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Protein

Dual specificity protein kinase CLK4

Gene

CLK4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei189 – 1891ATPPROSITE-ProRule annotation
Active sitei286 – 2861Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi165 – 1739ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. protein serine/threonine/tyrosine kinase activity Source: UniProtKB-EC
  3. protein serine/threonine kinase activity Source: UniProtKB
  4. protein tyrosine kinase activity Source: UniProtKB-KW

GO - Biological processi

  1. protein autophosphorylation Source: Ensembl
  2. regulation of RNA splicing Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

SignaLinkiQ9HAZ1.

Names & Taxonomyi

Protein namesi
Recommended name:
Dual specificity protein kinase CLK4 (EC:2.7.12.1)
Alternative name(s):
CDC-like kinase 4
Gene namesi
Name:CLK4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:13659. CLK4.

Subcellular locationi

  1. Nucleus By similarity

GO - Cellular componenti

  1. nucleus Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi189 – 1891K → R: Loss of function. 1 Publication

Organism-specific databases

PharmGKBiPA26598.

Polymorphism and mutation databases

BioMutaiCLK4.
DMDMi34922132.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 481481Dual specificity protein kinase CLK4PRO_0000085873Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei136 – 1361Phosphoserine1 Publication
Modified residuei138 – 1381Phosphoserine4 Publications

Post-translational modificationi

Autophosphorylates on all three types of residues.

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ9HAZ1.
PaxDbiQ9HAZ1.
PRIDEiQ9HAZ1.

PTM databases

PhosphoSiteiQ9HAZ1.

Expressioni

Tissue specificityi

Expressed in liver, kidney, heart, muscle, brain and endothelial cells.2 Publications

Gene expression databases

BgeeiQ9HAZ1.
CleanExiHS_CLK4.
ExpressionAtlasiQ9HAZ1. baseline and differential.
GenevestigatoriQ9HAZ1.

Organism-specific databases

HPAiHPA043746.
HPA048118.

Interactioni

Subunit structurei

Interacts with UBL5.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
KPNA1P522943EBI-633400,EBI-358383
KRTAP10-7P604093EBI-633400,EBI-10172290
KRTAP10-8P604103EBI-633400,EBI-10171774
KRTAP10-9P604113EBI-633400,EBI-10172052

Protein-protein interaction databases

BioGridi121501. 17 interactions.
IntActiQ9HAZ1. 9 interactions.
STRINGi9606.ENSP00000316948.

Structurei

3D structure databases

ProteinModelPortaliQ9HAZ1.
SMRiQ9HAZ1. Positions 146-480.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini159 – 475317Protein kinasePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00580000081366.
HOGENOMiHOG000203417.
HOVERGENiHBG107720.
InParanoidiQ9HAZ1.
KOiK08823.
OMAiCERYVPR.
OrthoDBiEOG7TBC1V.
PhylomeDBiQ9HAZ1.
TreeFamiTF101041.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9HAZ1-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRHSKRTHCP DWDSRESWGH ESYRGSHKRK RRSHSSTQEN RHCKPHHQFK
60 70 80 90 100
ESDCHYLEAR SLNERDYRDR RYVDEYRNDY CEGYVPRHYH RDIESGYRIH
110 120 130 140 150
CSKSSVRSRR SSPKRKRNRH CSSHQSRSKS HRRKRSRSIE DDEEGHLICQ
160 170 180 190 200
SGDVLRARYE IVDTLGEGAF GKVVECIDHG MDGMHVAVKI VKNVGRYREA
210 220 230 240 250
ARSEIQVLEH LNSTDPNSVF RCVQMLEWFD HHGHVCIVFE LLGLSTYDFI
260 270 280 290 300
KENSFLPFQI DHIRQMAYQI CQSINFLHHN KLTHTDLKPE NILFVKSDYV
310 320 330 340 350
VKYNSKMKRD ERTLKNTDIK VVDFGSATYD DEHHSTLVST RHYRAPEVIL
360 370 380 390 400
ALGWSQPCDV WSIGCILIEY YLGFTVFQTH DSKEHLAMME RILGPIPQHM
410 420 430 440 450
IQKTRKRKYF HHNQLDWDEH SSAGRYVRRR CKPLKEFMLC HDEEHEKLFD
460 470 480
LVRRMLEYDP TQRITLDEAL QHPFFDLLKK K
Length:481
Mass (Da):57,492
Last modified:March 1, 2001 - v1
Checksum:iF402C36835CDA306
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti352 – 3521L → F.1 Publication
Corresponds to variant rs35272416 [ dbSNP | Ensembl ].
VAR_040414
Natural varianti363 – 3631I → V.1 Publication
Corresponds to variant rs55746655 [ dbSNP | Ensembl ].
VAR_040415

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF294429 mRNA. Translation: AAG10074.1.
CCDSiCCDS4437.1.
RefSeqiNP_065717.1. NM_020666.2.
UniGeneiHs.406557.

Genome annotation databases

EnsembliENST00000316308; ENSP00000316948; ENSG00000113240.
GeneIDi57396.
KEGGihsa:57396.
UCSCiuc003mjf.1. human.

Polymorphism and mutation databases

BioMutaiCLK4.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF294429 mRNA. Translation: AAG10074.1.
CCDSiCCDS4437.1.
RefSeqiNP_065717.1. NM_020666.2.
UniGeneiHs.406557.

3D structure databases

ProteinModelPortaliQ9HAZ1.
SMRiQ9HAZ1. Positions 146-480.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121501. 17 interactions.
IntActiQ9HAZ1. 9 interactions.
STRINGi9606.ENSP00000316948.

Chemistry

BindingDBiQ9HAZ1.
ChEMBLiCHEMBL4203.
GuidetoPHARMACOLOGYi1993.

PTM databases

PhosphoSiteiQ9HAZ1.

Polymorphism and mutation databases

BioMutaiCLK4.
DMDMi34922132.

Proteomic databases

MaxQBiQ9HAZ1.
PaxDbiQ9HAZ1.
PRIDEiQ9HAZ1.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000316308; ENSP00000316948; ENSG00000113240.
GeneIDi57396.
KEGGihsa:57396.
UCSCiuc003mjf.1. human.

Organism-specific databases

CTDi57396.
GeneCardsiGC05M178029.
HGNCiHGNC:13659. CLK4.
HPAiHPA043746.
HPA048118.
MIMi607969. gene.
neXtProtiNX_Q9HAZ1.
PharmGKBiPA26598.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00580000081366.
HOGENOMiHOG000203417.
HOVERGENiHBG107720.
InParanoidiQ9HAZ1.
KOiK08823.
OMAiCERYVPR.
OrthoDBiEOG7TBC1V.
PhylomeDBiQ9HAZ1.
TreeFamiTF101041.

Enzyme and pathway databases

SignaLinkiQ9HAZ1.

Miscellaneous databases

ChiTaRSiCLK4. human.
GenomeRNAii57396.
NextBioi63494.
PROiQ9HAZ1.
SOURCEiSearch...

Gene expression databases

BgeeiQ9HAZ1.
CleanExiHS_CLK4.
ExpressionAtlasiQ9HAZ1. baseline and differential.
GenevestigatoriQ9HAZ1.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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. "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.
  3. Cited for: INTERACTION WITH UBL5.
  4. "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.
  5. "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.
  6. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-136 AND SER-138, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  7. "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.
  8. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-138, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  9. "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.

Entry informationi

Entry nameiCLK4_HUMAN
AccessioniPrimary (citable) accession number: Q9HAZ1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 19, 2003
Last sequence update: March 1, 2001
Last modified: April 29, 2015
This is version 120 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.