RABX5_BOVIN
ID RABX5_BOVIN Reviewed; 492 AA.
AC O18973;
DT 05-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 121.
DE RecName: Full=Rab5 GDP/GTP exchange factor;
DE AltName: Full=Rabex-5;
GN Name=RABGEF1; Synonyms=RABEX5;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 50-60; 142-148; 181-189;
RP 272-283; 332-341 AND 414-427, FUNCTION, INTERACTION WITH RABEP1,
RP IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Brain;
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 [2]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 9-73 IN COMPLEX WITH UBIQUITIN,
RP FUNCTION, UBIQUITINATION, AND MUTAGENESIS OF TYR-25; TYR-26; LEU-57 AND
RP ALA-58.
RX PubMed=16462746; DOI=10.1038/nsmb1064;
RA Lee S., Tsai Y.C., Mattera R., Smith W.J., Kostelansky M.S., Weissman A.M.,
RA Bonifacino J.S., Hurley J.H.;
RT "Structural basis for ubiquitin recognition and autoubiquitination by
RT Rabex-5.";
RL Nat. Struct. Mol. Biol. 13:264-271(2006).
CC -!- FUNCTION: Rab effector protein acting as linker between gamma-adaptin
CC and 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. {ECO:0000269|PubMed:16462746,
CC ECO:0000269|PubMed:9323142}.
CC -!- SUBUNIT: Heterodimer with RABEP1. The heterodimer binds RAB4A and RAB5A
CC that have been activated by GTP-binding. Binds TSC2, GGA1, GGA2, GGA3,
CC AP1G1 and AP1G2 (By similarity). Interacts with RAB21, and with 100-
CC fold lower affinity also with RAB22 (By similarity). Interacts with
CC ubiquitinated EGFR. Interacts with RGS14; the interaction is GTP-
CC dependent (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC O18973; P62990: UBC; NbExp=3; IntAct=EBI-447376, EBI-413053;
CC O18973; Q9UJY5: GGA1; Xeno; NbExp=2; IntAct=EBI-447376, EBI-447141;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:9323142}. Early
CC endosome {ECO:0000269|PubMed:9323142}. Recycling endosome
CC {ECO:0000269|PubMed:9323142}.
CC -!- TISSUE SPECIFICITY: Detected in brain. {ECO:0000269|PubMed:9323142}.
CC -!- PTM: Monoubiquitinated.
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; AJ001119; CAA04545.1; -; mRNA.
DR RefSeq; NP_777016.1; NM_174591.1.
DR PDB; 2FID; X-ray; 2.80 A; B=9-73.
DR PDB; 2FIF; X-ray; 2.49 A; B/D/F=9-73.
DR PDBsum; 2FID; -.
DR PDBsum; 2FIF; -.
DR AlphaFoldDB; O18973; -.
DR SMR; O18973; -.
DR BioGRID; 159596; 4.
DR DIP; DIP-29059N; -.
DR IntAct; O18973; 8.
DR STRING; 9913.ENSBTAP00000005011; -.
DR PaxDb; O18973; -.
DR PRIDE; O18973; -.
DR GeneID; 282335; -.
DR KEGG; bta:282335; -.
DR CTD; 27342; -.
DR eggNOG; KOG2319; Eukaryota.
DR eggNOG; KOG3173; Eukaryota.
DR HOGENOM; CLU_018416_1_1_1; -.
DR InParanoid; O18973; -.
DR OrthoDB; 944088at2759; -.
DR EvolutionaryTrace; O18973; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0030139; C:endocytic vesicle; IBA:GO_Central.
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; IBA:GO_Central.
DR GO; GO:0031267; F:small GTPase binding; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR Gene3D; 1.20.1050.80; -; 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; PTHR23101; 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; SSF109993; SSF109993; 1.
DR PROSITE; PS51205; VPS9; 1.
DR PROSITE; PS51036; ZF_A20; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Coiled coil; Cytoplasm;
KW Direct protein sequencing; Endocytosis; Endosome; Metal-binding;
KW Phosphoprotein; Protein transport; Reference proteome; Transport;
KW Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..492
FT /note="Rab5 GDP/GTP exchange factor"
FT /id="PRO_0000191314"
FT DOMAIN 233..376
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 471..492
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 408..449
FT /evidence="ECO:0000255"
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 125
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UJ41"
FT MOD_RES 133
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UJ41"
FT MOD_RES 152
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9UJ41"
FT MOD_RES 171
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9UJ41"
FT MOD_RES 374
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UJ41"
FT MOD_RES 378
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UJ41"
FT MOD_RES 391
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JM13"
FT MOD_RES 401
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UJ41"
FT MUTAGEN 25
FT /note="Y->A,P: Strongly reduced ubiquitin binding. Loss of
FT ubiquitin binding; when associated with D-58. Loss of
FT ubiquitin ligase activity; when associated with A-26."
FT /evidence="ECO:0000269|PubMed:16462746"
FT MUTAGEN 26
FT /note="Y->A,P: Strongly reduced ubiquitin binding. Loss of
FT ubiquitin ligase activity; when associated with A-25."
FT /evidence="ECO:0000269|PubMed:16462746"
FT MUTAGEN 57
FT /note="L->D: Strongly reduced ubiquitin binding."
FT /evidence="ECO:0000269|PubMed:16462746"
FT MUTAGEN 58
FT /note="A->D: Strongly reduced ubiquitin binding. Loss of
FT ubiquitin binding; when associated with A-25."
FT /evidence="ECO:0000269|PubMed:16462746"
FT STRAND 23..26
FT /evidence="ECO:0007829|PDB:2FIF"
FT HELIX 29..31
FT /evidence="ECO:0007829|PDB:2FIF"
FT HELIX 36..70
FT /evidence="ECO:0007829|PDB:2FIF"
SQ SEQUENCE 492 AA; 57009 MW; 98828A4344B15EE7 CRC64;
MSLKSERRGI HVDQSELLCK KGCGYYGNPA WQGFCSKCWR EEYHKARQKQ IQEDWELAER
LQREEEEAFA SSQSSQGAQS LTFSKFEEKK TNEKTRKVTT VKKFFSASSR VGAKKAEIQE
AKAPSPSINR QTSIETDRVS KEFIEFLKTF HKTGQEIYKQ TKLFLEAMHY KRDLSIEEQS
ECTQDFYQNV AERMQTRGKV PPERVEKIMD QIEKYIMTRL YKYVFCPETT DDEKKDLAIQ
KRIRALHWVT PQMLCVPVNE EIPEVSDMVV KAITDIIEMD SKRVPRDKLA CITKCSKHIF
NAIKITKNEP ASADDFLPTL IYIVLKGNPP RLQSNIQYIT RFCNPSRLMT GEDGYYFTNL
CCAVAFIEKL DAQSLNLSQE DFDRYMSGQT SPRKQESENW SPDACLGVKQ MYKNLDLLSQ
LNERQERIMN EAKKLEKDLI DWTDGIAKEV QDIVEKYPLE IRPPNQSVAA IDSENVENDK
LPPPLQPQVY AG
