RIPK1 receptor interacting serine/threonine kinase 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: RIPK1provided by HGNC
Official Full Name: receptor interacting serine/threonine kinase 1provided by HGNC
Primary source: HGNC:HGNC:10019
See related: Ensembl:ENSG00000137275 MIM:603453; AllianceGenome:HGNC:10019
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: RIP; RIP1; AIEFL; IMD57; RIP-1
Summary: This gene encodes a member of the receptor-interacting protein (RIP) family of serine/threonine protein kinases. The encoded protein plays a role in inflammation and cell death in response to tissue damage, pathogen recognition, and as part of developmental regulation. RIPK1/RIPK3 kinase-mediated necrosis is referred to as necroptosis. Genetic disruption of this gene in mice results in death shortly after birth. [provided by RefSeq, Aug 2017]
Expression: Ubiquitous expression in gall bladder (RPKM 7.8), colon (RPKM 7.5) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 6p25.2

Exon count:: 18

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (3063967..3115187)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (2932866..2983225)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (3064201..3115421)

Chromosome 6 - NC_000006.12 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.
Elevated peripheral levels of receptor-interacting protein kinase 1 (RIPK1) and IL-8 as biomarkers of human amyotrophic lateral sclerosis.
Title: Elevated peripheral levels of receptor-interacting protein kinase 1 (RIPK1) and IL-8 as biomarkers of human amyotrophic lateral sclerosis.
Caspase 6 promotes innate immune activation by functional crosstalk between RIPK1-IkappaBalpha axis in liver inflammation.
Title: Caspase 6 promotes innate immune activation by functional crosstalk between RIPK1-IκBα axis in liver inflammation.
RIPK1 kinase-dependent inflammation and cell death contribute to the pathogenesis of COPD.
Title: RIPK1 kinase-dependent inflammation and cell death contribute to the pathogenesis of COPD.
O-GlcNAcylation of RIPK1 rescues red blood cells from necroptosis.
Title: O-GlcNAcylation of RIPK1 rescues red blood cells from necroptosis.
IKK-mediated TRAF6 and RIPK1 interaction stifles cell death complex assembly leading to the suppression of TNF-alpha-induced cell death.
Title: IKK-mediated TRAF6 and RIPK1 interaction stifles cell death complex assembly leading to the suppression of TNF-α-induced cell death.
RIPK1-dependent necroptosis promotes vasculogenic mimicry formation via eIF4E in triple-negative breast cancer.
Title: RIPK1-dependent necroptosis promotes vasculogenic mimicry formation via eIF4E in triple-negative breast cancer.
RNF31 promotes tumorigenesis via inhibiting RIPK1 kinase-dependent apoptosis.
Title: RNF31 promotes tumorigenesis via inhibiting RIPK1 kinase-dependent apoptosis.
Upregulation of RIPK1 implicates in HEK 293T cell death upon transient transfection of A53T-alpha-synuclein.
Title: Upregulation of RIPK1 implicates in HEK 293T cell death upon transient transfection of A53T-α-synuclein.
Human ZBP1 induces cell death-independent inflammatory signaling via RIPK3 and RIPK1.
Title: Human ZBP1 induces cell death-independent inflammatory signaling via RIPK3 and RIPK1.

Submit: New GeneRIF Correction See all GeneRIFs (247)

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

Associated conditions

Description	Tests
Autoinflammation with episodic fever and lymphadenopathy MedGen: C5394286 OMIM: 618852 GeneReviews: Not available	Compare labs
Immunodeficiency 57 MedGen: C4748212 OMIM: 618108 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
A genome-wide association meta-analysis of preschool internalizing problems. 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
Vpr	vpr	Overexpression of RIPK1 is induced by HIV-1 Vpr in the transfected 293T cells	PubMed
retropepsin	gag-pol	PR cleavage of RIPK1 disrupts RIPK1 function	PubMed
	gag-pol	Majority of RIPK1 cleavage occurs due to post-integration expression of proviral genes (not by virion delivered PR) and is completely inhibited with the addiition of Saquinavir (PR inhibitor)	PubMed
	gag-pol	HIV-1 PR (WT, not D25N) cleaves endogeneously expressed (and over-expressed) RIPK1 with high specificity (RIPK1 amino acids L462-Y463)	PubMed
	gag-pol	HIV-1 PR (D25N) binds RIPK1	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH48319 (e-PCR)
- UniSTS:8024

D6S1338 (e-PCR)
- UniSTS:14974

D6S1199E (e-PCR)
- UniSTS:34000

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables JUN kinase kinase kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables death domain binding	IPI Inferred from Physical Interaction more info	PubMed
enables death receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
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 kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
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 protein serine/threonine kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables protein serine/threonine kinase activity	TAS Traceable Author Statement more info
enables protein-containing complex binding	IDA Inferred from Direct Assay more info	PubMed
enables signaling adaptor activity	IEA Inferred from Electronic Annotation more info
enables ubiquitin protein ligase binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in MAPK cascade	IEA Inferred from Electronic Annotation more info
involved_in T cell apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in amyloid fibril formation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to growth factor stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to hydrogen peroxide	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to tumor necrosis factor	IDA Inferred from Direct Assay more info	PubMed
involved_in extrinsic apoptotic signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in extrinsic apoptotic signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in inflammatory response	IEA Inferred from Electronic Annotation more info
involved_in intracellular signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in necroptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in necroptotic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in necroptotic process	TAS Traceable Author Statement more info
involved_in necroptotic signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in necroptotic signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of canonical NF-kappaB signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of extrinsic apoptotic signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of extrinsic apoptotic signaling pathway in absence of ligand	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of necroptotic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in peptidyl-serine autophosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in peptidyl-serine autophosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of JNK cascade	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 apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
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	IEP Inferred from Expression Pattern more info	PubMed
involved_in positive regulation of execution phase of apoptosis	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of extrinsic apoptotic signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of gene expression	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of inflammatory response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of interleukin-6-mediated signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of interleukin-8 production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of macrophage differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of positive regulation of miRNA processing	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of necroptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of neuron apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of non-canonical NF-kappaB signal transduction	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of programmed cell death	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of programmed necrotic cell death	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of protein phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of reactive oxygen species metabolic process	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of tumor necrosis factor production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of tumor necrosis factor-mediated signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in programmed necrotic cell death	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein autophosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in protein autophosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of ATP:ADP antiporter activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to oxidative stress	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to tumor necrosis factor	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in ripoptosome assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in ripoptosome assembly involved in necroptotic process	IEA Inferred from Electronic Annotation more info
involved_in tumor necrosis factor-mediated signaling pathway	IC Inferred by Curator more info	PubMed

Component	Evidence Code	Pubs
located_in cytosol	TAS Traceable Author Statement more info
part_of death-inducing signaling complex	IDA Inferred from Direct Assay more info	PubMed
located_in endosome membrane	TAS Traceable Author Statement more info
located_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed
part_of receptor complex	IDA Inferred from Direct Assay more info	PubMed
part_of ripoptosome	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: receptor-interacting serine/threonine-protein kinase 1

Names: cell death protein RIP; receptor (TNFRSF)-interacting serine-threonine kinase 1; receptor-interacting protein 1; receptor-interacting protein kinase 1; serine/threonine-protein kinase RIP

NP_001303990.1

EC 2.7.11.1

NP_001341859.1

EC 2.7.11.1

NP_001341860.1

EC 2.7.11.1

NP_001341861.1

EC 2.7.11.1

NP_001341862.1

EC 2.7.11.1

NP_001341863.1

EC 2.7.11.1

NP_003795.2

EC 2.7.11.1

XP_006715300.2

EC 2.7.11.1

XP_016866892.1

EC 2.7.11.1

XP_016866893.1

EC 2.7.11.1

XP_016866894.1

EC 2.7.11.1

XP_047275401.1

EC 2.7.11.1

XP_047275402.1

EC 2.7.11.1

XP_047275403.1

EC 2.7.11.1

XP_047275404.1

EC 2.7.11.1

XP_054212622.1

EC 2.7.11.1

XP_054212623.1

EC 2.7.11.1

XP_054212624.1

EC 2.7.11.1

XP_054212625.1

EC 2.7.11.1

XP_054212626.1

EC 2.7.11.1

XP_054212627.1

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_063914.1 RefSeqGene

Range

9654..56347

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001317061.3 → NP_001303990.1 receptor-interacting serine/threonine-protein kinase 1 isoform 2

Status: REVIEWED

Source sequence(s)

AB208926, AJ420482, AK314176, AL031963

Conserved Domains (2) summary

cd08777
Location:420 → 505

Death_RIP1; Death Domain of Receptor-Interacting Protein 1

cl21453
Location:1 → 127

PKc_like; Protein Kinases, catalytic domain
NM_001354930.2 → NP_001341859.1 receptor-interacting serine/threonine-protein kinase 1 isoform 1

Status: REVIEWED

Source sequence(s)

AL031963

Consensus CDS

CCDS4482.1

UniProtKB/Swiss-Prot

A0AV89, B2RAG1, B4E3F9, Q13180, Q13546, Q59H33

Related

ENSP00000259808.3, ENST00000259808.9

Conserved Domains (2) summary

cd08777
Location:583 → 668

Death_RIP1; Death Domain of Receptor-Interacting Protein 1

cd14027
Location:23 → 290

STKc_RIP1; Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1
NM_001354931.2 → NP_001341860.1 receptor-interacting serine/threonine-protein kinase 1 isoform 3

Status: REVIEWED

Source sequence(s)

AL031963

Consensus CDS

CCDS93851.1

Related

ENSP00000369773.3, ENST00000380409.3

Conserved Domains (2) summary

cd08777
Location:537 → 622

Death_RIP1; Death Domain of Receptor-Interacting Protein 1

cl21453
Location:23 → 244

PKc_like; Protein Kinases, catalytic domain
NM_001354932.2 → NP_001341861.1 receptor-interacting serine/threonine-protein kinase 1 isoform 2

Status: REVIEWED

Source sequence(s)

AL031963

Conserved Domains (2) summary

cd08777
Location:420 → 505

Death_RIP1; Death Domain of Receptor-Interacting Protein 1

cl21453
Location:1 → 127

PKc_like; Protein Kinases, catalytic domain
NM_001354933.2 → NP_001341862.1 receptor-interacting serine/threonine-protein kinase 1 isoform 2

Status: REVIEWED

Source sequence(s)

AL031963

Conserved Domains (2) summary

cd08777
Location:420 → 505

Death_RIP1; Death Domain of Receptor-Interacting Protein 1

cl21453
Location:1 → 127

PKc_like; Protein Kinases, catalytic domain
NM_001354934.2 → NP_001341863.1 receptor-interacting serine/threonine-protein kinase 1 isoform 2

Status: REVIEWED

Source sequence(s)

AL031963

Conserved Domains (2) summary

cd08777
Location:420 → 505

Death_RIP1; Death Domain of Receptor-Interacting Protein 1

cl21453
Location:1 → 127

PKc_like; Protein Kinases, catalytic domain
NM_003804.6 → NP_003795.2 receptor-interacting serine/threonine-protein kinase 1 isoform 1

See identical proteins and their annotated locations for NP_003795.2

Status: REVIEWED

Source sequence(s)

AB208926, AJ420482, AK314176, AL031963, U50062

Consensus CDS

CCDS4482.1

UniProtKB/Swiss-Prot

A0AV89, B2RAG1, B4E3F9, Q13180, Q13546, Q59H33

Related

ENST00000676758.1

Conserved Domains (2) summary

cd08777
Location:583 → 668

Death_RIP1; Death Domain of Receptor-Interacting Protein 1

cd14027
Location:23 → 290

STKc_RIP1; Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1

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_000006.12 Reference GRCh38.p14 Primary Assembly

Range

3063967..3115187

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047419447.1 → XP_047275403.1 receptor-interacting serine/threonine-protein kinase 1 isoform X1

UniProtKB/Swiss-Prot

A0AV89, B2RAG1, B4E3F9, Q13180, Q13546, Q59H33
XM_047419448.1 → XP_047275404.1 receptor-interacting serine/threonine-protein kinase 1 isoform X1

UniProtKB/Swiss-Prot

A0AV89, B2RAG1, B4E3F9, Q13180, Q13546, Q59H33
XM_017011405.2 → XP_016866894.1 receptor-interacting serine/threonine-protein kinase 1 isoform X2

Related

ENST00000676995.1

Conserved Domains (2) summary

smart00221
Location:22 → 285

STYKc; Protein kinase; unclassified specificity

cd14027
Location:23 → 290

STKc_RIP1; Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1
XM_006715237.4 → XP_006715300.2 receptor-interacting serine/threonine-protein kinase 1 isoform X2

Conserved Domains (2) summary

smart00221
Location:22 → 285

STYKc; Protein kinase; unclassified specificity

cd14027
Location:23 → 290

STKc_RIP1; Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1
XM_047419445.1 → XP_047275401.1 receptor-interacting serine/threonine-protein kinase 1 isoform X5
XM_047419446.1 → XP_047275402.1 receptor-interacting serine/threonine-protein kinase 1 isoform X5
XM_017011403.2 → XP_016866892.1 receptor-interacting serine/threonine-protein kinase 1 isoform X3

Conserved Domains (2) summary

cd08777
Location:420 → 505

Death_RIP1; Death Domain of Receptor-Interacting Protein 1

cl21453
Location:1 → 127

PKc_like; Protein Kinases, catalytic domain
XM_017011404.3 → XP_016866893.1 receptor-interacting serine/threonine-protein kinase 1 isoform X4

Alternate T2T-CHM13v2.0

Genomic

NC_060930.1 Alternate T2T-CHM13v2.0

Range

2932866..2983225

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054356647.1 → XP_054212622.1 receptor-interacting serine/threonine-protein kinase 1 isoform X1

UniProtKB/Swiss-Prot

A0AV89, B2RAG1, B4E3F9, Q13180, Q13546, Q59H33
XM_054356652.1 → XP_054212627.1 receptor-interacting serine/threonine-protein kinase 1 isoform X2
XM_054356648.1 → XP_054212623.1 receptor-interacting serine/threonine-protein kinase 1 isoform X2
XM_054356650.1 → XP_054212625.1 receptor-interacting serine/threonine-protein kinase 1 isoform X6
XM_054356649.1 → XP_054212624.1 receptor-interacting serine/threonine-protein kinase 1 isoform X3
XM_054356651.1 → XP_054212626.1 receptor-interacting serine/threonine-protein kinase 1 isoform X4