Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P61006 (RAB8A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 119. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Ras-related protein Rab-8A
Alternative name(s):
Oncogene c-mel
Gene names
Name:RAB8A
Synonyms:MEL, RAB8
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length207 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. That Rab is involved in polarized vesicular trafficking and neurotransmitter release. Together with RAB11A, RAB3IP, the exocyst complex, PARD3, PRKCI, ANXA2, CDC42 and DNMBP promotes transcytosis of PODXL to the apical membrane initiation sites (AMIS), apical surface formation and lumenogenesis. Together with MYO5B and RAB11A participates in epithelial cell polarization. Plays an important role in ciliogenesis. Together with MICALL2, may also regulate adherens junction assembly. May play a role in insulin-induced transport to the plasma membrane of the glucose transporter GLUT4 and therefore play a role in glucose homeostasis. Ref.16 Ref.20 Ref.23

Enzyme regulation

Activated in response to insulin By similarity.

Subunit structure

Interacts (GTP-bound form) with MICALL1; regulates RAB8A association with recycling endosomes. Interacts with MICALL2; competes with RAB13 and is involved in E-cadherin endocytic recycling. Interacts with MICAL1. Interacts with EHD1. Interacts with MAP4K2 and SYTL4. Interacts with SGSM1 and SGSM3. Interacts with RABIF, RIMS2, RPH3A and RPH3A. Interacts with OPTN. Interacts with RAB3IP. Interacts with MYO5B. Interacts with PIFO. Interacts with BIRC6/bruce. Interacts with OCRL. Ref.9 Ref.10 Ref.12 Ref.15 Ref.17 Ref.20 Ref.24

Subcellular location

Cell membrane; Lipid-anchor; Cytoplasmic side Potential. Golgi apparatus. Recycling endosome membrane. Cell projectioncilium. Cytoplasmic vesiclephagosome. Cytoplasmic vesiclephagosome membrane; Lipid-anchor; Cytoplasmic side By similarity. Note: Colocalizes with OPTN at the Golgi complex and in vesicular structures close to the plasma membrane. In the GDP-bound form, present in the perinuclear region. Shows a polarized distribution to distal regions of cell protrusions in the GTP-bound form. Colocalizes with PARD3, PRKCI, EXOC5, OCLN, PODXL and RAB11A in apical membrane initiation sites (AMIS) during the generation of apical surface and lumenogenesis. Localizes to tubular recycling endosome. Recruited to phagosomes containing S.aureus or M.tuberculosis. Ref.9 Ref.10 Ref.16 Ref.17 Ref.22 Ref.23

Sequence similarities

Belongs to the small GTPase superfamily. Rab family.

Ontologies

Keywords
   Biological processCilium biogenesis/degradation
Protein transport
Transport
   Cellular componentCell membrane
Cell projection
Cytoplasmic vesicle
Endosome
Golgi apparatus
Membrane
   DiseaseProto-oncogene
   LigandGTP-binding
Nucleotide-binding
   PTMLipoprotein
Methylation
Phosphoprotein
Prenylation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG2/M transition of mitotic cell cycle

Traceable author statement. Source: Reactome

GTP catabolic process

Inferred from experiment. Source: GOC

Golgi vesicle fusion to target membrane

Inferred from direct assay PubMed 17574030. Source: BHF-UCL

axonogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to insulin stimulus

Inferred from sequence or structural similarity. Source: UniProtKB

cilium assembly

Inferred from mutant phenotype Ref.23. Source: UniProtKB

membrane organization

Traceable author statement. Source: Reactome

mitotic cell cycle

Traceable author statement. Source: Reactome

protein localization to plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

protein transport

Inferred from electronic annotation. Source: UniProtKB-KW

regulation of long-term neuronal synaptic plasticity

Inferred from electronic annotation. Source: Ensembl

regulation of protein transport

Inferred from electronic annotation. Source: Ensembl

small GTPase mediated signal transduction

Inferred from electronic annotation. Source: InterPro

vesicle docking involved in exocytosis

Inferred from direct assay PubMed 17574030. Source: BHF-UCL

   Cellular_componentGolgi membrane

Traceable author statement. Source: Reactome

cytoplasmic vesicle membrane

Traceable author statement. Source: Reactome

dendrite

Inferred from electronic annotation. Source: Ensembl

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867PubMed 20458337. Source: UniProt

neuronal cell body

Inferred from electronic annotation. Source: Ensembl

nonmotile primary cilium

Inferred from direct assay PubMed 17574030. Source: BHF-UCL

phagocytic vesicle

Inferred from direct assay Ref.22. Source: UniProtKB

phagocytic vesicle membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

postsynaptic density

Inferred from electronic annotation. Source: Ensembl

recycling endosome membrane

Inferred from direct assay Ref.17PubMed 21951725. Source: UniProtKB

   Molecular_functionGDP binding

Inferred from direct assay PubMed 20937701. Source: UniProtKB

GTP binding

Inferred from direct assay PubMed 20937701. Source: UniProtKB

GTPase activity

Inferred from experiment. Source: Reactome

Rab GTPase binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.10Ref.12Ref.17Ref.15Ref.24. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

OCRLQ0196811EBI-722293,EBI-6148898
RABIFP472242EBI-722293,EBI-713992

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 204204Ras-related protein Rab-8A
PRO_0000121130
Propeptide205 – 2073Removed in mature form Potential
PRO_0000370793

Regions

Nucleotide binding15 – 228GTP By similarity
Nucleotide binding63 – 675GTP By similarity
Nucleotide binding121 – 1244GTP By similarity
Motif37 – 459Effector region By similarity

Amino acid modifications

Modified residue1811Phosphoserine Ref.18
Modified residue1851Phosphoserine Ref.11 Ref.18 Ref.21
Modified residue2041Cysteine methyl ester Potential
Lipidation2041S-geranylgeranyl cysteine Ref.8

Experimental info

Mutagenesis221T → N: Loss of interaction with MICALL1. Ref.17
Mutagenesis671Q → L: Probable constitutively active mutant locked in the active GTP-bound form. Stimulates interaction with MICALL1. Ref.17
Sequence conflict177 – 1837LEGNSPQ → WKATAP in AAB19681. Ref.2

Secondary structure

................................ 207
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P61006 [UniParc].

Last modified April 26, 2004. Version 1.
Checksum: AA52DBF54A2CD056

FASTA20723,668
        10         20         30         40         50         60 
MAKTYDYLFK LLLIGDSGVG KTCVLFRFSE DAFNSTFIST IGIDFKIRTI ELDGKRIKLQ 

        70         80         90        100        110        120 
IWDTAGQERF RTITTAYYRG AMGIMLVYDI TNEKSFDNIR NWIRNIEEHA SADVEKMILG 

       130        140        150        160        170        180 
NKCDVNDKRQ VSKERGEKLA LDYGIKFMET SAKANINVEN AFFTLARDIK AKMDKKLEGN 

       190        200 
SPQGSNQGVK ITPDQQKRSS FFRCVLL 

« Hide

References

« Hide 'large scale' references
[1]"A small rab GTPase is distributed in cytoplasmic vesicles in non polarized cells but colocalizes with the tight junction marker ZO-1 in polarized epithelial cells."
Zahraoui A., Joberty G., Arpin M., Fontaine J.J., Hellio R., Tavitian A., Louvard D.
J. Cell Biol. 124:101-115(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"The MEL gene: a new member of the RAB/YPT class of RAS-related genes."
Nimmo E.R., Sanders P.G., Padua R.A., Hughes D., Williamson R., Johnson K.J.
Oncogene 6:1347-1351(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."
Puhl H.L. III, Ikeda S.R., Aronstam R.S.
Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[4]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Skin.
[8]"Isoprenylation of Rab proteins possessing a C-terminal CaaX motif."
Joberty G., Tavitian A., Zahraoui A.
FEBS Lett. 330:323-328(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: ISOPRENYLATION AT CYS-204.
[9]"A Rab8-specific GDP/GTP exchange factor is involved in actin remodeling and polarized membrane transport."
Hattula K., Furuhjelm J., Arffman A., Peranen J.
Mol. Biol. Cell 13:3268-3280(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RAB3IP, SUBCELLULAR LOCATION.
Tissue: Brain.
[10]"Optineurin links myosin VI to the Golgi complex and is involved in Golgi organization and exocytosis."
Sahlender D.A., Roberts R.C., Arden S.D., Spudich G., Taylor M.J., Luzio J.P., Kendrick-Jones J., Buss F.
J. Cell Biol. 169:285-295(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION WITH OPTN.
[11]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-185, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[12]"Final stages of cytokinesis and midbody ring formation are controlled by BRUCE."
Pohl C., Jentsch S.
Cell 132:832-845(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH BIRC6/BRUCE.
[13]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[14]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]"Pitchfork regulates primary cilia disassembly and left-right asymmetry."
Kinzel D., Boldt K., Davis E.E., Burtscher I., Trumbach D., Diplas B., Attie-Bitach T., Wurst W., Katsanis N., Ueffing M., Lickert H.
Dev. Cell 19:66-77(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PIFO.
[16]"A molecular network for de novo generation of the apical surface and lumen."
Bryant D.M., Datta A., Rodriguez-Fraticelli A.E., Peraenen J., Martin-Belmonte F., Mostov K.E.
Nat. Cell Biol. 12:1035-1045(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[17]"MICAL-L1 links EHD1 to tubular recycling endosomes and regulates receptor recycling."
Sharma M., Giridharan S.S., Rahajeng J., Naslavsky N., Caplan S.
Mol. Biol. Cell 20:5181-5194(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION WITH EHD1 AND MICALL1, MUTAGENESIS OF THR-22 AND GLN-67.
[18]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181 AND SER-185, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[19]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[20]"Rab GTPase-Myo5B complexes control membrane recycling and epithelial polarization."
Roland J.T., Bryant D.M., Datta A., Itzen A., Mostov K.E., Goldenring J.R.
Proc. Natl. Acad. Sci. U.S.A. 108:2789-2794(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH MYO5B.
[21]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-185, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[22]"Rab GTPases regulating phagosome maturation are differentially recruited to mycobacterial phagosomes."
Seto S., Tsujimura K., Koide Y.
Traffic 12:407-420(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[23]"A SNX10/V-ATPase pathway regulates ciliogenesis in vitro and in vivo."
Chen Y., Wu B., Xu L., Li H., Xia J., Yin W., Li Z., Shi D., Li S., Lin S., Shu X., Pei D.
Cell Res. 22:333-345(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CILIOGENESIS, SUBCELLULAR LOCATION.
[24]"OCRL localizes to the primary cilium: a new role for cilia in Lowe syndrome."
Luo N., West C.C., Murga-Zamalloa C.A., Sun L., Anderson R.M., Wells C.D., Weinreb R.N., Travers J.B., Khanna H., Sun Y.
Hum. Mol. Genet. 21:3333-3344(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH OCRL.
[25]"A structural basis for Lowe syndrome caused by mutations in the Rab-binding domain of OCRL1."
Hou X., Hagemann N., Schoebel S., Blankenfeldt W., Goody R.S., Erdmann K.S., Itzen A.
EMBO J. 30:1659-1670(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 6-176 IN COMPLEX WITH OCRL.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X56741 mRNA. Translation: CAA40065.1.
S53268 mRNA. Translation: AAB19681.1.
AF498943 mRNA. Translation: AAM21091.1.
BT007184 mRNA. Translation: AAP35848.1.
CR536583 mRNA. Translation: CAG38820.1.
CR542274 mRNA. Translation: CAG47070.1.
CH471106 Genomic DNA. Translation: EAW84526.1.
BC002977 mRNA. Translation: AAH02977.1.
CCDSCCDS12339.1.
PIRB49647.
RefSeqNP_005361.2. NM_005370.4.
UniGeneHs.642874.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3QBTX-ray2.00A/C/E/G6-176[»]
3TNFX-ray2.50A6-176[»]
4LHVX-ray1.95A/B/C/D/E6-176[»]
4LHWX-ray1.55A/B/C/D/E6-176[»]
4LHXX-ray3.05A/B1-184[»]
4LHYX-ray3.10A/B1-184[»]
4LHZX-ray3.20A/B1-184[»]
4LI0X-ray3.30A/B1-184[»]
ProteinModelPortalP61006.
SMRP61006. Positions 6-176.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110382. 34 interactions.
DIPDIP-43703N.
IntActP61006. 11 interactions.
MINTMINT-1416277.
STRING9606.ENSP00000300935.

PTM databases

PhosphoSiteP61006.

Polymorphism databases

DMDM46810392.

Proteomic databases

MaxQBP61006.
PaxDbP61006.
PeptideAtlasP61006.
PRIDEP61006.

Protocols and materials databases

DNASU4218.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000300935; ENSP00000300935; ENSG00000167461.
GeneID4218.
KEGGhsa:4218.
UCSCuc002ndn.4. human.

Organism-specific databases

CTD4218.
GeneCardsGC19P016222.
HGNCHGNC:7007. RAB8A.
MIM165040. gene.
neXtProtNX_P61006.
PharmGKBPA30743.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1100.
HOGENOMHOG000233968.
HOVERGENHBG009351.
InParanoidP61006.
KOK07901.
OMAIDKAFYS.
PhylomeDBP61006.
TreeFamTF314097.

Enzyme and pathway databases

ReactomeREACT_11123. Membrane Trafficking.
REACT_115566. Cell Cycle.

Gene expression databases

ArrayExpressP61006.
BgeeP61006.
CleanExHS_RAB8A.
GenevestigatorP61006.

Family and domain databases

Gene3D3.40.50.300. 1 hit.
InterProIPR027417. P-loop_NTPase.
IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR003579. Small_GTPase_Rab_type.
[Graphical view]
PfamPF00071. Ras. 1 hit.
[Graphical view]
PRINTSPR00449. RASTRNSFRMNG.
SMARTSM00175. RAB. 1 hit.
[Graphical view]
SUPFAMSSF52540. SSF52540. 1 hit.
TIGRFAMsTIGR00231. small_GTP. 1 hit.
PROSITEPS51419. RAB. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSRAB8A. human.
GeneWikiRAB8A.
GenomeRNAi4218.
NextBio16637.
PROP61006.
SOURCESearch...

Entry information

Entry nameRAB8A_HUMAN
AccessionPrimary (citable) accession number: P61006
Secondary accession number(s): P24407, Q6FHV5
Entry history
Integrated into UniProtKB/Swiss-Prot: April 26, 2004
Last sequence update: April 26, 2004
Last modified: July 9, 2014
This is version 119 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM