Reviewed, UniProtKB/Swiss-Prot O35493 (CLK4_MOUSE)

Names and origin

Protein names

Recommended name:
    Dual specificity protein kinase CLK4
    EC=2.7.12.1
Alternative name(s):
    CDC-like kinase 4

Gene names

Name:

Clk4

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	481 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	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. Phosphorylates serines, threonines and tyrosines. Required for the regulation of alternative splicing of MAPT/TAU. Ref.5
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Subunit structure	Interacts with UBL5 By similarity.
Subcellular location	Nucleus By similarity.
Tissue specificity	Expressed in the hippocampus, the cerebellum and the olfactory bulb. Ref.6
Post-translational modification	Autophosphorylates on all three types of residues.
Sequence similarities	Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. Lammer subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase Tyrosine-protein kinase
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	peptidyl-tyrosine phosphorylation Ref.1 Inferred from direct assay. Source: MGI protein amino acid autophosphorylation Ref.1 Inferred from direct assay. Source: MGI
Cellular component	nucleus Ref.1 Inferred from direct assay. Source: MGI
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW protein tyrosine kinase activity Ref.1 Inferred from direct assay. Source: MGI
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O35493-1)

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.

Isoform 2 (identifier: O35493-2)

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 481	481	Dual specificity protein kinase CLK4		PRO_0000085874
Regions
	Domain	159 – 475	317	Protein kinase
	Nucleotide binding	165 – 173	9	ATP By similarity
Sites
	Active site	286	1	Proton acceptor By similarity
	Binding site	189	1	ATP By similarity
Amino acid modifications
	Modified residue	136	1	Phosphoserine By similarity
	Modified residue	138	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	1 – 180	180	Missing in isoform 2.		VSP_008205
Experimental info
	Mutagenesis	189	1	K → R: Loss of function. Ref.6
	Sequence conflict	58	1	E → Q in AAB62179. Ref.4
	Sequence conflict	141	1	D → N in AAB62179. Ref.4
	Sequence conflict	344	1	R → K in BAC25420. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: F2C56965900C12AA	FASTA	481	57,345
	10 20 30 40 50 60 MRHSKRTHCP DWDSRESWGH ESYSGSHKRK RRSHSSTQEN RHCKPHHQFK DSDCHYLEAR 70 80 90 100 110 120 CLNERDYRDR RYIDEYRNDY CEGYVPRHYH RDVESTYRIH CSKSSVRSRR SSPKRKRNRP 130 140 150 160 170 180 CASHQSHSKS HRRKRSRSIE DDEEGHLICQ SGDVLRARYE IVDTLGEGAF GKVVECIDHG 190 200 210 220 230 240 MDGLHVAVKI VKNVGRYREA ARSEIQVLEH LNSTDPNSVF RCVQMLEWFD HHGHVCIVFE 250 260 270 280 290 300 LLGLSTYDFI KENSFLPFQI DHIRQMAYQI CQSINFLHHN KLTHTDLKPE NILFVKSDYV 310 320 330 340 350 360 VKYNSKMKRD ERTLKNTDIK VVDFGSATYD DEHHSTLVST RHYRAPEVIL ALGWSQPCDV 370 380 390 400 410 420 WSIGCILIEY YLGFTVFQTH DSKEHLAMME RILGPIPAHM IQKTRKRKYF HHNQLDWDEH 430 440 450 460 470 480 SSAGRYVRRR CKPLKEFMLC HDEEHEKLFD LVRRMLEYDP ARRITLDEAL QHPFFDLLKR K
	Isoform 2. Checksum: 7F1757E2EF28C6C1	FASTA	301	35,768
	10 20 30 40 50 60 MDGLHVAVKI VKNVGRYREA ARSEIQVLEH LNSTDPNSVF RCVQMLEWFD HHGHVCIVFE 70 80 90 100 110 120 LLGLSTYDFI KENSFLPFQI DHIRQMAYQI CQSINFLHHN KLTHTDLKPE NILFVKSDYV 130 140 150 160 170 180 VKYNSKMKRD ERTLKNTDIK VVDFGSATYD DEHHSTLVST RHYRAPEVIL ALGWSQPCDV 190 200 210 220 230 240 WSIGCILIEY YLGFTVFQTH DSKEHLAMME RILGPIPAHM IQKTRKRKYF HHNQLDWDEH 250 260 270 280 290 300 SSAGRYVRRR CKPLKEFMLC HDEEHEKLFD LVRRMLEYDP ARRITLDEAL QHPFFDLLKR K

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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: 9307018] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[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: 16141072] [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: 15489334] [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: 9339371] [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: 11461155] [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: 12169693] [Abstract] Cited for: TISSUE SPECIFICITY, MUTAGENESIS OF LYS-189.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	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.
IPI	IPI00130955. IPI00341291.
RefSeq	NP_031740.1.
UniGene	Mm.239354
3D structure databases
HSSP	HSSP built from PDB template 1BI8 based on UniProtKB Q00534.
SMR	O35493. Positions 146-480.
ModBase	Search...
Protein-protein interaction databases
STRING	O35493.
PTM databases
PhosphoSite	O35493.
Proteomic databases
PRIDE	O35493.
Genome annotation databases
Ensembl	ENSMUST00000093132; ENSMUSP00000090820; ENSMUSG00000020385; Mus musculus. [Genome view]
GeneID	12750.
KEGG	mmu:12750.
UCSC	uc007itr.1. mouse.
Organism-specific databases
CTD	12750.
MGI	MGI:1098551. Clk4.
Phylogenomic databases
HOGENOM	O35493.
HOVERGEN	O35493.
OMA	PVKRITL.
Enzyme and pathway databases
BRENDA	2.7.12.1. 244.
Gene expression databases
ArrayExpress	O35493.
Bgee	O35493.
CleanEx	MM_CLK4.
Genevestigator	O35493.
GermOnline	ENSMUSG00000020385. Mus musculus.
Family and domain databases
InterPro	IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. IPR002290. Ser_thr_pkinase. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	282080.
SOURCE	Search...

Entry information

Entry name

CLK4_MOUSE

Accession

Primary (citable) accession number: O35493
Secondary accession number(s): O35721, Q8CEU9, Q99LU6

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 15, 1998
Last sequence update:	January 1, 1998
Last modified:	November 3, 2009
This is version 75 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)