Full text data of RAB8A
RAB8A
(MEL, RAB8)
[Confidence: high (present in two of the MS resources)]
Ras-related protein Rab-8A (Oncogene c-mel; Flags: Precursor)
Ras-related protein Rab-8A (Oncogene c-mel; Flags: Precursor)
hRBCD
IPI00028481
IPI00028481 Ras-related protein Rab-8A Ras-related protein Rab-8A membrane 1 1 1 2 1 2 n/a 4 2 n/a 5 4 2 5 n/a 3 3 2 n/a 3 cytoplasmic and membrane associated n/a expected molecular weight found in band ~ 17 kDa
IPI00028481 Ras-related protein Rab-8A Ras-related protein Rab-8A membrane 1 1 1 2 1 2 n/a 4 2 n/a 5 4 2 5 n/a 3 3 2 n/a 3 cytoplasmic and membrane associated n/a expected molecular weight found in band ~ 17 kDa
UniProt
P61006
ID RAB8A_HUMAN Reviewed; 207 AA.
AC P61006; P24407; Q6FHV5;
DT 26-APR-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 26-APR-2004, sequence version 1.
DT 22-JAN-2014, entry version 113.
DE RecName: Full=Ras-related protein Rab-8A;
DE AltName: Full=Oncogene c-mel;
DE Flags: Precursor;
GN Name=RAB8A; Synonyms=MEL, RAB8;
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=8294494; DOI=10.1083/jcb.124.1.101;
RA Zahraoui A., Joberty G., Arpin M., Fontaine J.J., Hellio R.,
RA Tavitian A., Louvard D.;
RT "A small rab GTPase is distributed in cytoplasmic vesicles in non
RT polarized cells but colocalizes with the tight junction marker ZO-1 in
RT polarized epithelial cells.";
RL J. Cell Biol. 124:101-115(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1886711;
RA Nimmo E.R., Sanders P.G., Padua R.A., Hughes D., Williamson R.,
RA Johnson K.J.;
RT "The MEL gene: a new member of the RAB/YPT class of RAS-related
RT genes.";
RL Oncogene 6:1347-1351(1991).
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].
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 (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [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;
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 ISOPRENYLATION AT CYS-204.
RX PubMed=8375503; DOI=10.1016/0014-5793(93)80897-4;
RA Joberty G., Tavitian A., Zahraoui A.;
RT "Isoprenylation of Rab proteins possessing a C-terminal CaaX motif.";
RL FEBS Lett. 330:323-328(1993).
RN [9]
RP INTERACTION WITH RAB3IP, AND SUBCELLULAR LOCATION.
RC TISSUE=Brain;
RX PubMed=12221131; DOI=10.1091/mbc.E02-03-0143;
RA Hattula K., Furuhjelm J., Arffman A., Peranen J.;
RT "A Rab8-specific GDP/GTP exchange factor is involved in actin
RT remodeling and polarized membrane transport.";
RL Mol. Biol. Cell 13:3268-3280(2002).
RN [10]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH OPTN.
RX PubMed=15837803; DOI=10.1083/jcb.200501162;
RA Sahlender D.A., Roberts R.C., Arden S.D., Spudich G., Taylor M.J.,
RA Luzio J.P., Kendrick-Jones J., Buss F.;
RT "Optineurin links myosin VI to the Golgi complex and is involved in
RT Golgi organization and exocytosis.";
RL J. Cell Biol. 169:285-295(2005).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-185, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [12]
RP INTERACTION WITH BIRC6/BRUCE.
RX PubMed=18329369; DOI=10.1016/j.cell.2008.01.012;
RA Pohl C., Jentsch S.;
RT "Final stages of cytokinesis and midbody ring formation are controlled
RT by BRUCE.";
RL Cell 132:832-845(2008).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [15]
RP INTERACTION WITH PIFO.
RX PubMed=20643351; DOI=10.1016/j.devcel.2010.06.005;
RA Kinzel D., Boldt K., Davis E.E., Burtscher I., Trumbach D., Diplas B.,
RA Attie-Bitach T., Wurst W., Katsanis N., Ueffing M., Lickert H.;
RT "Pitchfork regulates primary cilia disassembly and left-right
RT asymmetry.";
RL Dev. Cell 19:66-77(2010).
RN [16]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=20890297; DOI=10.1038/ncb2106;
RA Bryant D.M., Datta A., Rodriguez-Fraticelli A.E., Peraenen J.,
RA Martin-Belmonte F., Mostov K.E.;
RT "A molecular network for de novo generation of the apical surface and
RT lumen.";
RL Nat. Cell Biol. 12:1035-1045(2010).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181 AND SER-185, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [18]
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 [19]
RP SUBCELLULAR LOCATION, INTERACTION WITH EHD1 AND MICALL1, AND
RP MUTAGENESIS OF THR-22 AND GLN-67.
RX PubMed=19864458; DOI=10.1091/mbc.E09-06-0535;
RA Sharma M., Giridharan S.S., Rahajeng J., Naslavsky N., Caplan S.;
RT "MICAL-L1 links EHD1 to tubular recycling endosomes and regulates
RT receptor recycling.";
RL Mol. Biol. Cell 20:5181-5194(2009).
RN [20]
RP FUNCTION, AND INTERACTION WITH MYO5B.
RX PubMed=21282656; DOI=10.1073/pnas.1010754108;
RA Roland J.T., Bryant D.M., Datta A., Itzen A., Mostov K.E.,
RA Goldenring J.R.;
RT "Rab GTPase-Myo5B complexes control membrane recycling and epithelial
RT polarization.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:2789-2794(2011).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-185, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [22]
RP SUBCELLULAR LOCATION.
RX PubMed=21255211; DOI=10.1111/j.1600-0854.2011.01165.x;
RA Seto S., Tsujimura K., Koide Y.;
RT "Rab GTPases regulating phagosome maturation are differentially
RT recruited to mycobacterial phagosomes.";
RL Traffic 12:407-420(2011).
RN [23]
RP FUNCTION IN CILIOGENESIS, AND SUBCELLULAR LOCATION.
RX PubMed=21844891; DOI=10.1038/cr.2011.134;
RA Chen Y., Wu B., Xu L., Li H., Xia J., Yin W., Li Z., Shi D., Li S.,
RA Lin S., Shu X., Pei D.;
RT "A SNX10/V-ATPase pathway regulates ciliogenesis in vitro and in
RT vivo.";
RL Cell Res. 22:333-345(2012).
RN [24]
RP INTERACTION WITH OCRL.
RX PubMed=22543976; DOI=10.1093/hmg/dds163;
RA Luo N., West C.C., Murga-Zamalloa C.A., Sun L., Anderson R.M.,
RA Wells C.D., Weinreb R.N., Travers J.B., Khanna H., Sun Y.;
RT "OCRL localizes to the primary cilium: a new role for cilia in Lowe
RT syndrome.";
RL Hum. Mol. Genet. 21:3333-3344(2012).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 6-176 IN COMPLEX WITH OCRL.
RX PubMed=21378754; DOI=10.1038/emboj.2011.60;
RA Hou X., Hagemann N., Schoebel S., Blankenfeldt W., Goody R.S.,
RA Erdmann K.S., Itzen A.;
RT "A structural basis for Lowe syndrome caused by mutations in the Rab-
RT binding domain of OCRL1.";
RL EMBO J. 30:1659-1670(2011).
CC -!- FUNCTION: The small GTPases Rab are key regulators of
CC intracellular membrane trafficking, from the formation of
CC transport vesicles to their fusion with membranes. Rabs cycle
CC between an inactive GDP-bound form and an active GTP-bound form
CC that is able to recruit to membranes different sets of downstream
CC effectors directly responsible for vesicle formation, movement,
CC tethering and fusion. That Rab is involved in polarized vesicular
CC trafficking and neurotransmitter release. Together with RAB11A,
CC RAB3IP, the exocyst complex, PARD3, PRKCI, ANXA2, CDC42 and DNMBP
CC promotes transcytosis of PODXL to the apical membrane initiation
CC sites (AMIS), apical surface formation and lumenogenesis. Together
CC with MYO5B and RAB11A participates in epithelial cell
CC polarization. Plays an important role in ciliogenesis. Together
CC with MICALL2, may also regulate adherens junction assembly. May
CC play a role in insulin-induced transport to the plasma membrane of
CC the glucose transporter GLUT4 and therefore play a role in glucose
CC homeostasis.
CC -!- ENZYME REGULATION: Activated in response to insulin (By
CC similarity).
CC -!- SUBUNIT: Interacts (GTP-bound form) with MICALL1; regulates RAB8A
CC association with recycling endosomes. Interacts with MICALL2;
CC competes with RAB13 and is involved in E-cadherin endocytic
CC recycling. Interacts with MICAL1. Interacts with EHD1. Interacts
CC with MAP4K2 and SYTL4. Interacts with SGSM1 and SGSM3. Interacts
CC with RABIF, RIMS2, RPH3A and RPH3A. Interacts with OPTN. Interacts
CC with RAB3IP. Interacts with MYO5B. Interacts with PIFO. Interacts
CC with BIRC6/bruce. Interacts with OCRL.
CC -!- INTERACTION:
CC Q01968:OCRL; NbExp=11; IntAct=EBI-722293, EBI-6148898;
CC P47224:RABIF; NbExp=2; IntAct=EBI-722293, EBI-713992;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor; Cytoplasmic
CC side (Potential). Golgi apparatus. Recycling endosome membrane.
CC Cell projection, cilium. Cytoplasmic vesicle, phagosome.
CC Cytoplasmic vesicle, phagosome membrane; Lipid-anchor; Cytoplasmic
CC side (By similarity). Note=Colocalizes with OPTN at the Golgi
CC complex and in vesicular structures close to the plasma membrane.
CC In the GDP-bound form, present in the perinuclear region. Shows a
CC polarized distribution to distal regions of cell protrusions in
CC the GTP-bound form. Colocalizes with PARD3, PRKCI, EXOC5, OCLN,
CC PODXL and RAB11A in apical membrane initiation sites (AMIS) during
CC the generation of apical surface and lumenogenesis. Localizes to
CC tubular recycling endosome. Recruited to phagosomes containing
CC S.aureus or M.tuberculosis.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rab family.
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DR EMBL; X56741; CAA40065.1; -; mRNA.
DR EMBL; S53268; AAB19681.1; -; mRNA.
DR EMBL; AF498943; AAM21091.1; -; mRNA.
DR EMBL; BT007184; AAP35848.1; -; mRNA.
DR EMBL; CR536583; CAG38820.1; -; mRNA.
DR EMBL; CR542274; CAG47070.1; -; mRNA.
DR EMBL; CH471106; EAW84526.1; -; Genomic_DNA.
DR EMBL; BC002977; AAH02977.1; -; mRNA.
DR PIR; B49647; B49647.
DR RefSeq; NP_005361.2; NM_005370.4.
DR UniGene; Hs.642874; -.
DR PDB; 3QBT; X-ray; 2.00 A; A/C/E/G=6-176.
DR PDB; 3TNF; X-ray; 2.50 A; A=6-176.
DR PDB; 4LHV; X-ray; 1.95 A; A/B/C/D/E=6-176.
DR PDB; 4LHW; X-ray; 1.55 A; A/B/C/D/E=6-176.
DR PDB; 4LHX; X-ray; 3.05 A; A/B=1-184.
DR PDB; 4LHY; X-ray; 3.10 A; A/B=1-184.
DR PDB; 4LHZ; X-ray; 3.20 A; A/B=1-184.
DR PDB; 4LI0; X-ray; 3.30 A; A/B=1-184.
DR PDBsum; 3QBT; -.
DR PDBsum; 3TNF; -.
DR PDBsum; 4LHV; -.
DR PDBsum; 4LHW; -.
DR PDBsum; 4LHX; -.
DR PDBsum; 4LHY; -.
DR PDBsum; 4LHZ; -.
DR PDBsum; 4LI0; -.
DR ProteinModelPortal; P61006; -.
DR SMR; P61006; 6-176.
DR DIP; DIP-43703N; -.
DR IntAct; P61006; 11.
DR MINT; MINT-1416277; -.
DR STRING; 9606.ENSP00000300935; -.
DR PhosphoSite; P61006; -.
DR DMDM; 46810392; -.
DR PaxDb; P61006; -.
DR PeptideAtlas; P61006; -.
DR PRIDE; P61006; -.
DR DNASU; 4218; -.
DR Ensembl; ENST00000300935; ENSP00000300935; ENSG00000167461.
DR GeneID; 4218; -.
DR KEGG; hsa:4218; -.
DR UCSC; uc002ndn.4; human.
DR CTD; 4218; -.
DR GeneCards; GC19P016222; -.
DR HGNC; HGNC:7007; RAB8A.
DR MIM; 165040; gene.
DR neXtProt; NX_P61006; -.
DR PharmGKB; PA30743; -.
DR eggNOG; COG1100; -.
DR HOGENOM; HOG000233968; -.
DR HOVERGEN; HBG009351; -.
DR InParanoid; P61006; -.
DR KO; K07901; -.
DR OMA; IDKAFYS; -.
DR PhylomeDB; P61006; -.
DR Reactome; REACT_11123; Membrane Trafficking.
DR Reactome; REACT_115566; Cell Cycle.
DR ChiTaRS; RAB8A; human.
DR GeneWiki; RAB8A; -.
DR GenomeRNAi; 4218; -.
DR NextBio; 16637; -.
DR PRO; PR:P61006; -.
DR ArrayExpress; P61006; -.
DR Bgee; P61006; -.
DR CleanEx; HS_RAB8A; -.
DR Genevestigator; P61006; -.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; TAS:Reactome.
DR GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0005932; C:microtubule basal body; IEA:Ensembl.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0031513; C:nonmotile primary cilium; IDA:BHF-UCL.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0045335; C:phagocytic vesicle; IDA:UniProtKB.
DR GO; GO:0030670; C:phagocytic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl.
DR GO; GO:0055038; C:recycling endosome membrane; 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; EXP:Reactome.
DR GO; GO:0017137; F:Rab GTPase binding; ISS:UniProtKB.
DR GO; GO:0007409; P:axonogenesis; ISS:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; ISS:UniProtKB.
DR GO; GO:0042384; P:cilium assembly; IMP:UniProtKB.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; TAS:Reactome.
DR GO; GO:0048210; P:Golgi vesicle fusion to target membrane; IDA:BHF-UCL.
DR GO; GO:0072659; P:protein localization to plasma membrane; ISS:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0048169; P:regulation of long-term neuronal synaptic plasticity; IEA:Ensembl.
DR GO; GO:0051223; P:regulation of protein transport; IEA:Ensembl.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IEA:InterPro.
DR GO; GO:0006904; P:vesicle docking involved in exocytosis; IDA:BHF-UCL.
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; Cell membrane; Cell projection;
KW Cilium biogenesis/degradation; Complete proteome; Cytoplasmic vesicle;
KW Endosome; Golgi apparatus; GTP-binding; Lipoprotein; Membrane;
KW Methylation; Nucleotide-binding; Phosphoprotein; Prenylation;
KW Protein transport; Proto-oncogene; Reference proteome; Transport.
FT CHAIN 1 204 Ras-related protein Rab-8A.
FT /FTId=PRO_0000121130.
FT PROPEP 205 207 Removed in mature form (Potential).
FT /FTId=PRO_0000370793.
FT NP_BIND 15 22 GTP (By similarity).
FT NP_BIND 63 67 GTP (By similarity).
FT NP_BIND 121 124 GTP (By similarity).
FT MOTIF 37 45 Effector region (By similarity).
FT MOD_RES 181 181 Phosphoserine.
FT MOD_RES 185 185 Phosphoserine.
FT MOD_RES 204 204 Cysteine methyl ester (Potential).
FT LIPID 204 204 S-geranylgeranyl cysteine.
FT MUTAGEN 22 22 T->N: Loss of interaction with MICALL1.
FT MUTAGEN 67 67 Q->L: Probable constitutively active
FT mutant locked in the active GTP-bound
FT form. Stimulates interaction with
FT MICALL1.
FT CONFLICT 177 183 LEGNSPQ -> WKATAP (in Ref. 2; AAB19681).
FT STRAND 8 14
FT HELIX 21 30
FT STRAND 41 52
FT STRAND 55 63
FT HELIX 68 70
FT HELIX 71 74
FT HELIX 75 77
FT STRAND 82 89
FT HELIX 93 97
FT HELIX 99 109
FT STRAND 115 121
FT HELIX 126 128
FT HELIX 133 142
FT STRAND 146 149
FT TURN 152 155
FT HELIX 158 175
SQ SEQUENCE 207 AA; 23668 MW; AA52DBF54A2CD056 CRC64;
MAKTYDYLFK LLLIGDSGVG KTCVLFRFSE DAFNSTFIST IGIDFKIRTI ELDGKRIKLQ
IWDTAGQERF RTITTAYYRG AMGIMLVYDI TNEKSFDNIR NWIRNIEEHA SADVEKMILG
NKCDVNDKRQ VSKERGEKLA LDYGIKFMET SAKANINVEN AFFTLARDIK AKMDKKLEGN
SPQGSNQGVK ITPDQQKRSS FFRCVLL
//
ID RAB8A_HUMAN Reviewed; 207 AA.
AC P61006; P24407; Q6FHV5;
DT 26-APR-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 26-APR-2004, sequence version 1.
DT 22-JAN-2014, entry version 113.
DE RecName: Full=Ras-related protein Rab-8A;
DE AltName: Full=Oncogene c-mel;
DE Flags: Precursor;
GN Name=RAB8A; Synonyms=MEL, RAB8;
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=8294494; DOI=10.1083/jcb.124.1.101;
RA Zahraoui A., Joberty G., Arpin M., Fontaine J.J., Hellio R.,
RA Tavitian A., Louvard D.;
RT "A small rab GTPase is distributed in cytoplasmic vesicles in non
RT polarized cells but colocalizes with the tight junction marker ZO-1 in
RT polarized epithelial cells.";
RL J. Cell Biol. 124:101-115(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1886711;
RA Nimmo E.R., Sanders P.G., Padua R.A., Hughes D., Williamson R.,
RA Johnson K.J.;
RT "The MEL gene: a new member of the RAB/YPT class of RAS-related
RT genes.";
RL Oncogene 6:1347-1351(1991).
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].
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 (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [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;
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 ISOPRENYLATION AT CYS-204.
RX PubMed=8375503; DOI=10.1016/0014-5793(93)80897-4;
RA Joberty G., Tavitian A., Zahraoui A.;
RT "Isoprenylation of Rab proteins possessing a C-terminal CaaX motif.";
RL FEBS Lett. 330:323-328(1993).
RN [9]
RP INTERACTION WITH RAB3IP, AND SUBCELLULAR LOCATION.
RC TISSUE=Brain;
RX PubMed=12221131; DOI=10.1091/mbc.E02-03-0143;
RA Hattula K., Furuhjelm J., Arffman A., Peranen J.;
RT "A Rab8-specific GDP/GTP exchange factor is involved in actin
RT remodeling and polarized membrane transport.";
RL Mol. Biol. Cell 13:3268-3280(2002).
RN [10]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH OPTN.
RX PubMed=15837803; DOI=10.1083/jcb.200501162;
RA Sahlender D.A., Roberts R.C., Arden S.D., Spudich G., Taylor M.J.,
RA Luzio J.P., Kendrick-Jones J., Buss F.;
RT "Optineurin links myosin VI to the Golgi complex and is involved in
RT Golgi organization and exocytosis.";
RL J. Cell Biol. 169:285-295(2005).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-185, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [12]
RP INTERACTION WITH BIRC6/BRUCE.
RX PubMed=18329369; DOI=10.1016/j.cell.2008.01.012;
RA Pohl C., Jentsch S.;
RT "Final stages of cytokinesis and midbody ring formation are controlled
RT by BRUCE.";
RL Cell 132:832-845(2008).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [15]
RP INTERACTION WITH PIFO.
RX PubMed=20643351; DOI=10.1016/j.devcel.2010.06.005;
RA Kinzel D., Boldt K., Davis E.E., Burtscher I., Trumbach D., Diplas B.,
RA Attie-Bitach T., Wurst W., Katsanis N., Ueffing M., Lickert H.;
RT "Pitchfork regulates primary cilia disassembly and left-right
RT asymmetry.";
RL Dev. Cell 19:66-77(2010).
RN [16]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=20890297; DOI=10.1038/ncb2106;
RA Bryant D.M., Datta A., Rodriguez-Fraticelli A.E., Peraenen J.,
RA Martin-Belmonte F., Mostov K.E.;
RT "A molecular network for de novo generation of the apical surface and
RT lumen.";
RL Nat. Cell Biol. 12:1035-1045(2010).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181 AND SER-185, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [18]
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 [19]
RP SUBCELLULAR LOCATION, INTERACTION WITH EHD1 AND MICALL1, AND
RP MUTAGENESIS OF THR-22 AND GLN-67.
RX PubMed=19864458; DOI=10.1091/mbc.E09-06-0535;
RA Sharma M., Giridharan S.S., Rahajeng J., Naslavsky N., Caplan S.;
RT "MICAL-L1 links EHD1 to tubular recycling endosomes and regulates
RT receptor recycling.";
RL Mol. Biol. Cell 20:5181-5194(2009).
RN [20]
RP FUNCTION, AND INTERACTION WITH MYO5B.
RX PubMed=21282656; DOI=10.1073/pnas.1010754108;
RA Roland J.T., Bryant D.M., Datta A., Itzen A., Mostov K.E.,
RA Goldenring J.R.;
RT "Rab GTPase-Myo5B complexes control membrane recycling and epithelial
RT polarization.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:2789-2794(2011).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-185, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [22]
RP SUBCELLULAR LOCATION.
RX PubMed=21255211; DOI=10.1111/j.1600-0854.2011.01165.x;
RA Seto S., Tsujimura K., Koide Y.;
RT "Rab GTPases regulating phagosome maturation are differentially
RT recruited to mycobacterial phagosomes.";
RL Traffic 12:407-420(2011).
RN [23]
RP FUNCTION IN CILIOGENESIS, AND SUBCELLULAR LOCATION.
RX PubMed=21844891; DOI=10.1038/cr.2011.134;
RA Chen Y., Wu B., Xu L., Li H., Xia J., Yin W., Li Z., Shi D., Li S.,
RA Lin S., Shu X., Pei D.;
RT "A SNX10/V-ATPase pathway regulates ciliogenesis in vitro and in
RT vivo.";
RL Cell Res. 22:333-345(2012).
RN [24]
RP INTERACTION WITH OCRL.
RX PubMed=22543976; DOI=10.1093/hmg/dds163;
RA Luo N., West C.C., Murga-Zamalloa C.A., Sun L., Anderson R.M.,
RA Wells C.D., Weinreb R.N., Travers J.B., Khanna H., Sun Y.;
RT "OCRL localizes to the primary cilium: a new role for cilia in Lowe
RT syndrome.";
RL Hum. Mol. Genet. 21:3333-3344(2012).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 6-176 IN COMPLEX WITH OCRL.
RX PubMed=21378754; DOI=10.1038/emboj.2011.60;
RA Hou X., Hagemann N., Schoebel S., Blankenfeldt W., Goody R.S.,
RA Erdmann K.S., Itzen A.;
RT "A structural basis for Lowe syndrome caused by mutations in the Rab-
RT binding domain of OCRL1.";
RL EMBO J. 30:1659-1670(2011).
CC -!- FUNCTION: The small GTPases Rab are key regulators of
CC intracellular membrane trafficking, from the formation of
CC transport vesicles to their fusion with membranes. Rabs cycle
CC between an inactive GDP-bound form and an active GTP-bound form
CC that is able to recruit to membranes different sets of downstream
CC effectors directly responsible for vesicle formation, movement,
CC tethering and fusion. That Rab is involved in polarized vesicular
CC trafficking and neurotransmitter release. Together with RAB11A,
CC RAB3IP, the exocyst complex, PARD3, PRKCI, ANXA2, CDC42 and DNMBP
CC promotes transcytosis of PODXL to the apical membrane initiation
CC sites (AMIS), apical surface formation and lumenogenesis. Together
CC with MYO5B and RAB11A participates in epithelial cell
CC polarization. Plays an important role in ciliogenesis. Together
CC with MICALL2, may also regulate adherens junction assembly. May
CC play a role in insulin-induced transport to the plasma membrane of
CC the glucose transporter GLUT4 and therefore play a role in glucose
CC homeostasis.
CC -!- ENZYME REGULATION: Activated in response to insulin (By
CC similarity).
CC -!- SUBUNIT: Interacts (GTP-bound form) with MICALL1; regulates RAB8A
CC association with recycling endosomes. Interacts with MICALL2;
CC competes with RAB13 and is involved in E-cadherin endocytic
CC recycling. Interacts with MICAL1. Interacts with EHD1. Interacts
CC with MAP4K2 and SYTL4. Interacts with SGSM1 and SGSM3. Interacts
CC with RABIF, RIMS2, RPH3A and RPH3A. Interacts with OPTN. Interacts
CC with RAB3IP. Interacts with MYO5B. Interacts with PIFO. Interacts
CC with BIRC6/bruce. Interacts with OCRL.
CC -!- INTERACTION:
CC Q01968:OCRL; NbExp=11; IntAct=EBI-722293, EBI-6148898;
CC P47224:RABIF; NbExp=2; IntAct=EBI-722293, EBI-713992;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor; Cytoplasmic
CC side (Potential). Golgi apparatus. Recycling endosome membrane.
CC Cell projection, cilium. Cytoplasmic vesicle, phagosome.
CC Cytoplasmic vesicle, phagosome membrane; Lipid-anchor; Cytoplasmic
CC side (By similarity). Note=Colocalizes with OPTN at the Golgi
CC complex and in vesicular structures close to the plasma membrane.
CC In the GDP-bound form, present in the perinuclear region. Shows a
CC polarized distribution to distal regions of cell protrusions in
CC the GTP-bound form. Colocalizes with PARD3, PRKCI, EXOC5, OCLN,
CC PODXL and RAB11A in apical membrane initiation sites (AMIS) during
CC the generation of apical surface and lumenogenesis. Localizes to
CC tubular recycling endosome. Recruited to phagosomes containing
CC S.aureus or M.tuberculosis.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rab family.
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DR EMBL; X56741; CAA40065.1; -; mRNA.
DR EMBL; S53268; AAB19681.1; -; mRNA.
DR EMBL; AF498943; AAM21091.1; -; mRNA.
DR EMBL; BT007184; AAP35848.1; -; mRNA.
DR EMBL; CR536583; CAG38820.1; -; mRNA.
DR EMBL; CR542274; CAG47070.1; -; mRNA.
DR EMBL; CH471106; EAW84526.1; -; Genomic_DNA.
DR EMBL; BC002977; AAH02977.1; -; mRNA.
DR PIR; B49647; B49647.
DR RefSeq; NP_005361.2; NM_005370.4.
DR UniGene; Hs.642874; -.
DR PDB; 3QBT; X-ray; 2.00 A; A/C/E/G=6-176.
DR PDB; 3TNF; X-ray; 2.50 A; A=6-176.
DR PDB; 4LHV; X-ray; 1.95 A; A/B/C/D/E=6-176.
DR PDB; 4LHW; X-ray; 1.55 A; A/B/C/D/E=6-176.
DR PDB; 4LHX; X-ray; 3.05 A; A/B=1-184.
DR PDB; 4LHY; X-ray; 3.10 A; A/B=1-184.
DR PDB; 4LHZ; X-ray; 3.20 A; A/B=1-184.
DR PDB; 4LI0; X-ray; 3.30 A; A/B=1-184.
DR PDBsum; 3QBT; -.
DR PDBsum; 3TNF; -.
DR PDBsum; 4LHV; -.
DR PDBsum; 4LHW; -.
DR PDBsum; 4LHX; -.
DR PDBsum; 4LHY; -.
DR PDBsum; 4LHZ; -.
DR PDBsum; 4LI0; -.
DR ProteinModelPortal; P61006; -.
DR SMR; P61006; 6-176.
DR DIP; DIP-43703N; -.
DR IntAct; P61006; 11.
DR MINT; MINT-1416277; -.
DR STRING; 9606.ENSP00000300935; -.
DR PhosphoSite; P61006; -.
DR DMDM; 46810392; -.
DR PaxDb; P61006; -.
DR PeptideAtlas; P61006; -.
DR PRIDE; P61006; -.
DR DNASU; 4218; -.
DR Ensembl; ENST00000300935; ENSP00000300935; ENSG00000167461.
DR GeneID; 4218; -.
DR KEGG; hsa:4218; -.
DR UCSC; uc002ndn.4; human.
DR CTD; 4218; -.
DR GeneCards; GC19P016222; -.
DR HGNC; HGNC:7007; RAB8A.
DR MIM; 165040; gene.
DR neXtProt; NX_P61006; -.
DR PharmGKB; PA30743; -.
DR eggNOG; COG1100; -.
DR HOGENOM; HOG000233968; -.
DR HOVERGEN; HBG009351; -.
DR InParanoid; P61006; -.
DR KO; K07901; -.
DR OMA; IDKAFYS; -.
DR PhylomeDB; P61006; -.
DR Reactome; REACT_11123; Membrane Trafficking.
DR Reactome; REACT_115566; Cell Cycle.
DR ChiTaRS; RAB8A; human.
DR GeneWiki; RAB8A; -.
DR GenomeRNAi; 4218; -.
DR NextBio; 16637; -.
DR PRO; PR:P61006; -.
DR ArrayExpress; P61006; -.
DR Bgee; P61006; -.
DR CleanEx; HS_RAB8A; -.
DR Genevestigator; P61006; -.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; TAS:Reactome.
DR GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0005932; C:microtubule basal body; IEA:Ensembl.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0031513; C:nonmotile primary cilium; IDA:BHF-UCL.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0045335; C:phagocytic vesicle; IDA:UniProtKB.
DR GO; GO:0030670; C:phagocytic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl.
DR GO; GO:0055038; C:recycling endosome membrane; 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; EXP:Reactome.
DR GO; GO:0017137; F:Rab GTPase binding; ISS:UniProtKB.
DR GO; GO:0007409; P:axonogenesis; ISS:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; ISS:UniProtKB.
DR GO; GO:0042384; P:cilium assembly; IMP:UniProtKB.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; TAS:Reactome.
DR GO; GO:0048210; P:Golgi vesicle fusion to target membrane; IDA:BHF-UCL.
DR GO; GO:0072659; P:protein localization to plasma membrane; ISS:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0048169; P:regulation of long-term neuronal synaptic plasticity; IEA:Ensembl.
DR GO; GO:0051223; P:regulation of protein transport; IEA:Ensembl.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IEA:InterPro.
DR GO; GO:0006904; P:vesicle docking involved in exocytosis; IDA:BHF-UCL.
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; Cell membrane; Cell projection;
KW Cilium biogenesis/degradation; Complete proteome; Cytoplasmic vesicle;
KW Endosome; Golgi apparatus; GTP-binding; Lipoprotein; Membrane;
KW Methylation; Nucleotide-binding; Phosphoprotein; Prenylation;
KW Protein transport; Proto-oncogene; Reference proteome; Transport.
FT CHAIN 1 204 Ras-related protein Rab-8A.
FT /FTId=PRO_0000121130.
FT PROPEP 205 207 Removed in mature form (Potential).
FT /FTId=PRO_0000370793.
FT NP_BIND 15 22 GTP (By similarity).
FT NP_BIND 63 67 GTP (By similarity).
FT NP_BIND 121 124 GTP (By similarity).
FT MOTIF 37 45 Effector region (By similarity).
FT MOD_RES 181 181 Phosphoserine.
FT MOD_RES 185 185 Phosphoserine.
FT MOD_RES 204 204 Cysteine methyl ester (Potential).
FT LIPID 204 204 S-geranylgeranyl cysteine.
FT MUTAGEN 22 22 T->N: Loss of interaction with MICALL1.
FT MUTAGEN 67 67 Q->L: Probable constitutively active
FT mutant locked in the active GTP-bound
FT form. Stimulates interaction with
FT MICALL1.
FT CONFLICT 177 183 LEGNSPQ -> WKATAP (in Ref. 2; AAB19681).
FT STRAND 8 14
FT HELIX 21 30
FT STRAND 41 52
FT STRAND 55 63
FT HELIX 68 70
FT HELIX 71 74
FT HELIX 75 77
FT STRAND 82 89
FT HELIX 93 97
FT HELIX 99 109
FT STRAND 115 121
FT HELIX 126 128
FT HELIX 133 142
FT STRAND 146 149
FT TURN 152 155
FT HELIX 158 175
SQ SEQUENCE 207 AA; 23668 MW; AA52DBF54A2CD056 CRC64;
MAKTYDYLFK LLLIGDSGVG KTCVLFRFSE DAFNSTFIST IGIDFKIRTI ELDGKRIKLQ
IWDTAGQERF RTITTAYYRG AMGIMLVYDI TNEKSFDNIR NWIRNIEEHA SADVEKMILG
NKCDVNDKRQ VSKERGEKLA LDYGIKFMET SAKANINVEN AFFTLARDIK AKMDKKLEGN
SPQGSNQGVK ITPDQQKRSS FFRCVLL
//
MIM
165040
*RECORD*
*FIELD* NO
165040
*FIELD* TI
*165040 RAS-ASSOCIATED PROTEIN RAB8A; RAB8A
;;RAS-ASSOCIATED PROTEIN RAB8; RAB8;;
ONCOGENE MEL; MEL
read more*FIELD* TX
DESCRIPTION
Members of the RAS superfamily, such as RAB8A, are small GTP/GDP-binding
proteins with an average size of 200 amino acids. The RAS-related
proteins of the RAB/YPT family may play a role in the transport of
proteins from the endoplasmic reticulum to the Golgi and the plasma
membrane (Nimmo et al., 1991).
CLONING
Using DNA transfection into NIH 3T3 cells, Padua et al. (1984)
demonstrated that the human malignant melanoma cell line NK14 contains a
novel transforming gene. Nimmo et al. (1991) isolated human MEL genomic
clones and cDNAs, as well as a cDNA encoding the mouse MEL homolog. The
predicted 206-amino acid human MEL protein shares 97%, 96%, and 51%
identity with the dog RAB8, mouse MEL, and mouse YPT1 (RAB1; 179508)
proteins, respectively. MEL contains the 4 GTP/GDP-binding sites that
are present in all the RAS proteins. The putative effector-binding site
of MEL is similar to that of the RAB/YPT proteins. However, MEL contains
a C-terminal CAAX motif that is characteristic of many RAS superfamily
members but which is not found in YPT1 and the majority of RAB proteins.
GENE FUNCTION
Sato et al. (2007) showed that Rab8 is responsible for the localization
of apical proteins in intestinal epithelial cells. The authors found
that apical peptidases and transporters localized to lysosomes in the
small intestine of Rab8-deficient mice. Their mislocalization and
degradation in lysosomes led to a marked reduction in the absorption
rate of nutrients in the small intestine, and ultimately to death.
Ultrastructurally, a shortening of apical microvilli, an increased
number of enlarged lysosomes, and microvillus inclusions in the
enterocytes were also observed. One patient with microvillus inclusion
disease (251850) who showed an identical phenotype to that of
Rab8-deficient mice expressed a reduced amount of Rab8. Sato et al.
(2007) concluded that RAB8 is necessary for the proper localization of
apical proteins and the absorption and digestion of various nutrients in
the small intestine.
Omori et al. (2008) identified elipsa, the zebrafish ortholog of
TRAF3IP1 (607380), as a component of intraflagellar transport particles,
which are involved in the formation and function of cilia. Elipsa
interacted with rabaptin-5 (RABEP1; 603616), a regulator of endocytosis,
and rabaptin-5 in turn interacted with Rab8. Omori et al. (2008)
concluded that elipsa, rabaptin-5, and Rab8 provide a bridge between the
intraflagellar transport particle and protein complexes that assemble at
the ciliary membrane.
RAB8A regulates cilia assembly by targeting and promoting fusion of
vesicles near the ciliary membrane. Tsang et al. (2008) found that RAB8A
localized to the centrosome in growing human RPE1 retinal pigment
epithelial cells and to the ciliary membrane in quiescent cells. RAB8A
bound a central domain of CEP290 (610142) and interacted with CEP290 in
both growing and quiescent cells. Both RAB8A and CEP290 interacted with
CP110 (609544) in growing cells. Knockdown of CEP290 prevented
ciliogenesis in differentiating RPE1 cells and reduced the number of
RAB8A foci. Tsang et al. (2008) concluded that RAB8A requires CEP290 for
centrosome localization and that CEP290 regulates entry of RAB8A into
the cilium during assembly of this organelle.
Hsiao et al. (2009) showed that AHI1 (608894), which is mutated in
Joubert syndrome type 3 (JBTS3; 608629), regulated formation of the
primary nonmotile cilium via its interaction with RAB8A. Mouse Ahi1
protein localized to a single centriole, the mother centriole, which
becomes the basal body of the primary cilium. In mice, RNAi knockdown of
Ahi1 expression led to impairments in ciliogenesis. In Ahi1-knockdown
cells, Rab8a was destabilized and did not properly localize to the basal
body. Defects in the trafficking of endocytic vesicles from the plasma
membrane to the Golgi and back to the plasma membrane were observed in
Ahi1-knockdown cells. Hsiao et al. (2009) concluded that the
distribution and functioning of RAB8A is regulated by AHI1, not only
affecting cilium formation, but also vesicle transport.
By coimmunoprecipitation of bovine retinal extract, Murga-Zamalloa et
al. (2010) found that Rpgr (312610) interacted with Rab8a. Human RPGR
interacted predominantly with the GDP-bound form of human RAB8A and
stimulated GDP/GTP exchange. Disease-causing mutations in RPGR
diminished its interaction with RAB8A and/or reduced its GDP/GTP
exchange activity. Depletion of RPGR in human retinal pigment epithelial
cells disrupted association of RAB8A with cilia and resulted in
shortened primary cilia.
ANIMAL MODEL
Chi et al. (2010) described the phenotypic characteristics of transgenic
mice overexpressing wildtype or mutated optineurin (OPTN; 602432).
Mutations E50K (602432.0001), H486R, and Optn with a deletion of the
first or second leucine zipper were used for overexpression. After 16
months, histologic abnormalities were exclusively observed in the retina
of E50K mutant mice, with loss of retinal ganglion cells and connecting
synapses in the peripheral retina, thinning of the nerve fiber layer at
the optic nerve head at normal intraocular pressure, and massive
apoptosis and degeneration of the entire retina. Introduction of the
E50K mutation disrupted the interaction between Optn and Rab8. Wiltype
Optn and an active GTP-bound form of Rab8 colocalized to the Golgi. The
authors concluded that alteration of the Optn sequence can initiate
significant retinal degeneration in mice.
MAPPING
Although MEL was isolated as a transforming gene from a melanoma cell
line, no linkage between MEL and malignant melanoma (155600) was
demonstrable (Nimmo et al., 1989).
As a result of studies of human-mouse and human-hamster somatic cell
hybrids, Spurr et al. (1986) demonstrated that the MEL oncogene is
located in the segment 19p13.2-q13.2. By linkage analysis using an NcoI
RFLP, Nimmo et al. (1989, 1989) mapped the MEL gene to the region of
LDLR (606945), i.e., 19p13.2-cen. Bahler et al. (1997) performed cosmid
contig mapping indicating that the MEL locus was 800 kb distal to MY09B
(602129) on chromosome 19p13.1.
*FIELD* RF
1. Bahler, M.; Kehrer, I.; Gordon, L.; Stoffler, H.-E.; Olsen, A.
S.: Physical mapping of human myosin-IXB (MYO9B), the human orthologue
of the rat myosin myr 5, to chromosome 19p13.1. Genomics 43: 107-109,
1997.
2. Chi, Z.-L.; Akahori, M.; Obazawa, M.; Minami, M.; Noda, T.; Nakaya,
N.; Tomarev, S.; Kawase, K.; Yamamoto, T.; Noda, S.; Sasaoka, M.;
Shimazaki, A.; Takada, Y.; Iwata, T.: Overexpression of optineurin
E50K disrupts Rab8 interaction and leads to a progressive retinal
degeneration in mice. Hum. Molec. Genet. 19: 2606-2615, 2010.
3. Hsiao, Y.-C.; Tong, Z. J.; Westfall, J. E.; Ault, J. G.; Page-McCaw,
P. S.; Ferland, R. J.: Ahi1, whose human ortholog is mutated in Joubert
syndrome, is required for Rab8a localization, ciliogenesis and vesicle
trafficking. Hum. Molec. Genet. 18: 3926-3941, 2009.
4. Murga-Zamalloa, C. A.; Atkins, S. J.; Peranen, J.; Swaroop, A.;
Khanna, H.: Interaction of retinitis pigmentosa GTPase regulator
(RPGR) with RAB8A GTPase: implications for cilia dysfunction and photoreceptor
degeneration. Hum. Molec. Genet. 19: 3591-3598, 2010.
5. Nimmo, E.; Padua, R.-A.; Hughes, D.; Brook, J. D.; Williamson,
R.; Johnson, K. J.: Confirmation and refinement of the localisation
of the c-MEL locus on chromosome 19 by physical and genetic mapping. Hum.
Genet. 81: 382-384, 1989.
6. Nimmo, E.; Williamson, R.; Johnson, K.: Localization of the c-MEL
gene to 19(cen-p13.2). (Abstract) Cytogenet. Cell Genet. 51: 1053
only, 1989.
7. Nimmo, E. R.; Sanders, P. G.; Padua, R. A.; Hughes, D.; Williamson,
R.; Johnson, K. J.: The MEL gene: a new member of the RAB/YPT class
of RAS-related genes. Oncogene 6: 1347-1351, 1991.
8. Omori, Y.; Zhao, C.; Saras, A.; Mukhopadhyay, S.; Kim, W.; Furukawa,
T.; Sengupta, P.; Veraksa, A.; Malicki, J.: elipsa is an early determinant
of ciliogenesis that links the IFT particle to membrane-associated
small GTPase Rab8. Nature Cell Biol. 10: 437-444, 2008.
9. Padua, R. A.; Barrass, N.; Currie, G. A.: A novel transforming
gene in a human malignant melanoma cell line. Nature 311: 671-673,
1984.
10. Sato, T.; Mushiake, S.; Kato, Y.; Sato, K.; Sato, M.; Takeda,
N.; Ozono, K.; Miki, K.; Kubo, Y.; Tsuji, A.; Harada, R.; Harada,
A.: The Rab8 GTPase regulates apical protein localization in intestinal
cells. Nature 448: 366-369, 2007.
11. Spurr, N. K.; Hughes, D.; Goodfellow, P. N.; Brook, J. D.; Padua,
R. A.: Chromosomal assignment of c-MEL, a human transforming oncogene,
to chromosome 19(p13.2-q13.2). Somat. Cell Molec. Genet. 12: 637-640,
1986.
12. Tsang, W. Y.; Bossard, C.; Khanna, H.; Peranen, J.; Swaroop, A.;
Malhotra, V.; Dynlacht, B. D.: CP110 suppresses primary cilia formation
through its interaction with CEP290, a protein deficiency in human
ciliary disease. Dev. Cell 15: 187-197, 2008.
*FIELD* CN
George E. Tiller - updated: 8/20/2013
Patricia A. Hartz - updated: 4/26/2012
George E. Tiller - updated: 8/6/2010
Patricia A. Hartz - updated: 7/29/2009
Patricia A. Hartz - updated: 6/4/2009
Ada Hamosh - updated: 8/29/2007
Rebekah S. Rasooly - updated: 3/22/1999
Jennifer P. Macke - updated: 12/11/1997
*FIELD* CD
Victor A. McKusick: 2/9/1987
*FIELD* ED
carol: 08/21/2013
tpirozzi: 8/21/2013
tpirozzi: 8/20/2013
mgross: 5/2/2012
terry: 4/26/2012
wwang: 8/10/2010
terry: 8/6/2010
terry: 1/15/2010
mgross: 8/3/2009
terry: 7/29/2009
mgross: 6/4/2009
terry: 6/4/2009
alopez: 9/10/2007
terry: 8/29/2007
carol: 3/14/2006
ckniffin: 6/5/2002
alopez: 3/22/1999
dholmes: 12/11/1997
carol: 7/5/1996
supermim: 3/16/1992
supermim: 4/19/1990
supermim: 3/20/1990
carol: 12/12/1989
ddp: 10/27/1989
root: 9/5/1989
*RECORD*
*FIELD* NO
165040
*FIELD* TI
*165040 RAS-ASSOCIATED PROTEIN RAB8A; RAB8A
;;RAS-ASSOCIATED PROTEIN RAB8; RAB8;;
ONCOGENE MEL; MEL
read more*FIELD* TX
DESCRIPTION
Members of the RAS superfamily, such as RAB8A, are small GTP/GDP-binding
proteins with an average size of 200 amino acids. The RAS-related
proteins of the RAB/YPT family may play a role in the transport of
proteins from the endoplasmic reticulum to the Golgi and the plasma
membrane (Nimmo et al., 1991).
CLONING
Using DNA transfection into NIH 3T3 cells, Padua et al. (1984)
demonstrated that the human malignant melanoma cell line NK14 contains a
novel transforming gene. Nimmo et al. (1991) isolated human MEL genomic
clones and cDNAs, as well as a cDNA encoding the mouse MEL homolog. The
predicted 206-amino acid human MEL protein shares 97%, 96%, and 51%
identity with the dog RAB8, mouse MEL, and mouse YPT1 (RAB1; 179508)
proteins, respectively. MEL contains the 4 GTP/GDP-binding sites that
are present in all the RAS proteins. The putative effector-binding site
of MEL is similar to that of the RAB/YPT proteins. However, MEL contains
a C-terminal CAAX motif that is characteristic of many RAS superfamily
members but which is not found in YPT1 and the majority of RAB proteins.
GENE FUNCTION
Sato et al. (2007) showed that Rab8 is responsible for the localization
of apical proteins in intestinal epithelial cells. The authors found
that apical peptidases and transporters localized to lysosomes in the
small intestine of Rab8-deficient mice. Their mislocalization and
degradation in lysosomes led to a marked reduction in the absorption
rate of nutrients in the small intestine, and ultimately to death.
Ultrastructurally, a shortening of apical microvilli, an increased
number of enlarged lysosomes, and microvillus inclusions in the
enterocytes were also observed. One patient with microvillus inclusion
disease (251850) who showed an identical phenotype to that of
Rab8-deficient mice expressed a reduced amount of Rab8. Sato et al.
(2007) concluded that RAB8 is necessary for the proper localization of
apical proteins and the absorption and digestion of various nutrients in
the small intestine.
Omori et al. (2008) identified elipsa, the zebrafish ortholog of
TRAF3IP1 (607380), as a component of intraflagellar transport particles,
which are involved in the formation and function of cilia. Elipsa
interacted with rabaptin-5 (RABEP1; 603616), a regulator of endocytosis,
and rabaptin-5 in turn interacted with Rab8. Omori et al. (2008)
concluded that elipsa, rabaptin-5, and Rab8 provide a bridge between the
intraflagellar transport particle and protein complexes that assemble at
the ciliary membrane.
RAB8A regulates cilia assembly by targeting and promoting fusion of
vesicles near the ciliary membrane. Tsang et al. (2008) found that RAB8A
localized to the centrosome in growing human RPE1 retinal pigment
epithelial cells and to the ciliary membrane in quiescent cells. RAB8A
bound a central domain of CEP290 (610142) and interacted with CEP290 in
both growing and quiescent cells. Both RAB8A and CEP290 interacted with
CP110 (609544) in growing cells. Knockdown of CEP290 prevented
ciliogenesis in differentiating RPE1 cells and reduced the number of
RAB8A foci. Tsang et al. (2008) concluded that RAB8A requires CEP290 for
centrosome localization and that CEP290 regulates entry of RAB8A into
the cilium during assembly of this organelle.
Hsiao et al. (2009) showed that AHI1 (608894), which is mutated in
Joubert syndrome type 3 (JBTS3; 608629), regulated formation of the
primary nonmotile cilium via its interaction with RAB8A. Mouse Ahi1
protein localized to a single centriole, the mother centriole, which
becomes the basal body of the primary cilium. In mice, RNAi knockdown of
Ahi1 expression led to impairments in ciliogenesis. In Ahi1-knockdown
cells, Rab8a was destabilized and did not properly localize to the basal
body. Defects in the trafficking of endocytic vesicles from the plasma
membrane to the Golgi and back to the plasma membrane were observed in
Ahi1-knockdown cells. Hsiao et al. (2009) concluded that the
distribution and functioning of RAB8A is regulated by AHI1, not only
affecting cilium formation, but also vesicle transport.
By coimmunoprecipitation of bovine retinal extract, Murga-Zamalloa et
al. (2010) found that Rpgr (312610) interacted with Rab8a. Human RPGR
interacted predominantly with the GDP-bound form of human RAB8A and
stimulated GDP/GTP exchange. Disease-causing mutations in RPGR
diminished its interaction with RAB8A and/or reduced its GDP/GTP
exchange activity. Depletion of RPGR in human retinal pigment epithelial
cells disrupted association of RAB8A with cilia and resulted in
shortened primary cilia.
ANIMAL MODEL
Chi et al. (2010) described the phenotypic characteristics of transgenic
mice overexpressing wildtype or mutated optineurin (OPTN; 602432).
Mutations E50K (602432.0001), H486R, and Optn with a deletion of the
first or second leucine zipper were used for overexpression. After 16
months, histologic abnormalities were exclusively observed in the retina
of E50K mutant mice, with loss of retinal ganglion cells and connecting
synapses in the peripheral retina, thinning of the nerve fiber layer at
the optic nerve head at normal intraocular pressure, and massive
apoptosis and degeneration of the entire retina. Introduction of the
E50K mutation disrupted the interaction between Optn and Rab8. Wiltype
Optn and an active GTP-bound form of Rab8 colocalized to the Golgi. The
authors concluded that alteration of the Optn sequence can initiate
significant retinal degeneration in mice.
MAPPING
Although MEL was isolated as a transforming gene from a melanoma cell
line, no linkage between MEL and malignant melanoma (155600) was
demonstrable (Nimmo et al., 1989).
As a result of studies of human-mouse and human-hamster somatic cell
hybrids, Spurr et al. (1986) demonstrated that the MEL oncogene is
located in the segment 19p13.2-q13.2. By linkage analysis using an NcoI
RFLP, Nimmo et al. (1989, 1989) mapped the MEL gene to the region of
LDLR (606945), i.e., 19p13.2-cen. Bahler et al. (1997) performed cosmid
contig mapping indicating that the MEL locus was 800 kb distal to MY09B
(602129) on chromosome 19p13.1.
*FIELD* RF
1. Bahler, M.; Kehrer, I.; Gordon, L.; Stoffler, H.-E.; Olsen, A.
S.: Physical mapping of human myosin-IXB (MYO9B), the human orthologue
of the rat myosin myr 5, to chromosome 19p13.1. Genomics 43: 107-109,
1997.
2. Chi, Z.-L.; Akahori, M.; Obazawa, M.; Minami, M.; Noda, T.; Nakaya,
N.; Tomarev, S.; Kawase, K.; Yamamoto, T.; Noda, S.; Sasaoka, M.;
Shimazaki, A.; Takada, Y.; Iwata, T.: Overexpression of optineurin
E50K disrupts Rab8 interaction and leads to a progressive retinal
degeneration in mice. Hum. Molec. Genet. 19: 2606-2615, 2010.
3. Hsiao, Y.-C.; Tong, Z. J.; Westfall, J. E.; Ault, J. G.; Page-McCaw,
P. S.; Ferland, R. J.: Ahi1, whose human ortholog is mutated in Joubert
syndrome, is required for Rab8a localization, ciliogenesis and vesicle
trafficking. Hum. Molec. Genet. 18: 3926-3941, 2009.
4. Murga-Zamalloa, C. A.; Atkins, S. J.; Peranen, J.; Swaroop, A.;
Khanna, H.: Interaction of retinitis pigmentosa GTPase regulator
(RPGR) with RAB8A GTPase: implications for cilia dysfunction and photoreceptor
degeneration. Hum. Molec. Genet. 19: 3591-3598, 2010.
5. Nimmo, E.; Padua, R.-A.; Hughes, D.; Brook, J. D.; Williamson,
R.; Johnson, K. J.: Confirmation and refinement of the localisation
of the c-MEL locus on chromosome 19 by physical and genetic mapping. Hum.
Genet. 81: 382-384, 1989.
6. Nimmo, E.; Williamson, R.; Johnson, K.: Localization of the c-MEL
gene to 19(cen-p13.2). (Abstract) Cytogenet. Cell Genet. 51: 1053
only, 1989.
7. Nimmo, E. R.; Sanders, P. G.; Padua, R. A.; Hughes, D.; Williamson,
R.; Johnson, K. J.: The MEL gene: a new member of the RAB/YPT class
of RAS-related genes. Oncogene 6: 1347-1351, 1991.
8. Omori, Y.; Zhao, C.; Saras, A.; Mukhopadhyay, S.; Kim, W.; Furukawa,
T.; Sengupta, P.; Veraksa, A.; Malicki, J.: elipsa is an early determinant
of ciliogenesis that links the IFT particle to membrane-associated
small GTPase Rab8. Nature Cell Biol. 10: 437-444, 2008.
9. Padua, R. A.; Barrass, N.; Currie, G. A.: A novel transforming
gene in a human malignant melanoma cell line. Nature 311: 671-673,
1984.
10. Sato, T.; Mushiake, S.; Kato, Y.; Sato, K.; Sato, M.; Takeda,
N.; Ozono, K.; Miki, K.; Kubo, Y.; Tsuji, A.; Harada, R.; Harada,
A.: The Rab8 GTPase regulates apical protein localization in intestinal
cells. Nature 448: 366-369, 2007.
11. Spurr, N. K.; Hughes, D.; Goodfellow, P. N.; Brook, J. D.; Padua,
R. A.: Chromosomal assignment of c-MEL, a human transforming oncogene,
to chromosome 19(p13.2-q13.2). Somat. Cell Molec. Genet. 12: 637-640,
1986.
12. Tsang, W. Y.; Bossard, C.; Khanna, H.; Peranen, J.; Swaroop, A.;
Malhotra, V.; Dynlacht, B. D.: CP110 suppresses primary cilia formation
through its interaction with CEP290, a protein deficiency in human
ciliary disease. Dev. Cell 15: 187-197, 2008.
*FIELD* CN
George E. Tiller - updated: 8/20/2013
Patricia A. Hartz - updated: 4/26/2012
George E. Tiller - updated: 8/6/2010
Patricia A. Hartz - updated: 7/29/2009
Patricia A. Hartz - updated: 6/4/2009
Ada Hamosh - updated: 8/29/2007
Rebekah S. Rasooly - updated: 3/22/1999
Jennifer P. Macke - updated: 12/11/1997
*FIELD* CD
Victor A. McKusick: 2/9/1987
*FIELD* ED
carol: 08/21/2013
tpirozzi: 8/21/2013
tpirozzi: 8/20/2013
mgross: 5/2/2012
terry: 4/26/2012
wwang: 8/10/2010
terry: 8/6/2010
terry: 1/15/2010
mgross: 8/3/2009
terry: 7/29/2009
mgross: 6/4/2009
terry: 6/4/2009
alopez: 9/10/2007
terry: 8/29/2007
carol: 3/14/2006
ckniffin: 6/5/2002
alopez: 3/22/1999
dholmes: 12/11/1997
carol: 7/5/1996
supermim: 3/16/1992
supermim: 4/19/1990
supermim: 3/20/1990
carol: 12/12/1989
ddp: 10/27/1989
root: 9/5/1989