Q9HAZ1 (CLK4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Dual specificity protein kinase CLK4
EC=2.7.12.1

Alternative name(s):
CDC-like kinase 4

Gene names

Name:

CLK4

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	481 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase Tyrosine-protein kinase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	peptidyl-tyrosine phosphorylation Inferred from electronic annotation. Source: Compara protein autophosphorylation Inferred from electronic annotation. Source: Compara regulation of RNA splicing Inferred from mutant phenotype Ref.8. Source: UniProtKB
Cellular_component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Inferred from sequence or structural similarity. Source: UniProtKB protein serine/threonine/tyrosine kinase activity Inferred from electronic annotation. Source: EC protein tyrosine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 481	481	Dual specificity protein kinase CLK4		PRO_0000085873
Regions
	Domain	159 – 475	317	Protein kinase
	Nucleotide binding	165 – 173	9	ATP By similarity
Sites
	Active site	286	1	Proton acceptor By similarity
	Binding site	189	1	ATP By similarity
Amino acid modifications
	Modified residue	136	1	Phosphoserine Ref.7
	Modified residue	138	1	Phosphoserine Ref.5 Ref.6 Ref.7 Ref.9
Natural variations
	Natural variant	352	1	L → F. Ref.10 Corresponds to variant rs35272416 [ dbSNP | Ensembl ].		VAR_040414
	Natural variant	363	1	I → V. Ref.10 Corresponds to variant rs55746655 [ dbSNP | Ensembl ].		VAR_040415
Experimental info
	Mutagenesis	189	1	K → R: Loss of function. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q9HAZ1 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: F402C36835CDA306	FASTA	481	57,492
	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

References

	« Hide 'large scale' referencesShow '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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY.
[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. , 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.
IPI	IPI00180143.
RefSeq	NP_065717.1. NM_020666.2.
UniGene	Hs.406557.
3D structure databases
ProteinModelPortal	Q9HAZ1.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9HAZ1. 2 interactions.
STRING	9606.ENSP00000316948.
PTM databases
PhosphoSite	Q9HAZ1.
Polymorphism databases
DMDM	34922132.
Proteomic databases
PaxDb	Q9HAZ1.
PRIDE	Q9HAZ1.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000316308; ENSP00000316948; ENSG00000113240.
GeneID	57396.
KEGG	hsa:57396.
UCSC	uc003mjf.1. human.
Organism-specific databases
CTD	57396.
GeneCards	GC05M177962.
HGNC	HGNC:13659. CLK4.
HPA	HPA043746. HPA048118.
MIM	607969. gene.
neXtProt	NX_Q9HAZ1.
PharmGKB	PA26598.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000203417.
HOVERGEN	HBG107720.
InParanoid	Q9HAZ1.
KO	K08823.
OMA	HGMDGIH.
OrthoDB	EOG4XD3R2.
PhylomeDB	Q9HAZ1.
Gene expression databases
ArrayExpress	Q9HAZ1.
Bgee	Q9HAZ1.
CleanEx	HS_CLK4.
Genevestigator	Q9HAZ1.
GermOnline	ENSG00000113240. Homo sapiens.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR002290. Ser/Thr_dual-sp_kinase_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q9HAZ1.
ChEMBL	CHEMBL4203.
GenomeRNAi	57396.
NextBio	63494.
SOURCE	Search...

Entry information

Entry name

CLK4_HUMAN

Accession

Primary (citable) accession number: Q9HAZ1

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 19, 2003
Last sequence update:	March 1, 2001
Last modified:	May 1, 2013
This is version 101 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.