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Protein

Ras-related protein Rab-27A

Gene

RAB27A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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
  • myosin V binding Source: Ensembl
  • protein domain specific binding Source: Ensembl

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
  • neutrophil degranulation Source: Reactome
  • 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
  • synaptic vesicle transport Source: ParkinsonsUK-UCL

Keywordsi

Biological processExocytosis
LigandGTP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-264876 Insulin processing
R-HSA-6798695 Neutrophil degranulation
R-HSA-8873719 RAB geranylgeranylation
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

EuPathDBiHostDB:ENSG00000069974.15
HGNCiHGNC:9766 RAB27A
MIMi603868 gene
neXtProtiNX_P51159

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Endosome, Lysosome, Membrane

Pathology & Biotechi

Involvement in diseasei

Griscelli syndrome 2 (GS2)4 Publications
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 dbSNP:rs28938176EnsemblClinVar.1
Natural variantiVAR_011334130L → P in GS2; strongly affects GTP binding; cannot interact with MLPH. 3 PublicationsCorresponds to variant dbSNP:rs104894498EnsemblClinVar.1
Natural variantiVAR_011335152A → P in GS2; interferes with melanosome transport. 3 PublicationsCorresponds to variant dbSNP:rs104894499EnsemblClinVar.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

Chemistry databases

GuidetoPHARMACOLOGYi2916

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
ProteomicsDBi56289
56290 [P51159-2]

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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi111811, 35 interactors
CORUMiP51159
DIPiDIP-44244N
IntActiP51159, 16 interactors
MINTiP51159
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
GeneTreeiENSGT00890000139330
HOGENOMiHOG000233968
HOVERGENiHBG009351
InParanoidiP51159
KOiK07885
OMAiLVMQRIQ
OrthoDBiEOG091G0I51
PhylomeDBiP51159
TreeFamiTF312895

Family and domain databases

InterProiView protein in InterPro
IPR027417 P-loop_NTPase
IPR005225 Small_GTP-bd_dom
IPR001806 Small_GTPase
PfamiView protein in Pfam
PF00071 Ras, 1 hit
SUPFAMiSSF52540 SSF52540, 1 hit
TIGRFAMsiTIGR00231 small_GTP, 1 hit
PROSITEiView protein in PROSITE
PS51419 RAB, 1 hit

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 dbSNP:rs1050930Ensembl.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 dbSNP:rs28938176EnsemblClinVar.1
Natural variantiVAR_02820784L → F. Corresponds to variant dbSNP:rs4340274Ensembl.1
Natural variantiVAR_02820885T → P. Corresponds to variant dbSNP:rs719705Ensembl.1
Natural variantiVAR_011334130L → P in GS2; strongly affects GTP binding; cannot interact with MLPH. 3 PublicationsCorresponds to variant dbSNP:rs104894498EnsemblClinVar.1
Natural variantiVAR_011335152A → P in GS2; interferes with melanosome transport. 3 PublicationsCorresponds to variant dbSNP:rs104894499EnsemblClinVar.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.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

Similar proteinsi

Entry informationi

Entry nameiRB27A_HUMAN
AccessioniPrimary (citable) accession number: P51159
Secondary accession number(s): O00195
, Q6FI40, Q9UIR9, Q9Y5U3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 17, 2006
Last modified: June 20, 2018
This is version 185 of the entry and version 3 of the sequence. See 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

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