RIPK3

Receptor-interacting serine/threonine-protein kinase 3 is an enzyme that is encoded by the RIPK3 gene in humans.[5][6][7][8]

RIPK3
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesRIPK3, RIP3, receptor interacting serine/threonine kinase 3
External IDsOMIM: 605817 MGI: 2154952 HomoloGene: 31410 GeneCards: RIPK3
Orthologs
SpeciesHumanMouse
Entrez

11035

56532

Ensembl

ENSG00000129465
ENSG00000285379

ENSMUSG00000022221

UniProt

Q9Y572

Q9QZL0

RefSeq (mRNA)

NM_006871

NM_001164107
NM_001164108
NM_019955

RefSeq (protein)

NP_006862

NP_001157579
NP_001157580
NP_064339

Location (UCSC)Chr 14: 24.34 – 24.34 MbChr 14: 56.02 – 56.03 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

The product of this gene is a member of the receptor-interacting protein (RIP) family of serine/threonine protein kinases. It 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 necroptosis by interaction with RIPK1 and MLKL in a protein complex termed the necrosome.[7] Interactions between RIPK1 and RIPK3 also form a necrosome, which triggers apoptosis.[9]

The red highlighted region of RIPK3 represents the Protein Kinase domain. The cyan region highlights the RIP homotypic interaction motif (RHIM) motif.[10]

Interactions

RIPK3 has been shown to interact with RIPK1 to form an amyloid spine[5][8] The RIP Homotypic Interaction Motifs (RHIM) of RIPK3 allows it to form a necrosome with RIPK1.[9] This interaction makes heterotypic β sheets, which bind together to form an alternating “ladder” of Serine from RIPK1 and Cysteine from RIPK3.[9]

References

  1. ENSG00000285379 GRCh38: Ensembl release 89: ENSG00000129465, ENSG00000285379 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000022221 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Yu PW, Huang BC, Shen M, Quast J, Chan E, Xu X, et al. (May 1999). "Identification of RIP3, a RIP-like kinase that activates apoptosis and NFkappaB". Current Biology. 9 (10): 539–542. doi:10.1016/S0960-9822(99)80239-5. PMID 10339433.
  6. Sun X, Lee J, Navas T, Baldwin DT, Stewart TA, Dixit VM (June 1999). "RIP3, a novel apoptosis-inducing kinase". The Journal of Biological Chemistry. 274 (24): 16871–16875. doi:10.1074/jbc.274.24.16871. PMID 10358032.
  7. "Entrez Gene: RIPK3 receptor-interacting serine-threonine kinase 3".
  8. Li J, McQuade T, Siemer AB, Napetschnig J, Moriwaki K, Hsiao YS, et al. (July 2012). "The RIP1/RIP3 necrosome forms a functional amyloid signaling complex required for programmed necrosis". Cell. 150 (2): 339–350. doi:10.1016/j.cell.2012.06.019. PMC 3664196. PMID 22817896.
  9. Mompeán M, Li W, Li J, Laage S, Siemer AB, Bozkurt G, et al. (May 2018). "The Structure of the Necrosome RIPK1-RIPK3 Core, a Human Hetero-Amyloid Signaling Complex". Cell. 173 (5): 1244–1253.e10. doi:10.1016/j.cell.2018.03.032. PMC 6002806. PMID 29681455.
  10. "RIPK3 - Receptor-interacting serine/threonine-protein kinase 3 - Homo sapiens (Human) - RIPK3 gene & protein". www.uniprot.org. Retrieved 2022-05-13.

Further reading

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