Reviewed,
UniProtKB/Swiss-Prot Q60855 (RIPK1_MOUSE)
Last modified
December 15, 2009.
Version 97.
History...
Clusters with 100%,
90%,
50% identity |
Documents (3) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Receptor-interacting serine/threonine-protein kinase 1 EC=2.7.11.1 Alternative name(s): Serine/threonine-protein kinase RIP Cell death protein RIP Receptor-interacting protein | ||||
| Gene names |
| ||||
| Organism | Mus musculus (Mouse) | ||||
| Taxonomic identifier | 10090 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus |
Protein attributes
| Sequence length | 656 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Involved in the transduction of TNF signaling. TNF stimulation induces binding of RIPK1-TRADD-TRAF2-TRAF5 complex to TNFR1. TRAF proteins then catalyze the 'Lys-63'-linked polyubiquitination of RIPK1, inducing RIPK1 association with the IKK complex, which is subsequently activated, leading ultimately to the activation of NF-kappa-B. The inflammatory response is kept transient by the action of the NF-kappa-B target gene product TNFAIP3. TNFAIP3 is recruited to RIPK1 within a complex comprising also RNF11, ITCH and TAX1BP1. TNFAIP3 deubiquitinates 'Lys-63'-polyubiquitin chains on RIPK1 and catalyzes the formation of 'Lys-48'-polyubiquitin chains. This leads to RIPK1 proteosomal degradation and consequently to the termination of the TNF- or LPS-mediated activation of NF-kappa-B By similarity. |
| Catalytic activity | ATP + a protein = ADP + a phosphoprotein. |
| Subunit structure | Binds to the death domain of TNFRSF6 and TRADD. Is recruited by TRADD to TNFRSF1A in a TNF-dependent process. Binds RIPK3, UBCE7IP1, EGFR, IKBKG, TRAF1, TRAF2 and TRAF3. Interacts with BNLF1. Interacts with SQSTM1 upon TNF-alpha stimulation. May interact with MAVS/IPS1. Interacts with ZFAND5 By similarity. |
| Subcellular location | |
| Tissue specificity | Found at low levels in all tissues. |
| Induction | In concanavalin A-treated splenocytes. |
| Post-translational modification | Proteolytically cleaved by caspase-8 during TNF-induced apoptosis. Cleavage abolishes NF-kappa-B activation and enhances pro-apototic signaling through the TRADD-FADD interaction By similarity. Autophosphorylated on serine and threonine residues By similarity. Undergoes 'Lys-63'-polyubiquitination catalyzed by TRAF2 after TNF stimulation. Down-regulated by 'Lys-63'-deubiquitination and 'Lys-48'-ubiquitination, both reactions being catalyzed by TNFAIP3. 'Lys-48'-ubiquitination leads to proteasomal degradation By similarity. |
| Sequence similarities | Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. Contains 1 death domain. Contains 1 protein kinase domain. |
Ontologies
| Keywords | |
|---|---|
| Biological process | Apoptosis |
| Cellular component | Cytoplasm |
| Ligand | ATP-binding Nucleotide-binding |
| Molecular function | Kinase Serine/threonine-protein kinase Transferase |
| PTM | Phosphoprotein Ubl conjugation |
| Gene Ontology (GO) | |
| Biological process | apoptosis Inferred from electronic annotation. Source: UniProtKB-KW signal transductionInferred from electronic annotation. Source: InterPro |
| Molecular function | ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activityInferred from electronic annotation. Source: UniProtKB-KW |
| Complete GO annotation... | |
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| Map3k8 | Q07174 | 1 | EBI-529119,EBI-309771 | |
| Ripk3 | Q9QZL0 | 2 | EBI-529119,EBI-2367423 |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 656 | 656 | Receptor-interacting serine/threonine-protein kinase 1 | PRO_0000086607 | |||||
Regions | |||||||||
| Domain | 17 – 290 | 274 | Protein kinase | ||||||
| Domain | 568 – 654 | 87 | Death | ||||||
| Nucleotide binding | 23 – 31 | 9 | ATP By similarity | ||||||
| Region | 291 – 567 | 277 | Interaction with SQSTM1 | ||||||
Sites | |||||||||
| Active site | 138 | 1 | Proton acceptor By similarity | ||||||
| Binding site | 46 | 1 | ATP By similarity | ||||||
Amino acid modifications | |||||||||
| Modified residue | 313 | 1 | Phosphoserine Ref.4 | ||||||
| Modified residue | 321 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 383 | 1 | Phosphotyrosine By similarity | ||||||
Natural variations | |||||||||
| Natural variant | 473 | 1 | T → I | ||||||
Experimental info | |||||||||
| Sequence conflict | 66 | 1 | M → K in BAC27194. Ref.2 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "RIP: a novel protein containing a death domain that interacts with Fas/APO-1 (CD95) in yeast and causes cell death." Stanger B.Z., Leder P., Lee T.-H., Kim E., Seed B. Cell 81:513-523(1995) [PubMed: 7538908] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: C57BL/6 X CBA. Tissue: Thymus. |
| [2] | "The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. Hayashizaki Y.Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J and NOD. Tissue: Spleen and Thymus. |
| [3] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6. Tissue: Brain and Liver. |
| [4] | "The phagosomal proteome in interferon-gamma-activated macrophages." Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P. Immunity 30:143-154(2009) [PubMed: 19144319] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-313, MASS SPECTROMETRY. Tissue: Macrophage. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| U25995 mRNA. Translation: AAB60487.1. AK030959 mRNA. Translation: BAC27194.1. AK156803 mRNA. Translation: BAE33860.1. BC050905 mRNA. Translation: AAH50905.2. BC054542 mRNA. Translation: AAH54542.1. BC058162 mRNA. Translation: AAH58162.1. | |
| IPI | IPI00121472. |
| PIR | I49299. |
| RefSeq | NP_033094.3. |
| UniGene | Mm.374799 |
3D structure databases | |
| ModBase | Search... |
Protein-protein interaction databases | |
| DIP | DIP-34962N. |
| IntAct | Q60855. 4 interactions. |
| STRING | Q60855. |
PTM databases | |
| PhosphoSite | Q60855. |
Proteomic databases | |
| PRIDE | Q60855. |
Genome annotation databases | |
| Ensembl | ENSMUST00000021844; ENSMUSP00000021844; ENSMUSG00000021408; Mus musculus. [Genome view] |
| GeneID | 19766. |
| KEGG | mmu:19766. |
| UCSC | uc007qax.1. mouse. |
Organism-specific databases | |
| CTD | 19766. |
| MGI | MGI:108212. Ripk1. |
Phylogenomic databases | |
| HOGENOM | HBG445889. |
| HOVERGEN | Q60855. |
| InParanoid | Q60855. |
| OMA | SHDPFAQ. |
| OrthoDB | EOG9VDSJ8. |
Enzyme and pathway databases | |
| BRENDA | 2.7.10.2. 244. 2.7.11.1. 244. |
Gene expression databases | |
| ArrayExpress | Q60855. |
| Bgee | Q60855. |
| Genevestigator | Q60855. |
| GermOnline | ENSMUSG00000021408. Mus musculus. |
Family and domain databases | |
| InterPro | IPR000488. Death. IPR011029. DEATH-like. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017442. Se/Thr_prot_kinase-like_dom. IPR008271. Ser/Thr_prot_kinase_AS. [Graphical view] |
| Gene3D | G3DSA:1.10.533.10. DEATH_like. 1 hit. |
| Pfam | PF00531. Death. 1 hit. PF00069. Pkinase. 1 hit. [Graphical view] |
| SMART | SM00005. DEATH. 1 hit. [Graphical view] |
| PROSITE | PS50017. DEATH_DOMAIN. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 297220. |
| SOURCE | Search... |
Entry information
| Entry name | RIPK1_MOUSE | ||||||||
| Accession | Primary (citable) accession number: Q60855 Secondary accession number(s): Q3U0J3, Q8CD90 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| MGD cross-references Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot |
| Human and mouse protein kinases Human and mouse protein kinases: classification and index |
| SIMILARITY comments Index of protein domains and families |

Clusters with


