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Q9HAZ1 (CLK4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 111. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Dual specificity protein kinase CLK4

EC=2.7.12.1
Alternative name(s):
CDC-like kinase 4
Gene names
Name:CLK4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length481 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 and SRSF3. Required for the regulation of alternative splicing of MAPT/TAU. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. Ref.1 Ref.8

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation

TG003 inhibits its kinase activity and affects the regulation of alternative splicing mediated by phosphorylation of SR proteins By similarity.

Subunit structure

Interacts with UBL5. Ref.3 Ref.4

Subcellular location

Nucleus By similarity.

Tissue specificity

Expressed in liver, kidney, heart, muscle, brain and endothelial cells. Ref.1 Ref.8

Post-translational modification

Autophosphorylates on all three types of residues.

Sequence similarities

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

Contains 1 protein kinase domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 481481Dual specificity protein kinase CLK4
PRO_0000085873

Regions

Domain159 – 475317Protein kinase
Nucleotide binding165 – 1739ATP By similarity

Sites

Active site2861Proton acceptor By similarity
Binding site1891ATP By similarity

Amino acid modifications

Modified residue1361Phosphoserine Ref.7
Modified residue1381Phosphoserine Ref.5 Ref.6 Ref.7 Ref.9

Natural variations

Natural variant3521L → F. Ref.10
Corresponds to variant rs35272416 [ dbSNP | Ensembl ].
VAR_040414
Natural variant3631I → V. Ref.10
Corresponds to variant rs55746655 [ dbSNP | Ensembl ].
VAR_040415

Experimental info

Mutagenesis1891K → R: Loss of function. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q9HAZ1 [UniParc].

Last modified March 1, 2001. Version 1.
Checksum: F402C36835CDA306

FASTA48157,492
        10         20         30         40         50         60 
MRHSKRTHCP DWDSRESWGH ESYRGSHKRK RRSHSSTQEN RHCKPHHQFK ESDCHYLEAR 

        70         80         90        100        110        120 
SLNERDYRDR RYVDEYRNDY CEGYVPRHYH RDIESGYRIH CSKSSVRSRR SSPKRKRNRH 

       130        140        150        160        170        180 
CSSHQSRSKS HRRKRSRSIE DDEEGHLICQ SGDVLRARYE IVDTLGEGAF GKVVECIDHG 

       190        200        210        220        230        240 
MDGMHVAVKI VKNVGRYREA ARSEIQVLEH LNSTDPNSVF RCVQMLEWFD HHGHVCIVFE 

       250        260        270        280        290        300 
LLGLSTYDFI KENSFLPFQI DHIRQMAYQI CQSINFLHHN KLTHTDLKPE NILFVKSDYV 

       310        320        330        340        350        360 
VKYNSKMKRD ERTLKNTDIK VVDFGSATYD DEHHSTLVST RHYRAPEVIL ALGWSQPCDV 

       370        380        390        400        410        420 
WSIGCILIEY YLGFTVFQTH DSKEHLAMME RILGPIPQHM IQKTRKRKYF HHNQLDWDEH 

       430        440        450        460        470        480 
SSAGRYVRRR CKPLKEFMLC HDEEHEKLFD LVRRMLEYDP TQRITLDEAL QHPFFDLLKK 


K 

« Hide

References

« Hide 'large scale' references
[1]"Molecular characterization of a cDNA encoding functional human CLK4 kinase and localization to chromosome 5q35."
Schultz J., Jones T., Bork P., Sheer D., Blencke S., Steyrer S., Wellbrock U., Bevec D., Ullrich A., Wallasch C.
Genomics 71:368-370(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AUTOPHOSPHORYLATION, MUTAGENESIS OF LYS-189.
Tissue: Kidney.
[2]Erratum
Schultz J., Jones T., Bork P., Sheer D., Blencke S., Steyrer S., Wellbrock U., Bevec D., Ullrich A., Wallasch C.
Genomics 74:251-251(2001)
[3]"Structural analysis of UBL5, a novel ubiquitin-like modifier."
McNally T., Huang Q., Janis R.S., Liu Z., Olejniczak E.T., Reilly R.M.
Protein Sci. 12:1562-1566(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH UBL5.
[4]"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.
[5]"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-138, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[6]"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-138, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[7]"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 SER-136 AND SER-138, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[8]"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.
[9]"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-138, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"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-352 AND VAL-363.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF294429 mRNA. Translation: AAG10074.1.
RefSeqNP_065717.1. NM_020666.2.
UniGeneHs.406557.

3D structure databases

ProteinModelPortalQ9HAZ1.
SMRQ9HAZ1. Positions 146-480.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid121501. 9 interactions.
IntActQ9HAZ1. 5 interactions.
STRING9606.ENSP00000316948.

Chemistry

BindingDBQ9HAZ1.
ChEMBLCHEMBL4203.
GuidetoPHARMACOLOGY1993.

PTM databases

PhosphoSiteQ9HAZ1.

Polymorphism databases

DMDM34922132.

Proteomic databases

PaxDbQ9HAZ1.
PRIDEQ9HAZ1.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000316308; ENSP00000316948; ENSG00000113240.
GeneID57396.
KEGGhsa:57396.
UCSCuc003mjf.1. human.

Organism-specific databases

CTD57396.
GeneCardsGC05M177962.
HGNCHGNC:13659. CLK4.
HPAHPA043746.
HPA048118.
MIM607969. gene.
neXtProtNX_Q9HAZ1.
PharmGKBPA26598.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000203417.
HOVERGENHBG107720.
InParanoidQ9HAZ1.
KOK08823.
OMALGMCVYD.
OrthoDBEOG7TBC1V.
PhylomeDBQ9HAZ1.
TreeFamTF101041.

Enzyme and pathway databases

SignaLinkQ9HAZ1.

Gene expression databases

ArrayExpressQ9HAZ1.
BgeeQ9HAZ1.
CleanExHS_CLK4.
GenevestigatorQ9HAZ1.

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

GenomeRNAi57396.
NextBio63494.
PROQ9HAZ1.
SOURCESearch...

Entry information

Entry nameCLK4_HUMAN
AccessionPrimary (citable) accession number: Q9HAZ1
Entry history
Integrated into UniProtKB/Swiss-Prot: September 19, 2003
Last sequence update: March 1, 2001
Last modified: March 19, 2014
This is version 111 of the entry and version 1 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

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 5

Human chromosome 5: entries, gene names and cross-references to MIM