UniProtKB - P49761 (CLK3_HUMAN)
Dual specificity protein kinase CLK3
CLK3
Functioni
Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex. May be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing and can cause redistribution of SR proteins from speckles to a diffuse nucleoplasmic distribution. Phosphorylates SRSF1 and SRSF3. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells.
2 PublicationsCatalytic activityi
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 334 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 431 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 310 – 318 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- identical protein binding Source: IntAct
- protein serine/threonine/tyrosine kinase activity Source: UniProtKB-EC
- protein serine/threonine kinase activity Source: UniProtKB
- protein serine kinase activity Source: RHEA
- protein tyrosine kinase activity Source: UniProtKB-KW
- RNA binding Source: UniProtKB
GO - Biological processi
- protein autophosphorylation Source: Ensembl
- protein phosphorylation Source: UniProtKB
- 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 | P49761 |
SignaLinki | P49761 |
SIGNORi | P49761 |
Names & Taxonomyi
Protein namesi | Recommended name: Dual specificity protein kinase CLK3 (EC:2.7.12.1)Alternative name(s): CDC-like kinase 3 |
Gene namesi | Name:CLK3 |
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:2071, CLK3 |
MIMi | 602990, gene |
neXtProti | NX_P49761 |
VEuPathDBi | HostDB:ENSG00000179335 |
Subcellular locationi
Nucleus
Note: Co-localizes with serine- and arginine-rich (SR) proteins in the nuclear speckles.
Cytoskeleton
- intermediate filament cytoskeleton Source: HPA
Nucleus
- nuclear speck Source: UniProtKB-SubCell
- nucleoplasm Source: HPA
- nucleus Source: UniProtKB
Other locations
- acrosomal vesicle Source: UniProtKB-SubCell
- membrane Source: UniProtKB
Keywords - Cellular componenti
Cytoplasm, Cytoplasmic vesicle, NucleusPathology & Biotechi
Organism-specific databases
DisGeNETi | 1198 |
OpenTargetsi | ENSG00000179335 |
PharmGKBi | PA26597 |
Miscellaneous databases
Pharosi | P49761, Tchem |
Chemistry databases
ChEMBLi | CHEMBL4226 |
DrugBanki | DB08691, ethyl 3-[(E)-2-amino-1-cyanoethenyl]-6,7-dichloro-1-methyl-1H-indole-2-carboxylate DB12010, Fostamatinib DB07664, K-00546 |
DrugCentrali | P49761 |
GuidetoPHARMACOLOGYi | 1992 |
Genetic variation databases
BioMutai | CLK3 |
DMDMi | 148887358 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000085870 | 1 – 638 | Dual specificity protein kinase CLK3Add BLAST | 638 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 155 | PhosphotyrosineCombined sources | 1 | |
Modified residuei | 157 | PhosphoserineCombined sources | 1 | |
Modified residuei | 197 | PhosphoserineCombined sources | 1 | |
Modified residuei | 199 | PhosphoserineCombined sources | 1 | |
Modified residuei | 215 | PhosphoserineCombined sources | 1 | |
Modified residuei | 224 | PhosphoserineCombined sources | 1 | |
Modified residuei | 226 | PhosphoserineCombined sources | 1 | |
Modified residuei | 283 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | P49761 |
jPOSTi | P49761 |
MassIVEi | P49761 |
MaxQBi | P49761 |
PaxDbi | P49761 |
PeptideAtlasi | P49761 |
PRIDEi | P49761 |
ProteomicsDBi | 56096 [P49761-4] 56097 [P49761-1] 56098 [P49761-2] 56099 [P49761-3] |
PTM databases
iPTMneti | P49761 |
PhosphoSitePlusi | P49761 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000179335, Expressed in bone marrow and 230 other tissues |
ExpressionAtlasi | P49761, baseline and differential |
Genevisiblei | P49761, HS |
Organism-specific databases
HPAi | ENSG00000179335, Low tissue specificity |
Interactioni
Binary interactionsi
P49761
GO - Molecular functioni
- identical protein binding Source: IntAct
Protein-protein interaction databases
BioGRIDi | 107609, 177 interactors |
IntActi | P49761, 107 interactors |
MINTi | P49761 |
STRINGi | 9606.ENSP00000378505 |
Chemistry databases
BindingDBi | P49761 |
Miscellaneous databases
RNActi | P49761, protein |
Structurei
Secondary structure
3D structure databases
SMRi | P49761 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P49761 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 304 – 620 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 317 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 134 | DisorderedSequence analysisAdd BLAST | 134 | |
Regioni | 177 – 286 | DisorderedSequence analysisAdd BLAST | 110 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 177 – 226 | Basic and acidic residuesSequence analysisAdd BLAST | 50 | |
Compositional biasi | 237 – 266 | Basic residuesSequence analysisAdd BLAST | 30 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG0671, Eukaryota |
GeneTreei | ENSGT00940000160359 |
HOGENOMi | CLU_000288_5_16_1 |
InParanoidi | P49761 |
PhylomeDBi | P49761 |
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 (4+)i Sequence
Sequence statusi: Complete.
This entry describes 4 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 4 described isoforms and 12 potential isoforms that are computationally mapped.Show allAlign All
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
MPVLSARRRE LADHAGSGRR SGPSPTARSG PHLSALRAQP ARAAHLSGRG
60 70 80 90 100
TYVRRDTAGG GPGQARPLGP PGTSLLGRGA RRSGEGWCPG AFESGARAAR
110 120 130 140 150
PPSRVEPRLA TAASREGAGL PRAEVAAGSG RGARSGEWGL AAAGAWETMH
160 170 180 190 200
HCKRYRSPEP DPYLSYRWKR RRSYSREHEG RLRYPSRREP PPRRSRSRSH
210 220 230 240 250
DRLPYQRRYR ERRDSDTYRC EERSPSFGED YYGPSRSRHR RRSRERGPYR
260 270 280 290 300
TRKHAHHCHK RRTRSCSSAS SRSQQSSKRS SRSVEDDKEG HLVCRIGDWL
310 320 330 340 350
QERYEIVGNL GEGTFGKVVE CLDHARGKSQ VALKIIRNVG KYREAARLEI
360 370 380 390 400
NVLKKIKEKD KENKFLCVLM SDWFNFHGHM CIAFELLGKN TFEFLKENNF
410 420 430 440 450
QPYPLPHVRH MAYQLCHALR FLHENQLTHT DLKPENILFV NSEFETLYNE
460 470 480 490 500
HKSCEEKSVK NTSIRVADFG SATFDHEHHT TIVATRHYRP PEVILELGWA
510 520 530 540 550
QPCDVWSIGC ILFEYYRGFT LFQTHENREH LVMMEKILGP IPSHMIHRTR
560 570 580 590 600
KQKYFYKGGL VWDENSSDGR YVKENCKPLK SYMLQDSLEH VQLFDLMRRM
610 620 630
LEFDPAQRIT LAEALLHPFF AGLTPEERSF HTSRNPSR
The sequence of this isoform differs from the canonical sequence as follows:
1-148: Missing.
272-300: RSQQSSKRSSRSVEDDKEGHLVCRIGDWL → MRLWGTWVKAPLARWWSAWTMPEGSLRLP
301-638: Missing.
Computationally mapped potential isoform sequencesi
There are 12 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketH3BQG1 | H3BQG1_HUMAN | Dual-specificity protein kinase CLK... | CLK3 | 286 | Annotation score: | ||
H3BVF8 | H3BVF8_HUMAN | Dual-specificity protein kinase CLK... | CLK3 | 239 | Annotation score: | ||
H3BUL5 | H3BUL5_HUMAN | Dual-specificity protein kinase CLK... | CLK3 | 224 | Annotation score: | ||
H3BRT8 | H3BRT8_HUMAN | Dual-specificity protein kinase CLK... | CLK3 | 117 | Annotation score: | ||
H3BQR7 | H3BQR7_HUMAN | Dual-specificity protein kinase CLK... | CLK3 | 145 | Annotation score: | ||
H3BRK0 | H3BRK0_HUMAN | Dual-specificity protein kinase CLK... | CLK3 | 173 | Annotation score: | ||
H3BV35 | H3BV35_HUMAN | Dual-specificity protein kinase CLK... | CLK3 | 145 | Annotation score: | ||
H3BRE4 | H3BRE4_HUMAN | Dual-specificity protein kinase CLK... | CLK3 | 190 | Annotation score: | ||
H3BNQ5 | H3BNQ5_HUMAN | Dual-specificity protein kinase CLK... | CLK3 | 193 | Annotation score: | ||
H3BRW2 | H3BRW2_HUMAN | Dual-specificity protein kinase CLK... | CLK3 | 70 | Annotation score: | ||
There are more potential isoformsShow all |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 280 – 281 | SS → TG in AAA61484 (PubMed:7990150).Curated | 2 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_040413 | 486 | R → C1 PublicationCorresponds to variant dbSNP:rs975796055Ensembl. | 1 | |
Natural variantiVAR_045579 | 607 | Q → R1 PublicationCorresponds to variant dbSNP:rs910378995Ensembl. | 1 | |
Natural variantiVAR_045580 | 628 | R → W1 PublicationCorresponds to variant dbSNP:rs920443187Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_026138 | 1 – 148 | Missing in isoform 1, isoform 2 and isoform 3. 3 PublicationsAdd BLAST | 148 | |
Alternative sequenceiVSP_004858 | 272 – 300 | RSQQS…IGDWL → MRLWGTWVKAPLARWWSAWT MPEGSLRLP in isoform 2. 1 PublicationAdd BLAST | 29 | |
Alternative sequenceiVSP_004859 | 301 – 638 | Missing in isoform 2. 1 PublicationAdd BLAST | 338 | |
Alternative sequenceiVSP_004860 | 306 – 328 | Missing in isoform 3. 1 PublicationAdd BLAST | 23 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L29220 mRNA Translation: AAA61483.1 L29217 mRNA Translation: AAA61484.1 BT006993 mRNA Translation: AAP35639.1 AC100835 Genomic DNA No translation available. CH471136 Genomic DNA Translation: EAW99321.1 CH471136 Genomic DNA Translation: EAW99322.1 BC002555 mRNA Translation: AAH02555.1 Different initiation. BC006103 mRNA Translation: AAH06103.1 BC019881 mRNA Translation: AAH19881.1 Different initiation. |
CCDSi | CCDS10265.1 [P49761-1] CCDS45304.1 [P49761-1] |
PIRi | S53639 S53640 |
RefSeqi | NP_001123500.1, NM_001130028.1 [P49761-1] NP_003983.2, NM_003992.4 [P49761-1] XP_016877398.1, XM_017021909.1 XP_016877399.1, XM_017021910.1 |
Genome annotation databases
Ensembli | ENST00000345005; ENSP00000344112; ENSG00000179335 [P49761-1] ENST00000395066; ENSP00000378505; ENSG00000179335 [P49761-1] ENST00000483723; ENSP00000431825; ENSG00000179335 [P49761-2] |
GeneIDi | 1198 |
KEGGi | hsa:1198 |
MANE-Selecti | ENST00000395066.9; ENSP00000378505.4; NM_001130028.2; NP_001123500.2 [P49761-1] |
UCSCi | uc002ayg.4, human [P49761-4] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L29220 mRNA Translation: AAA61483.1 L29217 mRNA Translation: AAA61484.1 BT006993 mRNA Translation: AAP35639.1 AC100835 Genomic DNA No translation available. CH471136 Genomic DNA Translation: EAW99321.1 CH471136 Genomic DNA Translation: EAW99322.1 BC002555 mRNA Translation: AAH02555.1 Different initiation. BC006103 mRNA Translation: AAH06103.1 BC019881 mRNA Translation: AAH19881.1 Different initiation. |
CCDSi | CCDS10265.1 [P49761-1] CCDS45304.1 [P49761-1] |
PIRi | S53639 S53640 |
RefSeqi | NP_001123500.1, NM_001130028.1 [P49761-1] NP_003983.2, NM_003992.4 [P49761-1] XP_016877398.1, XM_017021909.1 XP_016877399.1, XM_017021910.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2EU9 | X-ray | 1.53 | A | 284-638 | [»] | |
2EXE | X-ray | 2.35 | A | 275-631 | [»] | |
2WU6 | X-ray | 1.92 | A | 275-632 | [»] | |
2WU7 | X-ray | 2.25 | A | 275-632 | [»] | |
3RAW | X-ray | 2.09 | A/B | 275-632 | [»] | |
6FT7 | X-ray | 2.02 | A/B | 275-632 | [»] | |
6FYP | X-ray | 2.29 | A | 275-632 | [»] | |
6FYR | X-ray | 1.42 | A | 275-632 | [»] | |
6KHF | X-ray | 2.60 | A | 149-638 | [»] | |
6RCT | X-ray | 2.32 | A/B | 275-632 | [»] | |
6YTW | X-ray | 2.00 | A/B | 275-632 | [»] | |
6YTY | X-ray | 1.76 | A | 275-632 | [»] | |
6YU1 | X-ray | 1.90 | a/c | 275-632 | [»] | |
6Z2V | X-ray | 2.60 | A | 275-632 | [»] | |
6Z51 | X-ray | 1.92 | A | 275-632 | [»] | |
6Z52 | X-ray | 2.12 | A/B | 275-632 | [»] | |
6Z53 | X-ray | 1.65 | A | 275-632 | [»] | |
6Z54 | X-ray | 1.73 | A | 275-632 | [»] | |
6Z55 | X-ray | 1.70 | A/B | 275-632 | [»] | |
SMRi | P49761 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 107609, 177 interactors |
IntActi | P49761, 107 interactors |
MINTi | P49761 |
STRINGi | 9606.ENSP00000378505 |
Chemistry databases
BindingDBi | P49761 |
ChEMBLi | CHEMBL4226 |
DrugBanki | DB08691, ethyl 3-[(E)-2-amino-1-cyanoethenyl]-6,7-dichloro-1-methyl-1H-indole-2-carboxylate DB12010, Fostamatinib DB07664, K-00546 |
DrugCentrali | P49761 |
GuidetoPHARMACOLOGYi | 1992 |
PTM databases
iPTMneti | P49761 |
PhosphoSitePlusi | P49761 |
Genetic variation databases
BioMutai | CLK3 |
DMDMi | 148887358 |
Proteomic databases
EPDi | P49761 |
jPOSTi | P49761 |
MassIVEi | P49761 |
MaxQBi | P49761 |
PaxDbi | P49761 |
PeptideAtlasi | P49761 |
PRIDEi | P49761 |
ProteomicsDBi | 56096 [P49761-4] 56097 [P49761-1] 56098 [P49761-2] 56099 [P49761-3] |
Protocols and materials databases
Antibodypediai | 26974, 152 antibodies from 26 providers |
DNASUi | 1198 |
Genome annotation databases
Ensembli | ENST00000345005; ENSP00000344112; ENSG00000179335 [P49761-1] ENST00000395066; ENSP00000378505; ENSG00000179335 [P49761-1] ENST00000483723; ENSP00000431825; ENSG00000179335 [P49761-2] |
GeneIDi | 1198 |
KEGGi | hsa:1198 |
MANE-Selecti | ENST00000395066.9; ENSP00000378505.4; NM_001130028.2; NP_001123500.2 [P49761-1] |
UCSCi | uc002ayg.4, human [P49761-4] |
Organism-specific databases
CTDi | 1198 |
DisGeNETi | 1198 |
GeneCardsi | CLK3 |
HGNCi | HGNC:2071, CLK3 |
HPAi | ENSG00000179335, Low tissue specificity |
MIMi | 602990, gene |
neXtProti | NX_P49761 |
OpenTargetsi | ENSG00000179335 |
PharmGKBi | PA26597 |
VEuPathDBi | HostDB:ENSG00000179335 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0671, Eukaryota |
GeneTreei | ENSGT00940000160359 |
HOGENOMi | CLU_000288_5_16_1 |
InParanoidi | P49761 |
PhylomeDBi | P49761 |
TreeFami | TF101041 |
Enzyme and pathway databases
BRENDAi | 2.7.12.1, 2681 |
PathwayCommonsi | P49761 |
SignaLinki | P49761 |
SIGNORi | P49761 |
Miscellaneous databases
BioGRID-ORCSi | 1198, 22 hits in 1077 CRISPR screens |
ChiTaRSi | CLK3, human |
EvolutionaryTracei | P49761 |
GeneWikii | CLK3_(gene) |
GenomeRNAii | 1198 |
Pharosi | P49761, Tchem |
PROi | PR:P49761 |
RNActi | P49761, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000179335, Expressed in bone marrow and 230 other tissues |
ExpressionAtlasi | P49761, baseline and differential |
Genevisiblei | P49761, 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 |
MobiDBi | Search... |
Entry informationi
Entry namei | CLK3_HUMAN | |
Accessioni | P49761Primary (citable) accession number: P49761 Secondary accession number(s): D3DW59 Q9BUJ7 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 1, 1996 |
Last sequence update: | June 12, 2007 | |
Last modified: | February 23, 2022 | |
This is version 214 of the entry and version 3 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 15
Human chromosome 15: 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