RIPK1 (Mus musculus)

Description [+]

Synonyms: RIPK1
Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Rodentia; Mus musculus
Short gene description: receptor (TNFRSF)-interacting serine-threonine kinase 1 Gene [Source:MGI Symbol;Acc:MGI:108212]
Family: Death Domain-containing protein : other
Process: necroptosis,
Pathways: TNF/NF-kappaB signaling,
Criteria: manually curated
Curator comment:
WIKI: RIPK1-M_musculus

References [+]

RIP kinases at the crossroads of cell death and survival.
Declercq W, Vanden Berghe T, Vandenabeele P
Protein kinases of the receptor interacting protein (RIP) family collaborate with death receptor proteins to regulate cell death. Recent studies (Cho et al., 2009; He et al., 2009; Zhang et al., 2009) reveal that the RIP3 kinase functions with RIP1 at the crossroads of apoptosis, necroptosis, and cell survival. Cell. 2009 Jul 23;138(2):229-32.

The death domain kinase RIP has an essential role in DNA damage-induced NF-kappa B activation.
Hur GM, Lewis J, Yang Q, Lin Y, Nakano H, Nedospasov S, Liu ZG
The transcription factor NF-kappaB is activated when cells are exposed to genotoxic stress. It has been suggested that DNA damage will trigger a cytoplasmic signaling that leads to the activation of IKK and NF-kappaB, but the signaling components upstream of IKK have not yet been identified. Here we report that the receptor interacting protein, RIP, is the IKK upstream component, essential for the activation of NF-kappaB by DNA damage. Also, our findings suggest that this NF-kappaB activation by DNA damage is not mediated by autocrine or TNF-R1 signaling pathway. In wild-type fibroblasts, DNA damage induced by agents such as adriamycin, campthothecin, and ionizing radiation induces NF-kappaB activation. We found, however, that DNA damage failed to activate NF-kappaB in RIP-/- fibroblasts. The induction of IkappaBalpha degradation by DNA damage was normal in TNF-R1-/-, TRAF2-/-, TRAF5-/- and FADD-/- fibroblasts or when de novo protein synthesis was blocked. More importantly, the reconstitution of RIP expression in RIP-/- cells restores DNA damage-induced NF-kappaB activation. We also found that RIP forms a complex with IKK in response to DNA damage. Therefore, our study provides a possible mechanism for the initiation of the cytoplasmic signaling to activate NF-kappaB in response to DNA damage. Genes Dev. 2003 Apr 1;17(7):873-82. Epub 2003 Mar 21.

Structure & Sequence [+]

Pfam domains: (Pfam is a large collection of protein families.)

Source	Domain Name	Start	End
PFAM A	Pkinase	17	286
PFAM A	Pkinase_Tyr	17	286
PFAM A	Death	569	654

Protein sequence [+]

Structure links:

Smartdomain prediction information: SM00219
Smartdomain prediction information: SM00220
Smartdomain prediction information: SM00005
Prosite motif and domain information: PS00108
Interpro domain information: Q60855
PFAM domain and domain family information: Q60855

Evolution [+]

Gene Ontology [+]

GO id	Name	Ontology type	Evidence
GO:0006468	protein amino acid phosphorylation	biological_proccess	IEA
GO:0006915	apoptosis	biological_proccess	IEA
GO:0007165	signal transduction	biological_proccess	IEA
GO:0043123	positive regulation of I-kappaB kinase/NF-kappaB cascade	biological_proccess	IEA
GO:0006917	induction of apoptosis	biological_proccess	IEA
GO:0051092	positive regulation of NF-kappaB transcription factor activity	biological_proccess	IEA
GO:0034612	response to tumor necrosis factor	biological_proccess	IEA
GO:0046777	protein amino acid autophosphorylation	biological_proccess	IEA
GO:0010940	positive regulation of necrotic cell death	biological_proccess	IEA
GO:0060555		biological_proccess	IEA
GO:0000166	nucleotide binding	mollecular_function	IEA
GO:0004674	protein serine/threonine kinase activity	mollecular_function	IEA
GO:0004713	protein tyrosine kinase activity	mollecular_function	IEA
GO:0005515	protein binding	mollecular_function	IPI
GO:0005524	ATP binding	mollecular_function	IEA
GO:0016740	transferase activity	mollecular_function	IEA
GO:0016301	kinase activity	mollecular_function	IEA
GO:0004672	protein kinase activity	mollecular_function	ISO
GO:0005515	protein binding	mollecular_function	IEA
GO:0070513	death domain binding	mollecular_function	IEA
GO:0005123	death receptor binding	mollecular_function	IEA
GO:0005737	cytoplasm	cell_component	IEA
GO:0005739	mitochondrion	cell_component	IEA
GO:0043235	receptor complex	cell_component	IEA
GO:0031264	death-inducing signaling complex	cell_component	IEA

Check GO Evidence Codes here

KEGG Pathways [+]

miRNAs [+]

miRNA	Regulation	Description	Pubmed
mmu-miR-155	overexpression by mature miRNA transfection	Based on the luciferase assay, miR-155 was also seemingly able to target Ripk1 transcripts, although not as efficiently as IKK_ and FADD mRNAs (Fig. 3, A and B).	Ref.
mmu-miR-155	overexpression by mature miRNA transfection	Based on the luciferase assay, miR-155 was also seemingly able to target Ripk1 transcripts, although not as efficiently as IKK_ and FADD mRNAs (Fig. 3, A and B).	Ref.

Information from other databases [+]

Gene related links:

Gene info from MGI [?] MGI:108212
Ensembl genome browser [?] : ENSMUSG00000021408
Expression info from Arrayexpress [?] : ENSMUSG00000021408
Protein expression from Protein Atlas: [?] ENSMUSG00000021408
Community gene edition from Wikigenes: [?] 19766

Protein related links:

Uniprot protein info: Q60855
PIR protein info: Q60855
Protein interactions from IntAct: Q60855

Other links

entrezgene: 19766
refseq_dna: NM_009068
refseq_peptide: NP_033094

Click on [?] for more information.