Q96SB4 (SRPK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
SRSF protein kinase 1
EC=2.7.11.1

Alternative name(s):
SFRS protein kinase 1
Serine/arginine-rich protein-specific kinase 1
Short name=SR-protein-specific kinase 1

Gene names

Name:

SRPK1

Organism

Homo sapiens (Human)

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.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Serine/arginine-rich protein-specific kinase which specifically phosphorylates its substrates at serine residues located in regions rich in arginine/serine dipeptides, known as RS domains and is involved in the phosphorylation of SR splicing factors and the regulation of splicing. 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. Can influence additional steps of mRNA maturation, as well as other cellular activities, such as chromatin reorganization in somatic and sperm cells and cell cycle progression. Isoform 2 phosphorylates SFRS2, ZRSR2, LBR and PRM1. Isoform 2 phosphorylates SRSF1 using a directional (C-terminal to N-terminal) and a dual-track mechanism incorporating both processive phosphorylation (in which the kinase stays attached to the substrate after each round of phosphorylation) and distributive phosphorylation steps (in which the kinase and substrate dissociate after each phosphorylation event). The RS domain of SRSF1 binds first to a docking groove in the large lobe of the kinase domain of SRPK1. This induces certain structural changes in SRPK1 and/or RRM2 domain of SRSF1, allowing RRM2 to bind the kinase and initiate phosphorylation. The cycles continue for several phosphorylation steps in a processive manner (steps 1-8) until the last few phosphorylation steps (approximately steps 9-12). During that time, a mechanical stress induces the unfolding of the beta-4 motif in RRM2, which then docks at the docking groove of SRPK1. This also signals RRM2 to begin to dissociate, which facilitates SRSF1 dissociation after phosphorylation is completed. Isoform 2 can mediate hepatitis B virus (HBV) core protein phosphorylation. It plays a negative role in the regulation of HBV replication through a mechanism not involving the phosphorylation of the core protein but by reducing the packaging efficiency of the pregenomic RNA (pgRNA) without affecting the formation of the viral core particles. Isoform 1 and isoform 2 can induce splicing of exon 10 in MAPT/TAU. The ratio of isoform 1/isoform 2 plays a decisive role in determining cell fate in K562 leukaemic cell line: isoform 2 favors proliferation where as isoform 1 favors differentiation. Ref.1 Ref.2 Ref.5 Ref.6 Ref.7 Ref.9 Ref.10 Ref.12 Ref.15 Ref.16 Ref.20 Ref.22 Ref.23 Ref.27 Ref.32
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. Ref.1 Ref.2 Ref.5 Ref.6 Ref.10 Ref.11
Cofactor	Magnesium. Ref.1 Ref.2 Ref.5 Ref.6 Ref.10 Ref.11
Enzyme regulation	Activated by phosphorylation on Ser-51 and Ser-555. Ref.11
Subunit structure	Monomer. Isoform 2 is found in a multisubunit complex containing seven proteins, named toposome, which separates entangled circular chromatin DNA during chromosome segregation. Isoform 2 interacts with HHV-1 ICP27 protein. Isoform 2 interacts with DNAJB1/HSP40 and AHSA1/AHA1 and this mediates formation of a complex with the Hsp70 /Hsp90 machinery. Isoform 1 is found in a complex with: DHX9, MOV10, MATR3, HNRNPU, NCL, DDX21, HSD17B4, PABPC1, HNRNPM, IGF2BP1, SYNCRIP, RPL3, VIM, YBX1, NPM1, HNRNPA2B1, HNRNPC, RPLP0, RPL7A and RALY. Isoform 2 binds to IGF2BP1, SYNCRIP, HNRNPA2B1 and HNRNPC. Isoform 1 and isoform 2 interact with SAFB which inhibits its activity. Isoform 2 interacts with SAFB2 which inhibits its activity. Ref.2 Ref.7 Ref.10 Ref.21 Ref.22 Ref.24 Ref.32 Ref.33
Subcellular location	Isoform 2: Cytoplasm. Nucleus. Nucleus matrix. Microsome. Note: Shuttles between the nucleus and the cytoplasm. Inhibition of the Hsp90 ATPase activity, osmotic stress and interaction with HHV-1 ICP27 protein can induce its translocation to the nucleus. KAT5/TIP60 inhibits its nuclear translocation. Ref.2 Ref.9 Ref.22 Ref.27 Ref.29 Isoform 1: Cytoplasm. Nucleus matrix. Microsome. Note: Mainly localized in the microsomal fraction and the cytoplasm, and to a lesser extent in the nuclear matrix. Ref.2 Ref.9 Ref.22 Ref.27 Ref.29
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. Highly expressed in different erythroid and lymphoid cell lines, with isoform 2 being far more abundant than isoform 1. Ref.2 Ref.9 Ref.27
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 Host-virus interaction mRNA processing mRNA splicing
Cellular component	Cytoplasm Endoplasmic reticulum Microsome Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	RNA splicing Traceable author statement. Source: ProtInc chromosome segregation Inferred from direct assay Ref.6. Source: UniProtKB innate immune response Inferred by curator. Source: BHF-UCL interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW intracellular protein kinase cascade Inferred from direct assay Ref.2. Source: UniProtKB mRNA processing Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of viral genome replication Inferred from direct assay. Source: BHF-UCL positive regulation of viral genome replication Inferred from direct assay. Source: BHF-UCL regulation of nuclear mRNA splicing, via spliceosome Traceable author statement Ref.30. Source: UniProtKB sperm chromatin condensation Traceable author statement Ref.30. Source: UniProtKB
Cellular component	cytoplasm Inferred from direct assay Ref.2. Source: UniProtKB nucleus Inferred from direct assay Ref.2. Source: UniProtKB
Molecular function	ATP binding Inferred from direct assay Ref.2. Source: UniProtKB magnesium ion binding Inferred from direct assay Ref.2. Source: UniProtKB protein binding Inferred from physical interaction Ref.7. Source: UniProtKB protein serine/threonine kinase activity Inferred from direct assay Ref.2Ref.7. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Safb	O88453	2	EBI-539478,EBI-539530	From a different organism.
SRSF1	Q07955	2	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:
     4-4: K → KGERWSGLRH...FALHPSLSPA

Note: Due to intron retention.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 655

655

SRSF protein kinase 1

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

37

1

Phosphoserine Ref.19

Modified residue

51

1

Phosphoserine; by CK2 Ref.11 Ref.13 Ref.17 Ref.19 Ref.25

Modified residue

309

1

Phosphoserine Ref.13 Ref.14 Ref.17 Ref.19

Modified residue

311

1

Phosphoserine Ref.13 Ref.17 Ref.19

Modified residue

555

1

Phosphoserine; by CK2 Ref.11

Modified residue

585

1

N6-acetyllysine Ref.26

Natural variations

Alternative sequence

4

1

K → KGERWSGLRHEGQWSPGRGP GQRRELRLTAAVRFPDVRRP STEVAPPHTPCLWAAGPRPS FRASSGAGRSRPLFPARPAR ALGPLQGPALGGRRRPPPAR PLTRPETPPAHPARALLCAP WAASPTPAASPSPQPPPRQA PQPGLAPLLGLHPHLGRLLS STFALHPSLSPA in isoform 1.

VSP_042130

Natural variant

72

1

I → T.
Corresponds to variant rs35519113 [ dbSNP | Ensembl ].

VAR_051669

Experimental info

Mutagenesis

37

1

S → A: No effect on protein phosphorylation. Ref.11

Mutagenesis

51

1

S → A: Protein phosphorylation impaired at this position. Ref.11

Mutagenesis

222

1

S → A: No effect on protein phosphorylation. Ref.11

Mutagenesis

311

1

S → G: No effect on protein phosphorylation. Ref.11

Mutagenesis

436

1

S → G: No effect on protein phosphorylation. Ref.11

Mutagenesis

555

1

S → A: Protein phosphorylation impaired at this position. Ref.11

Mutagenesis

619

1

S → A: No effect on protein phosphorylation. Ref.11

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) [UniParc]. Checksum: 9E4D86DE22A10D32	FASTA	826	92,412
	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 CAPWAASPTP AASPSPQPPP RQAPQPGLAP LLGLHPHLGR LLSSTFALHP SLSPAVLALQ 190 200 210 220 230 240 ARKKRTKAKK DKAQRKSETQ HRGSAPHSES DLPEQEEEIL GSDDDEQEDP NDYCKGGYHL 250 260 270 280 290 300 VKIGDLFNGR YHVIRKLGWG HFSTVWLSWD IQGKKFVAMK VVKSAEHYTE TALDEIRLLK 310 320 330 340 350 360 SVRNSDPNDP NREMVVQLLD DFKISGVNGT HICMVFEVLG HHLLKWIIKS NYQGLPLPCV 370 380 390 400 410 420 KKIIQQVLQG LDYLHTKCRI IHTDIKPENI LLSVNEQYIR RLAAEATEWQ RSGAPPPSGS 430 440 450 460 470 480 AVSTAPQPKP ADKMSKNKKK KLKKKQKRQA ELLEKRMQEI EEMEKESGPG QKRPNKQEES 490 500 510 520 530 540 ESPVERPLKE NPPNKMTQEK LEESSTIGQD QTLMERDTEG GAAEINCNGV IEVINYTQNS 550 560 570 580 590 600 NNETLRHKED LHNANDCDVQ NLNQESSFLS SQNGDSSTSQ ETDSCTPITS EVSDTMVCQS 610 620 630 640 650 660 SSTVGQSFSE QHISQLQESI RAEIPCEDEQ EQEHNGPLDN KGKSTAGNFL VNPLEPKNAE 670 680 690 700 710 720 KLKVKIADLG NACWVHKHFT EDIQTRQYRS LEVLIGSGYN TPADIWSTAC MAFELATGDY 730 740 750 760 770 780 LFEPHSGEEY TRDEDHIALI IELLGKVPRK LIVAGKYSKE FFTKKGDLKH ITKLKPWGLF 790 800 810 820 EVLVEKYEWS QEEAAGFTDF LLPMLELIPE KRATAAECLR HPWLNS

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 IN THE PHOSPHORYLATION OF HEPATITIS B VIRUS CORE PROTEIN.
[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]	"A protein related to splicing factor U2AF35 that interacts with U2AF65 and SR proteins in splicing of pre-mRNA." Tronchere H., Wang J., Fu X.D. Nature 388:397-400(1997) [PubMed: 9237760] [Abstract] Cited for: FUNCTION, INTERACTION WITH ZRSR2.
[8]	"SRPK1 and LBR protein kinases show identical substrate specificities." Papoutsopoulou S., Nikolakaki E., Giannakouros T. Biochem. Biophys. Res. Commun. 255:602-607(1999) [PubMed: 10049757] [Abstract] Cited for: FUNCTIION IN THE PHOSPHORYLATION OF LBR.
[9]	"SR protein-specific kinase 1 is highly expressed in testis and phosphorylates protamine 1." Papoutsopoulou S., Nikolakaki E., Chalepakis G., Kruft V., Chevaillier P., Giannakouros T. Nucleic Acids Res. 27:2972-2980(1999) [PubMed: 10390541] [Abstract] Cited for: FUNCTION IN THE PHOSPHORYLATION OF PRM1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[10]	"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.
[11]	"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.
[12]	"Suppression of hepatitis B virus replication by SRPK1 and SRPK2 via a pathway independent of the phosphorylation of the viral core protein." Zheng Y., Fu X.D., Ou J.H. Virology 342:150-158(2005) [PubMed: 16122776] [Abstract] Cited for: FUNCTION IN THE NEGATIVE REGULATION OF HEPATITIS B VIRUS (HBV) REPLICATION.
[13]	"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: Cervix carcinoma.
[14]	"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. Tissue: Cervix carcinoma.
[15]	"Ordered multi-site phosphorylation of the splicing factor ASF/SF2 by SRPK1." Ma C.T., Velazquez-Dones A., Hagopian J.C., Ghosh G., Fu X.D., Adams J.A. J. Mol. Biol. 376:55-68(2008) [PubMed: 18155240] [Abstract] Cited for: FUNCTION IN THE PHOSPHORYLATION OF SRSF1, THE MECHANISM OF PHOSPHORYATION.
[16]	"Adaptable molecular interactions guide phosphorylation of the SR protein ASF/SF2 by SRPK1." Hagopian J.C., Ma C.T., Meade B.R., Albuquerque C.P., Ngo J.C., Ghosh G., Jennings P.A., Fu X.D., Adams J.A. J. Mol. Biol. 382:894-909(2008) [PubMed: 18687337] [Abstract] Cited for: FUNCTION IN THE PHOSPHORYLATION OF SRSF1, THE MECHANISM OF PHOSPHORYATION.
[17]	"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. Tissue: Cervix carcinoma.
[18]	"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. Tissue: Cervix carcinoma.
[19]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37; SER-51; SER-309 AND SER-311, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[20]	"Allosteric interactions direct binding and phosphorylation of ASF/SF2 by SRPK1." Huynh N., Ma C.T., Giang N., Hagopian J., Ngo J., Adams J., Ghosh G. Biochemistry 48:11432-11440(2009) [PubMed: 19886675] [Abstract] Cited for: FUNCTION IN THE PHOSPHORYLATION OF SRSF1, THE MECHANISM OF PHOSPHORYATION.
[21]	"The enzymatic activity of SR protein kinases 1 and 1a is negatively affected by interaction with scaffold attachment factors B1 and 2." Tsianou D., Nikolakaki E., Tzitzira A., Bonanou S., Giannakouros T., Georgatsou E. FEBS J. 276:5212-5227(2009) [PubMed: 19674106] [Abstract] Cited for: INTERACTION WITH SAFB/SAFB1 AND SAFB2.
[22]	"Regulation of SR protein phosphorylation and alternative splicing by modulating kinetic interactions of SRPK1 with molecular chaperones." Zhong X.Y., Ding J.H., Adams J.A., Ghosh G., Fu X.D. Genes Dev. 23:482-495(2009) [PubMed: 19240134] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH DNAJB1/HSP40 AND AHSA1/AHA1.
[23]	"Regiospecific phosphorylation control of the SR protein ASF/SF2 by SRPK1." Ma C.T., Hagopian J.C., Ghosh G., Fu X.D., Adams J.A. J. Mol. Biol. 390:618-634(2009) [PubMed: 19477182] [Abstract] Cited for: FUNCTION IN THE PHOSPHORYLATION OF SRSF1, THE MECHANISM OF PHOSPHORYATION.
[24]	"Arginine methylation of the ICP27 RGG box regulates the functional interactions of ICP27 with SRPK1 and Aly/REF during herpes simplex virus 1 infection." Souki S.K., Sandri-Goldin R.M. J. Virol. 83:8970-8975(2009) [PubMed: 19553338] [Abstract] Cited for: INTERACTION WITH HHV-1 ICP27 PROTEIN.
[25]	"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-51, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[26]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-585, MASS SPECTROMETRY.
[27]	"The ratio of SRPK1/SRPK1a regulates erythroid differentiation in K562 leukaemic cells." Sanidas I., Kotoula V., Ritou E., Daans J., Lenz C., Mairhofer M., Daniilidou M., Kolbus A., Kruft V., Ponsaerts P., Nikolakaki E. Biochim. Biophys. Acta 1803:1319-1331(2010) [PubMed: 20708644] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, IDENTIFICATION OF ISOFORM 1 IN A COMPLEX WITH DHX9; MOV10; MATR3; HNRNPU; NCL; DDX21; HSD17B4; PABPC1; HNRNPM; IGF2BP1; SYNCRIP; RPL3; VIM; YBX1; NPM1; HNRNPA2B1; HNRNPC; RPLP0; RPL7A AND RALY.
[28]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[29]	"Acetylation and phosphorylation of SRSF2 control cell fate decision in response to cisplatin." Edmond V., Moysan E., Khochbin S., Matthias P., Brambilla C., Brambilla E., Gazzeri S., Eymin B. EMBO J. 30:510-523(2011) [PubMed: 21157427] [Abstract] Cited for: SUBCELLULAR LOCATION.
[30]	"Serine-arginine protein kinases: a small protein kinase family with a large cellular presence." Giannakouros T., Nikolakaki E., Mylonis I., Georgatsou E. FEBS J. 278:570-586(2011) [PubMed: 21205200] [Abstract] Cited for: REVIEW ON FUNCTION.
[31]	"Phosphorylation mechanism and structure of serine-arginine protein kinases." Ghosh G., Adams J.A. FEBS J. 278:587-597(2011) [PubMed: 21205204] [Abstract] Cited for: REVIEW ON FUNCTION.
[32]	"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.
[33]	"SR protein kinase 1 is resilient to inactivation." Ngo J.C., Gullingsrud J., Giang K., Yeh M.J., Fu X.D., Adams J.A., McCammon J.A., Ghosh G. Structure 15:123-133(2007) [PubMed: 17223538] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.73 ANGSTROMS) OF 42-655, SUBUNIT.
[34]	"A sliding docking interaction is essential for sequential and processive phosphorylation of an SR protein by SRPK1." Ngo J.C., Giang K., Chakrabarti S., Ma C.T., Huynh N., Hagopian J.C., Dorrestein P.C., Fu X.D., Adams J.A., Ghosh G. Mol. Cell 29:563-576(2008) [PubMed: 18342604] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 58-655 IN COMPLEX WITH SRSF1, MECHANISM OF PHOSPHORYLATION OF SRSF1.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U09564 mRNA. Translation: AAA20530.1.
AJ318054 mRNA. Translation: CAC39299.1.
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. NM_003137.4.

UniGene

Hs.443861.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]

ProteinModelPortal

Q96SB4.

SMR

Q96SB4. Positions 63-655.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q96SB4. 8 interactions.

MINT

MINT-262701.

STRING

Q96SB4.

PTM databases

PhosphoSite

Q96SB4.

Polymorphism databases

DMDM

209572680.

Proteomic databases

PRIDE

Q96SB4.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000423325; ENSP00000391069; ENSG00000096063.

GeneID

6732.

KEGG

hsa:6732.

Organism-specific databases

CTD

6732.

GeneCards

GC06M035847.

H-InvDB

HIX0005813.

HGNC

HGNC:11305. SRPK1.

HPA

HPA016431.

MIM

601939. gene.

neXtProt

NX_Q96SB4.

PharmGKB

PA36129.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG12521.

GeneTree

ENSGT00530000063566.

HOGENOM

HBG755340.

HOVERGEN

HBG108512.

OMA

HISQLQE.

PhylomeDB

Q96SB4.

Gene expression databases

ArrayExpress

Q96SB4.

Bgee

Q96SB4.

CleanEx

HS_SRPK1.

Genevestigator

Q96SB4.

GermOnline

ENSG00000096063. Homo sapiens.

Family and domain databases

InterPro

IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR017442. Se/Thr_kinase-like_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

KO

K15409.

Pfam

PF00069. Pkinase. 2 hits.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

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:	January 25, 2012
This is version 103 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.