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 27-MAR-2024, entry version 221. 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 87. 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; 9606-ENSP00000379601; -. DR PeptideAtlas; P51159; -. DR ProteomicsDB; 56289; -. [P51159-1] DR ProteomicsDB; 56290; -. [P51159-2] DR Pumba; P51159; -. DR Antibodypedia; 687; 513 antibodies from 38 providers. DR DNASU; 5873; -. DR Ensembl; ENST00000336787.6; ENSP00000337761.1; ENSG00000069974.17. [P51159-1] DR Ensembl; ENST00000396307.6; ENSP00000379601.2; ENSG00000069974.17. [P51159-1] DR Ensembl; ENST00000564609.5; ENSP00000455012.1; ENSG00000069974.17. [P51159-1] DR Ensembl; ENST00000569493.5; ENSP00000456059.1; ENSG00000069974.17. [P51159-1] DR Ensembl; ENST00000697642.1; ENSP00000513368.1; ENSG00000069974.17. [P51159-1] DR Ensembl; ENST00000697643.1; ENSP00000513369.1; ENSG00000069974.17. [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 AGR; HGNC:9766; -. 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; 8685at2759; -. 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; 11 hits in 1161 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 193 other cell types or tissues. DR ExpressionAtlas; P51159; baseline and differential. 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: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 CDD; cd04127; Rab27A; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 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 NCBIfam; TIGR00231; small_GTP; 1. DR PANTHER; PTHR47977; RAS-RELATED PROTEIN RAB; 1. DR PANTHER; PTHR47977:SF20; RAS-RELATED PROTEIN RAB-27A; 1. DR Pfam; PF00071; Ras; 1. DR PRINTS; PR00449; RASTRNSFRMNG. DR SMART; SM00175; RAB; 1. DR SMART; SM00176; RAN; 1. DR SMART; SM00173; RAS; 1. DR SMART; SM00174; RHO; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR PROSITE; PS51419; RAB; 1. DR Genevisible; P51159; HS. 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 7..15 FT /evidence="ECO:0007829|PDB:7OPQ" FT HELIX 22..31 FT /evidence="ECO:0007829|PDB:7OPQ" FT STRAND 43..53 FT /evidence="ECO:0007829|PDB:7OPQ" FT STRAND 58..60 FT /evidence="ECO:0007829|PDB:7OPQ" FT STRAND 66..75 FT /evidence="ECO:0007829|PDB:7OPQ" FT HELIX 79..81 FT /evidence="ECO:0007829|PDB:7OPQ" FT HELIX 82..86 FT /evidence="ECO:0007829|PDB:7OPQ" FT HELIX 87..91 FT /evidence="ECO:0007829|PDB:7OPQ" FT STRAND 93..100 FT /evidence="ECO:0007829|PDB:7OPQ" FT HELIX 104..108 FT /evidence="ECO:0007829|PDB:7OPQ" FT HELIX 110..120 FT /evidence="ECO:0007829|PDB:7OPQ" FT STRAND 121..125 FT /evidence="ECO:0007829|PDB:7OPQ" FT STRAND 128..133 FT /evidence="ECO:0007829|PDB:7OPQ" FT HELIX 138..140 FT /evidence="ECO:0007829|PDB:7OPQ" FT HELIX 145..155 FT /evidence="ECO:0007829|PDB:7OPQ" FT STRAND 159..161 FT /evidence="ECO:0007829|PDB:7OPQ" FT TURN 164..166 FT /evidence="ECO:0007829|PDB:7OPQ" FT HELIX 170..187 FT /evidence="ECO:0007829|PDB:7OPQ" 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 //