ID   RAB3D_HUMAN             Reviewed;         219 AA.
AC   O95716;
DT   15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1999, sequence version 1.
DT   27-MAR-2024, entry version 203.
DE   RecName: Full=Ras-related protein Rab-3D;
GN   Name=RAB3D; Synonyms=GOV, RAB16;
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].
RC   TISSUE=Hematopoietic;
RX   PubMed=10023084; DOI=10.1016/s0167-4781(98)00279-6;
RA   Nishio H., Suda T., Sawada K., Miyamoto T., Koike T., Yamaguchi Y.;
RT   "Molecular cloning of cDNA encoding human Rab3D whose expression is
RT   upregulated with myeloid differentiation.";
RL   Biochim. Biophys. Acta 1444:283-290(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Ovary;
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   [4]
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   [5]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP   METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP   [LARGE SCALE ANALYSIS].
RX   PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA   Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA   Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA   Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT   "N-terminal acetylome analyses and functional insights of the N-terminal
RT   acetyltransferase NatB.";
RL   Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN   [6]
RP   INTERACTION WITH CHM AND CHML, PHOSPHORYLATION AT THR-86, AND MUTAGENESIS
RP   OF THR-86.
RX   PubMed=29125462; DOI=10.7554/elife.31012;
RA   Steger M., Diez F., Dhekne H.S., Lis P., Nirujogi R.S., Karayel O.,
RA   Tonelli F., Martinez T.N., Lorentzen E., Pfeffer S.R., Alessi D.R.,
RA   Mann M.;
RT   "Systematic proteomic analysis of LRRK2-mediated Rab GTPase phosphorylation
RT   establishes a connection to ciliogenesis.";
RL   Elife 6:0-0(2017).
RN   [7]
RP   X-RAY CRYSTALLOGRAPHY (1.53 ANGSTROMS) OF 20-189 IN COMPLEX WITH GDP.
RG   Structural genomics consortium (SGC);
RT   "Crystal structure of human RAB3D in complex with GDP.";
RL   Submitted (FEB-2009) to the PDB data bank.
CC   -!- FUNCTION: Protein transport. Probably involved in regulated exocytosis
CC       (By similarity). {ECO:0000250}.
CC   -!- SUBUNIT: Interacts with RIMS1, RIMS2, RPH3A, RPH3AL and RAB3IP (By
CC       similarity). Interacts with CHM and CHML; phosphorylation at Thr-86
CC       disrupts these interactions (PubMed:29125462). Interacts with MADD (via
CC       uDENN domain); the GTP-bound form is preferred for interaction (By
CC       similarity). {ECO:0000250|UniProtKB:P35276,
CC       ECO:0000269|PubMed:29125462}.
CC   -!- INTERACTION:
CC       O95716; Q96QF0-7: RAB3IP; NbExp=3; IntAct=EBI-3386067, EBI-11984839;
CC       O95716; P47224: RABIF; NbExp=3; IntAct=EBI-3386067, EBI-713992;
CC       O95716; Q96C24: SYTL4; NbExp=3; IntAct=EBI-3386067, EBI-747142;
CC       O95716; Q9H8Y1: VRTN; NbExp=3; IntAct=EBI-3386067, EBI-12894399;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Lipid-anchor
CC       {ECO:0000305}; Cytoplasmic side {ECO:0000305}.
CC   -!- TISSUE SPECIFICITY: Highly expressed in granulocytes of peripheral
CC       blood. Constitutively expressed at low levels in all hematopoietic cell
CC       lines investigated.
CC   -!- INDUCTION: Activated in myeloid differentiation.
CC   -!- PTM: Phosphorylation of Thr-86 in the switch II region by LRRK2
CC       prevents the association of RAB regulatory proteins, including CHM and
CC       CHML. {ECO:0000269|PubMed:29125462}.
CC   -!- SIMILARITY: Belongs to the small GTPase superfamily. Rab family.
CC       {ECO:0000305}.
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DR   EMBL; AF081353; AAC72918.1; -; mRNA.
DR   EMBL; AF498933; AAM21081.1; -; mRNA.
DR   EMBL; BC016471; AAH16471.1; -; mRNA.
DR   CCDS; CCDS12257.1; -.
DR   RefSeq; NP_004274.1; NM_004283.3.
DR   PDB; 2GF9; X-ray; 1.53 A; A=20-189.
DR   PDBsum; 2GF9; -.
DR   AlphaFoldDB; O95716; -.
DR   SMR; O95716; -.
DR   BioGRID; 114919; 36.
DR   IntAct; O95716; 14.
DR   STRING; 9606.ENSP00000222120; -.
DR   iPTMnet; O95716; -.
DR   PhosphoSitePlus; O95716; -.
DR   SwissPalm; O95716; -.
DR   BioMuta; RAB3D; -.
DR   EPD; O95716; -.
DR   jPOST; O95716; -.
DR   MassIVE; O95716; -.
DR   MaxQB; O95716; -.
DR   PaxDb; 9606-ENSP00000222120; -.
DR   PeptideAtlas; O95716; -.
DR   ProteomicsDB; 51010; -.
DR   Pumba; O95716; -.
DR   Antibodypedia; 25779; 199 antibodies from 28 providers.
DR   DNASU; 9545; -.
DR   Ensembl; ENST00000222120.8; ENSP00000222120.2; ENSG00000105514.8.
DR   Ensembl; ENST00000589655.1; ENSP00000466000.1; ENSG00000105514.8.
DR   GeneID; 9545; -.
DR   KEGG; hsa:9545; -.
DR   MANE-Select; ENST00000222120.8; ENSP00000222120.2; NM_004283.4; NP_004274.1.
DR   UCSC; uc002mqx.3; human.
DR   AGR; HGNC:9779; -.
DR   CTD; 9545; -.
DR   DisGeNET; 9545; -.
DR   GeneCards; RAB3D; -.
DR   HGNC; HGNC:9779; RAB3D.
DR   HPA; ENSG00000105514; Tissue enhanced (pancreas, skin).
DR   MIM; 604350; gene.
DR   neXtProt; NX_O95716; -.
DR   OpenTargets; ENSG00000105514; -.
DR   PharmGKB; PA34134; -.
DR   VEuPathDB; HostDB:ENSG00000105514; -.
DR   eggNOG; KOG0093; Eukaryota.
DR   GeneTree; ENSGT00940000157552; -.
DR   HOGENOM; CLU_041217_10_1_1; -.
DR   InParanoid; O95716; -.
DR   OMA; CIVTGPP; -.
DR   OrthoDB; 8685at2759; -.
DR   PhylomeDB; O95716; -.
DR   TreeFam; TF313199; -.
DR   PathwayCommons; O95716; -.
DR   Reactome; R-HSA-6798695; Neutrophil degranulation.
DR   Reactome; R-HSA-8873719; RAB geranylgeranylation.
DR   SignaLink; O95716; -.
DR   BioGRID-ORCS; 9545; 19 hits in 1146 CRISPR screens.
DR   ChiTaRS; RAB3D; human.
DR   EvolutionaryTrace; O95716; -.
DR   GeneWiki; RAB3D; -.
DR   GenomeRNAi; 9545; -.
DR   Pharos; O95716; Tbio.
DR   PRO; PR:O95716; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   RNAct; O95716; Protein.
DR   Bgee; ENSG00000105514; Expressed in parotid gland and 172 other cell types or tissues.
DR   ExpressionAtlas; O95716; baseline and differential.
DR   GO; GO:0035577; C:azurophil granule membrane; TAS:Reactome.
DR   GO; GO:0005881; C:cytoplasmic microtubule; IDA:GO_Central.
DR   GO; GO:0005768; C:endosome; IBA:GO_Central.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0099503; C:secretory vesicle; IDA:GO_Central.
DR   GO; GO:0008021; C:synaptic vesicle; IBA:GO_Central.
DR   GO; GO:0042588; C:zymogen granule; IEA:Ensembl.
DR   GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR   GO; GO:0030742; F:GTP-dependent protein binding; IEA:Ensembl.
DR   GO; GO:0003924; F:GTPase activity; IBA:GO_Central.
DR   GO; GO:0031489; F:myosin V binding; IPI:UniProtKB.
DR   GO; GO:0045453; P:bone resorption; IDA:GO_Central.
DR   GO; GO:1903307; P:positive regulation of regulated secretory pathway; IMP:UniProtKB.
DR   GO; GO:0072659; P:protein localization to plasma membrane; IBA:GO_Central.
DR   GO; GO:0009306; P:protein secretion; IBA:GO_Central.
DR   GO; GO:0017157; P:regulation of exocytosis; IBA:GO_Central.
DR   GO; GO:0006904; P:vesicle docking involved in exocytosis; IBA:GO_Central.
DR   CDD; cd01865; Rab3; 1.
DR   Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   InterPro; IPR037872; Rab3.
DR   InterPro; IPR005225; Small_GTP-bd_dom.
DR   InterPro; IPR001806; Small_GTPase.
DR   NCBIfam; TIGR00231; small_GTP; 1.
DR   PANTHER; PTHR47980; LD44762P; 1.
DR   PANTHER; PTHR47980:SF17; RAS-RELATED PROTEIN RAB-3D; 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; O95716; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Cell membrane; Exocytosis; GTP-binding;
KW   Lipoprotein; Membrane; Methylation; Nucleotide-binding; Phosphoprotein;
KW   Prenylation; Protein transport; Reference proteome; Transport.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0007744|PubMed:22814378"
FT   CHAIN           2..219
FT                   /note="Ras-related protein Rab-3D"
FT                   /id="PRO_0000121088"
FT   REGION          190..219
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           51..59
FT                   /note="Effector region"
FT                   /evidence="ECO:0000250"
FT   BINDING         29..37
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0007744|PDB:2GF9"
FT   BINDING         48..54
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000250|UniProtKB:P63012"
FT   BINDING         77..81
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000250|UniProtKB:P62820"
FT   BINDING         135..138
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0007744|PDB:2GF9"
FT   BINDING         165..167
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0007744|PDB:2GF9"
FT   MOD_RES         2
FT                   /note="N-acetylalanine"
FT                   /evidence="ECO:0007744|PubMed:22814378"
FT   MOD_RES         86
FT                   /note="Phosphothreonine; by LRRK2"
FT                   /evidence="ECO:0000269|PubMed:29125462"
FT   MOD_RES         190
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P20337"
FT   MOD_RES         219
FT                   /note="Cysteine methyl ester"
FT                   /evidence="ECO:0000250"
FT   LIPID           217
FT                   /note="S-geranylgeranyl cysteine"
FT                   /evidence="ECO:0000250"
FT   LIPID           219
FT                   /note="S-geranylgeranyl cysteine"
FT                   /evidence="ECO:0000250"
FT   VARIANT         64
FT                   /note="V -> I (in dbSNP:rs3969860)"
FT                   /id="VAR_051710"
FT   MUTAGEN         86
FT                   /note="T->A: Loss of phosphorylation. Reduced binding of
FT                   CHM and CHML binding."
FT                   /evidence="ECO:0000269|PubMed:29125462"
FT   MUTAGEN         86
FT                   /note="T->E: Phosphomimetic mutant. Loss of CHM and CHML
FT                   binding."
FT                   /evidence="ECO:0000269|PubMed:29125462"
FT   STRAND          20..28
FT                   /evidence="ECO:0007829|PDB:2GF9"
FT   HELIX           35..44
FT                   /evidence="ECO:0007829|PDB:2GF9"
FT   STRAND          58..66
FT                   /evidence="ECO:0007829|PDB:2GF9"
FT   STRAND          69..77
FT                   /evidence="ECO:0007829|PDB:2GF9"
FT   HELIX           88..92
FT                   /evidence="ECO:0007829|PDB:2GF9"
FT   STRAND          96..103
FT                   /evidence="ECO:0007829|PDB:2GF9"
FT   HELIX           107..111
FT                   /evidence="ECO:0007829|PDB:2GF9"
FT   HELIX           113..123
FT                   /evidence="ECO:0007829|PDB:2GF9"
FT   STRAND          129..135
FT                   /evidence="ECO:0007829|PDB:2GF9"
FT   HELIX           140..142
FT                   /evidence="ECO:0007829|PDB:2GF9"
FT   HELIX           147..157
FT                   /evidence="ECO:0007829|PDB:2GF9"
FT   STRAND          160..163
FT                   /evidence="ECO:0007829|PDB:2GF9"
FT   TURN            166..169
FT                   /evidence="ECO:0007829|PDB:2GF9"
FT   HELIX           172..187
FT                   /evidence="ECO:0007829|PDB:2GF9"
SQ   SEQUENCE   219 AA;  24267 MW;  714754826C405EA7 CRC64;
     MASAGDTQAG PRDAADQNFD YMFKLLLIGN SSVGKTSFLF RYADDSFTPA FVSTVGIDFK
     VKTVYRHDKR IKLQIWDTAG QERYRTITTA YYRGAMGFLL MYDIANQESF AAVQDWATQI
     KTYSWDNAQV ILVGNKCDLE DERVVPAEDG RRLADDLGFE FFEASAKENI NVKQVFERLV
     DVICEKMNES LEPSSSSGSN GKGPAVGDAP APQPSSCSC
//