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Protein

Dual specificity protein kinase CLK4

Gene

Clk4

Organism
Mus musculus (Mouse)
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 and SRSF3. Required for the regulation of alternative splicing of MAPT/TAU. 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

TG003 inhibits its kinase activity and affects the regulation of alternative splicing mediated by phosphorylation of SR proteins.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei189 – 1891ATPPROSITE-ProRule annotation
Active sitei286 – 2861Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi165 – 1739ATPPROSITE-ProRule annotation

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • protein serine/threonine/tyrosine kinase activity Source: UniProtKB-EC
  • protein serine/threonine kinase activity Source: UniProtKB
  • protein tyrosine kinase activity Source: MGI

GO - Biological processi

  • peptidyl-tyrosine phosphorylation Source: MGI
  • protein autophosphorylation Source: MGI
  • regulation of RNA splicing Source: MGI
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

BRENDAi2.7.12.1. 3474.

Names & Taxonomyi

Protein namesi
Recommended name:
Dual specificity protein kinase CLK4 (EC:2.7.12.1)
Alternative name(s):
CDC-like kinase 4
Gene namesi
Name:Clk4
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:1098551. Clk4.

Subcellular locationi

  • Nucleus 1 Publication

GO - Cellular componenti

  • nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi189 – 1891K → R: Loss of function. 1 Publication

Chemistry

ChEMBLiCHEMBL1075283.
GuidetoPHARMACOLOGYi1993.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 481481Dual specificity protein kinase CLK4PRO_0000085874Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei136 – 1361PhosphoserineBy similarity
Modified residuei138 – 1381PhosphoserineCombined sources

Post-translational modificationi

Autophosphorylates on all three types of residues.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO35493.
PaxDbiO35493.
PRIDEiO35493.

PTM databases

iPTMnetiO35493.
PhosphoSiteiO35493.

Expressioni

Tissue specificityi

Expressed in the hippocampus, the cerebellum and the olfactory bulb.1 Publication

Gene expression databases

BgeeiO35493.
CleanExiMM_CLK4.
ExpressionAtlasiO35493. baseline and differential.
GenevisibleiO35493. MM.

Interactioni

Subunit structurei

Interacts with UBL5.By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000090820.

Chemistry

BindingDBiO35493.

Structurei

3D structure databases

ProteinModelPortaliO35493.
SMRiO35493. Positions 146-479.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini159 – 475317Protein kinasePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0671. Eukaryota.
ENOG410XQF2. LUCA.
GeneTreeiENSGT00580000081366.
HOGENOMiHOG000203417.
HOVERGENiHBG107720.
InParanoidiO35493.
KOiK08823.
OMAiCERYVPR.
PhylomeDBiO35493.
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 (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O35493-1) [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
MRHSKRTHCP DWDSRESWGH ESYSGSHKRK RRSHSSTQEN RHCKPHHQFK
60 70 80 90 100
DSDCHYLEAR CLNERDYRDR RYIDEYRNDY CEGYVPRHYH RDVESTYRIH
110 120 130 140 150
CSKSSVRSRR SSPKRKRNRP CASHQSHSKS HRRKRSRSIE DDEEGHLICQ
160 170 180 190 200
SGDVLRARYE IVDTLGEGAF GKVVECIDHG MDGLHVAVKI VKNVGRYREA
210 220 230 240 250
ARSEIQVLEH LNSTDPNSVF RCVQMLEWFD HHGHVCIVFE LLGLSTYDFI
260 270 280 290 300
KENSFLPFQI DHIRQMAYQI CQSINFLHHN KLTHTDLKPE NILFVKSDYV
310 320 330 340 350
VKYNSKMKRD ERTLKNTDIK VVDFGSATYD DEHHSTLVST RHYRAPEVIL
360 370 380 390 400
ALGWSQPCDV WSIGCILIEY YLGFTVFQTH DSKEHLAMME RILGPIPAHM
410 420 430 440 450
IQKTRKRKYF HHNQLDWDEH SSAGRYVRRR CKPLKEFMLC HDEEHEKLFD
460 470 480
LVRRMLEYDP ARRITLDEAL QHPFFDLLKR K
Length:481
Mass (Da):57,345
Last modified:January 1, 1998 - v1
Checksum:iF2C56965900C12AA
GO
Isoform 2 (identifier: O35493-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-180: Missing.

Show »
Length:301
Mass (Da):35,768
Checksum:i7F1757E2EF28C6C1
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti58 – 581E → Q in AAB62179 (PubMed:9339371).Curated
Sequence conflicti141 – 1411D → N in AAB62179 (PubMed:9339371).Curated
Sequence conflicti344 – 3441R → K in BAC25420 (PubMed:16141072).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 180180Missing in isoform 2. 2 PublicationsVSP_008205Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF033566 mRNA. Translation: AAB87510.1.
AK013974 mRNA. Translation: BAC25420.1.
BC002220 mRNA. Translation: AAH02220.1.
BC012675 mRNA. Translation: AAH12675.1.
U94846 mRNA. Translation: AAB62179.1.
CCDSiCCDS24651.1. [O35493-1]
CCDS78942.1. [O35493-2]
RefSeqiNP_001291673.1. NM_001304744.1. [O35493-2]
NP_031740.1. NM_007714.6. [O35493-1]
XP_006532177.1. XM_006532114.2. [O35493-2]
XP_006532178.1. XM_006532115.2. [O35493-2]
XP_006532179.1. XM_006532116.1. [O35493-2]
XP_006532181.1. XM_006532118.1. [O35493-2]
UniGeneiMm.239354.

Genome annotation databases

EnsembliENSMUST00000093132; ENSMUSP00000090820; ENSMUSG00000020385. [O35493-1]
ENSMUST00000109111; ENSMUSP00000104739; ENSMUSG00000020385. [O35493-2]
ENSMUST00000109113; ENSMUSP00000104741; ENSMUSG00000020385. [O35493-2]
GeneIDi12750.
KEGGimmu:12750.
UCSCiuc007itr.2. mouse. [O35493-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF033566 mRNA. Translation: AAB87510.1.
AK013974 mRNA. Translation: BAC25420.1.
BC002220 mRNA. Translation: AAH02220.1.
BC012675 mRNA. Translation: AAH12675.1.
U94846 mRNA. Translation: AAB62179.1.
CCDSiCCDS24651.1. [O35493-1]
CCDS78942.1. [O35493-2]
RefSeqiNP_001291673.1. NM_001304744.1. [O35493-2]
NP_031740.1. NM_007714.6. [O35493-1]
XP_006532177.1. XM_006532114.2. [O35493-2]
XP_006532178.1. XM_006532115.2. [O35493-2]
XP_006532179.1. XM_006532116.1. [O35493-2]
XP_006532181.1. XM_006532118.1. [O35493-2]
UniGeneiMm.239354.

3D structure databases

ProteinModelPortaliO35493.
SMRiO35493. Positions 146-479.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000090820.

Chemistry

BindingDBiO35493.
ChEMBLiCHEMBL1075283.
GuidetoPHARMACOLOGYi1993.

PTM databases

iPTMnetiO35493.
PhosphoSiteiO35493.

Proteomic databases

EPDiO35493.
PaxDbiO35493.
PRIDEiO35493.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000093132; ENSMUSP00000090820; ENSMUSG00000020385. [O35493-1]
ENSMUST00000109111; ENSMUSP00000104739; ENSMUSG00000020385. [O35493-2]
ENSMUST00000109113; ENSMUSP00000104741; ENSMUSG00000020385. [O35493-2]
GeneIDi12750.
KEGGimmu:12750.
UCSCiuc007itr.2. mouse. [O35493-1]

Organism-specific databases

CTDi57396.
MGIiMGI:1098551. Clk4.

Phylogenomic databases

eggNOGiKOG0671. Eukaryota.
ENOG410XQF2. LUCA.
GeneTreeiENSGT00580000081366.
HOGENOMiHOG000203417.
HOVERGENiHBG107720.
InParanoidiO35493.
KOiK08823.
OMAiCERYVPR.
PhylomeDBiO35493.
TreeFamiTF101041.

Enzyme and pathway databases

BRENDAi2.7.12.1. 3474.

Miscellaneous databases

ChiTaRSiClk4. mouse.
PROiO35493.
SOURCEiSearch...

Gene expression databases

BgeeiO35493.
CleanExiMM_CLK4.
ExpressionAtlasiO35493. baseline and differential.
GenevisibleiO35493. MM.

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...

Publicationsi

« Hide 'large scale' publications
  1. "Characterization and comparison of four serine- and arginine-rich (SR) protein kinases."
    Nayler O., Stamm S., Ullrich A.
    Biochem. J. 326:693-700(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, PHOSPHORYLATION, SUBCELLULAR LOCATION.
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Strain: C57BL/6J.
    Tissue: Head.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    Strain: Czech II.
    Tissue: Mammary tumor.
  4. "Construction of a 3-Mb contig and partial transcript map of the central region of mouse chromosome 11."
    Watkins-Chow D.E., Douglas K.R., Buckwalter M.S., Probst F.J., Camper S.A.
    Genomics 45:147-157(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-219.
  5. "Regulation of alternative splicing of human tau exon 10 by phosphorylation of splicing factors."
    Hartmann A.M., Rujescu D., Giannakouros T., Nikolakaki E., Goedert M., Mandelkow E.-M., Gao Q.S., Andreadis A., Stamm S.
    Mol. Cell. Neurosci. 18:80-90(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  6. "Novel SR-rich-related protein Clasp specifically interacts with inactivated Clk4 and induces the exon EB inclusion of Clk."
    Katsu R., Onogi H., Wada K., Kawaguchi Y., Hagiwara M.
    J. Biol. Chem. 277:44220-44228(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, MUTAGENESIS OF LYS-189.
  7. Cited for: ENZYME REGULATION.
  8. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-138, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  9. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-138, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Kidney, Liver, Lung, Pancreas, Spleen and Testis.

Entry informationi

Entry nameiCLK4_MOUSE
AccessioniPrimary (citable) accession number: O35493
Secondary accession number(s): O35721, Q8CEU9, Q99LU6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: January 1, 1998
Last modified: June 8, 2016
This is version 129 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. 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.