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Protein

Ras-related protein Rab-8A

Gene

Rab8a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

Enzyme regulationi

Activated in response to insulin.By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi15 – 228GTPBy similarity
Nucleotide bindingi63 – 675GTPBy similarity
Nucleotide bindingi121 – 1244GTPBy similarity

GO - Molecular functioni

  1. GDP binding Source: UniProtKB
  2. GTPase activity Source: MGI
  3. GTP binding Source: UniProtKB
  4. myosin V binding Source: MGI
  5. Rab GTPase binding Source: UniProtKB

GO - Biological processi

  1. axonogenesis Source: UniProtKB
  2. cellular response to insulin stimulus Source: UniProtKB
  3. cilium assembly Source: UniProtKB
  4. Golgi vesicle fusion to target membrane Source: MGI
  5. GTP catabolic process Source: MGI
  6. intracellular protein transport Source: GO_Central
  7. protein localization to plasma membrane Source: UniProtKB
  8. protein secretion Source: GO_Central
  9. Rab protein signal transduction Source: GO_Central
  10. regulation of exocytosis Source: GO_Central
  11. regulation of long-term neuronal synaptic plasticity Source: Ensembl
  12. regulation of protein transport Source: Ensembl
  13. synaptic vesicle exocytosis Source: GO_Central
  14. vesicle docking involved in exocytosis Source: MGI
Complete GO annotation...

Keywords - Biological processi

Cilium biogenesis/degradation, Protein transport, Transport

Keywords - Ligandi

GTP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiREACT_196635. Regulation of PLK1 Activity at G2/M Transition.
REACT_199054. Translocation of GLUT4 to the plasma membrane.

Names & Taxonomyi

Protein namesi
Recommended name:
Ras-related protein Rab-8A
Alternative name(s):
Oncogene c-mel
Gene namesi
Name:Rab8a
Synonyms:Mel, Rab8
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 8

Organism-specific databases

MGIiMGI:96960. Rab8a.

Subcellular locationi

Cell membrane 1 Publication; Lipid-anchor 1 Publication; Cytoplasmic side 1 Publication. Golgi apparatus By similarity. Recycling endosome membrane 1 Publication. Cell projectioncilium By similarity. Cytoplasmic vesiclephagosome By similarity. Cytoplasmic vesiclephagosome membrane By similarity; Lipid-anchor By similarity; 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 Mycobacterium (By similarity).By similarity

GO - Cellular componenti

  1. centrosome Source: MGI
  2. ciliary basal body Source: MGI
  3. cilium Source: MGI
  4. dendrite Source: Ensembl
  5. extracellular vesicular exosome Source: MGI
  6. neuronal cell body Source: Ensembl
  7. nonmotile primary cilium Source: MGI
  8. nucleolus Source: MGI
  9. nucleoplasm Source: MGI
  10. nucleus Source: MGI
  11. phagocytic vesicle Source: UniProtKB
  12. phagocytic vesicle membrane Source: UniProtKB-SubCell
  13. plasma membrane Source: UniProtKB
  14. postsynaptic density Source: Ensembl
  15. primary cilium Source: MGI
  16. recycling endosome Source: UniProtKB
  17. recycling endosome membrane Source: UniProtKB
  18. secretory granule membrane Source: GO_Central
  19. synaptic vesicle Source: GO_Central
  20. trans-Golgi network transport vesicle Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasmic vesicle, Endosome, Golgi apparatus, Membrane

Pathology & Biotechi

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 204204Ras-related protein Rab-8APRO_0000121132Add
BLAST
Propeptidei205 – 2073Removed in mature formSequence AnalysisPRO_0000370795

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei181 – 1811PhosphoserineBy similarity
Modified residuei185 – 1851PhosphoserineBy similarity
Modified residuei204 – 2041Cysteine methyl esterSequence Analysis
Lipidationi204 – 2041S-geranylgeranyl cysteineBy similarity

Keywords - PTMi

Lipoprotein, Methylation, Phosphoprotein, Prenylation

Proteomic databases

MaxQBiP55258.
PaxDbiP55258.
PRIDEiP55258.

PTM databases

PhosphoSiteiP55258.

Expressioni

Gene expression databases

BgeeiP55258.
CleanExiMM_RAB8A.
ExpressionAtlasiP55258. baseline and differential.
GenevestigatoriP55258.

Interactioni

Subunit structurei

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.7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Rph3aP477082EBI-398411,EBI-398376

Protein-protein interaction databases

BioGridi201387. 5 interactions.
IntActiP55258. 11 interactions.
MINTiMINT-1862635.

Structurei

Secondary structure

1
207
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi6 – 149Combined sources
Helixi37 – 415Combined sources
Beta strandi43 – 5210Combined sources
Beta strandi55 – 639Combined sources
Turni76 – 805Combined sources
Beta strandi82 – 898Combined sources
Helixi93 – 10917Combined sources
Beta strandi115 – 1217Combined sources
Helixi133 – 14210Combined sources
Beta strandi146 – 1494Combined sources
Helixi158 – 17518Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2FU5X-ray2.00C/D1-175[»]
ProteinModelPortaliP55258.
SMRiP55258. Positions 6-176.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP55258.

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi37 – 459Effector regionBy similarity

Sequence similaritiesi

Belongs to the small GTPase superfamily. Rab family.Curated

Phylogenomic databases

eggNOGiCOG1100.
HOGENOMiHOG000233968.
HOVERGENiHBG009351.
InParanoidiP55258.
KOiK07901.
OMAiIDKAFYS.
OrthoDBiEOG7VB2H4.
TreeFamiTF314097.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR027417. P-loop_NTPase.
IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR003579. Small_GTPase_Rab_type.
[Graphical view]
PfamiPF00071. Ras. 1 hit.
[Graphical view]
PRINTSiPR00449. RASTRNSFRMNG.
SMARTiSM00175. RAB. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR00231. small_GTP. 1 hit.
PROSITEiPS51419. RAB. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P55258-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAKTYDYLFK LLLIGDSGVG KTCVLFRFSE DAFNSTFIST IGIDFKIRTI
60 70 80 90 100
ELDGKRIKLQ IWDTAGQERF RTITTAYYRG AMGIMLVYDI TNEKSFDNIR
110 120 130 140 150
NWIRNIEEHA SADVEKMILG NKCDVNDKRQ VSKERGEKLA LDYGIKFMET
160 170 180 190 200
SAKANINVEN AFFTLARDIK AKMDKKLEGN SPQGSSHGVK ITVEQQKRTS

FFRCSLL
Length:207
Mass (Da):23,668
Last modified:November 22, 2005 - v2
Checksum:iAC89DC85588FB8F8
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti176 – 1838KLEGNSPQ → NWKATAA in AAB19682 (PubMed:1886711).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S53270 mRNA. Translation: AAB19682.1.
AK076048 mRNA. Translation: BAC36146.1.
AK079306 mRNA. Translation: BAC37603.1.
AK080740 mRNA. Translation: BAC38003.1.
BC019990 mRNA. Translation: AAH19990.1.
CCDSiCCDS22409.1.
RefSeqiNP_075615.2. NM_023126.2.
UniGeneiMm.162811.

Genome annotation databases

EnsembliENSMUST00000003121; ENSMUSP00000003121; ENSMUSG00000003037.
GeneIDi17274.
KEGGimmu:17274.
UCSCiuc009mfj.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S53270 mRNA. Translation: AAB19682.1.
AK076048 mRNA. Translation: BAC36146.1.
AK079306 mRNA. Translation: BAC37603.1.
AK080740 mRNA. Translation: BAC38003.1.
BC019990 mRNA. Translation: AAH19990.1.
CCDSiCCDS22409.1.
RefSeqiNP_075615.2. NM_023126.2.
UniGeneiMm.162811.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2FU5X-ray2.00C/D1-175[»]
ProteinModelPortaliP55258.
SMRiP55258. Positions 6-176.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201387. 5 interactions.
IntActiP55258. 11 interactions.
MINTiMINT-1862635.

PTM databases

PhosphoSiteiP55258.

Proteomic databases

MaxQBiP55258.
PaxDbiP55258.
PRIDEiP55258.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000003121; ENSMUSP00000003121; ENSMUSG00000003037.
GeneIDi17274.
KEGGimmu:17274.
UCSCiuc009mfj.1. mouse.

Organism-specific databases

CTDi4218.
MGIiMGI:96960. Rab8a.

Phylogenomic databases

eggNOGiCOG1100.
HOGENOMiHOG000233968.
HOVERGENiHBG009351.
InParanoidiP55258.
KOiK07901.
OMAiIDKAFYS.
OrthoDBiEOG7VB2H4.
TreeFamiTF314097.

Enzyme and pathway databases

ReactomeiREACT_196635. Regulation of PLK1 Activity at G2/M Transition.
REACT_199054. Translocation of GLUT4 to the plasma membrane.

Miscellaneous databases

EvolutionaryTraceiP55258.
NextBioi291770.
PROiP55258.
SOURCEiSearch...

Gene expression databases

BgeeiP55258.
CleanExiMM_RAB8A.
ExpressionAtlasiP55258. baseline and differential.
GenevestigatoriP55258.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR027417. P-loop_NTPase.
IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR003579. Small_GTPase_Rab_type.
[Graphical view]
PfamiPF00071. Ras. 1 hit.
[Graphical view]
PRINTSiPR00449. RASTRNSFRMNG.
SMARTiSM00175. RAB. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR00231. small_GTP. 1 hit.
PROSITEiPS51419. RAB. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "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].
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Cerebellum and Retina.
  3. "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].
    Strain: FVB/N.
    Tissue: Liver.
  4. Lubec G., Kang S.U.
    Submitted (APR-2007) to UniProtKB
    Cited for: PROTEIN SEQUENCE OF 11-21; 59-69 AND 139-153, IDENTIFICATION BY MASS SPECTROMETRY.
    Strain: C57BL/6.
    Tissue: Brain.
  5. "In its active form, the GTP-binding protein rab8 interacts with a stress-activated protein kinase."
    Ren M., Zeng J., De Lemos-Chiarandini C., Rosenfeld M., Adesnik M., Sabatini D.D.
    Proc. Natl. Acad. Sci. U.S.A. 93:5151-5155(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH MAP4K2.
    Strain: BALB/c.
    Tissue: Melanoma.
  6. "Distinct Rab binding specificity of Rim1, Rim2, rabphilin, and Noc2. Identification of a critical determinant of Rab3A/Rab27A recognition by Rim2."
    Fukuda M.
    J. Biol. Chem. 278:15373-15380(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH RIMS2; RPH3A AND RPH3AL.
  7. "Slp4-a/granuphilin-a inhibits dense-core vesicle exocytosis through interaction with the GDP-bound form of Rab27A in PC12 cells."
    Fukuda M.
    J. Biol. Chem. 278:15390-15396(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SYTL4.
  8. "Identification of three novel proteins (SGSM1, 2, 3) which modulate small G protein (RAP and RAB)-mediated signaling pathway."
    Yang H., Sasaki T., Minoshima S., Shimizu N.
    Genomics 90:249-260(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SGSM1 AND SGSM3.
  9. "The interaction of JRAB/MICAL-L2 with Rab8 and Rab13 coordinates the assembly of tight junctions and adherens junctions."
    Yamamura R., Nishimura N., Nakatsuji H., Arase S., Sasaki T.
    Mol. Biol. Cell 19:971-983(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN ENDOCYTIC RECYCLING, SUBCELLULAR LOCATION, INTERACTION WITH MICAL1; MICALL1 AND MICALL2.
  10. "The phagosomal proteome in interferon-gamma-activated macrophages."
    Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
    Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  11. Cited for: INTERACTION WITH PIFO.
  12. "Nucleotide exchange via local protein unfolding--structure of Rab8 in complex with MSS4."
    Itzen A., Pylypenko O., Goody R.S., Alexandrov K., Rak A.
    EMBO J. 25:1445-1455(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-175 IN COMPLEX WITH RABIF, INTERACTION WITH RABIF.

Entry informationi

Entry nameiRAB8A_MOUSE
AccessioniPrimary (citable) accession number: P55258
Secondary accession number(s): Q8VCF6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: November 22, 2005
Last modified: March 4, 2015
This is version 141 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.