ID MOK_HUMAN Reviewed; 419 AA. AC Q9UQ07; B2R6Z4; B7Z7P6; E7ER76; E7ERR8; Q92790; Q93067; DT 16-JAN-2004, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 1. DT 27-MAR-2024, entry version 187. DE RecName: Full=MAPK/MAK/MRK overlapping kinase; DE EC=2.7.11.22 {ECO:0000250|UniProtKB:Q9WVS4}; DE AltName: Full=MOK protein kinase; DE AltName: Full=Renal tumor antigen 1; DE Short=RAGE-1; GN Name=MOK; Synonyms=RAGE, RAGE1; 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 [MRNA] (ISOFORM 1). RC TISSUE=Fetal brain; RX PubMed=10421840; DOI=10.1046/j.1365-2443.1999.00261.x; RA Miyata Y., Akashi M., Nishida E.; RT "Molecular cloning and characterization of a novel member of the MAP kinase RT superfamily."; RL Genes Cells 4:299-309(1999). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4). RC TISSUE=Renal cell carcinoma; RX PubMed=8781117; DOI=10.1007/bf02602776; RA Gaugler B., Brouwenstijn N., Vantomme V., Szikora J.-P., Van der Spek C.W., RA Patard J.-J., Boon T., Schrier P., Van den Eynde B.J.; RT "A new gene coding for an antigen recognized by autologous cytolytic T RT lymphocytes on a human renal carcinoma."; RL Immunogenetics 44:323-330(1996). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5), AND VARIANT ILE-217. RC TISSUE=Testis; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12508121; DOI=10.1038/nature01348; RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., RA Waterston R., Hood L., Weissenbach J.; RT "The DNA sequence and analysis of human chromosome 14."; RL Nature 421:601-607(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain, Lung, and Testis; 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 [6] RP VARIANTS [LARGE SCALE ANALYSIS] HIS-38; ASN-86; ARG-230; SER-248; ASP-272 RP AND ARG-398. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., RA Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). CC -!- FUNCTION: Able to phosphorylate several exogenous substrates and to CC undergo autophosphorylation. Negatively regulates cilium length in a CC cAMP and mTORC1 signaling-dependent manner. CC {ECO:0000250|UniProtKB:Q9WVS4}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.22; CC Evidence={ECO:0000250|UniProtKB:Q9WVS4}; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; CC EC=2.7.11.22; Evidence={ECO:0000250|UniProtKB:Q9WVS4}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000250|UniProtKB:Q9WVS4}; CC -!- ACTIVITY REGULATION: Phosphorylation appears to increase the enzymatic CC activity. {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9WVS4}. Cell CC projection, cilium {ECO:0000250|UniProtKB:Q9WVS4}. Nucleus CC {ECO:0000250|UniProtKB:Q9WVS4}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=6; CC Name=1; CC IsoId=Q9UQ07-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9UQ07-2; Sequence=VSP_009144; CC Name=3; Synonyms=RAGE-1 ORF5, RAGE-2 ORF5, RAGE-3 ORF5; CC IsoId=Q9UQ07-3; Sequence=VSP_009143; CC Name=4; Synonyms=RAGE-4 ORF3; CC IsoId=Q9UQ07-4; Sequence=VSP_009142, VSP_009145, VSP_009146; CC Name=5; CC IsoId=Q9UQ07-5; Sequence=VSP_054734; CC Name=6; CC IsoId=Q9UQ07-6; Sequence=VSP_054735; CC -!- TISSUE SPECIFICITY: Expressed in heart, brain, lung, kidney, and CC pancreas, and at very low levels in placenta, liver and skeletal CC muscle. Detected in retina. CC -!- PTM: Autophosphorylated. {ECO:0000250}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr CC protein kinase family. CDC2/CDKX subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAB38087.1; Type=Frameshift; 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; AB022694; BAA81688.1; -; mRNA. DR EMBL; U46191; AAB38079.1; -; mRNA. DR EMBL; U46192; AAB38082.1; -; mRNA. DR EMBL; U46193; AAB38085.1; -; mRNA. DR EMBL; U46194; AAB38087.1; ALT_FRAME; mRNA. DR EMBL; AK302349; BAH13682.1; -; mRNA. DR EMBL; AK312778; BAG35641.1; -; mRNA. DR EMBL; AL352978; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL359402; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC053536; AAH53536.1; -; mRNA. DR CCDS; CCDS61552.1; -. [Q9UQ07-5] DR CCDS; CCDS81854.1; -. [Q9UQ07-6] DR CCDS; CCDS9971.1; -. [Q9UQ07-1] DR RefSeq; NP_001258940.1; NM_001272011.1. [Q9UQ07-5] DR RefSeq; NP_001317163.1; NM_001330234.1. [Q9UQ07-6] DR RefSeq; NP_055041.1; NM_014226.2. [Q9UQ07-1] DR AlphaFoldDB; Q9UQ07; -. DR SMR; Q9UQ07; -. DR BioGRID; 111828; 26. DR IntAct; Q9UQ07; 14. DR MINT; Q9UQ07; -. DR STRING; 9606.ENSP00000355304; -. DR BindingDB; Q9UQ07; -. DR ChEMBL; CHEMBL4295983; -. DR iPTMnet; Q9UQ07; -. DR PhosphoSitePlus; Q9UQ07; -. DR BioMuta; MOK; -. DR EPD; Q9UQ07; -. DR MassIVE; Q9UQ07; -. DR PaxDb; 9606-ENSP00000355304; -. DR PeptideAtlas; Q9UQ07; -. DR TopDownProteomics; Q9UQ07-4; -. [Q9UQ07-4] DR ABCD; Q9UQ07; 8 sequenced antibodies. DR Antibodypedia; 27789; 476 antibodies from 33 providers. DR DNASU; 5891; -. DR Ensembl; ENST00000361847.7; ENSP00000355304.2; ENSG00000080823.23. [Q9UQ07-1] DR Ensembl; ENST00000522874.5; ENSP00000429469.1; ENSG00000080823.23. [Q9UQ07-6] DR Ensembl; ENST00000524214.5; ENSP00000428942.1; ENSG00000080823.23. [Q9UQ07-5] DR GeneID; 5891; -. DR KEGG; hsa:5891; -. DR MANE-Select; ENST00000361847.7; ENSP00000355304.2; NM_014226.3; NP_055041.1. DR UCSC; uc001ylm.5; human. [Q9UQ07-1] DR AGR; HGNC:9833; -. DR CTD; 5891; -. DR DisGeNET; 5891; -. DR GeneCards; MOK; -. DR HGNC; HGNC:9833; MOK. DR HPA; ENSG00000080823; Tissue enhanced (retina, testis). DR MIM; 605762; gene. DR neXtProt; NX_Q9UQ07; -. DR OpenTargets; ENSG00000080823; -. DR PharmGKB; PA34187; -. DR VEuPathDB; HostDB:ENSG00000080823; -. DR eggNOG; KOG0661; Eukaryota. DR GeneTree; ENSGT00940000159582; -. DR InParanoid; Q9UQ07; -. DR OMA; WRKGYKI; -. DR OrthoDB; 1328218at2759; -. DR PhylomeDB; Q9UQ07; -. DR TreeFam; TF328769; -. DR PathwayCommons; Q9UQ07; -. DR SignaLink; Q9UQ07; -. DR BioGRID-ORCS; 5891; 69 hits in 1181 CRISPR screens. DR ChiTaRS; MOK; human. DR GeneWiki; RAGE_(gene); -. DR GenomeRNAi; 5891; -. DR Pharos; Q9UQ07; Tbio. DR PRO; PR:Q9UQ07; -. DR Proteomes; UP000005640; Chromosome 14. DR RNAct; Q9UQ07; Protein. DR Bgee; ENSG00000080823; Expressed in right uterine tube and 131 other cell types or tissues. DR ExpressionAtlas; Q9UQ07; baseline and differential. DR GO; GO:0097546; C:ciliary base; ISS:UniProtKB. DR GO; GO:0005929; C:cilium; ISS:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; IEA:UniProtKB-EC. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004672; F:protein kinase activity; TAS:ProtInc. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central. DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central. DR GO; GO:0006468; P:protein phosphorylation; TAS:ProtInc. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR CDD; cd07831; STKc_MOK; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR PANTHER; PTHR24055:SF606; MAPK_MAK_MRK OVERLAPPING KINASE; 1. DR PANTHER; PTHR24055; MITOGEN-ACTIVATED PROTEIN KINASE; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR Genevisible; Q9UQ07; HS. PE 2: Evidence at transcript level; KW Alternative splicing; ATP-binding; Cell projection; Cytoplasm; Kinase; KW Magnesium; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein; KW Reference proteome; Serine/threonine-protein kinase; Transferase. FT CHAIN 1..419 FT /note="MAPK/MAK/MRK overlapping kinase" FT /id="PRO_0000086341" FT DOMAIN 4..285 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 285..344 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 390..419 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 286..301 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 325..344 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 128 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 10..18 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 33 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT VAR_SEQ 1..346 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:8781117" FT /id="VSP_009143" FT VAR_SEQ 1..234 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:8781117" FT /id="VSP_009142" FT VAR_SEQ 42..71 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_054734" FT VAR_SEQ 138 FT /note="Missing (in isoform 6)" FT /evidence="ECO:0000305" FT /id="VSP_054735" FT VAR_SEQ 232..419 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_009144" FT VAR_SEQ 290..329 FT /note="KTEKRALGSHRKAGFPEHPVAPEPLSNSCQISKEGRKQKQ -> TQNGSEDE FT ASAVLLPIQTRSSLNPLLSTCMLPGRSVTLLV (in isoform 4)" FT /evidence="ECO:0000303|PubMed:8781117" FT /id="VSP_009145" FT VAR_SEQ 330..419 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:8781117" FT /id="VSP_009146" FT VARIANT 38 FT /note="R -> H (in dbSNP:rs34114580)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042011" FT VARIANT 86 FT /note="D -> N (in dbSNP:rs34084056)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042012" FT VARIANT 217 FT /note="V -> I (in dbSNP:rs148360666)" FT /evidence="ECO:0000269|PubMed:14702039" FT /id="VAR_070930" FT VARIANT 230 FT /note="K -> R (in dbSNP:rs34965156)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042013" FT VARIANT 248 FT /note="P -> S (in dbSNP:rs34299975)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042014" FT VARIANT 272 FT /note="E -> D (in a breast pleomorphic lobular carcinoma FT sample; somatic mutation; dbSNP:rs1567133856)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042015" FT VARIANT 398 FT /note="Q -> R (in dbSNP:rs2236493)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_024576" FT CONFLICT 269 FT /note="D -> G (in Ref. 3; BAG35641)" FT /evidence="ECO:0000305" FT CONFLICT 313 FT /note="P -> L (in Ref. 3; BAG35641)" FT /evidence="ECO:0000305" SQ SEQUENCE 419 AA; 48014 MW; CDA7D9C1E80AAE8F CRC64; MKNYKAIGKI GEGTFSEVMK MQSLRDGNYY ACKQMKQRFE SIEQVNNLRE IQALRRLNPH PNILMLHEVV FDRKSGSLAL ICELMDMNIY ELIRGRRYPL SEKKIMHYMY QLCKSLDHIH RNGIFHRDVK PENILIKQDV LKLGDFGSCR SVYSKQPYTE YISTRWYRAP ECLLTDGFYT YKMDLWSAGC VFYEIASLQP LFPGVNELDQ ISKIHDVIGT PAQKILTKFK QSRAMNFDFP FKKGSGIPLL TTNLSPQCLS LLHAMVAYDP DERIAAHQAL QHPYFQEQRK TEKRALGSHR KAGFPEHPVA PEPLSNSCQI SKEGRKQKQS LKQEEDRPKR RGPAYVMELP KLKLSGVVRL SSYSSPTLQS VLGSGTNGRV PVLRPLKCIP ASKKTDPQKD LKPAPQQCRL PTIVRKGGR //