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Protein

Ras-related protein Rab-27A

Gene

RAB27A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Plays a role in cytotoxic granule exocytosis in lymphocytes. Required for both granule maturation and granule docking and priming at the immunologic synapse.1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi16 – 24GTPBy similarity9
Nucleotide bindingi74 – 78GTPBy similarity5
Nucleotide bindingi133 – 136GTPBy similarity4
Nucleotide bindingi163 – 165GTPBy similarity3

GO - Molecular functioni

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

GO - Biological processi

  • antigen processing and presentation Source: UniProtKB
  • blood coagulation Source: Ensembl
  • complement-dependent cytotoxicity Source: UniProtKB
  • cytotoxic T cell degranulation Source: Ensembl
  • exocytosis Source: UniProtKB
  • exosomal secretion Source: UniProtKB
  • melanocyte differentiation Source: Ensembl
  • melanosome localization Source: UniProtKB
  • melanosome transport Source: GO_Central
  • multivesicular body organization Source: UniProtKB
  • multivesicular body sorting pathway Source: UniProtKB
  • natural killer cell degranulation Source: Ensembl
  • positive regulation of constitutive secretory pathway Source: UniProtKB
  • positive regulation of exocytosis Source: UniProtKB
  • positive regulation of gene expression Source: UniProtKB
  • positive regulation of phagocytosis Source: UniProtKB
  • positive regulation of reactive oxygen species biosynthetic process Source: UniProtKB
  • positive regulation of regulated secretory pathway Source: UniProtKB
  • protein targeting Source: Ensembl
  • small GTPase mediated signal transduction Source: InterPro
  • synaptic vesicle transport Source: ParkinsonsUK-UCL
Complete GO annotation...

Keywords - Biological processi

Exocytosis

Keywords - Ligandi

GTP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000069974-MONOMER.
ReactomeiR-HSA-264876. Insulin processing.
R-HSA-6798695. Neutrophil degranulation.
R-HSA-8876198. RAB GEFs exchange GTP for GDP on RABs.

Names & Taxonomyi

Protein namesi
Recommended name:
Ras-related protein Rab-27A
Short name:
Rab-27
Alternative name(s):
GTP-binding protein Ram
Gene namesi
Name:RAB27A
Synonyms:RAB27
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

HGNCiHGNC:9766. RAB27A.

Subcellular locationi

GO - Cellular componenti

  • apical plasma membrane Source: Ensembl
  • dendrite Source: UniProtKB
  • exocytic vesicle Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • Golgi apparatus Source: Ensembl
  • late endosome Source: UniProtKB
  • lysosome Source: UniProtKB
  • melanosome Source: UniProtKB
  • multivesicular body membrane Source: UniProtKB
  • photoreceptor outer segment Source: Ensembl
  • secretory granule Source: GO_Central
  • secretory granule membrane Source: Ensembl
  • Weibel-Palade body Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Endosome, Lysosome, Membrane

Pathology & Biotechi

Involvement in diseasei

Griscelli syndrome 2 (GS2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionRare autosomal recessive disorder that results in pigmentary dilution of the skin and hair, the presence of large clumps of pigment in hair shafts, and an accumulation of melanosomes in melanocytes. GS2 patients also develop an uncontrolled T-lymphocyte and macrophage activation syndrome, known as hemophagocytic syndrome, leading to death in the absence of bone marrow transplantation. Neurological impairment is present in some patients, likely as a result of hemophagocytic syndrome.
See also OMIM:607624
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01065473W → G in GS2; does not affect GTP binding; cannot interact with MLPH; significant reduction in interaction with UNC13D; abolishes localization to lysosomes. 4 PublicationsCorresponds to variant rs28938176dbSNPEnsembl.1
Natural variantiVAR_011334130L → P in GS2; strongly affects GTP binding; cannot interact with MLPH. 3 PublicationsCorresponds to variant rs104894498dbSNPEnsembl.1
Natural variantiVAR_011335152A → P in GS2; interferes with melanosome transport. 3 PublicationsCorresponds to variant rs104894499dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi23T → N: Abolishes interaction with UNC13D and localization to lysosomes. 1 Publication1
Mutagenesisi70L → P: Abolishes interaction with SYTL2. 1 Publication1
Mutagenesisi76A → V: Abolishes interaction with SYTL2. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi5873.
MalaCardsiRAB27A.
MIMi607624. phenotype.
OpenTargetsiENSG00000069974.
Orphaneti79477. Griscelli disease type 2.
PharmGKBiPA34117.

Polymorphism and mutation databases

BioMutaiRAB27A.
DMDMi116242744.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001212212 – 221Ras-related protein Rab-27AAdd BLAST220

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1
Modified residuei2PhosphoserineCombined sources1
Disulfide bondi123 ↔ 188By similarity
Lipidationi219S-geranylgeranyl cysteineBy similarity1
Modified residuei221Cysteine methyl esterBy similarity1
Lipidationi221S-geranylgeranyl cysteineBy similarity1

Keywords - PTMi

Acetylation, Disulfide bond, Lipoprotein, Methylation, Phosphoprotein, Prenylation

Proteomic databases

EPDiP51159.
MaxQBiP51159.
PaxDbiP51159.
PeptideAtlasiP51159.
PRIDEiP51159.

PTM databases

iPTMnetiP51159.
PhosphoSitePlusiP51159.
SwissPalmiP51159.

Expressioni

Tissue specificityi

Found in all the examined tissues except in brain. Low expression was found in thymus, kidney, muscle and placenta. Detected in melanocytes, and in most tumor cell lines examined. Expressed in cytotoxic T-lymphocytes (CTL) and mast cells.1 Publication

Gene expression databases

BgeeiENSG00000069974.
CleanExiHS_RAB27A.
ExpressionAtlasiP51159. baseline and differential.
GenevisibleiP51159. HS.

Organism-specific databases

HPAiCAB034046.
HPA001333.

Interactioni

Subunit structurei

Binds SYTL1, SLAC2B, MYRIP, SYTL3, SYTL4 and SYTL5. Interacts with RPH3A and RPH3A (By similarity). Binds MLPH and SYTL2. Interacts with UNC13D. Does not interact with the BLOC-3 complex (heterodimer of HPS1 and HPS4) (PubMed:20048159).By similarity5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
MLPHQ9BV363EBI-716881,EBI-7042162

Protein-protein interaction databases

BioGridi111811. 24 interactors.
DIPiDIP-44244N.
IntActiP51159. 13 interactors.
MINTiMINT-1377654.
STRINGi9606.ENSP00000337761.

Structurei

3D structure databases

ProteinModelPortaliP51159.
SMRiP51159.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi38 – 46Effector regionBy similarity9

Sequence similaritiesi

Belongs to the small GTPase superfamily. Rab family.Curated

Phylogenomic databases

eggNOGiKOG0081. Eukaryota.
ENOG410XQ3T. LUCA.
GeneTreeiENSGT00860000133677.
HOGENOMiHOG000233968.
HOVERGENiHBG009351.
InParanoidiP51159.
KOiK07885.
OMAiTSFLHRY.
OrthoDBiEOG091G0I51.
PhylomeDBiP51159.
TreeFamiTF312895.

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 Long (identifier: P51159-1) [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
MSDGDYDYLI KFLALGDSGV GKTSVLYQYT DGKFNSKFIT TVGIDFREKR
60 70 80 90 100
VVYRASGPDG ATGRGQRIHL QLWDTAGQER FRSLTTAFFR DAMGFLLLFD
110 120 130 140 150
LTNEQSFLNV RNWISQLQMH AYCENPDIVL CGNKSDLEDQ RVVKEEEAIA
160 170 180 190 200
LAEKYGIPYF ETSAANGTNI SQAIEMLLDL IMKRMERCVD KSWIPEGVVR
210 220
SNGHASTDQL SEEKEKGACG C
Length:221
Mass (Da):24,868
Last modified:October 17, 2006 - v3
Checksum:i4A6A0C8C5CC41A20
GO
Isoform Short (identifier: P51159-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     146-153: Missing.

Note: No experimental confirmation available.
Show »
Length:213
Mass (Da):24,041
Checksum:i9A2B95ECB4BC2BFE
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti48E → P in AAC51195 (PubMed:9066979).Curated1
Sequence conflicti48E → P in AAD43049 (PubMed:10931946).Curated1
Sequence conflicti61 – 62AT → PV in AAC51195 (PubMed:9066979).Curated2
Sequence conflicti61 – 62AT → PV in AAD43049 (PubMed:10931946).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02820662T → S.Corresponds to variant rs1050930dbSNPEnsembl.1
Natural variantiVAR_01065473W → G in GS2; does not affect GTP binding; cannot interact with MLPH; significant reduction in interaction with UNC13D; abolishes localization to lysosomes. 4 PublicationsCorresponds to variant rs28938176dbSNPEnsembl.1
Natural variantiVAR_02820784L → F.Corresponds to variant rs4340274dbSNPEnsembl.1
Natural variantiVAR_02820885T → P.Corresponds to variant rs719705dbSNPEnsembl.1
Natural variantiVAR_011334130L → P in GS2; strongly affects GTP binding; cannot interact with MLPH. 3 PublicationsCorresponds to variant rs104894498dbSNPEnsembl.1
Natural variantiVAR_011335152A → P in GS2; interferes with melanosome transport. 3 PublicationsCorresponds to variant rs104894499dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_005529146 – 153Missing in isoform Short. 1 Publication8

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U38654 mRNA. Translation: AAC50271.2.
U57094 mRNA. Translation: AAC51195.1.
AF154840
, AF154836, AF154837, AF154838, AF154839 Genomic DNA. Translation: AAD47629.1.
AF125393 mRNA. Translation: AAD43049.1.
AF443871 Genomic DNA. Translation: AAL39097.1.
AF498953 mRNA. Translation: AAM21101.1.
CR536496 mRNA. Translation: CAG38735.1.
CR541693 mRNA. Translation: CAG46494.1.
BC107680 mRNA. Translation: AAI07681.1.
CCDSiCCDS10153.1. [P51159-1]
PIRiI39198.
RefSeqiNP_004571.2. NM_004580.4. [P51159-1]
NP_899057.1. NM_183234.2. [P51159-1]
NP_899058.1. NM_183235.2. [P51159-1]
NP_899059.1. NM_183236.2. [P51159-1]
XP_005254633.1. XM_005254576.4. [P51159-1]
XP_011520154.1. XM_011521852.1. [P51159-1]
XP_011520156.1. XM_011521854.1. [P51159-1]
XP_011520157.1. XM_011521855.2. [P51159-1]
XP_011520158.1. XM_011521856.2. [P51159-1]
UniGeneiHs.626665.
Hs.654978.
Hs.735555.

Genome annotation databases

EnsembliENST00000336787; ENSP00000337761; ENSG00000069974. [P51159-1]
ENST00000396307; ENSP00000379601; ENSG00000069974. [P51159-1]
ENST00000564609; ENSP00000455012; ENSG00000069974. [P51159-1]
ENST00000569493; ENSP00000456059; ENSG00000069974. [P51159-1]
GeneIDi5873.
KEGGihsa:5873.
UCSCiuc002aco.4. human. [P51159-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

RAB27Abase

RAB27A mutation db

Mutations of the RAB27A gene

Retina International's Scientific Newsletter

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U38654 mRNA. Translation: AAC50271.2.
U57094 mRNA. Translation: AAC51195.1.
AF154840
, AF154836, AF154837, AF154838, AF154839 Genomic DNA. Translation: AAD47629.1.
AF125393 mRNA. Translation: AAD43049.1.
AF443871 Genomic DNA. Translation: AAL39097.1.
AF498953 mRNA. Translation: AAM21101.1.
CR536496 mRNA. Translation: CAG38735.1.
CR541693 mRNA. Translation: CAG46494.1.
BC107680 mRNA. Translation: AAI07681.1.
CCDSiCCDS10153.1. [P51159-1]
PIRiI39198.
RefSeqiNP_004571.2. NM_004580.4. [P51159-1]
NP_899057.1. NM_183234.2. [P51159-1]
NP_899058.1. NM_183235.2. [P51159-1]
NP_899059.1. NM_183236.2. [P51159-1]
XP_005254633.1. XM_005254576.4. [P51159-1]
XP_011520154.1. XM_011521852.1. [P51159-1]
XP_011520156.1. XM_011521854.1. [P51159-1]
XP_011520157.1. XM_011521855.2. [P51159-1]
XP_011520158.1. XM_011521856.2. [P51159-1]
UniGeneiHs.626665.
Hs.654978.
Hs.735555.

3D structure databases

ProteinModelPortaliP51159.
SMRiP51159.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111811. 24 interactors.
DIPiDIP-44244N.
IntActiP51159. 13 interactors.
MINTiMINT-1377654.
STRINGi9606.ENSP00000337761.

PTM databases

iPTMnetiP51159.
PhosphoSitePlusiP51159.
SwissPalmiP51159.

Polymorphism and mutation databases

BioMutaiRAB27A.
DMDMi116242744.

Proteomic databases

EPDiP51159.
MaxQBiP51159.
PaxDbiP51159.
PeptideAtlasiP51159.
PRIDEiP51159.

Protocols and materials databases

DNASUi5873.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000336787; ENSP00000337761; ENSG00000069974. [P51159-1]
ENST00000396307; ENSP00000379601; ENSG00000069974. [P51159-1]
ENST00000564609; ENSP00000455012; ENSG00000069974. [P51159-1]
ENST00000569493; ENSP00000456059; ENSG00000069974. [P51159-1]
GeneIDi5873.
KEGGihsa:5873.
UCSCiuc002aco.4. human. [P51159-1]

Organism-specific databases

CTDi5873.
DisGeNETi5873.
GeneCardsiRAB27A.
HGNCiHGNC:9766. RAB27A.
HPAiCAB034046.
HPA001333.
MalaCardsiRAB27A.
MIMi603868. gene.
607624. phenotype.
neXtProtiNX_P51159.
OpenTargetsiENSG00000069974.
Orphaneti79477. Griscelli disease type 2.
PharmGKBiPA34117.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0081. Eukaryota.
ENOG410XQ3T. LUCA.
GeneTreeiENSGT00860000133677.
HOGENOMiHOG000233968.
HOVERGENiHBG009351.
InParanoidiP51159.
KOiK07885.
OMAiTSFLHRY.
OrthoDBiEOG091G0I51.
PhylomeDBiP51159.
TreeFamiTF312895.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000069974-MONOMER.
ReactomeiR-HSA-264876. Insulin processing.
R-HSA-6798695. Neutrophil degranulation.
R-HSA-8876198. RAB GEFs exchange GTP for GDP on RABs.

Miscellaneous databases

ChiTaRSiRAB27A. human.
GeneWikiiRAB27A.
GenomeRNAii5873.
PROiP51159.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000069974.
CleanExiHS_RAB27A.
ExpressionAtlasiP51159. baseline and differential.
GenevisibleiP51159. 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 nameiRB27A_HUMAN
AccessioniPrimary (citable) accession number: P51159
Secondary accession number(s): O00195
, Q6FI40, Q9UIR9, Q9Y5U3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 17, 2006
Last modified: November 30, 2016
This is version 174 of the entry and version 3 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

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. 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.