DegronMD - Q9Y3Z3(SAMHD1)

FUNCTION: Protein that acts both as a host restriction factor involved in defense response to virus and as a regulator of DNA end resection at stalled replication forks (PubMed:19525956, PubMed:21613998, PubMed:21720370, PubMed:23602554, PubMed:23601106, PubMed:22056990, PubMed:24336198, PubMed:26294762, PubMed:26431200, PubMed:28229507, PubMed:28834754, PubMed:29670289). Has deoxynucleoside triphosphate (dNTPase) activity, which is required to restrict infection by viruses, such as HIV-1: dNTPase activity reduces cellular dNTP levels to levels too low for retroviral reverse transcription to occur, blocking early-stage virus replication in dendritic and other myeloid cells (PubMed:19525956, PubMed:21613998, PubMed:21720370, PubMed:23602554, PubMed:23601106, PubMed:23364794, PubMed:25038827, PubMed:26101257, PubMed:22056990, PubMed:24336198, PubMed:28229507, PubMed:26294762, PubMed:26431200). Likewise, suppresses LINE-1 retrotransposon activity (PubMed:24035396, PubMed:29610582, PubMed:24217394). Not able to restrict infection by HIV-2 virus; because restriction activity is counteracted by HIV-2 viral protein Vpx (PubMed:21613998, PubMed:21720370). In addition to virus restriction, dNTPase activity acts as a regulator of DNA precursor pools by regulating dNTP pools (PubMed:23858451). Phosphorylation at Thr-592 acts as a switch to control dNTPase-dependent and -independent functions: it inhibits dNTPase activity and ability to restrict infection by viruses, while it promotes DNA end resection at stalled replication forks (PubMed:23602554, PubMed:23601106, PubMed:29610582, PubMed:29670289). Functions during S phase at stalled DNA replication forks to promote the resection of gapped or reversed forks: acts by stimulating the exonuclease activity of MRE11, activating the ATR-CHK1 pathway and allowing the forks to restart replication (PubMed:29670289). Its ability to promote degradation of nascent DNA at stalled replication forks is required to prevent induction of type I interferons, thereby preventing chronic inflammation (PubMed:27477283, PubMed:29670289). Ability to promote DNA end resection at stalled replication forks is independent of dNTPase activity (PubMed:29670289). Enhances immunoglobulin hypermutation in B-lymphocytes by promoting transversion mutation (By similarity). {ECO:0000250|UniProtKB:Q60710, ECO:0000269|PubMed:19525956, ECO:0000269|PubMed:21613998, ECO:0000269|PubMed:21720370, ECO:0000269|PubMed:22056990, ECO:0000269|PubMed:23364794, ECO:0000269|PubMed:23601106, ECO:0000269|PubMed:23602554, ECO:0000269|PubMed:23858451, ECO:0000269|PubMed:24035396, ECO:0000269|PubMed:24217394, ECO:0000269|PubMed:24336198, ECO:0000269|PubMed:25038827, ECO:0000269|PubMed:26101257, ECO:0000269|PubMed:26294762, ECO:0000269|PubMed:26431200, ECO:0000269|PubMed:27477283, ECO:0000269|PubMed:28229507, ECO:0000269|PubMed:28834754, ECO:0000269|PubMed:29610582, ECO:0000269|PubMed:29670289}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.E37A	TCGA-19-5956	GBM	TCGA	LELHPD	LIG_APCC_ABBA_1	36:41	Mutation altering degron motif	0.659
p.E37A	DO13863	GBM	ICGC	LELHPD	LIG_APCC_ABBA_1	36:41	Mutation altering degron motif	0.659
p.R20K	TCGA-A5-A2K5	UCEC	TCGA	PRTPSNT	DEG_SCF_FBW7_1	19:25	Mutation altering degron motif	0.6126
p.R20K	DO41379	UCEC	ICGC	PRTPSNT	DEG_SCF_FBW7_1	19:25	Mutation altering degron motif	0.6126
p.R611Q	TCGA-AO-A128	BRCA	TCGA	VQLFKD	LIG_APCC_ABBA_1	618:623	Mutation rewiring degron network	0.1389
p.R611Q	TCGA-AO-A128	BRCA	TCGA	RVQLFKD	LIG_APCC_ABBAyCdc20_2	617:623	Mutation rewiring degron network	0.1667
p.R611Q	DO5326	BRCA	ICGC	VQLFKD	LIG_APCC_ABBA_1	618:623	Mutation rewiring degron network	0.1389
p.R611Q	DO5326	BRCA	ICGC	RVQLFKD	LIG_APCC_ABBAyCdc20_2	617:623	Mutation rewiring degron network	0.1667
p.R611Q	SIDM00845	Burkitt's Lymphoma	GDSC	VQLFKD	LIG_APCC_ABBA_1	618:623	Mutation rewiring degron network	0.1389
p.R611Q	SIDM00845	Burkitt's Lymphoma	GDSC	RVQLFKD	LIG_APCC_ABBAyCdc20_2	617:623	Mutation rewiring degron network	0.1667
p.R611Q	SIDM01072	Squamous Cell Lung Carcinoma	GDSC	VQLFKD	LIG_APCC_ABBA_1	618:623	Mutation rewiring degron network	0.1389
p.R611Q	SIDM01072	Squamous Cell Lung Carcinoma	GDSC	RVQLFKD	LIG_APCC_ABBAyCdc20_2	617:623	Mutation rewiring degron network	0.1667
p.R20I	TCGA-AX-A2HC	UCEC	TCGA	PRTPSNT	DEG_SCF_FBW7_1	19:25	Mutation altering degron motif	0.6991
p.R20I	TCGA-EY-A1G8	UCEC	TCGA	PRTPSNT	DEG_SCF_FBW7_1	19:25	Mutation altering degron motif	0.6991
p.R20I	DO43578	UCEC	ICGC	PRTPSNT	DEG_SCF_FBW7_1	19:25	Mutation altering degron motif	0.6991
p.R20I	DO41572	UCEC	ICGC	PRTPSNT	DEG_SCF_FBW7_1	19:25	Mutation altering degron motif	0.6991
p.T608A	TCGA-CD-A48C	STAD	TCGA	VQLFKD	LIG_APCC_ABBA_1	618:623	Mutation blocking phosphorylation signal	0.5
p.T608A	TCGA-CD-A48C	STAD	TCGA	RVQLFKD	LIG_APCC_ABBAyCdc20_2	617:623	Mutation blocking phosphorylation signal	0.5278
p.T608A	DO47912	STAD	ICGC	VQLFKD	LIG_APCC_ABBA_1	618:623	Mutation blocking phosphorylation signal	0.5
p.T608A	DO47912	STAD	ICGC	RVQLFKD	LIG_APCC_ABBAyCdc20_2	617:623	Mutation blocking phosphorylation signal	0.5278
p.H39Y	TCGA-D3-A3MR	SKCM	TCGA	LELHPD	LIG_APCC_ABBA_1	36:41	Mutation altering degron motif	0.6118
p.H39Y	DO47256	SKCM	ICGC	LELHPD	LIG_APCC_ABBA_1	36:41	Mutation altering degron motif	0.6118
p.E48V	TCGA-EO-A22R	UCEC	TCGA	LELHPD	LIG_APCC_ABBA_1	36:41	Mutation rewiring degron network	0.1389
p.E48V	DO42713	UCEC	ICGC	LELHPD	LIG_APCC_ABBA_1	36:41	Mutation rewiring degron network	0.1389
p.G46S	TCGA-FT-A3EE	BLCA	TCGA	LELHPD	LIG_APCC_ABBA_1	36:41	Mutation rewiring degron network	0.1944
p.G46S	DO720	BLCA	ICGC	LELHPD	LIG_APCC_ABBA_1	36:41	Mutation rewiring degron network	0.1944
p.D17N	TCGA-VQ-A8P2	STAD	TCGA	PRTPSNT	DEG_SCF_FBW7_1	19:25	Mutation rewiring degron network	0.2778
p.D17N	TCGA-VQ-A8P2	STAD	TCGA	PSNTPSAE	DEG_SCF_FBW7_2	22:29	Mutation rewiring degron network	0.1944
p.D17N	DO51761	STAD	ICGC	PRTPSNT	DEG_SCF_FBW7_1	19:25	Mutation rewiring degron network	0.2778
p.D17N	DO51761	STAD	ICGC	PSNTPSAE	DEG_SCF_FBW7_2	22:29	Mutation rewiring degron network	0.1944
p.S27F	TCGA-ZF-A9R2	BLCA	TCGA	PSNTPSAE	DEG_SCF_FBW7_2	22:29	Mutation altering degron motif	0.7982
p.S27F	DO219058	BLCA	ICGC	PSNTPSAE	DEG_SCF_FBW7_2	22:29	Mutation altering degron motif	0.7982
p.S18R	DO228971	LICA	ICGC	PRTPSNT	DEG_SCF_FBW7_1	19:25	Mutation blocking phosphorylation signal	0.75
p.S18R	DO228971	LICA	ICGC	PSNTPSAE	DEG_SCF_FBW7_2	22:29	Mutation blocking phosphorylation signal	0.6667
p.S18R	DO229211	THCA	ICGC	PRTPSNT	DEG_SCF_FBW7_1	19:25	Mutation blocking phosphorylation signal	0.75
p.S18R	DO229211	THCA	ICGC	PSNTPSAE	DEG_SCF_FBW7_2	22:29	Mutation blocking phosphorylation signal	0.6667
p.D31E	DO229026	LICA	ICGC	PRTPSNT	DEG_SCF_FBW7_1	19:25	Mutation rewiring degron network	0.1667
p.D31E	DO229026	LICA	ICGC	PSNTPSAE	DEG_SCF_FBW7_2	22:29	Mutation rewiring degron network	0.2778
p.D31E	DO229026	LICA	ICGC	LELHPD	LIG_APCC_ABBA_1	36:41	Mutation rewiring degron network	0.1944
p.V618L	SIDM01048	Plasma Cell Myeloma	GDSC	VQLFKD	LIG_APCC_ABBA_1	618:623	Mutation altering degron motif	0.5654
p.V618L	SIDM01048	Plasma Cell Myeloma	GDSC	RVQLFKD	LIG_APCC_ABBAyCdc20_2	617:623	Mutation altering degron motif	0.5654
p.V618L	ACH-000821	Myeloma	CCLE	VQLFKD	LIG_APCC_ABBA_1	618:623	Mutation altering degron motif	0.5654
p.V618L	ACH-000821	Myeloma	CCLE	RVQLFKD	LIG_APCC_ABBAyCdc20_2	617:623	Mutation altering degron motif	0.5654
p.V618L	EJM	haematopoietic and lymphoid tissue	COSMIC	VQLFKD	LIG_APCC_ABBA_1	618:623	Mutation altering degron motif	0.5654
p.V618L	EJM	haematopoietic and lymphoid tissue	COSMIC	RVQLFKD	LIG_APCC_ABBAyCdc20_2	617:623	Mutation altering degron motif	0.5654
p.P26L	SIDM00087	Plasma Cell Myeloma	GDSC	PSNTPSAE	DEG_SCF_FBW7_2	22:29	Mutation altering degron motif	0.7582
p.P26L	SIDM00846	Cervical Carcinoma	GDSC	PSNTPSAE	DEG_SCF_FBW7_2	22:29	Mutation altering degron motif	0.7582
p.P26L	SIDM00493	Other Solid Cancers	GDSC	PSNTPSAE	DEG_SCF_FBW7_2	22:29	Mutation altering degron motif	0.7582
p.L620P	ACH-000568	Breast Cancer	CCLE	VQLFKD	LIG_APCC_ABBA_1	618:623	Mutation altering degron motif	0.6471
p.L620P	ACH-000568	Breast Cancer	CCLE	RVQLFKD	LIG_APCC_ABBAyCdc20_2	617:623	Mutation altering degron motif	0.7582
p.C51F	ACH-000901	Lung Cancer	CCLE	LELHPD	LIG_APCC_ABBA_1	36:41	Mutation rewiring degron network	0.0556
p.S33F	ACH-001379	Pancreatic Cancer	CCLE	PRTPSNT	DEG_SCF_FBW7_1	19:25	Mutation blocking phosphorylation signal	0.5556
p.S33F	ACH-001379	Pancreatic Cancer	CCLE	PSNTPSAE	DEG_SCF_FBW7_2	22:29	Mutation blocking phosphorylation signal	0.6667
p.S33F	ACH-001379	Pancreatic Cancer	CCLE	LELHPD	LIG_APCC_ABBA_1	36:41	Mutation blocking phosphorylation signal	0.6944
p.D624G	ACH-001786	Colon/Colorectal Cancer	CCLE	VQLFKD	LIG_APCC_ABBA_1	618:623	Mutation rewiring degron network	0.3056
p.D624G	ACH-001786	Colon/Colorectal Cancer	CCLE	RVQLFKD	LIG_APCC_ABBAyCdc20_2	617:623	Mutation rewiring degron network	0.3056
p.P40L	ACH-001970	Metastasis	CCLE	LELHPD	LIG_APCC_ABBA_1	36:41	Mutation altering degron motif	0.6471

Kaplan plot for SAMHD1 in

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*NOTE: the Kaplan plots were collected from OncoLnc

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

SAMHD1

UniProt ID: Q9Y3Z3

Entrez ID: 25939

Protein name: Deoxynucleoside triphosphate triphosphohydrolase SAMHD1 (dNTPase) (EC 3.1.5.-) (Dendritic cell-derived IFNG-induced protein) (DCIP) (Monocyte protein 5) (MOP-5) (SAM domain and HD domain-containing protein 1) (hSAMHD1)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for SAMHD1 in