Full text data of RAB1A
RAB1A
(RAB1)
[Confidence: high (present in two of the MS resources)]
Ras-related protein Rab-1A (YPT1-related protein)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Ras-related protein Rab-1A (YPT1-related protein)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00005719
IPI00005719 Splice isoform 1 of P62820 Ras-related protein Rab-1A Splice isoform 1 of P62820 Ras-related protein Rab-1A membrane n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a 1 n/a n/a n/a n/a 2 n/a 2 n/a n/a cytoplasmic and membrane associated n/a expected molecular weight found in band between 98-188 kDa
IPI00005719 Splice isoform 1 of P62820 Ras-related protein Rab-1A Splice isoform 1 of P62820 Ras-related protein Rab-1A membrane n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a 1 n/a n/a n/a n/a 2 n/a 2 n/a n/a cytoplasmic and membrane associated n/a expected molecular weight found in band between 98-188 kDa
UniProt
P62820
ID RAB1A_HUMAN Reviewed; 205 AA.
AC P62820; P11476; Q6FIE7; Q96N61; Q9Y3T2;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 111.
DE RecName: Full=Ras-related protein Rab-1A;
DE AltName: Full=YPT1-related protein;
GN Name=RAB1A; Synonyms=RAB1;
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).
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 [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
RX PubMed=11230166; DOI=10.1101/gr.GR1547R;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H.,
RA Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N.,
RA Mewes H.-W., Ottenwaelder B., Obermaier B., Tampe J., Heubner D.,
RA Wambutt R., Korn B., Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and
RT analysis of 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 MRNA] (ISOFORM 1).
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
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 [9]
RP PROTEIN SEQUENCE OF 2-30; 52-58; 62-72; 75-111; 176-187 AND 192-198,
RP CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, AND MASS
RP SPECTROMETRY.
RC TISSUE=Platelet;
RA Bienvenut W.V., Claeys D.;
RL Submitted (NOV-2005) to UniProtKB.
RN [10]
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 [11]
RP ISOPRENYLATION AT CYS-204 AND CYS-205, AND MASS SPECTROMETRY.
RX PubMed=7991565; DOI=10.1073/pnas.91.25.11963;
RA Farnsworth C.C., Seabra M.C., Ericsson L.H., Gelb M.H., Glomset J.A.;
RT "Rab geranylgeranyl transferase catalyzes the geranylgeranylation of
RT adjacent cysteines in the small GTPases Rab1A, Rab3A, and Rab5A.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:11963-11967(1994).
RN [12]
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 [13]
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 [14]
RP INTERACTION WITH L.PNEUMOPHILA ANKX, AND CHOLINEPHOSPHORYLATION AT
RP SER-79.
RX PubMed=21822290; DOI=10.1038/nature10335;
RA Mukherjee S., Liu X., Arasaki K., McDonough J., Galan J.E., Roy C.R.;
RT "Modulation of Rab GTPase function by a protein phosphocholine
RT transferase.";
RL Nature 477:103-106(2011).
RN [15]
RP INTERACTION WITH L.PNEUMOPHILA LEM3, AND DECHOLINEPHOSPHORYLATION AT
RP SER-79.
RX PubMed=22158903; DOI=10.1073/pnas.1114023109;
RA Tan Y., Arnold R.J., Luo Z.Q.;
RT "Legionella pneumophila regulates the small GTPase Rab1 activity by
RT reversible phosphorylcholination.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:21212-21217(2011).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.63 ANGSTROMS) OF 6-177 IN COMPLEX WITH GDP.
RG Structural genomics consortium (SGC);
RT "Crystal structure of human RAB1A in complex with GDP.";
RL Submitted (FEB-2009) to the PDB data bank.
CC -!- FUNCTION: Probably required for transit of protein from the ER
CC through Golgi compartment. Binds GTP and GDP and possesses
CC intrinsic GTPase activity.
CC -!- SUBUNIT: May interact with YIPF5 (By similarity).
CC -!- INTERACTION:
CC Q5ZSQ3:drrA (xeno); NbExp=7; IntAct=EBI-716845, EBI-7632432;
CC Q01968:OCRL; NbExp=7; IntAct=EBI-716845, EBI-6148898;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus. Endoplasmic reticulum.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P62820-1, P11476-1;
CC Sequence=Displayed;
CC Name=2;
CC IsoId=P62820-2, P11476-2;
CC Sequence=VSP_005525;
CC Note=No experimental confirmation available;
CC Name=3;
CC IsoId=P62820-3, P11476-3;
CC Sequence=VSP_005526;
CC -!- PTM: Phosphorylated by CDK1 kinase during mitosis.
CC -!- PTM: Phosphocholinated at Ser-79 by L.pneumophila AnkX, leading to
CC displace GDP dissociation inhibitors (GDI). Both GDP-bound and
CC GTP-bound forms can be phosphocholinated. Dephosphocholinated by
CC L.pneumophila Lem3, restoring accessibility to L.pneumophila
CC GTPase effector LepB.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rab family.
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DR EMBL; M28209; AAA60240.1; -; mRNA.
DR EMBL; AL050268; CAB43369.1; -; mRNA.
DR EMBL; BX571747; CAE11872.1; -; mRNA.
DR EMBL; AK055927; BAB71048.1; -; mRNA.
DR EMBL; AF498929; AAM21077.1; -; mRNA.
DR EMBL; CR533479; CAG38510.1; -; mRNA.
DR EMBL; CH471053; EAW99921.1; -; Genomic_DNA.
DR EMBL; BC000905; AAH00905.1; -; mRNA.
DR PIR; A34323; TVHUYP.
DR RefSeq; NP_004152.1; NM_004161.4.
DR RefSeq; NP_056358.1; NM_015543.1.
DR RefSeq; XP_005264526.1; XM_005264469.1.
DR UniGene; Hs.310645; -.
DR PDB; 2FOL; X-ray; 2.63 A; A=6-176.
DR PDB; 2WWX; X-ray; 1.50 A; A=4-178.
DR PDB; 3L0I; X-ray; 2.85 A; B/D=1-177.
DR PDB; 3SFV; X-ray; 1.73 A; A=1-176.
DR PDB; 3TKL; X-ray; 2.18 A; A=1-191.
DR PDB; 4FMB; X-ray; 3.20 A; B/D/F=6-176.
DR PDB; 4FMC; X-ray; 2.80 A; B/D=6-176, F=14-130.
DR PDB; 4FMD; X-ray; 3.05 A; B/D=6-176, F=13-176.
DR PDB; 4FME; X-ray; 4.10 A; B/E=6-176.
DR PDB; 4IRU; X-ray; 3.20 A; B/D/F=3-177.
DR PDB; 4JVS; X-ray; 2.78 A; B=1-177.
DR PDBsum; 2FOL; -.
DR PDBsum; 2WWX; -.
DR PDBsum; 3L0I; -.
DR PDBsum; 3SFV; -.
DR PDBsum; 3TKL; -.
DR PDBsum; 4FMB; -.
DR PDBsum; 4FMC; -.
DR PDBsum; 4FMD; -.
DR PDBsum; 4FME; -.
DR PDBsum; 4IRU; -.
DR PDBsum; 4JVS; -.
DR ProteinModelPortal; P62820; -.
DR SMR; P62820; 6-176.
DR DIP; DIP-1063N; -.
DR IntAct; P62820; 32.
DR MINT; MINT-1343792; -.
DR STRING; 9606.ENSP00000387286; -.
DR PhosphoSite; P62820; -.
DR DMDM; 51338603; -.
DR PaxDb; P62820; -.
DR PRIDE; P62820; -.
DR DNASU; 5861; -.
DR Ensembl; ENST00000398529; ENSP00000381540; ENSG00000138069.
DR Ensembl; ENST00000409784; ENSP00000387286; ENSG00000138069.
DR Ensembl; ENST00000409892; ENSP00000386451; ENSG00000138069.
DR GeneID; 5861; -.
DR KEGG; hsa:5861; -.
DR UCSC; uc002sdm.3; human.
DR CTD; 5861; -.
DR GeneCards; GC02M065297; -.
DR HGNC; HGNC:9758; RAB1A.
DR HPA; CAB005331; -.
DR MIM; 179508; gene.
DR neXtProt; NX_P62820; -.
DR PharmGKB; PA34107; -.
DR eggNOG; COG1100; -.
DR HOGENOM; HOG000233968; -.
DR HOVERGEN; HBG009351; -.
DR KO; K07874; -.
DR OMA; NRVGPPS; -.
DR OrthoDB; EOG7VB2H4; -.
DR Reactome; REACT_115566; Cell Cycle.
DR Reactome; REACT_21300; Mitotic M-M/G1 phases.
DR ChiTaRS; RAB1A; human.
DR EvolutionaryTrace; P62820; -.
DR GeneWiki; RAB1A; -.
DR GenomeRNAi; 5861; -.
DR NextBio; 22762; -.
DR PRO; PR:P62820; -.
DR ArrayExpress; P62820; -.
DR Bgee; P62820; -.
DR CleanEx; HS_RAB1A; -.
DR Genevestigator; P62820; -.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0003924; F:GTPase activity; TAS:ProtInc.
DR GO; GO:0000278; P:mitotic cell cycle; TAS:Reactome.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IEA:InterPro.
DR GO; GO:0016192; P:vesicle-mediated transport; TAS:ProtInc.
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; Acetylation; Alternative splicing; Complete proteome;
KW Direct protein sequencing; Endoplasmic reticulum; ER-Golgi transport;
KW Golgi apparatus; GTP-binding; Lipoprotein; Nucleotide-binding;
KW Phosphoprotein; Prenylation; Protein transport; Reference proteome;
KW Transport.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 205 Ras-related protein Rab-1A.
FT /FTId=PRO_0000121056.
FT NP_BIND 18 26 GTP.
FT NP_BIND 66 70 GTP (By similarity).
FT NP_BIND 124 127 GTP.
FT NP_BIND 154 156 GTP.
FT MOTIF 40 48 Effector region (By similarity).
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 79 79 O-(2-cholinephosphoryl)serine; by
FT Legionella AnkX.
FT MOD_RES 194 194 Phosphoserine; by CDK1 (Probable).
FT LIPID 204 204 S-geranylgeranyl cysteine.
FT LIPID 205 205 S-geranylgeranyl cysteine.
FT VAR_SEQ 33 96 Missing (in isoform 2).
FT /FTId=VSP_005525.
FT VAR_SEQ 65 140 Missing (in isoform 3).
FT /FTId=VSP_005526.
FT STRAND 10 17
FT HELIX 24 28
FT STRAND 30 32
FT HELIX 39 44
FT STRAND 47 55
FT STRAND 58 65
FT HELIX 70 72
FT HELIX 78 80
FT TURN 81 83
FT STRAND 85 92
FT HELIX 96 112
FT STRAND 117 125
FT HELIX 129 131
FT HELIX 136 145
FT STRAND 150 154
FT TURN 155 157
FT HELIX 159 175
SQ SEQUENCE 205 AA; 22678 MW; B2A8F4E3B0FB17D6 CRC64;
MSSMNPEYDY LFKLLLIGDS GVGKSCLLLR FADDTYTESY ISTIGVDFKI RTIELDGKTI
KLQIWDTAGQ ERFRTITSSY YRGAHGIIVV YDVTDQESFN NVKQWLQEID RYASENVNKL
LVGNKCDLTT KKVVDYTTAK EFADSLGIPF LETSAKNATN VEQSFMTMAA EIKKRMGPGA
TAGGAEKSNV KIQSTPVKQS GGGCC
//
ID RAB1A_HUMAN Reviewed; 205 AA.
AC P62820; P11476; Q6FIE7; Q96N61; Q9Y3T2;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 111.
DE RecName: Full=Ras-related protein Rab-1A;
DE AltName: Full=YPT1-related protein;
GN Name=RAB1A; Synonyms=RAB1;
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).
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 [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
RX PubMed=11230166; DOI=10.1101/gr.GR1547R;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H.,
RA Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N.,
RA Mewes H.-W., Ottenwaelder B., Obermaier B., Tampe J., Heubner D.,
RA Wambutt R., Korn B., Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and
RT analysis of 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 MRNA] (ISOFORM 1).
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
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 [9]
RP PROTEIN SEQUENCE OF 2-30; 52-58; 62-72; 75-111; 176-187 AND 192-198,
RP CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, AND MASS
RP SPECTROMETRY.
RC TISSUE=Platelet;
RA Bienvenut W.V., Claeys D.;
RL Submitted (NOV-2005) to UniProtKB.
RN [10]
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 [11]
RP ISOPRENYLATION AT CYS-204 AND CYS-205, AND MASS SPECTROMETRY.
RX PubMed=7991565; DOI=10.1073/pnas.91.25.11963;
RA Farnsworth C.C., Seabra M.C., Ericsson L.H., Gelb M.H., Glomset J.A.;
RT "Rab geranylgeranyl transferase catalyzes the geranylgeranylation of
RT adjacent cysteines in the small GTPases Rab1A, Rab3A, and Rab5A.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:11963-11967(1994).
RN [12]
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 [13]
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 [14]
RP INTERACTION WITH L.PNEUMOPHILA ANKX, AND CHOLINEPHOSPHORYLATION AT
RP SER-79.
RX PubMed=21822290; DOI=10.1038/nature10335;
RA Mukherjee S., Liu X., Arasaki K., McDonough J., Galan J.E., Roy C.R.;
RT "Modulation of Rab GTPase function by a protein phosphocholine
RT transferase.";
RL Nature 477:103-106(2011).
RN [15]
RP INTERACTION WITH L.PNEUMOPHILA LEM3, AND DECHOLINEPHOSPHORYLATION AT
RP SER-79.
RX PubMed=22158903; DOI=10.1073/pnas.1114023109;
RA Tan Y., Arnold R.J., Luo Z.Q.;
RT "Legionella pneumophila regulates the small GTPase Rab1 activity by
RT reversible phosphorylcholination.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:21212-21217(2011).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.63 ANGSTROMS) OF 6-177 IN COMPLEX WITH GDP.
RG Structural genomics consortium (SGC);
RT "Crystal structure of human RAB1A in complex with GDP.";
RL Submitted (FEB-2009) to the PDB data bank.
CC -!- FUNCTION: Probably required for transit of protein from the ER
CC through Golgi compartment. Binds GTP and GDP and possesses
CC intrinsic GTPase activity.
CC -!- SUBUNIT: May interact with YIPF5 (By similarity).
CC -!- INTERACTION:
CC Q5ZSQ3:drrA (xeno); NbExp=7; IntAct=EBI-716845, EBI-7632432;
CC Q01968:OCRL; NbExp=7; IntAct=EBI-716845, EBI-6148898;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus. Endoplasmic reticulum.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P62820-1, P11476-1;
CC Sequence=Displayed;
CC Name=2;
CC IsoId=P62820-2, P11476-2;
CC Sequence=VSP_005525;
CC Note=No experimental confirmation available;
CC Name=3;
CC IsoId=P62820-3, P11476-3;
CC Sequence=VSP_005526;
CC -!- PTM: Phosphorylated by CDK1 kinase during mitosis.
CC -!- PTM: Phosphocholinated at Ser-79 by L.pneumophila AnkX, leading to
CC displace GDP dissociation inhibitors (GDI). Both GDP-bound and
CC GTP-bound forms can be phosphocholinated. Dephosphocholinated by
CC L.pneumophila Lem3, restoring accessibility to L.pneumophila
CC GTPase effector LepB.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rab family.
CC -----------------------------------------------------------------------
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DR EMBL; M28209; AAA60240.1; -; mRNA.
DR EMBL; AL050268; CAB43369.1; -; mRNA.
DR EMBL; BX571747; CAE11872.1; -; mRNA.
DR EMBL; AK055927; BAB71048.1; -; mRNA.
DR EMBL; AF498929; AAM21077.1; -; mRNA.
DR EMBL; CR533479; CAG38510.1; -; mRNA.
DR EMBL; CH471053; EAW99921.1; -; Genomic_DNA.
DR EMBL; BC000905; AAH00905.1; -; mRNA.
DR PIR; A34323; TVHUYP.
DR RefSeq; NP_004152.1; NM_004161.4.
DR RefSeq; NP_056358.1; NM_015543.1.
DR RefSeq; XP_005264526.1; XM_005264469.1.
DR UniGene; Hs.310645; -.
DR PDB; 2FOL; X-ray; 2.63 A; A=6-176.
DR PDB; 2WWX; X-ray; 1.50 A; A=4-178.
DR PDB; 3L0I; X-ray; 2.85 A; B/D=1-177.
DR PDB; 3SFV; X-ray; 1.73 A; A=1-176.
DR PDB; 3TKL; X-ray; 2.18 A; A=1-191.
DR PDB; 4FMB; X-ray; 3.20 A; B/D/F=6-176.
DR PDB; 4FMC; X-ray; 2.80 A; B/D=6-176, F=14-130.
DR PDB; 4FMD; X-ray; 3.05 A; B/D=6-176, F=13-176.
DR PDB; 4FME; X-ray; 4.10 A; B/E=6-176.
DR PDB; 4IRU; X-ray; 3.20 A; B/D/F=3-177.
DR PDB; 4JVS; X-ray; 2.78 A; B=1-177.
DR PDBsum; 2FOL; -.
DR PDBsum; 2WWX; -.
DR PDBsum; 3L0I; -.
DR PDBsum; 3SFV; -.
DR PDBsum; 3TKL; -.
DR PDBsum; 4FMB; -.
DR PDBsum; 4FMC; -.
DR PDBsum; 4FMD; -.
DR PDBsum; 4FME; -.
DR PDBsum; 4IRU; -.
DR PDBsum; 4JVS; -.
DR ProteinModelPortal; P62820; -.
DR SMR; P62820; 6-176.
DR DIP; DIP-1063N; -.
DR IntAct; P62820; 32.
DR MINT; MINT-1343792; -.
DR STRING; 9606.ENSP00000387286; -.
DR PhosphoSite; P62820; -.
DR DMDM; 51338603; -.
DR PaxDb; P62820; -.
DR PRIDE; P62820; -.
DR DNASU; 5861; -.
DR Ensembl; ENST00000398529; ENSP00000381540; ENSG00000138069.
DR Ensembl; ENST00000409784; ENSP00000387286; ENSG00000138069.
DR Ensembl; ENST00000409892; ENSP00000386451; ENSG00000138069.
DR GeneID; 5861; -.
DR KEGG; hsa:5861; -.
DR UCSC; uc002sdm.3; human.
DR CTD; 5861; -.
DR GeneCards; GC02M065297; -.
DR HGNC; HGNC:9758; RAB1A.
DR HPA; CAB005331; -.
DR MIM; 179508; gene.
DR neXtProt; NX_P62820; -.
DR PharmGKB; PA34107; -.
DR eggNOG; COG1100; -.
DR HOGENOM; HOG000233968; -.
DR HOVERGEN; HBG009351; -.
DR KO; K07874; -.
DR OMA; NRVGPPS; -.
DR OrthoDB; EOG7VB2H4; -.
DR Reactome; REACT_115566; Cell Cycle.
DR Reactome; REACT_21300; Mitotic M-M/G1 phases.
DR ChiTaRS; RAB1A; human.
DR EvolutionaryTrace; P62820; -.
DR GeneWiki; RAB1A; -.
DR GenomeRNAi; 5861; -.
DR NextBio; 22762; -.
DR PRO; PR:P62820; -.
DR ArrayExpress; P62820; -.
DR Bgee; P62820; -.
DR CleanEx; HS_RAB1A; -.
DR Genevestigator; P62820; -.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0003924; F:GTPase activity; TAS:ProtInc.
DR GO; GO:0000278; P:mitotic cell cycle; TAS:Reactome.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IEA:InterPro.
DR GO; GO:0016192; P:vesicle-mediated transport; TAS:ProtInc.
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; Acetylation; Alternative splicing; Complete proteome;
KW Direct protein sequencing; Endoplasmic reticulum; ER-Golgi transport;
KW Golgi apparatus; GTP-binding; Lipoprotein; Nucleotide-binding;
KW Phosphoprotein; Prenylation; Protein transport; Reference proteome;
KW Transport.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 205 Ras-related protein Rab-1A.
FT /FTId=PRO_0000121056.
FT NP_BIND 18 26 GTP.
FT NP_BIND 66 70 GTP (By similarity).
FT NP_BIND 124 127 GTP.
FT NP_BIND 154 156 GTP.
FT MOTIF 40 48 Effector region (By similarity).
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 79 79 O-(2-cholinephosphoryl)serine; by
FT Legionella AnkX.
FT MOD_RES 194 194 Phosphoserine; by CDK1 (Probable).
FT LIPID 204 204 S-geranylgeranyl cysteine.
FT LIPID 205 205 S-geranylgeranyl cysteine.
FT VAR_SEQ 33 96 Missing (in isoform 2).
FT /FTId=VSP_005525.
FT VAR_SEQ 65 140 Missing (in isoform 3).
FT /FTId=VSP_005526.
FT STRAND 10 17
FT HELIX 24 28
FT STRAND 30 32
FT HELIX 39 44
FT STRAND 47 55
FT STRAND 58 65
FT HELIX 70 72
FT HELIX 78 80
FT TURN 81 83
FT STRAND 85 92
FT HELIX 96 112
FT STRAND 117 125
FT HELIX 129 131
FT HELIX 136 145
FT STRAND 150 154
FT TURN 155 157
FT HELIX 159 175
SQ SEQUENCE 205 AA; 22678 MW; B2A8F4E3B0FB17D6 CRC64;
MSSMNPEYDY LFKLLLIGDS GVGKSCLLLR FADDTYTESY ISTIGVDFKI RTIELDGKTI
KLQIWDTAGQ ERFRTITSSY YRGAHGIIVV YDVTDQESFN NVKQWLQEID RYASENVNKL
LVGNKCDLTT KKVVDYTTAK EFADSLGIPF LETSAKNATN VEQSFMTMAA EIKKRMGPGA
TAGGAEKSNV KIQSTPVKQS GGGCC
//
MIM
179508
*RECORD*
*FIELD* NO
179508
*FIELD* TI
*179508 RAS-ASSOCIATED PROTEIN RAB1; RAB1
;;RAB1A
*FIELD* TX
DESCRIPTION
The small GTPase RAB1 controls vesicle traffic from the endoplasmic
read morereticulum (ER) to the Golgi apparatus. Rab1 belongs to the Ras
superfamily of GTPases that cycle between inactive GDP-bound and active
GTP-bound forms (Allan et al., 2000).
CLONING
From a human pheochromocytoma cDNA library, Zahraoui et al. (1989)
isolated 7 cDNA clones corresponding to RAB genes, including RAB1. The
predicted 205-amino acid human and rat RAB1 proteins are identical and
share 75% identity with YPT1, the S. cerevisiae homolog. Northern blot
analysis revealed that the RAB1 gene was expressed as a major (2.7 kb)
and a minor (1.7 kb) mRNA in a human fibroblast cell line.
GENE FUNCTION
Allan et al. (2000) demonstrated that the tethering factor p115 (603344)
is a RAB1 effector that binds directly to activated RAB1. RAB1 recruited
p115 to coat protein complex II (COPII; see 601924) vesicles during
budding from the endoplasmic reticulum (ER), where it interacted with a
select set of COPII vesicle-associated SNAREs (see 603215) to form a
cis-SNARE complex that promotes targeting to the Golgi apparatus. Allan
et al. (2000) proposed that RAB1-regulated assembly of functional
effector-SNARE complexes defines a conserved molecular mechanism to
coordinate recognition between subcellular compartments.
Cooper et al. (2006) found that the earliest defect following
alpha-synuclein (163890) expression in yeast was a block in ER-to-Golgi
vesicular trafficking. In a genomewide screen, the largest class of
toxicity modifiers were proteins functioning at this same step,
including the Rab guanosine triphosphate Ypt1p, which associated with
cytoplasmic alpha-synuclein inclusions. Elevated expression of Rab1, the
mammalian Ypt1 homolog, protected against alpha-synuclein-induced
dopaminergic neuron loss in animal models of Parkinson disease (168600).
Thus, Cooper et al. (2006) concluded that synucleinopathies may result
from disruptions in basic cellular functions that interface with the
unique biology of particular neurons to make them especially vulnerable.
Legionella pneumophila replicates in cellular vacuoles that recruit
material from the host cell ER. Vacuole development depends on
translocation of secreted bacterial proteins across host cell membranes.
Using binding assays and immunofluorescence microscopy, Machner and
Isberg (2006) found that the translocated protein SidM targeted host
cell RAB1. Acting as guanosine nucleotide exchange factor, SidM
recruited RAB1 to Legionella-containing vacuoles, and this process was
enhanced by bacterial LidA. Expression of SidM in mammalian cells
interfered with the secretory pathway and caused Golgi fragmentation.
Machner and Isberg (2006) proposed that SidM and LidA mimic host factors
involved in ER-derived vesicle trafficking and may facilitate vesicle
binding and integration of the Legionella-containing vacuole into the
host cell secretory pathway.
Rab GTPases regulate vesicle trafficking in eukaryotic cells by
reversibly associating with lipid membranes. Inactive Rab GTPases are
maintained in the cytosol by binding to GDP-dissociation inhibitor (GDI;
300104). It is believed that specialized proteins are required to
displace GDI from Rab GTPases before Rab activation by GDP-GTP exchange
factors (GEFs). Machner and Isberg (2007) found that SidM from
Legionella pneumophila could act as both GEF and GDI-displacement factor
(GDF) for Rab1. Rab1 released from GDI was inserted into liposomal
membranes and was used as a substrate for SidM-mediated nucleotide
exchange. During host cell infection, recruitment of Rab1 to
Legionella-containing vacuoles depended on the GDF activity of SidM.
Thus, Machner and Isberg (2007) concluded that GDF and GEF activity can
be promoted by a single protein, and GDF activity can coordinate Rab1
recruitment from the GDI-bound pool.
Ingmundson et al. (2007) expressed residues 61 to 450 of the L.
pneumophila protein SidM, which they called DrrA (defect in Rab1
recruitment A), in human embryonic kidney (HEK293) cells and found that
this region was necessary to displace GDI from a complex containing
RAB1, indicating that DrrA has GDF activity. Immunoprecipitation
analysis showed that liberated RAB1 interacted with the L. pneumophila
protein LepB in HEK293 cells. Confocal microscopy of mouse macrophages
revealed that both Rab1 and LepB were present on the early L.
pneumophila-containing vacuole membrane, but only LepB remained
associated with compartments supporting L. pneumophila replication,
while Rab1 cycled off. LepB inactivated RAB1 by stimulating GTP
hydrolysis, indicating that LepB has GAP activity. Ingmundson et al.
(2007) concluded that L. pneumophila encodes proteins that regulate
distinct biochemical reactions critical for RAB1 GTPase membrane cycling
to redirect RAB1 to the pathogen-occupied vacuole and to control RAB1
function.
Neunuebel et al. (2011) noted that bacterial SidM activates and then
AMPylates RAB1 (i.e., covalently attaches AMP to RAB1) after recruiting
RAB1 to L. pneumophila-containing vacuoles. LepB, which inactivates
RAB1, cannot bind AMPylated RAB1 in L. pneumophila-containing vacuoles.
Neunuebel et al. (2011) found that deletion of the gene adjacent to
SidM, SidD, eliminated deAMPylase activity, whereas introduction of
recombinant SidD removed AMP from RAB1. Confocal fluorescence microscopy
demonstrated a predominant perinuclear localization for SidD that
partially overlapped with Golgi markers. After SidD catalyzed AMP
release from RAB1, the deAMPylated protein was accessible for
inactivation by LepB. Neunuebel et al. (2011) concluded that SidD is the
link connecting the processes of early RAB1 accumulation and subsequent
RAB1 removal from L. pneumophila-containing vacuoles during infection.
Independently, Tan and Luo (2011) demonstrated that SidD preferentially
deAMPylated RAB1 and that the deAMPylation activity of SidD suppressed
the toxicity of SidM to yeast. They concluded that AMPylation-mediated
signal transduction is a reversible process regulated by specific
enzymes.
Mukherjee et al. (2011) used mass spectrometry to investigate
posttranslational modifications to Rab1 that occur during infection of
host cells by Legionella. Consistent with in vitro studies,
DrrA-mediated AMPylation of a conserved tyrosine residue in the switch
II region of Rab1 was detected during infection. In addition, a
modification to an adjacent serine residue in Rab1 was discovered, which
was independent of DrrA. The Legionella effector protein AnkX was
required for this modification. Biochemical studies determined that AnkX
directly mediates the covalent attachment of a phosphocholine moiety to
Rab1. This phosphocholine transferase activity used CDP-choline as a
substrate and required a conserved histidine residue located in the FIC
domain of the AnkX protein. During infection, AnkX modified both Rab1
and Rab35 (604199), which explains how this protein modulates membrane
transport through both the endocytic and exocytic pathways of the host
cell. Thus, Mukherjee et al. (2011) concluded that phosphocholination of
Rab GTPases represents a mechanism by which bacterial FIC
domain-containing proteins can alter host cell functions.
MAPPING
The 'wobbler' spinal muscular atrophy gene (see 614633) maps to proximal
mouse chromosome 11, tightly linked to Rab1 and Glns-ps1, an intronless
pseudogene of the glutamine synthetase gene (138290). Wedemeyer et al.
(1996) used these markers to construct a 1.3-Mb YAC contig of the Rab1
region on mouse chromosome 11. Two overlapping YACS were identified that
contained a 150-kb region of human chromosome 2p, comprising the RAB1
locus as well as a newly discovered STS (AHY1.1) and a trapped exon
(ETG1.1). The region was mapped to 2p14-p13.4 using somatic cell hybrids
and a radiation hybrid panel, thus extending a known region of conserved
syntenic homology between mouse chromosome 11 and human 2p.
*FIELD* RF
1. Allan, B. B.; Moyer, B. D.; Balch, W. E.: Rab1 recruitment of
p115 into a cis-SNARE complex: programming budding COPII vesicles
for fusion. Science 289: 444-448, 2000.
2. Cooper, A. A.; Gitler, A. D.; Cashikar, A.; Haynes, C. M.; Hill,
K. J.; Bhullar, B.; Liu, K.; Xu, K.; Strathearn, K. E.; Liu, F.; Cao,
S.; Caldwell, K. A.; Caldwell, G. A.; Marsischky, G.; Kolodner, R.
D.; LaBaer, J.; Rochet, J.-C.; Bonini, N. M.; Lindquist, S.: Alpha-synuclein
blocks ER-Golgi traffic and Rab1 rescues neuron loss in Parkinson's
models. Science 313: 324-328, 2006.
3. Ingmundson, A.; Delprato, A.; Lambright, D. G.; Roy, C. R.: Legionella
pneumophila proteins that regulate Rab1 membrane cycling. Nature 450:
365-369, 2007.
4. Machner, M. P.; Isberg, R. R.: A bifunctional bacterial protein
links GDI displacement to Rab1 activation. Science 318: 974-977,
2007.
5. Machner, M. P.; Isberg, R. R.: Targeting of host Rab GTPase function
by the intravacuolar pathogen Legionella pneumophila. Dev. Cell 11:
47-56, 2006.
6. Mukherjee, S.; Liu, X.; Arasaki, K.; McDonough, J.; Galan, J. E.;
Roy, C. R.: Modulation of Rab GTPase function by a protein phosphocholine
transferase. Nature 477: 103-106, 2011.
7. Neunuebel, M. R.; Chen, Y.; Gaspar, A. H.; Backlund, P. S., Jr.;
Yergey, A.; Machner, M. P.: De-AMPylation of the small GTPase Rab1
by the pathogen Legionella pneumophila. Science 333: 453-456, 2011.
8. Tan, Y.; Luo, Z.-Q.: Legionella pneumophila SidD is a deAMPylase
that modifies Rab1. Nature 475: 506-509, 2011.
9. Wedemeyer, N.; Lengeling, A.; Ronsiek, M.; Korthaus, D.; Baer,
K.; Wuttke, M.; Jockusch, H.: YAC contigs of the Rab1 and wobbler
(wr) spinal muscular atrophy gene region on proximal mouse chromosome
11 and of the homologous region on human chromosome 2p. Genomics 32:
447-454, 1996.
10. 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
Ada Hamosh - updated: 9/27/2011
Paul J. Converse - updated: 8/24/2011
Paul J. Converse - updated: 12/12/2007
Ada Hamosh - updated: 11/26/2007
Ada Hamosh - updated: 11/28/2006
Matthew B. Gross - updated: 8/8/2006
Paul J. Converse - updated: 7/28/2006
Ada Hamosh - updated: 8/1/2000
Rebekah S. Rasooly - updated: 3/8/1999
*FIELD* CD
Victor A. McKusick: 7/9/1990
*FIELD* ED
mgross: 05/11/2012
alopez: 10/5/2011
terry: 9/27/2011
mgross: 8/24/2011
terry: 8/24/2011
mgross: 12/12/2007
alopez: 11/28/2007
terry: 11/26/2007
alopez: 12/7/2006
terry: 11/28/2006
mgross: 8/8/2006
terry: 7/28/2006
carol: 2/1/2006
alopez: 8/1/2000
mgross: 3/10/1999
mgross: 3/9/1999
mgross: 3/8/1999
carol: 1/27/1998
mark: 3/28/1996
terry: 5/5/1994
carol: 10/19/1992
supermim: 3/16/1992
carol: 7/9/1990
*RECORD*
*FIELD* NO
179508
*FIELD* TI
*179508 RAS-ASSOCIATED PROTEIN RAB1; RAB1
;;RAB1A
*FIELD* TX
DESCRIPTION
The small GTPase RAB1 controls vesicle traffic from the endoplasmic
read morereticulum (ER) to the Golgi apparatus. Rab1 belongs to the Ras
superfamily of GTPases that cycle between inactive GDP-bound and active
GTP-bound forms (Allan et al., 2000).
CLONING
From a human pheochromocytoma cDNA library, Zahraoui et al. (1989)
isolated 7 cDNA clones corresponding to RAB genes, including RAB1. The
predicted 205-amino acid human and rat RAB1 proteins are identical and
share 75% identity with YPT1, the S. cerevisiae homolog. Northern blot
analysis revealed that the RAB1 gene was expressed as a major (2.7 kb)
and a minor (1.7 kb) mRNA in a human fibroblast cell line.
GENE FUNCTION
Allan et al. (2000) demonstrated that the tethering factor p115 (603344)
is a RAB1 effector that binds directly to activated RAB1. RAB1 recruited
p115 to coat protein complex II (COPII; see 601924) vesicles during
budding from the endoplasmic reticulum (ER), where it interacted with a
select set of COPII vesicle-associated SNAREs (see 603215) to form a
cis-SNARE complex that promotes targeting to the Golgi apparatus. Allan
et al. (2000) proposed that RAB1-regulated assembly of functional
effector-SNARE complexes defines a conserved molecular mechanism to
coordinate recognition between subcellular compartments.
Cooper et al. (2006) found that the earliest defect following
alpha-synuclein (163890) expression in yeast was a block in ER-to-Golgi
vesicular trafficking. In a genomewide screen, the largest class of
toxicity modifiers were proteins functioning at this same step,
including the Rab guanosine triphosphate Ypt1p, which associated with
cytoplasmic alpha-synuclein inclusions. Elevated expression of Rab1, the
mammalian Ypt1 homolog, protected against alpha-synuclein-induced
dopaminergic neuron loss in animal models of Parkinson disease (168600).
Thus, Cooper et al. (2006) concluded that synucleinopathies may result
from disruptions in basic cellular functions that interface with the
unique biology of particular neurons to make them especially vulnerable.
Legionella pneumophila replicates in cellular vacuoles that recruit
material from the host cell ER. Vacuole development depends on
translocation of secreted bacterial proteins across host cell membranes.
Using binding assays and immunofluorescence microscopy, Machner and
Isberg (2006) found that the translocated protein SidM targeted host
cell RAB1. Acting as guanosine nucleotide exchange factor, SidM
recruited RAB1 to Legionella-containing vacuoles, and this process was
enhanced by bacterial LidA. Expression of SidM in mammalian cells
interfered with the secretory pathway and caused Golgi fragmentation.
Machner and Isberg (2006) proposed that SidM and LidA mimic host factors
involved in ER-derived vesicle trafficking and may facilitate vesicle
binding and integration of the Legionella-containing vacuole into the
host cell secretory pathway.
Rab GTPases regulate vesicle trafficking in eukaryotic cells by
reversibly associating with lipid membranes. Inactive Rab GTPases are
maintained in the cytosol by binding to GDP-dissociation inhibitor (GDI;
300104). It is believed that specialized proteins are required to
displace GDI from Rab GTPases before Rab activation by GDP-GTP exchange
factors (GEFs). Machner and Isberg (2007) found that SidM from
Legionella pneumophila could act as both GEF and GDI-displacement factor
(GDF) for Rab1. Rab1 released from GDI was inserted into liposomal
membranes and was used as a substrate for SidM-mediated nucleotide
exchange. During host cell infection, recruitment of Rab1 to
Legionella-containing vacuoles depended on the GDF activity of SidM.
Thus, Machner and Isberg (2007) concluded that GDF and GEF activity can
be promoted by a single protein, and GDF activity can coordinate Rab1
recruitment from the GDI-bound pool.
Ingmundson et al. (2007) expressed residues 61 to 450 of the L.
pneumophila protein SidM, which they called DrrA (defect in Rab1
recruitment A), in human embryonic kidney (HEK293) cells and found that
this region was necessary to displace GDI from a complex containing
RAB1, indicating that DrrA has GDF activity. Immunoprecipitation
analysis showed that liberated RAB1 interacted with the L. pneumophila
protein LepB in HEK293 cells. Confocal microscopy of mouse macrophages
revealed that both Rab1 and LepB were present on the early L.
pneumophila-containing vacuole membrane, but only LepB remained
associated with compartments supporting L. pneumophila replication,
while Rab1 cycled off. LepB inactivated RAB1 by stimulating GTP
hydrolysis, indicating that LepB has GAP activity. Ingmundson et al.
(2007) concluded that L. pneumophila encodes proteins that regulate
distinct biochemical reactions critical for RAB1 GTPase membrane cycling
to redirect RAB1 to the pathogen-occupied vacuole and to control RAB1
function.
Neunuebel et al. (2011) noted that bacterial SidM activates and then
AMPylates RAB1 (i.e., covalently attaches AMP to RAB1) after recruiting
RAB1 to L. pneumophila-containing vacuoles. LepB, which inactivates
RAB1, cannot bind AMPylated RAB1 in L. pneumophila-containing vacuoles.
Neunuebel et al. (2011) found that deletion of the gene adjacent to
SidM, SidD, eliminated deAMPylase activity, whereas introduction of
recombinant SidD removed AMP from RAB1. Confocal fluorescence microscopy
demonstrated a predominant perinuclear localization for SidD that
partially overlapped with Golgi markers. After SidD catalyzed AMP
release from RAB1, the deAMPylated protein was accessible for
inactivation by LepB. Neunuebel et al. (2011) concluded that SidD is the
link connecting the processes of early RAB1 accumulation and subsequent
RAB1 removal from L. pneumophila-containing vacuoles during infection.
Independently, Tan and Luo (2011) demonstrated that SidD preferentially
deAMPylated RAB1 and that the deAMPylation activity of SidD suppressed
the toxicity of SidM to yeast. They concluded that AMPylation-mediated
signal transduction is a reversible process regulated by specific
enzymes.
Mukherjee et al. (2011) used mass spectrometry to investigate
posttranslational modifications to Rab1 that occur during infection of
host cells by Legionella. Consistent with in vitro studies,
DrrA-mediated AMPylation of a conserved tyrosine residue in the switch
II region of Rab1 was detected during infection. In addition, a
modification to an adjacent serine residue in Rab1 was discovered, which
was independent of DrrA. The Legionella effector protein AnkX was
required for this modification. Biochemical studies determined that AnkX
directly mediates the covalent attachment of a phosphocholine moiety to
Rab1. This phosphocholine transferase activity used CDP-choline as a
substrate and required a conserved histidine residue located in the FIC
domain of the AnkX protein. During infection, AnkX modified both Rab1
and Rab35 (604199), which explains how this protein modulates membrane
transport through both the endocytic and exocytic pathways of the host
cell. Thus, Mukherjee et al. (2011) concluded that phosphocholination of
Rab GTPases represents a mechanism by which bacterial FIC
domain-containing proteins can alter host cell functions.
MAPPING
The 'wobbler' spinal muscular atrophy gene (see 614633) maps to proximal
mouse chromosome 11, tightly linked to Rab1 and Glns-ps1, an intronless
pseudogene of the glutamine synthetase gene (138290). Wedemeyer et al.
(1996) used these markers to construct a 1.3-Mb YAC contig of the Rab1
region on mouse chromosome 11. Two overlapping YACS were identified that
contained a 150-kb region of human chromosome 2p, comprising the RAB1
locus as well as a newly discovered STS (AHY1.1) and a trapped exon
(ETG1.1). The region was mapped to 2p14-p13.4 using somatic cell hybrids
and a radiation hybrid panel, thus extending a known region of conserved
syntenic homology between mouse chromosome 11 and human 2p.
*FIELD* RF
1. Allan, B. B.; Moyer, B. D.; Balch, W. E.: Rab1 recruitment of
p115 into a cis-SNARE complex: programming budding COPII vesicles
for fusion. Science 289: 444-448, 2000.
2. Cooper, A. A.; Gitler, A. D.; Cashikar, A.; Haynes, C. M.; Hill,
K. J.; Bhullar, B.; Liu, K.; Xu, K.; Strathearn, K. E.; Liu, F.; Cao,
S.; Caldwell, K. A.; Caldwell, G. A.; Marsischky, G.; Kolodner, R.
D.; LaBaer, J.; Rochet, J.-C.; Bonini, N. M.; Lindquist, S.: Alpha-synuclein
blocks ER-Golgi traffic and Rab1 rescues neuron loss in Parkinson's
models. Science 313: 324-328, 2006.
3. Ingmundson, A.; Delprato, A.; Lambright, D. G.; Roy, C. R.: Legionella
pneumophila proteins that regulate Rab1 membrane cycling. Nature 450:
365-369, 2007.
4. Machner, M. P.; Isberg, R. R.: A bifunctional bacterial protein
links GDI displacement to Rab1 activation. Science 318: 974-977,
2007.
5. Machner, M. P.; Isberg, R. R.: Targeting of host Rab GTPase function
by the intravacuolar pathogen Legionella pneumophila. Dev. Cell 11:
47-56, 2006.
6. Mukherjee, S.; Liu, X.; Arasaki, K.; McDonough, J.; Galan, J. E.;
Roy, C. R.: Modulation of Rab GTPase function by a protein phosphocholine
transferase. Nature 477: 103-106, 2011.
7. Neunuebel, M. R.; Chen, Y.; Gaspar, A. H.; Backlund, P. S., Jr.;
Yergey, A.; Machner, M. P.: De-AMPylation of the small GTPase Rab1
by the pathogen Legionella pneumophila. Science 333: 453-456, 2011.
8. Tan, Y.; Luo, Z.-Q.: Legionella pneumophila SidD is a deAMPylase
that modifies Rab1. Nature 475: 506-509, 2011.
9. Wedemeyer, N.; Lengeling, A.; Ronsiek, M.; Korthaus, D.; Baer,
K.; Wuttke, M.; Jockusch, H.: YAC contigs of the Rab1 and wobbler
(wr) spinal muscular atrophy gene region on proximal mouse chromosome
11 and of the homologous region on human chromosome 2p. Genomics 32:
447-454, 1996.
10. 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
Ada Hamosh - updated: 9/27/2011
Paul J. Converse - updated: 8/24/2011
Paul J. Converse - updated: 12/12/2007
Ada Hamosh - updated: 11/26/2007
Ada Hamosh - updated: 11/28/2006
Matthew B. Gross - updated: 8/8/2006
Paul J. Converse - updated: 7/28/2006
Ada Hamosh - updated: 8/1/2000
Rebekah S. Rasooly - updated: 3/8/1999
*FIELD* CD
Victor A. McKusick: 7/9/1990
*FIELD* ED
mgross: 05/11/2012
alopez: 10/5/2011
terry: 9/27/2011
mgross: 8/24/2011
terry: 8/24/2011
mgross: 12/12/2007
alopez: 11/28/2007
terry: 11/26/2007
alopez: 12/7/2006
terry: 11/28/2006
mgross: 8/8/2006
terry: 7/28/2006
carol: 2/1/2006
alopez: 8/1/2000
mgross: 3/10/1999
mgross: 3/9/1999
mgross: 3/8/1999
carol: 1/27/1998
mark: 3/28/1996
terry: 5/5/1994
carol: 10/19/1992
supermim: 3/16/1992
carol: 7/9/1990