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Protein

SRSF protein kinase 2

Gene

SRPK2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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. Can mediate hepatitis B virus (HBV) core protein phosphorylation. 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.8 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.2 Publications

Cofactori

Mg2+2 Publications

Activity regulationi

Activated by phosphorylation on Ser-52 and Ser-588.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei110ATPPROSITE-ProRule annotationBy similarity1
Active sitei214Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi87 – 95ATPPROSITE-ProRule annotationBy similarity9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processDifferentiation, mRNA processing, mRNA splicing
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

SignaLinkiP78362
SIGNORiP78362

Protein family/group databases

MoonDBiP78362 Predicted

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000135250.16
HGNCiHGNC:11306 SRPK2
MIMi602980 gene
neXtProtiNX_P78362

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi6733
OpenTargetsiENSG00000135250
PharmGKBiPA36130

Chemistry databases

ChEMBLiCHEMBL5668
DrugBankiDB00173 Adenine
DB04395 Phosphoaminophosphonic Acid-Adenylate Ester
DB02733 Purvalanol

Polymorphism and mutation databases

DMDMi300669676

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000866771 – 688SRSF protein kinase 2Add BLAST688
ChainiPRO_00004147511 – 139SRSF protein kinase 2 N-terminalAdd BLAST139
ChainiPRO_0000414752140 – 688SRSF protein kinase 2 C-terminalAdd BLAST549

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei52PhosphoserineCombined sources1
Modified residuei380PhosphoserineCombined sources1
Modified residuei475PhosphoserineBy similarity1
Modified residuei478PhosphothreonineBy similarity1
Modified residuei484PhosphoserineBy similarity1
Modified residuei486PhosphoserineBy similarity1
Modified residuei490PhosphoserineBy similarity1
Modified residuei492Phosphothreonine; by PKB/AKT11 Publication1
Modified residuei494PhosphoserineCombined sources1
Modified residuei497PhosphoserineCombined sources1
Modified residuei588Phosphoserine; by CK2By similarity1

Post-translational modificationi

Phosphorylation at Thr-492 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.1 Publication
Proteolytically cleaved at Asp-139 and Asp-403 by caspase-3 during apoptotic cell death. Cleavage at Asp-139 which is the major site of cleavage, produces a small N-terminal fragment that translocates into nucleus and promotes VP16-induced apoptosis.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei139 – 140Cleavage; by caspase-31 Publication2
Sitei403 – 404Cleavage; by caspase-31 Publication2

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP78362
MaxQBiP78362
PaxDbiP78362
PeptideAtlasiP78362
PRIDEiP78362
ProteomicsDBi57591
57592 [P78362-2]

PTM databases

iPTMnetiP78362
PhosphoSitePlusiP78362

Expressioni

Tissue specificityi

Highly expressed in brain, moderately expressed in heart and skeletal muscle and at low levels in lung, liver, and kidney.1 Publication

Gene expression databases

BgeeiENSG00000135250 Expressed in 240 organ(s), highest expression level in sperm
CleanExiHS_SRPK2
ExpressionAtlasiP78362 baseline and differential
GenevisibleiP78362 HS

Organism-specific databases

HPAiHPA015522
HPA020876

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).2 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi112611, 454 interactors
IntActiP78362, 242 interactors
MINTiP78362
STRINGi9606.ENSP00000377262

Chemistry databases

BindingDBiP78362

Structurei

Secondary structure

1688
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP78362
SMRiP78362
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP78362

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini81 – 684Protein kinasePROSITE-ProRule annotationAdd BLAST604

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG1290 Eukaryota
ENOG410XRBH LUCA
GeneTreeiENSGT00530000063566
HOVERGENiHBG108512
InParanoidiP78362
KOiK08831
OMAiGNIPRHF
OrthoDBiEOG091G05H9
PhylomeDBiP78362
TreeFamiTF105334

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 2 hits
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 6 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P78362-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MSVNSEKSSS SERPEPQQKA PLVPPPPPPP PPPPPPLPDP TPPEPEEEIL
60 70 80 90 100
GSDDEEQEDP ADYCKGGYHP VKIGDLFNGR YHVIRKLGWG HFSTVWLCWD
110 120 130 140 150
MQGKRFVAMK VVKSAQHYTE TALDEIKLLK CVRESDPSDP NKDMVVQLID
160 170 180 190 200
DFKISGMNGI HVCMVFEVLG HHLLKWIIKS NYQGLPVRCV KSIIRQVLQG
210 220 230 240 250
LDYLHSKCKI IHTDIKPENI LMCVDDAYVR RMAAEATEWQ KAGAPPPSGS
260 270 280 290 300
AVSTAPQQKP IGKISKNKKK KLKKKQKRQA ELLEKRLQEI EELEREAERK
310 320 330 340 350
IIEENITSAA PSNDQDGEYC PEVKLKTTGL EEAAEAETAK DNGEAEDQEE
360 370 380 390 400
KEDAEKENIE KDEDDVDQEL ANIDPTWIES PKTNGHIENG PFSLEQQLDD
410 420 430 440 450
EDDDEEDCPN PEEYNLDEPN AESDYTYSSS YEQFNGELPN GRHKIPESQF
460 470 480 490 500
PEFSTSLFSG SLEPVACGSV LSEGSPLTEQ EESSPSHDRS RTVSASSTGD
510 520 530 540 550
LPKAKTRAAD LLVNPLDPRN ADKIRVKIAD LGNACWVHKH FTEDIQTRQY
560 570 580 590 600
RSIEVLIGAG YSTPADIWST ACMAFELATG DYLFEPHSGE DYSRDEDHIA
610 620 630 640 650
HIIELLGSIP RHFALSGKYS REFFNRRGEL RHITKLKPWS LFDVLVEKYG
660 670 680
WPHEDAAQFT DFLIPMLEMV PEKRASAGEC LRHPWLNS
Length:688
Mass (Da):77,527
Last modified:July 13, 2010 - v3
Checksum:iACCAF2A887444EC2
GO
Isoform 2 (identifier: P78362-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-13: MSVNSEKSSSSER → MSSRKVLAIQARKRRPKREKHPKK

Show »
Length:699
Mass (Da):79,029
Checksum:i70B084ABA32CC3DB
GO

Computationally mapped potential isoform sequencesi

There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H7C5L6H7C5L6_HUMAN
SRSF protein kinase 2
SRPK2
295Annotation score:
C9JWF7C9JWF7_HUMAN
SRSF protein kinase 2
SRPK2
231Annotation score:
C9J2M4C9J2M4_HUMAN
SRSF protein kinase 2
SRPK2
160Annotation score:
H7C521H7C521_HUMAN
SRSF protein kinase 2
SRPK2
204Annotation score:
F8WBW4F8WBW4_HUMAN
SRSF protein kinase 2
SRPK2
147Annotation score:
F8WAV6F8WAV6_HUMAN
SRSF protein kinase 2
SRPK2
68Annotation score:

Sequence cautioni

The sequence AAQ63886 differs from that shown. The cDNA appears to contain a duplicated region.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti137P → R in AAH68547 (PubMed:15489334).Curated1
Sequence conflicti236 – 237AT → P in AAC05299 (PubMed:9472028).Curated2
Sequence conflicti521A → R in AAC05299 (PubMed:9472028).Curated1
Sequence conflicti601H → L in AAC29141 (PubMed:12853948).Curated1
Sequence conflicti608 – 609SI → KV in AAC29141 (PubMed:12853948).Curated2
Sequence conflicti612 – 616HFALS → KYAML in AAC29141 (PubMed:12853948).Curated5
Sequence conflicti621R → K in AAC29141 (PubMed:12853948).Curated1
Sequence conflicti625 – 627NRR → TRK in AAC29141 (PubMed:12853948).Curated3
Sequence conflicti640S → G in AAH68547 (PubMed:15489334).Curated1
Sequence conflicti681Missing in AAC05299 (PubMed:9472028).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04111443P → L1 PublicationCorresponds to variant dbSNP:rs34699980Ensembl.1
Natural variantiVAR_041115243G → D in a glioblastoma multiforme sample; somatic mutation. 1 Publication1
Natural variantiVAR_041116426T → P1 PublicationCorresponds to variant dbSNP:rs55743527Ensembl.1
Natural variantiVAR_041117486S → F1 PublicationCorresponds to variant dbSNP:rs56112661Ensembl.1
Natural variantiVAR_041118515P → T1 PublicationCorresponds to variant dbSNP:rs56017595Ensembl.1
Natural variantiVAR_060390608S → N. Corresponds to variant dbSNP:rs1050413Ensembl.1
Natural variantiVAR_057111615L → I. Corresponds to variant dbSNP:rs1050418Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0393861 – 13MSVNS…SSSER → MSSRKVLAIQARKRRPKREK HPKK in isoform 2. 1 PublicationAdd BLAST13

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U88666 mRNA Translation: AAC05299.1
AC005070 Genomic DNA Translation: AAC29140.1
AC005070 Genomic DNA Translation: AAC29141.1
AC004884 Genomic DNA No translation available.
AC073138 Genomic DNA No translation available.
CH471070 Genomic DNA Translation: EAW83359.1
BC035214 mRNA Translation: AAH35214.1
BC068547 mRNA Translation: AAH68547.1
BE781215 mRNA No translation available.
AY354201 mRNA Translation: AAQ63886.1 Sequence problems.
CCDSiCCDS34724.1 [P78362-2]
CCDS5735.1 [P78362-1]
RefSeqiNP_001265202.1, NM_001278273.1 [P78362-1]
NP_872633.1, NM_182691.2 [P78362-1]
NP_872634.1, NM_182692.2 [P78362-2]
XP_016868055.1, XM_017012566.1
UniGeneiHs.285197

Genome annotation databases

EnsembliENST00000357311; ENSP00000349863; ENSG00000135250 [P78362-1]
ENST00000393651; ENSP00000377262; ENSG00000135250 [P78362-2]
ENST00000489828; ENSP00000419791; ENSG00000135250 [P78362-1]
GeneIDi6733
KEGGihsa:6733
UCSCiuc003vct.5 human [P78362-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U88666 mRNA Translation: AAC05299.1
AC005070 Genomic DNA Translation: AAC29140.1
AC005070 Genomic DNA Translation: AAC29141.1
AC004884 Genomic DNA No translation available.
AC073138 Genomic DNA No translation available.
CH471070 Genomic DNA Translation: EAW83359.1
BC035214 mRNA Translation: AAH35214.1
BC068547 mRNA Translation: AAH68547.1
BE781215 mRNA No translation available.
AY354201 mRNA Translation: AAQ63886.1 Sequence problems.
CCDSiCCDS34724.1 [P78362-2]
CCDS5735.1 [P78362-1]
RefSeqiNP_001265202.1, NM_001278273.1 [P78362-1]
NP_872633.1, NM_182691.2 [P78362-1]
NP_872634.1, NM_182692.2 [P78362-2]
XP_016868055.1, XM_017012566.1
UniGeneiHs.285197

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2X7GX-ray2.50A51-688[»]
5MYVX-ray2.90A/B/C/D51-688[»]
ProteinModelPortaliP78362
SMRiP78362
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112611, 454 interactors
IntActiP78362, 242 interactors
MINTiP78362
STRINGi9606.ENSP00000377262

Chemistry databases

BindingDBiP78362
ChEMBLiCHEMBL5668
DrugBankiDB00173 Adenine
DB04395 Phosphoaminophosphonic Acid-Adenylate Ester
DB02733 Purvalanol

Protein family/group databases

MoonDBiP78362 Predicted

PTM databases

iPTMnetiP78362
PhosphoSitePlusiP78362

Polymorphism and mutation databases

DMDMi300669676

Proteomic databases

EPDiP78362
MaxQBiP78362
PaxDbiP78362
PeptideAtlasiP78362
PRIDEiP78362
ProteomicsDBi57591
57592 [P78362-2]

Protocols and materials databases

DNASUi6733
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000357311; ENSP00000349863; ENSG00000135250 [P78362-1]
ENST00000393651; ENSP00000377262; ENSG00000135250 [P78362-2]
ENST00000489828; ENSP00000419791; ENSG00000135250 [P78362-1]
GeneIDi6733
KEGGihsa:6733
UCSCiuc003vct.5 human [P78362-1]

Organism-specific databases

CTDi6733
DisGeNETi6733
EuPathDBiHostDB:ENSG00000135250.16
GeneCardsiSRPK2
H-InvDBiHIX0006976
HGNCiHGNC:11306 SRPK2
HPAiHPA015522
HPA020876
MIMi602980 gene
neXtProtiNX_P78362
OpenTargetsiENSG00000135250
PharmGKBiPA36130
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1290 Eukaryota
ENOG410XRBH LUCA
GeneTreeiENSGT00530000063566
HOVERGENiHBG108512
InParanoidiP78362
KOiK08831
OMAiGNIPRHF
OrthoDBiEOG091G05H9
PhylomeDBiP78362
TreeFamiTF105334

Enzyme and pathway databases

SignaLinkiP78362
SIGNORiP78362

Miscellaneous databases

ChiTaRSiSRPK2 human
EvolutionaryTraceiP78362
GeneWikiiSRPK2
GenomeRNAii6733
PROiPR:P78362
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000135250 Expressed in 240 organ(s), highest expression level in sperm
CleanExiHS_SRPK2
ExpressionAtlasiP78362 baseline and differential
GenevisibleiP78362 HS

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 2 hits
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiSRPK2_HUMAN
AccessioniPrimary (citable) accession number: P78362
Secondary accession number(s): A8MVX2
, O75220, O75221, Q6NUL0, Q6V1X2, Q8IYQ3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 5, 2005
Last sequence update: July 13, 2010
Last modified: November 7, 2018
This is version 177 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  7. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
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