P51159 (RB27A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ras-related protein Rab-27A
Short name=Rab-27

Alternative name(s):
GTP-binding protein Ram

Gene names

Name:	RAB27A
Synonyms:	RAB27

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	221 AA.
Sequence status	Complete.
Protein existence	Evidence 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 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	Defects in RAB27A are a cause of Griscelli syndrome type 2 (GS2) [MIM:607624]. Griscelli syndrome is a 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. Ref.12 Ref.17 Ref.20 Ref.21
Sequence similarities	Belongs to the small GTPase superfamily. Rab family.

Ontologies

Keywords
Biological process	Exocytosis
Cellular component	Endosome Lysosome Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Ligand	GTP-binding Nucleotide-binding
PTM	Disulfide bond Lipoprotein Methylation Phosphoprotein Prenylation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	multivesicular body sorting pathway Inferred from mutant phenotype. Source: UniProtKB positive regulation of exocytosis Inferred from mutant phenotype. Source: UniProtKB small GTPase mediated signal transduction Inferred from electronic annotation. Source: InterPro
Cellular component	dendrite Inferred from direct assay. Source: UniProtKB exocytic vesicle Inferred from direct assay Ref.14Ref.15. Source: UniProtKB lysosome Inferred from direct assay Ref.12. Source: UniProtKB melanosome Inferred from direct assay. Source: UniProtKB multivesicular body membrane Inferred from direct assay. Source: UniProtKB
Molecular function	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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 221	221	Ras-related protein Rab-27A		PRO_0000121221
Regions
	Nucleotide binding	16 – 24	9	GTP By similarity
	Nucleotide binding	74 – 78	5	GTP By similarity
	Nucleotide binding	133 – 136	4	GTP By similarity
	Nucleotide binding	163 – 165	3	GTP By similarity
	Motif	38 – 46	9	Effector region By similarity
Amino acid modifications
	Modified residue	211	1	Phosphoserine By similarity
	Modified residue	221	1	Cysteine methyl ester By similarity
	Lipidation	219	1	S-geranylgeranyl cysteine By similarity
	Lipidation	221	1	S-geranylgeranyl cysteine By similarity
	Disulfide bond	123 ↔ 188		By similarity
Natural variations
	Alternative sequence	146 – 153	8	Missing in isoform Short.		VSP_005529
	Natural variant	62	1	T → S. Corresponds to variant rs1050930 [ dbSNP | Ensembl ].		VAR_028206
	Natural variant	73	1	W → 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.17 Ref.20 Ref.21 Corresponds to variant rs28938176 [ dbSNP | Ensembl ].		VAR_010654
	Natural variant	84	1	L → F. Corresponds to variant rs4340274 [ dbSNP | Ensembl ].		VAR_028207
	Natural variant	85	1	T → P. Corresponds to variant rs719705 [ dbSNP | Ensembl ].		VAR_028208
	Natural variant	130	1	L → P in GS2; strongly affects GTP binding; cannot interact with MLPH. Ref.17 Ref.20 Ref.21		VAR_011334
	Natural variant	152	1	A → P in GS2; may affect GTP binding; interferes with melanosome transport. Ref.17 Ref.20 Ref.21		VAR_011335
Experimental info
	Mutagenesis	23	1	T → N: Abolishes interaction with UNC13D and localization to lysosomes. Ref.12
	Mutagenesis	70	1	L → P: Abolishes interaction with SYTL2. Ref.15
	Mutagenesis	76	1	A → V: Abolishes interaction with SYTL2. Ref.15
	Sequence conflict	48	1	E → P in AAC51195. Ref.3
	Sequence conflict	48	1	E → P in AAD43049. Ref.5
	Sequence conflict	61 – 62	2	AT → PV in AAC51195. Ref.3
	Sequence conflict	61 – 62	2	AT → PV in AAD43049. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified October 17, 2006. Version 3. Checksum: 4A6A0C8C5CC41A20	FASTA	221	24,868
	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
	Isoform Short [UniParc]. Checksum: 9A2B95ECB4BC2BFE	FASTA	213	24,041
	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 RVVKEKYGIP YFETSAANGT NISQAIEMLL DLIMKRMERC 190 200 210 VDKSWIPEGV VRSNGHASTD QLSEEKEKGA CGC

References

	« Hide 'large scale' referencesShow '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: 7592656] [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: 9066979] [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: 10571040] [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. , 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: 10931946] [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: 15489334] [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: 12062444] [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: 12643545] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. 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: 15548590] [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: 17081065] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. 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: 17237785] [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: 18812475] [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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]	"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: 10835631] [Abstract] Cited for: VARIANTS GS2 GLY-73; PRO-130 AND PRO-152.
[18]	"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: 12058346] [Abstract] Cited for: INVOLVEMENT IN GRISCELLI SYNDROME.
[19]	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)
[20]	"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: 12446441] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS GS2 GLY-73; PRO-130 AND PRO-152.
[21]	"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: 12531900] [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 , 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.
IPI	IPI00016381. IPI00219858.
PIR	I39198.
RefSeq	NP_004571.2. NM_004580.4. NP_899057.1. NM_183234.2. NP_899058.1. NM_183235.2. NP_899059.1. NM_183236.2.
UniGene	Hs.654978.
3D structure databases
ProteinModelPortal	P51159.
SMR	P51159. Positions 4-187.
ModBase	Search...
Protein-protein interaction databases
IntAct	P51159. 9 interactions.
MINT	MINT-1377654.
STRING	P51159.
PTM databases
PhosphoSite	P51159.
Polymorphism databases
DMDM	116242744.
Proteomic databases
PeptideAtlas	P51159.
PRIDE	P51159.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000336787; ENSP00000337761; ENSG00000069974. ENST00000396307; ENSP00000379601; ENSG00000069974. ENST00000423492; ENSP00000407887; ENSG00000069974.
GeneID	5873.
KEGG	hsa:5873.
UCSC	uc002aco.1. human.
Organism-specific databases
CTD	5873.
GeneCards	GC15M055495.
H-InvDB	HIX0023096.
HGNC	HGNC:9766. RAB27A.
HPA	HPA001333.
MIM	603868. gene. 607624. phenotype.
neXtProt	NX_P51159.
Orphanet	79477. Griscelli disease type 2.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	HBG745225.
HOVERGEN	HBG009351.
InParanoid	P51159.
OMA	LQTHAYC.
OrthoDB	EOG4PRSRM.
PhylomeDB	P51159.
Enzyme and pathway databases
Reactome	REACT_15380. Diabetes pathways.
Gene expression databases
ArrayExpress	P51159.
Bgee	P51159.
CleanEx	HS_RAB27A.
Genevestigator	P51159.
GermOnline	ENSG00000069974. Homo sapiens.
Family and domain databases
InterPro	IPR005225. Small_GTP-bd_dom. IPR001806. Small_GTPase. IPR015597. Small_GTPase_Rab27. IPR003579. Small_GTPase_Rab_type. [Graphical view]
KO	K07885.
PANTHER	PTHR24073:SF223. PTHR24073:SF223. 1 hit.
Pfam	PF00071. Ras. 1 hit. [Graphical view]
PRINTS	PR00449. RASTRNSFRMNG.
SMART	SM00175. RAB. 1 hit. [Graphical view]
TIGRFAMs	TIGR00231. Small_GTP. 1 hit.
PROSITE	PS51419. RAB. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	22812.
SOURCE	Search...

Entry information

Entry name

RB27A_HUMAN

Accession

Primary (citable) accession number: P51159
Secondary accession number(s): O00195 , Q6FI40, Q9UIR9, Q9Y5U3

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 17, 2006
Last modified:	January 25, 2012
This is version 124 of the entry and version 3 of the sequence. [Complete history]

Entry status

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.