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Protein

SRSF protein kinase 2

Gene

Srpk2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. Promotes neuronal apoptosis by up-regulating cyclin-D1 (CCND1) expression. This is done by the phosphorylation of SRSF2, leading to the suppression of p53/TP53 phosphorylation thereby relieving the repressive effect of p53/TP53 on cyclin-D1 (CCND1) expression. Phosphorylates ACIN1, and redistributes it from the nuclear speckles to the nucleoplasm, resulting in cyclin A1 but not cyclin A2 up-regulation. Plays an essential role in spliceosomal B complex formation via the phosphorylation of DDX23/PRP28.2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.1 Publication

Cofactori

Mg2+1 Publication

Enzyme regulationi

Activated by phosphorylation on Ser-50 and Ser-581.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei108 – 1081ATPPROSITE-ProRule annotationBy similarity
Active sitei212 – 2121Proton acceptorPROSITE-ProRule annotationBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi85 – 939ATPPROSITE-ProRule annotationBy similarity

GO - Molecular functioni

  • 14-3-3 protein binding Source: BHF-UCL
  • ATP binding Source: UniProtKB
  • magnesium ion binding Source: UniProtKB
  • poly(A) RNA binding Source: MGI
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  • angiogenesis Source: BHF-UCL
  • cell differentiation Source: UniProtKB-KW
  • intracellular signal transduction Source: UniProtKB
  • negative regulation of viral genome replication Source: BHF-UCL
  • nuclear speck organization Source: BHF-UCL
  • positive regulation of cell cycle Source: BHF-UCL
  • positive regulation of cell proliferation Source: BHF-UCL
  • positive regulation of gene expression Source: BHF-UCL
  • positive regulation of neuron apoptotic process Source: BHF-UCL
  • positive regulation of viral genome replication Source: BHF-UCL
  • protein phosphorylation Source: UniProtKB
  • RNA splicing Source: UniProtKB
  • spliceosomal complex assembly Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Differentiation, mRNA processing, mRNA splicing

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
SRSF protein kinase 2 (EC:2.7.11.1)
Alternative name(s):
SFRS protein kinase 2
Serine/arginine-rich protein-specific kinase 2
Short name:
SR-protein-specific kinase 2
Cleaved into the following 2 chains:
Gene namesi
Name:Srpk2Imported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1201408. Srpk2.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • nucleolus Source: MGI
  • nucleoplasm Source: MGI
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 681681SRSF protein kinase 2PRO_0000086678Add
BLAST
Chaini1 – 137137SRSF protein kinase 2 N-terminalPRO_0000414753Add
BLAST
Chaini138 – 681544SRSF protein kinase 2 C-terminalPRO_0000414754Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei50 – 501PhosphoserineCombined sources
Modified residuei331 – 3311PhosphothreonineCombined sources
Modified residuei332 – 3321PhosphothreonineCombined sources
Modified residuei378 – 3781PhosphoserineCombined sources
Modified residuei468 – 4681PhosphoserineCombined sources
Modified residuei471 – 4711PhosphothreonineCombined sources
Modified residuei477 – 4771PhosphoserineCombined sources
Modified residuei479 – 4791PhosphoserineCombined sources
Modified residuei483 – 4831PhosphoserineCombined sources
Modified residuei485 – 4851Phosphothreonine; by PKB/AKT1By similarity
Modified residuei487 – 4871PhosphoserineCombined sources
Modified residuei490 – 4901PhosphoserineBy similarity
Modified residuei581 – 5811Phosphoserine; by CK2By similarity

Post-translational modificationi

Phosphorylation at Thr-485 by PKB/AKT1 enhances its stimulatory activity in triggering cyclin-D1 (CCND1) expression and promoting apoptosis in neurons, which can be blocked by YWHAB. It also enhances its protein kinase activity toward ACIN1 and SRSF2, promotes its nuclear translocation and prevents its proteolytic cleavage (By similarity).By similarity
Proteolytically cleaved at Asp-137 and Asp-401 by caspase-3 during apoptotic cell death. Cleavage at Asp-137 which is the major site of cleavage, produces a small N-terminal fragment that translocates into nucleus and promotes VP16-induced apoptosis (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei137 – 1382Cleavage; by caspase-3By similarity
Sitei401 – 4022Cleavage; by caspase-3By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO54781.
MaxQBiO54781.
PaxDbiO54781.
PeptideAtlasiO54781.
PRIDEiO54781.

PTM databases

iPTMnetiO54781.
PhosphoSiteiO54781.

Expressioni

Tissue specificityi

Expressed in testes, lung and brain.1 Publication

Gene expression databases

BgeeiO54781.
CleanExiMM_SRPK2.

Interactioni

Subunit structurei

Interacts with PKB/AKT1 in a phosphorylation-dependent manner. The phosphorylated form (by PKB/AKT1) interacts with YWHAB and YWHAE. Interaction with YWHAB suppresses its cleavage by caspases and inhibits the release of its N-terminal pro-apoptotic fragment. Interacts with SFN. Associates with U4/U6-U5 tri-small nuclear ribonucleoproteins (U4/U6-U5 tri-snRNPs) (By similarity). Interacts with ACIN1.By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
SRSF1Q079553EBI-593325,EBI-398920From a different organism.

GO - Molecular functioni

  • 14-3-3 protein binding Source: BHF-UCL

Protein-protein interaction databases

IntActiO54781. 1 interaction.
STRINGi10090.ENSMUSP00000085734.

Structurei

3D structure databases

ProteinModelPortaliO54781.
SMRiO54781. Positions 62-281, 501-681.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini79 – 681603Protein kinasePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG1290. Eukaryota.
ENOG410XRBH. LUCA.
HOGENOMiHOG000171558.
HOVERGENiHBG108512.
InParanoidiO54781.
KOiK08831.
OrthoDBiEOG70S74X.
PhylomeDBiO54781.
TreeFamiTF105334.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 2 hits.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 2 hits.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O54781-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSVNSEKSSS SERPEPQQKA PLVPPPPPPP PPPPLPDPAP PEPEEEILGS
60 70 80 90 100
DDEEQEDPAD YCKGGYHPVK IGDLFNGRYH VIRKLGWGHF STVWLCWDMQ
110 120 130 140 150
GKRFVAMKVV KSAQHYTETA LDEIKLLKCV RESDPSDPNK DMVVQLIDDF
160 170 180 190 200
KISGMNGIHV CMVFEVLGHH LLKWIIKSNY QGLPVRCVKS IIRQVLQGLD
210 220 230 240 250
YLHSKCKIIH TDIKPENILM CVDDAYVRRM AAEATEWQKA GAPPPSGSAV
260 270 280 290 300
STAPQQKPIG KISKNKKKKL KKKQKRQAEL LEKRLQEIEE LEREAERKIL
310 320 330 340 350
EENITSAEAS GEQDGEYQPE VTLKAADLED TTEEETAKDN GEVEDQEEKE
360 370 380 390 400
DAEKENAEKD EDDVEQELAN LDPTWVESPK ANGHIENGPF SLEQQLEDEE
410 420 430 440 450
DDEDDCANPE EYNLDEPNAE SDYTYSSSYE QFNGELPNGQ HKTSEFPTPL
460 470 480 490 500
FSGPLEPVAC GSVISEGSPL TEQEESSPSH DRSRTVSASS TGDLPKTKTR
510 520 530 540 550
AADLLVNPLD PRNADKIRVK IADLGNACWV HKHFTEDIQT RQYRSIEVLI
560 570 580 590 600
GAGYSTPADI WSTACMAFEL ATGDYLFEPH SGEDYSRDED HIAHIIELLG
610 620 630 640 650
SIPRHFALSG KYSREFFNRR GELRHITKLK PWSLFDVLVE KYGWPHEDAA
660 670 680
QFTDFLIPML EMVPEKRASA GECLRHPWLN S
Length:681
Mass (Da):76,757
Last modified:July 5, 2005 - v2
Checksum:i1857EA955B2F9C0E
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti313 – 3131Q → QQ in AAH20178 (PubMed:15489334).Curated
Sequence conflicti368 – 3681L → P in BAA24055 (PubMed:9446799).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB006036 mRNA. Translation: BAA24055.1.
BC020178 mRNA. Translation: AAH20178.1.
PIRiJC5929.
RefSeqiNP_033300.2. NM_009274.2.
UniGeneiMm.288728.

Genome annotation databases

GeneIDi20817.
KEGGimmu:20817.
UCSCiuc008wqe.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB006036 mRNA. Translation: BAA24055.1.
BC020178 mRNA. Translation: AAH20178.1.
PIRiJC5929.
RefSeqiNP_033300.2. NM_009274.2.
UniGeneiMm.288728.

3D structure databases

ProteinModelPortaliO54781.
SMRiO54781. Positions 62-281, 501-681.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiO54781. 1 interaction.
STRINGi10090.ENSMUSP00000085734.

PTM databases

iPTMnetiO54781.
PhosphoSiteiO54781.

Proteomic databases

EPDiO54781.
MaxQBiO54781.
PaxDbiO54781.
PeptideAtlasiO54781.
PRIDEiO54781.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi20817.
KEGGimmu:20817.
UCSCiuc008wqe.1. mouse.

Organism-specific databases

CTDi6733.
MGIiMGI:1201408. Srpk2.

Phylogenomic databases

eggNOGiKOG1290. Eukaryota.
ENOG410XRBH. LUCA.
HOGENOMiHOG000171558.
HOVERGENiHBG108512.
InParanoidiO54781.
KOiK08831.
OrthoDBiEOG70S74X.
PhylomeDBiO54781.
TreeFamiTF105334.

Miscellaneous databases

ChiTaRSiSrpk2. mouse.
PROiO54781.
SOURCEiSearch...

Gene expression databases

BgeeiO54781.
CleanExiMM_SRPK2.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 2 hits.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 2 hits.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Novel SR-protein-specific kinase, SRPK2, disassembles nuclear speckles."
    Kuroyanagi N., Onogi H., Wakabayashi T., Hagiwara M.
    Biochem. Biophys. Res. Commun. 242:357-364(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
    Tissue: Brain1 Publication.
  2. "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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: EyeImported.
  3. "Serine/arginine protein-specific kinase 2 promotes leukemia cell proliferation by phosphorylating acinus and regulating cyclin A1."
    Jang S.W., Yang S.J., Ehlen A., Dong S., Khoury H., Chen J., Persson J.L., Ye K.
    Cancer Res. 68:4559-4570(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ACIN1.
  4. "Interaction of Akt-phosphorylated SRPK2 with 14-3-3 mediates cell cycle and cell death in neurons."
    Jang S.W., Liu X., Fu H., Rees H., Yepes M., Levey A., Ye K.
    J. Biol. Chem. 284:24512-24525(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  5. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-50; THR-331; THR-332; SER-378; SER-468; THR-471; SER-477; SER-479; SER-483 AND SER-487, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, Spleen and Testis.

Entry informationi

Entry nameiSRPK2_MOUSE
AccessioniPrimary (citable) accession number: O54781
Secondary accession number(s): Q8VCD9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 5, 2005
Last sequence update: July 5, 2005
Last modified: July 6, 2016
This is version 126 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.