RAB12_RAT
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 03-AUG-2022, entry version 150.
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}.
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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; P35284; -.
DR PRIDE; P35284; -.
DR GeneID; 25530; -.
DR KEGG; rno:25530; -.
DR CTD; 201475; -.
DR RGD; 3527; Rab12.
DR eggNOG; KOG0078; Eukaryota.
DR InParanoid; P35284; -.
DR OrthoDB; 1149105at2759; -.
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: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:0045335; C:phagocytic vesicle; ISO:RGD.
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:0030141; C:secretory granule; IDA:RGD.
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; TAS:RGD.
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; ISO:RGD.
DR GO; GO:0008333; P:endosome to lysosome transport; ISS:UniProtKB.
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; -; 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_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
