ID CLK1_HUMAN Reviewed; 484 AA. AC P49759; Q8N5V8; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 23-SEP-2008, sequence version 2. DT 01-SEP-2009, entry version 94. DE RecName: Full=Dual specificity protein kinase CLK1; DE EC=2.7.12.1; DE AltName: Full=CDC-like kinase 1; GN Name=CLK1; Synonyms=CLK; 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 [MRNA] (ISOFORM 1). RX MEDLINE=91139618; PubMed=1704889; RA Johnson K.W., Smith K.A.; RT "Molecular cloning of a novel human cdc2/CDC28-like protein kinase."; RL J. Biol. Chem. 266:3402-3407(1991). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RX MEDLINE=95082033; PubMed=7990150; DOI=10.1006/jmbi.1994.1763; RA Hanes J.J., der Kammer H., Klaudiny J.J., Scheit K.H.; RT "Characterization by cDNA cloning of two new human protein kinases. RT Evidence by sequence comparison of a new family of mammalian protein RT kinases."; RL J. Mol. Biol. 244:665-672(1994). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J., RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., RA Waterston R.H., Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 RT and 4."; RL Nature 434:724-731(2005). RN [4] 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Bone; 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 [6] RP SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S). RX PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8; RA Hillman R.T., Green R.E., Brenner S.E.; RT "An unappreciated role for RNA surveillance."; RL Genome Biol. 5:RESEARCH008.1-RESEARCH008.16(2004). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-138 AND SER-140, AND RP MASS SPECTROMETRY. RC TISSUE=Epithelium; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., RA Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in RT signaling networks."; RL Cell 127:635-648(2006). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37; SER-61; THR-138; RP SER-140; SER-341 AND THR-342, AND MASS SPECTROMETRY. RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of RT the kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-138 AND SER-140, AND RP MASS SPECTROMETRY. 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 [10] RP VARIANTS [LARGE SCALE ANALYSIS] PHE-61; GLY-118; SER-307 AND THR-440. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E., RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., RA Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). CC -!- FUNCTION: Phosphorylates serine- and arginine-rich (SR) proteins CC of the spliceosomal complex may be a constituent of a network of CC regulatory mechanisms that enable SR proteins to control RNA CC splicing. Phosphorylates serines, threonines and tyrosines (By CC similarity). CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC -!- SUBUNIT: Interacts with PPIG. CC -!- SUBCELLULAR LOCATION: Nucleus. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=Long; CC IsoId=P49759-1; Sequence=Displayed; CC Name=Short; CC IsoId=P49759-2; Sequence=VSP_004852, VSP_004853; CC Note=Lacks the kinase domain. May be produced at very low levels CC due to a premature stop codon in the mRNA, leading to CC nonsense-mediated mRNA decay; CC -!- PTM: Autophosphorylates on all three types of residues (By CC similarity). CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC CC Ser/Thr protein kinase family. Lammer subfamily. CC -!- SIMILARITY: Contains 1 protein kinase domain. 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; L29219; AAA61480.1; -; mRNA. DR EMBL; L29222; AAB59459.1; -; mRNA. DR EMBL; AC005037; AAY14722.1; -; Genomic_DNA. DR EMBL; CH471063; EAW70217.1; -; Genomic_DNA. DR EMBL; BC031549; AAH31549.1; -; mRNA. DR IPI; IPI00028061; -. DR IPI; IPI00642857; -. DR PIR; S53641; S53641. DR RefSeq; NP_004062.2; -. DR UniGene; Hs.433732; -. DR PDB; 1Z57; X-ray; 1.70 A; A=148-484. DR PDB; 2VAG; X-ray; 1.80 A; A=148-484. DR PDBsum; 1Z57; -. DR PDBsum; 2VAG; -. DR IntAct; P49759; 5. DR STRING; P49759; -. DR PhosphoSite; P49759; -. DR PRIDE; P49759; -. DR Ensembl; ENST00000321356; ENSP00000326830; ENSG00000013441; Homo sapiens. DR Ensembl; ENST00000357369; ENSP00000349935; ENSG00000013441; Homo sapiens. DR Ensembl; ENST00000409403; ENSP00000386875; ENSG00000013441; Homo sapiens. DR GeneID; 1195; -. DR KEGG; hsa:1195; -. DR UCSC; uc002uwe.1; human. DR CTD; 1195; -. DR GeneCards; GC02M201417; -. DR HGNC; HGNC:2068; CLK1. DR MIM; 601951; gene. DR PharmGKB; PA26594; -. DR HOGENOM; P49759; -. DR HOVERGEN; P49759; -. DR BRENDA; 2.7.12.1; 247. DR NextBio; 4936; -. DR ArrayExpress; P49759; -. DR Bgee; P49759; -. DR CleanEx; HS_CLK1; -. DR GermOnline; ENSG00000013441; Homo sapiens. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kina...; TAS:ProtInc. DR GO; GO:0004674; F:protein serine/threonine kinase activity; TAS:ProtInc. DR GO; GO:0008283; P:cell proliferation; TAS:ProtInc. DR GO; GO:0006468; P:protein amino acid phosphorylation; IEA:InterPro. DR InterPro; IPR000719; Prot_kinase_core. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR017442; Se/Thr_pkinase-rel. DR InterPro; IPR008271; Ser_thr_pkin_AS. DR InterPro; IPR002290; Ser_thr_pkinase. DR Pfam; PF00069; Pkinase; 1. DR ProDom; PD000001; Prot_kinase; 1. DR SMART; SM00220; S_TKc; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Complete proteome; KW Kinase; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; KW Serine/threonine-protein kinase; Transferase; Tyrosine-protein kinase. FT CHAIN 1 484 Dual specificity protein kinase CLK1. FT /FTId=PRO_0000085866. FT DOMAIN 161 477 Protein kinase. FT NP_BIND 167 175 ATP (By similarity). FT ACT_SITE 288 288 Proton acceptor (By similarity). FT BINDING 191 191 ATP (By similarity). FT MOD_RES 37 37 Phosphoserine. FT MOD_RES 61 61 Phosphoserine. FT MOD_RES 138 138 Phosphothreonine. FT MOD_RES 140 140 Phosphoserine. FT MOD_RES 341 341 Phosphoserine. FT MOD_RES 342 342 Phosphothreonine. FT VAR_SEQ 131 136 KSHRRK -> MKLLIL (in isoform Short). FT /FTId=VSP_004852. FT VAR_SEQ 137 484 Missing (in isoform Short). FT /FTId=VSP_004853. FT VARIANT 61 61 S -> F. FT /FTId=VAR_040409. FT VARIANT 99 99 N -> D (in dbSNP:rs6735666). FT /FTId=VAR_046551. FT VARIANT 118 118 R -> G. FT /FTId=VAR_040410. FT VARIANT 307 307 P -> S. FT /FTId=VAR_040411. FT VARIANT 440 440 M -> T. FT /FTId=VAR_040412. FT VARIANT 459 459 E -> G (in dbSNP:rs12709). FT /FTId=VAR_051620. FT CONFLICT 432 432 R -> A (in Ref. 1; AAA61480). FT TURN 158 160 FT STRAND 161 170 FT STRAND 173 180 FT TURN 181 185 FT STRAND 187 193 FT HELIX 197 216 FT STRAND 227 233 FT STRAND 236 242 FT HELIX 248 254 FT TURN 255 257 FT HELIX 262 281 FT HELIX 291 293 FT STRAND 294 297 FT STRAND 301 305 FT STRAND 312 317 FT STRAND 321 323 FT HELIX 343 345 FT HELIX 348 351 FT HELIX 359 374 FT HELIX 384 395 FT HELIX 400 405 FT HELIX 409 411 FT HELIX 424 432 FT HELIX 436 439 FT HELIX 445 457 FT TURN 462 464 FT HELIX 468 471 FT HELIX 475 481 SQ SEQUENCE 484 AA; 57291 MW; F34B5B44988BD118 CRC64; MRHSKRTYCP DWDDKDWDYG KWRSSSSHKR RKRSHSSAQE NKRCKYNHSK MCDSHYLESR SINEKDYHSR RYIDEYRNDY TQGCEPGHRQ RDHESRYQNH SSKSSGRSGR SSYKSKHRIH HSTSHRRSHG KSHRRKRTRS VEDDEEGHLI CQSGDVLSAR YEIVDTLGEG AFGKVVECID HKAGGRHVAV KIVKNVDRYC EAARSEIQVL EHLNTTDPNS TFRCVQMLEW FEHHGHICIV FELLGLSTYD FIKENGFLPF RLDHIRKMAY QICKSVNFLH SNKLTHTDLK PENILFVQSD YTEAYNPKIK RDERTLINPD IKVVDFGSAT YDDEHHSTLV STRHYRAPEV ILALGWSQPC DVWSIGCILI EYYLGFTVFP THDSKEHLAM MERILGPLPK HMIQKTRKRK YFHHDRLDWD EHSSAGRYVS RRCKPLKEFM LSQDVEHERL FDLIQKMLEY DPAKRITLRE ALKHPFFDLL KKSI //