CPLM-019633

Genbank Nucleotide ID

SRSF protein kinase 1

Protein Synonyms/Alias

SFRS protein kinase 1; Serine/arginine-rich protein-specific kinase 1; SR-protein-specific kinase 1

Homo sapiens (Human)

Position	Peptide	Type	References
4	****MERKVLALQAR	ubiquitination	[1, 2]
284	RQAELLEKRMQEIEE	ubiquitination	[3]
472	GPLDNKGKSTAGNFL	ubiquitination	[3]
494	NAEKLKVKIADLGNA	ubiquitination	[3]
506	GNACWVHKHFTEDIQ	ubiquitination	[3]
579	LLGKVPRKLIVAGKY	ubiquitination	[3]
585	RKLIVAGKYSKEFFT	acetylation	[4]
585	RKLIVAGKYSKEFFT	ubiquitination	[1, 2, 3]

[1] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
[2] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
Chen Z, Zhou Y, Song J, Zhang Z.
Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
[3] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
[4] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]

Functional Description

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.

DOMAIN 80 653 Protein kinase.
NP_BIND 86 94 ATP.
NP_BIND 166 168 ATP.
ACT_SITE 213 213 Proton acceptor.
BINDING 109 109 ATP.
MOD_RES 51 51 Phosphoserine; by CK2.
MOD_RES 309 309 Phosphoserine (By similarity).
MOD_RES 311 311 Phosphoserine.
MOD_RES 555 555 Phosphoserine; by CK2.

3D-structure; Alternative splicing; ATP-binding; Chromosome partition; Complete proteome; Cytoplasm; Differentiation; Direct protein sequencing; Endoplasmic reticulum; Host-virus interaction; Kinase; Microsome; mRNA processing; mRNA splicing; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Serine/threonine-protein kinase; Transferase.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005737; C:cytoplasm; IDA:UniProtKB.
GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-KW.
GO:0016363; C:nuclear matrix; IEA:UniProtKB-SubCell.
GO:0005634; C:nucleus; IDA:UniProtKB.
GO:0005524; F:ATP binding; IDA:UniProtKB.
GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
GO:0007059; P:chromosome segregation; IDA:UniProtKB.
GO:0045087; P:innate immune response; IC:BHF-UCL.
GO:0007243; P:intracellular protein kinase cascade; IDA:UniProtKB.
GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
GO:0045071; P:negative regulation of viral genome replication; IDA:BHF-UCL.
GO:0045070; P:positive regulation of viral genome replication; IDA:BHF-UCL.
GO:0048024; P:regulation of mRNA splicing, via spliceosome; TAS:UniProtKB.
GO:0008380; P:RNA splicing; TAS:ProtInc.
GO:0035092; P:sperm chromatin condensation; TAS:UniProtKB.
GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW.

IPR011009; Kinase-like_dom.
IPR000719; Prot_kinase_cat_dom.
IPR017441; Protein_kinase_ATP_BS.
IPR008271; Ser/Thr_kinase_AS.

PS00107; PROTEIN_KINASE_ATP
PS50011; PROTEIN_KINASE_DOM
PS00108; PROTEIN_KINASE_ST