ID   RAB15_HUMAN             Reviewed;         212 AA.
AC   P59190; G5EMR7; Q86TX7; Q8IW89;
DT   10-JAN-2003, integrated into UniProtKB/Swiss-Prot.
DT   10-JAN-2003, sequence version 1.
DT   04-NOV-2026, entry version 191.
DE   RecName: Full=Ras-related protein Rab-15;
DE            EC=3.6.5.2 {ECO:0000250|UniProtKB:P61026};
GN   Name=RAB15 {ECO:0000312|HGNC:HGNC:20150};
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 2).
RA   Pham T., Hartoma T., Nishimura N.;
RT   "Aberrant Rab15 expression.";
RL   Submitted (OCT-2011) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=12508121; DOI=10.1038/nature01348;
RA   Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA   Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA   Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA   Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA   Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA   Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA   Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA   Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA   Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA   Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA   Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA   Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA   Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA   Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA   Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA   Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA   Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA   Waterston R., Hood L., Weissenbach J.;
RT   "The DNA sequence and analysis of human chromosome 14.";
RL   Nature 421:601-607(2003).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Brain;
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   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 42-212 (ISOFORM 2).
RC   TISSUE=Placenta;
RA   Li W.B., Gruber C., Jessee J., Polayes D.;
RT   "Full-length cDNA libraries and normalization.";
RL   Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   INTERACTION WITH REP15.
RX   PubMed=16195351; DOI=10.1091/mbc.e05-03-0204;
RA   Strick D.J., Elferink L.A.;
RT   "Rab15 effector protein: a novel protein for receptor recycling from the
RT   endocytic recycling compartment.";
RL   Mol. Biol. Cell 16:5699-5709(2005).
RN   [7]
RP   INTERACTION WITH MICAL1; MICALCL; MICAL3; EHBP1 AND EHBP1L1.
RX   PubMed=27552051; DOI=10.7554/elife.18675;
RA   Rai A., Oprisko A., Campos J., Fu Y., Friese T., Itzen A., Goody R.S.,
RA   Gazdag E.M., Muller M.P.;
RT   "bMERB domains are bivalent Rab8 family effectors evolved by gene
RT   duplication.";
RL   Elife 5:E18675-E18675(2016).
RN   [8]
RP   INTERACTION WITH REP15.
RX   PubMed=35871249; DOI=10.1038/s41467-022-31831-1;
RA   Rai A., Singh A.K., Bleimling N., Posern G., Vetter I.R., Goody R.S.;
RT   "Rep15 interacts with several Rab GTPases and has a distinct fold for a Rab
RT   effector.";
RL   Nat. Commun. 13:4262-4262(2022).
CC   -!- FUNCTION: The small GTPases Rab are key regulators of intracellular
CC       membrane trafficking, from the formation of transport vesicles to their
CC       fusion with membranes (By similarity). Rabs cycle between an inactive
CC       GDP-bound form and an active GTP-bound form that is able to recruit to
CC       membranes different sets of downstream effectors directly responsible
CC       for vesicle formation, movement, tethering and fusion (By similarity).
CC       RAB15 may act in concert with RAB3A in regulating aspects of synaptic
CC       vesicle membrane flow within the nerve terminal (By similarity).
CC       {ECO:0000250|UniProtKB:P35289, ECO:0000250|UniProtKB:P61026}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=GTP + H2O = GDP + phosphate + H(+); 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:0000250|UniProtKB:P61026};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670;
CC         Evidence={ECO:0000250|UniProtKB:P61026};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000250|UniProtKB:P61026};
CC   -!- ACTIVITY REGULATION: Regulated by guanine nucleotide exchange factors
CC       (GEFs) which promote the exchange of bound GDP for free GTP. Regulated
CC       by GTPase activating proteins (GAPs) which increase the GTP hydrolysis
CC       activity (Probable). Inhibited by GDP dissociation inhibitors (GDIs)
CC       (Probable). {ECO:0000305}.
CC   -!- SUBUNIT: The GTP bound form of RAB15 interacts with REP15
CC       (PubMed:16195351, PubMed:35871249). Interacts (GTP-bound form) with
CC       MICAL1, MICAL3, MICALCL, EHBP1 and EHBP1L1 (PubMed:27552051).
CC       {ECO:0000269|PubMed:16195351, ECO:0000269|PubMed:27552051,
CC       ECO:0000269|PubMed:35871249}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Lipid-anchor
CC       {ECO:0000305}; Cytoplasmic side {ECO:0000305}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=P59190-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P59190-2; Sequence=VSP_010420;
CC   -!- DOMAIN: Switch 1, switch 2 and the interswitch regions are
CC       characteristic of Rab GTPases and mediate the interactions with Rab
CC       downstream effectors. The switch regions undergo conformational changes
CC       upon nucleotide binding which drives interaction with specific sets of
CC       effector proteins, with most effectors only binding to GTP-bound Rab.
CC       {ECO:0000250|UniProtKB:P62820}.
CC   -!- SIMILARITY: Belongs to the small GTPase superfamily. Rab family.
CC       {ECO:0000305}.
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DR   EMBL; AB678452; BAL14289.1; -; mRNA.
DR   EMBL; AL139022; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471061; EAW80893.1; -; Genomic_DNA.
DR   EMBL; BC040679; AAH40679.2; -; mRNA.
DR   EMBL; BX248046; CAD62353.1; -; mRNA.
DR   CCDS; CCDS76691.1; -. [P59190-1]
DR   CCDS; CCDS9768.1; -. [P59190-2]
DR   RefSeq; NP_001295083.1; NM_001308154.2. [P59190-1]
DR   RefSeq; NP_941959.1; NM_198686.3. [P59190-2]
DR   AlphaFoldDB; P59190; -.
DR   SMR; P59190; -.
DR   BioGRID; 132005; 49.
DR   FunCoup; P59190; 365.
DR   IntAct; P59190; 30.
DR   STRING; 9606.ENSP00000434103; -.
DR   GlyGen; P59190; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P59190; -.
DR   PhosphoSitePlus; P59190; -.
DR   SwissPalm; P59190; -.
DR   BioMuta; RAB15; -.
DR   DMDM; 27734452; -.
DR   jPOST; P59190; -.
DR   MassIVE; P59190; -.
DR   PaxDb; 9606-ENSP00000434103; -.
DR   PeptideAtlas; P59190; -.
DR   ProteomicsDB; 57135; -. [P59190-1]
DR   ProteomicsDB; 57136; -. [P59190-2]
DR   Pumba; P59190; -.
DR   Antibodypedia; 24725; 128 antibodies from 26 providers.
DR   DNASU; 376267; -.
DR   Ensembl; ENST00000267512.9; ENSP00000267512.5; ENSG00000139998.17. [P59190-2]
DR   Ensembl; ENST00000533601.7; ENSP00000434103.3; ENSG00000139998.17. [P59190-1]
DR   Ensembl; ENST00000865638.1; ENSP00000535697.1; ENSG00000139998.17. [P59190-1]
DR   GeneID; 376267; -.
DR   KEGG; hsa:376267; -.
DR   MANE-Select; ENST00000533601.7; ENSP00000434103.3; NM_001308154.2; NP_001295083.1.
DR   UCSC; uc001xhz.2; human. [P59190-1]
DR   AGR; HGNC:20150; -.
DR   ClinPGx; PA134901572; -.
DR   CTD; 376267; -.
DR   DisGeNET; 376267; -.
DR   GeneCards; RAB15; -.
DR   HGNC; HGNC:20150; RAB15.
DR   HPA; ENSG00000139998; Tissue enhanced (brain).
DR   MIM; 619547; gene.
DR   OpenTargets; ENSG00000139998; -.
DR   VEuPathDB; HostDB:ENSG00000139998; -.
DR   GeneTree; ENSGT00940000157848; -.
DR   HOGENOM; CLU_041217_20_0_1; -.
DR   InParanoid; P59190; -.
DR   OMA; AAGDQHK; -.
DR   OrthoDB; 9989112at2759; -.
DR   PAN-GO; P59190; 2 GO annotations based on evolutionary models.
DR   PhylomeDB; P59190; -.
DR   PathwayCommons; P59190; -.
DR   Reactome; R-HSA-8873719; RAB geranylgeranylation.
DR   SignaLink; P59190; -.
DR   Agora; ENSG00000139998; -.
DR   BioGRID-ORCS; 376267; 10 hits in 1147 CRISPR screens.
DR   CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities.
DR   GeneWiki; RAB15; -.
DR   GenomeRNAi; 376267; -.
DR   Pharos; P59190; Tbio.
DR   PRO; PR:P59190; -.
DR   Proteomes; UP000005640; Chromosome 14.
DR   RNAct; P59190; protein.
DR   Bgee; ENSG00000139998; Expressed in right hemisphere of cerebellum and 175 other cell types or tissues.
DR   ExpressionAtlas; P59190; baseline and differential.
DR   GO; GO:0005929; C:cilium; IDA:UniProtKB.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0010008; C:endosome membrane; IDA:UniProtKB.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0003925; F:G protein activity; IDA:GO_Central.
DR   GO; GO:0005525; F:GTP binding; IEA:InterPro.
DR   GO; GO:0003924; F:GTPase activity; ISS:UniProtKB.
DR   GO; GO:0006887; P:exocytosis; IBA:GO_Central.
DR   GO; GO:1903307; P:positive regulation of regulated secretory pathway; IMP:UniProtKB.
DR   GO; GO:0032482; P:Rab protein signal transduction; IEA:InterPro.
DR   GO; GO:0006898; P:receptor-mediated endocytosis; IDA:GO_Central.
DR   CDD; cd04117; Rab15; 1.
DR   FunFam; 3.40.50.300:FF:000990; ras-related protein Rab-15 isoform X1; 1.
DR   Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   InterPro; IPR041826; Rab15.
DR   InterPro; IPR005225; Small_GTP-bd.
DR   InterPro; IPR001806; Small_GTPase.
DR   InterPro; IPR050305; Small_GTPase_Rab.
DR   NCBIfam; TIGR00231; small_GTP; 1.
DR   PANTHER; PTHR47980; LD44762P; 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.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cell membrane; GTP-binding; Hydrolase; Lipoprotein;
KW   Magnesium; Membrane; Metal-binding; Methylation; Nucleotide-binding;
KW   Prenylation; Protein transport; Proteomics identification;
KW   Reference proteome; Transport.
FT   CHAIN           1..212
FT                   /note="Ras-related protein Rab-15"
FT                   /id="PRO_0000121188"
FT   REGION          193..212
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           31..45
FT                   /note="Switch 1"
FT                   /evidence="ECO:0000250|UniProtKB:P62820"
FT   MOTIF           63..80
FT                   /note="Switch 2"
FT                   /evidence="ECO:0000250|UniProtKB:P62820"
FT   BINDING         17
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000250|UniProtKB:P61026"
FT   BINDING         18
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000250|UniProtKB:P61026"
FT   BINDING         19
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000250|UniProtKB:P61026"
FT   BINDING         20
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000250|UniProtKB:P61026"
FT   BINDING         21
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000250|UniProtKB:P61026"
FT   BINDING         22
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000250|UniProtKB:P61026"
FT   BINDING         22
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:P61026"
FT   BINDING         23
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000250|UniProtKB:P61026"
FT   BINDING         35
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000250|UniProtKB:P61026"
FT   BINDING         39
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000250|UniProtKB:P61026"
FT   BINDING         40
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000250|UniProtKB:P61026"
FT   BINDING         40
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:P61026"
FT   BINDING         63
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:P61026"
FT   BINDING         66
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000250|UniProtKB:P61026"
FT   BINDING         121
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000250|UniProtKB:P61026"
FT   BINDING         122
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000250|UniProtKB:P61026"
FT   BINDING         124
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000250|UniProtKB:P61026"
FT   BINDING         151
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000250|UniProtKB:P61026"
FT   BINDING         152
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000250|UniProtKB:P61026"
FT   MOD_RES         212
FT                   /note="Cysteine methyl ester"
FT                   /evidence="ECO:0000250"
FT   LIPID           210
FT                   /note="S-geranylgeranyl cysteine"
FT                   /evidence="ECO:0000250"
FT   LIPID           212
FT                   /note="S-geranylgeranyl cysteine"
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         109..212
FT                   /note="YAPEGVQKILIGNKADEEQKRQVGREQGQQLAKEYGMDFYETSACTNLNIKE
FT                   SFTRLTELVLQAHRKELEGLRMRASNELALAELEEEEGKPEGPANSSKTCWC -> VGD
FT                   ATSLPGCGEGASPGKARRGPDGKANASRKLCLPQPWMKTSGTHQKASRRSLLGIRLMRS
FT                   RNGRWEESKGSSWRRSMAWTSMKQVPAPTSTLKSHSRV (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.1,
FT                   ECO:0000303|Ref.5"
FT                   /id="VSP_010420"
SQ   SEQUENCE   212 AA;  24391 MW;  D16A0C71797ED782 CRC64;
     MAKQYDVLFR LLLIGDSGVG KTCLLCRFTD NEFHSSHIST IGVDFKMKTI EVDGIKVRIQ
     IWDTAGQERY QTITKQYYRR AQGIFLVYDI SSERSYQHIM KWVSDVDEYA PEGVQKILIG
     NKADEEQKRQ VGREQGQQLA KEYGMDFYET SACTNLNIKE SFTRLTELVL QAHRKELEGL
     RMRASNELAL AELEEEEGKP EGPANSSKTC WC
//