RIPK3
Receptor-interacting serine/threonine-protein kinase 3
Also known as: RIP3, RIPK3_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q9Y572
- Gene
- RIPK3
- Ensembl
- ENSG00000129465
- Chromosome
- 14
- Canonical length
- 518 aa
- Protein class
- Enzymes, Predicted intracellular proteins, Transporters
OverviewNCBI Gene
The product of this gene is a member of the receptor-interacting protein (RIP) family of serine/threonine protein kinases, and contains a C-terminal domain unique from other RIP family members. The encoded protein is predominantly localized to the cytoplasm, and can undergo nucleocytoplasmic shuttling dependent on novel nuclear localization and export signals. It is a component of the tumor necrosis factor (TNF) receptor-I signaling complex, and can induce apoptosis and weakly activate the NF-kappaB transcription factor. [provided by RefSeq, Jul 2008]
Canonical amino-acid sequenceUniProt
518 residues, UniProt reviewed canonical sequence.
>Q9Y572|RIPK3
1 MSCVKLWPSG APAPLVSIEE LENQELVGKG GFGTVFRAQH RKWGYDVAVK IVNSKAISRE
61 VKAMASLDNE FVLRLEGVIE KVNWDQDPKP ALVTKFMENG SLSGLLQSQC PRPWPLLCRL
121 LKEVVLGMFY LHDQNPVLLH RDLKPSNVLL DPELHVKLAD FGLSTFQGGS QSGTGSGEPG
181 GTLGYLAPEL FVNVNRKAST ASDVYSFGIL MWAVLAGREV ELPTEPSLVY EAVCNRQNRP
241 SLAELPQAGP ETPGLEGLKE LMQLCWSSEP KDRPSFQECL PKTDEVFQMV ENNMNAAVST
301 VKDFLSQLRS SNRRFSIPES GQGGTEMDGF RRTIENQHSR NDVMVSEWLN KLNLEEPPSS
361 VPKKCPSLTK RSRAQEEQVP QAWTAGTSSD SMAQPPQTPE TSTFRNQMPS PTSTGTPSPG
421 PRGNQGAERQ GMNWSCRTPE PNPVTGRPLV NIYNCSGVQV GDNNYLTMQQ TTALPTWGLA
481 PSGKGRGLQH PPPVGSQEGP KDPEAWSRPQ GWYNHSGKLocalizationUniProt · AlphaFold · HPA
Whether an antibody against RIPK3 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.44
- Highest tissue expression
- 19 nTPM
Expression across tissuesHPA
Tissue
- spleen: 19 nTPM
- small intestine: 19 nTPM
- colon: 15 nTPM
- esophagus: 12 nTPM
- thyroid gland: 11 nTPM
- stomach: 11 nTPM
Single-cell type
- microglia: 4.2 nCPM
- foveolar cells: 3.2 nCPM
- kupffer cells: 3.1 nCPM
- colonocytes: 2.8 nCPM
- enterocytes: 2.7 nCPM
- neuroendocrine cells: 2.6 nCPM
Immune cell
- T-reg: 6.1 nTPM
- non-classical monocyte: 6 nTPM
- intermediate monocyte: 5.1 nTPM
- eosinophil: 4.2 nTPM
- MAIT T-cell: 3.9 nTPM
- gdT-cell: 3.7 nTPM
Brain region
- medulla oblongata: 1.8 nTPM
- pons: 1.5 nTPM
- thalamus: 1.4 nTPM
- white matter: 1.4 nTPM
- choroid plexus: 0.9 nTPM
- spinal cord: 0.9 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about RIPK3.
Disease | ImmuneIEDB
Conditions an epitope on RIPK3 was assayed in.
- prostate cancer B cell
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 1.37
- gnomAD pLI
- 0
- gnomAD missense Z
- 0.02
- DepMap mean gene effect
- -0.22
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- activation of protein kinase activity
- amyloid fibril formation
- apoptotic signaling pathway
- cellular response to hydrogen peroxide
- defense response to virus
- execution phase of necroptosis
- lymph node development
- necroptotic process
- necroptotic signaling pathway
- non-canonical NF-kappaB signal transduction
- positive regulation of intrinsic apoptotic signaling pathway
- positive regulation of necroptotic process
- positive regulation of NF-kappaB transcription factor activity
- positive regulation of reactive oxygen species metabolic process
- programmed necrotic cell death
- protein modification process
- reactive oxygen species metabolic process
- regulation of activated T cell proliferation
- regulation of adaptive immune response
- regulation of apoptotic process
- regulation of T cell mediated cytotoxicity
- regulation of type II interferon production
- ripoptosome assembly involved in necroptotic process
- signal transduction
- spleen development
- T cell differentiation in thymus
- T cell homeostasis
- thymus development
- regulation of activation-induced cell death of T cells
- regulation of CD8-positive, alpha-beta cytotoxic T cell extravasation
Molecular functions
- ATP binding
- identical protein binding
- protein kinase activity
- protein serine kinase activity
- protein serine/threonine kinase activity
- protein serine/threonine kinase binding
- protein-containing complex binding
- transcription coactivator activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of RIPK3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads RIPK3 as an antibody target. Whether an autoantibody or antibody against RIPK3 could matter depends on whether native RIPK3 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
RIPK3 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label RIPK3 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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