RB27A_HUMAN
ID RB27A_HUMAN Reviewed; 221 AA.
AC P51159; O00195; Q6FI40; Q9UIR9; Q9Y5U3;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 3.
DT 03-AUG-2022, entry version 212.
DE RecName: Full=Ras-related protein Rab-27A;
DE Short=Rab-27;
DE EC=3.6.5.2 {ECO:0000305|PubMed:12531900, ECO:0000305|PubMed:15548590};
DE AltName: Full=GTP-binding protein Ram;
GN Name=RAB27A; Synonyms=RAB27;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Retina;
RX PubMed=7592656; DOI=10.1074/jbc.270.41.24420;
RA Seabra M.C., Ho Y.K., Anant J.S.;
RT "Deficient geranylgeranylation of Ram/Rab27 in choroideremia.";
RL J. Biol. Chem. 270:24420-24427(1995).
RN [2]
RP SEQUENCE REVISION TO 99.
RA Seabra M.C.;
RL Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
RC TISSUE=Melanocyte;
RX PubMed=9066979; DOI=10.1006/bmme.1996.2559;
RA Chen D., Guo J., Miki T., Tachibana M., Gahl W.A.;
RT "Molecular cloning and characterization of rab27a and rab27b, novel human
RT rab proteins shared by melanocytes and platelets.";
RL Biochem. Mol. Med. 60:27-37(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM LONG).
RX PubMed=10571040; DOI=10.1016/s0378-1119(99)00371-6;
RA Tolmachova T., Ramalho J.S., Anant J.S., Schultz R.A., Huxley C.M.,
RA Seabra M.C.;
RT "Cloning, mapping and characterization of the human RAB27A gene.";
RL Gene 239:109-116(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SHORT).
RC TISSUE=Pituitary;
RX PubMed=10931946; DOI=10.1073/pnas.160270997;
RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X.,
RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W.,
RA Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J., Xu S.-H., Gu J.,
RA Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z.,
RA Chen M.-D., Chen J.-L.;
RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis
RT and full-length cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING (ISOFORM LONG).
RA Anderson P.D., Huizing M., Anikster Y., Gahl W.A.;
RT "Genomic organization of the human RAB27A gene.";
RL Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
RC TISSUE=Brain;
RA Puhl H.L. III, Ikeda S.R., Aronstam R.S.;
RT "cDNA clones of human proteins involved in signal transduction sequenced by
RT the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP INTERACTION WITH MLPH.
RX PubMed=12062444; DOI=10.1016/s0014-5793(02)02634-0;
RA Nagashima K., Torii S., Yi Z., Igarashi M., Okamoto K., Takeuchi T.,
RA Izumi T.;
RT "Melanophilin directly links Rab27a and myosin Va through its distinct
RT coiled-coil regions.";
RL FEBS Lett. 517:233-238(2002).
RN [11]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Melanoma;
RX PubMed=12643545; DOI=10.1021/pr025562r;
RA Basrur V., Yang F., Kushimoto T., Higashimoto Y., Yasumoto K., Valencia J.,
RA Muller J., Vieira W.D., Watabe H., Shabanowitz J., Hearing V.J., Hunt D.F.,
RA Appella E.;
RT "Proteomic analysis of early melanosomes: identification of novel
RT melanosomal proteins.";
RL J. Proteome Res. 2:69-79(2003).
RN [12]
RP SUBCELLULAR LOCATION, INTERACTION WITH UNC13D, TISSUE SPECIFICITY,
RP MUTAGENESIS OF THR-23, AND CHARACTERIZATION OF VARIANT GS2 GLY-73.
RX PubMed=15548590; DOI=10.1091/mbc.e04-10-0923;
RA Neeft M., Wieffer M., de Jong A.S., Negroiu G., Metz C.H., van Loon A.,
RA Griffith J., Krijgsveld J., Wulffraat N., Koch H., Heck A.J.R., Brose N.,
RA Kleijmeer M., van der Sluijs P.;
RT "Munc13-4 is an effector of rab27a and controls secretion of lysosomes in
RT hematopoietic cells.";
RL Mol. Biol. Cell 16:731-741(2005).
RN [13]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J.,
RA Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S.,
RA Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [14]
RP INTERACTION WITH UNC13D, AND SUBCELLULAR LOCATION.
RX PubMed=17237785; DOI=10.1038/ni1431;
RA Menager M.M., Menasche G., Romao M., Knapnougel P., Ho C.-H., Garfa M.,
RA Raposo G., Feldmann J., Fischer A., de Saint Basile G.;
RT "Secretory cytotoxic granule maturation and exocytosis require the effector
RT protein hMunc13-4.";
RL Nat. Immunol. 8:257-267(2007).
RN [15]
RP FUNCTION, INTERACTION WITH SYTL2, AND MUTAGENESIS OF LEU-70 AND ALA-76.
RX PubMed=18812475; DOI=10.1182/blood-2008-02-141069;
RA Menasche G., Menager M.M., Lefebvre J.M., Deutsch E., Athman R.,
RA Lambert N., Mahlaoui N., Court M., Garin J., Fischer A.,
RA de Saint Basile G.;
RT "A newly identified isoform of Slp2a associates with Rab27a in cytotoxic T
RT cells and participates in cytotoxic granule secretion.";
RL Blood 112:5052-5062(2008).
RN [16]
RP LACK OF INTERACTION WITH THE BLOC-3 COMPLEX.
RX PubMed=20048159; DOI=10.1074/jbc.m109.069088;
RA Kloer D.P., Rojas R., Ivan V., Moriyama K., van Vlijmen T., Murthy N.,
RA Ghirlando R., van der Sluijs P., Hurley J.H., Bonifacino J.S.;
RT "Assembly of the biogenesis of lysosome-related organelles complex-3 (BLOC-
RT 3) and its interaction with Rab9.";
RL J. Biol. Chem. 285:7794-7804(2010).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [18]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [20]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [21]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH DENND10, ACTIVITY
RP REGULATION, AND MUTAGENESIS OF THR-23 AND GLN-78.
RX PubMed=30771381; DOI=10.1016/j.bbamcr.2019.02.006;
RA Zhang J., Zhang K., Qi L., Hu Q., Shen Z., Liu B., Deng J., Zhang C.,
RA Zhang Y.;
RT "DENN domain-containing protein FAM45A regulates the homeostasis of
RT late/multivesicular endosomes.";
RL Biochim. Biophys. Acta 1866:916-929(2019).
RN [22]
RP VARIANTS GS2 GLY-73; PRO-130 AND PRO-152.
RX PubMed=10835631; DOI=10.1038/76024;
RA Menasche G., Pastural E., Feldmann J., Certain S., Ersoy F., Dupuis S.,
RA Wulffraat N., Bianchi D., Fischer A., Le Deist F., de Saint Basile G.;
RT "Mutations in RAB27A cause Griscelli syndrome associated with
RT haemophagocytic syndrome.";
RL Nat. Genet. 25:173-176(2000).
RN [23]
RP INVOLVEMENT IN GRISCELLI SYNDROME.
RX PubMed=12058346; DOI=10.1086/341606;
RA Anikster Y., Huizing M., Anderson P.D., Fitzpatrick D.L., Klar A.,
RA Gross-Kieselstein E., Berkun Y., Shazberg G., Gahl W.A., Hurvitz H.;
RT "Evidence that Griscelli syndrome with neurological involvement is caused
RT by mutations in RAB27A, not MYO5A.";
RL Am. J. Hum. Genet. 71:407-414(2002).
RN [24]
RP ERRATUM OF PUBMED:12058346.
RA Anikster Y., Huizing M., Anderson P.D., Fitzpatrick D.L., Klar A.,
RA Gross-Kieselstein E., Berkun Y., Shazberg G., Gahl W.A., Hurvitz H.;
RL Am. J. Hum. Genet. 71:1007-1007(2002).
RN [25]
RP CHARACTERIZATION OF VARIANTS GS2 GLY-73; PRO-130 AND PRO-152.
RX PubMed=12446441; DOI=10.1182/blood-2002-09-2789;
RA Menasche G., Feldmann J., Houdusse A., Desaymard C., Fischer A., Goud B.,
RA de Saint Basile G.;
RT "Biochemical and functional characterization of Rab27a mutations occurring
RT in Griscelli syndrome patients.";
RL Blood 101:2736-2742(2003).
RN [26]
RP CHARACTERIZATION OF VARIANTS GS2 GLY-73; PRO-130 AND PRO-152.
RX PubMed=12531900; DOI=10.1074/jbc.m211996200;
RA Bahadoran P., Busca R., Chiaverini C., Westbroek W., Lambert J., Bille K.,
RA Valony G., Fukuda M., Naeyaert J.-M., Ortonne J.-P., Ballotti R.;
RT "Characterization of the molecular defects in Rab27a, caused by RAB27A
RT missense mutations found in patients with Griscelli syndrome.";
RL J. Biol. Chem. 278:11386-11392(2003).
CC -!- FUNCTION: Small GTPase which cycles between active GTP-bound and
CC inactive GDP-bound states. In its active state, binds to a variety of
CC effector proteins to regulate homeostasis of late endocytic pathway,
CC including endosomal positioning, maturation and secretion
CC (PubMed:30771381). Plays a role in cytotoxic granule exocytosis in
CC lymphocytes. Required for both granule maturation and granule docking
CC and priming at the immunologic synapse. {ECO:0000269|PubMed:18812475,
CC ECO:0000269|PubMed:30771381}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; EC=3.6.5.2;
CC Evidence={ECO:0000305|PubMed:12531900, ECO:0000305|PubMed:15548590};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670;
CC Evidence={ECO:0000305|PubMed:12531900, ECO:0000305|PubMed:15548590};
CC -!- ACTIVITY REGULATION: Regulated by guanine nucleotide exchange factors
CC (GEFs) which promote the exchange of bound GDP for free GTP, GTPase
CC activating proteins (GAPs) which increase the GTP hydrolysis activity,
CC and GDP dissociation inhibitors which inhibit the dissociation of the
CC nucleotide from the GTPase. Activated by GEFs such as DENND10.
CC {ECO:0000305|PubMed:30771381}.
CC -!- SUBUNIT: Binds SYTL1, SLAC2B, MYRIP, SYTL3, SYTL4 and SYTL5. Interacts
CC with RPH3A and RPH3A (By similarity). Binds MLPH and SYTL2. Interacts
CC with UNC13D. Does not interact with the BLOC-3 complex (heterodimer of
CC HPS1 and HPS4) (PubMed:20048159). Interacts (GDP-bound form
CC preferentially) with DENND10 (PubMed:30771381).
CC {ECO:0000250|UniProtKB:Q9ERI2, ECO:0000269|PubMed:12062444,
CC ECO:0000269|PubMed:15548590, ECO:0000269|PubMed:17237785,
CC ECO:0000269|PubMed:18812475, ECO:0000269|PubMed:20048159,
CC ECO:0000269|PubMed:30771381}.
CC -!- INTERACTION:
CC P51159; Q9BV36: MLPH; NbExp=4; IntAct=EBI-716881, EBI-7042162;
CC P51159; Q8NFW9: MYRIP; NbExp=3; IntAct=EBI-716881, EBI-1759414;
CC P51159; Q8IYJ3: SYTL1; NbExp=3; IntAct=EBI-716881, EBI-2802861;
CC P51159; Q4VX76: SYTL3; NbExp=3; IntAct=EBI-716881, EBI-2840607;
CC P51159; Q96C24: SYTL4; NbExp=3; IntAct=EBI-716881, EBI-747142;
CC P51159; Q8TDW5-2: SYTL5; NbExp=3; IntAct=EBI-716881, EBI-12243980;
CC P51159; Q70J99: UNC13D; NbExp=3; IntAct=EBI-716881, EBI-11479429;
CC P51159-1; Q9BV36: MLPH; NbExp=2; IntAct=EBI-15528760, EBI-7042162;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Lipid-anchor
CC {ECO:0000305}. Melanosome {ECO:0000269|PubMed:12643545,
CC ECO:0000269|PubMed:17081065}. Late endosome
CC {ECO:0000269|PubMed:15548590, ECO:0000269|PubMed:30771381}. Lysosome
CC {ECO:0000269|PubMed:15548590}. Note=Identified by mass spectrometry in
CC melanosome fractions from stage I to stage IV (PubMed:12643545,
CC PubMed:17081065). Localizes to endosomal exocytic vesicles
CC (PubMed:17237785). {ECO:0000269|PubMed:12643545,
CC ECO:0000269|PubMed:17081065, ECO:0000269|PubMed:17237785}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=P51159-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=P51159-2; Sequence=VSP_005529;
CC -!- TISSUE SPECIFICITY: Found in all the examined tissues except in brain.
CC Low expression was found in thymus, kidney, muscle and placenta.
CC Detected in melanocytes, and in most tumor cell lines examined.
CC Expressed in cytotoxic T-lymphocytes (CTL) and mast cells.
CC {ECO:0000269|PubMed:15548590}.
CC -!- DISEASE: Griscelli syndrome 2 (GS2) [MIM:607624]: Rare autosomal
CC recessive disorder that results in pigmentary dilution of the skin and
CC hair, the presence of large clumps of pigment in hair shafts, and an
CC accumulation of melanosomes in melanocytes. GS2 patients also develop
CC an uncontrolled T-lymphocyte and macrophage activation syndrome, known
CC as hemophagocytic syndrome, leading to death in the absence of bone
CC marrow transplantation. Neurological impairment is present in some
CC patients, likely as a result of hemophagocytic syndrome.
CC {ECO:0000269|PubMed:10835631, ECO:0000269|PubMed:12446441,
CC ECO:0000269|PubMed:12531900, ECO:0000269|PubMed:15548590}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rab family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=RAB27Abase; Note=RAB27A mutation db;
CC URL="http://structure.bmc.lu.se/idbase/RAB27Abase/";
CC -!- WEB RESOURCE: Name=Mutations of the RAB27A gene; Note=Retina
CC International's Scientific Newsletter;
CC URL="https://www.retina-international.org/files/sci-news/rab27mut.htm";
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DR EMBL; U38654; AAC50271.2; -; mRNA.
DR EMBL; U57094; AAC51195.1; -; mRNA.
DR EMBL; AF154840; AAD47629.1; -; Genomic_DNA.
DR EMBL; AF154836; AAD47629.1; JOINED; Genomic_DNA.
DR EMBL; AF154837; AAD47629.1; JOINED; Genomic_DNA.
DR EMBL; AF154838; AAD47629.1; JOINED; Genomic_DNA.
DR EMBL; AF154839; AAD47629.1; JOINED; Genomic_DNA.
DR EMBL; AF125393; AAD43049.1; -; mRNA.
DR EMBL; AF443871; AAL39097.1; -; Genomic_DNA.
DR EMBL; AF498953; AAM21101.1; -; mRNA.
DR EMBL; CR536496; CAG38735.1; -; mRNA.
DR EMBL; CR541693; CAG46494.1; -; mRNA.
DR EMBL; BC107680; AAI07681.1; -; mRNA.
DR CCDS; CCDS10153.1; -. [P51159-1]
DR PIR; I39198; I39198.
DR RefSeq; NP_004571.2; NM_004580.4. [P51159-1]
DR RefSeq; NP_899057.1; NM_183234.2. [P51159-1]
DR RefSeq; NP_899058.1; NM_183235.2. [P51159-1]
DR RefSeq; NP_899059.1; NM_183236.2. [P51159-1]
DR RefSeq; XP_005254633.1; XM_005254576.4. [P51159-1]
DR RefSeq; XP_011520154.1; XM_011521852.1. [P51159-1]
DR RefSeq; XP_011520156.1; XM_011521854.1. [P51159-1]
DR RefSeq; XP_011520157.1; XM_011521855.2. [P51159-1]
DR RefSeq; XP_011520158.1; XM_011521856.2. [P51159-1]
DR PDB; 6HUF; X-ray; 2.82 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P=2-192.
DR PDB; 7OPP; X-ray; 2.32 A; A/C=1-192.
DR PDB; 7OPQ; X-ray; 2.23 A; A/B=1-192.
DR PDB; 7OPR; X-ray; 2.32 A; A/B=1-192.
DR PDBsum; 6HUF; -.
DR PDBsum; 7OPP; -.
DR PDBsum; 7OPQ; -.
DR PDBsum; 7OPR; -.
DR AlphaFoldDB; P51159; -.
DR SMR; P51159; -.
DR BioGRID; 111811; 86.
DR CORUM; P51159; -.
DR DIP; DIP-44244N; -.
DR IntAct; P51159; 50.
DR MINT; P51159; -.
DR STRING; 9606.ENSP00000379601; -.
DR ChEMBL; CHEMBL4105702; -.
DR GuidetoPHARMACOLOGY; 2916; -.
DR GlyGen; P51159; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P51159; -.
DR PhosphoSitePlus; P51159; -.
DR SwissPalm; P51159; -.
DR BioMuta; RAB27A; -.
DR DMDM; 116242744; -.
DR EPD; P51159; -.
DR jPOST; P51159; -.
DR MassIVE; P51159; -.
DR MaxQB; P51159; -.
DR PaxDb; P51159; -.
DR PeptideAtlas; P51159; -.
DR PRIDE; P51159; -.
DR ProteomicsDB; 56289; -. [P51159-1]
DR ProteomicsDB; 56290; -. [P51159-2]
DR Antibodypedia; 687; 470 antibodies from 38 providers.
DR DNASU; 5873; -.
DR Ensembl; ENST00000336787.6; ENSP00000337761.1; ENSG00000069974.16. [P51159-1]
DR Ensembl; ENST00000396307.6; ENSP00000379601.2; ENSG00000069974.16. [P51159-1]
DR Ensembl; ENST00000564609.5; ENSP00000455012.1; ENSG00000069974.16. [P51159-1]
DR Ensembl; ENST00000569493.5; ENSP00000456059.1; ENSG00000069974.16. [P51159-1]
DR GeneID; 5873; -.
DR KEGG; hsa:5873; -.
DR MANE-Select; ENST00000336787.6; ENSP00000337761.1; NM_183235.3; NP_899058.1.
DR UCSC; uc002aco.4; human. [P51159-1]
DR CTD; 5873; -.
DR DisGeNET; 5873; -.
DR GeneCards; RAB27A; -.
DR HGNC; HGNC:9766; RAB27A.
DR HPA; ENSG00000069974; Tissue enhanced (stomach).
DR MalaCards; RAB27A; -.
DR MIM; 603868; gene.
DR MIM; 607624; phenotype.
DR neXtProt; NX_P51159; -.
DR OpenTargets; ENSG00000069974; -.
DR Orphanet; 79477; Griscelli syndrome type 2.
DR PharmGKB; PA34117; -.
DR VEuPathDB; HostDB:ENSG00000069974; -.
DR eggNOG; KOG0081; Eukaryota.
DR GeneTree; ENSGT00940000156218; -.
DR InParanoid; P51159; -.
DR OMA; CTGANIQ; -.
DR OrthoDB; 1190514at2759; -.
DR PhylomeDB; P51159; -.
DR TreeFam; TF312895; -.
DR PathwayCommons; P51159; -.
DR Reactome; R-HSA-264876; Insulin processing.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-8873719; RAB geranylgeranylation.
DR Reactome; R-HSA-8876198; RAB GEFs exchange GTP for GDP on RABs.
DR SignaLink; P51159; -.
DR BioGRID-ORCS; 5873; 9 hits in 1082 CRISPR screens.
DR ChiTaRS; RAB27A; human.
DR GeneWiki; RAB27A; -.
DR GenomeRNAi; 5873; -.
DR Pharos; P51159; Tchem.
DR PRO; PR:P51159; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; P51159; protein.
DR Bgee; ENSG00000069974; Expressed in trabecular bone tissue and 191 other tissues.
DR ExpressionAtlas; P51159; baseline and differential.
DR Genevisible; P51159; HS.
DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030425; C:dendrite; IDA:UniProtKB.
DR GO; GO:0070382; C:exocytic vesicle; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
DR GO; GO:0005770; C:late endosome; IDA:UniProtKB.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0042470; C:melanosome; IDA:UniProtKB.
DR GO; GO:0033162; C:melanosome membrane; TAS:Reactome.
DR GO; GO:0032585; C:multivesicular body membrane; IDA:UniProtKB.
DR GO; GO:0001750; C:photoreceptor outer segment; IEA:Ensembl.
DR GO; GO:0030141; C:secretory granule; IBA:GO_Central.
DR GO; GO:0030667; C:secretory granule membrane; IEA:Ensembl.
DR GO; GO:0035580; C:specific granule lumen; TAS:Reactome.
DR GO; GO:0033093; C:Weibel-Palade body; IEA:Ensembl.
DR GO; GO:0003925; F:G protein activity; IEA:UniProtKB-EC.
DR GO; GO:0019003; F:GDP binding; IDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IDA:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; ISS:UniProtKB.
DR GO; GO:0031489; F:myosin V binding; IEA:Ensembl.
DR GO; GO:0019904; F:protein domain specific binding; IEA:Ensembl.
DR GO; GO:0019882; P:antigen processing and presentation; IMP:UniProtKB.
DR GO; GO:0007596; P:blood coagulation; IEA:Ensembl.
DR GO; GO:0097278; P:complement-dependent cytotoxicity; IMP:UniProtKB.
DR GO; GO:0043316; P:cytotoxic T cell degranulation; IEA:Ensembl.
DR GO; GO:0006887; P:exocytosis; IDA:UniProtKB.
DR GO; GO:1990182; P:exosomal secretion; IMP:UniProtKB.
DR GO; GO:0030318; P:melanocyte differentiation; IEA:Ensembl.
DR GO; GO:0032400; P:melanosome localization; IMP:UniProtKB.
DR GO; GO:0032402; P:melanosome transport; NAS:UniProtKB.
DR GO; GO:0036257; P:multivesicular body organization; IMP:UniProtKB.
DR GO; GO:0071985; P:multivesicular body sorting pathway; IMP:UniProtKB.
DR GO; GO:0043320; P:natural killer cell degranulation; IEA:Ensembl.
DR GO; GO:1903435; P:positive regulation of constitutive secretory pathway; IMP:UniProtKB.
DR GO; GO:0045921; P:positive regulation of exocytosis; IMP:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0050766; P:positive regulation of phagocytosis; IMP:UniProtKB.
DR GO; GO:1903428; P:positive regulation of reactive oxygen species biosynthetic process; IMP:UniProtKB.
DR GO; GO:1903307; P:positive regulation of regulated secretory pathway; IMP:UniProtKB.
DR GO; GO:0048489; P:synaptic vesicle transport; TAS:ParkinsonsUK-UCL.
DR GO; GO:0016192; P:vesicle-mediated transport; IBA:GO_Central.
DR CDD; cd04127; Rab27A; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR041837; Rab27a/b.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR001806; Small_GTPase.
DR Pfam; PF00071; Ras; 1.
DR SMART; SM00174; RHO; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51419; RAB; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Direct protein sequencing;
KW Disease variant; Disulfide bond; Endosome; Exocytosis; GTP-binding;
KW Hydrolase; Lipoprotein; Lysosome; Membrane; Methylation;
KW Nucleotide-binding; Phosphoprotein; Prenylation; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:25944712"
FT CHAIN 2..221
FT /note="Ras-related protein Rab-27A"
FT /id="PRO_0000121221"
FT MOTIF 38..46
FT /note="Effector region"
FT /evidence="ECO:0000250"
FT BINDING 16..24
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 74..78
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 133..136
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 163..165
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:25944712"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 221
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000250"
FT LIPID 219
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 221
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000250"
FT DISULFID 123..188
FT /evidence="ECO:0000250"
FT VAR_SEQ 146..153
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:10931946"
FT /id="VSP_005529"
FT VARIANT 62
FT /note="T -> S (in dbSNP:rs1050930)"
FT /id="VAR_028206"
FT VARIANT 73
FT /note="W -> G (in GS2; does not affect GTP binding; cannot
FT interact with MLPH; significant reduction in interaction
FT with UNC13D; abolishes localization to lysosomes;
FT dbSNP:rs28938176)"
FT /evidence="ECO:0000269|PubMed:10835631,
FT ECO:0000269|PubMed:12446441, ECO:0000269|PubMed:12531900,
FT ECO:0000269|PubMed:15548590"
FT /id="VAR_010654"
FT VARIANT 84
FT /note="L -> F (in dbSNP:rs4340274)"
FT /id="VAR_028207"
FT VARIANT 85
FT /note="T -> P (in dbSNP:rs719705)"
FT /id="VAR_028208"
FT VARIANT 130
FT /note="L -> P (in GS2; strongly affects GTP binding; cannot
FT interact with MLPH; dbSNP:rs104894498)"
FT /evidence="ECO:0000269|PubMed:10835631,
FT ECO:0000269|PubMed:12446441, ECO:0000269|PubMed:12531900"
FT /id="VAR_011334"
FT VARIANT 152
FT /note="A -> P (in GS2; interferes with melanosome
FT transport; dbSNP:rs104894499)"
FT /evidence="ECO:0000269|PubMed:10835631,
FT ECO:0000269|PubMed:12446441, ECO:0000269|PubMed:12531900"
FT /id="VAR_011335"
FT MUTAGEN 23
FT /note="T->N: GDP-locked. Abolishes interaction with UNC13D
FT and localization to lysosomes. Increases interaction with
FT DENND10. Disrupts late endocytic pathway homeostasis."
FT /evidence="ECO:0000269|PubMed:15548590,
FT ECO:0000269|PubMed:30771381"
FT MUTAGEN 70
FT /note="L->P: Abolishes interaction with SYTL2."
FT /evidence="ECO:0000269|PubMed:18812475"
FT MUTAGEN 76
FT /note="A->V: Abolishes interaction with SYTL2."
FT /evidence="ECO:0000269|PubMed:18812475"
FT MUTAGEN 78
FT /note="Q->L: GTP-locked. decreases interaction with
FT DENND10."
FT /evidence="ECO:0000269|PubMed:30771381"
FT CONFLICT 48
FT /note="E -> P (in Ref. 3; AAC51195 and 5; AAD43049)"
FT /evidence="ECO:0000305"
FT CONFLICT 61..62
FT /note="AT -> PV (in Ref. 3; AAC51195 and 5; AAD43049)"
FT /evidence="ECO:0000305"
FT STRAND 9..15
FT /evidence="ECO:0007829|PDB:6HUF"
FT HELIX 22..31
FT /evidence="ECO:0007829|PDB:6HUF"
FT STRAND 46..49
FT /evidence="ECO:0007829|PDB:6HUF"
FT STRAND 64..66
FT /evidence="ECO:0007829|PDB:6HUF"
FT STRAND 68..73
FT /evidence="ECO:0007829|PDB:6HUF"
FT STRAND 85..87
FT /evidence="ECO:0007829|PDB:6HUF"
FT HELIX 88..91
FT /evidence="ECO:0007829|PDB:6HUF"
FT STRAND 93..100
FT /evidence="ECO:0007829|PDB:6HUF"
FT HELIX 104..120
FT /evidence="ECO:0007829|PDB:6HUF"
FT STRAND 121..125
FT /evidence="ECO:0007829|PDB:6HUF"
FT STRAND 127..133
FT /evidence="ECO:0007829|PDB:6HUF"
FT HELIX 138..140
FT /evidence="ECO:0007829|PDB:6HUF"
FT HELIX 145..155
FT /evidence="ECO:0007829|PDB:6HUF"
FT STRAND 159..161
FT /evidence="ECO:0007829|PDB:6HUF"
FT TURN 164..166
FT /evidence="ECO:0007829|PDB:6HUF"
FT HELIX 170..187
FT /evidence="ECO:0007829|PDB:6HUF"
SQ SEQUENCE 221 AA; 24868 MW; 4A6A0C8C5CC41A20 CRC64;
MSDGDYDYLI KFLALGDSGV GKTSVLYQYT DGKFNSKFIT TVGIDFREKR VVYRASGPDG
ATGRGQRIHL QLWDTAGQER FRSLTTAFFR DAMGFLLLFD LTNEQSFLNV RNWISQLQMH
AYCENPDIVL CGNKSDLEDQ RVVKEEEAIA LAEKYGIPYF ETSAANGTNI SQAIEMLLDL
IMKRMERCVD KSWIPEGVVR SNGHASTDQL SEEKEKGACG C
