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Protein

Dual specificity protein kinase CLK3

Gene

CLK3

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. 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.

Activity 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

Keywordsi

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

Enzyme and pathway databases

BRENDAi2.7.12.1 2681
SignaLinkiP49761
SIGNORiP49761

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

EuPathDBiHostDB:ENSG00000179335.18
HGNCiHGNC:2071 CLK3
MIMi602990 gene
neXtProtiNX_P49761

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

Cytoplasm, Cytoplasmic vesicle, Nucleus

Pathology & Biotechi

Organism-specific databases

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
ProteomicsDBi56096
56097 [P49761-1]
56098 [P49761-2]
56099 [P49761-3]

PTM databases

iPTMnetiP49761
PhosphoSitePlusiP49761

Expressioni

Tissue specificityi

Endothelial cells.1 Publication

Gene expression databases

BgeeiENSG00000179335 Expressed in 219 organ(s), highest expression level in lower esophagus mucosa
CleanExiHS_CLK3
ExpressionAtlasiP49761 baseline and differential
GenevisibleiP49761 HS

Organism-specific databases

HPAiHPA046817

Interactioni

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi107609, 106 interactors
IntActiP49761, 69 interactors
MINTiP49761
STRINGi9606.ENSP00000378505

Chemistry databases

BindingDBiP49761

Structurei

Secondary structure

1638
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Phylogenomic databases

eggNOGiKOG0671 Eukaryota
ENOG410XQF2 LUCA
GeneTreeiENSGT00580000081366
HOGENOMiHOG000203417
HOVERGENiHBG107720
InParanoidiP49761
KOiK08823
OMAiWDENTSD
OrthoDBiEOG091G033A
PhylomeDBiP49761
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 (4+)i

Sequence statusi: Complete.

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

This entry has 4 described isoforms and 12 potential isoforms that are computationally mapped.iShow all

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

Computationally mapped potential isoform sequencesi

There are 12 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H3BQG1H3BQG1_HUMAN
Dual-specificity protein kinase CLK...
CLK3
306Annotation score:
H3BUL5H3BUL5_HUMAN
Dual-specificity protein kinase CLK...
CLK3
224Annotation score:
H3BVF8H3BVF8_HUMAN
Dual-specificity protein kinase CLK...
CLK3
239Annotation score:
H3BNQ5H3BNQ5_HUMAN
Dual-specificity protein kinase CLK...
CLK3
193Annotation score:
H3BRE4H3BRE4_HUMAN
Dual-specificity protein kinase CLK...
CLK3
190Annotation score:
H3BRT8H3BRT8_HUMAN
Dual-specificity protein kinase CLK...
CLK3
117Annotation score:
H3BNC8H3BNC8_HUMAN
Dual-specificity protein kinase CLK...
CLK3
59Annotation score:
H3BRK0H3BRK0_HUMAN
Dual-specificity protein kinase CLK...
CLK3
173Annotation score:
H3BQR7H3BQR7_HUMAN
Dual-specificity protein kinase CLK...
CLK3
145Annotation score:
H3BRW2H3BRW2_HUMAN
Dual-specificity protein kinase CLK...
CLK3
70Annotation score:
There are more potential isoformsShow all

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 → C1 Publication1
Natural variantiVAR_045579607Q → R1 PublicationCorresponds to variant dbSNP:rs910378995Ensembl.1
Natural variantiVAR_045580628R → W1 PublicationCorresponds to variant dbSNP:rs920443187Ensembl.1

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

Similar proteinsi

Entry informationi

Entry nameiCLK3_HUMAN
AccessioniPrimary (citable) accession number: P49761
Secondary accession number(s): D3DW59
, Q53Y48, Q9BRS3, Q9BUJ7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: June 12, 2007
Last modified: September 12, 2018
This is version 190 of the entry and version 3 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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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