Reviewed,
UniProtKB/Swiss-Prot Q13546 (RIPK1_HUMAN)
Last modified
November 25, 2008.
Version 88.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
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 | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 671 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Promotes apoptosis and activation of NF-kappa-B. Required for TNFRSF1A mediated activation of NF-kappa-B. |
| 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 isoform 3 (ZIN), EGFR, IKBKG, TRAF1, TRAF2 and TRAF3. Interacts with BNLF1. Interacts with SQSTM1 upon TNF-alpha stimulation. May interacts with MAVS/IPS1. |
| Subcellular location | |
| 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. Autophosphorylated on serine and threonine residues. |
| 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 |
| Coding sequence diversity | Polymorphism |
| Ligand | ATP-binding Nucleotide-binding |
| Molecular function | Kinase Serine/threonine-protein kinase Transferase |
| PTM | Phosphoprotein |
Gene Ontology (GO) | |
| Biological process | activation of pro-apoptotic gene products Inferred from Experiment. Source: Reactome positive regulation of I-kappaB kinase/NF-kappaB cascadeInferred from expression pattern. Source: UniProtKB protein amino acid phosphorylationInferred from electronic annotation. Source: InterPro |
| Cellular component | cytosol Inferred from Experiment. Source: Reactome |
| Molecular function | ATP binding Inferred from electronic annotation. Source: InterPro protein binding Ref.8Inferred from physical interaction. Source: UniProtKB protein serine/threonine kinase activity Ref.1Traceable author statement. Source: ProtInc protein tyrosine kinase activityInferred from electronic annotation. Source: InterPro |
| Complete GO annotation... | |
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| CASP8 | Q14790 | 1 | EBI-358507,EBI-78060 | |
| CCDC50 | Q8IVM0 | 2 | EBI-358507,EBI-723996 | |
| CSNK1A1 | Q4JJA0 | 4 | EBI-358507,EBI-1383726 | |
| IKBKG | Q9Y6K9 | 1 | EBI-358507,EBI-81279 | |
| Map3k8 | Q07174 | 1 | EBI-358507,EBI-309771 | From a different organism. |
| Nfkb1 | P25799 | 1 | EBI-358507,EBI-643958 | From a different organism. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 671 | 671 | Receptor-interacting serine/threonine-protein kinase 1 | PRO_0000086606 | |||||
Regions | |||||||||
| Domain | 17 – 289 | 273 | Protein kinase | ||||||
| Domain | 583 – 669 | 87 | Death | ||||||
| Nucleotide binding | 23 – 31 | 9 | ATP By similarity | ||||||
| Region | 290 – 582 | 293 | Interaction with SQSTM1 | ||||||
| Compositional bias | 411 – 414 | 4 | Poly-Arg | ||||||
Sites | |||||||||
| Active site | 138 | 1 | Proton acceptor By similarity | ||||||
| Binding site | 49 | 1 | ATP By similarity | ||||||
| Site | 324 – 325 | 2 | Cleavage; by caspase-8 | ||||||
Amino acid modifications | |||||||||
| Modified residue | 320 | 1 | Phosphoserine | ||||||
| Modified residue | 384 | 1 | Phosphotyrosine | ||||||
| Modified residue | 387 | 1 | Phosphotyrosine | ||||||
| Modified residue | 389 | 1 | Phosphoserine | ||||||
Natural variations | |||||||||
| Natural variant | 64 | 1 | A → V in a colorectal adenocarcinoma sample; somatic mutation. | VAR_041039 | |||||
| Natural variant | 81 | 1 | V → I in a colorectal adenocarcinoma sample; somatic mutation. | VAR_041040 | |||||
| Natural variant | 220 | 1 | A → V in a colorectal adenocarcinoma sample; somatic mutation. | VAR_041041 | |||||
| Natural variant | 234 | 1 | E → K: dbSNP rs17548383. | VAR_021109 | |||||
| Natural variant | 404 | 1 | A → S | VAR_041042 | |||||
| Natural variant | 443 | 1 | A → V | VAR_041043 | |||||
| Natural variant | 569 | 1 | A → V | VAR_041044 | |||||
Experimental info | |||||||||
| Mutagenesis | 45 | 1 | K → A: Abolishes kinase activity | ||||||
| Mutagenesis | 324 | 1 | D → K: Abolishes cleavage by caspase-8 | ||||||
| Sequence conflict | 438 | 1 | A → V Ref.1 Ref.6 | ||||||
| Sequence conflict | 514 | 1 | T → S in AAC50137. Ref.6 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "TNF-dependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex." Hsu H., Huang J., Shu H.-B., Baichwal V.R., Goeddel D.V. Immunity 4:387-396(1996) [PubMed: 8612133] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], AUTOPHOSPHORYLATION, MUTAGENESIS OF LYS-45, INTERACTION WITH TRADD; TRAF1; TRAF2 AND TRAF3. Tissue: Umbilical vein endothelial cell. |
| [2] | Huang J., Hsu H., Baichwal V.R., Goeddel D.V. Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION TO 120. |
| [3] | SeattleSNPs program for genomic applications Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT LYS-234. |
| [4] | "The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. Beck S.Nature 425:805-811(2003) [PubMed: 14574404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [5] | "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]. |
| [6] | "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] OF 300-671. Tissue: Leukemic T-cell. |
| [7] | "Cleavage of the death domain kinase RIP by caspase-8 prompts TNF-induced apoptosis." Lin Y., Devin A., Rodriguez Y., Liu Z.-G. Genes Dev. 13:2514-2526(1999) [PubMed: 10521396] [Abstract] Cited for: CLEAVAGE BY CASPASE-8, MUTAGENESIS OF ASP-324. |
| [8] | "The interaction of p62 with RIP links the atypical PKCs to NF-kappaB activation." Sanz L., Sanchez P., Lallena M.-J., Diaz-Meco M.T., Moscat J. EMBO J. 18:3044-3053(1999) [PubMed: 10356400] [Abstract] Cited for: INTERACTION WITH SQSTM1 AND TRAF2, DOMAIN. |
| [9] | "RIP3, a novel apoptosis-inducing kinase." Sun X., Lee J., Navas T., Baldwin D.T., Stewart T.A., Dixit V.M. J. Biol. Chem. 274:16871-16875(1999) [PubMed: 10358032] [Abstract] Cited for: INTERACTION WITH RIPK3. |
| [10] | "The Epstein-Barr virus oncoprotein latent membrane protein 1 engages the tumor necrosis factor receptor-associated proteins TRADD and receptor-interacting protein (RIP) but does not induce apoptosis or require RIP for NF-kappaB activation." Izumi K.M., Cahir McFarland E., Ting A.T., Riley E.A., Seed B., Kieff E.D. Mol. Cell. Biol. 19:5759-5767(1999) [PubMed: 10409763] [Abstract] Cited for: INTERACTION WITH BNLF1. |
| [11] | "Identification of a cell protein (FIP-3) as a modulator of NF-kappaB activity and as a target of an adenovirus inhibitor of tumor necrosis factor alpha-induced apoptosis." Li Y., Kang J., Friedman J., Tarassishin L., Ye J., Kovalenko A., Wallach D., Horwitz M.S. Proc. Natl. Acad. Sci. U.S.A. 96:1042-1047(1999) [PubMed: 9927690] [Abstract] Cited for: INTERACTION WITH IKBKG. |
| [12] | "The epidermal growth factor receptor engages receptor interacting protein and nuclear factor-kappa B (NF-kappa B)-inducing kinase to activate NF-kappa B. Identification of a novel receptor-tyrosine kinase signalosome." Habib A.A., Chatterjee S., Park S.-K., Ratan R.R., Lefebvre S., Vartanian T. J. Biol. Chem. 276:8865-8874(2001) [PubMed: 11116146] [Abstract] Cited for: INTERACTION WITH EGFR. |
| [13] | "A novel zinc finger protein interacts with receptor-interacting protein (RIP) and inhibits tumor necrosis factor (TNF)- and IL1-induced NF-kappa B activation." Chen D., Li X., Zhai Z., Shu H.-B. J. Biol. Chem. 277:15985-15991(2002) [PubMed: 11854271] [Abstract] Cited for: INTERACTION WITH UBCE7IP1. |
| [14] | "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry." Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., Peters E.C. Anal. Chem. 76:2763-2772(2004) [PubMed: 15144186] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-384; TYR-387 AND SER-389, MASS SPECTROMETRY. Tissue: T-cell. |
| [15] | "IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction." Kawai T., Takahashi K., Sato S., Coban C., Kumar H., Kato H., Ishii K.J., Takeuchi O., Akira S. Nat. Immunol. 6:981-988(2005) [PubMed: 16127453] [Abstract] Cited for: INTERACTION WITH MAVS. |
| [16] | "A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-320, MASS SPECTROMETRY. |
| [17] | "Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. Stratton M.R.Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] VAL-64; ILE-81; VAL-220; SER-404; VAL-443 AND VAL-569. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| U50062 mRNA. Translation: AAC32232.1. AY682848 Genomic DNA. Translation: AAT74626.1. AL031963 Genomic DNA. Translation: CAD70625.1. BC126254 mRNA. Translation: AAI26255.1. BC126256 mRNA. Translation: AAI26257.1. U25994 mRNA. Translation: AAC50137.1. | |
| PIR | T09479. |
| RefSeq | NP_003795.2. |
| UniGene | Hs.519842 |
3D structure databases | |
| HSSP | HSSP built from PDB template 1BYG based on UniProtKB P41240. |
| ModBase | Search... |
Protein-protein interaction databases | |
| DIP | DIP:433N. |
| IntAct | Q13546. |
PTM databases | |
| PhosphoSite | Q13546. |
Genome annotation databases | |
| Ensembl | ENSG00000137275. Homo sapiens. [Contig view] |
| GeneID | 8737. |
| KEGG | hsa:8737. |
Organism-specific databases | |
| H-InvDB | HIX0005535. |
| HGNC | HGNC:10019. RIPK1. |
| HPA | CAB010302. HPA015257. |
| MIM | 603453. gene. |
| PharmGKB | PA34394. |
| GenAtlas | Search... |
| GeneCards | Search... |
Phylogenomic databases | |
| HOGENOM | Q13546. |
| HOVERGEN | Q13546. |
Enzyme and pathway databases | |
| Reactome | REACT_578. Apoptosis. REACT_6900. Signaling in Immune System. |
Gene expression databases | |
| ArrayExpress | Q13546. |
| CleanEx | HS_RIPK1. |
Family and domain databases | |
| InterPro | IPR000488. Death. IPR011029. DEATH_like. IPR000719. Prot_kinase_core. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. IPR001245. Tyr_pkinase. [Graphical view] |
| Gene3D | G3DSA:1.10.533.10. DEATH_like. 1 hit. |
| Pfam | PF00531. Death. 1 hit. PF00069. Pkinase. 1 hit. [Graphical view] |
| PRINTS | PR00109. TYRKINASE. |
| ProDom | PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain] |
| 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 | 32775. |
| SOURCE | Search... |
Entry information
| Entry name | RIPK1_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q13546 Secondary accession number(s): A0AV89, Q13180 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 6 Human chromosome 6: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) 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