Full text data of RAB4A
RAB4A
(RAB4)
[Confidence: low (only semi-automatic identification from reviews)]
Ras-related protein Rab-4A
Ras-related protein Rab-4A
UniProt
P20338
ID RAB4A_HUMAN Reviewed; 218 AA.
AC P20338; Q5T7P7; Q9BQ44;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
read moreDT 06-MAR-2013, sequence version 3.
DT 22-JAN-2014, entry version 153.
DE RecName: Full=Ras-related protein Rab-4A;
GN Name=RAB4A; Synonyms=RAB4;
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].
RX PubMed=2501306;
RA Zahraoui A., Touchot N., Chardin P., Tavitian A.;
RT "The human Rab genes encode a family of GTP-binding proteins related
RT to yeast YPT1 and SEC4 products involved in secretion.";
RL J. Biol. Chem. 264:12394-12401(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=16935861; DOI=10.1074/jbc.M606301200;
RA Nagy G., Ward J., Mosser D.D., Koncz A., Gergely P. Jr., Stancato C.,
RA Qian Y., Fernandez D., Niland B., Grossman C.E., Telarico T.,
RA Banki K., Perl A.;
RT "Regulation of CD4 expression via recycling by HRES-1/RAB4 controls
RT susceptibility to HIV infection.";
RL J. Biol. Chem. 281:34574-34591(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RA Puhl H.L. III, Ikeda S.R., Aronstam R.S.;
RT "cDNA clones of human proteins involved in signal transduction
RT sequenced by the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Caudate nucleus;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin, and Uterus;
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 [8]
RP PHOSPHORYLATION BY CDK1.
RX PubMed=1902553; DOI=10.1038/350715a0;
RA Bailly E., McCaffrey M., Touchot N., Zahraoui A., Goud B., Bornens M.;
RT "Phosphorylation of two small GTP-binding proteins of the Rab family
RT by p34cdc2.";
RL Nature 350:715-718(1991).
RN [9]
RP PHOSPHORYLATION BY CDK1.
RX PubMed=1425574;
RA van der Sluijs P., Hull M., Huber L.A., Male P., Goud B., Mellman I.;
RT "Reversible phosphorylation-dephosphorylation determines the
RT localization of rab4 during the cell cycle.";
RL EMBO J. 11:4379-4389(1992).
RN [10]
RP INTERACTION WITH RABEP1.
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 [11]
RP INTERACTION WITH RAB11FIP1.
RC TISSUE=Cervix carcinoma;
RX PubMed=11786538; DOI=10.1074/jbc.M108665200;
RA Lindsay A.J., Hendrick A.G., Cantalupo G., Senic-Matuglia F., Goud B.,
RA Bucci C., McCaffrey M.W.;
RT "Rab coupling protein (RCP), a novel Rab4 and Rab11 effector
RT protein.";
RL J. Biol. Chem. 277:12190-12199(2002).
RN [12]
RP INTERACTION WITH ZFYVE20.
RX PubMed=11788822; DOI=10.1038/ncb744;
RA de Renzis S., Soennichsen B., Zerial M.;
RT "Divalent Rab effectors regulate the sub-compartmental organization
RT and sorting of early endosomes.";
RL Nat. Cell Biol. 4:124-133(2002).
RN [13]
RP INTERACTION WITH RAB11FIP1.
RX PubMed=15280022; DOI=10.1016/j.febslet.2004.06.068;
RA Lindsay A.J., McCaffrey M.W.;
RT "Characterisation of the Rab binding properties of Rab coupling
RT protein (RCP) by site-directed mutagenesis.";
RL FEBS Lett. 571:86-92(2004).
RN [14]
RP INTERACTION WITH RUFY1.
RX PubMed=14617813; DOI=10.1091/mbc.E03-05-0343;
RA Fouraux M.A., Deneka M., Ivan V., van der Heijden A., Raymackers J.,
RA van Suylekom D., van Venrooij W.J., van der Sluijs P., Pruijn G.J.M.;
RT "Rabip4' is an effector of rab5 and rab4 and regulates transport
RT through early endosomes.";
RL Mol. Biol. Cell 15:611-624(2004).
RN [15]
RP INTERACTION WITH NDRG1.
RX PubMed=17786215; DOI=10.1371/journal.pone.0000844;
RA Kachhap S.K., Faith D., Qian D.Z., Shabbeer S., Galloway N.L.,
RA Pili R., Denmeade S.R., DeMarzo A.M., Carducci M.A.;
RT "The N-Myc down regulated Gene1 (NDRG1) is a Rab4a effector involved
RT in vesicular recycling of E-cadherin.";
RL PLoS ONE 2:E844-E844(2007).
RN [16]
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 [17]
RP X-RAY CRYSTALLOGRAPHY (1.57 ANGSTROMS) OF 6-189 IN COMPLEX WITH GTP
RP ANALOG AND GDP.
RX PubMed=15907487; DOI=10.1016/j.febslet.2005.04.020;
RA Huber S.K., Scheidig A.J.;
RT "High resolution crystal structures of human Rab4a in its active and
RT inactive conformations.";
RL FEBS Lett. 579:2821-2829(2005).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (1.92 ANGSTROMS) OF 7-177 IN COMPLEX WITH GTP,
RP INTERACTION WITH ZFYVE20, AND MUTAGENESIS OF GLY-51.
RX PubMed=16034420; DOI=10.1038/nature03798;
RA Eathiraj S., Pan X., Ritacco C., Lambright D.G.;
RT "Structural basis of family-wide Rab GTPase recognition by rabenosyn-
RT 5.";
RL Nature 436:415-419(2005).
CC -!- FUNCTION: Protein transport. Probably involved in vesicular
CC traffic (By similarity).
CC -!- SUBUNIT: Interacts with SGSM1, SGSM2 and SGSM3 (By similarity).
CC Interacts with RAB11FIP1, RABEP1, ZFYVE20 and RUFY1. Interacts
CC (membrane-bound form) with NDRG1; the interaction involves NDRG1
CC in vesicular recycling of E-cadherin.
CC -!- INTERACTION:
CC P31150:GDI1; NbExp=2; IntAct=EBI-722284, EBI-946999;
CC P50395:GDI2; NbExp=2; IntAct=EBI-722284, EBI-1049143;
CC -!- SUBCELLULAR LOCATION: Membrane; Peripheral membrane protein.
CC Cytoplasm. Note=Generally associated with membranes. Cytoplasmic
CC when phosphorylated by CDK1.
CC -!- PTM: Phosphorylated by CDK1 kinase during mitosis.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rab family.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-6 is the initiator.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA60244.1; Type=Frameshift; Positions=6;
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DR EMBL; M28211; AAA60244.1; ALT_FRAME; mRNA.
DR EMBL; AY585832; AAT91347.1; -; mRNA.
DR EMBL; AF498934; AAM21082.1; -; mRNA.
DR EMBL; AK313807; BAG36543.1; -; mRNA.
DR EMBL; AL162595; CAI19037.1; -; Genomic_DNA.
DR EMBL; AL117350; CAI19037.1; JOINED; Genomic_DNA.
DR EMBL; AL117350; CAI22870.1; -; Genomic_DNA.
DR EMBL; AL162595; CAI22870.1; JOINED; Genomic_DNA.
DR EMBL; CH471098; EAW69890.1; -; Genomic_DNA.
DR EMBL; BC002438; AAH02438.1; -; mRNA.
DR EMBL; BC004309; AAH04309.1; -; mRNA.
DR PIR; E34323; E34323.
DR RefSeq; NP_001258927.1; NM_001271998.1.
DR RefSeq; NP_004569.2; NM_004578.3.
DR UniGene; Hs.296169; -.
DR PDB; 1YU9; X-ray; 2.07 A; A=7-177.
DR PDB; 1Z0K; X-ray; 1.92 A; A/C=7-177.
DR PDB; 2BMD; X-ray; 1.80 A; A=6-189.
DR PDB; 2BME; X-ray; 1.57 A; A/B/C/D=6-189.
DR PDBsum; 1YU9; -.
DR PDBsum; 1Z0K; -.
DR PDBsum; 2BMD; -.
DR PDBsum; 2BME; -.
DR ProteinModelPortal; P20338; -.
DR SMR; P20338; 7-182.
DR DIP; DIP-372N; -.
DR IntAct; P20338; 14.
DR MINT; MINT-1376149; -.
DR STRING; 9606.ENSP00000355651; -.
DR PhosphoSite; P20338; -.
DR DMDM; 29337213; -.
DR PaxDb; P20338; -.
DR PRIDE; P20338; -.
DR DNASU; 5867; -.
DR Ensembl; ENST00000366690; ENSP00000355651; ENSG00000168118.
DR GeneID; 5867; -.
DR KEGG; hsa:5867; -.
DR UCSC; uc001hth.4; human.
DR CTD; 5867; -.
DR GeneCards; GC01P229406; -.
DR HGNC; HGNC:9781; RAB4A.
DR HPA; CAB004990; -.
DR MIM; 179511; gene.
DR neXtProt; NX_P20338; -.
DR PharmGKB; PA34141; -.
DR eggNOG; COG1100; -.
DR HOVERGEN; HBG009351; -.
DR InParanoid; P20338; -.
DR KO; K07879; -.
DR OMA; DESNHTI; -.
DR OrthoDB; EOG7QK0CV; -.
DR Reactome; REACT_11123; Membrane Trafficking.
DR SignaLink; P20338; -.
DR EvolutionaryTrace; P20338; -.
DR GeneWiki; RAB4A; -.
DR GenomeRNAi; 5867; -.
DR NextBio; 22786; -.
DR PRO; PR:P20338; -.
DR Bgee; P20338; -.
DR CleanEx; HS_RAB4A; -.
DR Genevestigator; P20338; -.
DR GO; GO:0005768; C:endosome; IEA:Ensembl.
DR GO; GO:0070062; C:extracellular vesicular exosome; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0019003; F:GDP binding; IDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IDA:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; IDA:UniProtKB.
DR GO; GO:0008565; F:protein transporter activity; IEA:Ensembl.
DR GO; GO:0019882; P:antigen processing and presentation; IMP:UniProtKB.
DR GO; GO:0030100; P:regulation of endocytosis; IEA:Ensembl.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IEA:InterPro.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR001806; Small_GTPase.
DR InterPro; IPR003579; Small_GTPase_Rab_type.
DR Pfam; PF00071; Ras; 1.
DR PRINTS; PR00449; RASTRNSFRMNG.
DR SMART; SM00175; RAB; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51419; RAB; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Complete proteome; Cytoplasm; GTP-binding; Lipoprotein;
KW Membrane; Methylation; Nucleotide-binding; Phosphoprotein;
KW Prenylation; Protein transport; Reference proteome; Transport.
FT CHAIN 1 218 Ras-related protein Rab-4A.
FT /FTId=PRO_0000121093.
FT NP_BIND 20 28 GTP.
FT NP_BIND 68 72 GTP.
FT NP_BIND 126 129 GTP.
FT NP_BIND 156 158 GTP.
FT MOTIF 42 50 Effector region (By similarity).
FT MOD_RES 204 204 Phosphoserine; by CDK1.
FT MOD_RES 218 218 Cysteine methyl ester (By similarity).
FT LIPID 216 216 S-geranylgeranyl cysteine (By
FT similarity).
FT LIPID 218 218 S-geranylgeranyl cysteine (By
FT similarity).
FT MUTAGEN 51 51 G->A: 10-fold decrease in ZFYVE20 binding
FT affinity.
FT MUTAGEN 51 51 G->L: 10-fold decrease in ZFYVE20 binding
FT affinity.
FT CONFLICT 162 162 N -> D (in Ref. 1; AAA60244).
FT CONFLICT 208 208 A -> T (in Ref. 1; AAA60244).
FT STRAND 11 21
FT HELIX 26 35
FT STRAND 46 57
FT STRAND 60 69
FT HELIX 73 75
FT HELIX 76 80
FT STRAND 87 94
FT HELIX 98 102
FT HELIX 104 114
FT STRAND 120 126
FT HELIX 128 133
FT HELIX 138 147
FT STRAND 151 154
FT TURN 157 159
FT HELIX 163 179
SQ SEQUENCE 218 AA; 24390 MW; 983D65E1162741B0 CRC64;
MSQTAMSETY DFLFKFLVIG NAGTGKSCLL HQFIEKKFKD DSNHTIGVEF GSKIINVGGK
YVKLQIWDTA GQERFRSVTR SYYRGAAGAL LVYDITSRET YNALTNWLTD ARMLASQNIV
IILCGNKKDL DADREVTFLE ASRFAQENEL MFLETSALTG ENVEEAFVQC ARKILNKIES
GELDPERMGS GIQYGDAALR QLRSPRRAQA PNAQECGC
//
ID RAB4A_HUMAN Reviewed; 218 AA.
AC P20338; Q5T7P7; Q9BQ44;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
read moreDT 06-MAR-2013, sequence version 3.
DT 22-JAN-2014, entry version 153.
DE RecName: Full=Ras-related protein Rab-4A;
GN Name=RAB4A; Synonyms=RAB4;
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].
RX PubMed=2501306;
RA Zahraoui A., Touchot N., Chardin P., Tavitian A.;
RT "The human Rab genes encode a family of GTP-binding proteins related
RT to yeast YPT1 and SEC4 products involved in secretion.";
RL J. Biol. Chem. 264:12394-12401(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=16935861; DOI=10.1074/jbc.M606301200;
RA Nagy G., Ward J., Mosser D.D., Koncz A., Gergely P. Jr., Stancato C.,
RA Qian Y., Fernandez D., Niland B., Grossman C.E., Telarico T.,
RA Banki K., Perl A.;
RT "Regulation of CD4 expression via recycling by HRES-1/RAB4 controls
RT susceptibility to HIV infection.";
RL J. Biol. Chem. 281:34574-34591(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RA Puhl H.L. III, Ikeda S.R., Aronstam R.S.;
RT "cDNA clones of human proteins involved in signal transduction
RT sequenced by the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Caudate nucleus;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin, and Uterus;
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 [8]
RP PHOSPHORYLATION BY CDK1.
RX PubMed=1902553; DOI=10.1038/350715a0;
RA Bailly E., McCaffrey M., Touchot N., Zahraoui A., Goud B., Bornens M.;
RT "Phosphorylation of two small GTP-binding proteins of the Rab family
RT by p34cdc2.";
RL Nature 350:715-718(1991).
RN [9]
RP PHOSPHORYLATION BY CDK1.
RX PubMed=1425574;
RA van der Sluijs P., Hull M., Huber L.A., Male P., Goud B., Mellman I.;
RT "Reversible phosphorylation-dephosphorylation determines the
RT localization of rab4 during the cell cycle.";
RL EMBO J. 11:4379-4389(1992).
RN [10]
RP INTERACTION WITH RABEP1.
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 [11]
RP INTERACTION WITH RAB11FIP1.
RC TISSUE=Cervix carcinoma;
RX PubMed=11786538; DOI=10.1074/jbc.M108665200;
RA Lindsay A.J., Hendrick A.G., Cantalupo G., Senic-Matuglia F., Goud B.,
RA Bucci C., McCaffrey M.W.;
RT "Rab coupling protein (RCP), a novel Rab4 and Rab11 effector
RT protein.";
RL J. Biol. Chem. 277:12190-12199(2002).
RN [12]
RP INTERACTION WITH ZFYVE20.
RX PubMed=11788822; DOI=10.1038/ncb744;
RA de Renzis S., Soennichsen B., Zerial M.;
RT "Divalent Rab effectors regulate the sub-compartmental organization
RT and sorting of early endosomes.";
RL Nat. Cell Biol. 4:124-133(2002).
RN [13]
RP INTERACTION WITH RAB11FIP1.
RX PubMed=15280022; DOI=10.1016/j.febslet.2004.06.068;
RA Lindsay A.J., McCaffrey M.W.;
RT "Characterisation of the Rab binding properties of Rab coupling
RT protein (RCP) by site-directed mutagenesis.";
RL FEBS Lett. 571:86-92(2004).
RN [14]
RP INTERACTION WITH RUFY1.
RX PubMed=14617813; DOI=10.1091/mbc.E03-05-0343;
RA Fouraux M.A., Deneka M., Ivan V., van der Heijden A., Raymackers J.,
RA van Suylekom D., van Venrooij W.J., van der Sluijs P., Pruijn G.J.M.;
RT "Rabip4' is an effector of rab5 and rab4 and regulates transport
RT through early endosomes.";
RL Mol. Biol. Cell 15:611-624(2004).
RN [15]
RP INTERACTION WITH NDRG1.
RX PubMed=17786215; DOI=10.1371/journal.pone.0000844;
RA Kachhap S.K., Faith D., Qian D.Z., Shabbeer S., Galloway N.L.,
RA Pili R., Denmeade S.R., DeMarzo A.M., Carducci M.A.;
RT "The N-Myc down regulated Gene1 (NDRG1) is a Rab4a effector involved
RT in vesicular recycling of E-cadherin.";
RL PLoS ONE 2:E844-E844(2007).
RN [16]
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 [17]
RP X-RAY CRYSTALLOGRAPHY (1.57 ANGSTROMS) OF 6-189 IN COMPLEX WITH GTP
RP ANALOG AND GDP.
RX PubMed=15907487; DOI=10.1016/j.febslet.2005.04.020;
RA Huber S.K., Scheidig A.J.;
RT "High resolution crystal structures of human Rab4a in its active and
RT inactive conformations.";
RL FEBS Lett. 579:2821-2829(2005).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (1.92 ANGSTROMS) OF 7-177 IN COMPLEX WITH GTP,
RP INTERACTION WITH ZFYVE20, AND MUTAGENESIS OF GLY-51.
RX PubMed=16034420; DOI=10.1038/nature03798;
RA Eathiraj S., Pan X., Ritacco C., Lambright D.G.;
RT "Structural basis of family-wide Rab GTPase recognition by rabenosyn-
RT 5.";
RL Nature 436:415-419(2005).
CC -!- FUNCTION: Protein transport. Probably involved in vesicular
CC traffic (By similarity).
CC -!- SUBUNIT: Interacts with SGSM1, SGSM2 and SGSM3 (By similarity).
CC Interacts with RAB11FIP1, RABEP1, ZFYVE20 and RUFY1. Interacts
CC (membrane-bound form) with NDRG1; the interaction involves NDRG1
CC in vesicular recycling of E-cadherin.
CC -!- INTERACTION:
CC P31150:GDI1; NbExp=2; IntAct=EBI-722284, EBI-946999;
CC P50395:GDI2; NbExp=2; IntAct=EBI-722284, EBI-1049143;
CC -!- SUBCELLULAR LOCATION: Membrane; Peripheral membrane protein.
CC Cytoplasm. Note=Generally associated with membranes. Cytoplasmic
CC when phosphorylated by CDK1.
CC -!- PTM: Phosphorylated by CDK1 kinase during mitosis.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rab family.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-6 is the initiator.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA60244.1; Type=Frameshift; Positions=6;
CC -----------------------------------------------------------------------
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DR EMBL; M28211; AAA60244.1; ALT_FRAME; mRNA.
DR EMBL; AY585832; AAT91347.1; -; mRNA.
DR EMBL; AF498934; AAM21082.1; -; mRNA.
DR EMBL; AK313807; BAG36543.1; -; mRNA.
DR EMBL; AL162595; CAI19037.1; -; Genomic_DNA.
DR EMBL; AL117350; CAI19037.1; JOINED; Genomic_DNA.
DR EMBL; AL117350; CAI22870.1; -; Genomic_DNA.
DR EMBL; AL162595; CAI22870.1; JOINED; Genomic_DNA.
DR EMBL; CH471098; EAW69890.1; -; Genomic_DNA.
DR EMBL; BC002438; AAH02438.1; -; mRNA.
DR EMBL; BC004309; AAH04309.1; -; mRNA.
DR PIR; E34323; E34323.
DR RefSeq; NP_001258927.1; NM_001271998.1.
DR RefSeq; NP_004569.2; NM_004578.3.
DR UniGene; Hs.296169; -.
DR PDB; 1YU9; X-ray; 2.07 A; A=7-177.
DR PDB; 1Z0K; X-ray; 1.92 A; A/C=7-177.
DR PDB; 2BMD; X-ray; 1.80 A; A=6-189.
DR PDB; 2BME; X-ray; 1.57 A; A/B/C/D=6-189.
DR PDBsum; 1YU9; -.
DR PDBsum; 1Z0K; -.
DR PDBsum; 2BMD; -.
DR PDBsum; 2BME; -.
DR ProteinModelPortal; P20338; -.
DR SMR; P20338; 7-182.
DR DIP; DIP-372N; -.
DR IntAct; P20338; 14.
DR MINT; MINT-1376149; -.
DR STRING; 9606.ENSP00000355651; -.
DR PhosphoSite; P20338; -.
DR DMDM; 29337213; -.
DR PaxDb; P20338; -.
DR PRIDE; P20338; -.
DR DNASU; 5867; -.
DR Ensembl; ENST00000366690; ENSP00000355651; ENSG00000168118.
DR GeneID; 5867; -.
DR KEGG; hsa:5867; -.
DR UCSC; uc001hth.4; human.
DR CTD; 5867; -.
DR GeneCards; GC01P229406; -.
DR HGNC; HGNC:9781; RAB4A.
DR HPA; CAB004990; -.
DR MIM; 179511; gene.
DR neXtProt; NX_P20338; -.
DR PharmGKB; PA34141; -.
DR eggNOG; COG1100; -.
DR HOVERGEN; HBG009351; -.
DR InParanoid; P20338; -.
DR KO; K07879; -.
DR OMA; DESNHTI; -.
DR OrthoDB; EOG7QK0CV; -.
DR Reactome; REACT_11123; Membrane Trafficking.
DR SignaLink; P20338; -.
DR EvolutionaryTrace; P20338; -.
DR GeneWiki; RAB4A; -.
DR GenomeRNAi; 5867; -.
DR NextBio; 22786; -.
DR PRO; PR:P20338; -.
DR Bgee; P20338; -.
DR CleanEx; HS_RAB4A; -.
DR Genevestigator; P20338; -.
DR GO; GO:0005768; C:endosome; IEA:Ensembl.
DR GO; GO:0070062; C:extracellular vesicular exosome; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0019003; F:GDP binding; IDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IDA:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; IDA:UniProtKB.
DR GO; GO:0008565; F:protein transporter activity; IEA:Ensembl.
DR GO; GO:0019882; P:antigen processing and presentation; IMP:UniProtKB.
DR GO; GO:0030100; P:regulation of endocytosis; IEA:Ensembl.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IEA:InterPro.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR001806; Small_GTPase.
DR InterPro; IPR003579; Small_GTPase_Rab_type.
DR Pfam; PF00071; Ras; 1.
DR PRINTS; PR00449; RASTRNSFRMNG.
DR SMART; SM00175; RAB; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51419; RAB; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Complete proteome; Cytoplasm; GTP-binding; Lipoprotein;
KW Membrane; Methylation; Nucleotide-binding; Phosphoprotein;
KW Prenylation; Protein transport; Reference proteome; Transport.
FT CHAIN 1 218 Ras-related protein Rab-4A.
FT /FTId=PRO_0000121093.
FT NP_BIND 20 28 GTP.
FT NP_BIND 68 72 GTP.
FT NP_BIND 126 129 GTP.
FT NP_BIND 156 158 GTP.
FT MOTIF 42 50 Effector region (By similarity).
FT MOD_RES 204 204 Phosphoserine; by CDK1.
FT MOD_RES 218 218 Cysteine methyl ester (By similarity).
FT LIPID 216 216 S-geranylgeranyl cysteine (By
FT similarity).
FT LIPID 218 218 S-geranylgeranyl cysteine (By
FT similarity).
FT MUTAGEN 51 51 G->A: 10-fold decrease in ZFYVE20 binding
FT affinity.
FT MUTAGEN 51 51 G->L: 10-fold decrease in ZFYVE20 binding
FT affinity.
FT CONFLICT 162 162 N -> D (in Ref. 1; AAA60244).
FT CONFLICT 208 208 A -> T (in Ref. 1; AAA60244).
FT STRAND 11 21
FT HELIX 26 35
FT STRAND 46 57
FT STRAND 60 69
FT HELIX 73 75
FT HELIX 76 80
FT STRAND 87 94
FT HELIX 98 102
FT HELIX 104 114
FT STRAND 120 126
FT HELIX 128 133
FT HELIX 138 147
FT STRAND 151 154
FT TURN 157 159
FT HELIX 163 179
SQ SEQUENCE 218 AA; 24390 MW; 983D65E1162741B0 CRC64;
MSQTAMSETY DFLFKFLVIG NAGTGKSCLL HQFIEKKFKD DSNHTIGVEF GSKIINVGGK
YVKLQIWDTA GQERFRSVTR SYYRGAAGAL LVYDITSRET YNALTNWLTD ARMLASQNIV
IILCGNKKDL DADREVTFLE ASRFAQENEL MFLETSALTG ENVEEAFVQC ARKILNKIES
GELDPERMGS GIQYGDAALR QLRSPRRAQA PNAQECGC
//
MIM
179511
*RECORD*
*FIELD* NO
179511
*FIELD* TI
*179511 RAS-ASSOCIATED PROTEIN RAB4; RAB4
*FIELD* TX
CLONING
The mammalian RAB proteins show striking similarities to the S.
read morecerevisiae YPT1 and SEC4 proteins, Ras-related GTP-binding proteins
involved in the regulation of secretion. Zahraoui et al. (1989) isolated
cDNAs encoding RAB4 and several other human RAB proteins. See RAB5A
(179512). The predicted 213-amino acid human RAB4 protein shares 98% and
50% identity with rat Rab4 and human RAB2, respectively. Northern blot
analysis revealed that the RAB4 gene was expressed weakly as 1.8-, 3.1-,
and 3.6-kb mRNAs in a human fibroblast cell line.
MAPPING
By in situ hybridization, Rousseau-Merck et al. (1991) assigned the RAB4
gene to 1q42-q43. Barbosa et al. (1995) referred to this locus as RAV4A
and mapped the mouse homolog by interspecific backcross analysis to the
distal end of mouse chromosome 8. The authors mapped Rab4b (612945) to
proximal mouse chromosome 7. They also reported that 4 additional
members of the mouse Rab gene family exist on mouse chromosomes 2, 9,
12, and 13.
ANIMAL MODEL
Odley et al. (2004) developed transgenic mice expressing constitutively
active (GTPase-deficient) or dominant-inhibitory (non-GTP-binding) Rab4
mutants. Expression of constitutively active Rab4 had no effect on
cardiac structure or function, but the dominant-inhibitory Rab4 mutant
impaired the responsiveness of beta-2-adrenergic receptors (ADRB2;
109690) to endogenous and exogenous catecholamines. These defects were
accompanied by bizarre vesicular structures and abnormal accumulation of
Adrb2 in the sarcoplasm and subsarcolemma. Odley et al. (2004) presented
further evidence that Rab4 is involved in bidirectional
sarcolemmal-vesicular Adrb2 trafficking, which occurs continuously in
healthy hearts and is necessary for normal baseline adrenergic
responsiveness and resensitization after catecholamine exposure.
*FIELD* RF
1. Barbosa, M. D. F. S.; Johnson, S. A.; Achey, K.; Gutierrez, M.;
Wakeland, E. K.; Zerial, M.; Kingsmore, S. F.: The Rab protein family:
genetic mapping of six Rab genes in the mouse. Genomics 30: 439-444,
1995.
2. Odley, A.; Hahn, H. S.; Lynch, R. A.; Marreez, Y.; Osinska, H.;
Robbins, J.; Dorn, G. W., II: Regulation of cardiac contractility
by Rab4-modulated beta-2-adrenergic receptor recycling. Proc. Nat.
Acad. Sci. 101: 7082-7087, 2004.
3. Rousseau-Merck, M.-F.; Zahraoui, A.; Touchot, N.; Tavitian, A.;
Berger, R.: Chromosome assignment of four RAS-related RAB genes. Hum.
Genet. 86: 350-354, 1991.
4. Zahraoui, A.; Touchot, N.; Chardin, P.; Tavitian, A.: The human
rab genes encode a family of GTP-binding proteins related to yeast
YPT1 and SEC4 products involved in secretion. J. Biol. Chem. 264:
12394-12401, 1989.
*FIELD* CN
Patricia A. Hartz - updated: 6/17/2004
Rebekah S. Rasooly - updated: 3/8/1999
Alan F. Scott - updated: 2/27/1996
*FIELD* CD
Victor A. McKusick: 7/9/1990
*FIELD* ED
mgross: 07/30/2009
mgross: 6/28/2004
terry: 6/17/2004
mgross: 3/10/1999
mgross: 3/9/1999
mgross: 3/8/1999
psherman: 6/6/1998
terry: 4/17/1996
mark: 2/27/1996
supermim: 3/16/1992
carol: 3/22/1991
carol: 9/9/1990
carol: 7/9/1990
*RECORD*
*FIELD* NO
179511
*FIELD* TI
*179511 RAS-ASSOCIATED PROTEIN RAB4; RAB4
*FIELD* TX
CLONING
The mammalian RAB proteins show striking similarities to the S.
read morecerevisiae YPT1 and SEC4 proteins, Ras-related GTP-binding proteins
involved in the regulation of secretion. Zahraoui et al. (1989) isolated
cDNAs encoding RAB4 and several other human RAB proteins. See RAB5A
(179512). The predicted 213-amino acid human RAB4 protein shares 98% and
50% identity with rat Rab4 and human RAB2, respectively. Northern blot
analysis revealed that the RAB4 gene was expressed weakly as 1.8-, 3.1-,
and 3.6-kb mRNAs in a human fibroblast cell line.
MAPPING
By in situ hybridization, Rousseau-Merck et al. (1991) assigned the RAB4
gene to 1q42-q43. Barbosa et al. (1995) referred to this locus as RAV4A
and mapped the mouse homolog by interspecific backcross analysis to the
distal end of mouse chromosome 8. The authors mapped Rab4b (612945) to
proximal mouse chromosome 7. They also reported that 4 additional
members of the mouse Rab gene family exist on mouse chromosomes 2, 9,
12, and 13.
ANIMAL MODEL
Odley et al. (2004) developed transgenic mice expressing constitutively
active (GTPase-deficient) or dominant-inhibitory (non-GTP-binding) Rab4
mutants. Expression of constitutively active Rab4 had no effect on
cardiac structure or function, but the dominant-inhibitory Rab4 mutant
impaired the responsiveness of beta-2-adrenergic receptors (ADRB2;
109690) to endogenous and exogenous catecholamines. These defects were
accompanied by bizarre vesicular structures and abnormal accumulation of
Adrb2 in the sarcoplasm and subsarcolemma. Odley et al. (2004) presented
further evidence that Rab4 is involved in bidirectional
sarcolemmal-vesicular Adrb2 trafficking, which occurs continuously in
healthy hearts and is necessary for normal baseline adrenergic
responsiveness and resensitization after catecholamine exposure.
*FIELD* RF
1. Barbosa, M. D. F. S.; Johnson, S. A.; Achey, K.; Gutierrez, M.;
Wakeland, E. K.; Zerial, M.; Kingsmore, S. F.: The Rab protein family:
genetic mapping of six Rab genes in the mouse. Genomics 30: 439-444,
1995.
2. Odley, A.; Hahn, H. S.; Lynch, R. A.; Marreez, Y.; Osinska, H.;
Robbins, J.; Dorn, G. W., II: Regulation of cardiac contractility
by Rab4-modulated beta-2-adrenergic receptor recycling. Proc. Nat.
Acad. Sci. 101: 7082-7087, 2004.
3. Rousseau-Merck, M.-F.; Zahraoui, A.; Touchot, N.; Tavitian, A.;
Berger, R.: Chromosome assignment of four RAS-related RAB genes. Hum.
Genet. 86: 350-354, 1991.
4. Zahraoui, A.; Touchot, N.; Chardin, P.; Tavitian, A.: The human
rab genes encode a family of GTP-binding proteins related to yeast
YPT1 and SEC4 products involved in secretion. J. Biol. Chem. 264:
12394-12401, 1989.
*FIELD* CN
Patricia A. Hartz - updated: 6/17/2004
Rebekah S. Rasooly - updated: 3/8/1999
Alan F. Scott - updated: 2/27/1996
*FIELD* CD
Victor A. McKusick: 7/9/1990
*FIELD* ED
mgross: 07/30/2009
mgross: 6/28/2004
terry: 6/17/2004
mgross: 3/10/1999
mgross: 3/9/1999
mgross: 3/8/1999
psherman: 6/6/1998
terry: 4/17/1996
mark: 2/27/1996
supermim: 3/16/1992
carol: 3/22/1991
carol: 9/9/1990
carol: 7/9/1990