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Protein

Dual specificity protein kinase CLK3

Gene

CLK3

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. Phosphorylates SRSF1 and SRSF3. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells.2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

Leucettine L41 inhibits its kinase activity and affects the regulation of alternative splicing mediated by phosphorylation of SR proteins.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei334ATPPROSITE-ProRule annotation1
Active sitei431Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi310 – 318ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

  • protein autophosphorylation Source: Ensembl
  • protein phosphorylation Source: UniProtKB
  • 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:HS11371-MONOMER.
BRENDAi2.7.12.1. 2681.
SignaLinkiP49761.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

HGNCiHGNC:2071. CLK3.

Subcellular locationi

Isoform 2 :
  • Nucleus speckle

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

GO - Cellular componenti

  • acrosomal vesicle Source: UniProtKB-SubCell
  • intermediate filament cytoskeleton Source: HPA
  • membrane Source: UniProtKB
  • nuclear speck Source: UniProtKB-SubCell
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoplasmic vesicle, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi1198.
OpenTargetsiENSG00000179335.
PharmGKBiPA26597.

Chemistry databases

ChEMBLiCHEMBL4226.
GuidetoPHARMACOLOGYi1992.

Polymorphism and mutation databases

BioMutaiCLK3.
DMDMi148887358.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000858701 – 638Dual specificity protein kinase CLK3Add BLAST638

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei155PhosphotyrosineCombined sources1
Modified residuei157PhosphoserineCombined sources1
Modified residuei197PhosphoserineCombined sources1
Modified residuei199PhosphoserineCombined sources1
Modified residuei215PhosphoserineCombined sources1
Modified residuei224PhosphoserineCombined sources1
Modified residuei226PhosphoserineCombined sources1
Modified residuei283PhosphoserineCombined sources1

Post-translational modificationi

Autophosphorylates on all three types of residues.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP49761.
PaxDbiP49761.
PeptideAtlasiP49761.
PRIDEiP49761.

PTM databases

iPTMnetiP49761.
PhosphoSitePlusiP49761.

Expressioni

Tissue specificityi

Endothelial cells.1 Publication

Gene expression databases

BgeeiENSG00000179335.
CleanExiHS_CLK3.
ExpressionAtlasiP49761. baseline and differential.
GenevisibleiP49761. HS.

Organism-specific databases

HPAiHPA046817.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-745579,EBI-745579
CLK2P4976012EBI-745579,EBI-750020
HOXB6P175095EBI-745579,EBI-741308
HOXB7P096295EBI-745579,EBI-1248457
HOXC4P090174EBI-745579,EBI-3923226
OAS2P297283EBI-745579,EBI-10211452
RBMXP381593EBI-745579,EBI-743526
RBMY1A1P0DJD33EBI-745579,EBI-8638511
RBMY1JQ154153EBI-745579,EBI-8642021
RSRP1Q9BUV06EBI-745579,EBI-745604
SDCBPO005605EBI-745579,EBI-727004
SRPK2P783624EBI-745579,EBI-593303
SUV39H1O434632EBI-745579,EBI-349968
TINF2Q9BSI42EBI-745579,EBI-717399
ZNF263O149783EBI-745579,EBI-744493

Protein-protein interaction databases

BioGridi107609. 93 interactors.
IntActiP49761. 55 interactors.
MINTiMINT-1448658.
STRINGi9606.ENSP00000378505.

Chemistry databases

BindingDBiP49761.

Structurei

Secondary structure

1638
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni301 – 303Combined sources3
Beta strandi304 – 313Combined sources10
Beta strandi316 – 323Combined sources8
Turni324 – 328Combined sources5
Beta strandi330 – 336Combined sources7
Helixi340 – 359Combined sources20
Beta strandi370 – 376Combined sources7
Beta strandi379 – 385Combined sources7
Helixi391 – 397Combined sources7
Turni398 – 400Combined sources3
Helixi405 – 423Combined sources19
Turni424 – 426Combined sources3
Helixi434 – 436Combined sources3
Beta strandi437 – 440Combined sources4
Beta strandi444 – 448Combined sources5
Turni450 – 453Combined sources4
Beta strandi456 – 460Combined sources5
Beta strandi464 – 466Combined sources3
Helixi469 – 471Combined sources3
Helixi486 – 488Combined sources3
Helixi491 – 494Combined sources4
Helixi502 – 517Combined sources16
Helixi527 – 538Combined sources12
Helixi543 – 548Combined sources6
Helixi552 – 554Combined sources3
Helixi567 – 575Combined sources9
Helixi579 – 582Combined sources4
Helixi588 – 600Combined sources13
Turni605 – 607Combined sources3
Helixi611 – 614Combined sources4
Helixi618 – 622Combined sources5
Helixi625 – 628Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2EU9X-ray1.53A284-638[»]
2EXEX-ray2.35A275-631[»]
2WU6X-ray1.92A275-632[»]
2WU7X-ray2.25A275-632[»]
3RAWX-ray2.09A/B275-632[»]
ProteinModelPortaliP49761.
SMRiP49761.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP49761.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini304 – 620Protein kinasePROSITE-ProRule annotationAdd BLAST317

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi167 – 264Arg-richAdd BLAST98

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0671. Eukaryota.
ENOG410XQF2. LUCA.
GeneTreeiENSGT00580000081366.
HOGENOMiHOG000203417.
HOVERGENiHBG107720.
InParanoidiP49761.
KOiK08823.
OMAiNENKSCE.
OrthoDBiEOG091G033A.
PhylomeDBiP49761.
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 (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 4 (identifier: P49761-4) [UniParc]FASTAAdd to basket

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
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
Length:638
Mass (Da):73,515
Last modified:June 12, 2007 - v3
Checksum:iD3B60A9DB4ECEC94
GO
Isoform 1 (identifier: P49761-1) [UniParc]FASTAAdd to basket
Also known as: Long

The sequence of this isoform differs from the canonical sequence as follows:
     1-148: Missing.

Show »
Length:490
Mass (Da):58,588
Checksum:i86A342ABB8AB24CA
GO
Isoform 2 (identifier: P49761-2) [UniParc]FASTAAdd to basket
Also known as: Short

The sequence of this isoform differs from the canonical sequence as follows:
     1-148: Missing.
     272-300: RSQQSSKRSSRSVEDDKEGHLVCRIGDWL → MRLWGTWVKAPLARWWSAWTMPEGSLRLP
     301-638: 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:152
Mass (Da):18,971
Checksum:i5BABA6574A0E9801
GO
Isoform 3 (identifier: P49761-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-148: Missing.
     306-328: Missing.

Show »
Length:467
Mass (Da):56,207
Checksum:i2890E88AE23AE7BC
GO

Sequence cautioni

The sequence AAH02555 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAH19881 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti280 – 281SS → TG in AAA61484 (PubMed:7990150).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_040413486R → C.1 Publication1
Natural variantiVAR_045579607Q → R.1 Publication1
Natural variantiVAR_045580628R → W.1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0261381 – 148Missing in isoform 1, isoform 2 and isoform 3. 3 PublicationsAdd BLAST148
Alternative sequenceiVSP_004858272 – 300RSQQS…IGDWL → MRLWGTWVKAPLARWWSAWT MPEGSLRLP in isoform 2. 1 PublicationAdd BLAST29
Alternative sequenceiVSP_004859301 – 638Missing in isoform 2. 1 PublicationAdd BLAST338
Alternative sequenceiVSP_004860306 – 328Missing in isoform 3. 1 PublicationAdd BLAST23

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.
CCDSiCCDS10265.1. [P49761-1]
CCDS45304.1. [P49761-4]
PIRiS53639.
S53640.
RefSeqiNP_001123500.1. NM_001130028.1. [P49761-4]
NP_003983.2. NM_003992.4. [P49761-1]
XP_016877398.1. XM_017021909.1. [P49761-1]
XP_016877399.1. XM_017021910.1. [P49761-1]
UniGeneiHs.511790.
Hs.584748.

Genome annotation databases

EnsembliENST00000345005; ENSP00000344112; ENSG00000179335. [P49761-1]
ENST00000395066; ENSP00000378505; ENSG00000179335. [P49761-4]
ENST00000483723; ENSP00000431825; ENSG00000179335. [P49761-2]
GeneIDi1198.
KEGGihsa:1198.
UCSCiuc002ayg.4. human. [P49761-4]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

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.
CCDSiCCDS10265.1. [P49761-1]
CCDS45304.1. [P49761-4]
PIRiS53639.
S53640.
RefSeqiNP_001123500.1. NM_001130028.1. [P49761-4]
NP_003983.2. NM_003992.4. [P49761-1]
XP_016877398.1. XM_017021909.1. [P49761-1]
XP_016877399.1. XM_017021910.1. [P49761-1]
UniGeneiHs.511790.
Hs.584748.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2EU9X-ray1.53A284-638[»]
2EXEX-ray2.35A275-631[»]
2WU6X-ray1.92A275-632[»]
2WU7X-ray2.25A275-632[»]
3RAWX-ray2.09A/B275-632[»]
ProteinModelPortaliP49761.
SMRiP49761.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107609. 93 interactors.
IntActiP49761. 55 interactors.
MINTiMINT-1448658.
STRINGi9606.ENSP00000378505.

Chemistry databases

BindingDBiP49761.
ChEMBLiCHEMBL4226.
GuidetoPHARMACOLOGYi1992.

PTM databases

iPTMnetiP49761.
PhosphoSitePlusiP49761.

Polymorphism and mutation databases

BioMutaiCLK3.
DMDMi148887358.

Proteomic databases

EPDiP49761.
PaxDbiP49761.
PeptideAtlasiP49761.
PRIDEiP49761.

Protocols and materials databases

DNASUi1198.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000345005; ENSP00000344112; ENSG00000179335. [P49761-1]
ENST00000395066; ENSP00000378505; ENSG00000179335. [P49761-4]
ENST00000483723; ENSP00000431825; ENSG00000179335. [P49761-2]
GeneIDi1198.
KEGGihsa:1198.
UCSCiuc002ayg.4. human. [P49761-4]

Organism-specific databases

CTDi1198.
DisGeNETi1198.
GeneCardsiCLK3.
HGNCiHGNC:2071. CLK3.
HPAiHPA046817.
MIMi602990. gene.
neXtProtiNX_P49761.
OpenTargetsiENSG00000179335.
PharmGKBiPA26597.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0671. Eukaryota.
ENOG410XQF2. LUCA.
GeneTreeiENSGT00580000081366.
HOGENOMiHOG000203417.
HOVERGENiHBG107720.
InParanoidiP49761.
KOiK08823.
OMAiNENKSCE.
OrthoDBiEOG091G033A.
PhylomeDBiP49761.
TreeFamiTF101041.

Enzyme and pathway databases

BioCyciZFISH:HS11371-MONOMER.
BRENDAi2.7.12.1. 2681.
SignaLinkiP49761.

Miscellaneous databases

ChiTaRSiCLK3. human.
EvolutionaryTraceiP49761.
GeneWikiiCLK3_(gene).
GenomeRNAii1198.
PROiP49761.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000179335.
CleanExiHS_CLK3.
ExpressionAtlasiP49761. baseline and differential.
GenevisibleiP49761. 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 nameiCLK3_HUMAN
AccessioniPrimary (citable) accession number: P49761
Secondary accession number(s): D3DW59
, Q53Y48, Q9BRS3, Q9BUJ7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: June 12, 2007
Last modified: November 30, 2016
This is version 175 of the entry and version 3 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 15
    Human chromosome 15: 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.