Reviewed, UniProtKB/Swiss-Prot Q96SB4 (SRPK1_HUMAN)

Names and origin

Protein names

Recommended name:
    Serine/threonine-protein kinase SRPK1
    EC=2.7.11.1
Alternative name(s):
    Serine/arginine-rich protein-specific kinase 1
      Short name=SR-protein-specific kinase 1
    SFRS protein kinase 1

Gene names

Name:

SRPK1

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

General annotation (Comments)

Function	Plays a central role in the regulatory network for splicing, controlling the intranuclear distribution of splicing factors in interphase cells and the reorganization of nuclear speckles during mitosis. Hyperphosphorylates RS domain-containing proteins such as SFRS1 and SFRS2 on serine residues during metaphase but at lower levels during interphase. Locks onto SFRS1 to form a stable complex and processively phosphorylates the RS domain. Appears to mediate HBV core protein phosphorylation which is a prerequisite for pregenomic RNA encapsidation into viral capsids. Ref.1 Ref.2 Ref.5 Ref.6 Ref.7 Ref.14 Ref.8
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. Ref.1 Ref.2 Ref.5 Ref.6 Ref.7 Ref.8
Cofactor	Magnesium. Ref.1 Ref.2 Ref.5 Ref.6 Ref.7 Ref.8
Enzyme regulation	Activated by phosphorylation on Ser-51 and Ser-555. Ref.8
Subunit structure	Present in a seven component complex, the toposome, which separates entangled circular chromatin DNA during chromosome segregation. The extended N-terminal domain of isoform 1 binds to the nuclear scaffold-associated protein SAFB suggesting this isoform may phosphorylate splicing factors in close vicinity to the nuclear matrix. Ref.2 Ref.6
Subcellular location	Isoform 1: Cytoplasm. Nucleus. Ref.2 Isoform 2: Cytoplasm. Nucleus. Ref.2
Tissue specificity	Isoform 2 is predominantly expressed in the testis but is also present at lower levels in heart, ovary, small intestine, liver, kidney, pancreas and skeletal muscle. Isoform 1 is only seen in the testis, at lower levels than isoform 2. Ref.2
Sequence similarities	Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. Contains 1 protein kinase domain.
Sequence caution	The sequence CAI20544.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAI20545.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Chromosome partition Differentiation mRNA processing mRNA splicing
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	RNA splicing Ref.1 Traceable author statement. Source: ProtInc cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW chromosome segregation Ref.6 Inferred from direct assay. Source: UniProtKB mRNA processing Inferred from electronic annotation. Source: UniProtKB-KW protein amino acid phosphorylation Ref.2 Inferred from direct assay. Source: UniProtKB protein kinase cascade Ref.2 Inferred from direct assay. Source: UniProtKB regulation of mRNA processing Ref.1 Inferred from direct assay. Source: UniProtKB
Cellular component	cytoplasm Ref.2 Inferred from direct assay. Source: UniProtKB nucleus Ref.1 Ref.2 Inferred from direct assay. Source: UniProtKB
Molecular function	ATP binding Ref.2 Inferred from direct assay. Source: UniProtKB magnesium ion binding Ref.2 Inferred from direct assay. Source: UniProtKB protein binding Ref.2 Inferred from physical interaction. Source: IntAct protein serine/threonine kinase activity Ref.2 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RNPS1	Q15287	1	EBI-539478,EBI-395959
Safb	O88453	2	EBI-539478,EBI-539530	From a different organism.
SFRS1	Q07955	1	EBI-539478,EBI-398920

Alternative products

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

Isoform 2 Ref.1 Ref.2 (identifier: Q96SB4-2)

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 Ref.2 (identifier: Q96SB4-3)

Also known as: 1a;

The sequence of this isoform differs from the canonical sequence as follows:
     5-241: VLALQARKKR...AAEATEWQRS → GERWSGLRHE...MIIVKEVIIL
     242-655: Missing.

Note: No experimental confirmation available. Ref.2 (CAC39299) isoform 1 sequence differs from that shown due to a frameshift in position 131.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 655

655

Serine/threonine-protein kinase SRPK1

PRO_0000086674

Regions

Domain

80 – 653

574

Protein kinase

Nucleotide binding

86 – 94

9

ATP

Nucleotide binding

166 – 168

3

ATP

Sites

Active site

213

1

Proton acceptor

Binding site

109

1

ATP

Amino acid modifications

Modified residue

51

1

Phosphoserine; by CK2 Ref.8 Ref.9 Ref.11

Modified residue

309

1

Phosphoserine Ref.9 Ref.11 Ref.10

Modified residue

311

1

Phosphoserine Ref.9 Ref.11

Modified residue

555

1

Phosphoserine; by CK2 Ref.8

Natural variations

Alternative sequence

5 – 241

237

VLALQ…EWQRS → GERWSGLRHEGQWSPGRGPG QRRELRLTAAVRFPDVRRPS TEVAPPHTPCLWAAGPRPSF RASSGAGRSRPLFPARPARA LGPLQGPALGGRRRPPPARP LTRPETPPAHPARALLCAPW AASPTAGRLAEARSRPRGRP RSRAWRPCWVSTLTLVASFP PHSPFIHPSLLQCLRSRPER KGPRPRRTKPKGNLKLSTEA LLPTLRVIYQSRKRRFWDLM MMSKKILMIIVKEVIIL in isoform 1.

VSP_035581

Alternative sequence

242 – 655

414

Missing in isoform 1.

VSP_035582

Natural variant

72

1

I → T: dbSNP rs35519113.

VAR_051669

Experimental info

Mutagenesis

37

1

S → A: No effect on protein phosphorylation. Ref.8

Mutagenesis

51

1

S → A: Protein phosphorylation impaired at this position. Ref.8

Mutagenesis

222

1

S → A: No effect on protein phosphorylation. Ref.8

Mutagenesis

311

1

S → G: No effect on protein phosphorylation. Ref.8

Mutagenesis

436

1

S → G: No effect on protein phosphorylation. Ref.8

Mutagenesis

555

1

S → A: Protein phosphorylation impaired at this position. Ref.8

Mutagenesis

619

1

S → A: No effect on protein phosphorylation. Ref.8

Sequence conflict

210

1

I → T in AAH38292. Ref.4

Sequence conflict

360

1

I → L AA sequence Ref.5

Sequence conflict

363

1

I → L AA sequence Ref.5

Sequence conflict

400 – 401

2

SQ → LP in AAA20530. Ref.1

Secondary structure

1

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655

Helix Strand Turn

Details...

Turn

77 – 79

3

Beta strand

80 – 88

9

Beta strand

90 – 99

10

Turn

100 – 103

4

Beta strand

104 – 111

8

Helix

115 – 133

19

Helix

139 – 143

5

Beta strand

147 – 155

9

Beta strand

158 – 165

8

Helix

172 – 178

7

Turn

179 – 181

3

Helix

186 – 205

20

Helix

216 – 218

3

Beta strand

219 – 221

3

Helix

225 – 235

11

Helix

268 – 273

6

Beta strand

276 – 278

3

Helix

281 – 283

3

Helix

298 – 300

3

Helix

303 – 307

5

Helix

314 – 329

16

Beta strand

340 – 342

3

Helix

344 – 356

13

Helix

361 – 366

6

Helix

370 – 372

3

Beta strand

378 – 382

5

Helix

391 – 397

7

Helix

403 – 413

11

Helix

414 – 417

4

Helix

421 – 423

3

Helix

427 – 431

5

Helix

434 – 437

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 2 [UniParc]. Last modified October 14, 2008. Version 2. Checksum: 900E980FE1C16B9A	FASTA	655	74,325
	10 20 30 40 50 60 MERKVLALQA RKKRTKAKKD KAQRKSETQH RGSAPHSESD LPEQEEEILG SDDDEQEDPN 70 80 90 100 110 120 DYCKGGYHLV KIGDLFNGRY HVIRKLGWGH FSTVWLSWDI QGKKFVAMKV VKSAEHYTET 130 140 150 160 170 180 ALDEIRLLKS VRNSDPNDPN REMVVQLLDD FKISGVNGTH ICMVFEVLGH HLLKWIIKSN 190 200 210 220 230 240 YQGLPLPCVK KIIQQVLQGL DYLHTKCRII HTDIKPENIL LSVNEQYIRR LAAEATEWQR 250 260 270 280 290 300 SGAPPPSGSA VSTAPQPKPA DKMSKNKKKK LKKKQKRQAE LLEKRMQEIE EMEKESGPGQ 310 320 330 340 350 360 KRPNKQEESE SPVERPLKEN PPNKMTQEKL EESSTIGQDQ TLMERDTEGG AAEINCNGVI 370 380 390 400 410 420 EVINYTQNSN NETLRHKEDL HNANDCDVQN LNQESSFLSS QNGDSSTSQE TDSCTPITSE 430 440 450 460 470 480 VSDTMVCQSS STVGQSFSEQ HISQLQESIR AEIPCEDEQE QEHNGPLDNK GKSTAGNFLV 490 500 510 520 530 540 NPLEPKNAEK LKVKIADLGN ACWVHKHFTE DIQTRQYRSL EVLIGSGYNT PADIWSTACM 550 560 570 580 590 600 AFELATGDYL FEPHSGEEYT RDEDHIALII ELLGKVPRKL IVAGKYSKEF FTKKGDLKHI 610 620 630 640 650 TKLKPWGLFE VLVEKYEWSQ EEAAGFTDFL LPMLELIPEK RATAAECLRH PWLNS
	Isoform 1 (1a). Checksum: 2A521048CC38386F	FASTA	241	27,065
	10 20 30 40 50 60 MERKGERWSG LRHEGQWSPG RGPGQRRELR LTAAVRFPDV RRPSTEVAPP HTPCLWAAGP 70 80 90 100 110 120 RPSFRASSGA GRSRPLFPAR PARALGPLQG PALGGRRRPP PARPLTRPET PPAHPARALL 130 140 150 160 170 180 CAPWAASPTA GRLAEARSRP RGRPRSRAWR PCWVSTLTLV ASFPPHSPFI HPSLLQCLRS 190 200 210 220 230 240 RPERKGPRPR RTKPKGNLKL STEALLPTLR VIYQSRKRRF WDLMMMSKKI LMIIVKEVII L

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A serine kinase regulates intracellular localization of splicing factors in the cell cycle." Gui J.F., Lane W.S., Fu X.-D. Nature 369:678-682(1994) [PubMed: 8208298] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION. Tissue: Cervix carcinoma.
[2]	"Cloning and characterization of an alternatively spliced form of SR protein kinase 1 that interacts specifically with scaffold attachment factor-B." Nikolakaki E., Kohen R., Hartmann A.M., Stamm S., Georgatsou E., Giannakouros T. J. Biol. Chem. 276:40175-40182(2001) [PubMed: 11509566] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH SAFB. Tissue: Testis.
[3]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed: 14574404] [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 2). Tissue: Testis.
[5]	"Identification of SRPK1 and SRPK2 as the major cellular protein kinases phosphorylating hepatitis B virus core protein." Daub H., Blencke S., Habenberger P., Kurtenbach A., Dennenmoser J., Wissing J., Ullrich A., Cotten M. J. Virol. 76:8124-8137(2002) [PubMed: 12134018] [Abstract] Cited for: PROTEIN SEQUENCE OF 330-345 AND 353-375, FUNCTION.
[6]	"Identification of toposome, a novel multisubunit complex containing topoisomerase IIalpha." Lee C.G., Hague L.K., Li H., Donnelly R. Cell Cycle 3:638-647(2004) [PubMed: 15034300] [Abstract] Cited for: PROTEIN SEQUENCE OF 376-400 AND 616-636, FUNCTION, IDENTIFICATION IN A TOPOSOME COMPLEX.
[7]	"Processive phosphorylation of alternative splicing factor/splicing factor 2." Aubol B.E., Chakrabarti S., Ngo J., Shaffer J., Nolen B., Fu X.-D., Ghosh G., Adams J.A. Proc. Natl. Acad. Sci. U.S.A. 100:12601-12606(2003) [PubMed: 14555757] [Abstract] Cited for: FUNCTION, INTERACTION WITH SFRS1.
[8]	"Protein kinase CK2 phosphorylates and activates the SR protein-specific kinase 1." Mylonis I., Giannakouros T. Biochem. Biophys. Res. Commun. 301:650-656(2003) [PubMed: 12565829] [Abstract] Cited for: ENZYME REGULATION, PHOSPHORYLATION AT SER-51 AND SER-555, MUTAGENESIS OF SER-37; SER-51; SER-222; SER-311; SER-436; SER-555 AND SER-619.
[9]	"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 SER-51; SER-309 AND SER-311, MASS SPECTROMETRY. Tissue: Epithelium.
[10]	"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column." Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y. Anal. Sci. 24:161-166(2008) [PubMed: 18187866] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-309, MASS SPECTROMETRY.
[11]	"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 SER-51; SER-309 AND SER-311, MASS SPECTROMETRY.
[12]	"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 SER-222, MASS SPECTROMETRY.
[13]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[14]	"Interplay between SRPK and Clk/Sty kinases in phosphorylation of the splicing factor ASF/SF2 is regulated by a docking motif in ASF/SF2." Ngo J.C.K., Chakrabarti S., Ding J.-H., Velazquez-Dones A., Nolen B., Aubol B.E., Adams J.A., Fu X.-D., Ghosh G. Mol. Cell 20:77-89(2005) [PubMed: 16209947] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 42-438 IN COMPLEX WITH ATP AND SUBSTRATE PEPTIDE, FUNCTION, INTERACTION WITH SFRS1.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

U09564 mRNA. Translation: AAA20530.1.
AJ318054 mRNA. Translation: CAC39299.1. Frameshift.
Z99128 Genomic DNA. Translation: CAI20544.1. Sequence problems.
Z99128 Genomic DNA. Translation: CAI20545.1. Sequence problems.
BC038292 mRNA. Translation: AAH38292.1.

IPI

IPI00412344.
IPI00914014.

PIR

S45337.

RefSeq

NP_003128.3.

UniGene

Hs.443861

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1WAK	X-ray	1.73	A	42-655	[»]
1WBP	X-ray	2.40	A	42-655	[»]
3BEG	X-ray	2.90	A	58-655	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q96SB4. 8 interactions.

PTM databases

PhosphoSite

Q96SB4.

Proteomic databases

PRIDE

Q96SB4.

Genome annotation databases

Ensembl

ENSG00000096063. Homo sapiens. [Contig view]

GeneID

6732.

KEGG

hsa:6732.

Organism-specific databases

GeneCards

GC06M035908.

H-InvDB

HIX0005813.

HGNC

HGNC:11305. SRPK1.

HPA

HPA016431.

MIM

601939. gene.

PharmGKB

PA36129.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q96SB4.

HOVERGEN

Q96SB4.

Enzyme and pathway databases

BRENDA

2.7.11.1. 247.

Gene expression databases

ArrayExpress

Q96SB4.

Bgee

Q96SB4.

CleanEx

HS_SRPK1.

GermOnline

ENSG00000096063. Homo sapiens.

Family and domain databases

InterPro

IPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_BS.
IPR017442. Se/Thr_pkinase-rel.
IPR008271. Ser_thr_pkin_AS.
[Graphical view]

Pfam

PF00069. Pkinase. 1 hit.
[Graphical view]

ProDom

PD000001. Prot_kinase. 2 hits.
[Graphical view] [Entries sharing at least one domain]

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

26262.

SOURCE

Search...

Entry information

Entry name

SRPK1_HUMAN

Accession

Primary (citable) accession number: Q96SB4
Secondary accession number(s): Q12890 , Q5R364, Q5R365, Q8IY12

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 21, 2005
Last sequence update:	October 14, 2008
Last modified:	July 7, 2009
This is version 76 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)