UniProtKB - Q9HAZ1 (CLK4_HUMAN)
Protein
Dual specificity protein kinase CLK4
Gene
CLK4
Organism
Homo sapiens (Human)
Status
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
Activity regulationi
TG003 inhibits its kinase activity and affects the regulation of alternative splicing mediated by phosphorylation of SR proteins.By similarity
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 189 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 286 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 165 – 173 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- protein serine/threonine/tyrosine kinase activity Source: UniProtKB-EC
- protein serine/threonine kinase activity Source: UniProtKB
- protein tyrosine kinase activity Source: UniProtKB-KW
GO - Biological processi
- protein autophosphorylation Source: Ensembl
- regulation of RNA splicing Source: UniProtKB
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase, Tyrosine-protein kinase |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
PathwayCommonsi | Q9HAZ1 |
SignaLinki | Q9HAZ1 |
SIGNORi | Q9HAZ1 |
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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:13659, CLK4 |
MIMi | 607969, gene |
neXtProti | NX_Q9HAZ1 |
VEuPathDBi | HostDB:ENSG00000113240.12 |
Subcellular locationi
Keywords - Cellular componenti
NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 189 | K → R: Loss of function. 1 Publication | 1 |
Organism-specific databases
OpenTargetsi | ENSG00000113240 |
PharmGKBi | PA26598 |
Miscellaneous databases
Pharosi | Q9HAZ1, Tchem |
Chemistry databases
ChEMBLi | CHEMBL4203 |
DrugBanki | DB12010, Fostamatinib |
DrugCentrali | Q9HAZ1 |
GuidetoPHARMACOLOGYi | 1993 |
Genetic variation databases
BioMutai | CLK4 |
DMDMi | 34922132 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000085873 | 1 – 481 | Dual specificity protein kinase CLK4Add BLAST | 481 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 136 | PhosphoserineCombined sources | 1 | |
Modified residuei | 138 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Autophosphorylates on all three types of residues.
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | Q9HAZ1 |
jPOSTi | Q9HAZ1 |
MassIVEi | Q9HAZ1 |
MaxQBi | Q9HAZ1 |
PaxDbi | Q9HAZ1 |
PeptideAtlasi | Q9HAZ1 |
PRIDEi | Q9HAZ1 |
ProteomicsDBi | 81459 |
PTM databases
iPTMneti | Q9HAZ1 |
PhosphoSitePlusi | Q9HAZ1 |
Expressioni
Tissue specificityi
Expressed in liver, kidney, heart, muscle, brain and endothelial cells.2 Publications
Gene expression databases
Bgeei | ENSG00000113240, Expressed in right hemisphere of cerebellum and 244 other tissues |
ExpressionAtlasi | Q9HAZ1, baseline and differential |
Genevisiblei | Q9HAZ1, HS |
Organism-specific databases
HPAi | ENSG00000113240, Low tissue specificity |
Interactioni
Subunit structurei
Interacts with UBL5.
2 PublicationsBinary interactionsi
Hide detailsQ9HAZ1
Protein-protein interaction databases
BioGRIDi | 121501, 23 interactors |
IntActi | Q9HAZ1, 16 interactors |
STRINGi | 9606.ENSP00000316948 |
Chemistry databases
BindingDBi | Q9HAZ1 |
Miscellaneous databases
RNActi | Q9HAZ1, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q9HAZ1 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 159 – 475 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 317 |
Sequence similaritiesi
Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. Lammer subfamily.Curated
Phylogenomic databases
eggNOGi | KOG0671, Eukaryota |
GeneTreei | ENSGT00940000160245 |
HOGENOMi | CLU_000288_5_16_1 |
InParanoidi | Q9HAZ1 |
OMAi | ECIDHDM |
OrthoDBi | 915778at2759 |
PhylomeDBi | Q9HAZ1 |
TreeFami | TF101041 |
Family and domain databases
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 6 potential isoforms that are computationally mapped.Show allAlign All
Q9HAZ1-1 [UniParc]FASTAAdd to basket
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
Computationally mapped potential isoform sequencesi
There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketB7ZL31 | B7ZL31_HUMAN | CLK4 protein | CLK4 | 373 | Annotation score: | ||
A0A087WX74 | A0A087WX74_HUMAN | Dual-specificity protein kinase CLK... | CLK4 | 373 | Annotation score: | ||
Q68D95 | Q68D95_HUMAN | Dual-specificity protein kinase CLK... | CLK4 DKFZp686A20267 | 53 | Annotation score: | ||
E7ES88 | E7ES88_HUMAN | Dual-specificity protein kinase CLK... | CLK4 | 143 | Annotation score: | ||
E7EWJ6 | E7EWJ6_HUMAN | Dual-specificity protein kinase CLK... | CLK4 | 89 | Annotation score: | ||
Q6P090 | Q6P090_HUMAN | CLK4 protein | CLK4 | 54 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_040414 | 352 | L → F1 PublicationCorresponds to variant dbSNP:rs35272416Ensembl. | 1 | |
Natural variantiVAR_040415 | 363 | I → V1 PublicationCorresponds to variant dbSNP:rs55746655Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF294429 mRNA Translation: AAG10074.1 |
CCDSi | CCDS4437.1 |
RefSeqi | NP_065717.1, NM_020666.2 |
Genome annotation databases
Ensembli | ENST00000316308; ENSP00000316948; ENSG00000113240 |
GeneIDi | 57396 |
KEGGi | hsa:57396 |
UCSCi | uc003mjf.2, human |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF294429 mRNA Translation: AAG10074.1 |
CCDSi | CCDS4437.1 |
RefSeqi | NP_065717.1, NM_020666.2 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
6FYV | X-ray | 2.46 | A | 146-480 | [»] | |
SMRi | Q9HAZ1 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 121501, 23 interactors |
IntActi | Q9HAZ1, 16 interactors |
STRINGi | 9606.ENSP00000316948 |
Chemistry databases
BindingDBi | Q9HAZ1 |
ChEMBLi | CHEMBL4203 |
DrugBanki | DB12010, Fostamatinib |
DrugCentrali | Q9HAZ1 |
GuidetoPHARMACOLOGYi | 1993 |
PTM databases
iPTMneti | Q9HAZ1 |
PhosphoSitePlusi | Q9HAZ1 |
Genetic variation databases
BioMutai | CLK4 |
DMDMi | 34922132 |
Proteomic databases
EPDi | Q9HAZ1 |
jPOSTi | Q9HAZ1 |
MassIVEi | Q9HAZ1 |
MaxQBi | Q9HAZ1 |
PaxDbi | Q9HAZ1 |
PeptideAtlasi | Q9HAZ1 |
PRIDEi | Q9HAZ1 |
ProteomicsDBi | 81459 |
Protocols and materials databases
Antibodypediai | 29447, 108 antibodies |
Genome annotation databases
Ensembli | ENST00000316308; ENSP00000316948; ENSG00000113240 |
GeneIDi | 57396 |
KEGGi | hsa:57396 |
UCSCi | uc003mjf.2, human |
Organism-specific databases
CTDi | 57396 |
GeneCardsi | CLK4 |
HGNCi | HGNC:13659, CLK4 |
HPAi | ENSG00000113240, Low tissue specificity |
MIMi | 607969, gene |
neXtProti | NX_Q9HAZ1 |
OpenTargetsi | ENSG00000113240 |
PharmGKBi | PA26598 |
VEuPathDBi | HostDB:ENSG00000113240.12 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0671, Eukaryota |
GeneTreei | ENSGT00940000160245 |
HOGENOMi | CLU_000288_5_16_1 |
InParanoidi | Q9HAZ1 |
OMAi | ECIDHDM |
OrthoDBi | 915778at2759 |
PhylomeDBi | Q9HAZ1 |
TreeFami | TF101041 |
Enzyme and pathway databases
PathwayCommonsi | Q9HAZ1 |
SignaLinki | Q9HAZ1 |
SIGNORi | Q9HAZ1 |
Miscellaneous databases
BioGRID-ORCSi | 57396, 2 hits in 902 CRISPR screens |
ChiTaRSi | CLK4, human |
GenomeRNAii | 57396 |
Pharosi | Q9HAZ1, Tchem |
PROi | PR:Q9HAZ1 |
RNActi | Q9HAZ1, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000113240, Expressed in right hemisphere of cerebellum and 244 other tissues |
ExpressionAtlasi | Q9HAZ1, baseline and differential |
Genevisiblei | Q9HAZ1, HS |
Family and domain databases
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | CLK4_HUMAN | |
Accessioni | Q9HAZ1Primary (citable) accession number: Q9HAZ1 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | September 19, 2003 |
Last sequence update: | March 1, 2001 | |
Last modified: | February 10, 2021 | |
This is version 161 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human and mouse protein kinases
Human and mouse protein kinases: classification and index - Human chromosome 5
Human chromosome 5: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families