RAB12_HUMAN
ID RAB12_HUMAN Reviewed; 244 AA.
AC Q6IQ22; A6NEF5; Q4KMQ3;
DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Ras-related protein Rab-12;
GN Name=RAB12;
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [6]
RP ACTIVITY REGULATION.
RX PubMed=20937701; DOI=10.1083/jcb.201008051;
RA Yoshimura S., Gerondopoulos A., Linford A., Rigden D.J., Barr F.A.;
RT "Family-wide characterization of the DENN domain Rab GDP-GTP exchange
RT factors.";
RL J. Cell Biol. 191:367-381(2010).
RN [7]
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 [8]
RP INTERACTION WITH RABIF.
RX PubMed=21194374; DOI=10.1515/bc.2011.022;
RA Wixler V., Wixler L., Altenfeld A., Ludwig S., Goody R.S., Itzen A.;
RT "Identification and characterisation of novel Mss4-binding Rab GTPases.";
RL Biol. Chem. 392:239-248(2011).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [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 [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21 AND SER-106, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and 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 [12]
RP INTERACTION WITH LRRK2; GDI1 AND GDI2, PHOSPHORYLATION AT SER-106, AND
RP MUTAGENESIS OF SER-106.
RX PubMed=26824392; DOI=10.7554/elife.12813;
RA Steger M., Tonelli F., Ito G., Davies P., Trost M., Vetter M., Wachter S.,
RA Lorentzen E., Duddy G., Wilson S., Baptista M.A., Fiske B.K., Fell M.J.,
RA Morrow J.A., Reith A.D., Alessi D.R., Mann M.;
RT "Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates
RT a subset of Rab GTPases.";
RL Elife 5:0-0(2016).
RN [13]
RP INTERACTION WITH GDI1; GDI2; CHM; CHML; RILPL1 AND RILPL2, PHOSPHORYLATION
RP AT SER-106, AND MUTAGENESIS OF SER-106.
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 [14]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 36-208 IN COMPLEX WITH MAGNESIUM
RP AND GDP.
RG Structural genomics consortium (SGC);
RT "Crystal structure of a predicted human GTPase in complex with GDP.";
RL Submitted (FEB-2009) to the PDB data bank.
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. Rabs cycle between an inactive GDP-bound form
CC and an active GTP-bound form that is able to recruit to membranes
CC different set of downstream effectors directly responsible for vesicle
CC formation, movement, tethering and fusion. That Rab may play a role in
CC protein transport from recycling endosomes to lysosomes regulating, for
CC instance, the degradation of the transferrin receptor. Involved in
CC autophagy (By similarity). {ECO:0000250}.
CC -!- ACTIVITY REGULATION: Rab activation is generally mediated by a guanine
CC exchange factor (GEF), while inactivation through hydrolysis of bound
CC GTP is catalyzed by a GTPase activating protein (GAP) (By similarity).
CC That Rab is activated by DENND3, a guanine exchange factor.
CC {ECO:0000250, ECO:0000269|PubMed:20937701}.
CC -!- SUBUNIT: Interacts with RABIF (PubMed:21194374). Interacts with OPTN
CC (By similarity). Interacts with LRRK2; interaction facilitates
CC phosphorylation of Ser-106 (PubMed:26824392). Interacts with GDI1,
CC GDI2, CHM and CHML; these interactions are disrupted by phosphorylation
CC on Ser-106 (PubMed:26824392, PubMed:29125462). Interacts with RILPL1
CC and RILPL2; these interactions are dependent on phosphorylation of Ser-
CC 106 (PubMed:26824392, PubMed:29125462). {ECO:0000250|UniProtKB:P35283,
CC ECO:0000269|PubMed:21194374, ECO:0000269|PubMed:26824392,
CC ECO:0000269|PubMed:29125462}.
CC -!- INTERACTION:
CC Q6IQ22; Q5S007: LRRK2; NbExp=2; IntAct=EBI-4289591, EBI-5323863;
CC -!- SUBCELLULAR LOCATION: Recycling endosome membrane
CC {ECO:0000250|UniProtKB:P35283}; Lipid-anchor {ECO:0000305}; Cytoplasmic
CC side {ECO:0000305}. Lysosome membrane {ECO:0000250|UniProtKB:P35283};
CC Lipid-anchor {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Golgi
CC apparatus membrane {ECO:0000250|UniProtKB:P51152}. Cytoplasmic vesicle,
CC autophagosome {ECO:0000250|UniProtKB:P35283}.
CC -!- PTM: Phosphorylation of Ser-106 in the switch II region by LRRK2
CC prevents the association of RAB regulatory proteins, including CHM,
CC CHML and RAB GDP dissociation inhibitors GDI1 and GDI2.
CC {ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:29125462}.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rab family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH71600.2; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
CC Sequence=AAH98407.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
CC Sequence=BC050338; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AP001793; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471113; EAX01616.1; -; Genomic_DNA.
DR EMBL; BC050338; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC071600; AAH71600.2; ALT_SEQ; mRNA.
DR EMBL; BC098407; AAH98407.1; ALT_SEQ; mRNA.
DR RefSeq; NP_001020471.2; NM_001025300.2.
DR PDB; 2IL1; X-ray; 2.10 A; A=36-208.
DR PDBsum; 2IL1; -.
DR AlphaFoldDB; Q6IQ22; -.
DR SMR; Q6IQ22; -.
DR BioGRID; 128387; 17.
DR IntAct; Q6IQ22; 11.
DR STRING; 9606.ENSP00000331748; -.
DR iPTMnet; Q6IQ22; -.
DR PhosphoSitePlus; Q6IQ22; -.
DR BioMuta; RAB12; -.
DR DMDM; 122064944; -.
DR EPD; Q6IQ22; -.
DR jPOST; Q6IQ22; -.
DR MassIVE; Q6IQ22; -.
DR MaxQB; Q6IQ22; -.
DR PaxDb; Q6IQ22; -.
DR PeptideAtlas; Q6IQ22; -.
DR PRIDE; Q6IQ22; -.
DR ProteomicsDB; 66478; -.
DR Antibodypedia; 41715; 127 antibodies from 23 providers.
DR DNASU; 201475; -.
DR GeneID; 201475; -.
DR KEGG; hsa:201475; -.
DR UCSC; uc002knp.4; human.
DR CTD; 201475; -.
DR DisGeNET; 201475; -.
DR GeneCards; RAB12; -.
DR HGNC; HGNC:31332; RAB12.
DR HPA; ENSG00000206418; Tissue enhanced (skeletal).
DR MIM; 616448; gene.
DR neXtProt; NX_Q6IQ22; -.
DR PharmGKB; PA142671102; -.
DR VEuPathDB; HostDB:ENSG00000206418; -.
DR eggNOG; KOG0078; Eukaryota.
DR eggNOG; KOG0395; Eukaryota.
DR HOGENOM; CLU_041217_2_1_1; -.
DR InParanoid; Q6IQ22; -.
DR OrthoDB; 1149105at2759; -.
DR PhylomeDB; Q6IQ22; -.
DR TreeFam; TF314097; -.
DR PathwayCommons; Q6IQ22; -.
DR Reactome; R-HSA-8873719; RAB geranylgeranylation.
DR Reactome; R-HSA-8876198; RAB GEFs exchange GTP for GDP on RABs.
DR SignaLink; Q6IQ22; -.
DR SIGNOR; Q6IQ22; -.
DR BioGRID-ORCS; 201475; 12 hits in 1074 CRISPR screens.
DR ChiTaRS; RAB12; human.
DR EvolutionaryTrace; Q6IQ22; -.
DR GenomeRNAi; 201475; -.
DR Pharos; Q6IQ22; Tbio.
DR PRO; PR:Q6IQ22; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; Q6IQ22; protein.
DR Genevisible; Q6IQ22; HS.
DR GO; GO:0005776; C:autophagosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005768; C:endosome; IBA:GO_Central.
DR GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0032593; C:insulin-responsive compartment; IBA:GO_Central.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0055037; C:recycling endosome; IBA:GO_Central.
DR GO; GO:0055038; C:recycling endosome membrane; ISS:UniProtKB.
DR GO; GO:0008021; C:synaptic vesicle; IBA:GO_Central.
DR GO; GO:0019003; F:GDP binding; IDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0003924; F:GTPase activity; IBA:GO_Central.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IBA:GO_Central.
DR GO; GO:0008333; P:endosome to lysosome transport; ISS:UniProtKB.
DR GO; GO:0030163; P:protein catabolic process; ISS: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:0032482; P:Rab protein signal transduction; IEA:InterPro.
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; cd04120; Rab12; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR041830; Rab12.
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; Autophagy; Cytoplasmic vesicle; Endosome;
KW Golgi apparatus; GTP-binding; Lipoprotein; Lysosome; Membrane;
KW Nucleotide-binding; Phosphoprotein; Prenylation; Protein transport;
KW Reference proteome; Transport.
FT CHAIN 1..244
FT /note="Ras-related protein Rab-12"
FT /id="PRO_0000271377"
FT REGION 1..37
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 225..244
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 71..79
FT /note="Effector region"
FT /evidence="ECO:0000250"
FT BINDING 49..57
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT BINDING 97..101
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 155..159
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT BINDING 187..188
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:22814378"
FT MOD_RES 21
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 25
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35283"
FT MOD_RES 106
FT /note="Phosphoserine; by LRRK2"
FT /evidence="ECO:0000269|PubMed:26824392,
FT ECO:0000269|PubMed:29125462, ECO:0007744|PubMed:23186163"
FT LIPID 243
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 244
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000250"
FT MUTAGEN 106
FT /note="S->A: Loss of phosphorylation. No effect on GDI1 and
FT GDI2 binding."
FT /evidence="ECO:0000269|PubMed:26824392,
FT ECO:0000269|PubMed:29125462"
FT MUTAGEN 106
FT /note="S->E: Phosphomimetic mutant. Loss of GDI1, GDI2, CHM
FT and CHML binding."
FT /evidence="ECO:0000269|PubMed:26824392,
FT ECO:0000269|PubMed:29125462"
FT STRAND 40..48
FT /evidence="ECO:0007829|PDB:2IL1"
FT HELIX 55..62
FT /evidence="ECO:0007829|PDB:2IL1"
FT STRAND 77..86
FT /evidence="ECO:0007829|PDB:2IL1"
FT STRAND 89..98
FT /evidence="ECO:0007829|PDB:2IL1"
FT HELIX 102..104
FT /evidence="ECO:0007829|PDB:2IL1"
FT HELIX 105..114
FT /evidence="ECO:0007829|PDB:2IL1"
FT STRAND 116..123
FT /evidence="ECO:0007829|PDB:2IL1"
FT HELIX 127..131
FT /evidence="ECO:0007829|PDB:2IL1"
FT HELIX 133..143
FT /evidence="ECO:0007829|PDB:2IL1"
FT STRAND 149..155
FT /evidence="ECO:0007829|PDB:2IL1"
FT HELIX 157..162
FT /evidence="ECO:0007829|PDB:2IL1"
FT HELIX 167..175
FT /evidence="ECO:0007829|PDB:2IL1"
FT STRAND 181..184
FT /evidence="ECO:0007829|PDB:2IL1"
FT TURN 187..190
FT /evidence="ECO:0007829|PDB:2IL1"
FT HELIX 193..206
FT /evidence="ECO:0007829|PDB:2IL1"
SQ SEQUENCE 244 AA; 27248 MW; B4DC65DD0DCB45C4 CRC64;
MDPGAALQRR AGGGGGLGAG SPALSGGQGR RRKQPPRPAD FKLQVIIIGS RGVGKTSLME
RFTDDTFCEA CKSTVGVDFK IKTVELRGKK IRLQIWDTAG QERFNSITSA YYRSAKGIIL
VYDITKKETF DDLPKWMKMI DKYASEDAEL LLVGNKLDCE TDREITRQQG EKFAQQITGM
RFCEASAKDN FNVDEIFLKL VDDILKKMPL DILRNELSNS ILSLQPEPEI PPELPPPRPH
VRCC
