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Protein

SRSF protein kinase 1

Gene

SRPK1

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. 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 K-562 leukaemic cell line: isoform 2 favors proliferation where as isoform 1 favors differentiation.16 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.6 Publications

Cofactori

Mg2+6 Publications

Activity regulationi

Activated by phosphorylation on Ser-51 and Ser-555.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei109ATPPROSITE-ProRule annotation1 Publication1
Active sitei213Proton acceptor1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi86 – 94ATPPROSITE-ProRule annotation1 Publication9
Nucleotide bindingi166 – 168ATPPROSITE-ProRule annotation1 Publication3

GO - Molecular functioni

  • ATP binding Source: UniProtKB
  • magnesium ion binding Source: UniProtKB
  • protein kinase activity Source: ProtInc
  • protein serine/threonine kinase activity Source: UniProtKB
  • RNA binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processChromosome partition, Differentiation, Host-virus interaction, mRNA processing, mRNA splicing
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

SignaLinkiQ96SB4
SIGNORiQ96SB4

Protein family/group databases

MoonDBiQ96SB4 Predicted

Names & Taxonomyi

Protein namesi
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 namesi
Name:SRPK1Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000096063.14
HGNCiHGNC:11305 SRPK1
MIMi601939 gene
neXtProtiNX_Q96SB4

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, Endoplasmic reticulum, Microsome, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi37S → A: No effect on protein phosphorylation. 1 Publication1
Mutagenesisi51S → A: Protein phosphorylation impaired at this position. 1 Publication1
Mutagenesisi222S → A: No effect on protein phosphorylation. 1 Publication1
Mutagenesisi311S → G: No effect on protein phosphorylation. 1 Publication1
Mutagenesisi436S → G: No effect on protein phosphorylation. 1 Publication1
Mutagenesisi555S → A: Protein phosphorylation impaired at this position. 1 Publication1
Mutagenesisi619S → A: No effect on protein phosphorylation. 1 Publication1

Organism-specific databases

DisGeNETi6732
OpenTargetsiENSG00000096063
PharmGKBiPA36129

Chemistry databases

ChEMBLiCHEMBL4375
GuidetoPHARMACOLOGYi2208

Polymorphism and mutation databases

BioMutaiSRPK1
DMDMi209572680

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000866741 – 655SRSF protein kinase 1Add BLAST655

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei51Phosphoserine; by CK2Combined sources1 Publication1
Modified residuei309PhosphoserineCombined sources1
Modified residuei311PhosphoserineCombined sources1
Modified residuei333PhosphoserineCombined sources1
Modified residuei555Phosphoserine; by CK21 Publication1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ96SB4
PaxDbiQ96SB4
PeptideAtlasiQ96SB4
PRIDEiQ96SB4
ProteomicsDBi78098
78099 [Q96SB4-3]

PTM databases

iPTMnetiQ96SB4
PhosphoSitePlusiQ96SB4

Expressioni

Tissue specificityi

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 1.3 Publications

Gene expression databases

BgeeiENSG00000096063 Expressed in 224 organ(s), highest expression level in testis
CleanExiHS_SRPK1
ExpressionAtlasiQ96SB4 baseline and differential
GenevisibleiQ96SB4 HS

Organism-specific databases

HPAiHPA016431
HPA056486

Interactioni

Subunit structurei

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 DNAJC8 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.9 Publications
(Microbial infection) Isoform 2 interacts with HHV-1 ICP27 protein.1 Publication

Binary interactionsi

Protein-protein interaction databases

BioGridi112610, 244 interactors
CORUMiQ96SB4
DIPiDIP-33888N
IntActiQ96SB4, 243 interactors
MINTiQ96SB4
STRINGi9606.ENSP00000362931

Chemistry databases

BindingDBiQ96SB4

Structurei

Secondary structure

1655
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ96SB4
SMRiQ96SB4
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96SB4

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini80 – 653Protein kinasePROSITE-ProRule annotationAdd BLAST574

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG1290 Eukaryota
ENOG410XRBH LUCA
GeneTreeiENSGT00530000063566
HOGENOMiHOG000171558
HOVERGENiHBG108512
InParanoidiQ96SB4
KOiK15409
PhylomeDBiQ96SB4
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 (3+)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 6 potential isoforms that are computationally mapped.Show allAlign All

Isoform 22 Publications (identifier: Q96SB4-2) [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
MERKVLALQA RKKRTKAKKD KAQRKSETQH RGSAPHSESD LPEQEEEILG
60 70 80 90 100
SDDDEQEDPN DYCKGGYHLV KIGDLFNGRY HVIRKLGWGH FSTVWLSWDI
110 120 130 140 150
QGKKFVAMKV VKSAEHYTET ALDEIRLLKS VRNSDPNDPN REMVVQLLDD
160 170 180 190 200
FKISGVNGTH ICMVFEVLGH HLLKWIIKSN YQGLPLPCVK KIIQQVLQGL
210 220 230 240 250
DYLHTKCRII HTDIKPENIL LSVNEQYIRR LAAEATEWQR SGAPPPSGSA
260 270 280 290 300
VSTAPQPKPA DKMSKNKKKK LKKKQKRQAE LLEKRMQEIE EMEKESGPGQ
310 320 330 340 350
KRPNKQEESE SPVERPLKEN PPNKMTQEKL EESSTIGQDQ TLMERDTEGG
360 370 380 390 400
AAEINCNGVI EVINYTQNSN NETLRHKEDL HNANDCDVQN LNQESSFLSS
410 420 430 440 450
QNGDSSTSQE TDSCTPITSE VSDTMVCQSS STVGQSFSEQ HISQLQESIR
460 470 480 490 500
AEIPCEDEQE QEHNGPLDNK GKSTAGNFLV NPLEPKNAEK LKVKIADLGN
510 520 530 540 550
ACWVHKHFTE DIQTRQYRSL EVLIGSGYNT PADIWSTACM AFELATGDYL
560 570 580 590 600
FEPHSGEEYT RDEDHIALII ELLGKVPRKL IVAGKYSKEF FTKKGDLKHI
610 620 630 640 650
TKLKPWGLFE VLVEKYEWSQ EEAAGFTDFL LPMLELIPEK RATAAECLRH

PWLNS
Length:655
Mass (Da):74,325
Last modified:October 14, 2008 - v2
Checksum:i900E980FE1C16B9A
GO
Isoform 1 (identifier: Q96SB4-3) [UniParc]FASTAAdd to basket
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.
Show »
Length:826
Mass (Da):92,412
Checksum:i9E4D86DE22A10D32
GO
Isoform 3 (identifier: Q96SB4-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-25: MERKVLALQARKKRTKAKKDKAQRK → MGIFVSFLR

Note: No experimental confirmation available.
Show »
Length:639
Mass (Da):72,383
Checksum:iC8E469D4EE9D0563
GO

Computationally mapped potential isoform sequencesi

There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H3BLV9H3BLV9_HUMAN
SRSF protein kinase 1
SRPK1
671Annotation score:
D6RBM8D6RBM8_HUMAN
SRSF protein kinase 1
SRPK1
155Annotation score:
D6RBF8D6RBF8_HUMAN
SRSF protein kinase 1
SRPK1
146Annotation score:
H0Y932H0Y932_HUMAN
SRSF protein kinase 1
SRPK1
42Annotation score:
D6RB98D6RB98_HUMAN
SRSF protein kinase 1
SRPK1
118Annotation score:
D6RDZ3D6RDZ3_HUMAN
SRSF protein kinase 1
SRPK1
76Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti210I → T in AAH38292 (PubMed:15489334).Curated1
Sequence conflicti360I → L AA sequence (PubMed:12134018).Curated1
Sequence conflicti363I → L AA sequence (PubMed:12134018).Curated1
Sequence conflicti400 – 401SQ → LP in AAA20530 (PubMed:8208298).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05166972I → T. Corresponds to variant dbSNP:rs35519113Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0573561 – 25MERKV…KAQRK → MGIFVSFLR in isoform 3. 1 PublicationAdd BLAST25
Alternative sequenceiVSP_0421304K → KGERWSGLRHEGQWSPGRGP GQRRELRLTAAVRFPDVRRP STEVAPPHTPCLWAAGPRPS FRASSGAGRSRPLFPARPAR ALGPLQGPALGGRRRPPPAR PLTRPETPPAHPARALLCAP WAASPTPAASPSPQPPPRQA PQPGLAPLLGLHPHLGRLLS STFALHPSLSPA in isoform 1. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U09564 mRNA Translation: AAA20530.1
AJ318054 mRNA Translation: CAC39299.1
AK299591 mRNA Translation: BAG61523.1
Z99128 Genomic DNA No translation available.
CH471081 Genomic DNA Translation: EAX03859.1
BC038292 mRNA Translation: AAH38292.1
CCDSiCCDS47415.1 [Q96SB4-2]
PIRiS45337
RefSeqiNP_003128.3, NM_003137.4 [Q96SB4-2]
UniGeneiHs.443861

Genome annotation databases

EnsembliENST00000373825; ENSP00000362931; ENSG00000096063 [Q96SB4-2]
ENST00000423325; ENSP00000391069; ENSG00000096063 [Q96SB4-4]
GeneIDi6732
KEGGihsa:6732
UCSCiuc003olj.4 human [Q96SB4-2]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U09564 mRNA Translation: AAA20530.1
AJ318054 mRNA Translation: CAC39299.1
AK299591 mRNA Translation: BAG61523.1
Z99128 Genomic DNA No translation available.
CH471081 Genomic DNA Translation: EAX03859.1
BC038292 mRNA Translation: AAH38292.1
CCDSiCCDS47415.1 [Q96SB4-2]
PIRiS45337
RefSeqiNP_003128.3, NM_003137.4 [Q96SB4-2]
UniGeneiHs.443861

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1WAKX-ray1.73A42-655[»]
1WBPX-ray2.40A42-655[»]
3BEGX-ray2.90A58-255[»]
A474-655[»]
4WUAX-ray2.00A42-255[»]
A474-655[»]
5MXXX-ray1.75A40-655[»]
5MY8X-ray1.70A58-255[»]
A474-655[»]
5NNGX-ray1.20B582-591[»]
5XV7X-ray2.32A67-655[»]
ProteinModelPortaliQ96SB4
SMRiQ96SB4
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112610, 244 interactors
CORUMiQ96SB4
DIPiDIP-33888N
IntActiQ96SB4, 243 interactors
MINTiQ96SB4
STRINGi9606.ENSP00000362931

Chemistry databases

BindingDBiQ96SB4
ChEMBLiCHEMBL4375
GuidetoPHARMACOLOGYi2208

Protein family/group databases

MoonDBiQ96SB4 Predicted

PTM databases

iPTMnetiQ96SB4
PhosphoSitePlusiQ96SB4

Polymorphism and mutation databases

BioMutaiSRPK1
DMDMi209572680

Proteomic databases

EPDiQ96SB4
PaxDbiQ96SB4
PeptideAtlasiQ96SB4
PRIDEiQ96SB4
ProteomicsDBi78098
78099 [Q96SB4-3]

Protocols and materials databases

DNASUi6732
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000373825; ENSP00000362931; ENSG00000096063 [Q96SB4-2]
ENST00000423325; ENSP00000391069; ENSG00000096063 [Q96SB4-4]
GeneIDi6732
KEGGihsa:6732
UCSCiuc003olj.4 human [Q96SB4-2]

Organism-specific databases

CTDi6732
DisGeNETi6732
EuPathDBiHostDB:ENSG00000096063.14
GeneCardsiSRPK1
H-InvDBiHIX0005813
HGNCiHGNC:11305 SRPK1
HPAiHPA016431
HPA056486
MIMi601939 gene
neXtProtiNX_Q96SB4
OpenTargetsiENSG00000096063
PharmGKBiPA36129
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1290 Eukaryota
ENOG410XRBH LUCA
GeneTreeiENSGT00530000063566
HOGENOMiHOG000171558
HOVERGENiHBG108512
InParanoidiQ96SB4
KOiK15409
PhylomeDBiQ96SB4
TreeFamiTF105334

Enzyme and pathway databases

SignaLinkiQ96SB4
SIGNORiQ96SB4

Miscellaneous databases

ChiTaRSiSRPK1 human
EvolutionaryTraceiQ96SB4
GeneWikiiSRPK1
GenomeRNAii6732
PROiPR:Q96SB4
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000096063 Expressed in 224 organ(s), highest expression level in testis
CleanExiHS_SRPK1
ExpressionAtlasiQ96SB4 baseline and differential
GenevisibleiQ96SB4 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 nameiSRPK1_HUMAN
AccessioniPrimary (citable) accession number: Q96SB4
Secondary accession number(s): B4DS61
, Q12890, Q5R364, Q5R365, Q8IY12
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 21, 2005
Last sequence update: October 14, 2008
Last modified: November 7, 2018
This is version 172 of the entry and version 2 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, Direct protein sequencing, 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 6
    Human chromosome 6: 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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