RAB4A_MOUSE
ID RAB4A_MOUSE Reviewed; 218 AA.
AC P56371; Q3TSQ6;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2013, sequence version 2.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Ras-related protein Rab-4A;
DE EC=3.6.5.2 {ECO:0000250|UniProtKB:P20338};
GN Name=Rab4a; Synonyms=Rab4;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=8950022; DOI=10.1080/15216549600201243;
RA Ikeda H., Ikegami T., Mitsui T., Senda D., Hayasaka K.;
RT "Isolation and sequence determination of cDNA encoding mouse rab 4 and
RT candidate approach for the beige mutation in mice.";
RL Biochem. Mol. Biol. Int. 40:647-651(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=16923123; DOI=10.1111/j.1365-2443.2006.00997.x;
RA Itoh T., Satoh M., Kanno E., Fukuda M.;
RT "Screening for target Rabs of TBC (Tre-2/Bub2/Cdc16) domain-containing
RT proteins based on their Rab-binding activity.";
RL Genes Cells 11:1023-1037(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Cecum, and Medulla oblongata;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP INTERACTION WITH RUFY1.
RX PubMed=11172003; DOI=10.1073/pnas.98.4.1637;
RA Cormont M., Mari M., Galmiche A., Hofman P., Le Marchand-Brustel Y.;
RT "A FYVE-finger-containing protein, Rabip4, is a Rab4 effector involved in
RT early endosomal traffic.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:1637-1642(2001).
RN [7]
RP FUNCTION, AND SEROTONYLATION AT GLN-72.
RX PubMed=14697203; DOI=10.1016/s0092-8674(03)01014-6;
RA Walther D.J., Peter J.U., Winter S., Hoeltje M., Paulmann N., Grohmann M.,
RA Vowinckel J., Alamo-Bethencourt V., Wilhelm C.S., Ahnert-Hilger G.,
RA Bader M.;
RT "Serotonylation of small GTPases is a signal transduction pathway that
RT triggers platelet alpha-granule release.";
RL Cell 115:851-862(2003).
RN [8]
RP INTERACTION WITH SGSM1; SGSM2 AND SGSM3.
RX PubMed=17509819; DOI=10.1016/j.ygeno.2007.03.013;
RA Yang H., Sasaki T., Minoshima S., Shimizu N.;
RT "Identification of three novel proteins (SGSM1, 2, 3) which modulate small
RT G protein (RAP and RAB)-mediated signaling pathway.";
RL Genomics 90:249-260(2007).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Kidney, Liver, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [10]
RP LACK OF INTERACTION WITH HPS4.
RX PubMed=20048159; DOI=10.1074/jbc.m109.069088;
RA Kloer D.P., Rojas R., Ivan V., Moriyama K., van Vlijmen T., Murthy N.,
RA Ghirlando R., van der Sluijs P., Hurley J.H., Bonifacino J.S.;
RT "Assembly of the biogenesis of lysosome-related organelles complex-3 (BLOC-
RT 3) and its interaction with Rab9.";
RL J. Biol. Chem. 285:7794-7804(2010).
RN [11]
RP TISSUE SPECIFICITY.
RX PubMed=20098723; DOI=10.1371/journal.pbio.1000283;
RA Hoogenraad C.C., Popa I., Futai K., Martinez-Sanchez E.,
RA Sanchez-Martinez E., Wulf P.S., van Vlijmen T., Dortland B.R., Oorschot V.,
RA Govers R., Monti M., Heck A.J., Sheng M., Klumperman J., Rehmann H.,
RA Jaarsma D., Kapitein L.C., van der Sluijs P.;
RT "Neuron specific Rab4 effector GRASP-1 coordinates membrane specialization
RT and maturation of recycling endosomes.";
RL PLoS Biol. 8:E1000283-E1000283(2010).
CC -!- FUNCTION: Small GTPase which cycles between an active GTP-bound and an
CC inactive GDP-bound state (PubMed:14697203). Involved in protein
CC transport. Plays a role in vesicular traffic. Mediates VEGFR2 endosomal
CC trafficking to enhance VEGFR2 signaling (By similarity). Acts as a
CC regulator of platelet alpha-granule release during activation and
CC aggregation of platelets (PubMed:14697203).
CC {ECO:0000250|UniProtKB:P20338, ECO:0000269|PubMed:14697203}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; EC=3.6.5.2;
CC Evidence={ECO:0000250|UniProtKB:P20338};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670;
CC Evidence={ECO:0000250|UniProtKB:P20338};
CC -!- SUBUNIT: Interacts with SGSM1, SGSM2 and SGSM3 (PubMed:17509819).
CC Interacts with RAB11FIP1, RABEP1, ZFYVE20 and RUFY1 (PubMed:11172003).
CC Interacts (membrane-bound form) with NDRG1; the interaction involves
CC NDRG1 in vesicular recycling of E-cadherin. Interacts (in GTP-bound
CC form) with GRIPAP1 (via N-terminus). Interacts with RABEP1 and RBSN (By
CC similarity). Does not interact with HPS4 (By similarity). Does not
CC interact with HPS4 (PubMed:20048159). Interacts with RABEP2; this
CC interaction may mediate VEGFR2 cell surface expression (By similarity).
CC {ECO:0000250|UniProtKB:P20338, ECO:0000269|PubMed:11172003,
CC ECO:0000269|PubMed:17509819, ECO:0000269|PubMed:20048159}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:P20338};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:P20338}. Cytoplasm
CC {ECO:0000250|UniProtKB:P20338}. Early endosome membrane
CC {ECO:0000250|UniProtKB:P05714}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P05714}. Recycling endosome membrane
CC {ECO:0000250|UniProtKB:P05714}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P05714}. Note=Generally associated with
CC membranes. Cytoplasmic when phosphorylated by CDK1.
CC {ECO:0000250|UniProtKB:P20338}.
CC -!- TISSUE SPECIFICITY: Expressed in the central nervous system, including
CC cortex, cerebellum, midbrain and spinal cord, and in the kidney, lung,
CC liver and spleen. {ECO:0000269|PubMed:20098723}.
CC -!- PTM: Serotonylation of Gln-72 by TGM2 during activation and aggregation
CC of platelets leads to constitutive activation of GTPase activity.
CC {ECO:0000269|PubMed:14697203}.
CC -!- PTM: Phosphorylated by CDK1 kinase during mitosis.
CC {ECO:0000250|UniProtKB:P20338}.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rab family.
CC {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-6 is the initiator.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA24034.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; D86563; BAA24034.1; ALT_INIT; mRNA.
DR EMBL; AB232591; BAF02853.1; -; mRNA.
DR EMBL; AK136566; BAE23048.1; -; mRNA.
DR EMBL; AK161877; BAE36619.1; -; mRNA.
DR EMBL; AC147266; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466525; EDL11755.1; -; Genomic_DNA.
DR CCDS; CCDS52703.1; -.
DR RefSeq; NP_033029.2; NM_009003.3.
DR AlphaFoldDB; P56371; -.
DR SMR; P56371; -.
DR BioGRID; 202546; 1.
DR IntAct; P56371; 19.
DR MINT; P56371; -.
DR STRING; 10090.ENSMUSP00000113886; -.
DR PhosphoSitePlus; P56371; -.
DR SwissPalm; P56371; -.
DR jPOST; P56371; -.
DR PaxDb; P56371; -.
DR PRIDE; P56371; -.
DR ProteomicsDB; 253149; -.
DR Antibodypedia; 34673; 339 antibodies from 35 providers.
DR DNASU; 19341; -.
DR Ensembl; ENSMUST00000117702; ENSMUSP00000113401; ENSMUSG00000019478.
DR Ensembl; ENSMUST00000118535; ENSMUSP00000113886; ENSMUSG00000019478.
DR GeneID; 19341; -.
DR KEGG; mmu:19341; -.
DR UCSC; uc009nwo.2; mouse.
DR CTD; 5867; -.
DR MGI; MGI:105069; Rab4a.
DR VEuPathDB; HostDB:ENSMUSG00000019478; -.
DR eggNOG; KOG0086; Eukaryota.
DR GeneTree; ENSGT00940000157464; -.
DR HOGENOM; CLU_041217_23_1_1; -.
DR InParanoid; P56371; -.
DR OMA; STQECGC; -.
DR OrthoDB; 1146851at2759; -.
DR PhylomeDB; P56371; -.
DR TreeFam; TF300032; -.
DR Reactome; R-MMU-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-MMU-8854214; TBC/RABGAPs.
DR Reactome; R-MMU-8873719; RAB geranylgeranylation.
DR Reactome; R-MMU-8875656; MET receptor recycling.
DR BioGRID-ORCS; 19341; 2 hits in 74 CRISPR screens.
DR PRO; PR:P56371; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; P56371; protein.
DR Bgee; ENSMUSG00000019478; Expressed in parotid gland and 256 other tissues.
DR ExpressionAtlas; P56371; baseline and differential.
DR Genevisible; P56371; MM.
DR GO; GO:0098993; C:anchored component of synaptic vesicle membrane; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; TAS:Reactome.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005768; C:endosome; IDA:MGI.
DR GO; GO:0070062; C:extracellular exosome; ISO:MGI.
DR GO; GO:0032593; C:insulin-responsive compartment; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0098837; C:postsynaptic recycling endosome; ISO:MGI.
DR GO; GO:0055037; C:recycling endosome; ISO:MGI.
DR GO; GO:0055038; C:recycling endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0031982; C:vesicle; ISO:MGI.
DR GO; GO:0001671; F:ATPase activator activity; ISO:MGI.
DR GO; GO:0051117; F:ATPase binding; ISO:MGI.
DR GO; GO:0003925; F:G protein activity; IEA:UniProtKB-EC.
DR GO; GO:0019003; F:GDP binding; ISS:UniProtKB.
DR GO; GO:0005525; F:GTP binding; ISS:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; ISS:UniProtKB.
DR GO; GO:0035255; F:ionotropic glutamate receptor binding; ISO:MGI.
DR GO; GO:0019905; F:syntaxin binding; ISO:MGI.
DR GO; GO:0019882; P:antigen processing and presentation; ISO:MGI.
DR GO; GO:0015031; P:protein transport; IDA:MGI.
DR GO; GO:0032482; P:Rab protein signal transduction; ISO:MGI.
DR GO; GO:0030100; P:regulation of endocytosis; IDA:MGI.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IDA:MGI.
DR GO; GO:0016192; P:vesicle-mediated transport; IBA:GO_Central.
DR CDD; cd04113; Rab4; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR041819; Rab4.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR001806; Small_GTPase.
DR Pfam; PF00071; Ras; 1.
DR SMART; SM00174; RHO; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51419; RAB; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Endosome; GTP-binding; Hydrolase; Lipoprotein; Membrane;
KW Methylation; Nucleotide-binding; Phosphoprotein; Prenylation;
KW Protein transport; Reference proteome; Transport.
FT CHAIN 1..218
FT /note="Ras-related protein Rab-4A"
FT /id="PRO_0000121094"
FT MOTIF 42..50
FT /note="Effector region"
FT /evidence="ECO:0000250"
FT BINDING 20..28
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P61018"
FT BINDING 68..72
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P62820"
FT BINDING 126..129
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P61018"
FT BINDING 156..158
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P61018"
FT MOD_RES 72
FT /note="5-glutamyl serotonin"
FT /evidence="ECO:0000305|PubMed:14697203"
FT MOD_RES 190
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P20338"
FT MOD_RES 204
FT /note="Phosphoserine; by CDK1"
FT /evidence="ECO:0000250|UniProtKB:P20338"
FT MOD_RES 218
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000250"
FT LIPID 216
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 218
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000250"
FT CONFLICT 48
FT /note="V -> M (in Ref. 1; BAA24034)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 218 AA; 24409 MW; E471820A506CDA01 CRC64;
MAQTAMSETY DFLFKFLVIG NAGTGKSCLL HQFIEKKFKD DSNHTIGVEF GSKIINVGGK
YVKLQIWDTA GQERFRSVTR SYYRGAAGAL LVYDITSRET YNALTNWLTD ARMLASQNIV
LILCGNKKDL DADREVTFLE ASRFAQENEL MFLETSALTG ENVEEAFMQC ARKILNKIES
GELDPERMGS GIQYGDAALR QLRSPRRTQA PSAQECGC
