UniProtKB - P49759 (CLK1_HUMAN)
Protein
Dual specificity protein kinase CLK1
Gene
CLK1
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, SRSF3 and PTPN1. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells and adenovirus E1A pre-mRNA.2 Publications
Catalytic activityi
Activity regulationi
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).By similarity
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 191 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 288 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 167 – 175 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- non-membrane spanning protein tyrosine kinase activity Source: ProtInc
- protein serine/threonine/tyrosine kinase activity Source: UniProtKB-EC
- protein serine/threonine kinase activity Source: UniProtKB
GO - Biological processi
- peptidyl-serine phosphorylation Source: Ensembl
- peptidyl-threonine phosphorylation Source: Ensembl
- 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
BRENDAi | 2.7.12.1, 2681 |
PathwayCommonsi | P49759 |
SignaLinki | P49759 |
SIGNORi | P49759 |
Names & Taxonomyi
Protein namesi | Recommended name: Dual specificity protein kinase CLK1 (EC:2.7.12.1)Alternative name(s): CDC-like kinase 1 |
Gene namesi | Name:CLK1 Synonyms:CLK |
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
EuPathDBi | HostDB:ENSG00000013441.15 |
HGNCi | HGNC:2068, CLK1 |
MIMi | 601951, gene |
neXtProti | NX_P49759 |
Pathology & Biotechi
Organism-specific databases
DisGeNETi | 1195 |
OpenTargetsi | ENSG00000013441 |
PharmGKBi | PA26594 |
Miscellaneous databases
Pharosi | P49759, Tchem |
Chemistry databases
ChEMBLi | CHEMBL4224 |
DrugBanki | DB06376, CHGN111 DB04367, Debromohymenialdisine DB08691, ethyl 3-[(E)-2-amino-1-cyanoethenyl]-6,7-dichloro-1-methyl-1H-indole-2-carboxylate DB12010, Fostamatinib |
DrugCentrali | P49759 |
GuidetoPHARMACOLOGYi | 1990 |
Polymorphism and mutation databases
BioMutai | CLK1 |
DMDMi | 206729857 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000085866 | 1 – 484 | Dual specificity protein kinase CLK1Add BLAST | 484 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 61 | PhosphoserineCombined sources | 1 | |
Modified residuei | 138 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 140 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Autophosphorylates on all three types of residues.By similarity
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | P49759 |
jPOSTi | P49759 |
MassIVEi | P49759 |
MaxQBi | P49759 |
PaxDbi | P49759 |
PeptideAtlasi | P49759 |
PRIDEi | P49759 |
ProteomicsDBi | 56090 [P49759-1] 56091 [P49759-2] 56092 [P49759-3] |
PTM databases
iPTMneti | P49759 |
PhosphoSitePlusi | P49759 |
Expressioni
Tissue specificityi
Endothelial cells.1 Publication
Gene expression databases
Bgeei | ENSG00000013441, Expressed in left lobe of thyroid gland and 244 other tissues |
ExpressionAtlasi | P49759, baseline and differential |
Genevisiblei | P49759, HS |
Organism-specific databases
HPAi | ENSG00000013441, Low tissue specificity |
Interactioni
Subunit structurei
Interacts with PPIG and UBL5.
1 PublicationBinary interactionsi
Hide detailsP49759
With | #Exp. | IntAct |
---|---|---|
KRTAP10-7 [P60409] | 3 | EBI-473775,EBI-10172290 |
PDE9A [O76083] | 3 | EBI-473775,EBI-742764 |
Isoform 3 [P49759-3]
Protein-protein interaction databases
BioGRIDi | 107606, 177 interactors |
IntActi | P49759, 36 interactors |
MINTi | P49759 |
STRINGi | 9606.ENSP00000394734 |
Chemistry databases
BindingDBi | P49759 |
Miscellaneous databases
RNActi | P49759, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | P49759 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P49759 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 161 – 477 | 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 | ENSGT00940000159722 |
HOGENOMi | CLU_126079_0_0_1 |
InParanoidi | P49759 |
OMAi | YVEEYNP |
OrthoDBi | 915778at2759 |
PhylomeDBi | P49759 |
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 |
s (3+)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: P49759-1) [UniParc]FASTAAdd to basket
Also known as: Long
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MRHSKRTYCP DWDDKDWDYG KWRSSSSHKR RKRSHSSAQE NKRCKYNHSK
60 70 80 90 100
MCDSHYLESR SINEKDYHSR RYIDEYRNDY TQGCEPGHRQ RDHESRYQNH
110 120 130 140 150
SSKSSGRSGR SSYKSKHRIH HSTSHRRSHG KSHRRKRTRS VEDDEEGHLI
160 170 180 190 200
CQSGDVLSAR YEIVDTLGEG AFGKVVECID HKAGGRHVAV KIVKNVDRYC
210 220 230 240 250
EAARSEIQVL EHLNTTDPNS TFRCVQMLEW FEHHGHICIV FELLGLSTYD
260 270 280 290 300
FIKENGFLPF RLDHIRKMAY QICKSVNFLH SNKLTHTDLK PENILFVQSD
310 320 330 340 350
YTEAYNPKIK RDERTLINPD IKVVDFGSAT YDDEHHSTLV STRHYRAPEV
360 370 380 390 400
ILALGWSQPC DVWSIGCILI EYYLGFTVFP THDSKEHLAM MERILGPLPK
410 420 430 440 450
HMIQKTRKRK YFHHDRLDWD EHSSAGRYVS RRCKPLKEFM LSQDVEHERL
460 470 480
FDLIQKMLEY DPAKRITLRE ALKHPFFDLL KKSI
Isoform 2 (identifier: P49759-2) [UniParc]FASTAAdd to basket
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.Curated
Show »Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketF8WBF5 | F8WBF5_HUMAN | Dual-specificity protein kinase CLK... | CLK1 | 355 | Annotation score: | ||
A0A087WVK0 | A0A087WVK0_HUMAN | Dual-specificity protein kinase CLK... | CLK1 | 454 | Annotation score: | ||
B8ZZR0 | B8ZZR0_HUMAN | Dual-specificity protein kinase CLK... | CLK1 | 307 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 432 | R → A in AAA61480 (PubMed:1704889).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_040409 | 61 | S → F1 PublicationCorresponds to variant dbSNP:rs55989135Ensembl. | 1 | |
Natural variantiVAR_046551 | 99 | N → D. Corresponds to variant dbSNP:rs6735666Ensembl. | 1 | |
Natural variantiVAR_040410 | 118 | R → G1 PublicationCorresponds to variant dbSNP:rs56135616Ensembl. | 1 | |
Natural variantiVAR_040411 | 307 | P → S1 PublicationCorresponds to variant dbSNP:rs35412475Ensembl. | 1 | |
Natural variantiVAR_040412 | 440 | M → T1 PublicationCorresponds to variant dbSNP:rs35393352Ensembl. | 1 | |
Natural variantiVAR_051620 | 459 | E → G. Corresponds to variant dbSNP:rs12709Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_043578 | 1 | M → MAAGRRPASALWPERRGSPL RGDLLGFQNVREPSSCGETL SGM in isoform 3. 1 Publication | 1 | |
Alternative sequenceiVSP_004852 | 131 – 136 | KSHRRK → MKLLIL in isoform 2. 3 Publications | 6 | |
Alternative sequenceiVSP_004853 | 137 – 484 | Missing in isoform 2. 3 PublicationsAdd BLAST | 348 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | 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 |
CCDSi | CCDS2331.1 [P49759-1] CCDS54427.1 [P49759-3] |
PIRi | S53641 |
RefSeqi | NP_001155879.1, NM_001162407.1 [P49759-3] NP_004062.2, NM_004071.3 [P49759-1] |
Genome annotation databases
Ensembli | ENST00000321356; ENSP00000326830; ENSG00000013441 [P49759-1] ENST00000432425; ENSP00000400487; ENSG00000013441 [P49759-2] ENST00000434813; ENSP00000394734; ENSG00000013441 [P49759-3] |
GeneIDi | 1195 |
KEGGi | hsa:1195 |
UCSCi | uc002uwe.3, human [P49759-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | 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 |
CCDSi | CCDS2331.1 [P49759-1] CCDS54427.1 [P49759-3] |
PIRi | S53641 |
RefSeqi | NP_001155879.1, NM_001162407.1 [P49759-3] NP_004062.2, NM_004071.3 [P49759-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1Z57 | X-ray | 1.70 | A | 148-484 | [»] | |
2VAG | X-ray | 1.80 | A | 148-484 | [»] | |
5J1V | X-ray | 2.52 | A/B/C | 148-484 | [»] | |
5J1W | X-ray | 2.42 | A/B/C | 148-484 | [»] | |
5X8I | X-ray | 1.90 | A/B | 148-484 | [»] | |
6FT8 | X-ray | 1.45 | A | 148-484 | [»] | |
6FT9 | X-ray | 1.87 | A/B/C | 148-484 | [»] | |
6FYO | X-ray | 2.32 | A | 148-484 | [»] | |
6G33 | X-ray | 2.05 | A/B/C | 148-484 | [»] | |
6I5H | X-ray | 1.49 | A | 148-484 | [»] | |
6I5I | X-ray | 1.60 | A | 148-484 | [»] | |
6I5K | X-ray | 2.30 | A/B/C | 148-484 | [»] | |
6I5L | X-ray | 2.55 | A/B/C | 148-484 | [»] | |
6KHD | X-ray | 2.70 | A/B/C | 1-484 | [»] | |
6Q8K | X-ray | 2.29 | A | 148-484 | [»] | |
6Q8P | X-ray | 3.00 | A/B/C | 148-484 | [»] | |
6QTY | X-ray | 1.65 | A | 148-484 | [»] | |
6R3D | X-ray | 1.85 | A | 148-484 | [»] | |
6R6E | X-ray | 2.25 | A | 148-484 | [»] | |
6R6X | X-ray | 2.05 | A | 148-484 | [»] | |
6R8J | X-ray | 1.75 | A | 148-484 | [»] | |
6RAA | X-ray | 2.10 | A | 148-484 | [»] | |
6TW2 | X-ray | 1.80 | E | 148-484 | [»] | |
6YTA | X-ray | 2.30 | A | 148-484 | [»] | |
6YTD | X-ray | 2.00 | A | 148-484 | [»] | |
6YTE | X-ray | 2.30 | C | 148-484 | [»] | |
6YTG | X-ray | 1.95 | A | 148-484 | [»] | |
6YTI | X-ray | 2.40 | A | 148-484 | [»] | |
6Z4Z | X-ray | 2.07 | A/B/C | 148-484 | [»] | |
6Z50 | X-ray | 1.60 | A | 148-484 | [»] | |
6ZLN | X-ray | 1.70 | A | 148-484 | [»] | |
SMRi | P49759 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 107606, 177 interactors |
IntActi | P49759, 36 interactors |
MINTi | P49759 |
STRINGi | 9606.ENSP00000394734 |
Chemistry databases
BindingDBi | P49759 |
ChEMBLi | CHEMBL4224 |
DrugBanki | DB06376, CHGN111 DB04367, Debromohymenialdisine DB08691, ethyl 3-[(E)-2-amino-1-cyanoethenyl]-6,7-dichloro-1-methyl-1H-indole-2-carboxylate DB12010, Fostamatinib |
DrugCentrali | P49759 |
GuidetoPHARMACOLOGYi | 1990 |
PTM databases
iPTMneti | P49759 |
PhosphoSitePlusi | P49759 |
Polymorphism and mutation databases
BioMutai | CLK1 |
DMDMi | 206729857 |
Proteomic databases
EPDi | P49759 |
jPOSTi | P49759 |
MassIVEi | P49759 |
MaxQBi | P49759 |
PaxDbi | P49759 |
PeptideAtlasi | P49759 |
PRIDEi | P49759 |
ProteomicsDBi | 56090 [P49759-1] 56091 [P49759-2] 56092 [P49759-3] |
Protocols and materials databases
Antibodypediai | 34923, 208 antibodies |
DNASUi | 1195 |
Genome annotation databases
Ensembli | ENST00000321356; ENSP00000326830; ENSG00000013441 [P49759-1] ENST00000432425; ENSP00000400487; ENSG00000013441 [P49759-2] ENST00000434813; ENSP00000394734; ENSG00000013441 [P49759-3] |
GeneIDi | 1195 |
KEGGi | hsa:1195 |
UCSCi | uc002uwe.3, human [P49759-1] |
Organism-specific databases
CTDi | 1195 |
DisGeNETi | 1195 |
EuPathDBi | HostDB:ENSG00000013441.15 |
GeneCardsi | CLK1 |
HGNCi | HGNC:2068, CLK1 |
HPAi | ENSG00000013441, Low tissue specificity |
MIMi | 601951, gene |
neXtProti | NX_P49759 |
OpenTargetsi | ENSG00000013441 |
PharmGKBi | PA26594 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0671, Eukaryota |
GeneTreei | ENSGT00940000159722 |
HOGENOMi | CLU_126079_0_0_1 |
InParanoidi | P49759 |
OMAi | YVEEYNP |
OrthoDBi | 915778at2759 |
PhylomeDBi | P49759 |
TreeFami | TF101041 |
Enzyme and pathway databases
BRENDAi | 2.7.12.1, 2681 |
PathwayCommonsi | P49759 |
SignaLinki | P49759 |
SIGNORi | P49759 |
Miscellaneous databases
BioGRID-ORCSi | 1195, 4 hits in 874 CRISPR screens |
ChiTaRSi | CLK1, human |
EvolutionaryTracei | P49759 |
GeneWikii | CLK1 |
GenomeRNAii | 1195 |
Pharosi | P49759, Tchem |
PROi | PR:P49759 |
RNActi | P49759, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000013441, Expressed in left lobe of thyroid gland and 244 other tissues |
ExpressionAtlasi | P49759, baseline and differential |
Genevisiblei | P49759, 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 | CLK1_HUMAN | |
Accessioni | P49759Primary (citable) accession number: P49759 Secondary accession number(s): B4DFW7, Q0P694, Q8N5V8 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 1, 1996 |
Last sequence update: | September 23, 2008 | |
Last modified: | December 2, 2020 | |
This is version 195 of the entry and version 2 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 polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - 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 - Human chromosome 2
Human chromosome 2: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations - Human and mouse protein kinases
Human and mouse protein kinases: classification and index