBI-746453; CC Q9UJ41-4; Q86YV0: RASAL3; NbExp=3; IntAct=EBI-14093916, EBI-3437896; CC Q9UJ41-4; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-14093916, EBI-396669; CC Q9UJ41-4; Q86VW0: SESTD1; NbExp=3; IntAct=EBI-14093916, EBI-6117072; CC Q9UJ41-4; O95295: SNAPIN; NbExp=3; IntAct=EBI-14093916, EBI-296723; CC Q9UJ41-4; P37840: SNCA; NbExp=3; IntAct=EBI-14093916, EBI-985879; CC Q9UJ41-4; Q8N0X7: SPART; NbExp=3; IntAct=EBI-14093916, EBI-2643803; CC Q9UJ41-4; Q99909: SSX3; NbExp=3; IntAct=EBI-14093916, EBI-10295431; CC Q9UJ41-4; Q9BT92: TCHP; NbExp=3; IntAct=EBI-14093916, EBI-740781; CC Q9UJ41-4; Q9BYV2: TRIM54; NbExp=3; IntAct=EBI-14093916, EBI-2130429; CC Q9UJ41-4; P62987: UBA52; NbExp=3; IntAct=EBI-14093916, EBI-357304; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12505986}. Early CC endosome {ECO:0000269|PubMed:12505986}. Recycling endosome CC {ECO:0000269|PubMed:12505986}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q9UJ41-2; Sequence=Displayed; CC Name=2; Synonyms=Long; CC IsoId=Q9UJ41-3; Sequence=VSP_060131; CC Name=3; CC IsoId=Q9UJ41-4; Sequence=VSP_060130; CC -!- PTM: Monoubiquitinated. CC -!- SEQUENCE CAUTION: CC Sequence=BAC87138.1; Type=Miscellaneous discrepancy; Note=Readthrough transcript KCTD7-RABGEF1.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AJ250042; CAB57359.1; -; mRNA. DR EMBL; DQ230533; ABA64473.1; -; mRNA. DR EMBL; DQ230534; ABA64474.1; -; mRNA. DR EMBL; BT007107; AAP35771.1; -; mRNA. DR EMBL; AK127790; BAC87138.1; ALT_SEQ; mRNA. DR EMBL; AK303006; BAG64139.1; -; mRNA. DR EMBL; AK223329; BAD97049.1; -; mRNA. DR EMBL; AC027644; AAQ93362.1; -; Genomic_DNA. DR EMBL; AC079588; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC015330; AAH15330.1; -; mRNA. DR CCDS; CCDS5535.1; -. [Q9UJ41-2] DR RefSeq; NP_001273989.1; NM_001287060.1. DR RefSeq; NP_001273990.1; NM_001287061.1. [Q9UJ41-4] DR RefSeq; NP_001273991.1; NM_001287062.1. [Q9UJ41-2] DR RefSeq; NP_055319.1; NM_014504.2. [Q9UJ41-2] DR PDB; 1TXU; X-ray; 2.35 A; A=134-387. DR PDB; 2C7M; X-ray; 2.40 A; A=17-74. DR PDB; 2C7N; X-ray; 2.10 A; A/C/E/G/I/K=17-74. DR PDB; 2OT3; X-ray; 2.10 A; A=134-387. DR PDB; 4N3X; X-ray; 2.00 A; A/B/C/D=409-455. DR PDB; 4N3Y; X-ray; 2.20 A; A=413-455. DR PDB; 4N3Z; X-ray; 3.10 A; A=134-452. DR PDB; 4Q9U; X-ray; 4.62 A; A/E=134-452. DR PDBsum; 1TXU; -. DR PDBsum; 2C7M; -. DR PDBsum; 2C7N; -. DR PDBsum; 2OT3; -. DR PDBsum; 4N3X; -. DR PDBsum; 4N3Y; -. DR PDBsum; 4N3Z; -. DR PDBsum; 4Q9U; -. DR AlphaFoldDB; Q9UJ41; -. DR SMR; Q9UJ41; -. DR BioGRID; 118154; 199. DR CORUM; Q9UJ41; -. DR DIP; DIP-29348N; -. DR IntAct; Q9UJ41; 80. DR MINT; Q9UJ41; -. DR STRING; 9606.ENSP00000370208; -. DR TCDB; 1.F.1.1.5; the synaptosomal vesicle fusion pore (svf-pore) family. DR GlyGen; Q9UJ41; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9UJ41; -. DR MetOSite; Q9UJ41; -. DR PhosphoSitePlus; Q9UJ41; -. DR BioMuta; RABGEF1; -. DR DMDM; 56405102; -. DR EPD; Q9UJ41; -. DR jPOST; Q9UJ41; -. DR MassIVE; Q9UJ41; -. DR MaxQB; Q9UJ41; -. DR PaxDb; 9606-ENSP00000370208; -. DR PeptideAtlas; Q9UJ41; -. DR ProteomicsDB; 5608; -. DR ProteomicsDB; 84585; -. [Q9UJ41-3] DR Pumba; Q9UJ41; -. DR Antibodypedia; 14115; 187 antibodies from 30 providers. DR DNASU; 27342; -. DR Ensembl; ENST00000284957.9; ENSP00000284957.4; ENSG00000154710.18. [Q9UJ41-2] DR Ensembl; ENST00000450873.6; ENSP00000415815.1; ENSG00000154710.18. [Q9UJ41-2] DR GeneID; 27342; -. DR KEGG; hsa:27342; -. DR MANE-Select; ENST00000284957.9; ENSP00000284957.4; NM_014504.3; NP_055319.1. DR UCSC; uc003tvh.4; human. [Q9UJ41-2] DR AGR; HGNC:17676; -. DR CTD; 27342; -. DR DisGeNET; 27342; -. DR GeneCards; RABGEF1; -. DR HGNC; HGNC:17676; RABGEF1. DR HPA; ENSG00000154710; Tissue enhanced (bone). DR MIM; 609700; gene. DR neXtProt; NX_Q9UJ41; -. DR OpenTargets; ENSG00000154710; -. DR PharmGKB; PA134946532; -. DR VEuPathDB; HostDB:ENSG00000154710; -. DR GeneTree; ENSGT00940000154540; -. DR InParanoid; Q9UJ41; -. DR OMA; PTITCAT; -. DR OrthoDB; 20678at2759; -. DR PhylomeDB; Q9UJ41; -. DR TreeFam; TF321331; -. DR PathwayCommons; Q9UJ41; -. DR Reactome; R-HSA-8854214; TBC/RABGAPs. DR Reactome; R-HSA-8876198; RAB GEFs exchange GTP for GDP on RABs. DR SignaLink; Q9UJ41; -. DR SIGNOR; Q9UJ41; -. DR BioGRID-ORCS; 27342; 36 hits in 1190 CRISPR screens. DR ChiTaRS; RABGEF1; human. DR EvolutionaryTrace; Q9UJ41; -. DR GeneWiki; RABGEF1; -. DR GenomeRNAi; 27342; -. DR Pharos; Q9UJ41; Tbio. DR PRO; PR:Q9UJ41; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; Q9UJ41; Protein. DR Bgee; ENSG00000154710; Expressed in bone marrow and 99 other cell types or tissues. DR ExpressionAtlas; Q9UJ41; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0030425; C:dendrite; IEA:GOC. DR GO; GO:0005769; C:early endosome; IMP:UniProtKB. DR GO; GO:0031901; C:early endosome membrane; TAS:Reactome. DR GO; GO:0030139; C:endocytic vesicle; IBA:GO_Central. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0055037; C:recycling endosome; IEA:UniProtKB-SubCell. DR GO; GO:0003677; F:DNA binding; IEA:InterPro. DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB. DR GO; GO:0031267; F:small GTPase binding; IPI:UniProtKB. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IEA:Ensembl. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0098935; P:dendritic transport; IEA:Ensembl. DR GO; GO:0038109; P:Kit signaling pathway; IEA:Ensembl. DR GO; GO:0043303; P:mast cell degranulation; IEA:Ensembl. DR GO; GO:0097531; P:mast cell migration; IEA:Ensembl. DR GO; GO:0050728; P:negative regulation of inflammatory response; IEA:Ensembl. DR GO; GO:0032715; P:negative regulation of interleukin-6 production; IEA:Ensembl. DR GO; GO:1900235; P:negative regulation of Kit signaling pathway; IEA:Ensembl. DR GO; GO:0002686; P:negative regulation of leukocyte migration; IEA:Ensembl. DR GO; GO:0033004; P:negative regulation of mast cell activation; IEA:Ensembl. DR GO; GO:0032764; P:negative regulation of mast cell cytokine production; IEA:Ensembl. DR GO; GO:0043305; P:negative regulation of mast cell degranulation; IEA:Ensembl. DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IEA:Ensembl. DR GO; GO:0046580; P:negative regulation of Ras protein signal transduction; IEA:Ensembl. DR GO; GO:0048261; P:negative regulation of receptor-mediated endocytosis; IEA:Ensembl. DR GO; GO:0006612; P:protein targeting to membrane; IMP:UniProtKB. DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW. DR GO; GO:0007265; P:Ras protein signal transduction; IEA:Ensembl. DR GO; GO:0006898; P:receptor-mediated endocytosis; IEA:Ensembl. DR GO; GO:0060368; P:regulation of Fc receptor mediated stimulatory signaling pathway; IEA:Ensembl. DR Gene3D; 1.10.246.120; -; 1. DR Gene3D; 1.20.5.4770; -; 1. DR Gene3D; 1.20.1050.80; VPS9 domain; 1. DR InterPro; IPR041545; DUF5601. DR InterPro; IPR003123; VPS9. DR InterPro; IPR045046; Vps9-like. DR InterPro; IPR037191; VPS9_dom_sf. DR InterPro; IPR002653; Znf_A20. DR PANTHER; PTHR23101; RAB GDP/GTP EXCHANGE FACTOR; 1. DR PANTHER; PTHR23101:SF122; RAB5 GDP_GTP EXCHANGE FACTOR; 1. DR Pfam; PF18151; DUF5601; 1. DR Pfam; PF02204; VPS9; 1. DR Pfam; PF01754; zf-A20; 1. DR SMART; SM00167; VPS9; 1. DR SMART; SM00259; ZnF_A20; 1. DR SUPFAM; SSF57716; Glucocorticoid receptor-like (DNA-binding domain); 1. DR SUPFAM; SSF109993; VPS9 domain; 1. DR PROSITE; PS51205; VPS9; 1. DR PROSITE; PS51036; ZF_A20; 1. DR Genevisible; Q9UJ41; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm; Endocytosis; KW Endosome; Metal-binding; Phosphoprotein; Protein transport; KW Reference proteome; Transport; Ubl conjugation; Ubl conjugation pathway; KW Zinc; Zinc-finger. FT CHAIN 1..491 FT /note="Rab5 GDP/GTP exchange factor" FT /id="PRO_0000191315" FT DOMAIN 232..375 FT /note="VPS9" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00550" FT ZN_FING 13..47 FT /note="A20-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451" FT REGION 1..74 FT /note="Interaction with ubiquitinated proteins" FT REGION 66..85 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 462..491 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 68..85 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 19 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451" FT BINDING 23 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451" FT BINDING 35 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451" FT BINDING 38 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451" FT MOD_RES 124 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 132 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 151 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 170 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 373 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 377 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 390 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9JM13" FT MOD_RES 400 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 1 FT /note="M -> MMASSYHEVVSRKKM (in isoform 3)" FT /id="VSP_060130" FT VAR_SEQ 60 FT /note="R -> RALLCYPGWSAMVQFQLTATSASWAQVILLLQPPKWLGLQK (in FT isoform 2)" FT /id="VSP_060131" FT MUTAGEN 58 FT /note="A->G: Reduces affinity for ubiquitin 3-fold." FT /evidence="ECO:0000269|PubMed:16499958" FT MUTAGEN 313 FT /note="D->A: Strongly reduced activity." FT /evidence="ECO:0000269|PubMed:15339665" FT MUTAGEN 317 FT /note="P->A: Strongly reduced activity." FT /evidence="ECO:0000269|PubMed:15339665" FT MUTAGEN 354 FT /note="Y->A: Strongly reduced activity." FT /evidence="ECO:0000269|PubMed:15339665" FT MUTAGEN 357 FT /note="T->A: Strongly reduced activity." FT /evidence="ECO:0000269|PubMed:15339665" FT CONFLICT 270 FT /note="K -> R (in Ref. 5; BAD97049)" FT /evidence="ECO:0000305" FT STRAND 23..25 FT /evidence="ECO:0007829|PDB:2C7N" FT HELIX 29..31 FT /evidence="ECO:0007829|PDB:2C7N" FT HELIX 36..70 FT /evidence="ECO:0007829|PDB:2C7N" FT HELIX 140..147 FT /evidence="ECO:0007829|PDB:2OT3" FT HELIX 150..168 FT /evidence="ECO:0007829|PDB:2OT3" FT TURN 169..172 FT /evidence="ECO:0007829|PDB:2OT3" FT HELIX 175..194 FT /evidence="ECO:0007829|PDB:2OT3" FT HELIX 201..223 FT /evidence="ECO:0007829|PDB:2OT3" FT HELIX 231..244 FT /evidence="ECO:0007829|PDB:2OT3" FT TURN 245..247 FT /evidence="ECO:0007829|PDB:2OT3" FT TURN 250..254 FT /evidence="ECO:0007829|PDB:2OT3" FT HELIX 262..277 FT /evidence="ECO:0007829|PDB:2OT3" FT HELIX 278..280 FT /evidence="ECO:0007829|PDB:2OT3" FT HELIX 284..306 FT /evidence="ECO:0007829|PDB:2OT3" FT HELIX 312..326 FT /evidence="ECO:0007829|PDB:2OT3" FT HELIX 331..341 FT /evidence="ECO:0007829|PDB:2OT3" FT TURN 344..348 FT /evidence="ECO:0007829|PDB:2OT3" FT HELIX 351..368 FT /evidence="ECO:0007829|PDB:2OT3" FT HELIX 372..374 FT /evidence="ECO:0007829|PDB:2OT3" FT HELIX 378..385 FT /evidence="ECO:0007829|PDB:2OT3" FT HELIX 409..415 FT /evidence="ECO:0007829|PDB:4N3X" FT HELIX 417..452 FT /evidence="ECO:0007829|PDB:4N3X" SQ SEQUENCE 491 AA; 56891 MW; 49ACABA276E65E91 CRC64; MSLKSERRGI HVDQSDLLCK KGCGYYGNPA WQGFCSKCWR EEYHKARQKQ IQEDWELAER LQREEEEAFA SSQSSQGAQS LTFSKFEEKK TNEKTRKVTT VKKFFSASSR VGSKKEIQEA KAPSPSINRQ TSIETDRVSK EFIEFLKTFH KTGQEIYKQT KLFLEGMHYK RDLSIEEQSE CAQDFYHNVA ERMQTRGKVP PERVEKIMDQ IEKYIMTRLY KYVFCPETTD DEKKDLAIQK RIRALRWVTP QMLCVPVNED IPEVSDMVVK AITDIIEMDS KRVPRDKLAC ITKCSKHIFN AIKITKNEPA SADDFLPTLI YIVLKGNPPR LQSNIQYITR FCNPSRLMTG EDGYYFTNLC CAVAFIEKLD AQSLNLSQED FDRYMSGQTS PRKQEAESWS PDACLGVKQM YKNLDLLSQL NERQERIMNE AKKLEKDLID WTDGIAREVQ DIVEKYPLEI KPPNQPLAAI DSENVENDKL PPPLQPQVYA G //