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Protein

Ras-related protein Rab-5A

Gene

RAB5A

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. RAB5A is required for the fusion of plasma membranes and early endosomes (PubMed:10818110, PubMed:14617813, PubMed:16410077, PubMed:15378032). Contributes to the regulation of filopodia extension (PubMed:14978216). Required for the exosomal release of SDCBP, CD63, PDCD6IP and syndecan (PubMed:22660413). Regulates maturation of apoptotic cell-containing phagosomes, probably downstream of DYN2 and PIK3C3 (By similarity).By similarity6 Publications

Enzyme regulationi

Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi27 – 35GTPCombined sources4 Publications9
Nucleotide bindingi46 – 52GTPCombined sources4 Publications7
Nucleotide bindingi75 – 79GTPCombined sources4 Publications5
Nucleotide bindingi133 – 136GTPCombined sources4 Publications4
Nucleotide bindingi163 – 165GTPCombined sources4 Publications3

GO - Molecular functioni

  • GDP binding Source: UniProtKB
  • GTPase activity Source: UniProtKB
  • GTP binding Source: UniProtKB

GO - Biological processi

  • blood coagulation Source: Reactome
  • early endosome to late endosome transport Source: UniProtKB
  • endocytosis Source: UniProtKB
  • phagocytosis Source: UniProtKB-KW
  • positive regulation of exocytosis Source: UniProtKB
  • protein transport Source: UniProtKB-KW
  • receptor internalization involved in canonical Wnt signaling pathway Source: BHF-UCL
  • regulation of autophagosome assembly Source: ParkinsonsUK-UCL
  • regulation of endocytosis Source: GO_Central
  • regulation of endosome size Source: UniProtKB
  • regulation of filopodium assembly Source: UniProtKB
  • regulation of synaptic vesicle exocytosis Source: ParkinsonsUK-UCL
  • small GTPase mediated signal transduction Source: InterPro
  • synaptic vesicle recycling Source: ParkinsonsUK-UCL
  • viral RNA genome replication Source: ParkinsonsUK-UCL
Complete GO annotation...

Keywords - Biological processi

Endocytosis, Phagocytosis, Protein transport, Transport

Keywords - Ligandi

GTP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000144566-MONOMER.
ReactomeiR-HSA-1660499. Synthesis of PIPs at the plasma membrane.
R-HSA-8856828. Clathrin-mediated endocytosis.
R-HSA-8876198. RAB GEFs exchange GTP for GDP on RABs.
R-HSA-983231. Factors involved in megakaryocyte development and platelet production.
SIGNORiP20339.

Names & Taxonomyi

Protein namesi
Recommended name:
Ras-related protein Rab-5A
Gene namesi
Name:RAB5A
Synonyms:RAB5
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:9783. RAB5A.

Subcellular locationi

GO - Cellular componenti

  • actin cytoskeleton Source: Ensembl
  • axon Source: ParkinsonsUK-UCL
  • axon terminus Source: ParkinsonsUK-UCL
  • cytoplasm Source: MGI
  • cytoplasmic side of early endosome membrane Source: UniProtKB
  • cytosol Source: UniProtKB
  • dendrite Source: ParkinsonsUK-UCL
  • early endosome Source: UniProtKB
  • endocytic vesicle Source: GO_Central
  • endosome Source: ParkinsonsUK-UCL
  • endosome membrane Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • melanosome Source: UniProtKB-SubCell
  • membrane raft Source: Ensembl
  • neuronal cell body Source: ParkinsonsUK-UCL
  • phagocytic vesicle membrane Source: UniProtKB-SubCell
  • plasma membrane Source: GO_Central
  • ruffle Source: UniProtKB-SubCell
  • somatodendritic compartment Source: ParkinsonsUK-UCL
  • synaptic vesicle Source: ParkinsonsUK-UCL
  • terminal bouton Source: ParkinsonsUK-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Cytoplasmic vesicle, Endosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi54G → Q: Strongly decreases ZFYVE20 binding affinity. 1 Publication1
Mutagenesisi56A → E: Strongly decreases ZFYVE20 binding affinity. 1 Publication1
Mutagenesisi57F → A: Strongly decreases RABEP1 and ZFYVE20 binding affinity. 2 Publications1
Mutagenesisi74W → A: Strongly decreases RABEP1 binding affinity. 1 Publication1
Mutagenesisi79Q → L: Loss of GTPase activity. Does not inhibit filopodia formation. 2 Publications1
Mutagenesisi82Y → A: Strongly decreases RABEP1 binding affinity. Impairs endosome fusion. 1 Publication1
Mutagenesisi89Y → A: Strongly decreases RABEP1 binding affinity. 1 Publication1
Mutagenesisi116K → E: No effect on RABEP1 binding affinity. 1 Publication1
Mutagenesisi120R → E: No effect on RABEP1 binding affinity. 1 Publication1

Organism-specific databases

DisGeNETi5868.
OpenTargetsiENSG00000144566.
PharmGKBiPA34143.

Polymorphism and mutation databases

BioMutaiRAB5A.
DMDMi1346958.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001211041 – 215Ras-related protein Rab-5AAdd BLAST215

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi212S-geranylgeranyl cysteine1 Publication1
Lipidationi213S-geranylgeranyl cysteine1 Publication1

Keywords - PTMi

Lipoprotein, Prenylation

Proteomic databases

EPDiP20339.
PaxDbiP20339.
PeptideAtlasiP20339.
PRIDEiP20339.
TopDownProteomicsiP20339-1. [P20339-1]

PTM databases

iPTMnetiP20339.
PhosphoSitePlusiP20339.
SwissPalmiP20339.

Expressioni

Gene expression databases

BgeeiENSG00000144566.
CleanExiHS_RAB5A.
ExpressionAtlasiP20339. baseline and differential.
GenevisibleiP20339. HS.

Organism-specific databases

HPAiCAB004567.

Interactioni

Subunit structurei

Interacts with SGSM1 and SGSM3 (By similarity). Interacts with PIK3CB (By similarity). Interacts with GDI1; this promotes dissociation from membranes (PubMed:23815289). Interacts with EEA1 (PubMed:10491193, PubMed:20534488). Interacts with RIN1 and GAPVD1, which regulate its pathway, probably by acting as a GEF (PubMed:11703925, PubMed:16410077). Interacts with RINL. Interacts with ALS2CL, SUN2, ZFYVE20 and RUFY1 (PubMed:10818110, PubMed:11062261, PubMed:15388334, PubMed:14617813, PubMed:16034420). Interacts with RABEP1; one RABEP1 homodimer binds two RAB5A chains, but at opposite sides of the dimer (PubMed:15378032). Interacts with OCRL (PubMed:25869668). Interacts with INPP5F. May be a component of a complex composed of RAB5A, DYN2 and PIK3C3 (By similarity). Does not interact with BLOC-3 complex (heterodimer of HPS1 and HPS4) (By similarity). Interacts with CLN5 (PubMed:22431521).By similarity14 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ALS2Q96Q422EBI-399437,EBI-1044902
APPL1Q9UKG117EBI-399437,EBI-741243
EEA1Q150754EBI-399437,EBI-298113
OCRLQ0196810EBI-399437,EBI-6148898
PIK3R1P237275EBI-399437,EBI-520244From a different organism.

Protein-protein interaction databases

BioGridi111806. 106 interactors.
DIPiDIP-380N.
IntActiP20339. 35 interactors.
MINTiMINT-209361.
STRINGi9606.ENSP00000273047.

Structurei

Secondary structure

1215
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi17 – 26Combined sources10
Beta strandi28 – 32Combined sources5
Helixi33 – 42Combined sources10
Beta strandi53 – 64Combined sources12
Beta strandi67 – 76Combined sources10
Helixi80 – 85Combined sources6
Helixi86 – 90Combined sources5
Beta strandi94 – 101Combined sources8
Helixi105 – 121Combined sources17
Beta strandi127 – 133Combined sources7
Helixi135 – 140Combined sources6
Helixi145 – 154Combined sources10
Beta strandi158 – 161Combined sources4
Turni164 – 166Combined sources3
Helixi170 – 179Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1N6HX-ray1.51A15-184[»]
1N6IX-ray1.60A15-184[»]
1N6KX-ray1.55A15-184[»]
1N6LX-ray1.60A15-184[»]
1N6NX-ray1.60A15-184[»]
1N6OX-ray1.80A15-184[»]
1N6PX-ray1.54A15-184[»]
1N6RX-ray1.55A15-184[»]
1R2QX-ray1.05A15-184[»]
1TU3X-ray2.31A/B/C/D/E15-184[»]
1TU4X-ray2.20A/B/C/D15-184[»]
3MJHX-ray2.03A/C16-183[»]
4Q9UX-ray4.62B/F15-184[»]
ProteinModelPortaliP20339.
SMRiP20339.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP20339.

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi49 – 57Effector regionBy similarity9

Sequence similaritiesi

Belongs to the small GTPase superfamily. Rab family.Curated

Phylogenomic databases

eggNOGiKOG0092. Eukaryota.
ENOG410YCCP. LUCA.
GeneTreeiENSGT00760000119101.
HOGENOMiHOG000233968.
HOVERGENiHBG009351.
InParanoidiP20339.
KOiK07887.
OMAiPKSQCCS.
OrthoDBiEOG091G0HKN.
PhylomeDBiP20339.
TreeFamiTF300199.

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.

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

Isoform 1 (identifier: P20339-1) [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
MASRGATRPN GPNTGNKICQ FKLVLLGESA VGKSSLVLRF VKGQFHEFQE
60 70 80 90 100
STIGAAFLTQ TVCLDDTTVK FEIWDTAGQE RYHSLAPMYY RGAQAAIVVY
110 120 130 140 150
DITNEESFAR AKNWVKELQR QASPNIVIAL SGNKADLANK RAVDFQEAQS
160 170 180 190 200
YADDNSLLFM ETSAKTSMNV NEIFMAIAKK LPKNEPQNPG ANSARGRGVD
210
LTEPTQPTRN QCCSN
Length:215
Mass (Da):23,659
Last modified:February 1, 1996 - v2
Checksum:iEC03DDF96BBEF821
GO
Isoform 2 (identifier: P20339-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     55-68: Missing.

Note: No experimental confirmation available.
Show »
Length:201
Mass (Da):22,178
Checksum:i4A63017DEF84F328
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti81R → G in AAA60245 (PubMed:2501306).Curated1
Sequence conflicti197R → G in AAA60245 (PubMed:2501306).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_05583055 – 68Missing in isoform 2. 1 PublicationAdd BLAST14

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M28215 mRNA. Translation: AAA60245.1.
AF464088 mRNA. Translation: AAO15677.1.
AF498936 mRNA. Translation: AAM21084.1.
AK295992 mRNA. Translation: BAG58767.1.
AK312618 mRNA. Translation: BAG35504.1.
CR536492 mRNA. Translation: CAG38731.1.
AC097635 Genomic DNA. No translation available.
CH471055 Genomic DNA. Translation: EAW64301.1.
BC001267 mRNA. Translation: AAH01267.1.
BC018288 mRNA. Translation: AAH18288.1.
CCDSiCCDS2633.1. [P20339-1]
CCDS77710.1. [P20339-2]
PIRiF34323.
RefSeqiNP_001278977.1. NM_001292048.1. [P20339-2]
NP_004153.2. NM_004162.4. [P20339-1]
UniGeneiHs.475663.

Genome annotation databases

EnsembliENST00000273047; ENSP00000273047; ENSG00000144566. [P20339-1]
ENST00000422242; ENSP00000411941; ENSG00000144566. [P20339-2]
GeneIDi5868.
KEGGihsa:5868.
UCSCiuc003cbn.4. human. [P20339-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M28215 mRNA. Translation: AAA60245.1.
AF464088 mRNA. Translation: AAO15677.1.
AF498936 mRNA. Translation: AAM21084.1.
AK295992 mRNA. Translation: BAG58767.1.
AK312618 mRNA. Translation: BAG35504.1.
CR536492 mRNA. Translation: CAG38731.1.
AC097635 Genomic DNA. No translation available.
CH471055 Genomic DNA. Translation: EAW64301.1.
BC001267 mRNA. Translation: AAH01267.1.
BC018288 mRNA. Translation: AAH18288.1.
CCDSiCCDS2633.1. [P20339-1]
CCDS77710.1. [P20339-2]
PIRiF34323.
RefSeqiNP_001278977.1. NM_001292048.1. [P20339-2]
NP_004153.2. NM_004162.4. [P20339-1]
UniGeneiHs.475663.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1N6HX-ray1.51A15-184[»]
1N6IX-ray1.60A15-184[»]
1N6KX-ray1.55A15-184[»]
1N6LX-ray1.60A15-184[»]
1N6NX-ray1.60A15-184[»]
1N6OX-ray1.80A15-184[»]
1N6PX-ray1.54A15-184[»]
1N6RX-ray1.55A15-184[»]
1R2QX-ray1.05A15-184[»]
1TU3X-ray2.31A/B/C/D/E15-184[»]
1TU4X-ray2.20A/B/C/D15-184[»]
3MJHX-ray2.03A/C16-183[»]
4Q9UX-ray4.62B/F15-184[»]
ProteinModelPortaliP20339.
SMRiP20339.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111806. 106 interactors.
DIPiDIP-380N.
IntActiP20339. 35 interactors.
MINTiMINT-209361.
STRINGi9606.ENSP00000273047.

PTM databases

iPTMnetiP20339.
PhosphoSitePlusiP20339.
SwissPalmiP20339.

Polymorphism and mutation databases

BioMutaiRAB5A.
DMDMi1346958.

Proteomic databases

EPDiP20339.
PaxDbiP20339.
PeptideAtlasiP20339.
PRIDEiP20339.
TopDownProteomicsiP20339-1. [P20339-1]

Protocols and materials databases

DNASUi5868.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000273047; ENSP00000273047; ENSG00000144566. [P20339-1]
ENST00000422242; ENSP00000411941; ENSG00000144566. [P20339-2]
GeneIDi5868.
KEGGihsa:5868.
UCSCiuc003cbn.4. human. [P20339-1]

Organism-specific databases

CTDi5868.
DisGeNETi5868.
GeneCardsiRAB5A.
HGNCiHGNC:9783. RAB5A.
HPAiCAB004567.
MIMi179512. gene.
neXtProtiNX_P20339.
OpenTargetsiENSG00000144566.
PharmGKBiPA34143.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0092. Eukaryota.
ENOG410YCCP. LUCA.
GeneTreeiENSGT00760000119101.
HOGENOMiHOG000233968.
HOVERGENiHBG009351.
InParanoidiP20339.
KOiK07887.
OMAiPKSQCCS.
OrthoDBiEOG091G0HKN.
PhylomeDBiP20339.
TreeFamiTF300199.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000144566-MONOMER.
ReactomeiR-HSA-1660499. Synthesis of PIPs at the plasma membrane.
R-HSA-8856828. Clathrin-mediated endocytosis.
R-HSA-8876198. RAB GEFs exchange GTP for GDP on RABs.
R-HSA-983231. Factors involved in megakaryocyte development and platelet production.
SIGNORiP20339.

Miscellaneous databases

ChiTaRSiRAB5A. human.
EvolutionaryTraceiP20339.
GeneWikiiRAB5A.
GenomeRNAii5868.
PROiP20339.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000144566.
CleanExiHS_RAB5A.
ExpressionAtlasiP20339. baseline and differential.
GenevisibleiP20339. 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 nameiRAB5A_HUMAN
AccessioniPrimary (citable) accession number: P20339
Secondary accession number(s): B4DJA5, Q6FI44
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: February 1, 1996
Last modified: November 30, 2016
This is version 189 of the entry and version 2 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 3
    Human chromosome 3: 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.