RAB12_MOUSE
ID RAB12_MOUSE Reviewed; 243 AA.
AC P35283; Q0PD43; Q9CUW7;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Ras-related protein Rab-12;
DE AltName: Full=Rab-13;
GN Name=Rab12;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=16923123; DOI=10.1111/j.1365-2443.2006.00997.x;
RA Itoh T., Satoh M., Kanno E., Fukuda M.;
RT "Screening for target Rabs of TBC (Tre-2/Bub2/Cdc16) domain-containing
RT proteins based on their Rab-binding activity.";
RL Genes Cells 11:1023-1037(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 53-101.
RC TISSUE=Kidney;
RX PubMed=1555775; DOI=10.1016/0378-1119(92)90387-5;
RA Chavrier P., Simons K., Zerial M.;
RT "The complexity of the Rab and Rho GTP-binding protein subfamilies revealed
RT by a PCR cloning approach.";
RL Gene 112:261-264(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 83-243.
RC STRAIN=C57BL/6J; TISSUE=Hippocampus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain cortex;
RX PubMed=17114649; DOI=10.1074/mcp.m600046-mcp200;
RA Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F.,
RA Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B.,
RA Panse C., Schlapbach R., Mansuy I.M.;
RT "Qualitative and quantitative analyses of protein phosphorylation in naive
RT and stimulated mouse synaptosomal preparations.";
RL Mol. Cell. Proteomics 6:283-293(2007).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-15; SER-20 AND SER-105, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-20, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT "Large scale localization of protein phosphorylation by use of electron
RT capture dissociation mass spectrometry.";
RL Mol. Cell. Proteomics 8:904-912(2009).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-15; SER-20; SER-24 AND
RP SER-105, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Lung, Pancreas, Spleen,
RC and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MUTAGENESIS OF GLN-100,
RP AND ACTIVITY REGULATION.
RX PubMed=21718402; DOI=10.1111/j.1600-0854.2011.01240.x;
RA Matsui T., Itoh T., Fukuda M.;
RT "Small GTPase Rab12 regulates constitutive degradation of transferrin
RT receptor.";
RL Traffic 12:1432-1443(2011).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH OPTN.
RX PubMed=23357852; DOI=10.4161/auto.23458;
RA Sirohi K., Chalasani M.L., Sudhakar C., Kumari A., Radha V., Swarup G.;
RT "M98K-OPTN induces transferrin receptor degradation and RAB12-mediated
RT autophagic death in retinal ganglion cells.";
RL Autophagy 9:510-527(2013).
RN [10]
RP PHOSPHORYLATION AT SER-105.
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 [11]
RP PHOSPHORYLATION AT SER-105.
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).
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 (By similarity). That Rab may
CC play a role in protein transport from recycling endosomes to lysosomes
CC regulating, for instance, the degradation of the transferrin receptor.
CC Involved in autophagy. {ECO:0000250, ECO:0000269|PubMed:21718402,
CC ECO:0000269|PubMed:23357852}.
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:21718402}.
CC -!- SUBUNIT: Interacts with RABIF and OPTN (PubMed:23357852). Interacts
CC with LRRK2; interaction facilitates phosphorylation of Ser-105 (By
CC similarity). Interacts with GDI1, GDI2, CHM and CHML; these
CC interactions are disrupted by phosphorylation on Ser-105 (By
CC similarity). Interacts with RILPL1 and RILPL2; these interactions are
CC dependent on phosphorylation of Ser-105 (By similarity).
CC {ECO:0000250|UniProtKB:Q6IQ22, ECO:0000269|PubMed:23357852}.
CC -!- SUBCELLULAR LOCATION: Recycling endosome membrane
CC {ECO:0000269|PubMed:21718402}; Lipid-anchor {ECO:0000305}; Cytoplasmic
CC side {ECO:0000305}. Lysosome membrane {ECO:0000269|PubMed:21718402};
CC Lipid-anchor {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Golgi
CC apparatus membrane {ECO:0000250|UniProtKB:P51152}. Cytoplasmic vesicle,
CC autophagosome {ECO:0000269|PubMed:23357852}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:21718402}.
CC -!- PTM: Phosphorylation of Ser-105 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:0000250|UniProtKB:Q6IQ22}.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rab family.
CC {ECO:0000305}.
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DR EMBL; AB232607; BAF02869.1; -; mRNA.
DR EMBL; M79303; AAK14827.1; -; mRNA.
DR EMBL; AK013690; BAB28956.1; -; mRNA.
DR PIR; JH0643; JH0643.
DR RefSeq; NP_077768.2; NM_024448.2.
DR AlphaFoldDB; P35283; -.
DR SMR; P35283; -.
DR BioGRID; 202534; 3.
DR IntAct; P35283; 5.
DR MINT; P35283; -.
DR STRING; 10090.ENSMUSP00000070134; -.
DR iPTMnet; P35283; -.
DR PhosphoSitePlus; P35283; -.
DR jPOST; P35283; -.
DR MaxQB; P35283; -.
DR PaxDb; P35283; -.
DR PeptideAtlas; P35283; -.
DR PRIDE; P35283; -.
DR ProteomicsDB; 253140; -.
DR Antibodypedia; 41715; 127 antibodies from 23 providers.
DR DNASU; 19328; -.
DR GeneID; 19328; -.
DR KEGG; mmu:19328; -.
DR UCSC; uc008djy.1; mouse.
DR CTD; 201475; -.
DR MGI; MGI:894284; Rab12.
DR VEuPathDB; HostDB:ENSMUSG00000023460; -.
DR eggNOG; KOG0078; Eukaryota.
DR eggNOG; KOG0395; Eukaryota.
DR HOGENOM; CLU_041217_2_1_1; -.
DR InParanoid; P35283; -.
DR OrthoDB; 1149105at2759; -.
DR PhylomeDB; P35283; -.
DR Reactome; R-MMU-8873719; RAB geranylgeranylation.
DR Reactome; R-MMU-8876198; RAB GEFs exchange GTP for GDP on RABs.
DR BioGRID-ORCS; 19328; 3 hits in 72 CRISPR screens.
DR ChiTaRS; Rab12; mouse.
DR PRO; PR:P35283; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; P35283; protein.
DR Bgee; ENSMUSG00000023460; Expressed in hindlimb stylopod muscle and 256 other tissues.
DR ExpressionAtlas; P35283; baseline and differential.
DR Genevisible; P35283; MM.
DR GO; GO:0005776; C:autophagosome; IDA:UniProtKB.
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; IDA:UniProtKB.
DR GO; GO:0045335; C:phagocytic vesicle; IDA:MGI.
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; IDA:UniProtKB.
DR GO; GO:0030141; C:secretory granule; ISO:MGI.
DR GO; GO:0008021; C:synaptic vesicle; IBA:GO_Central.
DR GO; GO:0019003; F:GDP binding; ISS: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:0071346; P:cellular response to interferon-gamma; IDA:MGI.
DR GO; GO:0008333; P:endosome to lysosome transport; IMP:UniProtKB.
DR GO; GO:0016239; P:positive regulation of macroautophagy; IMP:UniProtKB.
DR GO; GO:0030163; P:protein catabolic process; 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: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 Acetylation; Autophagy; Cytoplasmic vesicle; Endosome; Golgi apparatus;
KW GTP-binding; Lipoprotein; Lysosome; Membrane; Nucleotide-binding;
KW Phosphoprotein; Prenylation; Protein transport; Reference proteome;
KW Transport.
FT CHAIN 1..243
FT /note="Ras-related protein Rab-12"
FT /id="PRO_0000121180"
FT REGION 1..36
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 70..78
FT /note="Effector region"
FT /evidence="ECO:0000250"
FT BINDING 48..56
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 96..100
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 154..158
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 186..187
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q6IQ22"
FT MOD_RES 15
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 20
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19131326,
FT ECO:0007744|PubMed:19144319, ECO:0007744|PubMed:21183079"
FT MOD_RES 24
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 105
FT /note="Phosphoserine; by LRRK2"
FT /evidence="ECO:0000269|PubMed:26824392,
FT ECO:0000269|PubMed:29125462, ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT LIPID 242
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 243
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000250"
FT MUTAGEN 100
FT /note="Q->L: Probable constitutively active mutant unable
FT to hydrolyze GTP; increases degradation of the transferrin
FT receptor."
FT /evidence="ECO:0000269|PubMed:21718402"
FT CONFLICT 83
FT /note="V -> L (in Ref. 3; BAB28956)"
FT /evidence="ECO:0000305"
FT CONFLICT 86
FT /note="R -> T (in Ref. 3; BAB28956)"
FT /evidence="ECO:0000305"
FT CONFLICT 184..185
FT /note="AS -> PD (in Ref. 3; BAB28956)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 243 AA; 27329 MW; 34E4EDC67F710510 CRC64;
MDPSAALHRR PAGGSLGAVS PALSGGQARR RKQPPRPADF KLQVIIIGSR GVGKTSLMER
FTDDTFCEAC KSTVGVDFKI KTVELRGKKI RLQIWDTAGQ ERFNSITSAY YRSAKGIILV
YDITKKETFD DLPKWMKMID KYASEDAELL LVGNKLDCET DREISRQQGE KFAQQITGMR
FCEASAKDNF NVDEIFLKLV DDILKKMPLD VLRNELSNSI LSLQPEPEIP PELPPPRPHV
RCC
