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 confidence score 0.50 |
Supporting publications (n) 1 | Transmembrane count | Protein classification Disease related genesEnzymesHuman disease related genesPotential drug targetsPredicted intracellular proteins |
EVMP confidence score
Annotation confidence score; open for threshold definitions.
Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40Basic Information11
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 (5)
Disease related genesEnzymesHuman disease related genesPotential drug targetsPredicted intracellular proteins
Protein Function (8)
- 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 (3)
RIPRIP-1RIP1
Gene Description
Receptor interacting serine/threonine kinase 1
Chromosome
6
Position
3063824-3115187
Supporting publications (n)
1
EVMP confidence score
0.50
Fluorescence & Localization5
Tissue Specificlymphoid tissueCell SpecificB-cellsSingle-Nuclei Brain SpecificleukocyteBlood Lineage SpecificB-cells
Function & Pathway7
Protein Function (8)
- 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 (9)
Molecular Function (14)
- 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
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Biological Process (3)
KEGG (16)
- 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
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Reactome (42)
- 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
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Mediation Categories (5)
Clinical-translation mediationFusion and delivery mediationImmune mediationMetabolism mediationReceptor-signaling mediation
Relations & Evidence78
Enzyme-Mediated Modification (25)
25 records.
| Substrate Gene Symbol | Enzyme Gene Symbol | Enzyme UniProt ID | Residue Type | Residue Offset | Modification | Database | References |
|---|---|---|---|---|---|---|---|
| RIPK1 | TRAF2 | Q12933 | K | 377 | ubiquitination | SIGNOR | SIGNOR:9712898SIGNOR:21232017SIGNOR:18621737SIGNOR:8702708 |
| RIPK1 | CASP8 | Q14790 | D | 324 | cleavage | HPRDSIGNOR | SIGNOR:10521396HPRD:10521396HPRD:12215447 |
| RIPK1 | BIRC3 | Q13489 | K | 377 | ubiquitination | SIGNOR | SIGNOR:18570872SIGNOR:16603398SIGNOR:18621737 |
| RIPK1 | MAPKAPK2 | P49137 | S | 320 | phosphorylation | Sparser_ProtMapperProtMapperRLIMS-P_ProtMapperREACH_ProtMapperPhosphoSitePhosphoSite_ProtMapper | ProtMapper:29452637ProtMapper:29642005ProtMapper:29471568ProtMapper:28506461 |
| RIPK1 | MAPKAPK2 | P49137 | S | 166 | phosphorylation | Sparser_ProtMapperProtMapper | ProtMapper:29452637 |
| RIPK1 | MAPKAPK2 | P49137 | S | 335 | phosphorylation | REACH_ProtMapperSparser_ProtMapperProtMapper | ProtMapper:29452637ProtMapper:29642005 |
| RIPK1 | ULK1 | O75385 | T | 337 | phosphorylation | PhosphoSite | |
| RIPK1 | ULK1 | O75385 | S | 296 | phosphorylation | PhosphoSite | |
| RIPK1 | ULK1 | O75385 | S | 335 | phosphorylation | PhosphoSite | |
| RIPK1 | ULK1 | O75385 | S | 291 | phosphorylation | PhosphoSite |
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Ligand-Receptor Signaling (10)
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)
31 records.
Protein Complex Composition (11)
Sequence, Structure & Domains16
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 (2)
- Protein kinase superfamily
- TKL Ser/Thr protein kinase family
Sequence Similarities
Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.
Clinical Relevance8
Disease Involvement
Disease variant
Related Diseases (11)
Biomarker
Phase 1; Phase 2; Investigative; Phase 1/2; Preclinical
Drugs (3)
Interaction Protein (13)
ENSG00000023445ENSG00000056558ENSG00000064012ENSG00000067182ENSG00000102871ENSG00000110330ENSG00000114316ENSG00000127191ENSG00000129465ENSG00000131323ENSG00000135046ENSG00000168040ENSG00000269335
Interaction Count
13
Interaction Dataset
intact_biogrid
Supporting Publications1
| PMID | Title | Abstract |
|---|---|---|
| 31753726 | Serum extracellular vesicles contain SPARC and LRG1 as biomarkers of colon cancer and differ by tumour primary location. | No abstract available |