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Overview

Uniprot ID	Q96SB4
Protein Name	SRSF protein kinase 1
Gene Name	SRPK1
Organism	Homo sapiens

Kla Sites from experimental identification

Position	Flanking peptide
4	****MERKVLALQAR

Function

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 leukemic cell line: isoform 2 favors proliferation where as isoform 1 favors differentiation. Phosphorylates the N-terminus of ERC1 (PubMed:30745339)

Protein Sequence

10 MERKVLALQA 20 RKKRTKAKKD 30 KAQRKSETQH 40 RGSAPHSESD 50 LPEQEEEILG 60 SDDDEQEDPN 70 DYCKGGYHLV 80 KIGDLFNGRY 90 HVIRKLGWGH 100 FSTVWLSWDI 110 QGKKFVAMKV 120 VKSAEHYTET 130 ALDEIRLLKS 140 VRNSDPNDPN 150 REMVVQLLDD 160 FKISGVNGTH 170 ICMVFEVLGH 180 HLLKWIIKSN 190 YQGLPLPCVK 200 KIIQQVLQGL 210 DYLHTKCRII 220 HTDIKPENIL 230 LSVNEQYIRR 240 LAAEATEWQR 250 SGAPPPSGSA 260 VSTAPQPKPA 270 DKMSKNKKKK 280 LKKKQKRQAE 290 LLEKRMQEIE 300 EMEKESGPGQ 310 KRPNKQEESE 320 SPVERPLKEN 330 PPNKMTQEKL 340 EESSTIGQDQ 350 TLMERDTEGG 360 AAEINCNGVI 370 EVINYTQNSN 380 NETLRHKEDL 390 HNANDCDVQN 400 LNQESSFLSS 410 QNGDSSTSQE 420 TDSCTPITSE 430 VSDTMVCQSS 440 STVGQSFSEQ 450 HISQLQESIR 460 AEIPCEDEQE 470 QEHNGPLDNK 480 GKSTAGNFLV 490 NPLEPKNAEK 500 LKVKIADLGN 510 ACWVHKHFTE 520 DIQTRQYRSL 530 EVLIGSGYNT 540 PADIWSTACM 550 AFELATGDYL 560 FEPHSGEEYT 570 RDEDHIALII 580 ELLGKVPRKL 590 IVAGKYSKEF 600 FTKKGDLKHI 610 TKLKPWGLFE 620 VLVEKYEWSQ 630 EEAAGFTDFL 640 LPMLELIPEK 650 RATAAECLRH PWLNS

Gene Ontology

Classification	GO ID	Description
Cellular Component	GO:0000785	chromatin
Biological Process	GO:0050684	regulation of mRNA processing
Biological Process	GO:0048024	regulation of mRNA splicing, via spliceosome
Biological Process	GO:0008380	RNA splicing
Biological Process	GO:0035092	sperm DNA condensation
Biological Process	GO:0000245	spliceosomal complex assembly
Cellular Component	GO:0005737	cytoplasm
Cellular Component	GO:0005829	cytosol
Cellular Component	GO:0016363	nuclear matrix
Cellular Component	GO:0016607	nuclear speck
Cellular Component	GO:0005654	nucleoplasm
Cellular Component	GO:0005634	nucleus
Molecular Function	GO:0005524	ATP binding
Molecular Function	GO:0000287	magnesium ion binding
Molecular Function	GO:0004672	protein kinase activity
Molecular Function	GO:0106310	protein serine kinase activity
Molecular Function	GO:0004674	protein serine/threonine kinase activity
Molecular Function	GO:0003723	RNA binding
Biological Process	GO:0007059	chromosome segregation
Biological Process	GO:0045087	innate immune response
Biological Process	GO:0035556	intracellular signal transduction
Biological Process	GO:0045071	negative regulation of viral genome replication
Biological Process	GO:0045070	positive regulation of viral genome replication
Biological Process	GO:0006468	protein phosphorylation

Reference

[1] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.

[2] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.