Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P49759 (CLK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 140. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Dual specificity protein kinase CLK1

EC=2.7.12.1
Alternative name(s):
CDC-like kinase 1
Gene names
Name:CLK1
Synonyms:CLK
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length484 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex and may be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing. Phosphorylates: SRSF1, SRSF3 and PTPN1. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells and adenovirus E1A pre-mRNA. Ref.7 Ref.13

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation

Regulates splicing of its own pre-mRNA according to its kinase activity; increased expression of the catalytically active form influences splicing to generate the catalytically inactive splicing variant lacking the kinase domain. Leucettine L41 inhibits its kinase activity and affects the regulation of alternative splicing mediated by phosphorylation of SR proteins By similarity.

Subunit structure

Interacts with PPIG and UBL5. Ref.8

Subcellular location

Nucleus.

Tissue specificity

Endothelial cells. Ref.13

Post-translational modification

Autophosphorylates on all three types of residues By similarity.

Sequence similarities

Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. Lammer subfamily.

Contains 1 protein kinase domain.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P49759-1)

Also known as: Long;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P49759-2)

Also known as: Short;

The sequence of this isoform differs from the canonical sequence as follows:
     131-136: KSHRRK → MKLLIL
     137-484: Missing.
Note: Lacks the kinase domain. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Isoform 3 (identifier: P49759-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MAAGRRPASALWPERRGSPLRGDLLGFQNVREPSSCGETLSGM
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 484484Dual specificity protein kinase CLK1
PRO_0000085866

Regions

Domain161 – 477317Protein kinase
Nucleotide binding167 – 1759ATP By similarity

Sites

Active site2881Proton acceptor By similarity
Binding site1911ATP By similarity

Amino acid modifications

Modified residue611Phosphoserine Ref.11
Modified residue1381Phosphothreonine Ref.12
Modified residue1401Phosphoserine Ref.10 Ref.11 Ref.12 Ref.14

Natural variations

Alternative sequence11M → MAAGRRPASALWPERRGSPL RGDLLGFQNVREPSSCGETL SGM in isoform 3.
VSP_043578
Alternative sequence131 – 1366KSHRRK → MKLLIL in isoform 2.
VSP_004852
Alternative sequence137 – 484348Missing in isoform 2.
VSP_004853
Natural variant611S → F. Ref.15
Corresponds to variant rs55989135 [ dbSNP | Ensembl ].
VAR_040409
Natural variant991N → D.
Corresponds to variant rs6735666 [ dbSNP | Ensembl ].
VAR_046551
Natural variant1181R → G. Ref.15
Corresponds to variant rs56135616 [ dbSNP | Ensembl ].
VAR_040410
Natural variant3071P → S. Ref.15
Corresponds to variant rs35412475 [ dbSNP | Ensembl ].
VAR_040411
Natural variant4401M → T. Ref.15
Corresponds to variant rs35393352 [ dbSNP | Ensembl ].
VAR_040412
Natural variant4591E → G.
Corresponds to variant rs12709 [ dbSNP | Ensembl ].
VAR_051620

Experimental info

Sequence conflict4321R → A in AAA61480. Ref.1

Secondary structure

....................................................... 484
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Long) [UniParc].

Last modified September 23, 2008. Version 2.
Checksum: F34B5B44988BD118

FASTA48457,291
        10         20         30         40         50         60 
MRHSKRTYCP DWDDKDWDYG KWRSSSSHKR RKRSHSSAQE NKRCKYNHSK MCDSHYLESR 

        70         80         90        100        110        120 
SINEKDYHSR RYIDEYRNDY TQGCEPGHRQ RDHESRYQNH SSKSSGRSGR SSYKSKHRIH 

       130        140        150        160        170        180 
HSTSHRRSHG KSHRRKRTRS VEDDEEGHLI CQSGDVLSAR YEIVDTLGEG AFGKVVECID 

       190        200        210        220        230        240 
HKAGGRHVAV KIVKNVDRYC EAARSEIQVL EHLNTTDPNS TFRCVQMLEW FEHHGHICIV 

       250        260        270        280        290        300 
FELLGLSTYD FIKENGFLPF RLDHIRKMAY QICKSVNFLH SNKLTHTDLK PENILFVQSD 

       310        320        330        340        350        360 
YTEAYNPKIK RDERTLINPD IKVVDFGSAT YDDEHHSTLV STRHYRAPEV ILALGWSQPC 

       370        380        390        400        410        420 
DVWSIGCILI EYYLGFTVFP THDSKEHLAM MERILGPLPK HMIQKTRKRK YFHHDRLDWD 

       430        440        450        460        470        480 
EHSSAGRYVS RRCKPLKEFM LSQDVEHERL FDLIQKMLEY DPAKRITLRE ALKHPFFDLL 


KKSI 

« Hide

Isoform 2 (Short) [UniParc].

Checksum: 3A1B92FD19E2A521
Show »

FASTA13616,570
Isoform 3 [UniParc].

Checksum: 8514814549CC0655
Show »

FASTA52661,757

References

« Hide 'large scale' references
[1]"Molecular cloning of a novel human cdc2/CDC28-like protein kinase."
Johnson K.W., Smith K.A.
J. Biol. Chem. 266:3402-3407(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Characterization by cDNA cloning of two new human protein kinases. Evidence by sequence comparison of a new family of mammalian protein kinases."
Hanes J.J., der Kammer H., Klaudiny J.J., Scheit K.H.
J. Mol. Biol. 244:665-672(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
Tissue: Amygdala.
[4]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Blood and Bone.
[7]"The CLK family kinases, CLK1 and CLK2, phosphorylate and activate the tyrosine phosphatase, PTP-1B."
Moeslein F.M., Myers M.P., Landreth G.E.
J. Biol. Chem. 274:26697-26704(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[8]"Beacon interacts with cdc2/cdc28-like kinases."
Kantham L., Kerr-Bayles L., Godde N., Quick M., Webb R., Sunderland T., Bond J., Walder K., Augert G., Collier G.
Biochem. Biophys. Res. Commun. 304:125-129(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH UBL5.
[9]"An unappreciated role for RNA surveillance."
Hillman R.T., Green R.E., Brenner S.E.
Genome Biol. 5:R8.1-R8.16(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
[10]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-140, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[11]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-61 AND SER-140, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[12]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-138 AND SER-140, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[13]"Cdc2-like kinases and DNA topoisomerase I regulate alternative splicing of tissue factor in human endothelial cells."
Eisenreich A., Bogdanov V.Y., Zakrzewicz A., Pries A., Antoniak S., Poller W., Schultheiss H.P., Rauch U.
Circ. Res. 104:589-599(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ALTERNATIVE SPLICING, TISSUE SPECIFICITY.
[14]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-140, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] PHE-61; GLY-118; SER-307 AND THR-440.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L29219 mRNA. Translation: AAA61480.1.
L29222 mRNA. Translation: AAB59459.1.
AK289365 mRNA. Translation: BAF82054.1.
AK294295 mRNA. Translation: BAG57578.1.
AC005037 Genomic DNA. Translation: AAY14722.1.
CH471063 Genomic DNA. Translation: EAW70217.1.
BC028149 mRNA. Translation: AAH28149.1.
BC031549 mRNA. Translation: AAH31549.1.
PIRS53641.
RefSeqNP_001155879.1. NM_001162407.1.
NP_004062.2. NM_004071.3.
UniGeneHs.433732.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1Z57X-ray1.70A148-484[»]
2VAGX-ray1.80A148-484[»]
ProteinModelPortalP49759.
SMRP49759. Positions 97-482.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107606. 17 interactions.
IntActP49759. 9 interactions.
MINTMINT-8417657.
STRING9606.ENSP00000326830.

Chemistry

BindingDBP49759.
ChEMBLCHEMBL4224.
GuidetoPHARMACOLOGY1990.

PTM databases

PhosphoSiteP49759.

Polymorphism databases

DMDM206729857.

Proteomic databases

PaxDbP49759.
PRIDEP49759.

Protocols and materials databases

DNASU1195.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000321356; ENSP00000326830; ENSG00000013441. [P49759-1]
ENST00000432425; ENSP00000400487; ENSG00000013441. [P49759-2]
ENST00000434813; ENSP00000394734; ENSG00000013441. [P49759-3]
GeneID1195.
KEGGhsa:1195.
UCSCuc002uwe.2. human. [P49759-1]
uc010zhi.1. human. [P49759-3]

Organism-specific databases

CTD1195.
GeneCardsGC02M201717.
HGNCHGNC:2068. CLK1.
HPACAB033141.
MIM601951. gene.
neXtProtNX_P49759.
PharmGKBPA26594.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000203417.
HOVERGENHBG107720.
InParanoidP49759.
KOK08823.
OMAWPERRGS.
OrthoDBEOG7TBC1V.
PhylomeDBP49759.
TreeFamTF101041.

Enzyme and pathway databases

BRENDA2.7.12.1. 2681.
SignaLinkP49759.

Gene expression databases

ArrayExpressP49759.
BgeeP49759.
CleanExHS_CLK1.
GenevestigatorP49759.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCLK1. human.
EvolutionaryTraceP49759.
GeneWikiCLK1.
GenomeRNAi1195.
NextBio4936.
PROP49759.
SOURCESearch...

Entry information

Entry nameCLK1_HUMAN
AccessionPrimary (citable) accession number: P49759
Secondary accession number(s): B4DFW7, Q0P694, Q8N5V8
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: September 23, 2008
Last modified: March 19, 2014
This is version 140 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM