DegronMD - P15918(RAG1)

FUNCTION: Catalytic component of the RAG complex, a multiprotein complex that mediates the DNA cleavage phase during V(D)J recombination. V(D)J recombination assembles a diverse repertoire of immunoglobulin and T-cell receptor genes in developing B and T-lymphocytes through rearrangement of different V (variable), in some cases D (diversity), and J (joining) gene segments. In the RAG complex, RAG1 mediates the DNA-binding to the conserved recombination signal sequences (RSS) and catalyzes the DNA cleavage activities by introducing a double-strand break between the RSS and the adjacent coding segment. RAG2 is not a catalytic component but is required for all known catalytic activities. DNA cleavage occurs in 2 steps: a first nick is introduced in the top strand immediately upstream of the heptamer, generating a 3'-hydroxyl group that can attack the phosphodiester bond on the opposite strand in a direct transesterification reaction, thereby creating 4 DNA ends: 2 hairpin coding ends and 2 blunt, 5'-phosphorylated ends. The chromatin structure plays an essential role in the V(D)J recombination reactions and the presence of histone H3 trimethylated at 'Lys-4' (H3K4me3) stimulates both the nicking and haipinning steps. The RAG complex also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B-lymphocytes. The introduction of DNA breaks by the RAG complex on one immunoglobulin allele induces ATM-dependent repositioning of the other allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. In addition to its endonuclease activity, RAG1 also acts as an E3 ubiquitin-protein ligase that mediates monoubiquitination of histone H3. Histone H3 monoubiquitination is required for the joining step of V(D)J recombination. Mediates polyubiquitination of KPNA1 (By similarity). {ECO:0000250}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.G392V	TCGA-06-2569	GBM	TCGA	PRQHLLSLT	DEG_APCC_DBOX_1	395:403	Mutation rewiring degron network	0.25
p.G392V	DO12202	GBM	ICGC	PRQHLLSLT	DEG_APCC_DBOX_1	395:403	Mutation rewiring degron network	0.25
p.L402P	TCGA-AD-6889	COAD	TCGA	PRQHLLSLT	DEG_APCC_DBOX_1	395:403	Mutation altering degron motif	0.7582
p.L402P	DO8463	COAD	ICGC	PRQHLLSLT	DEG_APCC_DBOX_1	395:403	Mutation altering degron motif	0.7582
p.R410W	TCGA-BR-4370	STAD	TCGA	PRQHLLSLT	DEG_APCC_DBOX_1	395:403	Mutation rewiring degron network	0.1389
p.R410W	DO38499	STAD	ICGC	PRQHLLSLT	DEG_APCC_DBOX_1	395:403	Mutation rewiring degron network	0.1389
p.R396C	TCGA-CN-4741	HNSC	TCGA	PRQHLLSLT	DEG_APCC_DBOX_1	395:403	Mutation altering degron motif	0.8301
p.R396C	TCGA-XP-A8T6	ESCA	TCGA	PRQHLLSLT	DEG_APCC_DBOX_1	395:403	Mutation altering degron motif	0.8301
p.R396C	DO233254	GACA	ICGC	PRQHLLSLT	DEG_APCC_DBOX_1	395:403	Mutation altering degron motif	0.8301
p.R396C	DO14313	HNSC	ICGC	PRQHLLSLT	DEG_APCC_DBOX_1	395:403	Mutation altering degron motif	0.8301
p.S401L	TCGA-WE-A8K4	SKCM	TCGA	PRQHLLSLT	DEG_APCC_DBOX_1	395:403	Mutation altering degron motif	0.6556
p.S401L	DO222880	MELA	ICGC	PRQHLLSLT	DEG_APCC_DBOX_1	395:403	Mutation altering degron motif	0.6556
p.S401L	DO229586	PRAD	ICGC	PRQHLLSLT	DEG_APCC_DBOX_1	395:403	Mutation altering degron motif	0.6556
p.S401L	DO51281	SKCM	ICGC	PRQHLLSLT	DEG_APCC_DBOX_1	395:403	Mutation altering degron motif	0.6556
p.R410Q	DO233132	GACA	ICGC	PRQHLLSLT	DEG_APCC_DBOX_1	395:403	Mutation rewiring degron network	0.1389
p.R405S	SIDM00545	Melanoma	GDSC	PRQHLLSLT	DEG_APCC_DBOX_1	395:403	Mutation rewiring degron network	0.2778
p.R405S	ACH-000987	Skin Cancer	CCLE	PRQHLLSLT	DEG_APCC_DBOX_1	395:403	Mutation rewiring degron network	0.2778
p.R405S	Mewo	skin	COSMIC	PRQHLLSLT	DEG_APCC_DBOX_1	395:403	Mutation rewiring degron network	0.2778
p.R396H	SIDM01622	Breast Carcinoma	GDSC	PRQHLLSLT	DEG_APCC_DBOX_1	395:403	Mutation altering degron motif	0.8244
p.R396H	ACH-000721	Breast Cancer	CCLE	PRQHLLSLT	DEG_APCC_DBOX_1	395:403	Mutation altering degron motif	0.8244
p.R412T	SIDM01471	Chronic Myelogenous Leukemia	GDSC	PRQHLLSLT	DEG_APCC_DBOX_1	395:403	Mutation rewiring degron network	0.0833
p.R412T	ACH-000604	Leukemia	CCLE	PRQHLLSLT	DEG_APCC_DBOX_1	395:403	Mutation rewiring degron network	0.0833

Kaplan plot for RAG1 in

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*NOTE: the Kaplan plots were collected from OncoLnc

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

RAG1

UniProt ID: P15918

Entrez ID: 5896

Protein name: V(D)J recombination-activating protein 1 (RAG-1) (RING finger protein 74) [Includes: Endonuclease RAG1 (EC 3.1.-.-); E3 ubiquitin-protein ligase RAG1 (EC 2.3.2.27) (RING-type E3 ubiquitin transferase RAG1)]

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for RAG1 in