Ripk2 receptor (TNFRSF)-interacting serine-threonine kinase 2 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Ripk2provided by MGI
Official Full Name: receptor (TNFRSF)-interacting serine-threonine kinase 2provided by MGI
Primary source: MGI:MGI:1891456
See related: Ensembl:ENSMUSG00000041135 AllianceGenome:MGI:1891456
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: CCK; RICK; RIP2; CARD3; CARDIAK; D4Bwg0615e; 2210420D18Rik
Summary: This gene encodes a member of the receptor-interacting protein family of serine/threonine protein kinases. The encoded protein contains a C-terminal caspase activation and recruitment domain, and is a component of signaling complexes in both the innate and adaptive immune pathways. It is a potent activator of nuclear factor kappa B and inducer of apoptosis in response to various stimuli. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]
Expression: Ubiquitous expression in ovary adult (RPKM 9.1), adrenal adult (RPKM 8.0) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 4 A2; 4 6.7 cM

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	4	NC_000070.7 (16122740..16163674, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	4	NC_000070.6 (16122732..16163678, complement)

Chromosome 4 - NC_000070.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

LACC1 Promoted Nerve Injury in an Anesthesia-Induced Cognitive Disorder Model via RIP2 Expression through ROS-NOD2 Induction.
Title: LACC1 Promoted Nerve Injury in an Anesthesia-Induced Cognitive Disorder Model via RIP2 Expression through ROS-NOD2 Induction.
Pharmacological inhibition of receptor-interacting protein kinase 2 (RIPK2) elicits neuroprotective effects following experimental ischemic stroke.
Title: Pharmacological inhibition of receptor-interacting protein kinase 2 (RIPK2) elicits neuroprotective effects following experimental ischemic stroke.
Receptor-interacting protein kinase 2 (RIPK2) profoundly contributes to post-stroke neuroinflammation and behavioral deficits with microglia as unique perpetrators.
Title: Receptor-interacting protein kinase 2 (RIPK2) profoundly contributes to post-stroke neuroinflammation and behavioral deficits with microglia as unique perpetrators.
The Ubiquitination of RIPK2 is Mediated by Peli3 and Negatively Regulates the Onset of Infectious Osteomyelitis.
Title: The Ubiquitination of RIPK2 is Mediated by Peli3 and Negatively Regulates the Onset of Infectious Osteomyelitis.
Ubiquitin-Specific Peptidase 8 Is Critical for the Onset of Infectious Osteomyelitis by Targeting RIPK2 Ubiquitination.
Title: Ubiquitin-Specific Peptidase 8 Is Critical for the Onset of Infectious Osteomyelitis by Targeting RIPK2 Ubiquitination.
Receptor-interacting protein kinase 2 contributes to host innate immune responses against Fusobacterium nucleatum in macrophages and decidual stromal cells.
Title: Receptor-interacting protein kinase 2 contributes to host innate immune responses against Fusobacterium nucleatum in macrophages and decidual stromal cells.
ASK1 disrupts the RIPK2 signaling complex and inhibits the NOD-RIPK2 pathway to downregulate the production of inflammatory cytokines.
Title: ASKA technology-based pull-down method reveals a suppressive effect of ASK1 on the inflammatory NOD-RIPK2 pathway in brown adipocytes.
Immune Modulation of Allergic Asthma by Early Pharmacological Inhibition of RIP2.
Title: Immune Modulation of Allergic Asthma by Early Pharmacological Inhibition of RIP2.
Innate Immune Nod1/RIP2 Signaling Is Essential for Cardiac Hypertrophy but Requires Mitochondrial Antiviral Signaling Protein for Signal Transductions and Energy Balance.
Title: Innate Immune Nod1/RIP2 Signaling Is Essential for Cardiac Hypertrophy but Requires Mitochondrial Antiviral Signaling Protein for Signal Transductions and Energy Balance.
NOD1/RIP2 signalling enhances the microglia-driven inflammatory response and undergoes crosstalk with inflammatory cytokines to exacerbate brain damage following intracerebral haemorrhage in mice.
Title: NOD1/RIP2 signalling enhances the microglia-driven inflammatory response and undergoes crosstalk with inflammatory cytokines to exacerbate brain damage following intracerebral haemorrhage in mice.

Submit: New GeneRIF Correction See all GeneRIFs (79)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (3) 1 citation
Targeted (4) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D4Bwg0615e (e-PCR), detects polymorphism
- UniSTS:142445

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables 3-phosphoinositide-dependent protein kinase activity	IEA Inferred from Electronic Annotation more info
enables AMP-activated protein kinase activity	IEA Inferred from Electronic Annotation more info
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables CARD domain binding	ISO Inferred from Sequence Orthology more info
enables DNA-dependent protein kinase activity	IEA Inferred from Electronic Annotation more info
enables JUN kinase kinase kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables LIM domain binding	IEA Inferred from Electronic Annotation more info
enables LIM domain binding	ISO Inferred from Sequence Orthology more info
enables Rho-dependent protein serine/threonine kinase activity	IEA Inferred from Electronic Annotation more info
enables caspase binding	IEA Inferred from Electronic Annotation more info
enables caspase binding	ISO Inferred from Sequence Orthology more info
enables eukaryotic translation initiation factor 2alpha kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AS1 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AS121 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AT120 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AXS139 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AXY142 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2BS14 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2BS36 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3S10 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3S28 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3S57 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T11 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T3 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T45 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T6 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3Y41 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H4S1 kinase activity	IEA Inferred from Electronic Annotation more info
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables non-membrane spanning protein tyrosine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein homodimerization activity	IEA Inferred from Electronic Annotation more info
enables protein homodimerization activity	ISO Inferred from Sequence Orthology more info
enables protein serine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables ribosomal protein S6 kinase activity	IEA Inferred from Electronic Annotation more info
enables signaling adaptor activity	ISO Inferred from Sequence Orthology more info
enables signaling adaptor activity	ISS Inferred from Sequence or Structural Similarity more info
enables signaling receptor binding	IEA Inferred from Electronic Annotation more info
enables signaling receptor binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
acts_upstream_of CD4-positive, alpha-beta T cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in ERK1 and ERK2 cascade	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of ERK1 and ERK2 cascade	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of ERK1 and ERK2 cascade	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in JNK cascade	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of JNK cascade	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within T cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within T cell receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in T cell receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in activation of cysteine-type endopeptidase activity	ISO Inferred from Sequence Orthology more info
involved_in adaptive immune response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in canonical NF-kappaB signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cellular response to lipopolysaccharide	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cellular response to lipoteichoic acid	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to muramyl dipeptide	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to muramyl dipeptide	ISO Inferred from Sequence Orthology more info
involved_in cellular response to muramyl dipeptide	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within cellular response to peptidoglycan	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of chemokine production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
acts_upstream_of cytokine-mediated signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within defense response to Gram-positive bacterium	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in defense response to bacterium	ISO Inferred from Sequence Orthology more info
acts_upstream_of immature T cell proliferation in thymus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in innate immune response	IBA Inferred from Biological aspect of Ancestor more info
involved_in innate immune response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in innate immune response	ISO Inferred from Sequence Orthology more info
acts_upstream_of interleukin-2 production	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of interleukin-6 production	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within lipopolysaccharide-mediated signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of macrophage cytokine production	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within nucleotide-binding oligomerization domain containing 1 signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in nucleotide-binding oligomerization domain containing 1 signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in nucleotide-binding oligomerization domain containing 2 signaling pathway	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within nucleotide-binding oligomerization domain containing 2 signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in nucleotide-binding oligomerization domain containing 2 signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in nucleotide-binding oligomerization domain containing 2 signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within positive regulation of CD4-positive, alpha-beta T cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of ERK1 and ERK2 cascade	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within positive regulation of ERK1 and ERK2 cascade	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of JNK cascade	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of NF-kappaB transcription factor activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of NF-kappaB transcription factor activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of NF-kappaB transcription factor activity	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of NF-kappaB transcription factor activity	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within positive regulation of T-helper 1 cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of T-helper 1 type immune response	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of canonical NF-kappaB signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of canonical NF-kappaB signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of canonical NF-kappaB signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of canonical NF-kappaB signal transduction	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of chemokine production	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of cytokine-mediated signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of immature T cell proliferation in thymus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of interleukin-1 beta production	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of interleukin-1 beta production	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of interleukin-2 production	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of interleukin-6 production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of interleukin-6 production	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of macrophage cytokine production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of peptidyl-serine phosphorylation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of peptidyl-serine phosphorylation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of peptidyl-threonine phosphorylation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of peptidyl-threonine phosphorylation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of peptidyl-tyrosine phosphorylation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of peptidyl-tyrosine phosphorylation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of protein K63-linked ubiquitination	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of protein K63-linked ubiquitination	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of protein binding	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of protein ubiquitination	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of stress-activated MAPK cascade	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of tumor necrosis factor production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of tumor necrosis factor production	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of type II interferon production	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of xenophagy	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein homooligomerization	IEA Inferred from Electronic Annotation more info
involved_in protein homooligomerization	ISO Inferred from Sequence Orthology more info
NOT acts_upstream_of_or_within regulation of cysteine-type endopeptidase activity	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to exogenous dsRNA	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to interleukin-1	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to interleukin-12	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to interleukin-18	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of stress-activated MAPK cascade	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within toll-like receptor 2 signaling pathway	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within toll-like receptor 4 signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of tumor necrosis factor production	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of type II interferon production	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of xenophagy	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
located_in cytoskeleton	ISO Inferred from Sequence Orthology more info
located_in cytoskeleton	ISS Inferred from Sequence or Structural Similarity more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in cytosol	TAS Traceable Author Statement more info
located_in endoplasmic reticulum	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	ISO Inferred from Sequence Orthology more info
is_active_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
part_of protein-containing complex	ISO Inferred from Sequence Orthology more info
part_of protein-containing complex	ISS Inferred from Sequence or Structural Similarity more info
located_in vesicle	ISO Inferred from Sequence Orthology more info
located_in vesicle	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: receptor-interacting serine/threonine-protein kinase 2

Names: receptor-interacting protein 2; tyrosine-protein kinase RIPK2

NP_001316680.1

EC 2.7.10.2

EC 2.7.11.1

NP_620402.1

EC 2.7.10.2

EC 2.7.11.1

XP_006537740.1

EC 2.7.10.2

EC 2.7.11.1

XP_006537741.1

EC 2.7.10.2

EC 2.7.11.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001329751.1 → NP_001316680.1 receptor-interacting serine/threonine-protein kinase 2 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) contains an alternate internal exon, compared to variant 1. This difference causes translation initiation at a downstream AUG and results in an isoform (2) with a shorter N-terminus, compared to isoform 1.

Source sequence(s)

AL807379, BC058088

Conserved Domains (2) summary

cd08786
Location:300 → 385

CARD_RIP2_CARD3; Caspase activation and recruitment domain of Receptor Interacting Protein 2

cl21453
Location:1 → 166

PKc_like; Protein Kinases, catalytic domain
NM_138952.4 → NP_620402.1 receptor-interacting serine/threonine-protein kinase 2 isoform 1

See identical proteins and their annotated locations for NP_620402.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the shortest transcript and encodes the longest isoform (1).

Source sequence(s)

AL807379, BC058088

Consensus CDS

CCDS17988.1

UniProtKB/Swiss-Prot

P58801

UniProtKB/TrEMBL

Q547H1

Related

ENSMUSP00000038833.6, ENSMUST00000037035.12

Conserved Domains (2) summary

cd08786
Location:437 → 522

CARD_RIP2_CARD3; Caspase activation and recruitment domain of Receptor Interacting Protein 2

cd14026
Location:20 → 303

STKc_RIP2; Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 2

RNA

NR_138102.1 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (3) contains an alternate internal exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AL807379, BC058088

Related

ENSMUST00000183871.2

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000070.7 Reference GRCm39 C57BL/6J

Range

16122740..16163674 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006537678.4 → XP_006537741.1 receptor-interacting serine/threonine-protein kinase 2 isoform X2

Conserved Domains (2) summary

cd08786
Location:300 → 385

CARD_RIP2_CARD3; Caspase activation and recruitment domain of Receptor Interacting Protein 2

cl21453
Location:1 → 166

PKc_like; Protein Kinases, catalytic domain
XM_006537677.5 → XP_006537740.1 receptor-interacting serine/threonine-protein kinase 2 isoform X1

Conserved Domains (2) summary

cd08786
Location:385 → 470

CARD_RIP2_CARD3; Caspase activation and recruitment domain of Receptor Interacting Protein 2

cl21453
Location:20 → 251

PKc_like; Protein Kinases, catalytic domain