ID RAB12_RAT Reviewed; 243 AA. AC P35284; DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot. DT 06-FEB-2013, sequence version 2. DT 08-NOV-2023, entry version 155. DE RecName: Full=Ras-related protein Rab-12; GN Name=Rab12; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Brown Norway; RX PubMed=15057822; DOI=10.1038/nature02426; RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., RA Mockrin S., Collins F.S.; RT "Genome sequence of the Brown Norway rat yields insights into mammalian RT evolution."; RL Nature 428:493-521(2004). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] OF 47-243. RC STRAIN=Sprague-Dawley; TISSUE=Brain; RX PubMed=1313420; DOI=10.1016/s0021-9258(18)42619-1; RA Elferink L.A., Anzai K., Scheller R.H.; RT "Rab15, a novel low molecular weight GTP-binding protein specifically RT expressed in rat brain."; RL J. Biol. Chem. 267:5768-5775(1992). RN [3] RP TISSUE SPECIFICITY. RX PubMed=15791598; DOI=10.1002/mrd.20294; RA Iida H., Noda M., Kaneko T., Doiguchi M., Mori T.; RT "Identification of rab12 as a vesicle-associated small GTPase highly RT expressed in Sertoli cells of rat testis."; RL Mol. Reprod. Dev. 71:178-185(2005). RN [4] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-20, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22673903; DOI=10.1038/ncomms1871; RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., RA Olsen J.V.; RT "Quantitative maps of protein phosphorylation sites across 14 different rat RT organs and tissues."; RL Nat. Commun. 3:876-876(2012). 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). That Rab is CC activated by DENND3, a guanine exchange factor (By similarity). CC {ECO:0000250}. CC -!- SUBUNIT: Interacts with RABIF and OPTN (By similarity). Interacts with CC LRRK2; interaction facilitates phosphorylation of Ser-105 (By CC similarity). Interacts with GDI1, GDI2 and CHM; these interactions are CC disrupted by phosphorylation on Ser-105 (By similarity). Interacts with CC RILPL1 and RILPL2; these interactions are dependent on phosphorylation CC of Ser-105 (By similarity). {ECO:0000250|UniProtKB:Q6IQ22}. 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 -!- TISSUE SPECIFICITY: Highest levels in skeletal and cardiac muscle. Also CC found in comparable amounts in brain, spinal cord and lung. Also CC detected in testis where it is expressed by Sertoli cells of the CC seminiferous tubules (at protein level). {ECO:0000269|PubMed:15791598}. CC -!- PTM: Phosphorylation of Ser-105 in the switch II region by LRRK2 CC prevents the association of RAB regulatory proteins, including CHM and CC 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M83676; AAA41992.1; -; mRNA. DR PIR; C42148; C42148. DR RefSeq; NP_037149.1; NM_013017.1. DR AlphaFoldDB; P35284; -. DR SMR; P35284; -. DR DIP; DIP-36918N; -. DR IntAct; P35284; 2. DR STRING; 10116.ENSRNOP00000059602; -. DR iPTMnet; P35284; -. DR PhosphoSitePlus; P35284; -. DR jPOST; P35284; -. DR PaxDb; 10116-ENSRNOP00000059602; -. DR GeneID; 25530; -. DR KEGG; rno:25530; -. DR AGR; RGD:3527; -. DR CTD; 201475; -. DR RGD; 3527; Rab12. DR eggNOG; KOG0078; Eukaryota. DR InParanoid; P35284; -. DR OrthoDB; 5357878at2759; -. DR Reactome; R-RNO-8873719; RAB geranylgeranylation. DR Reactome; R-RNO-8876198; RAB GEFs exchange GTP for GDP on RABs. DR PRO; PR:P35284; -. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0005776; C:autophagosome; ISO:RGD. DR GO; GO:0005768; C:endosome; IBA:GO_Central. DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005764; C:lysosome; ISS:UniProtKB. DR GO; GO:0045335; C:phagocytic vesicle; ISO:RGD. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0055038; C:recycling endosome membrane; ISS:UniProtKB. DR GO; GO:0030141; C:secretory granule; IDA:RGD. DR GO; GO:0008021; C:synaptic vesicle; IBA:GO_Central. DR GO; GO:0030140; C:trans-Golgi network transport vesicle; IBA:GO_Central. DR GO; GO:0019003; F:GDP binding; ISS:UniProtKB. DR GO; GO:0005525; F:GTP binding; TAS:RGD. DR GO; GO:0003924; F:GTPase activity; IBA:GO_Central. DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW. DR GO; GO:0071346; P:cellular response to type II interferon; ISO:RGD. DR GO; GO:0032456; P:endocytic recycling; IBA:GO_Central. DR GO; GO:0008333; P:endosome to lysosome transport; ISS:UniProtKB. DR GO; GO:0048210; P:Golgi vesicle fusion to target membrane; IBA:GO_Central. DR GO; GO:0016239; P:positive regulation of macroautophagy; ISO:RGD. 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; P-loop containing nucleotide triphosphate hydrolases; 1. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR041830; Rab12. 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:SF35; RAS-RELATED PROTEIN RAB-12; 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 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_0000121181" 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 20 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 24 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P35283" FT MOD_RES 105 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6IQ22" 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 CONFLICT 152 FT /note="V -> A (in Ref. 2; AAA41992)" FT /evidence="ECO:0000305" FT CONFLICT 181 FT /note="F -> L (in Ref. 2; AAA41992)" FT /evidence="ECO:0000305" FT CONFLICT 182 FT /note="C -> S (in Ref. 2; AAA41992)" FT /evidence="ECO:0000305" FT CONFLICT 184 FT /note="A -> P (in Ref. 2; AAA41992)" FT /evidence="ECO:0000305" SQ SEQUENCE 243 AA; 27271 MW; 237A9421E6784584 CRC64; MDPSAALHRR PAGGGLGAVS PALSGGQARR RKQPPRPADF KLQVIIIGSR GVGKTSLMER FTDDTFCEAC KSTVGVDFKI KTVELRGKKI RLQIWDTAGQ ERFNSITSAY YRSAKGIILV YDITKKETFD DLPKWMKMID KYASEDAELL LVGNKLDCET DREISRQQGE KFAQQITGMR FCEASAKDNF NVDEIFLKLV DDILKKMPLD VLRSELSNSI LSLQPEPEIP PELPPPRPHV RCC //