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Protein

Dual specificity protein kinase CLK1

Gene

CLK1

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, 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

ATP + a protein = ADP + a phosphoprotein.

Enzyme 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 keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei191ATPPROSITE-ProRule annotation1
Active sitei288Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi167 – 175ATPPROSITE-ProRule annotation9

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

  • cell proliferation Source: ProtInc
  • peptidyl-serine phosphorylation Source: Ensembl
  • peptidyl-threonine phosphorylation Source: Ensembl
  • protein autophosphorylation Source: Ensembl
  • 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

BioCyciZFISH:HS00348-MONOMER.
BRENDAi2.7.12.1. 2681.
SignaLinkiP49759.
SIGNORiP49759.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:2068. CLK1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi1195.
MalaCardsiCLK1.
OpenTargetsiENSG00000013441.
PharmGKBiPA26594.

Chemistry databases

ChEMBLiCHEMBL4224.
GuidetoPHARMACOLOGYi1990.

Polymorphism and mutation databases

BioMutaiCLK1.
DMDMi206729857.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000858661 – 484Dual specificity protein kinase CLK1Add BLAST484

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei61PhosphoserineCombined sources1
Modified residuei138PhosphothreonineCombined sources1
Modified residuei140PhosphoserineCombined sources1

Post-translational modificationi

Autophosphorylates on all three types of residues.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP49759.
MaxQBiP49759.
PaxDbiP49759.
PeptideAtlasiP49759.
PRIDEiP49759.

PTM databases

iPTMnetiP49759.
PhosphoSitePlusiP49759.

Expressioni

Tissue specificityi

Endothelial cells.1 Publication

Gene expression databases

BgeeiENSG00000013441.
CleanExiHS_CLK1.
ExpressionAtlasiP49759. baseline and differential.
GenevisibleiP49759. HS.

Organism-specific databases

HPAiCAB033141.
HPA062405.

Interactioni

Subunit structurei

Interacts with PPIG and UBL5.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
KRTAP10-7P604093EBI-473775,EBI-10172290
PDE9AO760833EBI-473775,EBI-742764

Protein-protein interaction databases

BioGridi107606. 167 interactors.
IntActiP49759. 28 interactors.
MINTiMINT-8417657.
STRINGi9606.ENSP00000394734.

Chemistry databases

BindingDBiP49759.

Structurei

Secondary structure

1484
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi148 – 150Combined sources3
Turni158 – 160Combined sources3
Beta strandi161 – 170Combined sources10
Beta strandi173 – 180Combined sources8
Turni181 – 185Combined sources5
Beta strandi187 – 193Combined sources7
Helixi197 – 216Combined sources20
Beta strandi227 – 233Combined sources7
Beta strandi236 – 242Combined sources7
Helixi248 – 254Combined sources7
Turni255 – 257Combined sources3
Helixi262 – 281Combined sources20
Helixi291 – 293Combined sources3
Beta strandi294 – 297Combined sources4
Beta strandi301 – 305Combined sources5
Turni307 – 310Combined sources4
Beta strandi312 – 317Combined sources6
Beta strandi321 – 323Combined sources3
Helixi343 – 345Combined sources3
Helixi348 – 351Combined sources4
Helixi359 – 374Combined sources16
Helixi384 – 395Combined sources12
Helixi400 – 405Combined sources6
Helixi409 – 411Combined sources3
Helixi424 – 432Combined sources9
Helixi436 – 439Combined sources4
Helixi445 – 457Combined sources13
Turni462 – 464Combined sources3
Helixi468 – 471Combined sources4
Helixi475 – 481Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1Z57X-ray1.70A148-484[»]
2VAGX-ray1.80A148-484[»]
5J1VX-ray2.52A/B/C148-484[»]
5J1WX-ray2.42A/B/C148-484[»]
ProteinModelPortaliP49759.
SMRiP49759.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP49759.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini161 – 477Protein kinasePROSITE-ProRule annotationAdd BLAST317

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0671. Eukaryota.
ENOG410XQF2. LUCA.
GeneTreeiENSGT00580000081366.
HOGENOMiHOG000203417.
HOVERGENiHBG107720.
InParanoidiP49759.
KOiK08823.
OMAiYVEEYNP.
OrthoDBiEOG091G033A.
PhylomeDBiP49759.
TreeFamiTF101041.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
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]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P49759-1) [UniParc]FASTAAdd to basket
Also known as: Long

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        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
Length:484
Mass (Da):57,291
Last modified:September 23, 2008 - v2
Checksum:iF34B5B44988BD118
GO
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.
Show »
Length:136
Mass (Da):16,570
Checksum:i3A1B92FD19E2A521
GO
Isoform 3 (identifier: P49759-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MAAGRRPASALWPERRGSPLRGDLLGFQNVREPSSCGETLSGM

Note: No experimental confirmation available.
Show »
Length:526
Mass (Da):61,757
Checksum:i8514814549CC0655
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti432R → A in AAA61480 (PubMed:1704889).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04040961S → F.1 PublicationCorresponds to variant rs55989135dbSNPEnsembl.1
Natural variantiVAR_04655199N → D.Corresponds to variant rs6735666dbSNPEnsembl.1
Natural variantiVAR_040410118R → G.1 PublicationCorresponds to variant rs56135616dbSNPEnsembl.1
Natural variantiVAR_040411307P → S.1 PublicationCorresponds to variant rs35412475dbSNPEnsembl.1
Natural variantiVAR_040412440M → T.1 PublicationCorresponds to variant rs35393352dbSNPEnsembl.1
Natural variantiVAR_051620459E → G.Corresponds to variant rs12709dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0435781M → MAAGRRPASALWPERRGSPL RGDLLGFQNVREPSSCGETL SGM in isoform 3. 1 Publication1
Alternative sequenceiVSP_004852131 – 136KSHRRK → MKLLIL in isoform 2. 3 Publications6
Alternative sequenceiVSP_004853137 – 484Missing in isoform 2. 3 PublicationsAdd BLAST348

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.
CCDSiCCDS2331.1. [P49759-1]
CCDS54427.1. [P49759-3]
PIRiS53641.
RefSeqiNP_001155879.1. NM_001162407.1. [P49759-3]
NP_004062.2. NM_004071.3. [P49759-1]
UniGeneiHs.433732.

Genome annotation databases

EnsembliENST00000321356; ENSP00000326830; ENSG00000013441. [P49759-1]
ENST00000432425; ENSP00000400487; ENSG00000013441. [P49759-2]
ENST00000434813; ENSP00000394734; ENSG00000013441. [P49759-3]
GeneIDi1195.
KEGGihsa:1195.
UCSCiuc002uwe.3. human. [P49759-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

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.
CCDSiCCDS2331.1. [P49759-1]
CCDS54427.1. [P49759-3]
PIRiS53641.
RefSeqiNP_001155879.1. NM_001162407.1. [P49759-3]
NP_004062.2. NM_004071.3. [P49759-1]
UniGeneiHs.433732.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1Z57X-ray1.70A148-484[»]
2VAGX-ray1.80A148-484[»]
5J1VX-ray2.52A/B/C148-484[»]
5J1WX-ray2.42A/B/C148-484[»]
ProteinModelPortaliP49759.
SMRiP49759.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107606. 167 interactors.
IntActiP49759. 28 interactors.
MINTiMINT-8417657.
STRINGi9606.ENSP00000394734.

Chemistry databases

BindingDBiP49759.
ChEMBLiCHEMBL4224.
GuidetoPHARMACOLOGYi1990.

PTM databases

iPTMnetiP49759.
PhosphoSitePlusiP49759.

Polymorphism and mutation databases

BioMutaiCLK1.
DMDMi206729857.

Proteomic databases

EPDiP49759.
MaxQBiP49759.
PaxDbiP49759.
PeptideAtlasiP49759.
PRIDEiP49759.

Protocols and materials databases

DNASUi1195.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000321356; ENSP00000326830; ENSG00000013441. [P49759-1]
ENST00000432425; ENSP00000400487; ENSG00000013441. [P49759-2]
ENST00000434813; ENSP00000394734; ENSG00000013441. [P49759-3]
GeneIDi1195.
KEGGihsa:1195.
UCSCiuc002uwe.3. human. [P49759-1]

Organism-specific databases

CTDi1195.
DisGeNETi1195.
GeneCardsiCLK1.
HGNCiHGNC:2068. CLK1.
HPAiCAB033141.
HPA062405.
MalaCardsiCLK1.
MIMi601951. gene.
neXtProtiNX_P49759.
OpenTargetsiENSG00000013441.
PharmGKBiPA26594.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0671. Eukaryota.
ENOG410XQF2. LUCA.
GeneTreeiENSGT00580000081366.
HOGENOMiHOG000203417.
HOVERGENiHBG107720.
InParanoidiP49759.
KOiK08823.
OMAiYVEEYNP.
OrthoDBiEOG091G033A.
PhylomeDBiP49759.
TreeFamiTF101041.

Enzyme and pathway databases

BioCyciZFISH:HS00348-MONOMER.
BRENDAi2.7.12.1. 2681.
SignaLinkiP49759.
SIGNORiP49759.

Miscellaneous databases

ChiTaRSiCLK1. human.
EvolutionaryTraceiP49759.
GeneWikiiCLK1.
GenomeRNAii1195.
PROiP49759.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000013441.
CleanExiHS_CLK1.
ExpressionAtlasiP49759. baseline and differential.
GenevisibleiP49759. HS.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
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...

Entry informationi

Entry nameiCLK1_HUMAN
AccessioniPrimary (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: November 30, 2016
This is version 164 of the entry and version 2 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

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 one 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.