RIPK2 receptor interacting serine/threonine kinase 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: RIPK2provided by HGNC
Official Full Name: receptor interacting serine/threonine kinase 2provided by HGNC
Primary source: HGNC:HGNC:10020
See related: Ensembl:ENSG00000104312 MIM:603455; AllianceGenome:HGNC:10020
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CCK; RICK; RIP2; CARD3; GIG30; CARDIAK
Summary: This gene encodes a member of the receptor-interacting protein (RIP) family of serine/threonine protein kinases. The encoded protein contains a C-terminal caspase activation and recruitment domain (CARD), and is a component of signaling complexes in both the innate and adaptive immune pathways. It is a potent activator of NF-kappaB and inducer of apoptosis in response to various stimuli. [provided by RefSeq, Jul 2008]
Expression: Broad expression in bone marrow (RPKM 26.8), gall bladder (RPKM 8.2) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 8q21.3

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	8	NC_000008.11 (89757816..89791064)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	8	NC_060932.1 (90880976..90914226)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	8	NC_000008.10 (90770044..90803292)

Chromosome 8 - NC_000008.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Simultaneous substrate and ubiquitin modification recognition by bispecific antibodies enables detection of ubiquitinated RIP1 and RIP2.
Title: Simultaneous substrate and ubiquitin modification recognition by bispecific antibodies enables detection of ubiquitinated RIP1 and RIP2.
NOD1 cooperates with HAX-1 to promote cell migration in a RIPK2- and NF-kB-independent manner.
Title: NOD1 cooperates with HAX-1 to promote cell migration in a RIPK2- and NF-ĸB-independent manner.
Mechanism of Human Cytomegalovirus-Induced Epithelial-Mesenchymal Transition in Glioma Cells via the Upregulation of RIP2 Expression.
Title: Mechanism of Human Cytomegalovirus-Induced Epithelial-Mesenchymal Transition in Glioma Cells via the Upregulation of RIP2 Expression.
Paired protein kinases PRKCI-RIPK2 promote pancreatic cancer growth and metastasis via enhancing NF-kappaB/JNK/ERK phosphorylation.
Title: Paired protein kinases PRKCI-RIPK2 promote pancreatic cancer growth and metastasis via enhancing NF-κB/JNK/ERK phosphorylation.
Expression and Prognostic Value of PIK3CA, VEGF, IL-8, IL-10, and RIP2 in Diffuse Large B-Cell Lymphoma.
Title: Expression and Prognostic Value of PIK3CA, VEGF, IL-8, IL-10, and RIP2 in Diffuse Large B-Cell Lymphoma.
Mechanism of RIP2 enhancing stemness of glioma cells induces temozolomide resistance.
Title: Mechanism of RIP2 enhancing stemness of glioma cells induces temozolomide resistance.
RIP2 Knockdown Attenuates Vascular Smooth Muscle Cells Activation via Negative Regulating Myocardin Expression.
Title: RIP2 Knockdown Attenuates Vascular Smooth Muscle Cells Activation via Negative Regulating Myocardin Expression.
Pan-cancer analysis reveals RIPK2 predicts prognosis and promotes immune therapy resistance via triggering cytotoxic T lymphocytes dysfunction.
Title: Pan-cancer analysis reveals RIPK2 predicts prognosis and promotes immune therapy resistance via triggering cytotoxic T lymphocytes dysfunction.
High expression of RIPK2 is associated with Taxol resistance in serous ovarian cancer.
Title: High expression of RIPK2 is associated with Taxol resistance in serous ovarian cancer.
A pancancer analysis of the carcinogenic role of receptor-interacting serine/threonine protein kinase-2 (RIPK2) in human tumours.
Title: A pancancer analysis of the carcinogenic role of receptor-interacting serine/threonine protein kinase-2 (RIPK2) in human tumours.

Submit: New GeneRIF Correction See all GeneRIFs (102)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Common genetic variation and performance on standardized cognitive tests. EBI GWAS Catalog EBI GWAS CatalogPubMed
Discovery of six new susceptibility loci and analysis of pleiotropic effects in leprosy. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genomewide association study of leprosy. EBI GWAS Catalog EBI GWAS CatalogPubMed
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
retropepsin	gag-pol	HIV-1 PR (WT, not D25N) cleaves over-expressed RIPK2 with high specificity and this cleavage is prevent by addition of Saquinavir (protease inhibitor)	PubMed
	gag-pol	HIV-1 PR (D25N) binds RIPK2	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables CARD domain binding	IDA Inferred from Direct Assay more info	PubMed
enables CARD domain binding	IPI Inferred from Physical Interaction more info	PubMed
enables JUN kinase kinase kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables LIM domain binding	IPI Inferred from Physical Interaction more info	PubMed
enables caspase binding	IPI Inferred from Physical Interaction more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables non-membrane spanning protein tyrosine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed
enables protein serine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein serine/threonine kinase activity	ISS Inferred from Sequence or Structural Similarity more info
enables protein serine/threonine kinase activity	TAS Traceable Author Statement more info
enables signaling adaptor activity	IDA Inferred from Direct Assay more info	PubMed
enables signaling receptor binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in CD4-positive, alpha-beta T cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in ERK1 and ERK2 cascade	IEA Inferred from Electronic Annotation more info
involved_in JNK cascade	IEA Inferred from Electronic Annotation more info
involved_in T cell receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in T cell receptor signaling pathway	TAS Traceable Author Statement more info
involved_in activation of cysteine-type endopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in adaptive immune response	ISS Inferred from Sequence or Structural Similarity more info
involved_in apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in canonical NF-kappaB signal transduction	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to lipoteichoic acid	IEA Inferred from Electronic Annotation more info
involved_in cellular response to muramyl dipeptide	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to peptidoglycan	IEA Inferred from Electronic Annotation more info
involved_in cytokine-mediated signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in defense response to Gram-positive bacterium	IEA Inferred from Electronic Annotation more info
involved_in defense response to bacterium	IDA Inferred from Direct Assay more info	PubMed
involved_in immature T cell proliferation in thymus	IEA Inferred from Electronic Annotation more info
involved_in inflammatory response	TAS Traceable Author Statement more info	PubMed
involved_in innate immune response	IBA Inferred from Biological aspect of Ancestor more info
involved_in innate immune response	IDA Inferred from Direct Assay more info	PubMed
involved_in innate immune response	ISS Inferred from Sequence or Structural Similarity more info
involved_in lipopolysaccharide-mediated signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in nucleotide-binding oligomerization domain containing 1 signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in nucleotide-binding oligomerization domain containing 2 signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of CD4-positive, alpha-beta T cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of ERK1 and ERK2 cascade	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of JNK cascade	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of NF-kappaB transcription factor activity	IDA Inferred from Direct Assay 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 T-helper 1 cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of T-helper 1 type immune response	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of canonical NF-kappaB signal transduction	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within positive regulation of canonical NF-kappaB signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of chemokine production	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cytokine-mediated signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of immature T cell proliferation in thymus	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of interferon-alpha production	NAS Non-traceable Author Statement more info	PubMed
involved_in positive regulation of interferon-beta production	NAS Non-traceable Author Statement more info	PubMed
involved_in positive regulation of interleukin-1 beta production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of interleukin-12 production	NAS Non-traceable Author Statement more info	PubMed
involved_in positive regulation of interleukin-2 production	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of interleukin-6 production	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of macrophage cytokine production	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of peptidyl-serine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of peptidyl-threonine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of peptidyl-tyrosine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of protein K63-linked ubiquitination	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of protein binding	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of protein ubiquitination	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of protein ubiquitination	NAS Non-traceable Author Statement more info	PubMed
involved_in positive regulation of stress-activated MAPK cascade	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of transcription by RNA polymerase II	NAS Non-traceable Author Statement more info	PubMed
involved_in positive regulation of tumor necrosis factor production	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of type II interferon production	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of xenophagy	IEA Inferred from Electronic Annotation more info
involved_in protein homooligomerization	IDA Inferred from Direct Assay more info	PubMed
involved_in response to exogenous dsRNA	IEA Inferred from Electronic Annotation more info
involved_in response to interleukin-1	IEA Inferred from Electronic Annotation more info
involved_in response to interleukin-12	IEA Inferred from Electronic Annotation more info
involved_in response to interleukin-18	IEA Inferred from Electronic Annotation more info
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in stress-activated MAPK cascade	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within toll-like receptor 2 signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in toll-like receptor 4 signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in xenophagy	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoskeleton	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay 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	IDA Inferred from Direct Assay more info	PubMed
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed
part_of protein-containing complex	IMP Inferred from Mutant Phenotype more info	PubMed
located_in vesicle	IDA Inferred from Direct Assay more info	PubMed

General protein information

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

Names: CARD-carrying kinase; CARD-containing IL-1 beta ICE-kinase; CARD-containing interleukin-1 beta-converting enzyme (ICE)-associated kinase; RIP-2; growth-inhibiting gene 30; receptor-interacting protein (RIP)-like interacting caspase-like apoptosis regulatory protein (CLARP) kinase; receptor-interacting protein 2; tyrosine-protein kinase RIPK2

NP_001362289.1

EC 2.7.10.2

EC 2.7.11.1

NP_003812.1

EC 2.7.10.2

EC 2.7.11.1

XP_011515659.1

EC 2.7.10.2

EC 2.7.11.1

XP_054217414.1

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.

Genomic

NG_033016.2 RefSeqGene

Range

5070..38318

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001375360.1 → NP_001362289.1 receptor-interacting serine/threonine-protein kinase 2 isoform 2

Status: REVIEWED

Source sequence(s)

AF117829

Conserved Domains (2) summary

cd08786
Location:301 → 387

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

cl21453
Location:1 → 166

PKc_like; Protein Kinases, catalytic domain
NM_003821.6 → NP_003812.1 receptor-interacting serine/threonine-protein kinase 2 isoform 1

See identical proteins and their annotated locations for NP_003812.1

Status: REVIEWED

Source sequence(s)

AI824070, AY358814

Consensus CDS

CCDS6247.1

UniProtKB/Swiss-Prot

B7Z748, O43353, Q6UWF0

UniProtKB/TrEMBL

A0A0S2Z4Z8, Q2TU65

Related

ENSP00000220751.4, ENST00000220751.5

Conserved Domains (2) summary

cd08786
Location:438 → 524

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

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000008.11 Reference GRCh38.p14 Primary Assembly

Range

89757816..89791064

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011517357.3 → XP_011515659.1 receptor-interacting serine/threonine-protein kinase 2 isoform X1

Conserved Domains (2) summary

cd08786
Location:267 → 353

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

cl21453
Location:1 → 132

PKc_like; Protein Kinases, catalytic domain