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Protein

Dual specificity protein kinase CLK1

Gene

CLK1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase, Tyrosine-protein kinase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000013441.15
HGNCiHGNC:2068 CLK1
MIMi601951 gene
neXtProtiNX_P49759

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi1195
OpenTargetsiENSG00000013441
PharmGKBiPA26594

Chemistry databases

ChEMBLiCHEMBL4224
DrugBankiDB04367 Debromohymenialdisine
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
ProteomicsDBi56090
56091 [P49759-2]
56092 [P49759-3]

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

Show more details

Protein-protein interaction databases

BioGridi107606, 168 interactors
IntActiP49759, 34 interactors
MINTiP49759
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

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

Phylogenomic databases

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

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

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 → F1 PublicationCorresponds to variant dbSNP:rs55989135Ensembl.1
Natural variantiVAR_04655199N → D. Corresponds to variant dbSNP:rs6735666Ensembl.1
Natural variantiVAR_040410118R → G1 PublicationCorresponds to variant dbSNP:rs56135616Ensembl.1
Natural variantiVAR_040411307P → S1 PublicationCorresponds to variant dbSNP:rs35412475Ensembl.1
Natural variantiVAR_040412440M → T1 PublicationCorresponds to variant dbSNP:rs35393352Ensembl.1
Natural variantiVAR_051620459E → G. Corresponds to variant dbSNP:rs12709Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiCLK1_HUMAN
AccessioniPrimary (citable) accession number: P49759
Secondary accession number(s): B4DFW7, Q0P694, Q8N5V8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: September 23, 2008
Last modified: July 18, 2018
This is version 176 of the entry and version 2 of the sequence. See 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

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