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Protein

Ras-related protein Rab-8A

Gene

RAB8A

Organism
Homo sapiens (Human)
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.3 Publications

Enzyme regulationi

Activated in response to insulin.By similarity

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi15 – 22GTPBy similarity8
Nucleotide bindingi63 – 67GTPBy similarity5
Nucleotide bindingi121 – 124GTPBy similarity4

GO - Molecular functioni

  • GDP binding Source: UniProtKB
  • GTPase activity Source: UniProtKB
  • GTP binding Source: UniProtKB
  • myosin V binding Source: UniProtKB
  • Rab GTPase binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Cilium biogenesis/degradation, Protein transport, Transport

Keywords - Ligandi

GTP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-1445148. Translocation of GLUT4 to the plasma membrane.
R-HSA-2565942. Regulation of PLK1 Activity at G2/M Transition.
R-HSA-5620912. Anchoring of the basal body to the plasma membrane.
R-HSA-5620916. VxPx cargo-targeting to cilium.
R-HSA-8876198. RAB GEFs exchange GTP for GDP on RABs.

Names & Taxonomyi

Protein namesi
Recommended name:
Ras-related protein Rab-8A
Alternative name(s):
Oncogene c-mel
Gene namesi
Name:RAB8A
Synonyms:MEL, RAB8
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:7007. RAB8A.

Subcellular locationi

GO - Cellular componenti

  • centriole Source: UniProtKB-SubCell
  • centrosome Source: MGI
  • ciliary basal body Source: Ensembl
  • ciliary base Source: Ensembl
  • cilium Source: UniProtKB
  • cytoplasmic vesicle membrane Source: Reactome
  • cytosol Source: Reactome
  • dendrite Source: Ensembl
  • extracellular exosome Source: UniProtKB
  • extracellular matrix Source: BHF-UCL
  • Golgi membrane Source: Reactome
  • neuronal cell body Source: Ensembl
  • non-motile cilium Source: BHF-UCL
  • nucleolus Source: HPA
  • nucleus Source: HPA
  • phagocytic vesicle Source: UniProtKB
  • phagocytic vesicle membrane Source: UniProtKB-SubCell
  • plasma membrane Source: HPA
  • postsynaptic density Source: Ensembl
  • recycling endosome membrane Source: UniProtKB
  • synaptic vesicle Source: GO_Central
  • trans-Golgi network transport vesicle Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cilium, Cytoplasm, Cytoplasmic vesicle, Cytoskeleton, Endosome, Golgi apparatus, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi22T → N: Loss of interaction with MICALL1. 1 Publication1
Mutagenesisi67Q → L: Probable constitutively active mutant locked in the active GTP-bound form. Stimulates interaction with MICALL1. 1 Publication1

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

DisGeNETi4218.
OpenTargetsiENSG00000167461.
PharmGKBiPA30743.

Polymorphism and mutation databases

BioMutaiRAB8A.
DMDMi46810392.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001211301 – 204Ras-related protein Rab-8AAdd BLAST204
PropeptideiPRO_0000370793205 – 207Removed in mature formSequence analysis3

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei181PhosphoserineCombined sources1
Modified residuei185PhosphoserineCombined sources1
Modified residuei204Cysteine methyl esterSequence analysis1
Lipidationi204S-geranylgeranyl cysteine1 Publication1

Keywords - PTMi

Lipoprotein, Methylation, Phosphoprotein, Prenylation

Proteomic databases

EPDiP61006.
MaxQBiP61006.
PaxDbiP61006.
PeptideAtlasiP61006.
PRIDEiP61006.

PTM databases

iPTMnetiP61006.
PhosphoSitePlusiP61006.
SwissPalmiP61006.

Expressioni

Gene expression databases

BgeeiENSG00000167461.
CleanExiHS_RAB8A.
ExpressionAtlasiP61006. baseline and differential.
GenevisibleiP61006. HS.

Organism-specific databases

HPAiHPA041945.

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. Interacts with AHI1 (By similarity).By similarity8 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
LRRK2Q5S0076EBI-722293,EBI-5323863
OCRLQ0196813EBI-722293,EBI-6148898
OPTNQ96CV94EBI-722293,EBI-748974
RAB3IPQ96QF05EBI-722293,EBI-747844
RABIFP472244EBI-722293,EBI-713992

GO - Molecular functioni

  • myosin V binding Source: UniProtKB
  • Rab GTPase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi110382. 61 interactors.
DIPiDIP-43703N.
IntActiP61006. 70 interactors.
MINTiMINT-1416277.
STRINGi9606.ENSP00000300935.

Structurei

Secondary structure

1207
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi7 – 14Combined sources8
Helixi21 – 30Combined sources10
Turni38 – 41Combined sources4
Beta strandi42 – 52Combined sources11
Beta strandi55 – 64Combined sources10
Turni69 – 72Combined sources4
Helixi73 – 78Combined sources6
Beta strandi82 – 89Combined sources8
Helixi93 – 97Combined sources5
Helixi99 – 109Combined sources11
Beta strandi115 – 121Combined sources7
Turni122 – 124Combined sources3
Helixi126 – 128Combined sources3
Helixi133 – 142Combined sources10
Beta strandi146 – 149Combined sources4
Turni152 – 155Combined sources4
Helixi158 – 174Combined sources17

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
5SZIX-ray2.85A1-207[»]
ProteinModelPortaliP61006.
SMRiP61006.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi37 – 45Effector regionBy similarity9

Sequence similaritiesi

Belongs to the small GTPase superfamily. Rab family.Curated

Phylogenomic databases

eggNOGiKOG0078. Eukaryota.
ENOG410XPUI. LUCA.
GeneTreeiENSGT00860000133675.
HOGENOMiHOG000233968.
HOVERGENiHBG009351.
InParanoidiP61006.
KOiK07901.
OMAiFTNIRTW.
OrthoDBiEOG091G0LA6.
PhylomeDBiP61006.
TreeFamiTF314097.

Family and domain databases

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

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P61006-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« 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 SPQGSNQGVK ITPDQQKRSS

FFRCVLL
Length:207
Mass (Da):23,668
Last modified:April 26, 2004 - v1
Checksum:iAA52DBF54A2CD056
GO
Isoform 2 (identifier: P61006-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     161-205: AFFTLARDIK...QKRSSFFRCV → RYQSKNGQKI...PMCSSVRNTA

Note: No experimental confirmation available.
Show »
Length:207
Mass (Da):23,564
Checksum:i249CB68DDF955162
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti177 – 183LEGNSPQ → WKATAP in AAB19681 (PubMed:1886711).Curated7

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_056399161 – 205AFFTL…FFRCV → RYQSKNGQKIGRQQPPGEQP GSQNHTGPAEEEQLFPMCSS VRNTA in isoform 2. 1 PublicationAdd BLAST45

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X56741 mRNA. Translation: CAA40065.1.
S53268 mRNA. Translation: AAB19681.1.
AF498943 mRNA. Translation: AAM21091.1.
BT007184 mRNA. Translation: AAP35848.1.
AK293676 mRNA. Translation: BAG57118.1.
CR536583 mRNA. Translation: CAG38820.1.
AC008894 Genomic DNA. No translation available.
CR542274 mRNA. Translation: CAG47070.1.
CH471106 Genomic DNA. Translation: EAW84526.1.
BC002977 mRNA. Translation: AAH02977.1.
CCDSiCCDS12339.1. [P61006-1]
PIRiB49647.
RefSeqiNP_005361.2. NM_005370.4. [P61006-1]
UniGeneiHs.642874.

Genome annotation databases

EnsembliENST00000300935; ENSP00000300935; ENSG00000167461. [P61006-1]
ENST00000586682; ENSP00000467501; ENSG00000167461. [P61006-2]
GeneIDi4218.
KEGGihsa:4218.
UCSCiuc002ndn.5. human. [P61006-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X56741 mRNA. Translation: CAA40065.1.
S53268 mRNA. Translation: AAB19681.1.
AF498943 mRNA. Translation: AAM21091.1.
BT007184 mRNA. Translation: AAP35848.1.
AK293676 mRNA. Translation: BAG57118.1.
CR536583 mRNA. Translation: CAG38820.1.
AC008894 Genomic DNA. No translation available.
CR542274 mRNA. Translation: CAG47070.1.
CH471106 Genomic DNA. Translation: EAW84526.1.
BC002977 mRNA. Translation: AAH02977.1.
CCDSiCCDS12339.1. [P61006-1]
PIRiB49647.
RefSeqiNP_005361.2. NM_005370.4. [P61006-1]
UniGeneiHs.642874.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
5SZIX-ray2.85A1-207[»]
ProteinModelPortaliP61006.
SMRiP61006.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110382. 61 interactors.
DIPiDIP-43703N.
IntActiP61006. 70 interactors.
MINTiMINT-1416277.
STRINGi9606.ENSP00000300935.

PTM databases

iPTMnetiP61006.
PhosphoSitePlusiP61006.
SwissPalmiP61006.

Polymorphism and mutation databases

BioMutaiRAB8A.
DMDMi46810392.

Proteomic databases

EPDiP61006.
MaxQBiP61006.
PaxDbiP61006.
PeptideAtlasiP61006.
PRIDEiP61006.

Protocols and materials databases

DNASUi4218.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000300935; ENSP00000300935; ENSG00000167461. [P61006-1]
ENST00000586682; ENSP00000467501; ENSG00000167461. [P61006-2]
GeneIDi4218.
KEGGihsa:4218.
UCSCiuc002ndn.5. human. [P61006-1]

Organism-specific databases

CTDi4218.
DisGeNETi4218.
GeneCardsiRAB8A.
HGNCiHGNC:7007. RAB8A.
HPAiHPA041945.
MIMi165040. gene.
neXtProtiNX_P61006.
OpenTargetsiENSG00000167461.
PharmGKBiPA30743.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0078. Eukaryota.
ENOG410XPUI. LUCA.
GeneTreeiENSGT00860000133675.
HOGENOMiHOG000233968.
HOVERGENiHBG009351.
InParanoidiP61006.
KOiK07901.
OMAiFTNIRTW.
OrthoDBiEOG091G0LA6.
PhylomeDBiP61006.
TreeFamiTF314097.

Enzyme and pathway databases

ReactomeiR-HSA-1445148. Translocation of GLUT4 to the plasma membrane.
R-HSA-2565942. Regulation of PLK1 Activity at G2/M Transition.
R-HSA-5620912. Anchoring of the basal body to the plasma membrane.
R-HSA-5620916. VxPx cargo-targeting to cilium.
R-HSA-8876198. RAB GEFs exchange GTP for GDP on RABs.

Miscellaneous databases

ChiTaRSiRAB8A. human.
GeneWikiiRAB8A.
GenomeRNAii4218.
PROiP61006.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000167461.
CleanExiHS_RAB8A.
ExpressionAtlasiP61006. baseline and differential.
GenevisibleiP61006. HS.

Family and domain databases

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

Entry informationi

Entry nameiRAB8A_HUMAN
AccessioniPrimary (citable) accession number: P61006
Secondary accession number(s): B4DEK7, P24407, Q6FHV5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 26, 2004
Last sequence update: April 26, 2004
Last modified: November 30, 2016
This is version 146 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

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 one 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.