Reviewed, UniProtKB/Swiss-Prot P49761 (CLK3_HUMAN)

Names and origin

Protein names

Recommended name:
    Dual specificity protein kinase CLK3
    EC=2.7.12.1
Alternative name(s):
    CDC-like kinase 3

Gene names

Name:

CLK3

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	638 AA.
Sequence status	Complete.
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. Ref.5
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Subcellular location	Nucleus. Cytoplasm By similarity. Cytoplasmic vesicle › secretory vesicle › acrosome By similarity Ref.5.
Post-translational modification	Autophosphorylates on all three types of residues By similarity.
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	Cytoplasm Cytoplasmic vesicle Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase Tyrosine-protein kinase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Cellular component	acrosomal vesicle Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Ref.1 Traceable author statement. Source: ProtInc protein tyrosine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 4 (identifier: P49761-4)

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 1 (identifier: P49761-1)

Also known as: Long;

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

Isoform 2 (identifier: P49761-2)

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.

Isoform 3 (identifier: P49761-3)

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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 638

638

Dual specificity protein kinase CLK3

PRO_0000085870

Regions

Domain

304 – 620

317

Protein kinase

Nucleotide binding

310 – 318

9

ATP By similarity

Compositional bias

167 – 264

98

Arg-rich

Sites

Active site

431

1

Proton acceptor By similarity

Binding site

334

1

ATP By similarity

Amino acid modifications

Modified residue

155

1

Phosphotyrosine Ref.7 Ref.9 Ref.10

Modified residue

157

1

Phosphoserine Ref.9 Ref.10 Ref.8 Ref.11

Modified residue

197

1

Phosphoserine Ref.7

Modified residue

199

1

Phosphoserine Ref.7

Modified residue

215

1

Phosphoserine Ref.9

Modified residue

224

1

Phosphoserine Ref.7 Ref.9 Ref.10

Modified residue

226

1

Phosphoserine Ref.7 Ref.9 Ref.10

Modified residue

283

1

Phosphoserine Ref.9

Natural variations

Alternative sequence

1 – 148

148

Missing in isoform 1, isoform 2 and isoform 3.

VSP_026138

Alternative sequence

272 – 300

29

RSQQS…IGDWL → MRLWGTWVKAPLARWWSAWT MPEGSLRLP in isoform 2.

VSP_004858

Alternative sequence

301 – 638

338

Missing in isoform 2.

VSP_004859

Alternative sequence

306 – 328

23

Missing in isoform 3.

VSP_004860

Natural variant

486

1

R → C

VAR_040413

Natural variant

607

1

Q → R

VAR_045579

Natural variant

628

1

R → W

VAR_045580

Experimental info

Sequence conflict

280 – 281

2

SS → TG in AAA61484. Ref.1

Secondary structure

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638

Helix Strand Turn

Details...

Turn

301 – 303

3

Beta strand

304 – 313

10

Beta strand

316 – 323

8

Turn

324 – 328

5

Beta strand

330 – 336

7

Helix

340 – 359

20

Beta strand

370 – 376

7

Beta strand

379 – 385

7

Helix

391 – 397

7

Turn

398 – 400

3

Helix

405 – 423

19

Turn

424 – 426

3

Helix

434 – 436

3

Beta strand

437 – 440

4

Beta strand

444 – 448

5

Beta strand

456 – 460

5

Beta strand

464 – 466

3

Helix

486 – 488

3

Helix

491 – 494

4

Helix

502 – 517

16

Helix

527 – 538

12

Helix

543 – 548

6

Helix

552 – 554

3

Helix

567 – 575

9

Helix

579 – 582

4

Helix

588 – 600

13

Turn

605 – 607

3

Helix

611 – 614

4

Helix

618 – 622

5

Helix

625 – 628

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 4 [UniParc]. Last modified June 12, 2007. Version 3. Checksum: D3B60A9DB4ECEC94	FASTA	638	73,515
	10 20 30 40 50 60 MPVLSARRRE LADHAGSGRR SGPSPTARSG PHLSALRAQP ARAAHLSGRG TYVRRDTAGG 70 80 90 100 110 120 GPGQARPLGP PGTSLLGRGA RRSGEGWCPG AFESGARAAR PPSRVEPRLA TAASREGAGL 130 140 150 160 170 180 PRAEVAAGSG RGARSGEWGL AAAGAWETMH HCKRYRSPEP DPYLSYRWKR RRSYSREHEG 190 200 210 220 230 240 RLRYPSRREP PPRRSRSRSH DRLPYQRRYR ERRDSDTYRC EERSPSFGED YYGPSRSRHR 250 260 270 280 290 300 RRSRERGPYR TRKHAHHCHK RRTRSCSSAS SRSQQSSKRS SRSVEDDKEG HLVCRIGDWL 310 320 330 340 350 360 QERYEIVGNL GEGTFGKVVE CLDHARGKSQ VALKIIRNVG KYREAARLEI NVLKKIKEKD 370 380 390 400 410 420 KENKFLCVLM SDWFNFHGHM CIAFELLGKN TFEFLKENNF QPYPLPHVRH MAYQLCHALR 430 440 450 460 470 480 FLHENQLTHT DLKPENILFV NSEFETLYNE HKSCEEKSVK NTSIRVADFG SATFDHEHHT 490 500 510 520 530 540 TIVATRHYRP PEVILELGWA QPCDVWSIGC ILFEYYRGFT LFQTHENREH LVMMEKILGP 550 560 570 580 590 600 IPSHMIHRTR KQKYFYKGGL VWDENSSDGR YVKENCKPLK SYMLQDSLEH VQLFDLMRRM 610 620 630 LEFDPAQRIT LAEALLHPFF AGLTPEERSF HTSRNPSR
	Isoform 1 (Long). Checksum: 86A342ABB8AB24CA	FASTA	490	58,588
	10 20 30 40 50 60 MHHCKRYRSP EPDPYLSYRW KRRRSYSREH EGRLRYPSRR EPPPRRSRSR SHDRLPYQRR 70 80 90 100 110 120 YRERRDSDTY RCEERSPSFG EDYYGPSRSR HRRRSRERGP YRTRKHAHHC HKRRTRSCSS 130 140 150 160 170 180 ASSRSQQSSK RSSRSVEDDK EGHLVCRIGD WLQERYEIVG NLGEGTFGKV VECLDHARGK 190 200 210 220 230 240 SQVALKIIRN VGKYREAARL EINVLKKIKE KDKENKFLCV LMSDWFNFHG HMCIAFELLG 250 260 270 280 290 300 KNTFEFLKEN NFQPYPLPHV RHMAYQLCHA LRFLHENQLT HTDLKPENIL FVNSEFETLY 310 320 330 340 350 360 NEHKSCEEKS VKNTSIRVAD FGSATFDHEH HTTIVATRHY RPPEVILELG WAQPCDVWSI 370 380 390 400 410 420 GCILFEYYRG FTLFQTHENR EHLVMMEKIL GPIPSHMIHR TRKQKYFYKG GLVWDENSSD 430 440 450 460 470 480 GRYVKENCKP LKSYMLQDSL EHVQLFDLMR RMLEFDPAQR ITLAEALLHP FFAGLTPEER 490 SFHTSRNPSR
	Isoform 2 (Short). Checksum: 5BABA6574A0E9801	FASTA	152	18,971
	10 20 30 40 50 60 MHHCKRYRSP EPDPYLSYRW KRRRSYSREH EGRLRYPSRR EPPPRRSRSR SHDRLPYQRR 70 80 90 100 110 120 YRERRDSDTY RCEERSPSFG EDYYGPSRSR HRRRSRERGP YRTRKHAHHC HKRRTRSCSS 130 140 150 ASSMRLWGTW VKAPLARWWS AWTMPEGSLR LP
	Isoform 3. Checksum: 2890E88AE23AE7BC	FASTA	467	56,207
	10 20 30 40 50 60 MHHCKRYRSP EPDPYLSYRW KRRRSYSREH EGRLRYPSRR EPPPRRSRSR SHDRLPYQRR 70 80 90 100 110 120 YRERRDSDTY RCEERSPSFG EDYYGPSRSR HRRRSRERGP YRTRKHAHHC HKRRTRSCSS 130 140 150 160 170 180 ASSRSQQSSK RSSRSVEDDK EGHLVCRIGD WLQERYESQV ALKIIRNVGK YREAARLEIN 190 200 210 220 230 240 VLKKIKEKDK ENKFLCVLMS DWFNFHGHMC IAFELLGKNT FEFLKENNFQ PYPLPHVRHM 250 260 270 280 290 300 AYQLCHALRF LHENQLTHTD LKPENILFVN SEFETLYNEH KSCEEKSVKN TSIRVADFGS 310 320 330 340 350 360 ATFDHEHHTT IVATRHYRPP EVILELGWAQ PCDVWSIGCI LFEYYRGFTL FQTHENREHL 370 380 390 400 410 420 VMMEKILGPI PSHMIHRTRK QKYFYKGGLV WDENSSDGRY VKENCKPLKS YMLQDSLEHV 430 440 450 460 QLFDLMRRML EFDPAQRITL AEALLHPFFA GLTPEERSFH TSRNPSR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization by cDNA cloning of two new human protein kinases. Evidence by sequence comparison of a new family of mammalian protein kinases." Hanes J.J., der Kammer H., Klaudiny J.J., Scheit K.H. J. Mol. Biol. 244:665-672(1994) [PubMed: 7990150] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
[2]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[3]	"Analysis of the DNA sequence and duplication history of human chromosome 15." Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C. Nature 440:671-675(2006) [PubMed: 16572171] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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] (ISOFORM 3), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 137-638 (ISOFORM 4). Tissue: Cervix and Placenta.
[5]	"The Clk2 and Clk3 dual-specificity protein kinases regulate the intranuclear distribution of SR proteins and influence pre-mRNA splicing." Duncan P.I., Stojdl D.F., Marius R.M., Scheit K.H., Bell J.C. Exp. Cell Res. 241:300-308(1998) [PubMed: 9637771] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[6]	"An unappreciated role for RNA surveillance." Hillman R.T., Green R.E., Brenner S.E. Genome Biol. 5:R8.1-R8.16(2004) [PubMed: 14759258] [Abstract] Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
[7]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-155; SER-197; SER-199; SER-224 AND SER-226, MASS SPECTROMETRY. Tissue: Epithelium.
[8]	"Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry." Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R., Keri G., Wehland J., Daub H. Mol. Cell. Proteomics 6:537-547(2007) [PubMed: 17192257] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-157, MASS SPECTROMETRY.
[9]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-155; SER-157; SER-215; SER-224; SER-226 AND SER-283, MASS SPECTROMETRY.
[10]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-155; SER-157; SER-224 AND SER-226, MASS SPECTROMETRY.
[11]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-157, MASS SPECTROMETRY. Tissue: T-cell.
[12]	"Crystal structure of CLK3." Papagrigoriou E., Rellos P., Das S., Ugochukwu E., Turnbull A., von Delft F., Bunkoczi G., Sobott F., Bullock A., Fedorov O., Gileadi C., Savitsky P., Edwards A., Aerrowsmith C., Weigel J., Sundstrom M., Knapp S. Submitted (NOV-2005) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (1.53 ANGSTROMS) OF 284-638.
[13]	"Crystal structure of the phosphorylated clk3." Structural genomics consortium (SGC) Submitted (APR-2007) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 275-627.
[14]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] CYS-486; ARG-607 AND TRP-628.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L29220 mRNA. Translation: AAA61483.1.
L29217 mRNA. Translation: AAA61484.1.
BT006993 mRNA. Translation: AAP35639.1.
AC100835 Genomic DNA. No translation available.
BC002555 mRNA. Translation: AAH02555.1. Different initiation.
BC006103 mRNA. Translation: AAH06103.1.
BC019881 mRNA. Translation: AAH19881.1. Different initiation.

IPI

IPI00219340.
IPI00219341.
IPI00298896.
IPI00847415.

PIR

S53639.
S53640.

RefSeq

NP_001123500.1.
NP_003983.2.

UniGene

Hs.584748

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2EU9	X-ray	1.53	A	284-638	[»]
2EXE	X-ray	2.35	A	275-631	[»]
2WU6	X-ray	1.92	A	275-632	[»]
2WU7	X-ray	2.25	A	275-632	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P49761. 4 interactions.

STRING

P49761.

PTM databases

PhosphoSite

P49761.

Genome annotation databases

Ensembl

ENST00000454830; ENSP00000391518; ENSG00000179335; Homo sapiens. [Genome view]

GeneID

1198.

KEGG

hsa:1198.

UCSC

uc002ayg.2. human.
uc002ayj.2. human.

Organism-specific databases

CTD

1198.

GeneCards

GC15P072687.

HGNC

HGNC:2071. CLK3.

MIM

602990. gene.

PharmGKB

PA26597.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG05054.

HOGENOM

HBG755340.

HOVERGEN

P49761.

OrthoDB

EOG9X3KM2.

Enzyme and pathway databases

BRENDA

2.7.12.1. 247.

Gene expression databases

ArrayExpress

P49761.

Bgee

P49761.

CleanEx

HS_CLK3.

Genevestigator

P49761.

GermOnline

ENSG00000179335. Homo sapiens.

Family and domain databases

InterPro

IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR017442. Se/Thr_prot_kinase-like_dom.
IPR008271. Ser/Thr_prot_kinase_AS.
IPR002290. Ser/Thr_prot_kinase_dom.
[Graphical view]

Pfam

PF00069. Pkinase. 1 hit.
[Graphical view]

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

4949.

SOURCE

Search...

Entry information

Entry name

CLK3_HUMAN

Accession

Primary (citable) accession number: P49761
Secondary accession number(s): Q53Y48, Q9BRS3, Q9BUJ7

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	June 12, 2007
Last modified:	January 19, 2010
This is version 104 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.