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P51159 (RB27A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 146. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Ras-related protein Rab-27A

Short name=Rab-27
Alternative name(s):
GTP-binding protein Ram
Gene names
Name:RAB27A
Synonyms:RAB27
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length221 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Plays a role in cytotoxic granule exocytosis in lymphocytes. Required for both granule maturation and granule docking and priming at the immunologic synapse. Ref.15

Subunit structure

Binds SYTL1, SLAC2B, MYRIP, SYTL3, SYTL4 and SYTL5. Interacts with RPH3A and RPH3A By similarity. Binds MLPH and SYTL2. Interacts with UNC13D. Ref.10 Ref.12 Ref.14 Ref.15

Subcellular location

Membrane; Lipid-anchor. Melanosome. Late endosome. Lysosome. Note: Identified by mass spectrometry in melanosome fractions from stage I to stage IV. Localizes to endosomal exocytic vesicles. Ref.11 Ref.12 Ref.13 Ref.14

Tissue specificity

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. Ref.12

Involvement in disease

Griscelli syndrome 2 (GS2) [MIM:607624]: Rare 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12 Ref.18 Ref.21 Ref.22

Sequence similarities

Belongs to the small GTPase superfamily. Rab family.

Ontologies

Keywords
   Biological processExocytosis
   Cellular componentEndosome
Lysosome
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
   LigandGTP-binding
Nucleotide-binding
   PTMAcetylation
Disulfide bond
Lipoprotein
Methylation
Prenylation
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processantigen processing and presentation

Inferred from mutant phenotype PubMed 19717423. Source: UniProt

blood coagulation

Inferred from electronic annotation. Source: Ensembl

cellular protein metabolic process

Traceable author statement. Source: Reactome

cytotoxic T cell degranulation

Inferred from electronic annotation. Source: Ensembl

exocytosis

Inferred from direct assay Ref.15. Source: UniProtKB

melanocyte differentiation

Inferred from electronic annotation. Source: Ensembl

melanosome transport

Inferred from electronic annotation. Source: Ensembl

multivesicular body sorting pathway

Inferred from mutant phenotype PubMed 19966785. Source: UniProtKB

natural killer cell degranulation

Inferred from electronic annotation. Source: Ensembl

positive regulation of exocytosis

Inferred from mutant phenotype PubMed 19966785. Source: UniProtKB

protein targeting

Inferred from electronic annotation. Source: Ensembl

small GTPase mediated signal transduction

Inferred from electronic annotation. Source: InterPro

   Cellular_componentGolgi apparatus

Inferred from electronic annotation. Source: Ensembl

apical plasma membrane

Inferred from electronic annotation. Source: Ensembl

dendrite

Inferred from direct assay PubMed 11266474. Source: UniProtKB

exocytic vesicle

Inferred from direct assay Ref.14Ref.15. Source: UniProtKB

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867. Source: UniProt

late endosome

Inferred from direct assay Ref.14. Source: UniProtKB

lysosome

Inferred from direct assay Ref.12. Source: UniProtKB

melanosome

Inferred from direct assay PubMed 11266474. Source: UniProtKB

multivesicular body membrane

Inferred from direct assay PubMed 19966785. Source: UniProtKB

photoreceptor outer segment

Inferred from electronic annotation. Source: Ensembl

secretory granule membrane

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionGDP binding

Inferred from direct assay PubMed 20937701. Source: UniProtKB

GTP binding

Inferred from sequence or structural similarity. Source: UniProtKB

GTPase activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform Long (identifier: P51159-1)

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.
Isoform Short (identifier: P51159-2)

The sequence of this isoform differs from the canonical sequence as follows:
     146-153: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.17
Chain2 – 221220Ras-related protein Rab-27A
PRO_0000121221

Regions

Nucleotide binding16 – 249GTP By similarity
Nucleotide binding74 – 785GTP By similarity
Nucleotide binding133 – 1364GTP By similarity
Nucleotide binding163 – 1653GTP By similarity
Motif38 – 469Effector region By similarity

Amino acid modifications

Modified residue21N-acetylserine Ref.17
Modified residue2211Cysteine methyl ester By similarity
Lipidation2191S-geranylgeranyl cysteine By similarity
Lipidation2211S-geranylgeranyl cysteine By similarity
Disulfide bond123 ↔ 188 By similarity

Natural variations

Alternative sequence146 – 1538Missing in isoform Short.
VSP_005529
Natural variant621T → S.
Corresponds to variant rs1050930 [ dbSNP | Ensembl ].
VAR_028206
Natural variant731W → G in GS2; does not affect GTP binding; cannot interact with MLPH; significant reduction in interaction with UNC13D; abolishes localization to lysosomes. Ref.12 Ref.18 Ref.21 Ref.22
Corresponds to variant rs28938176 [ dbSNP | Ensembl ].
VAR_010654
Natural variant841L → F.
Corresponds to variant rs4340274 [ dbSNP | Ensembl ].
VAR_028207
Natural variant851T → P.
Corresponds to variant rs719705 [ dbSNP | Ensembl ].
VAR_028208
Natural variant1301L → P in GS2; strongly affects GTP binding; cannot interact with MLPH. Ref.18 Ref.21 Ref.22
VAR_011334
Natural variant1521A → P in GS2; may affect GTP binding; interferes with melanosome transport. Ref.18 Ref.21 Ref.22
VAR_011335

Experimental info

Mutagenesis231T → N: Abolishes interaction with UNC13D and localization to lysosomes. Ref.12
Mutagenesis701L → P: Abolishes interaction with SYTL2. Ref.15
Mutagenesis761A → V: Abolishes interaction with SYTL2. Ref.15
Sequence conflict481E → P in AAC51195. Ref.3
Sequence conflict481E → P in AAD43049. Ref.5
Sequence conflict61 – 622AT → PV in AAC51195. Ref.3
Sequence conflict61 – 622AT → PV in AAD43049. Ref.5

Sequences

Sequence LengthMass (Da)Tools
Isoform Long [UniParc].

Last modified October 17, 2006. Version 3.
Checksum: 4A6A0C8C5CC41A20

FASTA22124,868
        10         20         30         40         50         60 
MSDGDYDYLI KFLALGDSGV GKTSVLYQYT DGKFNSKFIT TVGIDFREKR VVYRASGPDG 

        70         80         90        100        110        120 
ATGRGQRIHL QLWDTAGQER FRSLTTAFFR DAMGFLLLFD LTNEQSFLNV RNWISQLQMH 

       130        140        150        160        170        180 
AYCENPDIVL CGNKSDLEDQ RVVKEEEAIA LAEKYGIPYF ETSAANGTNI SQAIEMLLDL 

       190        200        210        220 
IMKRMERCVD KSWIPEGVVR SNGHASTDQL SEEKEKGACG C 

« Hide

Isoform Short [UniParc].

Checksum: 9A2B95ECB4BC2BFE
Show »

FASTA21324,041

References

« Hide 'large scale' references
[1]"Deficient geranylgeranylation of Ram/Rab27 in choroideremia."
Seabra M.C., Ho Y.K., Anant J.S.
J. Biol. Chem. 270:24420-24427(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), PARTIAL PROTEIN SEQUENCE.
Tissue: Retina.
[2]Seabra M.C.
Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION TO 99.
[3]"Molecular cloning and characterization of rab27a and rab27b, novel human rab proteins shared by melanocytes and platelets."
Chen D., Guo J., Miki T., Tachibana M., Gahl W.A.
Biochem. Mol. Med. 60:27-37(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
Tissue: Melanocyte.
[4]"Cloning, mapping and characterization of the human RAB27A gene."
Tolmachova T., Ramalho J.S., Anant J.S., Schultz R.A., Huxley C.M., Seabra M.C.
Gene 239:109-116(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM LONG).
[5]"Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning."
Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X., Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M. expand/collapse author list , Zhou J., Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L.
Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SHORT).
Tissue: Pituitary.
[6]"Genomic organization of the human RAB27A gene."
Anderson P.D., Huizing M., Anikster Y., Gahl W.A.
Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORM LONG).
[7]"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."
Puhl H.L. III, Ikeda S.R., Aronstam R.S.
Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
Tissue: Brain.
[8]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[9]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Mammary gland.
[10]"Melanophilin directly links Rab27a and myosin Va through its distinct coiled-coil regions."
Nagashima K., Torii S., Yi Z., Igarashi M., Okamoto K., Takeuchi T., Izumi T.
FEBS Lett. 517:233-238(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MLPH.
[11]"Proteomic analysis of early melanosomes: identification of novel melanosomal proteins."
Basrur V., Yang F., Kushimoto T., Higashimoto Y., Yasumoto K., Valencia J., Muller J., Vieira W.D., Watabe H., Shabanowitz J., Hearing V.J., Hunt D.F., Appella E.
J. Proteome Res. 2:69-79(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
Tissue: Melanoma.
[12]"Munc13-4 is an effector of rab27a and controls secretion of lysosomes in hematopoietic cells."
Neeft M., Wieffer M., de Jong A.S., Negroiu G., Metz C.H., van Loon A., Griffith J., Krijgsveld J., Wulffraat N., Koch H., Heck A.J.R., Brose N., Kleijmeer M., van der Sluijs P.
Mol. Biol. Cell 16:731-741(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION WITH UNC13D, TISSUE SPECIFICITY, MUTAGENESIS OF THR-23, CHARACTERIZATION OF VARIANT GS2 GLY-73.
[13]"Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes."
Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F.
J. Proteome Res. 5:3135-3144(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
Tissue: Melanoma.
[14]"Secretory cytotoxic granule maturation and exocytosis require the effector protein hMunc13-4."
Menager M.M., Menasche G., Romao M., Knapnougel P., Ho C.-H., Garfa M., Raposo G., Feldmann J., Fischer A., de Saint Basile G.
Nat. Immunol. 8:257-267(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH UNC13D, SUBCELLULAR LOCATION.
[15]"A newly identified isoform of Slp2a associates with Rab27a in cytotoxic T cells and participates in cytotoxic granule secretion."
Menasche G., Menager M.M., Lefebvre J.M., Deutsch E., Athman R., Lambert N., Mahlaoui N., Court M., Garin J., Fischer A., de Saint Basile G.
Blood 112:5052-5062(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH SYTL2, MUTAGENESIS OF LEU-70 AND ALA-76.
[16]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[18]"Mutations in RAB27A cause Griscelli syndrome associated with haemophagocytic syndrome."
Menasche G., Pastural E., Feldmann J., Certain S., Ersoy F., Dupuis S., Wulffraat N., Bianchi D., Fischer A., Le Deist F., de Saint Basile G.
Nat. Genet. 25:173-176(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GS2 GLY-73; PRO-130 AND PRO-152.
[19]"Evidence that Griscelli syndrome with neurological involvement is caused by mutations in RAB27A, not MYO5A."
Anikster Y., Huizing M., Anderson P.D., Fitzpatrick D.L., Klar A., Gross-Kieselstein E., Berkun Y., Shazberg G., Gahl W.A., Hurvitz H.
Am. J. Hum. Genet. 71:407-414(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN GRISCELLI SYNDROME.
[20]Erratum
Anikster Y., Huizing M., Anderson P.D., Fitzpatrick D.L., Klar A., Gross-Kieselstein E., Berkun Y., Shazberg G., Gahl W.A., Hurvitz H.
Am. J. Hum. Genet. 71:1007-1007(2002)
[21]"Biochemical and functional characterization of Rab27a mutations occurring in Griscelli syndrome patients."
Menasche G., Feldmann J., Houdusse A., Desaymard C., Fischer A., Goud B., de Saint Basile G.
Blood 101:2736-2742(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS GS2 GLY-73; PRO-130 AND PRO-152.
[22]"Characterization of the molecular defects in Rab27a, caused by RAB27A missense mutations found in patients with Griscelli syndrome."
Bahadoran P., Busca R., Chiaverini C., Westbroek W., Lambert J., Bille K., Valony G., Fukuda M., Naeyaert J.-M., Ortonne J.-P., Ballotti R.
J. Biol. Chem. 278:11386-11392(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS GS2 GLY-73; PRO-130 AND PRO-152.
+Additional computationally mapped references.

Web resources

RAB27Abase

RAB27A mutation db

Mutations of the RAB27A gene

Retina International's Scientific Newsletter

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U38654 mRNA. Translation: AAC50271.2.
U57094 mRNA. Translation: AAC51195.1.
AF154840 expand/collapse EMBL AC list , 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.
PIRI39198.
RefSeqNP_004571.2. NM_004580.4.
NP_899057.1. NM_183234.2.
NP_899058.1. NM_183235.2.
NP_899059.1. NM_183236.2.
XP_005254633.1. XM_005254576.2.
UniGeneHs.654978.
Hs.735555.

3D structure databases

ProteinModelPortalP51159.
SMRP51159. Positions 4-187.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111811. 23 interactions.
IntActP51159. 11 interactions.
MINTMINT-1377654.
STRING9606.ENSP00000337761.

PTM databases

PhosphoSiteP51159.

Polymorphism databases

DMDM116242744.

Proteomic databases

PaxDbP51159.
PeptideAtlasP51159.
PRIDEP51159.

Protocols and materials databases

DNASU5873.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000336787; ENSP00000337761; ENSG00000069974. [P51159-1]
ENST00000396307; ENSP00000379601; ENSG00000069974. [P51159-1]
ENST00000564609; ENSP00000455012; ENSG00000069974. [P51159-1]
ENST00000569493; ENSP00000456059; ENSG00000069974. [P51159-1]
GeneID5873.
KEGGhsa:5873.
UCSCuc002aco.3. human. [P51159-1]

Organism-specific databases

CTD5873.
GeneCardsGC15M055495.
HGNCHGNC:9766. RAB27A.
HPACAB034046.
HPA001333.
MIM603868. gene.
607624. phenotype.
neXtProtNX_P51159.
Orphanet79477. Griscelli disease type 2.
PharmGKBPA34117.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1100.
HOGENOMHOG000233968.
HOVERGENHBG009351.
InParanoidP51159.
KOK07885.
OMADQRAVKE.
OrthoDBEOG7FFMSC.
PhylomeDBP51159.
TreeFamTF312895.

Enzyme and pathway databases

ReactomeREACT_17015. Metabolism of proteins.

Gene expression databases

ArrayExpressP51159.
BgeeP51159.
CleanExHS_RAB27A.
GenevestigatorP51159.

Family and domain databases

Gene3D3.40.50.300. 1 hit.
InterProIPR027417. P-loop_NTPase.
IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR003579. Small_GTPase_Rab_type.
[Graphical view]
PfamPF00071. Ras. 1 hit.
[Graphical view]
PRINTSPR00449. RASTRNSFRMNG.
SMARTSM00175. RAB. 1 hit.
[Graphical view]
SUPFAMSSF52540. SSF52540. 1 hit.
TIGRFAMsTIGR00231. small_GTP. 1 hit.
PROSITEPS51419. RAB. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSRAB27A. human.
GeneWikiRAB27A.
GenomeRNAi5873.
NextBio22812.
PROP51159.
SOURCESearch...

Entry information

Entry nameRB27A_HUMAN
AccessionPrimary (citable) accession number: P51159
Secondary accession number(s): O00195 expand/collapse secondary AC list , Q6FI40, Q9UIR9, Q9Y5U3
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 17, 2006
Last modified: April 16, 2014
This is version 146 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM