DegronMD - Q96SB4(SRPK1)

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 leukaemic cell line: isoform 2 favors proliferation where as isoform 1 favors differentiation. {ECO:0000269|PubMed:10049757, ECO:0000269|PubMed:10390541, ECO:0000269|PubMed:11509566, ECO:0000269|PubMed:12134018, ECO:0000269|PubMed:14555757, ECO:0000269|PubMed:15034300, ECO:0000269|PubMed:16122776, ECO:0000269|PubMed:16209947, ECO:0000269|PubMed:18155240, ECO:0000269|PubMed:18687337, ECO:0000269|PubMed:19240134, ECO:0000269|PubMed:19477182, ECO:0000269|PubMed:19886675, ECO:0000269|PubMed:20708644, ECO:0000269|PubMed:8208298, ECO:0000269|PubMed:9237760}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.E308Q	TCGA-34-8454	LUSC	TCGA	LKENP	DEG_APCC_KENBOX_2	317:321	Mutation rewiring degron network	0.0833
p.E331K	TCGA-55-8302	LUAD	TCGA	LKENP	DEG_APCC_KENBOX_2	317:321	Mutation rewiring degron network	0.0556
p.E319D	TCGA-AA-3984	COAD	TCGA	LKENP	DEG_APCC_KENBOX_2	317:321	Mutation altering degron motif	0.6758
p.K324E	TCGA-EE-A2GI	SKCM	TCGA	LKENP	DEG_APCC_KENBOX_2	317:321	Mutation substituting flanking lysine	0.3611
p.E319K	TCGA-QC-A7B5	SARC	TCGA	LKENP	DEG_APCC_KENBOX_2	317:321	Mutation altering degron motif	0.7022
p.K318N	TCGA-QC-A7B5	SARC	TCGA	LKENP	DEG_APCC_KENBOX_2	317:321	Mutation altering degron motif	0.6918
p.E310D	TCGA-VQ-A8P2	STAD	TCGA	LKENP	DEG_APCC_KENBOX_2	317:321	Mutation rewiring degron network	0.1389
p.Q324R	DO1658	BRCA	ICGC	LKENP	DEG_APCC_KENBOX_2	317:321	Mutation substituting flanking lysine	0.3611
p.C307Y	DO222574	BTCA	ICGC	LKENP	DEG_APCC_KENBOX_2	317:321	Mutation rewiring degron network	0.0556
p.C307Y	DO26898	LUSC	ICGC	LKENP	DEG_APCC_KENBOX_2	317:321	Mutation rewiring degron network	0.0556
p.D316H	DO44448	HNSC	ICGC	LKENP	DEG_APCC_KENBOX_2	317:321	Mutation rewiring degron network	0.3056
p.Q311K	DO228986	LICA	ICGC	LKENP	DEG_APCC_KENBOX_2	317:321	Mutation blocking phosphorylation signal	0.6111
p.E315K	DO45312	LUAD	ICGC	LKENP	DEG_APCC_KENBOX_2	317:321	Mutation rewiring degron network	0.2778
p.E314D	SIDM00845	Burkitt's Lymphoma	GDSC	LKENP	DEG_APCC_KENBOX_2	317:321	Mutation rewiring degron network	0.25
p.E314D	Daudi	haematopoietic and lymphoid tissue	COSMIC	LKENP	DEG_APCC_KENBOX_2	317:321	Mutation rewiring degron network	0.25
p.K318T	Daudi	haematopoietic and lymphoid tissue	COSMIC	LKENP	DEG_APCC_KENBOX_2	317:321	Mutation altering degron motif	0.7306
p.D323Y	KNS-62	lung	COSMIC	LKENP	DEG_APCC_KENBOX_2	317:321	Mutation rewiring degron network	0.2778
p.Q324H	KNS-62	lung	COSMIC	LKENP	DEG_APCC_KENBOX_2	317:321	Mutation substituting flanking lysine	0.3611

Kaplan plot for SRPK1 in

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*NOTE: the Kaplan plots were collected from OncoLnc

DegronMD: protein-targeted degradation, mutation and drug response to degrons

SRPK1

UniProt ID: Q96SB4

Entrez ID: 6732

Protein name: SRSF protein kinase 1 (EC 2.7.11.1) (SFRS protein kinase 1) (Serine/arginine-rich protein-specific kinase 1) (SR-protein-specific kinase 1)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for SRPK1 in