UniProtKB - Q13546 (RIPK1_HUMAN)
Receptor-interacting serine/threonine-protein kinase 1
RIPK1
Functioni
Serine-threonine kinase which is a key regulator of TNF-mediated apoptosis, necroptosis and inflammatory pathways (PubMed:32657447, PubMed:31827280, PubMed:31827281).
Exhibits kinase activity-dependent functions that regulate cell death and kinase-independent scaffold functions regulating inflammatory signaling and cell survival (PubMed:11101870, PubMed:19524512, PubMed:19524513, PubMed:29440439, PubMed:30988283).
Has kinase-independent scaffold functions: upon binding of TNF to TNFR1, RIPK1 is recruited to the TNF-R1 signaling complex (TNF-RSC also known as complex I) where it acts as a scaffold protein promoting cell survival, in part, by activating the canonical NF-kappa-B pathway (By similarity).
Kinase activity is essential to regulate necroptosis and apoptosis, two parallel forms of cell death: upon activation of its protein kinase activity, regulates assembly of two death-inducing complexes, namely complex IIa (RIPK1-FADD-CASP8), which drives apoptosis, and the complex IIb (RIPK1-RIPK3-MLKL), which drives necroptosis (By similarity).
RIPK1 is required to limit CASP8-dependent TNFR1-induced apoptosis (By similarity).
In normal conditions, RIPK1 acts as an inhibitor of RIPK3-dependent necroptosis, a process mediated by RIPK3 component of complex IIb, which catalyzes phosphorylation of MLKL upon induction by ZBP1 (PubMed:19524512, PubMed:19524513, PubMed:29440439, PubMed:30988283).
Inhibits RIPK3-mediated necroptosis via FADD-mediated recruitment of CASP8, which cleaves RIPK1 and limits TNF-induced necroptosis (PubMed:19524512, PubMed:19524513, PubMed:29440439, PubMed:30988283).
Required to inhibit apoptosis and necroptosis during embryonic development: acts by preventing the interaction of TRADD with FADD thereby limiting aberrant activation of CASP8 (By similarity).
In addition to apoptosis and necroptosis, also involved in inflammatory response by promoting transcriptional production of pro-inflammatory cytokines, such as interleukin-6 (IL6) (PubMed:31827280, PubMed:31827281).
Phosphorylates RIPK3: RIPK1 and RIPK3 undergo reciprocal auto- and trans-phosphorylation (PubMed:19524513).
Phosphorylates DAB2IP at 'Ser-728' in a TNF-alpha-dependent manner, and thereby activates the MAP3K5-JNK apoptotic cascade (PubMed:17389591, PubMed:15310755).
Required for ZBP1-induced NF-kappa-B activation in response to DNA damage (By similarity).
By similarity10 PublicationsCatalytic activityi
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 45 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 138 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 23 – 31 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- death domain binding Source: BHF-UCL
- death receptor binding Source: BHF-UCL
- identical protein binding Source: IntAct
- JUN kinase kinase kinase activity Source: GO_Central
- protein-containing complex binding Source: UniProtKB
- protein homodimerization activity Source: UniProtKB
- protein kinase activity Source: UniProtKB
- protein serine/threonine/tyrosine kinase activity Source: RHEA
- protein serine/threonine kinase activity Source: UniProtKB
- protein serine kinase activity Source: RHEA
- ubiquitin protein ligase binding Source: UniProtKB
GO - Biological processi
- amyloid fibril formation Source: UniProtKB
- apoptotic process Source: UniProtKB
- cell death Source: UniProtKB
- cellular protein catabolic process Source: UniProtKB
- cellular response to growth factor stimulus Source: Ensembl
- cellular response to hydrogen peroxide Source: ARUK-UCL
- cellular response to tumor necrosis factor Source: UniProtKB
- extrinsic apoptotic signaling pathway Source: BHF-UCL
- inflammatory response Source: UniProtKB-KW
- necroptotic process Source: UniProtKB
- necroptotic signaling pathway Source: UniProtKB
- negative regulation of apoptotic process Source: UniProtKB
- negative regulation of extrinsic apoptotic signaling pathway Source: UniProtKB
- negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: Ensembl
- negative regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
- negative regulation of necroptotic process Source: UniProtKB
- peptidyl-serine autophosphorylation Source: UniProtKB
- positive regulation of apoptotic process Source: UniProtKB
- positive regulation of extrinsic apoptotic signaling pathway Source: UniProtKB
- positive regulation of hydrogen peroxide-induced cell death Source: BHF-UCL
- positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
- positive regulation of inflammatory response Source: UniProtKB
- positive regulation of interleukin-6-mediated signaling pathway Source: UniProtKB
- positive regulation of interleukin-8 production Source: BHF-UCL
- positive regulation of JNK cascade Source: UniProtKB
- positive regulation of macrophage differentiation Source: UniProtKB
- positive regulation of necroptotic process Source: UniProtKB
- positive regulation of necrotic cell death Source: BHF-UCL
- positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
- positive regulation of production of miRNAs involved in gene silencing by miRNA Source: ARUK-UCL
- positive regulation of programmed cell death Source: UniProtKB
- positive regulation of protein phosphorylation Source: UniProtKB
- positive regulation of reactive oxygen species metabolic process Source: BHF-UCL
- positive regulation of transcription by RNA polymerase II Source: UniProtKB
- positive regulation of tumor necrosis factor-mediated signaling pathway Source: Ensembl
- positive regulation of tumor necrosis factor production Source: BHF-UCL
- programmed necrotic cell death Source: ARUK-UCL
- protein autophosphorylation Source: BHF-UCL
- regulation of ATP:ADP antiporter activity Source: BHF-UCL
- response to tumor necrosis factor Source: BHF-UCL
- ripoptosome assembly Source: UniProtKB
- ripoptosome assembly involved in necroptotic process Source: Ensembl
- T cell apoptotic process Source: UniProtKB
- tumor necrosis factor-mediated signaling pathway Source: BHF-UCL
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase |
Biological process | Apoptosis, Host-virus interaction, Inflammatory response, Necrosis |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.10.2, 2681 |
PathwayCommonsi | Q13546 |
Reactomei | R-HSA-140534, Caspase activation via Death Receptors in the presence of ligand R-HSA-168927, TICAM1, RIP1-mediated IKK complex recruitment R-HSA-1810476, RIP-mediated NFkB activation via ZBP1 R-HSA-2562578, TRIF-mediated programmed cell death R-HSA-3295583, TRP channels R-HSA-3371378, Regulation by c-FLIP R-HSA-5213460, RIPK1-mediated regulated necrosis R-HSA-5218900, CASP8 activity is inhibited R-HSA-5357786, TNFR1-induced proapoptotic signaling R-HSA-5357905, Regulation of TNFR1 signaling R-HSA-5357956, TNFR1-induced NFkappaB signaling pathway R-HSA-5675482, Regulation of necroptotic cell death R-HSA-5689880, Ub-specific processing proteases R-HSA-5689896, Ovarian tumor domain proteases R-HSA-69416, Dimerization of procaspase-8 R-HSA-75893, TNF signaling R-HSA-9013957, TLR3-mediated TICAM1-dependent programmed cell death R-HSA-933543, NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 R-HSA-937041, IKK complex recruitment mediated by RIP1 R-HSA-9679191, Potential therapeutics for SARS R-HSA-9686347, Microbial modulation of RIPK1-mediated regulated necrosis R-HSA-9693928, Defective RIPK1-mediated regulated necrosis |
SignaLinki | Q13546 |
SIGNORi | Q13546 |
Names & Taxonomyi
Protein namesi | Recommended name: Receptor-interacting serine/threonine-protein kinase 1 (EC:2.7.11.14 Publications)Alternative name(s): Cell death protein RIP1 Publication Receptor-interacting protein 11 Publication Short name: RIP-11 Publication |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:10019, RIPK1 |
MIMi | 603453, gene |
neXtProti | NX_Q13546 |
VEuPathDBi | HostDB:ENSG00000137275 |
Subcellular locationi
Plasma membrane
- Cell membrane By similarity
Cytoplasm and Cytosol
- Cytoplasm By similarity
Cytosol
- cytosol Source: HPA
- ripoptosome Source: UniProtKB
Endosome
- endosome membrane Source: Reactome
Mitochondrion
- mitochondrion Source: BHF-UCL
Plasma Membrane
- death-inducing signaling complex Source: BHF-UCL
- plasma membrane Source: HPA
Other locations
- membrane raft Source: Ensembl
- protein-containing complex Source: UniProtKB
- receptor complex Source: BHF-UCL
Keywords - Cellular componenti
Cell membrane, Cytoplasm, MembranePathology & Biotechi
Involvement in diseasei
Immunodeficiency 57 with autoinflammation (IMD57)1 Publication
Autoinflammation with episodic fever and lymphadenopathy (AIEFL)2 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_083518 | 324 | D → H in AIEFL; prevents cleavage by CASP8; increased kinase activity; increased inflammatory response. 2 Publications | 1 | |
Natural variantiVAR_083519 | 324 | D → N in AIEFL; prevents cleavage by CASP8; changed inflammatory response. 1 Publication | 1 | |
Natural variantiVAR_084135 | 324 | D → V in AIEFL; prevents cleavage by CASP8; increased kinase activity; increased inflammatory response. 1 Publication | 1 | |
Natural variantiVAR_083520 | 324 | D → Y in AIEFL; prevents cleavage by CASP8; changed inflammatory response. 1 Publication | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 25 | S → D: Phophomimetic mutant. Significant loss of kinase activity. 1 Publication | 1 | |
Mutagenesisi | 45 | K → A: Abolishes kinase activity. 2 Publications | 1 | |
Mutagenesisi | 161 | S → A: Decreases RIPK1 kinase activity. 1 Publication | 1 | |
Mutagenesisi | 161 | S → E: No effect on RIPK1 autophosphorylation. 1 Publication | 1 | |
Mutagenesisi | 324 | D → K: Abolishes cleavage by caspase-8. 1 Publication | 1 | |
Mutagenesisi | 377 | K → R: Abolishes RIP-mediated NF-Kappa-B activation. 1 Publication | 1 | |
Mutagenesisi | 536 | S → C: Strongly reduced homodimerization and interaction with RIPK3. 1 Publication | 1 | |
Mutagenesisi | 539 – 542 | IQIG → AAAA: Abolished cleavage by S.flexneri OspD3. 1 Publication | 4 | |
Mutagenesisi | 599 | K → R: Blocks homodimerization, necroptosis and apoptosis. 1 Publication | 1 | |
Mutagenesisi | 603 | R → A: Abolished GlcNAcylation by E.coli NleB1. 1 Publication | 1 |
Keywords - Diseasei
Disease variantOrganism-specific databases
DisGeNETi | 8737 |
MalaCardsi | RIPK1 |
MIMi | 618108, phenotype 618852, phenotype |
OpenTargetsi | ENSG00000137275 |
Orphaneti | 529977, Immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections-lymphopenia syndrome |
PharmGKBi | PA34394 |
Miscellaneous databases
Pharosi | Q13546, Tchem |
Chemistry databases
ChEMBLi | CHEMBL5464 |
DrugBanki | DB12010, Fostamatinib |
DrugCentrali | Q13546 |
GuidetoPHARMACOLOGYi | 2189 |
Genetic variation databases
BioMutai | RIPK1 |
DMDMi | 60393639 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000086606 | 1 – 671 | Receptor-interacting serine/threonine-protein kinase 1Add BLAST | 671 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 6 | Phosphoserine; by IKKA and IKKB1 Publication | 1 | |
Modified residuei | 20 | Phosphoserine; by autocatalysisSequence analysis | 1 | |
Modified residuei | 25 | Phosphoserine; by IKKA and IKKB2 Publications | 1 | |
Modified residuei | 161 | Phosphoserine; by RIPK3 and autocatalysisSequence analysis | 1 | |
Modified residuei | 166 | Phosphoserine; by autocatalysisSequence analysis2 Publications | 1 | |
Modified residuei | 303 | Phosphoserine1 Publication | 1 | |
Modified residuei | 320 | Phosphoserine; by MAP3K7Combined sources1 Publication | 1 | |
Modified residuei | 331 | Phosphoserine; by MAP3K7By similarity | 1 | |
Modified residuei | 333 | Phosphoserine; by MAP3K71 Publication | 1 | |
Cross-linki | 377 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication | ||
Modified residuei | 384 | PhosphotyrosineCombined sources | 1 | |
Glycosylationi | 603 | (Microbial infection) N-beta-linked (GlcNAc) arginineCombined sources1 Publication1 Publication | 1 |
Post-translational modificationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 324 – 325 | Cleavage; by CASP83 Publications | 2 |
Keywords - PTMi
Glycoprotein, Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
CPTACi | CPTAC-1053 CPTAC-900 CPTAC-901 CPTAC-902 |
EPDi | Q13546 |
jPOSTi | Q13546 |
MassIVEi | Q13546 |
MaxQBi | Q13546 |
PaxDbi | Q13546 |
PeptideAtlasi | Q13546 |
PRIDEi | Q13546 |
ProteomicsDBi | 59527 [Q13546-1] 59528 [Q13546-2] |
PTM databases
GlyGeni | Q13546, 2 sites, 1 O-linked glycan (2 sites) |
iPTMneti | Q13546 |
MetOSitei | Q13546 |
PhosphoSitePlusi | Q13546 |
Expressioni
Gene expression databases
Bgeei | ENSG00000137275, Expressed in sural nerve and 199 other tissues |
ExpressionAtlasi | Q13546, baseline and differential |
Genevisiblei | Q13546, HS |
Organism-specific databases
HPAi | ENSG00000137275, Low tissue specificity |
Interactioni
Subunit structurei
Homodimer (PubMed:29440439, PubMed:29681455).
Interacts (via RIP homotypic interaction motif) with RIPK3 (via RIP homotypic interaction motif); this interaction induces RIPK1 phosphorylation and formation of a RIPK1-RIPK3 necroptosis-inducing complex (PubMed:11734559, PubMed:29883609, PubMed:19524512, PubMed:10358032, PubMed:29681455). Upon TNF-induced necrosis, the RIPK1-RIPK3 dimer further interacts with PGAM5 and MLKL; the formation of this complex leads to PGAM5 phosphorylation and increase in PGAM5 phosphatase activity (PubMed:22265414).
Interacts (via the death domain) with TNFRSF6 (via the death domain) and TRADD (via the death domain) (PubMed:8612133). Is recruited by TRADD to TNFRSF1A in a TNF-dependent process (PubMed:24130170). Binds RNF216, EGFR, IKBKG, TRAF1, TRAF2 and TRAF3 (PubMed:8612133, PubMed:9927690, PubMed:11854271, PubMed:11116146).
Interacts with BNLF1 (PubMed:10409763).
Interacts with SQSTM1 upon TNF-alpha stimulation (PubMed:10356400). May interact with MAVS/IPS1 (PubMed:16127453).
Interacts with ZFAND5 (PubMed:14754897).
Interacts with RBCK1 (PubMed:17449468).
Interacts with ZBP1 (By similarity).
Interacts with BIRC2/c-IAP1, BIRC3/c-IAP2 and XIAP/BIRC4 (PubMed:21931591).
Interacts (via kinase domain) with DAB2IP (via Ras-GAP domain); the interaction occurs in a TNF-alpha-dependent manner (PubMed:17389591, PubMed:15310755).
Interacts with ARHGEF2 (PubMed:21887730).
Interacts (via protein kinase domain) with RFFL; involved in RIPK1 ubiquitination (PubMed:18450452).
Interacts with RNF34; involved in RIPK1 ubiquitination (Ref. 34).
Interacts with TICAM1 and this interaction is enhanced in the presence of WDFY1 (PubMed:25736436).
Interacts with PELI1 (PubMed:29883609).
Interacts (via death domain) with CRADD (via death domain); the interaction is direct (PubMed:9044836).
Component of complex IIa composed of at least RIPK1, FADD and CASP8 (By similarity).
Component of the AIM2 PANoptosome complex, a multiprotein complex that drives inflammatory cell death (PANoptosis) (By similarity).
Interacts with MAP3K7, CFLAR, CASP8, FADD and NEMO (By similarity).
By similarity24 Publications(Microbial infection) Interacts with mumps virus protein SH; this interaction inhibits downstream NF-kappa-B pathway activation.
1 Publication(Microbial infection) Interacts with Murid herpesvirus 1 protein RIR1.
1 Publication(Microbial infection) Interacts (via RIP homotypic interaction motif) with herpes simplex virus 1/HHV-1 protein RIR1/ICP6 (via RIP homotypic interaction motif); this interaction prevents necroptosis activation.
1 Publication(Microbial infection) Interacts (via RIP homotypic interaction motif) with herpes simplex virus 2/HHV-2 protein RIR1/ICP10 (via RIP homotypic interaction motif); this interaction prevents necroptosis activation.
1 PublicationBinary interactionsi
Q13546
GO - Molecular functioni
- death domain binding Source: BHF-UCL
- death receptor binding Source: BHF-UCL
- identical protein binding Source: IntAct
- protein homodimerization activity Source: UniProtKB
- ubiquitin protein ligase binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 114274, 160 interactors |
ComplexPortali | CPX-1907, Ripoptosome |
CORUMi | Q13546 |
DIPi | DIP-433N |
IntActi | Q13546, 76 interactors |
MINTi | Q13546 |
STRINGi | 9606.ENSP00000259808 |
Chemistry databases
BindingDBi | Q13546 |
Miscellaneous databases
RNActi | Q13546, protein |
Structurei
Secondary structure
3D structure databases
BMRBi | Q13546 |
SMRi | Q13546 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 17 – 289 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 273 | |
Domaini | 583 – 669 | DeathPROSITE-ProRule annotationAdd BLAST | 87 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 290 – 582 | Interaction with SQSTM11 PublicationAdd BLAST | 293 | |
Regioni | 331 – 354 | DisorderedSequence analysisAdd BLAST | 24 | |
Regioni | 389 – 458 | DisorderedSequence analysisAdd BLAST | 70 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 531 – 547 | RIP homotypic interaction motif (RHIM)2 PublicationsAdd BLAST | 17 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 331 – 346 | Polar residuesSequence analysisAdd BLAST | 16 | |
Compositional biasi | 403 – 420 | Basic and acidic residuesSequence analysisAdd BLAST | 18 | |
Compositional biasi | 423 – 458 | Polar residuesSequence analysisAdd BLAST | 36 |
Domaini
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG0192, Eukaryota |
GeneTreei | ENSGT00940000159347 |
HOGENOMi | CLU_017229_0_0_1 |
InParanoidi | Q13546 |
OrthoDBi | 346354at2759 |
PhylomeDBi | Q13546 |
TreeFami | TF106506 |
Family and domain databases
CDDi | cd08777, Death_RIP1, 1 hit |
Gene3Di | 1.10.533.10, 1 hit |
InterProi | View protein in InterPro IPR011029, DEATH-like_dom_sf IPR000488, Death_domain IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR025735, RHIM_dom IPR037934, RIP1_Death IPR001245, Ser-Thr/Tyr_kinase_cat_dom IPR008271, Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF00531, Death, 1 hit PF07714, PK_Tyr_Ser-Thr, 1 hit PF12721, RHIM, 1 hit |
PRINTSi | PR00109, TYRKINASE |
SMARTi | View protein in SMART SM00005, DEATH, 1 hit SM00220, S_TKc, 1 hit |
SUPFAMi | SSF47986, SSF47986, 1 hit SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS50017, DEATH_DOMAIN, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MQPDMSLNVI KMKSSDFLES AELDSGGFGK VSLCFHRTQG LMIMKTVYKG
60 70 80 90 100
PNCIEHNEAL LEEAKMMNRL RHSRVVKLLG VIIEEGKYSL VMEYMEKGNL
110 120 130 140 150
MHVLKAEMST PLSVKGRIIL EIIEGMCYLH GKGVIHKDLK PENILVDNDF
160 170 180 190 200
HIKIADLGLA SFKMWSKLNN EEHNELREVD GTAKKNGGTL YYMAPEHLND
210 220 230 240 250
VNAKPTEKSD VYSFAVVLWA IFANKEPYEN AICEQQLIMC IKSGNRPDVD
260 270 280 290 300
DITEYCPREI ISLMKLCWEA NPEARPTFPG IEEKFRPFYL SQLEESVEED
310 320 330 340 350
VKSLKKEYSN ENAVVKRMQS LQLDCVAVPS SRSNSATEQP GSLHSSQGLG
360 370 380 390 400
MGPVEESWFA PSLEHPQEEN EPSLQSKLQD EANYHLYGSR MDRQTKQQPR
410 420 430 440 450
QNVAYNREEE RRRRVSHDPF AQQRPYENFQ NTEGKGTAYS SAASHGNAVH
460 470 480 490 500
QPSGLTSQPQ VLYQNNGLYS SHGFGTRPLD PGTAGPRVWY RPIPSHMPSL
510 520 530 540 550
HNIPVPETNY LGNTPTMPFS SLPPTDESIK YTIYNSTGIQ IGAYNYMEIG
560 570 580 590 600
GTSSSLLDST NTNFKEEPAA KYQAIFDNTT SLTDKHLDPI RENLGKHWKN
610 620 630 640 650
CARKLGFTQS QIDEIDHDYE RDGLKEKVYQ MLQKWVMREG IKGATVGKLA
660 670
QALHQCSRID LLSSLIYVSQ N
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A7I2V404 | A0A7I2V404_HUMAN | Receptor-interacting serine/threoni... | RIPK1 | 160 | Annotation score: | ||
A0A7I2V5Y1 | A0A7I2V5Y1_HUMAN | Receptor-interacting serine/threoni... | RIPK1 | 189 | Annotation score: |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 258 | R → I in BAG36858 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 286 | R → S in BAG36858 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 514 | T → S in AAC50137 (PubMed:7538908).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_041039 | 64 | A → V in a colorectal adenocarcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs774996232Ensembl. | 1 | |
Natural variantiVAR_041040 | 81 | V → I in a colorectal adenocarcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs758268804Ensembl. | 1 | |
Natural variantiVAR_041041 | 220 | A → V in a colorectal adenocarcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs759012409Ensembl. | 1 | |
Natural variantiVAR_021109 | 234 | E → K1 PublicationCorresponds to variant dbSNP:rs17548383Ensembl. | 1 | |
Natural variantiVAR_083518 | 324 | D → H in AIEFL; prevents cleavage by CASP8; increased kinase activity; increased inflammatory response. 2 Publications | 1 | |
Natural variantiVAR_083519 | 324 | D → N in AIEFL; prevents cleavage by CASP8; changed inflammatory response. 1 Publication | 1 | |
Natural variantiVAR_084135 | 324 | D → V in AIEFL; prevents cleavage by CASP8; increased kinase activity; increased inflammatory response. 1 Publication | 1 | |
Natural variantiVAR_083520 | 324 | D → Y in AIEFL; prevents cleavage by CASP8; changed inflammatory response. 1 Publication | 1 | |
Natural variantiVAR_041042 | 404 | A → S1 PublicationCorresponds to variant dbSNP:rs34872409Ensembl. | 1 | |
Natural variantiVAR_058285 | 438 | A → V3 PublicationsCorresponds to variant dbSNP:rs3173519Ensembl. | 1 | |
Natural variantiVAR_041043 | 443 | A → V1 PublicationCorresponds to variant dbSNP:rs35722193Ensembl. | 1 | |
Natural variantiVAR_041044 | 569 | A → V1 PublicationCorresponds to variant dbSNP:rs55861377Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_037690 | 108 – 153 | Missing in isoform 2. 1 PublicationAdd BLAST | 46 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U50062 mRNA Translation: AAC32232.1 AK314176 mRNA Translation: BAG36858.1 AK304701 mRNA Translation: BAG65471.1 Different initiation. AY682848 Genomic DNA Translation: AAT74626.1 AL031963 Genomic DNA No translation available. BC126254 mRNA Translation: AAI26255.1 BC126256 mRNA Translation: AAI26257.1 AB208926 mRNA Translation: BAD92163.1 U25994 mRNA Translation: AAC50137.1 |
CCDSi | CCDS4482.1 [Q13546-1] |
PIRi | T09479 |
RefSeqi | NP_003795.2, NM_003804.4 [Q13546-1] XP_005249514.2, XM_005249457.3 |
Genome annotation databases
Ensembli | ENST00000259808; ENSP00000259808; ENSG00000137275 ENST00000380409; ENSP00000369773; ENSG00000137275 [Q13546-2] |
GeneIDi | 8737 |
KEGGi | hsa:8737 |
MANE-Selecti | ENST00000259808.9; ENSP00000259808.3; NM_001354930.2; NP_001341859.1 |
UCSCi | uc003mux.4, human [Q13546-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
SeattleSNPs |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U50062 mRNA Translation: AAC32232.1 AK314176 mRNA Translation: BAG36858.1 AK304701 mRNA Translation: BAG65471.1 Different initiation. AY682848 Genomic DNA Translation: AAT74626.1 AL031963 Genomic DNA No translation available. BC126254 mRNA Translation: AAI26255.1 BC126256 mRNA Translation: AAI26257.1 AB208926 mRNA Translation: BAD92163.1 U25994 mRNA Translation: AAC50137.1 |
CCDSi | CCDS4482.1 [Q13546-1] |
PIRi | T09479 |
RefSeqi | NP_003795.2, NM_003804.4 [Q13546-1] XP_005249514.2, XM_005249457.3 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
4ITH | X-ray | 2.25 | A/B | 1-294 | [»] | |
4ITI | X-ray | 2.86 | A/B | 1-294 | [»] | |
4ITJ | X-ray | 1.80 | A/B | 1-294 | [»] | |
4NEU | X-ray | 2.57 | A/B | 1-324 | [»] | |
5HX6 | X-ray | 2.23 | A/B | 1-294 | [»] | |
5TX5 | X-ray | 2.56 | A/B | 1-294 | [»] | |
5V7Z | NMR | - | B/D/F/H | 532-549 | [»] | |
6AC5 | X-ray | 1.45 | A | 561-671 | [»] | |
6C3E | X-ray | 2.60 | A/B | 2-294 | [»] | |
6C4D | X-ray | 2.52 | A/B/C/D | 2-294 | [»] | |
6HHO | X-ray | 3.49 | A/B | 1-294 | [»] | |
6NW2 | X-ray | 2.00 | A/B | 1-294 | [»] | |
6NYH | X-ray | 2.10 | A/B | 1-294 | [»] | |
6OCQ | X-ray | 2.79 | A/B | 1-294 | [»] | |
6R5F | X-ray | 3.25 | A/B/C/D | 1-294 | [»] | |
6RLN | X-ray | 2.87 | A/B | 1-294 | [»] | |
7CJB | X-ray | 2.80 | D/H/L/P | 189-203 | [»] | |
BMRBi | Q13546 | |||||
SMRi | Q13546 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 114274, 160 interactors |
ComplexPortali | CPX-1907, Ripoptosome |
CORUMi | Q13546 |
DIPi | DIP-433N |
IntActi | Q13546, 76 interactors |
MINTi | Q13546 |
STRINGi | 9606.ENSP00000259808 |
Chemistry databases
BindingDBi | Q13546 |
ChEMBLi | CHEMBL5464 |
DrugBanki | DB12010, Fostamatinib |
DrugCentrali | Q13546 |
GuidetoPHARMACOLOGYi | 2189 |
PTM databases
GlyGeni | Q13546, 2 sites, 1 O-linked glycan (2 sites) |
iPTMneti | Q13546 |
MetOSitei | Q13546 |
PhosphoSitePlusi | Q13546 |
Genetic variation databases
BioMutai | RIPK1 |
DMDMi | 60393639 |
Proteomic databases
CPTACi | CPTAC-1053 CPTAC-900 CPTAC-901 CPTAC-902 |
EPDi | Q13546 |
jPOSTi | Q13546 |
MassIVEi | Q13546 |
MaxQBi | Q13546 |
PaxDbi | Q13546 |
PeptideAtlasi | Q13546 |
PRIDEi | Q13546 |
ProteomicsDBi | 59527 [Q13546-1] 59528 [Q13546-2] |
Protocols and materials databases
Antibodypediai | 4145, 627 antibodies from 43 providers |
DNASUi | 8737 |
Genome annotation databases
Ensembli | ENST00000259808; ENSP00000259808; ENSG00000137275 ENST00000380409; ENSP00000369773; ENSG00000137275 [Q13546-2] |
GeneIDi | 8737 |
KEGGi | hsa:8737 |
MANE-Selecti | ENST00000259808.9; ENSP00000259808.3; NM_001354930.2; NP_001341859.1 |
UCSCi | uc003mux.4, human [Q13546-1] |
Organism-specific databases
CTDi | 8737 |
DisGeNETi | 8737 |
GeneCardsi | RIPK1 |
HGNCi | HGNC:10019, RIPK1 |
HPAi | ENSG00000137275, Low tissue specificity |
MalaCardsi | RIPK1 |
MIMi | 603453, gene 618108, phenotype 618852, phenotype |
neXtProti | NX_Q13546 |
OpenTargetsi | ENSG00000137275 |
Orphaneti | 529977, Immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections-lymphopenia syndrome |
PharmGKBi | PA34394 |
VEuPathDBi | HostDB:ENSG00000137275 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0192, Eukaryota |
GeneTreei | ENSGT00940000159347 |
HOGENOMi | CLU_017229_0_0_1 |
InParanoidi | Q13546 |
OrthoDBi | 346354at2759 |
PhylomeDBi | Q13546 |
TreeFami | TF106506 |
Enzyme and pathway databases
BRENDAi | 2.7.10.2, 2681 |
PathwayCommonsi | Q13546 |
Reactomei | R-HSA-140534, Caspase activation via Death Receptors in the presence of ligand R-HSA-168927, TICAM1, RIP1-mediated IKK complex recruitment R-HSA-1810476, RIP-mediated NFkB activation via ZBP1 R-HSA-2562578, TRIF-mediated programmed cell death R-HSA-3295583, TRP channels R-HSA-3371378, Regulation by c-FLIP R-HSA-5213460, RIPK1-mediated regulated necrosis R-HSA-5218900, CASP8 activity is inhibited R-HSA-5357786, TNFR1-induced proapoptotic signaling R-HSA-5357905, Regulation of TNFR1 signaling R-HSA-5357956, TNFR1-induced NFkappaB signaling pathway R-HSA-5675482, Regulation of necroptotic cell death R-HSA-5689880, Ub-specific processing proteases R-HSA-5689896, Ovarian tumor domain proteases R-HSA-69416, Dimerization of procaspase-8 R-HSA-75893, TNF signaling R-HSA-9013957, TLR3-mediated TICAM1-dependent programmed cell death R-HSA-933543, NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 R-HSA-937041, IKK complex recruitment mediated by RIP1 R-HSA-9679191, Potential therapeutics for SARS R-HSA-9686347, Microbial modulation of RIPK1-mediated regulated necrosis R-HSA-9693928, Defective RIPK1-mediated regulated necrosis |
SignaLinki | Q13546 |
SIGNORi | Q13546 |
Miscellaneous databases
BioGRID-ORCSi | 8737, 28 hits in 1086 CRISPR screens |
ChiTaRSi | RIPK1, human |
GeneWikii | RIPK1 |
GenomeRNAii | 8737 |
Pharosi | Q13546, Tchem |
PROi | PR:Q13546 |
RNActi | Q13546, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000137275, Expressed in sural nerve and 199 other tissues |
ExpressionAtlasi | Q13546, baseline and differential |
Genevisiblei | Q13546, HS |
Family and domain databases
CDDi | cd08777, Death_RIP1, 1 hit |
Gene3Di | 1.10.533.10, 1 hit |
InterProi | View protein in InterPro IPR011029, DEATH-like_dom_sf IPR000488, Death_domain IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR025735, RHIM_dom IPR037934, RIP1_Death IPR001245, Ser-Thr/Tyr_kinase_cat_dom IPR008271, Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF00531, Death, 1 hit PF07714, PK_Tyr_Ser-Thr, 1 hit PF12721, RHIM, 1 hit |
PRINTSi | PR00109, TYRKINASE |
SMARTi | View protein in SMART SM00005, DEATH, 1 hit SM00220, S_TKc, 1 hit |
SUPFAMi | SSF47986, SSF47986, 1 hit SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS50017, DEATH_DOMAIN, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | RIPK1_HUMAN | |
Accessioni | Q13546Primary (citable) accession number: Q13546 Secondary accession number(s): A0AV89 Q59H33 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1997 |
Last sequence update: | February 1, 2005 | |
Last modified: | February 23, 2022 | |
This is version 224 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human and mouse protein kinases
Human and mouse protein kinases: classification and index - Human chromosome 6
Human chromosome 6: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families