Protein detail
RIPK1
Receptor-interacting serine/threonine-protein kinase 1 (EC 2.7.11.1) (Cell death protein RIP) (Receptor-interacting protein 1) (RIP-1)
Entry name RIPK1 | UniProt ID | EVMP score 0.50 |
Frequency 1 | Transmembrane count | Protein classification Disease related genesEnzymesHuman disease related genesPotential drug targetsPredicted intracellular proteins |
EVMP score: annotation confidence score.
Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40
Basic Information
Protein Names
Receptor-interacting serine/threonine-protein kinase 1 (EC 2.7.11.1) (Cell death protein RIP) (Receptor-interacting protein 1) (RIP-1)
Protein Class
Disease related genesEnzymesHuman disease related genesPotential drug targetsPredicted intracellular proteins
Protein Function
- Human disease related genes:Immune system diseases:Allergies and autoimmune diseases
- Predicted intracellular proteins
- ENZYME proteins:Transferases
- Potential drug targets
- Human disease related genes:Immune system diseases:Primary immunodeficiency
- Enzymes
- Kinases:TKL Ser/Thr protein kinases
- Disease related genes
Ensembl
Entrez Gene Symbol
Gene Synonym
RIPRIP-1RIP1
Gene Description
Receptor interacting serine/threonine kinase 1
Chromosome
6
Position
3063824-3115187
Frequency
1
EVMP Score
0.50
Fluorescence & Localization
Tissue Specificlymphoid tissueCell SpecificB-cellsSingle-Nuclei Brain SpecificleukocyteBlood Lineage SpecificB-cells
Function & Pathway
Protein Function
- Human disease related genes:Immune system diseases:Allergies and autoimmune diseases
- Predicted intracellular proteins
- ENZYME proteins:Transferases
- Potential drug targets
- Human disease related genes:Immune system diseases:Primary immunodeficiency
- Enzymes
- Kinases:TKL Ser/Thr protein kinases
- Disease related genes
Cellular Component
Molecular Function
- GO:0004672 protein kinase activity
- GO:0004674 protein serine/threonine kinase activity
- GO:0004706 JUN kinase kinase kinase activity
- GO:0005123 death receptor binding
- GO:0005515 protein binding
- GO:0005524 ATP binding
- GO:0031625 ubiquitin protein ligase binding
- GO:0035591 signaling adaptor activity
- GO:0042802 identical protein binding
- GO:0042803 protein homodimerization activity
- GO:0044024 histone H2AS1 kinase activity
- GO:0044877 protein-containing complex binding
- GO:0070513 death domain binding
- GO:0106310 protein serine kinase activity
Biological Process
KEGG
- hsa04064 NF-kappa B signaling pathway
- KEGG:hsa04210 Apoptosis
- KEGG:hsa04217 Necroptosis
- KEGG:hsa04620 Toll-like receptor signaling pathway
- KEGG:hsa04621 NOD-like receptor signaling pathway
- KEGG:hsa04622 RIG-I-like receptor signaling pathway
- KEGG:hsa04623 Cytosolic DNA-sensing pathway
- KEGG:hsa04668 TNF signaling pathway
- KEGG:hsa04936 Alcoholic liver disease
- KEGG:hsa05130 Pathogenic Escherichia coli infection
- KEGG:hsa05131 Shigellosis
- KEGG:hsa05132 Salmonella infection
- KEGG:hsa05160 Hepatitis C
- KEGG:hsa05163 Human cytomegalovirus infection
- KEGG:hsa05169 Epstein-Barr virus infection
- KEGG:hsa05170 Human immunodeficiency virus 1 infection
Reactome
- R-hsa-109581 apoptosis
- R-hsa-140534 caspase activation via death receptors in the presence of ligand
- R-hsa-5357769 caspase activation via extrinsic apoptotic signalling pathway
- R-hsa-1834949 cytosolic sensors of pathogen associated dna
- R-hsa-168928 ddx58 ifih1 mediated induction of interferon alpha beta
- R-hsa-73887 death receptor signaling
- R-hsa-9693928 defective ripk1 mediated regulated necrosis
- R-hsa-9918481 dengue virus host interactions
- R-hsa-9839923 dengue virus infection
- R-hsa-9920951 dengue virus modulates apoptosis
- R-hsa-5688426 deubiquitination
- R-hsa-9645723 diseases of programmed cell death
- R-hsa-937041 ikk complex recruitment mediated by rip1
- R-hsa-5663205 infectious disease
- R-hsa-168249 innate immune system
- R-hsa-983712 ion channel transport
- R-hsa-166166 myd88 independent tlr4 cascade
- R-hsa-933543 nf kb activation through fadd rip 1 pathway mediated by caspase 8 and 10
- R-hsa-5689896 ovarian tumor domain proteases
- R-hsa-597592 post translational protein modification
- R-hsa-9679191 potential therapeutics for sars
- R-hsa-5357801 programmed cell death
- R-hsa-5218859 regulated necrosis
- R-hsa-3371378 regulation by c flip
- R-hsa-5213460 ripk1 mediated regulated necrosis
- R-hsa-1810476 rip mediated nfkb activation via zbp1
- R-hsa-9692914 sars cov 1 host interactions
- R-hsa-9678108 sars cov 1 infection
- R-hsa-9679506 sars cov infections
- R-hsa-2672351 stimuli sensing channels
- R-hsa-168927 ticam1 rip1 mediated ikk complex recruitment
- R-hsa-9013957 tlr3 mediated ticam1 dependent programmed cell death
- R-hsa-5357956 tnfr1 induced nf kappa b signaling pathway
- R-hsa-5357786 tnfr1 induced proapoptotic signaling
- R-hsa-75893 tnf signaling
- R-hsa-168898 toll like receptor cascades
- R-hsa-382551 transport of small molecules
- R-hsa-2562578 trif mediated programmed cell death
- R-hsa-3295583 trp channels
- R-hsa-5689880 ub specific processing proteases
- R-hsa-9824446 viral infection pathways
- R-hsa-1606322 zbp1 dai mediated induction of type i ifns
Mediation Categories
Clinical-translation mediationFusion and delivery mediationImmune mediationMetabolism mediationReceptor-signaling mediation
Relations & Evidence
Enzyme-Mediated Modification
25 records.
| Substrate Gene Symbol | Enzyme Gene Symbol | Enzyme UniProt ID | Residue Type | Residue Offset | Modification | Database | References |
|---|---|---|---|---|---|---|---|
| RIPK1 | ULK1 | O75385 | S | 345 | phosphorylation | PhosphoSite | |
| RIPK1 | ULK1 | O75385 | S | 357 | phosphorylation | PhosphoSite | |
| RIPK1 | ULK1 | O75385 | S | 389 | phosphorylation | PhosphoSite | |
| RIPK1 | ULK1 | O75385 | S | 320 | phosphorylation | PhosphoSite | |
| RIPK1 | ULK1 | O75385 | S | 333 | phosphorylation | PhosphoSite | |
| RIPK1 | ULK1 | O75385 | S | 346 | phosphorylation | PhosphoSite | |
| RIPK1 | ULK1 | O75385 | S | 262 | phosphorylation | PhosphoSite | |
| RIPK1 | MAP3K7 | O43318 | S | 320 | phosphorylation | REACH_ProtMapperSparser_ProtMapperProtMapper | ProtMapper:28842570ProtMapper:29955050 |
| RIPK1 | TAB2 | Q9NYJ8 | S | 320 | phosphorylation | REACH_ProtMapperProtMapper | ProtMapper:28842570 |
| RIPK1 | TNF | P01375 | S | 320 | phosphorylation | REACH_ProtMapperSparser_ProtMapperProtMapper | ProtMapper:28842570ProtMapper:28506461 |
Ligand-Receptor Signaling
10 records.
| Category | Parent | Database | Transmitter | Receiver | Secreted | Plasma Membrane (Transmembrane) | Plasma Membrane (Peripheral) |
|---|---|---|---|---|---|---|---|
| receptor | receptor | CellTalkDB | No | Yes | No | No | No |
| receptor | receptor | OmniPath | No | Yes | No | No | No |
| intracellular | intracellular | LOCATE | No | No | No | No | No |
| intracellular | intracellular | ComPPI | No | No | No | No | No |
| intracellular | intracellular | GO_Intercell | No | No | No | No | No |
| intracellular | intracellular | UniProt_location | No | No | No | No | No |
| intracellular | intracellular | OmniPath | No | No | No | No | No |
| plasma_membrane | plasma_membrane | UniProt_location | No | No | No | No | No |
| plasma_membrane | plasma_membrane | OmniPath | No | No | No | No | No |
| receptor | receptor | scConnect | No | Yes | No | No | No |
Regulatory Interaction Network
31 records.
| Source Protein Symbol | Source UniProt ID | Target Protein Symbol | Target UniProt ID | Is Directed | Is Stimulation | Is Inhibition | Database | References |
|---|---|---|---|---|---|---|---|---|
| RN216 | Q9NWF9 | RIPK1 | Q13546 | Yes | No | Yes | HPRDLit-BM-17SIGNOR | Lit-BM-17:27995769Lit-BM-17:16968706HPRD:11854271SIGNOR:16968706Lit-BM-17:11854271 |
Page 4 of 4Previous
Protein Complex Composition
11 records.
| Component Name | Component Gene Symbols | Component UniProt ID | Stoichiometry | Database | Database IDs | References |
|---|---|---|---|---|---|---|
| RIPK1-FADD-caspase-8 complex | CASP8FADDRIPK1 | Q13158Q13546Q14790 | 1:1:1 | CORUMComplexPortal | CORUM:6414 | 200386791475529222274400 |
| TNF-R1 signaling complex | RIPK1TNFTNFRSF1ATRADDTRAF2 | P01375P19438Q12933Q13546Q15628 | 0:0:0:0:0 | SPIKECORUM | CORUM:6347 | 8612133 |
| RIPK1RIPK3TRADDTRAF2TRAF5 | O00463Q12933Q13546Q15628Q9Y572 | 0:0:0:0:0 | KEGG-MEDICUS | |||
| RIPK1TRADDTRAF5 | O00463Q13546Q15628 | 0:0:0 | KEGG-MEDICUS | |||
| ELOBELOCRIPK1VHL | P40337Q13546Q15369Q15370 | 4:4:4:4 | PDB | PDB:7cjb | ||
| RIPK1TRAF2 | Q12933Q13546 | 0:0 | KEGG-MEDICUS | |||
| RIPK1TRADDTRAF2 | Q12933Q13546Q15628 | 0:0:0 | KEGG-MEDICUS | |||
| CASP8FADDRIPK1RIPK3 | Q13158Q13546Q14790Q9Y572 | 0:0:0:0 | KEGG-MEDICUS | |||
| RIPK1 | Q13546 | 2 | PDB | PDB:9mzxPDB:7xmkPDB:6c4dPDB:9gtgPDB:5tx5PDB:9mzyPDB:6r5fPDB:4neuPDB:6nyhPDB:9mzzPDB:7ydxPDB:6rlnPDB:4itiPDB:8z93PDB:6hhoPDB:4ithPDB:7fczPDB:9gtyPDB:6nw2PDB:5hx6PDB:8i2nPDB:4itjPDB:6ocqPDB:6c3ePDB:7fd0 | ||
| NTAN1RIPK1 | Q13546Q96AB6 | 0:0 | hu.MAPhu.MAP2 |
Page 1 of 2Next
Sequence, Structure & Domains
Sequences
Length
671
Mass
75,931
Sequence
MQPDMSLNVIKMKSSDFLESAELDSGGFGKVSLCFHRTQGLMIMKTVYKGPNCIEHNEALLEEAKMMNRLRHSRVVKLLGVIIEEGKYSLVMEYMEKGNLMHVLKAEMSTPLSVKGRIILEIIEGMCYLHGKGVIHKDLKPENILVDNDFHIKIADLGLASFKMWSKLNNEEHNELREVDGTAKKNGGTLYYMAPEHLNDVNAKPTEKSDVYSFAVVLWAIFANKEPYENAICEQQLIMCIKSGNRPDVDDITEYCPREIISLMKLCWEANPEARPTFPGIEEKFRPFYLSQLEESVEEDVKSLKKEYSNENAVVKRMQSLQLDCVAVPSSRSNSATEQPGSLHSSQGLGMGPVEESWFAPSLEHPQEENEPSLQSKLQDEANYHLYGSRMDRQTKQQPRQNVAYNREEERRRRVSHDPFAQQRPYENFQNTEGKGTAYSSAASHGNAVHQPSGLTSQPQVLYQNNGLYSSHGFGTRPLDPGTAGPRVWYRPIPSHMPSLHNIPVPETNYLGNTPTMPFSSLPPTDESIKYTIYNSTGIQIGAYNYMEIGGTSSSLLDSTNTNFKEEPAAKYQAIFDNTTSLTDKHLDPIRENLGKHWKNCARKLGFTQSQIDEIDHDYERDGLKEKVYQMLQKWVMREGIKGATVGKLAQALHQCSRIDLLSSLIYVSQN
Alternative Products
Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=Q13546-1; Sequence=Displayed; Name=2; IsoId=Q13546-2; Sequence=VSP_037690
Alternative Sequence
108..153; Missing (in isoform 2)
3D Structural Models
Turn
37..39; 252..255; 310..312; 619..622
Helix
14..16; 54..56; 57..68; 100..104; 112..131; 141..143; 163..168; 190..192; 195..197; 207..223; 228..230; 234..242; 249..251; 258..267; 272..274; 278..292; 294..296; 297..309; 575..577; 584..593; 599..604; 609..618; 624..643; 646..655; 659..668
Beta Strand
10..12; 17..19; 20..22; 26..28; 30..36; 40..51; 78..84; 87..93; 106..108; 144..146; 152..154; 171..173; 201..203; 533..542
3D Structure
Electron microscopy (1); NMR spectroscopy (1); X-ray crystallography (24)
Domain & Motif Annotations
Compositional Bias
331..348; Polar residues; 428..444; Polar residues
Motif
531..547; RIP homotypic interaction motif (RHIM)
Domain (CC)
The RIP homotypic interaction motif (RHIM) mediates interaction with the RHIM motif of RIPK1. Both motifs form a hetero-amyloid serpentine fold, stabilized by hydrophobic packing and featuring an unusual Cys-Ser ladder of alternating Ser (from RIPK1) and Cys (from RIPK3).; DOMAIN: The death domain mediates dimerization and activation of its kinase activity during necroptosis and apoptosis (PubMed:29440439). It engages other DD-containing proteins as well as a central (intermediate) region important for NF-kB activation and RHIM-dependent signaling (PubMed:10356400).
Domain (FT)
17..289; Protein kinase; 583..669; Death
Region
290..582; Interaction with SQSTM1; 331..354; Disordered; 389..455; Disordered
Protein Families
- Protein kinase superfamily
- TKL Ser/Thr protein kinase family
Sequence Similarities
Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.
Clinical Relevance
Disease Involvement
Disease variant
Related Diseases
Biomarker
Phase 1; Phase 2; Investigative; Phase 1/2; Preclinical
Interaction Protein
ENSG00000023445ENSG00000056558ENSG00000064012ENSG00000067182ENSG00000102871ENSG00000110330ENSG00000114316ENSG00000127191ENSG00000129465ENSG00000131323ENSG00000135046ENSG00000168040ENSG00000269335
Interaction Count
13
Interaction Dataset
intact_biogrid