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Protein

Dual specificity protein kinase CLK2

Gene

CLK2

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. 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. Acts as a suppressor of hepatic gluconeogenesis and glucose output by repressing PPARGC1A transcriptional activity on gluconeogenic genes via its phosphorylation. Phosphorylates PPP2R5B thereby stimulating the assembly of PP2A phosphatase with the PPP2R5B-AKT1 complex leading to dephosphorylation of AKT1. Phosphorylates: PTPN1, SRSF1 and SRSF3. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells.4 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

5,6-dichloro-1-b-D-ribofuranosylbenzimidazole (DRB) inhibits autophosphorylation. TG003 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 sitei193ATPPROSITE-ProRule annotation1
Active sitei290Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi169 – 177ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

  • negative regulation of gluconeogenesis Source: UniProtKB
  • protein autophosphorylation Source: UniProtKB
  • protein phosphorylation Source: UniProtKB
  • regulation of RNA splicing Source: UniProtKB
  • response to ionizing radiation Source: UniProtKB
  • response to retinoic acid Source: Ensembl
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:HS11052-MONOMER.
BRENDAi2.7.12.1. 2681.
SignaLinkiP49760.
SIGNORiP49760.

Names & Taxonomyi

Protein namesi
Recommended name:
Dual specificity protein kinase CLK2 (EC:2.7.12.1)
Alternative name(s):
CDC-like kinase 2
Gene namesi
Name:CLK2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:2069. CLK2.

Subcellular locationi

Isoform 1 :
  • Nucleus
  • Nucleus speckle

  • Note: Inhibition of phosphorylation at Ser-142 results in accumulation in the nuclear speckle.By similarity
Isoform 2 :
  • Nucleus speckle

  • Note: Co-localizes with serine- and arginine-rich (SR) proteins in the nuclear speckles.

GO - Cellular componenti

  • nuclear speck Source: UniProtKB-SubCell
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi1196.
OpenTargetsiENSG00000176444.
ENSG00000261893.
PharmGKBiPA26595.

Chemistry databases

ChEMBLiCHEMBL4225.
GuidetoPHARMACOLOGYi1991.

Polymorphism and mutation databases

BioMutaiCLK2.
DMDMi1705919.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000858681 – 499Dual specificity protein kinase CLK2Add BLAST499

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei34Phosphoserine; by PKB/AKT11 Publication1
Modified residuei98PhosphoserineCombined sources1
Modified residuei99Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei127Phosphothreonine; by PKB/AKT11 Publication1
Modified residuei142Phosphoserine; by autocatalysisCombined sources1
Modified residuei153PhosphotyrosineCombined sources1
Modified residuei344Phosphothreonine; by PKB/AKT2By similarity1

Post-translational modificationi

Autophosphorylates on all three types of residues. Phosphorylation on Ser-34 and Thr-127 by AKT1 is induced by ionizing radiation or insulin. Phosphorylation plays a critical role in cell proliferation following low dose radiation and prevents cell death following high dose radiation. Phosphorylation at Thr-344 by PKB/AKT2 induces its kinase activity which is required for its stability. The phosphorylation status at Ser-142 influences its subnuclear localization; inhibition of phosphorylation at Ser-142 results in accumulation in the nuclear speckle.2 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiP49760.
PaxDbiP49760.
PeptideAtlasiP49760.
PRIDEiP49760.

PTM databases

iPTMnetiP49760.
PhosphoSitePlusiP49760.

Expressioni

Tissue specificityi

Endothelial cells.1 Publication

Gene expression databases

BgeeiENSG00000176444.
CleanExiHS_CLK2.
ExpressionAtlasiP49760. baseline and differential.
GenevisibleiP49760. HS.

Organism-specific databases

HPAiHPA055366.
HPA059507.

Interactioni

Subunit structurei

Interacts with RBMX. Interacts with AKT1 and UBL5.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-750020,EBI-750020
CLK3P4976112EBI-750020,EBI-745579
CPSF7Q8N6843EBI-750020,EBI-746909
ECE1P428925EBI-750020,EBI-2859983
FLJ13057Q53SE73EBI-750020,EBI-10172181
KLHL2O951985EBI-750020,EBI-746999
LNX1Q8TBB17EBI-750020,EBI-739832
LUZP4Q9P1275EBI-750020,EBI-10198848
MRPL4Q9BYD33EBI-750020,EBI-721368
PRPF38AQ8NAV13EBI-750020,EBI-715374
RBM39Q144986EBI-750020,EBI-395290
RNPS1D3DU925EBI-750020,EBI-10176640
RSRP1Q9BUV05EBI-750020,EBI-745604
SDCBPO005603EBI-750020,EBI-727004
SNIP1Q8TAD84EBI-750020,EBI-749336
SNRNP70P086212EBI-750020,EBI-1049228
SRPK2P783623EBI-750020,EBI-593303
SRRM1Q8IYB33EBI-750020,EBI-1055880
TRIM27P143733EBI-750020,EBI-719493
U2AF1Q01081-23EBI-750020,EBI-10176676
UBE2IQ7KZS03EBI-750020,EBI-10180829
YTHDC1Q96MU75EBI-750020,EBI-2849854
ZNF263O149783EBI-750020,EBI-744493
ZNF394Q53GI33EBI-750020,EBI-10211248
ZNF398Q8TD175EBI-750020,EBI-8643207
ZNF473Q8WTR73EBI-750020,EBI-751409
ZRSR2Q156965EBI-750020,EBI-6657923

Protein-protein interaction databases

BioGridi107607. 97 interactors.
DIPiDIP-42277N.
IntActiP49760. 61 interactors.
MINTiMINT-1683264.
STRINGi9606.ENSP00000354856.

Chemistry databases

BindingDBiP49760.

Structurei

Secondary structure

1499
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni146 – 149Combined sources4
Turni160 – 162Combined sources3
Beta strandi163 – 172Combined sources10
Beta strandi175 – 182Combined sources8
Turni183 – 187Combined sources5
Beta strandi189 – 195Combined sources7
Helixi199 – 218Combined sources20
Beta strandi229 – 235Combined sources7
Beta strandi238 – 244Combined sources7
Helixi250 – 256Combined sources7
Turni257 – 259Combined sources3
Helixi264 – 283Combined sources20
Helixi293 – 295Combined sources3
Beta strandi296 – 299Combined sources4
Turni309 – 311Combined sources3
Beta strandi317 – 319Combined sources3
Beta strandi323 – 325Combined sources3
Beta strandi332 – 336Combined sources5
Helixi345 – 347Combined sources3
Helixi350 – 353Combined sources4
Helixi361 – 376Combined sources16
Helixi386 – 397Combined sources12
Helixi402 – 407Combined sources6
Helixi411 – 413Combined sources3
Helixi426 – 434Combined sources9
Helixi438 – 441Combined sources4
Helixi447 – 459Combined sources13
Turni464 – 466Combined sources3
Helixi470 – 475Combined sources6
Helixi477 – 479Combined sources3
Helixi480 – 483Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3NR9X-ray2.89A/B/C135-496[»]
ProteinModelPortaliP49760.
SMRiP49760.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP49760.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini163 – 479Protein kinasePROSITE-ProRule annotationAdd BLAST317

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0671. Eukaryota.
ENOG410XQF2. LUCA.
GeneTreeiENSGT00580000081366.
HOGENOMiHOG000203417.
HOVERGENiHBG107720.
InParanoidiP49760.
KOiK08823.
OMAiYSIGQVR.
OrthoDBiEOG091G033A.
PhylomeDBiP49760.
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: P49760-1) [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
MPHPRRYHSS ERGSRGSYRE HYRSRKHKRR RSRSWSSSSD RTRRRRREDS
60 70 80 90 100
YHVRSRSSYD DRSSDRRVYD RRYCGSYRRN DYSRDRGDAY YDTDYRHSYE
110 120 130 140 150
YQRENSSYRS QRSSRRKHRR RRRRSRTFSR SSSQHSSRRA KSVEDDAEGH
160 170 180 190 200
LIYHVGDWLQ ERYEIVSTLG EGTFGRVVQC VDHRRGGARV ALKIIKNVEK
210 220 230 240 250
YKEAARLEIN VLEKINEKDP DNKNLCVQMF DWFDYHGHMC ISFELLGLST
260 270 280 290 300
FDFLKDNNYL PYPIHQVRHM AFQLCQAVKF LHDNKLTHTD LKPENILFVN
310 320 330 340 350
SDYELTYNLE KKRDERSVKS TAVRVVDFGS ATFDHEHHST IVSTRHYRAP
360 370 380 390 400
EVILELGWSQ PCDVWSIGCI IFEYYVGFTL FQTHDNREHL AMMERILGPI
410 420 430 440 450
PSRMIRKTRK QKYFYRGRLD WDENTSAGRY VRENCKPLRR YLTSEAEEHH
460 470 480 490
QLFDLIESML EYEPAKRLTL GEALQHPFFA RLRAEPPNKL WDSSRDISR
Length:499
Mass (Da):60,090
Last modified:October 1, 1996 - v1
Checksum:iE43BBF3BAD6EF991
GO
Isoform 2 (identifier: P49760-2) [UniParc]FASTAAdd to basket
Also known as: Short

The sequence of this isoform differs from the canonical sequence as follows:
     134-139: QHSSRR → MKSLAP
     140-499: 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:139
Mass (Da):17,569
Checksum:iCC9C9C63B3B07667
GO
Isoform 3 (identifier: P49760-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     134-134: Missing.

Show »
Length:498
Mass (Da):59,962
Checksum:i0A21FC66FD22DBC6
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_004856134 – 139QHSSRR → MKSLAP in isoform 2. 1 Publication6
Alternative sequenceiVSP_038744134Missing in isoform 3. 1 Publication1
Alternative sequenceiVSP_004857140 – 499Missing in isoform 2. 1 PublicationAdd BLAST360

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L29218 mRNA. Translation: AAA61482.1.
L29216 mRNA. Translation: AAA61481.1.
AF023268 Genomic DNA. Translation: AAC51817.1.
AL713999 Genomic DNA. Translation: CAI95098.1.
BC014067 mRNA. Translation: AAH14067.1.
BC053603 mRNA. Translation: AAH53603.1.
CCDSiCCDS1107.1. [P49760-3]
CCDS72939.1. [P49760-1]
PIRiS53637.
S53638.
RefSeqiNP_001281267.1. NM_001294338.1. [P49760-1]
NP_001281268.1. NM_001294339.1.
NP_003984.2. NM_003993.3. [P49760-3]
UniGeneiHs.73986.

Genome annotation databases

EnsembliENST00000361168; ENSP00000354856; ENSG00000176444. [P49760-3]
ENST00000368361; ENSP00000357345; ENSG00000176444. [P49760-1]
ENST00000572269; ENSP00000459461; ENSG00000261893. [P49760-3]
ENST00000574445; ENSP00000460443; ENSG00000261893. [P49760-1]
GeneIDi1196.
KEGGihsa:1196.
UCSCiuc001fjw.4. human. [P49760-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L29218 mRNA. Translation: AAA61482.1.
L29216 mRNA. Translation: AAA61481.1.
AF023268 Genomic DNA. Translation: AAC51817.1.
AL713999 Genomic DNA. Translation: CAI95098.1.
BC014067 mRNA. Translation: AAH14067.1.
BC053603 mRNA. Translation: AAH53603.1.
CCDSiCCDS1107.1. [P49760-3]
CCDS72939.1. [P49760-1]
PIRiS53637.
S53638.
RefSeqiNP_001281267.1. NM_001294338.1. [P49760-1]
NP_001281268.1. NM_001294339.1.
NP_003984.2. NM_003993.3. [P49760-3]
UniGeneiHs.73986.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3NR9X-ray2.89A/B/C135-496[»]
ProteinModelPortaliP49760.
SMRiP49760.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107607. 97 interactors.
DIPiDIP-42277N.
IntActiP49760. 61 interactors.
MINTiMINT-1683264.
STRINGi9606.ENSP00000354856.

Chemistry databases

BindingDBiP49760.
ChEMBLiCHEMBL4225.
GuidetoPHARMACOLOGYi1991.

PTM databases

iPTMnetiP49760.
PhosphoSitePlusiP49760.

Polymorphism and mutation databases

BioMutaiCLK2.
DMDMi1705919.

Proteomic databases

MaxQBiP49760.
PaxDbiP49760.
PeptideAtlasiP49760.
PRIDEiP49760.

Protocols and materials databases

DNASUi1196.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000361168; ENSP00000354856; ENSG00000176444. [P49760-3]
ENST00000368361; ENSP00000357345; ENSG00000176444. [P49760-1]
ENST00000572269; ENSP00000459461; ENSG00000261893. [P49760-3]
ENST00000574445; ENSP00000460443; ENSG00000261893. [P49760-1]
GeneIDi1196.
KEGGihsa:1196.
UCSCiuc001fjw.4. human. [P49760-1]

Organism-specific databases

CTDi1196.
DisGeNETi1196.
GeneCardsiCLK2.
H-InvDBHIX0001112.
HGNCiHGNC:2069. CLK2.
HPAiHPA055366.
HPA059507.
MIMi602989. gene.
neXtProtiNX_P49760.
OpenTargetsiENSG00000176444.
ENSG00000261893.
PharmGKBiPA26595.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0671. Eukaryota.
ENOG410XQF2. LUCA.
GeneTreeiENSGT00580000081366.
HOGENOMiHOG000203417.
HOVERGENiHBG107720.
InParanoidiP49760.
KOiK08823.
OMAiYSIGQVR.
OrthoDBiEOG091G033A.
PhylomeDBiP49760.
TreeFamiTF101041.

Enzyme and pathway databases

BioCyciZFISH:HS11052-MONOMER.
BRENDAi2.7.12.1. 2681.
SignaLinkiP49760.
SIGNORiP49760.

Miscellaneous databases

ChiTaRSiCLK2. human.
EvolutionaryTraceiP49760.
GeneWikiiCLK2.
GenomeRNAii1196.
PROiP49760.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000176444.
CleanExiHS_CLK2.
ExpressionAtlasiP49760. baseline and differential.
GenevisibleiP49760. 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 nameiCLK2_HUMAN
AccessioniPrimary (citable) accession number: P49760
Secondary accession number(s): B1AVS9, B5MBX6, Q96CQ0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: November 30, 2016
This is version 170 of the entry and version 1 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 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  5. 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.