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UniProtKB/Swiss-Prot entry Q13546


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name RIPK1_HUMAN
Primary accession number Q13546
Secondary accession numbers A0AV89 Q13180
Integrated into Swiss-Prot on November 1, 1997
Sequence was last modified on February 1, 2005 (Sequence version 3)
Annotations were last modified on    June 16, 2009 (Entry version 95)
Name and origin of the protein
Protein name Receptor-interacting serine/threonine-protein kinase 1
Synonyms EC 2.7.11.1
Serine/threonine-protein kinase RIP
Cell death protein RIP
Receptor-interacting protein
Gene name
Name: RIPK1
Synonyms: RIP
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA], AUTOPHOSPHORYLATION, MUTAGENESIS OF LYS-45, AND INTERACTION WITH TRADD; TRAF1; TRAF2 AND TRAF3.
TISSUE=Umbilical vein endothelial cell;
DOI=10.1016/S1074-7613(00)80252-6; PubMed=8612133 [NCBI, ExPASy, EBI, Israel, Japan]
Hsu H., Huang J., Shu H.-B., Baichwal V.R., Goeddel D.V.;
"TNF-dependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex.";
Immunity 4:387-396(1996).
[2]
SEQUENCE REVISION TO 120.
Huang J., Hsu H., Baichwal V.R., Goeddel D.V.;
Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
[3]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LYS-234.
SeattleSNPs variation discovery resource;
Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
DOI=10.1038/nature02055; PubMed=14574404 [NCBI, ExPASy, EBI, Israel, Japan]
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., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.;
"The DNA sequence and analysis of human chromosome 6.";
Nature 425:805-811(2003).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[6]
NUCLEOTIDE SEQUENCE [MRNA] OF 300-671.
TISSUE=Leukemic T-cell;
DOI=10.1016/0092-8674(95)90072-1; PubMed=7538908 [NCBI, ExPASy, EBI, Israel, Japan]
Stanger B.Z., Leder P., Lee T.-H., 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 81:513-523(1995).
[7]
CLEAVAGE BY CASPASE-8, AND MUTAGENESIS OF ASP-324.
DOI=10.1101/gad.13.19.2514; PubMed=10521396 [NCBI, ExPASy, EBI, Israel, Japan]
Lin Y., Devin A., Rodriguez Y., Liu Z.-G.;
"Cleavage of the death domain kinase RIP by caspase-8 prompts TNF-induced apoptosis.";
Genes Dev. 13:2514-2526(1999).
[8]
INTERACTION WITH SQSTM1 AND TRAF2, AND DOMAIN.
DOI=10.1093/emboj/18.11.3044; PubMed=10356400 [NCBI, ExPASy, EBI, Israel, Japan]
Sanz L., Sanchez P., Lallena M.-J., Diaz-Meco M.T., Moscat J.;
"The interaction of p62 with RIP links the atypical PKCs to NF-kappaB activation.";
EMBO J. 18:3044-3053(1999).
[9]
INTERACTION WITH RIPK3.
DOI=10.1074/jbc.274.24.16871; PubMed=10358032 [NCBI, ExPASy, EBI, Israel, Japan]
Sun X., Lee J., Navas T., Baldwin D.T., Stewart T.A., Dixit V.M.;
"RIP3, a novel apoptosis-inducing kinase.";
J. Biol. Chem. 274:16871-16875(1999).
[10]
INTERACTION WITH BNLF1.
PubMed=10409763 [NCBI, ExPASy, EBI, Israel, Japan]
Izumi K.M., Cahir McFarland E., Ting A.T., Riley E.A., Seed B., Kieff E.D.;
"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. 19:5759-5767(1999).
[11]
INTERACTION WITH IKBKG.
DOI=10.1073/pnas.96.3.1042; PubMed=9927690 [NCBI, ExPASy, EBI, Israel, Japan]
Li Y., Kang J., Friedman J., Tarassishin L., Ye J., Kovalenko A., Wallach D., Horwitz M.S.;
"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.";
Proc. Natl. Acad. Sci. U.S.A. 96:1042-1047(1999).
[12]
INTERACTION WITH EGFR.
DOI=10.1074/jbc.M008458200; PubMed=11116146 [NCBI, ExPASy, EBI, Israel, Japan]
Habib A.A., Chatterjee S., Park S.-K., Ratan R.R., 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. 276:8865-8874(2001).
[13]
INTERACTION WITH UBCE7IP1.
DOI=10.1074/jbc.M108675200; PubMed=11854271 [NCBI, ExPASy, EBI, Israel, Japan]
Chen D., Li X., Zhai Z., Shu H.-B.;
"A novel zinc finger protein interacts with receptor-interacting protein (RIP) and inhibits tumor necrosis factor (TNF)- and IL1-induced NF-kappa B activation.";
J. Biol. Chem. 277:15985-15991(2002).
[14]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-384; TYR-387 AND SER-389, AND MASS SPECTROMETRY.
TISSUE=T-cell;
DOI=10.1021/ac035352d; PubMed=15144186 [NCBI, ExPASy, EBI, Israel, Japan]
Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., Peters E.C.;
"Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry.";
Anal. Chem. 76:2763-2772(2004).
[15]
INTERACTION WITH MAVS.
DOI=10.1038/ni1243; PubMed=16127453 [NCBI, ExPASy, EBI, Israel, Japan]
Kawai T., Takahashi K., Sato S., Coban C., Kumar H., Kato H., Ishii K.J., Takeuchi O., Akira S.;
"IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction.";
Nat. Immunol. 6:981-988(2005).
[16]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-320, AND MASS SPECTROMETRY.
DOI=10.1073/pnas.0805139105; PubMed=18669648 [NCBI, ExPASy, EBI, Israel, Japan]
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.;
"A quantitative atlas of mitotic phosphorylation.";
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
[17]
VARIANTS [LARGE SCALE ANALYSIS] VAL-64; ILE-81; VAL-220; SER-404; VAL-443 AND VAL-569.
DOI=10.1038/nature05610; PubMed=17344846 [NCBI, ExPASy, EBI, Israel, Japan]
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., 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 D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.;
"Patterns of somatic mutation in human cancer genomes.";
Nature 446:153-158(2007).
Comments
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
U50062; AAC32232.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AY682848; AAT74626.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AL031963; CAD70625.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC126254; AAI26255.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC126256; AAI26257.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U25994; AAC50137.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
IPI IPI00013773; -.
PIR T09479; T09479.
RefSeq NP_003795.2; -.
UniGene Hs.519842
3D structure databases
HSSP P41240; 1BYG. [HSSP ENTRY / PDB]
ModBase Q13546.
Protein-protein interaction databases
DIP DIP:433N; -.
IntAct Q13546; 27.
PTM databases
PhosphoSite Q13546; -.
Enzyme and pathway databases
BRENDA 2.7.10.2; 247.
2.7.11.1; 247.
Pathway_Interaction_DB caspase_pathway; Caspase cascade in apoptosis.
ceramidepathway; Ceramide signaling pathway.
faspathway; FAS signaling pathway (CD95).
hivnefpathway; HIV-1 Nef: Negative effector of Fas and TNF-alpha.
p38alphabetapathway; Regulation of p38-alpha and p38-beta.
tnfpathway; TNF receptor signaling pathway.
trail_pathway; TRAIL signaling pathway.
Reactome REACT_578; Apoptosis.
REACT_6900; Signaling in Immune system.
Organism-specific databases
GeneCards GC06P003022; -.
H-InvDB HIX0005535; -.
HGNC HGNC:10019; RIPK1.
GenAtlas RIPK1.
HPA CAB010302; -.
HPA015257; -.
MIM 603453; gene. [NCBI / EBI]
PharmGKB PA34394; -.
Gene expression databases
ArrayExpress Q13546; -.
Bgee Q13546; -.
CleanEx HS_RIPK1; -.
Ontologies
GO
GO:0005829; Cellular component: cytosol (inferred from experiment from Reactome).
GO:0031264; Cellular component: death-inducing signaling complex (inferred from direct assay from UniProtKB).
GO:0005739; Cellular component: mitochondrion (inferred from direct assay from UniProtKB).
GO:0043235; Cellular component: receptor complex (inferred from direct assay from UniProtKB).
GO:0005524; Molecular function: ATP binding (inferred from electronic annotation from UniProtKB-KW).
GO:0070513; Molecular function: death domain binding (inferred from physical interaction from UniProtKB).
GO:0005123; Molecular function: death receptor binding (inferred from physical interaction from UniProtKB).
GO:0004674; Molecular function: protein serine/threonine kinase activity (inferred from direct assay from UniProtKB).
GO:0004713; Molecular function: protein tyrosine kinase activity (inferred from electronic annotation from InterPro).
GO:0007257; Biological process: activation of JUN kinase activity (traceable author statement from UniProtKB).
GO:0008633; Biological process: activation of pro-apoptotic gene products (inferred from experiment from Reactome).
GO:0007249; Biological process: I-kappaB kinase/NF-kappaB cascade (inferred from experiment from Reactome).
GO:0006917; Biological process: induction of apoptosis (inferred from mutant phenotype from UniProtKB).
GO:0045768; Biological process: positive regulation of anti-apoptosis (traceable author statement from UniProtKB).
GO:0043123; Biological process: positive regulation of I-kappaB kinase/NF-kappaB cascade (inferred from expression pattern from UniProtKB).
GO:0010940; Biological process: positive regulation of necrotic cell death (inferred from mutant phenotype from UniProtKB).
GO:0051092; Biological process: positive regulation of NF-kappaB transcription factor activity (inferred from mutant phenotype from UniProtKB).
GO:0046777; Biological process: protein amino acid autophosphorylation (inferred from direct assay from UniProtKB).
GO:0080010; Biological process: regulation of oxygen and reactive oxygen species metabolic process (traceable author statement from UniProtKB).
GO:0034612; Biological process: response to tumor necrosis factor (inferred from mutant phenotype from UniProtKB).
GO:0033209; Biological process: tumor necrosis factor-mediated signaling pathway (inferred by curator from UniProtKB).
QuickGo view.
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 of domain structure.
Gene3D G3DSA:1.10.533.10; DEATH_like; 1.
Pfam PF00531; Death; 1.
PF00069; Pkinase; 1.
Pfam graphical view of domain structure.
PRINTS PR00109; TYRKINASE.
ProDom PD000001; Prot_kinase; 1.
[Domain structure / List of seq. sharing at least 1 domain]
SMART SM00005; DEATH; 1.
SMART graphical view of domain structure.
PROSITE PS50017; DEATH_DOMAIN; 1.
PS50011; PROTEIN_KINASE_DOM; 1.
PS00108; PROTEIN_KINASE_ST; 1.
PROSITE graphical view of domain structure (profiles).
Proteomic databases
PRIDE Q13546; -.
Genome annotation databases
Ensembl ENSG00000137275; Homo sapiens. [Contig view]
GeneID 8737; -.
KEGG hsa:8737; -.
Phylogenomic databases
HOGENOM Q13546; -.
HOVERGEN Q13546; -.
OMA Q13546; SHDPFAQ.
Other
NextBio 32775; -.
PMAP-CutDB Q13546; -.
SOURCE RIPK1; Homo sapiens.
ProtoNet Q13546.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
Apoptosis; ATP-binding; Cytoplasm; Kinase; Nucleotide-binding; Phosphoprotein; Polymorphism; Serine/threonine-protein kinase; Transferase.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
CHAIN   1   671  671     Receptor-interacting serine/threonine-protein kinase 1. PRO_0000086606
DOMAIN   17   289  273     Protein kinase. 
DOMAIN   583   669  87     Death. 
NP_BIND   23    31  9     ATP (By similarity). 
REGION   290   582  293     Interaction with SQSTM1. 
COMPBIAS   411   414  4     Poly-Arg. 
ACT_SITE   138   138        Proton acceptor (By similarity). 
BINDING   49    49        ATP (By similarity). 
SITE   324   325  2     Cleavage; by caspase-8. 
MOD_RES   320   320        Phosphoserine. 
MOD_RES   384   384        Phosphotyrosine. 
MOD_RES   387   387        Phosphotyrosine. 
MOD_RES   389   389        Phosphoserine. 
VARIANT   64    64  1     A -> V (in a colorectal adenocarcinoma sample; somatic mutation). VAR_041039 
VARIANT   81    81  1     V -> I (in a colorectal adenocarcinoma sample; somatic mutation). VAR_041040 
VARIANT   220   220  1     A -> V (in a colorectal adenocarcinoma sample; somatic mutation). VAR_041041 
VARIANT   234   234  1     E -> K (in dbSNP:rs17548383 [NCBI]). VAR_021109 
VARIANT   404   404  1     A -> S. VAR_041042 
VARIANT   443   443  1     A -> V. VAR_041043 
VARIANT   569   569  1     A -> V. VAR_041044 
MUTAGEN   45    45        K->A: Abolishes kinase activity. 
MUTAGEN   324   324        D->K: Abolishes cleavage by caspase-8. 
CONFLICT   438   438        A -> V (in Ref. 1 and 6). 
CONFLICT   514   514        T -> S (in Ref. 6; AAC50137). 
Sequence information
Length: 671 AA [This is the length of the unprocessed precursor] Molecular weight: 75931 Da [This is the MW of the unprocessed precursor] CRC64: 976E2428D525A9B2 [This is a checksum on the sequence]
        10         20         30         40         50         60 
MQPDMSLNVI KMKSSDFLES AELDSGGFGK VSLCFHRTQG LMIMKTVYKG PNCIEHNEAL 

        70         80         90        100        110        120 
LEEAKMMNRL RHSRVVKLLG VIIEEGKYSL VMEYMEKGNL MHVLKAEMST PLSVKGRIIL 

       130        140        150        160        170        180 
EIIEGMCYLH GKGVIHKDLK PENILVDNDF HIKIADLGLA SFKMWSKLNN EEHNELREVD 

       190        200        210        220        230        240 
GTAKKNGGTL YYMAPEHLND VNAKPTEKSD VYSFAVVLWA IFANKEPYEN AICEQQLIMC 

       250        260        270        280        290        300 
IKSGNRPDVD DITEYCPREI ISLMKLCWEA NPEARPTFPG IEEKFRPFYL SQLEESVEED 

       310        320        330        340        350        360 
VKSLKKEYSN ENAVVKRMQS LQLDCVAVPS SRSNSATEQP GSLHSSQGLG MGPVEESWFA 

       370        380        390        400        410        420 
PSLEHPQEEN EPSLQSKLQD EANYHLYGSR MDRQTKQQPR QNVAYNREEE RRRRVSHDPF 

       430        440        450        460        470        480 
AQQRPYENFQ NTEGKGTAYS SAASHGNAVH QPSGLTSQPQ VLYQNNGLYS SHGFGTRPLD 

       490        500        510        520        530        540 
PGTAGPRVWY RPIPSHMPSL HNIPVPETNY LGNTPTMPFS SLPPTDESIK YTIYNSTGIQ 

       550        560        570        580        590        600 
IGAYNYMEIG GTSSSLLDST NTNFKEEPAA KYQAIFDNTT SLTDKHLDPI RENLGKHWKN 

       610        620        630        640        650        660 
CARKLGFTQS QIDEIDHDYE RDGLKEKVYQ MLQKWVMREG IKGATVGKLA QALHQCSRID 

       670 
LLSSLIYVSQ N 

Q13546 in FASTA format

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