RAB3D_HUMAN
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 03-AUG-2022, entry version 194.
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; 31.
DR IntAct; O95716; 12.
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; O95716; -.
DR PeptideAtlas; O95716; -.
DR PRIDE; O95716; -.
DR ProteomicsDB; 51010; -.
DR Antibodypedia; 25779; 165 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 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; 1218073at2759; -.
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; 16 hits in 1067 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 170 other tissues.
DR ExpressionAtlas; O95716; baseline and differential.
DR Genevisible; O95716; HS.
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:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
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:0018125; P:peptidyl-cysteine methylation; IEA:Ensembl.
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; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR037872; Rab3.
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; 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
