DegronMD - Q9H040(SPRTN)

FUNCTION: DNA-dependent metalloendopeptidase that mediates the proteolytic cleavage of covalent DNA-protein cross-links (DPCs) during DNA synthesis, thereby playing a key role in maintaining genomic integrity (PubMed:27852435, PubMed:27871366, PubMed:27871365, PubMed:32649882, PubMed:30893605). DPCs are highly toxic DNA lesions that interfere with essential chromatin transactions, such as replication and transcription, and which are induced by reactive agents, such as UV light or formaldehyde (PubMed:27852435, PubMed:27871366, PubMed:27871365, PubMed:32649882). Associates with the DNA replication machinery and specifically removes DPCs during DNA synthesis (PubMed:27852435, PubMed:27871366, PubMed:27871365, PubMed:32649882). Acts as a pleiotropic protease for DNA-binding proteins cross-linked with DNA, such as TOP1, TOP2A, histones H3 and H4 (PubMed:27871366). Mediates degradation of DPCs that are not ubiquitinated, while it is not able to degrade ubiquitinated DPCs (By similarity). SPRTN activation requires polymerase collision with DPCs followed by helicase bypass of DPCs (By similarity). Involved in recruitment of VCP/p97 to sites of DNA damage (PubMed:22902628, PubMed:23042605, PubMed:23042607, PubMed:32152270). Also acts as an activator of CHEK1 during normal DNA replication by mediating proteolytic cleavage of CHEK1, thereby promoting CHEK1 removal from chromatin and subsequent activation (PubMed:31316063). Does not activate CHEK1 in response to DNA damage (PubMed:31316063). May also act as a 'reader' of ubiquitinated PCNA: recruited to sites of UV damage and interacts with ubiquitinated PCNA and RAD18, the E3 ubiquitin ligase that monoubiquitinates PCNA (PubMed:22681887, PubMed:22894931, PubMed:22902628, PubMed:22987070). Facilitates chromatin association of RAD18 and is required for efficient PCNA monoubiquitination, promoting a feed-forward loop to enhance PCNA ubiquitination and translesion DNA synthesis (PubMed:22681887). {ECO:0000250|UniProtKB:A0A1L8G2K9, ECO:0000269|PubMed:22681887, ECO:0000269|PubMed:22894931, ECO:0000269|PubMed:22902628, ECO:0000269|PubMed:22987070, ECO:0000269|PubMed:23042605, ECO:0000269|PubMed:23042607, ECO:0000269|PubMed:27852435, ECO:0000269|PubMed:27871365, ECO:0000269|PubMed:27871366, ECO:0000269|PubMed:30893605, ECO:0000269|PubMed:31316063, ECO:0000269|PubMed:32152270, ECO:0000269|PubMed:32649882}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.S367T	TCGA-21-1075	LUSC	TCGA	VSSSS	DEG_SPOP_SBC_1	364:368	Mutation altering degron motif	0.6005
p.S367T	DO26484	LUSC	ICGC	VSSSS	DEG_SPOP_SBC_1	364:368	Mutation altering degron motif	0.6005
p.P172L	TCGA-78-7154	LUAD	TCGA	PPYY	ITCH	177:180	Mutation rewiring degron network	0.1944
p.P172L	DO24070	LUAD	ICGC	PPYY	ITCH	177:180	Mutation rewiring degron network	0.1944
p.R168C	TCGA-A7-A2KD	BRCA	TCGA	PPYY	ITCH	177:180	Mutation rewiring degron network	0.0833
p.R168C	DO3083	BRCA	ICGC	PPYY	ITCH	177:180	Mutation rewiring degron network	0.0833
p.R168C	SIDM01154	T-Lymphoblastic Leukemia	GDSC	PPYY	ITCH	177:180	Mutation rewiring degron network	0.0833
p.R168C	ACH-000953	Leukemia	CCLE	PPYY	ITCH	177:180	Mutation rewiring degron network	0.0833
p.R168C	SUP-T1	haematopoietic and lymphoid tissue	COSMIC	PPYY	ITCH	177:180	Mutation rewiring degron network	0.0833
p.G181S	TCGA-A8-A09Z	BRCA	TCGA	PPYY	ITCH	177:180	Mutation rewiring degron network	0.3056
p.G181S	DO5521	BRCA	ICGC	PPYY	ITCH	177:180	Mutation rewiring degron network	0.3056
p.P178L	TCGA-AX-A2HG	UCEC	TCGA	PPYY	ITCH	177:180	Mutation altering degron motif	0.7582
p.S368F	TCGA-B5-A3FA	UCEC	TCGA	VSSSS	DEG_SPOP_SBC_1	364:368	Mutation altering degron motif	0.7982
p.S368F	DO52402	UCEC	ICGC	VSSSS	DEG_SPOP_SBC_1	364:368	Mutation altering degron motif	0.7982
p.V372I	TCGA-B5-A3FC	UCEC	TCGA	VSSSS	DEG_SPOP_SBC_1	364:368	Mutation rewiring degron network	0.2222
p.V372I	DO41871	UCEC	ICGC	VSSSS	DEG_SPOP_SBC_1	364:368	Mutation rewiring degron network	0.2222
p.R370I	TCGA-BS-A0UF	UCEC	TCGA	VSSSS	DEG_SPOP_SBC_1	364:368	Mutation rewiring degron network	0.2778
p.R370I	DO41488	UCEC	ICGC	VSSSS	DEG_SPOP_SBC_1	364:368	Mutation rewiring degron network	0.2778
p.S378P	TCGA-CN-5355	HNSC	TCGA	VSSSS	DEG_SPOP_SBC_1	364:368	Mutation rewiring degron network	0.0556
p.S378P	DO14638	HNSC	ICGC	VSSSS	DEG_SPOP_SBC_1	364:368	Mutation rewiring degron network	0.0556
p.R371M	TCGA-D3-A2JC	SKCM	TCGA	VSSSS	DEG_SPOP_SBC_1	364:368	Mutation rewiring degron network	0.25
p.R371M	DO47578	SKCM	ICGC	VSSSS	DEG_SPOP_SBC_1	364:368	Mutation rewiring degron network	0.25
p.S365C	TCGA-D8-A147	BRCA	TCGA	VSSSS	DEG_SPOP_SBC_1	364:368	Mutation altering degron motif	0.643
p.S365C	DO4347	BRCA	ICGC	VSSSS	DEG_SPOP_SBC_1	364:368	Mutation altering degron motif	0.643
p.N170S	TCGA-HU-8249	STAD	TCGA	PPYY	ITCH	177:180	Mutation rewiring degron network	0.1389
p.N170S	DO47845	STAD	ICGC	PPYY	ITCH	177:180	Mutation rewiring degron network	0.1389
p.S373L	TCGA-JY-A93C	ESCA	TCGA	VSSSS	DEG_SPOP_SBC_1	364:368	Mutation blocking phosphorylation signal	0.6389
p.R370K	DO222637	BTCA	ICGC	VSSSS	DEG_SPOP_SBC_1	364:368	Mutation rewiring degron network	0.2778
p.G179D	DO9876	COAD	ICGC	PPYY	ITCH	177:180	Mutation altering degron motif	0.7198
p.K187Q	DO36556	READ	ICGC	PPYY	ITCH	177:180	Mutation rewiring degron network	0.1389
p.R189W	SIDM00422	Hodgkin's Lymphoma	GDSC	PPYY	ITCH	177:180	Mutation rewiring degron network	0.0833
p.R189W	ACH-001203	Lymphoma	CCLE	PPYY	ITCH	177:180	Mutation rewiring degron network	0.0833
p.R189W	SUP-HD1	haematopoietic and lymphoid tissue	COSMIC	PPYY	ITCH	177:180	Mutation rewiring degron network	0.0833
p.T187A	SIDM00435	Acute Myeloid Leukemia	GDSC	PPYY	ITCH	177:180	Mutation rewiring degron network	0.1389
p.T187A	SIDM01619	Endometrial Carcinoma	GDSC	PPYY	ITCH	177:180	Mutation rewiring degron network	0.1389
p.T187A	ACH-000369	Leukemia	CCLE	PPYY	ITCH	177:180	Mutation rewiring degron network	0.1389
p.T187A	ACH-000984	Endometrial/Uterine Cancer	CCLE	PPYY	ITCH	177:180	Mutation rewiring degron network	0.1389
p.T187A	MOLM-16	haematopoietic and lymphoid tissue	COSMIC	PPYY	ITCH	177:180	Mutation rewiring degron network	0.1389
p.E190K	SIDM00270	Head and Neck Carcinoma	GDSC	PPYY	ITCH	177:180	Mutation rewiring degron network	0.0556
p.E190K	ACH-001035	Bone Cancer	CCLE	PPYY	ITCH	177:180	Mutation rewiring degron network	0.0556
p.E190K	ACH-002294	Head and Neck Cancer	CCLE	PPYY	ITCH	177:180	Mutation rewiring degron network	0.0556
p.E190K	PCI-15A	upper aerodigestive tract	COSMIC	PPYY	ITCH	177:180	Mutation rewiring degron network	0.0556
p.G181R	SIDM00495	B-Cell Non-Hodgkin's Lymphoma	GDSC	PPYY	ITCH	177:180	Mutation rewiring degron network	0.3056
p.G181R	ACH-000697	Lymphoma	CCLE	PPYY	ITCH	177:180	Mutation rewiring degron network	0.3056
p.G181R	A3-KAW	haematopoietic and lymphoid tissue	COSMIC	PPYY	ITCH	177:180	Mutation rewiring degron network	0.3056
p.R168H	SIDM00661	B-Cell Non-Hodgkin's Lymphoma	GDSC	PPYY	ITCH	177:180	Mutation rewiring degron network	0.0833
p.Y182C	SIDM00350	Head and Neck Carcinoma	GDSC	PPYY	ITCH	177:180	Mutation rewiring degron network	0.2778
p.Y182C	ACH-001641	Head and Neck Cancer	CCLE	PPYY	ITCH	177:180	Mutation rewiring degron network	0.2778
p.Y182C	SAT	upper aerodigestive tract	COSMIC	PPYY	ITCH	177:180	Mutation rewiring degron network	0.2778
p.E173D	SNU-81	large intestine	COSMIC	PPYY	ITCH	177:180	Mutation rewiring degron network	0.2222
p.L185I	NB13	autonomic ganglia	COSMIC	PPYY	ITCH	177:180	Mutation rewiring degron network	0.1944

Kaplan plot for SPRTN in

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*NOTE: the Kaplan plots were collected from OncoLnc

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

SPRTN

UniProt ID: Q9H040

Entrez ID: 83932

Protein name: DNA-dependent metalloprotease SPRTN (EC 3.4.24.-) (DNA damage protein targeting VCP) (DVC1) (Protein with SprT-like domain at the N terminus) (Spartan)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for SPRTN in