RBCC

Full text data of RAB18

RAB18 [Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Ras-related protein Rab-18; Flags: Precursor

UniProt Q9NP72
ID RAB18_HUMAN Reviewed; 206 AA.
AC Q9NP72; B3KMC7; B7Z333; D3DRW1; Q53FX8; Q56UN9; Q6FIH1;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-2000, sequence version 1.
DT 22-JAN-2014, entry version 137.
DE RecName: Full=Ras-related protein Rab-18;
DE Flags: Precursor;
GN Name=RAB18;
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 [GENOMIC DNA].
RA Chikri M.M., Boutin M.P., Vaxillaire M.M., Froguel M.P.;
RT "In silico cloning of the human Rab18 gene.";
RL Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=10648831; DOI=10.1016/S0014-5793(99)01778-0;
RA Schaefer U., Seibold S., Schneider A., Neugebauer E.;
RT "Isolation and characterisation of the human rab18 gene after
RT stimulation of endothelial cells with histamine.";
RL FEBS Lett. 466:148-154(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND ALTERNATIVE SPLICING.
RX PubMed=16147880; DOI=10.1080/10425170500061681;
RA Dou T., Ji C., Gu S., Chen F., Xu J., Ye X., Ying K., Xie Y., Mao Y.;
RT "Cloning and characterization of a novel splice variant of human Rab18
RT gene (RAB18).";
RL DNA Seq. 16:230-234(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Cui W.C., Yu L., Liu Q., Lin W., Han X.F., Zhao S.Y.;
RT "Cloning and expression of a novel human cDNA homologous to murine
RT ras-related protein (rab18) mRNA.";
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
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 1).
RC TISSUE=Adrenal gland;
RX PubMed=10931946; DOI=10.1073/pnas.160270997;
RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X.,
RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H.,
RA Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J.,
RA Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M.,
RA Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L.;
RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal
RT axis and full-length cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Corpus callosum;
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 [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [13]
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 [14]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Hippocampus, and Skin;
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 [15]
RP PROTEIN SEQUENCE OF 1-21; 59-69 AND 99-123, ACETYLATION AT MET-1, AND
RP MASS SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RA Bienvenut W.V., Waridel P., Quadroni M.;
RL Submitted (MAR-2009) to UniProtKB.
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 (1.32 ANGSTROMS) OF 1-184 IN COMPLEX WITH GTP
RP ANALOG.
RG RIKEN structural genomics initiative (RSGI);
RT "Crystal structure of human RAB18 in complex with GPPNHP.";
RL Submitted (FEB-2009) to the PDB data bank.
RN [18]
RP VARIANTS WARBM3 GLN-24 AND ARG-93 DEL, AND FUNCTION.
RX PubMed=21473985; DOI=10.1016/j.ajhg.2011.03.012;
RA Bem D., Yoshimura S., Nunes-Bastos R., Bond F.C., Kurian M.A.,
RA Rahman F., Handley M.T., Hadzhiev Y., Masood I.,
RA Straatman-Iwanowska A.A., Cullinane A.R., McNeill A., Pasha S.S.,
RA Kirby G.A., Foster K., Ahmed Z., Morton J.E., Williams D.,
RA Graham J.M., Dobyns W.B., Burglen L., Ainsworth J.R., Gissen P.,
RA Muller F., Maher E.R., Barr F.A., Aligianis I.A.;
RT "Loss-of-function mutations in RAB18 cause Warburg micro syndrome.";
RL Am. J. Hum. Genet. 88:499-507(2011).
CC -!- FUNCTION: Plays a role in apical endocytosis/recycling. May be
CC implicated in transport between the plasma membrane and early
CC endosomes. Plays a key role in eye and brain development and
CC neurodegeneration.
CC -!- INTERACTION:
CC Q99IB8:- (xeno); NbExp=5; IntAct=EBI-722247, EBI-6931023;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor; Cytoplasmic
CC side (Potential).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9NP72-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NP72-2; Sequence=VSP_043912;
CC Note=Highly expressed in testis;
CC Name=3;
CC IsoId=Q9NP72-3; Sequence=VSP_044883;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- DISEASE: Warburg micro syndrome 3 (WARBM3) [MIM:614222]: A rare
CC syndrome characterized by microcephaly, microphthalmia,
CC microcornia, congenital cataracts, optic atrophy, cortical
CC dysplasia, in particular corpus callosum hypoplasia, severe mental
CC retardation, spastic diplegia, and hypogonadism. Note=The disease
CC is caused by mutations affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rab family.
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DR EMBL; AJ277145; CAB86486.1; -; Genomic_DNA.
DR EMBL; AJ277146; CAB86486.1; JOINED; Genomic_DNA.
DR EMBL; AJ277147; CAB86486.1; JOINED; Genomic_DNA.
DR EMBL; AJ277148; CAB86486.1; JOINED; Genomic_DNA.
DR EMBL; AJ277149; CAB86486.1; JOINED; Genomic_DNA.
DR EMBL; AF137372; AAF61433.1; -; mRNA.
DR EMBL; AY574034; AAU08232.1; -; mRNA.
DR EMBL; AF087860; AAP97170.1; -; mRNA.
DR EMBL; AF498950; AAM21098.1; -; mRNA.
DR EMBL; AF136974; AAG49435.1; -; mRNA.
DR EMBL; AL136734; CAB66668.1; -; mRNA.
DR EMBL; BT009840; AAP88842.1; -; mRNA.
DR EMBL; CR533455; CAG38486.1; -; mRNA.
DR EMBL; AK001555; BAG50939.1; -; mRNA.
DR EMBL; AK295443; BAH12069.1; -; mRNA.
DR EMBL; AK223153; BAD96873.1; -; mRNA.
DR EMBL; AL138920; CAH70590.1; -; Genomic_DNA.
DR EMBL; CH471072; EAW86054.1; -; Genomic_DNA.
DR EMBL; CH471072; EAW86055.1; -; Genomic_DNA.
DR EMBL; BC015014; AAH15014.1; -; mRNA.
DR EMBL; BC029350; AAH29350.1; -; mRNA.
DR RefSeq; NP_001243339.1; NM_001256410.1.
DR RefSeq; NP_001243340.1; NM_001256411.1.
DR RefSeq; NP_001243341.1; NM_001256412.1.
DR RefSeq; NP_001243344.1; NM_001256415.1.
DR RefSeq; NP_067075.1; NM_021252.4.
DR UniGene; Hs.406799; -.
DR PDB; 1X3S; X-ray; 1.32 A; A=1-184.
DR PDBsum; 1X3S; -.
DR ProteinModelPortal; Q9NP72; -.
DR SMR; Q9NP72; 2-178.
DR IntAct; Q9NP72; 7.
DR MINT; MINT-5003598; -.
DR STRING; 9606.ENSP00000349415; -.
DR PhosphoSite; Q9NP72; -.
DR DMDM; 12230528; -.
DR PaxDb; Q9NP72; -.
DR PRIDE; Q9NP72; -.
DR DNASU; 22931; -.
DR Ensembl; ENST00000356940; ENSP00000349415; ENSG00000099246.
DR Ensembl; ENST00000535776; ENSP00000439321; ENSG00000099246.
DR GeneID; 22931; -.
DR KEGG; hsa:22931; -.
DR UCSC; uc010qdr.3; human.
DR CTD; 22931; -.
DR GeneCards; GC10P027793; -.
DR HGNC; HGNC:14244; RAB18.
DR HPA; HPA025928; -.
DR MIM; 602207; gene.
DR MIM; 614222; phenotype.
DR neXtProt; NX_Q9NP72; -.
DR Orphanet; 2510; Micro syndrome.
DR PharmGKB; PA34106; -.
DR eggNOG; COG1100; -.
DR HOGENOM; HOG000233968; -.
DR HOVERGEN; HBG009351; -.
DR KO; K07910; -.
DR OMA; TYTTRND; -.
DR OrthoDB; EOG7CVQ04; -.
DR PhylomeDB; Q9NP72; -.
DR ChiTaRS; RAB18; human.
DR EvolutionaryTrace; Q9NP72; -.
DR GeneWiki; RAB18; -.
DR GenomeRNAi; 22931; -.
DR NextBio; 43659; -.
DR PRO; PR:Q9NP72; -.
DR ArrayExpress; Q9NP72; -.
DR Bgee; Q9NP72; -.
DR CleanEx; HS_RAB18; -.
DR Genevestigator; Q9NP72; -.
DR GO; GO:0005622; C:intracellular; IDA:LIFEdb.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0019003; F:GDP binding; IDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0003924; F:GTPase activity; NAS:UniProtKB.
DR GO; GO:0007420; P:brain development; ISS:UniProtKB.
DR GO; GO:0006897; P:endocytosis; NAS:UniProtKB.
DR GO; GO:0001654; P:eye development; ISS:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; NAS:UniProtKB.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR025662; Sigma_54_int_dom_ATP-bd_1.
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; Cell membrane;
KW Complete proteome; Developmental protein; Direct protein sequencing;
KW GTP-binding; Lipoprotein; Membrane; Methylation; Nucleotide-binding;
KW Palmitate; Polymorphism; Prenylation; Protein transport;
KW Reference proteome; Transport.
FT CHAIN 1 203 Ras-related protein Rab-18.
FT /FTId=PRO_0000121193.
FT PROPEP 204 206 Removed in mature form (Potential).
FT /FTId=PRO_0000370761.
FT NP_BIND 15 23 GTP.
FT NP_BIND 63 67 GTP.
FT NP_BIND 122 125 GTP.
FT NP_BIND 151 153 GTP.
FT MOTIF 37 45 Effector region (By similarity).
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 203 203 Cysteine methyl ester (Potential).
FT LIPID 199 199 S-palmitoyl cysteine (Potential).
FT LIPID 203 203 S-geranylgeranyl cysteine (By
FT similarity).
FT VAR_SEQ 62 62 W -> WVTLHQQTANFFLKSQIGNSPILKWAMWQY (in
FT isoform 2).
FT /FTId=VSP_043912.
FT VAR_SEQ 63 126 Missing (in isoform 3).
FT /FTId=VSP_044883.
FT VARIANT 24 24 L -> Q (in WARBM3).
FT /FTId=VAR_066495.
FT VARIANT 93 93 Missing (in WARBM3).
FT /FTId=VAR_066496.
FT VARIANT 113 113 N -> S (in dbSNP:rs12268932).
FT /FTId=VAR_051713.
FT VARIANT 198 198 A -> T (in dbSNP:rs11015859).
FT /FTId=VAR_034432.
FT CONFLICT 61 61 I -> L (in Ref. 11; BAD96873).
FT STRAND 5 14
FT HELIX 21 30
FT STRAND 42 52
FT STRAND 55 64
FT HELIX 68 70
FT HELIX 74 78
FT STRAND 83 89
FT HELIX 93 97
FT HELIX 99 106
FT STRAND 116 122
FT STRAND 126 128
FT HELIX 133 142
FT STRAND 146 149
FT TURN 152 154
FT HELIX 158 170
FT HELIX 173 175
SQ SEQUENCE 206 AA; 22977 MW; D1B0F4866547DF77 CRC64;
MDEDVLTTLK ILIIGESGVG KSSLLLRFTD DTFDPELAAT IGVDFKVKTI SVDGNKAKLA
IWDTAGQERF RTLTPSYYRG AQGVILVYDV TRRDTFVKLD NWLNELETYC TRNDIVNMLV
GNKIDKENRE VDRNEGLKFA RKHSMLFIEA SAKTCDGVQC AFEELVEKII QTPGLWESEN
QNKGVKLSHR EEGQGGGACG GYCSVL
//

MIM 602207
*RECORD*
*FIELD* NO
602207
*FIELD* TI
*602207 RAS-ASSOCIATED PROTEIN RAB18; RAB18
*FIELD* TX

DESCRIPTION

Rab proteins are members of a family of Ras-related small GTPases that
read moreregulate membrane trafficking in organelles and transport vesicles.

CLONING

By stimulating umbilical vein endothelial cells (HUVEC) with histamine
and differential display gene expression analysis, Schafer et al. (2000)
isolated a cDNA encoding RAB18. The deduced 206-amino acid protein
shares 98%, 92%, and 85% identity with the mouse, snail, and worm
sequences, respectively. RAB18 contains totally conserved
phosphate/Mg(2+)-binding motifs and guanine-binding motifs as well as
somewhat variable organelle-targeting regions. Northern blot analysis
detected 2.5- and 1.0-kb transcripts in endothelial cells but not in
smooth muscle cells or leukocytes. RT-PCR analysis suggested ubiquitous
expression, which HPLC analysis determined to be strongest in heart,
kidney, pancreas, lung, and liver, with weak expression in brain,
placenta, and skeletal muscle.

GENE FUNCTION

Schafer et al. (2000) reported that stimulation of polarized HUVEC or
nonpolarized mononuclear cells with histamine showed a significant time-
and dose-dependent increase of RAB18 transcript in both cell types,
suggesting a possible role for Rab proteins in inflammation.

MAPPING

McMurtrie et al. (1997) mapped the mouse Rab18 gene to chromosome 18.

Hartz (2009) mapped the RAB18 gene to chromosome 10p12.1 based on an
alignment of the RAB18 sequence (GenBank GENBANK AA216667) with the
genomic sequence (GRCh37).

MOLECULAR GENETICS

In affected members of 5 large consanguineous families, 4 Pakistani and
1 Turkish, segregating Warburg Micro syndrome (WARBM3; 614222), Bem et
al. (2011) identified homozygous loss-of-function mutations in the RAB18
gene (602207.0001 and 602207.0002, respectively). Direct sequencing for
RAB18 mutations in 58 additional families segregating Warburg Micro
syndrome detected compound heterozygous mutations
(602207.0003-602207.0004) in affected sibs of 1 family. Bem et al.
(2011) performed nucleotide-binding assays and showed that although
RAB18 bound GDP and GTP comparably to other RABs (RAB5A, 179512; RAB35,
604199), the RAB18 L24Q (602207.0001) and R93del (602207.0003) mutant
proteins did not bind detectable levels of either GDP or GTP and are
therefore functionally null. Bem et al. (2011) noted that the
pathogenicity of these mutations could be explained by their lack of
guanosine nucleotide binding because, as for other RAB proteins, this is
a prerequisite for correct subcellular localization and function.

ANIMAL MODEL

Bem et al. (2011) investigated the effect of knockdown of rab18 in
zebrafish to establish whether rab18 has a conserved role in brain and
eye development. The most common abnormalities observed at 3 days
post-fertilization in both the rab18a and rab18b morphants were
microphthalmia, microcephaly, pericardial edema, delayed jaw formation,
a reduced overall body size, and a general developmental delay. Further
characterization of the rab18b eye phenotype revealed that the rab18b
morphants had delayed retinal development and abnormal retinal
lamination, residual nucleated lens fiber cells, widely open choroid
fissure, and microphthalmia at day 3. To assess the specificity of the
rab18b phenotype, Bem et al. (2011) conducted a rescue experiment by
synthesizing rab18b mRNA. Partial rescue of the eye defects, pericardial
edema, and overall developmental delay was observed at 3 days.

*FIELD* AV
.0001
WARBURG MICRO SYNDROME 3
RAB18, LEU24GLN

In affected members of 4 large consanguineous Pakistani families
segregating Warburg Micro syndrome-3 (614222), Bem et al. (2011)
identified a homozygous founder mutation in the RAB18 gene: a 71T-A
transition resulting in a leu24-to-gln (L24Q) substitution.

.0002
WARBURG MICRO SYNDROME 3
RAB18, EX2DEL

In 2 affected sibs in a consanguineous Turkish family segregating
Warburg Micro syndrome-3 (614222), Bem et al. (2011) identified a
homozygous exon 2 deletion predicted to result in a frameshift. The
parents were heterozygous for the deletion.

.0003
WARBURG MICRO SYNDROME 3
RAB18, 3-BP DEL, NT277

In affected members of a family segregating Warburg Micro syndrome-3
(614222), Bem et al. (2011) identified compound heterozygous mutations
in the RAB18 gene: a 3-bp deletion (277_279del) resulting in deletion of
arginine-93 (R93del), and an antitermination mutation, a 619T-C
transition resulting in a ter207-to-gln (X207Q; 602207.0004)
substitution, predicted to extend RAB18 by 20 amino acids (X207QextX20)
and thus abolish C-terminal prenylation and membrane targeting.

.0004
WARBURG MICRO SYNDROME 3
RAB18, TER207GLN

See 602207.0003 and Bem et al. (2011).

*FIELD* RF
1. Bem, D.; Yoshimura, S.-I.; Nunes-Bastos, R.; Bond, F. C.; Kurian,
M. A.; Rahman, F.; Handley, M. T. W.; Hadzhiev, Y.; Masood, I.; Straatman-Iwanowska,
A. A.; Cullinane, A. R.; McNeill, A.; and 15 others: Loss-of-function
mutations in RAB18 cause Warburg Micro syndrome. Am. J. Hum. Genet. 88:
499-507, 2011. Note: Erratum: Am. J. Hum. Genet. 88: 678 only, 2011.

2. Hartz, P. A.: Personal Communication. Baltimore, Md. 10/28/2009.

3. McMurtrie, E. B.; Barbosa, M. D. F. S.; Zerial, M.; Kingsmore,
S. F.: Rab17 and Rab18, small GTPases with specificity for polarized
epithelial cells: genetic mapping in the mouse. Genomics 45: 623-625,
1997.

4. Schafer, U.; Seibold, S.; Schneider, A.; Neugebauer, E.: Isolation
and characterisation of the human rab18 gene after stimulation of
endothelial cells with histamine. FEBS Lett. 466: 148-154, 2000.

*FIELD* CN
Nara Sobreira - updated: 9/12/2011
Paul J. Converse - updated: 1/16/2001

*FIELD* CD
Victor A. McKusick: 12/18/1997

*FIELD* ED
carol: 09/29/2011
terry: 9/14/2011
carol: 9/14/2011
terry: 9/12/2011
carol: 10/28/2009
carol: 10/27/2009
mgross: 1/23/2001
terry: 1/16/2001
carol: 12/14/2000
mark: 12/18/1997

MIM 614222
*RECORD*
*FIELD* NO
614222
*FIELD* TI
#614222 WARBURG MICRO SYNDROME 3; WARBM3
;;MICRO SYNDROME 3
*FIELD* TX
A number sign (#) is used with this entry because Warburg Micro
read moresyndrome-3 (WARBM3) can be caused by homozygous or compound heterozygous
mutation in the RAB18 gene (602207) on chromosome 10p12.1.

For a general phenotypic description and a discussion of genetic
heterogeneity of Warburg Micro syndrome, see 600118.

CLINICAL FEATURES

Bem et al. (2011) reported 6 consanguineous families, 5 Pakistani and 1
Turkish, segregating Warburg Micro syndrome. All of the affected
children had microcephaly, brachycephaly, microphthalmia, microcornea,
low anterior hairline, large protruding pinnae, and downturned mouth
corners. The older children were wheelchair bound and had
kyphoscoliosis, severe spastic quadriplegia with contractures, and
diminished muscle bulk. The clinical features were indistinguishable
from those in patients with WARBM1 (600118) with RAB3GAP1 (602356)
mutations and from those in patients with WARBM2 (614225) with RAB3GAP2
(609275) mutations, but mutations in these genes were excluded by
linkage and direct sequencing.

MAPPING

Bem et al. (2011) performed a genomewide linkage scan in 5 large
consanguineous families segregating Warburg Micro syndrome and genotyped
11 affected children and 4 unaffected sibs. In all affected children, a
10,113.089-kb region of shared homozygosity was identified on chromosome
10p12.1. The genotyping was consistent with linkage; the parents were
heterozygous and the unaffected sibs had a haplotype different from that
of their affected sibs. A maximum 2-point lod score of 8.93 (theta = 0
at D10S1749) was calculated on the assembled haplotypes.

MOLECULAR GENETICS

In affected members of 5 large consanguineous families, 4 Pakistani and
1 Turkish, segregating Warburg Micro syndrome, Bem et al. (2011)
identified homozygous loss-of-function mutations in the RAB18 gene
(602207.0001 and 602207.0002, respectively). The mutation in the
Pakistani families was a founder mutation. Direct sequencing for RAB18
mutations in 58 additional families segregating Warburg Micro syndrome
detected compound heterozygous mutations (602207.0003-602207.0004) in
affected sibs of 1 family. Bem et al. (2011) performed
nucleotide-binding assays and showed that although RAB18 bound GDP and
GTP comparably to other RABs (RAB5A, 179512; RAB35, 604199), the RAB18
L24Q (602207.0001) and R93del (602207.0003) mutant proteins did not bind
detectable levels of either GDP or GTP and are therefore functionally
null. Bem et al. (2011) noted that the pathogenicity of these mutations
could be explained by their lack of guanosine nucleotide binding
because, as for other RAB proteins, this is a prerequisite for correct
subcellular localization and function.

*FIELD* RF
1. Bem, D.; Yoshimura, S.-I.; Nunes-Bastos, R.; Bond, F. C.; Kurian,
M. A.; Rahman, F.; Handley, M. T. W.; Hadzhiev, Y.; Masood, I.; Straatman-Iwanowska,
A. A.; Cullinane, A. R.; McNeill, A.; and 15 others: Loss-of-function
mutations in RAB18 cause Warburg Micro syndrome. Am. J. Hum. Genet. 88:
499-507, 2011. Note: Erratum: Am. J. Hum. Genet. 88: 678 only, 2011.

*FIELD* CD
Nara Sobreira: 9/12/2011

*FIELD* ED
carol: 09/29/2011
terry: 9/14/2011
carol: 9/14/2011

RBCC Red Blood Cell Collection

Full text data of RAB18