UniProtKB - P51159 (RB27A_HUMAN)
Ras-related protein Rab-27A
RAB27A
Functioni
Small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins to regulate homeostasis of late endocytic pathway, including endosomal positioning, maturation and secretion (PubMed:30771381).
Plays a role in cytotoxic granule exocytosis in lymphocytes. Required for both granule maturation and granule docking and priming at the immunologic synapse.
2 PublicationsCatalytic activityi
Activity regulationi
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 16 – 24 | GTPBy similarity | 9 | |
Nucleotide bindingi | 74 – 78 | GTPBy similarity | 5 | |
Nucleotide bindingi | 133 – 136 | GTPBy similarity | 4 | |
Nucleotide bindingi | 163 – 165 | GTPBy similarity | 3 |
GO - Molecular functioni
- GDP binding Source: UniProtKB
- G protein activity Source: UniProtKB-EC
- 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
- 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
Molecular function | Hydrolase |
Biological process | Exocytosis |
Ligand | GTP-binding, Nucleotide-binding |
Enzyme and pathway databases
PathwayCommonsi | P51159 |
Reactomei | R-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 |
SignaLinki | P51159 |
Names & Taxonomyi
Protein namesi | Recommended name: Ras-related protein Rab-27A (EC:3.6.5.22 Publications)Short name: Rab-27 Alternative name(s): GTP-binding protein Ram |
Gene namesi | Name:RAB27A Synonyms:RAB27 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:9766, RAB27A |
MIMi | 603868, gene |
neXtProti | NX_P51159 |
VEuPathDBi | HostDB:ENSG00000069974 |
Subcellular locationi
Endosome
- Late endosome 2 Publications
Lysosome
- Lysosome 1 Publication
Other locations
- Membrane Curated; Lipid-anchor Curated
- Melanosome 2 Publications
Note: Identified by mass spectrometry in melanosome fractions from stage I to stage IV (PubMed:12643545, PubMed:17081065). Localizes to endosomal exocytic vesicles (PubMed:17237785).3 Publications
Cytosol
- cytosol Source: Reactome
Endosome
- late endosome Source: UniProtKB
- multivesicular body membrane Source: UniProtKB
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
- extracellular region Source: Reactome
Golgi apparatus
- Golgi apparatus Source: Ensembl
Lysosome
- lysosome Source: UniProtKB
Plasma Membrane
- apical plasma membrane Source: Ensembl
Other locations
- dendrite Source: UniProtKB
- exocytic vesicle Source: UniProtKB
- melanosome Source: UniProtKB
- melanosome membrane Source: Reactome
- photoreceptor outer segment Source: Ensembl
- secretory granule Source: GO_Central
- secretory granule membrane Source: Ensembl
- specific granule lumen Source: Reactome
- Weibel-Palade body Source: Ensembl
Keywords - Cellular componenti
Endosome, Lysosome, MembranePathology & Biotechi
Involvement in diseasei
Griscelli syndrome 2 (GS2)4 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_010654 | 73 | W → 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_011334 | 130 | L → P in GS2; strongly affects GTP binding; cannot interact with MLPH. 3 PublicationsCorresponds to variant dbSNP:rs104894498EnsemblClinVar. | 1 | |
Natural variantiVAR_011335 | 152 | A → P in GS2; interferes with melanosome transport. 3 PublicationsCorresponds to variant dbSNP:rs104894499EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 23 | T → N: GDP-locked. Abolishes interaction with UNC13D and localization to lysosomes. Increases interaction with DENND10. Disrupts late endocytic pathway homeostasis. 2 Publications | 1 | |
Mutagenesisi | 70 | L → P: Abolishes interaction with SYTL2. 1 Publication | 1 | |
Mutagenesisi | 76 | A → V: Abolishes interaction with SYTL2. 1 Publication | 1 | |
Mutagenesisi | 78 | Q → L: GTP-locked. decreases interaction with DENND10. 1 Publication | 1 |
Keywords - Diseasei
Disease variantOrganism-specific databases
DisGeNETi | 5873 |
MalaCardsi | RAB27A |
MIMi | 607624, phenotype |
OpenTargetsi | ENSG00000069974 |
Orphaneti | 79477, Griscelli syndrome type 2 |
PharmGKBi | PA34117 |
Miscellaneous databases
Pharosi | P51159, Tchem |
Chemistry databases
ChEMBLi | CHEMBL4105702 |
GuidetoPHARMACOLOGYi | 2916 |
Genetic variation databases
BioMutai | RAB27A |
DMDMi | 116242744 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedCombined sources | |||
ChainiPRO_0000121221 | 2 – 221 | Ras-related protein Rab-27AAdd BLAST | 220 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylserineCombined sources | 1 | |
Modified residuei | 2 | PhosphoserineCombined sources | 1 | |
Disulfide bondi | 123 ↔ 188 | By similarity | ||
Lipidationi | 219 | S-geranylgeranyl cysteineBy similarity | 1 | |
Modified residuei | 221 | Cysteine methyl esterBy similarity | 1 | |
Lipidationi | 221 | S-geranylgeranyl cysteineBy similarity | 1 |
Keywords - PTMi
Acetylation, Disulfide bond, Lipoprotein, Methylation, Phosphoprotein, PrenylationProteomic databases
EPDi | P51159 |
jPOSTi | P51159 |
MassIVEi | P51159 |
MaxQBi | P51159 |
PaxDbi | P51159 |
PeptideAtlasi | P51159 |
PRIDEi | P51159 |
ProteomicsDBi | 56289 [P51159-1] 56290 [P51159-2] |
PTM databases
GlyGeni | P51159, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | P51159 |
PhosphoSitePlusi | P51159 |
SwissPalmi | P51159 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000069974, Expressed in bone marrow and 231 other tissues |
ExpressionAtlasi | P51159, baseline and differential |
Genevisiblei | P51159, HS |
Organism-specific databases
HPAi | ENSG00000069974, Tissue enhanced (stomach) |
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).
Interacts (GDP-bound form preferentially) with DENND10 (PubMed:30771381).
By similarity6 PublicationsBinary interactionsi
P51159
Isoform Long [P51159-1]
With | #Exp. | IntAct |
---|---|---|
MLPH [Q9BV36] | 2 | EBI-15528760,EBI-7042162 |
GO - Molecular functioni
- myosin V binding Source: Ensembl
- protein domain specific binding Source: Ensembl
Protein-protein interaction databases
BioGRIDi | 111811, 86 interactors |
CORUMi | P51159 |
DIPi | DIP-44244N |
IntActi | P51159, 50 interactors |
MINTi | P51159 |
STRINGi | 9606.ENSP00000379601 |
Miscellaneous databases
RNActi | P51159, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | P51159 |
SMRi | P51159 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 38 – 46 | Effector regionBy similarity | 9 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG0081, Eukaryota |
GeneTreei | ENSGT00940000156218 |
InParanoidi | P51159 |
OMAi | CTGANIQ |
OrthoDBi | 1190514at2759 |
PhylomeDBi | P51159 |
TreeFami | TF312895 |
Family and domain databases
CDDi | cd04127, Rab27A, 1 hit |
Gene3Di | 3.40.50.300, 1 hit |
InterProi | View protein in InterPro IPR027417, P-loop_NTPase IPR041837, Rab27a/b IPR005225, Small_GTP-bd_dom IPR001806, Small_GTPase |
Pfami | View protein in Pfam PF00071, Ras, 1 hit |
SMARTi | View protein in SMART SM00174, RHO, 1 hit |
SUPFAMi | SSF52540, SSF52540, 1 hit |
TIGRFAMsi | TIGR00231, small_GTP, 1 hit |
PROSITEi | View protein in PROSITE PS51419, RAB, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
The sequence of this isoform differs from the canonical sequence as follows:
146-153: Missing.
Computationally mapped potential isoform sequencesi
There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketH3BN55 | H3BN55_HUMAN | Small monomeric GTPase | RAB27A | 185 | Annotation score: | ||
H3BVH7 | H3BVH7_HUMAN | Ras-related protein Rab-27A | RAB27A | 146 | Annotation score: | ||
H3BS49 | H3BS49_HUMAN | Ras-related protein Rab-27A | RAB27A | 136 | Annotation score: | ||
H3BU81 | H3BU81_HUMAN | Ras-related protein Rab-27A | RAB27A | 71 | Annotation score: | ||
H3BUD9 | H3BUD9_HUMAN | Ras-related protein Rab-27A | RAB27A | 95 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 48 | E → P in AAC51195 (PubMed:9066979).Curated | 1 | |
Sequence conflicti | 48 | E → P in AAD43049 (PubMed:10931946).Curated | 1 | |
Sequence conflicti | 61 – 62 | AT → PV in AAC51195 (PubMed:9066979).Curated | 2 | |
Sequence conflicti | 61 – 62 | AT → PV in AAD43049 (PubMed:10931946).Curated | 2 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_028206 | 62 | T → S. Corresponds to variant dbSNP:rs1050930Ensembl. | 1 | |
Natural variantiVAR_010654 | 73 | W → 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_028207 | 84 | L → F. Corresponds to variant dbSNP:rs4340274Ensembl. | 1 | |
Natural variantiVAR_028208 | 85 | T → P. Corresponds to variant dbSNP:rs719705Ensembl. | 1 | |
Natural variantiVAR_011334 | 130 | L → P in GS2; strongly affects GTP binding; cannot interact with MLPH. 3 PublicationsCorresponds to variant dbSNP:rs104894498EnsemblClinVar. | 1 | |
Natural variantiVAR_011335 | 152 | A → P in GS2; interferes with melanosome transport. 3 PublicationsCorresponds to variant dbSNP:rs104894499EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_005529 | 146 – 153 | Missing in isoform Short. 1 Publication | 8 |
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 |
CCDSi | CCDS10153.1 [P51159-1] |
PIRi | I39198 |
RefSeqi | NP_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] |
Genome annotation databases
Ensembli | ENST00000336787.6; ENSP00000337761.1; ENSG00000069974.16 ENST00000396307.6; ENSP00000379601.2; ENSG00000069974.16 ENST00000564609.5; ENSP00000455012.1; ENSG00000069974.16 ENST00000569493.5; ENSP00000456059.1; ENSG00000069974.16 |
GeneIDi | 5873 |
KEGGi | hsa:5873 |
MANE-Selecti | ENST00000336787.6; ENSP00000337761.1; NM_183235.3; NP_899058.1 |
UCSCi | uc002aco.4, human [P51159-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
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 |
CCDSi | CCDS10153.1 [P51159-1] |
PIRi | I39198 |
RefSeqi | NP_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] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
6HUF | X-ray | 2.82 | A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P | 2-192 | [»] | |
AlphaFoldDBi | P51159 | |||||
SMRi | P51159 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 111811, 86 interactors |
CORUMi | P51159 |
DIPi | DIP-44244N |
IntActi | P51159, 50 interactors |
MINTi | P51159 |
STRINGi | 9606.ENSP00000379601 |
Chemistry databases
ChEMBLi | CHEMBL4105702 |
GuidetoPHARMACOLOGYi | 2916 |
PTM databases
GlyGeni | P51159, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | P51159 |
PhosphoSitePlusi | P51159 |
SwissPalmi | P51159 |
Genetic variation databases
BioMutai | RAB27A |
DMDMi | 116242744 |
Proteomic databases
EPDi | P51159 |
jPOSTi | P51159 |
MassIVEi | P51159 |
MaxQBi | P51159 |
PaxDbi | P51159 |
PeptideAtlasi | P51159 |
PRIDEi | P51159 |
ProteomicsDBi | 56289 [P51159-1] 56290 [P51159-2] |
Protocols and materials databases
Antibodypediai | 687, 464 antibodies from 38 providers |
DNASUi | 5873 |
Genome annotation databases
Ensembli | ENST00000336787.6; ENSP00000337761.1; ENSG00000069974.16 ENST00000396307.6; ENSP00000379601.2; ENSG00000069974.16 ENST00000564609.5; ENSP00000455012.1; ENSG00000069974.16 ENST00000569493.5; ENSP00000456059.1; ENSG00000069974.16 |
GeneIDi | 5873 |
KEGGi | hsa:5873 |
MANE-Selecti | ENST00000336787.6; ENSP00000337761.1; NM_183235.3; NP_899058.1 |
UCSCi | uc002aco.4, human [P51159-1] |
Organism-specific databases
CTDi | 5873 |
DisGeNETi | 5873 |
GeneCardsi | RAB27A |
HGNCi | HGNC:9766, RAB27A |
HPAi | ENSG00000069974, Tissue enhanced (stomach) |
MalaCardsi | RAB27A |
MIMi | 603868, gene 607624, phenotype |
neXtProti | NX_P51159 |
OpenTargetsi | ENSG00000069974 |
Orphaneti | 79477, Griscelli syndrome type 2 |
PharmGKBi | PA34117 |
VEuPathDBi | HostDB:ENSG00000069974 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0081, Eukaryota |
GeneTreei | ENSGT00940000156218 |
InParanoidi | P51159 |
OMAi | CTGANIQ |
OrthoDBi | 1190514at2759 |
PhylomeDBi | P51159 |
TreeFami | TF312895 |
Enzyme and pathway databases
PathwayCommonsi | P51159 |
Reactomei | R-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 |
SignaLinki | P51159 |
Miscellaneous databases
BioGRID-ORCSi | 5873, 9 hits in 1082 CRISPR screens |
ChiTaRSi | RAB27A, human |
GeneWikii | RAB27A |
GenomeRNAii | 5873 |
Pharosi | P51159, Tchem |
PROi | PR:P51159 |
RNActi | P51159, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000069974, Expressed in bone marrow and 231 other tissues |
ExpressionAtlasi | P51159, baseline and differential |
Genevisiblei | P51159, HS |
Family and domain databases
CDDi | cd04127, Rab27A, 1 hit |
Gene3Di | 3.40.50.300, 1 hit |
InterProi | View protein in InterPro IPR027417, P-loop_NTPase IPR041837, Rab27a/b IPR005225, Small_GTP-bd_dom IPR001806, Small_GTPase |
Pfami | View protein in Pfam PF00071, Ras, 1 hit |
SMARTi | View protein in SMART SM00174, RHO, 1 hit |
SUPFAMi | SSF52540, SSF52540, 1 hit |
TIGRFAMsi | TIGR00231, small_GTP, 1 hit |
PROSITEi | View protein in PROSITE PS51419, RAB, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | RB27A_HUMAN | |
Accessioni | P51159Primary (citable) accession number: P51159 Secondary accession number(s): O00195 Q9Y5U3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 1, 1996 |
Last sequence update: | October 17, 2006 | |
Last modified: | May 25, 2022 | |
This is version 211 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 15
Human chromosome 15: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families