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Identification
HMDB Protein ID HMDBP09499
Secondary Accession Numbers
  • 15394
Name Receptor-interacting serine/threonine-protein kinase 1
Synonyms
  1. Cell death protein RIP
  2. RIP-1
  3. Receptor-interacting protein 1
  4. Serine/threonine-protein kinase RIP
Gene Name RIPK1
Protein Type Enzyme
Biological Properties
General Function Involved in protein binding
Specific Function Essential adapter molecule for the activation of NF- kappa-B. Following different upstream signals (binding of inflammatory cytokines, stimulation of pathogen recognition receptors, or DNA damage), particular RIPK1-containing complexes are formed, initiating a limited number of cellular responses. Upon TNFA stimulation RIPK1 is recruited to a TRADD-TRAF complex initiated by TNFR1 trimerization. There, it is ubiquitinated via 'Lys-63'-link chains, inducing its association with the IKK complex, and its activation through NEMO binding of polyubiquitin chains
Pathways Not Available
Reactions Not Available
GO Classification
Function
binding
catalytic activity
transferase activity
transferase activity, transferring phosphorus-containing groups
kinase activity
nucleoside binding
purine nucleoside binding
adenyl nucleotide binding
adenyl ribonucleotide binding
atp binding
protein binding
protein kinase activity
protein serine/threonine kinase activity
Process
phosphorus metabolic process
phosphate metabolic process
metabolic process
biological regulation
regulation of biological process
cellular metabolic process
regulation of cellular process
signal transduction
protein amino acid phosphorylation
phosphorylation
Cellular Location
  1. Cytoplasm
Gene Properties
Chromosome Location Chromosome:6
Locus 6p25.2
SNPs RIPK1
Gene Sequence
>2016 bp
ATGCAACCAGACATGTCCTTGAATGTCATTAAGATGAAATCCAGTGACTTCCTGGAGAGT
GCAGAACTGGACAGCGGAGGCTTTGGGAAGGTGTCTCTGTGTTTCCACAGAACCCAGGGA
CTCATGATCATGAAAACAGTGTACAAGGGGCCCAACTGCATTGAGCACAACGAGGCCCTC
TTGGAGGAGGCGAAGATGATGAACAGACTGAGACACAGCCGGGTGGTGAAGCTCCTGGGC
GTCATCATAGAGGAAGGGAAGTACTCCCTGGTGATGGAGTACATGGAGAAGGGCAACCTG
ATGCACGTGCTGAAAGCCGAGATGAGTACTCCGCTTTCTGTAAAAGGAAGGATAATTTTG
GAAATCATTGAAGGAATGTGCTACTTACATGGAAAAGGCGTGATACACAAGGACCTGAAG
CCTGAAAATATCCTTGTTGATAATGACTTCCACATTAAGATCGCAGACCTCGGCCTTGCC
TCCTTTAAGATGTGGAGCAAACTGAATAATGAAGAGCACAATGAGCTGAGGGAAGTGGAC
GGCACCGCTAAGAAGAATGGCGGCACCCTCTACTACATGGCGCCCGAGCACCTGAATGAC
GTCAACGCAAAGCCCACAGAGAAGTCGGATGTGTACAGCTTTGCTGTAGTACTCTGGGCG
ATATTTGCAAATAAGGAGCCATATGAAAATGCTATCTGTGAGCAGCAGTTGATAATGTGC
ATAAAATCTGGGAACAGGCCAGATGTGGATGACATCACTGAGTACTGCCCAAGAGAAATT
ATCAGTCTCATGAAGCTCTGCTGGGAAGCGAATCCGGAAGCTCGGCCGACATTTCCTGGC
ATTGAAGAAAAATTTAGGCCTTTTTATTTAAGTCAATTAGAAGAAAGTGTAGAAGAGGAC
GTGAAGAGTTTAAAGAAAGAGTATTCAAACGAAAATGCAGTTGTGAAGAGAATGCAGTCT
CTTCAACTTGATTGTGTGGCAGTACCTTCAAGCCGGTCAAATTCAGCCACAGAACAGCCT
GGTTCACTGCACAGTTCCCAGGGACTTGGGATGGGTCCTGTGGAGGAGTCCTGGTTTGCT
CCTTCCCTGGAGCACCCACAAGAAGAGAATGAGCCCAGCCTGCAGAGTAAACTCCAAGAC
GAAGCCAACTACCATCTTTATGGCAGCCGCATGGACAGGCAGACGAAACAGCAGCCCAGA
CAGAATGTGGCTTACAACAGAGAGGAGGAAAGGAGACGCAGGGTCTCCCATGACCCTTTT
GCACAGCAAAGACCTTACGAGAATTTTCAGAATACAGAGGGAAAAGGCACTGCTTATTCC
AGTGCAGCCAGTCATGGTAATGCAGTGCACCAGCCCTCAGGGCTCACCAGCCAACCTCAA
GTACTGTATCAGAACAATGGATTATATAGCTCACATGGCTTTGGAACAAGACCACTGGAT
CCAGGAACAGCAGGTCCCAGAGTTTGGTACAGGCCAATTCCAAGTCATATGCCTAGTCTG
CATAATATCCCAGTGCCTGAGACCAACTATCTAGGAAATACACCCACCATGCCATTCAGC
TCCTTGCCACCAACAGATGAATCTATAAAATATACCATATACAATAGTACTGGCATTCAG
ATTGGAGCCTACAATTATATGGAGATTGGTGGGACGAGTTCATCACTACTAGACAGCACA
AATACGAACTTCAAAGAAGAGCCAGCTGCTAAGTACCAAGCTATCTTTGATAATACCACT
AGTCTGACGGATAAACACCTGGACCCAATCAGGGAAAATCTGGGAAAGCACTGGAAAAAC
TGTGCCCGTAAACTGGGCTTCACACAGTCTCAGATTGATGAAATTGACCATGACTATGAG
CGAGATGGACTGAAAGAAAAGGTTTACCAGATGCTCCAAAAGTGGGTGATGAGGGAAGGC
ATAAAGGGAGCCACGGTGGGGAAGCTGGCCCAGGCGCTCCACCAGTGTTCCAGGATCGAC
CTTCTGAGCAGCTTGATTTACGTCAGCCAGAACTAA
Protein Properties
Number of Residues 671
Molecular Weight 75930.3
Theoretical pI 6.29
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>Receptor-interacting serine/threonine-protein kinase 1
MQPDMSLNVIKMKSSDFLESAELDSGGFGKVSLCFHRTQGLMIMKTVYKGPNCIEHNEAL
LEEAKMMNRLRHSRVVKLLGVIIEEGKYSLVMEYMEKGNLMHVLKAEMSTPLSVKGRIIL
EIIEGMCYLHGKGVIHKDLKPENILVDNDFHIKIADLGLASFKMWSKLNNEEHNELREVD
GTAKKNGGTLYYMAPEHLNDVNAKPTEKSDVYSFAVVLWAIFANKEPYENAICEQQLIMC
IKSGNRPDVDDITEYCPREIISLMKLCWEANPEARPTFPGIEEKFRPFYLSQLEESVEED
VKSLKKEYSNENAVVKRMQSLQLDCVAVPSSRSNSATEQPGSLHSSQGLGMGPVEESWFA
PSLEHPQEENEPSLQSKLQDEANYHLYGSRMDRQTKQQPRQNVAYNREEERRRRVSHDPF
AQQRPYENFQNTEGKGTAYSSAASHGNAVHQPSGLTSQPQVLYQNNGLYSSHGFGTRPLD
PGTAGPRVWYRPIPSHMPSLHNIPVPETNYLGNTPTMPFSSLPPTDESIKYTIYNSTGIQ
IGAYNYMEIGGTSSSLLDSTNTNFKEEPAAKYQAIFDNTTSLTDKHLDPIRENLGKHWKN
CARKLGFTQSQIDEIDHDYERDGLKEKVYQMLQKWVMREGIKGATVGKLAQALHQCSRID
LLSSLIYVSQN
GenBank ID Protein 57242761
UniProtKB/Swiss-Prot ID Q13546
UniProtKB/Swiss-Prot Entry Name RIPK1_HUMAN
PDB IDs Not Available
GenBank Gene ID NM_003804.3
GeneCard ID RIPK1
GenAtlas ID RIPK1
HGNC ID HGNC:10019
References
General References
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  4. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648 ]
  5. Brill LM, Salomon AR, Ficarro SB, Mukherji M, Stettler-Gill M, Peters EC: Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry. Anal Chem. 2004 May 15;76(10):2763-72. [PubMed:15144186 ]
  6. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [PubMed:17344846 ]
  7. Sun X, Lee J, Navas T, Baldwin DT, Stewart TA, Dixit VM: RIP3, a novel apoptosis-inducing kinase. J Biol Chem. 1999 Jun 11;274(24):16871-5. [PubMed:10358032 ]
  8. Sanz L, Sanchez P, Lallena MJ, Diaz-Meco MT, Moscat J: The interaction of p62 with RIP links the atypical PKCs to NF-kappaB activation. EMBO J. 1999 Jun 1;18(11):3044-53. [PubMed:10356400 ]
  9. Tian Y, Zhang Y, Zhong B, Wang YY, Diao FC, Wang RP, Zhang M, Chen DY, Zhai ZH, Shu HB: RBCK1 negatively regulates tumor necrosis factor- and interleukin-1-triggered NF-kappaB activation by targeting TAB2/3 for degradation. J Biol Chem. 2007 Jun 8;282(23):16776-82. Epub 2007 Apr 20. [PubMed:17449468 ]
  10. Habib AA, Chatterjee S, Park SK, Ratan RR, Lefebvre S, Vartanian T: 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. J Biol Chem. 2001 Mar 23;276(12):8865-74. Epub 2000 Dec 14. [PubMed:11116146 ]
  11. Stanger BZ, Leder P, Lee TH, Kim E, Seed B: RIP: a novel protein containing a death domain that interacts with Fas/APO-1 (CD95) in yeast and causes cell death. Cell. 1995 May 19;81(4):513-23. [PubMed:7538908 ]
  12. Hsu H, Huang J, Shu HB, Baichwal V, Goeddel DV: TNF-dependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex. Immunity. 1996 Apr;4(4):387-96. [PubMed:8612133 ]
  13. Lin Y, Devin A, Rodriguez Y, Liu ZG: Cleavage of the death domain kinase RIP by caspase-8 prompts TNF-induced apoptosis. Genes Dev. 1999 Oct 1;13(19):2514-26. [PubMed:10521396 ]
  14. Izumi KM, Cahir McFarland ED, Ting AT, Riley EA, Seed B, Kieff ED: 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. Mol Cell Biol. 1999 Aug;19(8):5759-67. [PubMed:10409763 ]
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  20. Ea CK, Deng L, Xia ZP, Pineda G, Chen ZJ: Activation of IKK by TNFalpha requires site-specific ubiquitination of RIP1 and polyubiquitin binding by NEMO. Mol Cell. 2006 Apr 21;22(2):245-57. Epub 2006 Apr 6. [PubMed:16603398 ]
  21. Festjens N, Vanden Berghe T, Cornelis S, Vandenabeele P: RIP1, a kinase on the crossroads of a cell's decision to live or die. Cell Death Differ. 2007 Mar;14(3):400-10. [PubMed:17301840 ]