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 27-SEP-2017, entry version 135. DE RecName: Full=Ras-related protein Rab-12; GN Name=RAB12; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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., RA Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., RA FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S., RA Bloom T., Bugalter B., Butler J., Cook A., DeCaprio D., Engels R., RA Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T., RA Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E., RA Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H., RA 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., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA 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 RT project: 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., RA Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in RT a refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [6] RP ENZYME 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., RA Buerckstuemmer T., 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 RT GTPases."; RL Biol. Chem. 392:239-248(2011). RN [9] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY RP MASS 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., RA Meinnel T., 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 RP MASS 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., RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., RA Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N- RT terminal 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 X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 36-208 IN COMPLEX WITH RP MAGNESIUM 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 CC intracellular membrane trafficking, from the formation of CC transport vesicles to their fusion with membranes. Rabs cycle CC between an inactive GDP-bound form and an active GTP-bound form CC that is able to recruit to membranes different set of downstream CC effectors directly responsible for vesicle formation, movement, CC tethering and fusion. That Rab may play a role in protein CC 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 -!- ENZYME REGULATION: Rab activation is generally mediated by a CC guanine exchange factor (GEF), while inactivation through CC hydrolysis of bound GTP is catalyzed by a GTPase activating CC protein (GAP) (By similarity). That Rab is activated by DENND3, a CC guanine exchange factor. {ECO:0000250, CC ECO:0000269|PubMed:20937701}. CC -!- SUBUNIT: Interacts with RABIF and OPTN. CC {ECO:0000269|PubMed:21194374, ECO:0000269|Ref.12}. CC -!- INTERACTION: CC Q5S007:LRRK2; NbExp=2; IntAct=EBI-4289591, EBI-5323863; CC -!- SUBCELLULAR LOCATION: Recycling endosome membrane CC {ECO:0000250|UniProtKB:P35283}; Lipid-anchor {ECO:0000305}; CC Cytoplasmic side {ECO:0000305}. Lysosome membrane CC {ECO:0000250|UniProtKB:P35283}; Lipid-anchor {ECO:0000305}; CC Cytoplasmic side {ECO:0000305}. Golgi apparatus membrane CC {ECO:0000250|UniProtKB:P51152}. Cytoplasmic vesicle, autophagosome CC {ECO:0000250|UniProtKB:P35283}. 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; Positions=195; Evidence={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; 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 CCDS; CCDS42410.1; -. DR RefSeq; NP_001020471.2; NM_001025300.2. DR UniGene; Hs.270074; -. DR PDB; 2IL1; X-ray; 2.10 A; A=36-208. DR PDBsum; 2IL1; -. DR ProteinModelPortal; Q6IQ22; -. DR SMR; Q6IQ22; -. DR BioGrid; 128387; 5. DR IntAct; Q6IQ22; 8. DR STRING; 9606.ENSP00000331748; -. DR iPTMnet; Q6IQ22; -. DR PhosphoSitePlus; Q6IQ22; -. DR BioMuta; RAB12; -. DR DMDM; 122064944; -. DR EPD; Q6IQ22; -. DR MaxQB; Q6IQ22; -. DR PaxDb; Q6IQ22; -. DR PeptideAtlas; Q6IQ22; -. DR PRIDE; Q6IQ22; -. DR DNASU; 201475; -. DR Ensembl; ENST00000329286; ENSP00000331748; ENSG00000206418. DR GeneID; 201475; -. DR KEGG; hsa:201475; -. DR UCSC; uc002knp.4; human. DR CTD; 201475; -. DR DisGeNET; 201475; -. DR EuPathDB; HostDB:ENSG00000206418.3; -. DR GeneCards; RAB12; -. DR HGNC; HGNC:31332; RAB12. DR HPA; HPA040727; -. DR MIM; 616448; gene. DR neXtProt; NX_Q6IQ22; -. DR OpenTargets; ENSG00000206418; -. DR PharmGKB; PA142671102; -. DR eggNOG; KOG0078; Eukaryota. DR eggNOG; ENOG410XPUI; LUCA. DR GeneTree; ENSGT00890000139529; -. DR HOGENOM; HOG000233968; -. DR HOVERGEN; HBG009351; -. DR InParanoid; Q6IQ22; -. DR KO; K07907; -. DR OMA; ADFKLQI; -. DR OrthoDB; EOG091G0PS6; -. DR PhylomeDB; Q6IQ22; -. DR TreeFam; TF314097; -. DR Reactome; R-HSA-8873719; RAB geranylgeranylation. DR Reactome; R-HSA-8876198; RAB GEFs exchange GTP for GDP on RABs. DR ChiTaRS; RAB12; human. DR EvolutionaryTrace; Q6IQ22; -. DR GenomeRNAi; 201475; -. DR PRO; PR:Q6IQ22; -. DR Proteomes; UP000005640; Chromosome 18. DR Bgee; ENSG00000206418; -. DR CleanEx; HS_RAB12; -. 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:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005764; C:lysosome; ISS:UniProtKB. DR GO; GO:0055038; C:recycling endosome membrane; ISS:UniProtKB. 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; IEA:InterPro. DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW. DR GO; GO:0044257; P:cellular protein catabolic process; ISS:UniProtKB. DR GO; GO:0008333; P:endosome to lysosome transport; ISS:UniProtKB. DR GO; GO:0061024; P:membrane organization; TAS:Reactome. DR GO; GO:0016239; P:positive regulation of macroautophagy; IEA:Ensembl. DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR005225; Small_GTP-bd_dom. DR InterPro; IPR001806; Small_GTPase. DR Pfam; PF00071; Ras; 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; Complete proteome; KW Cytoplasmic vesicle; Endosome; Golgi apparatus; GTP-binding; KW Lipoprotein; Lysosome; Membrane; Nucleotide-binding; Phosphoprotein; KW Prenylation; Protein transport; Reference proteome; Transport. FT CHAIN 1 244 Ras-related protein Rab-12. FT /FTId=PRO_0000271377. FT NP_BIND 49 57 GTP. FT NP_BIND 97 101 GTP. {ECO:0000250}. FT NP_BIND 155 159 GTP. FT NP_BIND 187 188 GTP. FT MOTIF 71 79 Effector region. {ECO:0000250}. FT MOD_RES 1 1 N-acetylmethionine. FT {ECO:0000244|PubMed:22223895, FT ECO:0000244|PubMed:22814378}. FT MOD_RES 21 21 Phosphoserine. FT {ECO:0000244|PubMed:23186163}. FT MOD_RES 25 25 Phosphoserine. FT {ECO:0000250|UniProtKB:P35283}. FT MOD_RES 106 106 Phosphoserine. FT {ECO:0000244|PubMed:23186163}. FT LIPID 243 243 S-geranylgeranyl cysteine. {ECO:0000250}. FT LIPID 244 244 S-geranylgeranyl cysteine. {ECO:0000250}. FT STRAND 40 48 {ECO:0000244|PDB:2IL1}. FT HELIX 55 62 {ECO:0000244|PDB:2IL1}. FT STRAND 77 86 {ECO:0000244|PDB:2IL1}. FT STRAND 89 98 {ECO:0000244|PDB:2IL1}. FT HELIX 102 104 {ECO:0000244|PDB:2IL1}. FT HELIX 105 114 {ECO:0000244|PDB:2IL1}. FT STRAND 116 123 {ECO:0000244|PDB:2IL1}. FT HELIX 127 131 {ECO:0000244|PDB:2IL1}. FT HELIX 133 143 {ECO:0000244|PDB:2IL1}. FT STRAND 149 155 {ECO:0000244|PDB:2IL1}. FT HELIX 157 162 {ECO:0000244|PDB:2IL1}. FT HELIX 167 175 {ECO:0000244|PDB:2IL1}. FT STRAND 181 184 {ECO:0000244|PDB:2IL1}. FT TURN 187 190 {ECO:0000244|PDB:2IL1}. FT HELIX 193 206 {ECO:0000244|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 //