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Reviewed, UniProtKB/Swiss-Prot Q96SB4 (SRPK1_HUMAN)

Last modified July 7, 2009. Version 76. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length655 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence 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.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

RNPS1Q152871EBI-539478,EBI-395959
SafbO884532EBI-539478,EBI-539530From a different organism.
SFRS1Q079551EBI-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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 655655Serine/threonine-protein kinase SRPK1
PRO_0000086674

Regions

Domain80 – 653574Protein kinase
Nucleotide binding86 – 949ATP
Nucleotide binding166 – 1683ATP

Sites

Active site2131Proton acceptor
Binding site1091ATP

Amino acid modifications

Modified residue511Phosphoserine; by CK2 Ref.8 Ref.9 Ref.11
Modified residue3091Phosphoserine Ref.9 Ref.11 Ref.10
Modified residue3111Phosphoserine Ref.9 Ref.11
Modified residue5551Phosphoserine; by CK2 Ref.8

Natural variations

Alternative sequence5 – 241237VLALQ…EWQRS → GERWSGLRHEGQWSPGRGPG QRRELRLTAAVRFPDVRRPS TEVAPPHTPCLWAAGPRPSF RASSGAGRSRPLFPARPARA LGPLQGPALGGRRRPPPARP LTRPETPPAHPARALLCAPW AASPTAGRLAEARSRPRGRP RSRAWRPCWVSTLTLVASFP PHSPFIHPSLLQCLRSRPER KGPRPRRTKPKGNLKLSTEA LLPTLRVIYQSRKRRFWDLM MMSKKILMIIVKEVIIL in isoform 1.
VSP_035581
Alternative sequence242 – 655414Missing in isoform 1.
VSP_035582
Natural variant721I → T: dbSNP rs35519113.
VAR_051669

Experimental info

Mutagenesis371S → A: No effect on protein phosphorylation. Ref.8
Mutagenesis511S → A: Protein phosphorylation impaired at this position. Ref.8
Mutagenesis2221S → A: No effect on protein phosphorylation. Ref.8
Mutagenesis3111S → G: No effect on protein phosphorylation. Ref.8
Mutagenesis4361S → G: No effect on protein phosphorylation. Ref.8
Mutagenesis5551S → A: Protein phosphorylation impaired at this position. Ref.8
Mutagenesis6191S → A: No effect on protein phosphorylation. Ref.8
Sequence conflict2101I → T in AAH38292. Ref.4
Sequence conflict3601I → L AA sequence Ref.5
Sequence conflict3631I → L AA sequence Ref.5
Sequence conflict400 – 4012SQ → LP in AAA20530. Ref.1

Secondary structure

........................................................... 655
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 2 [UniParc].

Last modified October 14, 2008. Version 2.
Checksum: 900E980FE1C16B9A

FASTA65574,325
        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 

« Hide

Isoform 1 (1a).

Checksum: 2A521048CC38386F
Show »

FASTA24127,065

References

« Hide '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. expand/collapse author list , 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

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.
IPIIPI00412344.
IPI00914014.
PIRS45337.
RefSeqNP_003128.3.
UniGeneHs.443861

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1WAKX-ray1.73A42-655[»]
1WBPX-ray2.40A42-655[»]
3BEGX-ray2.90A58-655[»]
ModBaseSearch...

Protein-protein interaction databases

IntActQ96SB4. 8 interactions.

PTM databases

PhosphoSiteQ96SB4.

Proteomic databases

PRIDEQ96SB4.

Genome annotation databases

EnsemblENSG00000096063. Homo sapiens. [Contig view]
GeneID6732.
KEGGhsa:6732.

Organism-specific databases

GeneCardsGC06M035908.
H-InvDBHIX0005813.
HGNCHGNC:11305. SRPK1.
HPAHPA016431.
MIM601939. gene.
PharmGKBPA36129.
GenAtlasSearch...

Phylogenomic databases

HOGENOMQ96SB4.
HOVERGENQ96SB4.

Enzyme and pathway databases

BRENDA2.7.11.1. 247.

Gene expression databases

ArrayExpressQ96SB4.
BgeeQ96SB4.
CleanExHS_SRPK1.
GermOnlineENSG00000096063. Homo sapiens.

Family and domain databases

InterProIPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_BS.
IPR017442. Se/Thr_pkinase-rel.
IPR008271. Ser_thr_pkin_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
ProDomPD000001. Prot_kinase. 2 hits.
[Graphical view] [Entries sharing at least one domain]
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio26262.
SOURCESearch...

Entry information

Entry nameSRPK1_HUMAN
AccessionPrimary (citable) accession number: Q96SB4
Secondary accession number(s): Q12890 expand/collapse secondary AC list , 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 statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents