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
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:: 16

Annotation release	Status	Assembly	Chr	Location
109.20201120	current	GRCh38.p13 (GCF_000001405.39)	6	NC_000006.12 (3063967..3115187)
105	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?

Ubiquitination of RIPK1 regulates its activation mediated by TNFR1 and TLRs signaling in distinct manners.
Title: Ubiquitination of RIPK1 regulates its activation mediated by TNFR1 and TLRs signaling in distinct manners.
RIPK1 polymorphisms alter the susceptibility to cervical Cancer among the Uyghur population in China.
Title: RIPK1 polymorphisms alter the susceptibility to cervical Cancer among the Uyghur population in China.
The Trend of ripk1/ripk3 and mlkl Mediated Necroptosis Pathway in Patients with Different Stages of Prostate Cancer as Promising Progression Biomarkers.
Title: The Trend of ripk1/ripk3 and mlkl Mediated Necroptosis Pathway in Patients with Different Stages of Prostate Cancer as Promising Progression Biomarkers.
Identification of MYC as an antinecroptotic protein that stifles RIPK1-RIPK3 complex formation.
Title: Identification of MYC as an antinecroptotic protein that stifles RIPK1-RIPK3 complex formation.
[Correlation of NK cell RIPK1 with Prognosis of Acute Myeloid Leukemia Patients with FLT3-ITD Mutation].
Title: [Correlation of NK cell RIPK1 with Prognosis of Acute Myeloid Leukemia Patients with FLT3-ITD Mutation].
Changes in plasma levels of RIPK1, RIPK3, and MLKL in patients with coronary atherosclerotic heart disease and its clinical predictive value.", trans "RIPK1RIPK3MLKL.
Title: Changes in plasma levels of RIPK1, RIPK3, and MLKL in patients with coronary atherosclerotic heart disease and its clinical predictive value.
MuicroRNA421 participates in vitiligo development through regulating human melanocyte survival by targeting receptorinteracting serine/threonine kinase 1.
Title: ΜicroRNA‑421 participates in vitiligo development through regulating human melanocyte survival by targeting receptor‑interacting serine/threonine kinase 1.
Dectin-1-induced RIPK1 and RIPK3 activation protects host against Candida albicans infection.
Title: Dectin-1-induced RIPK1 and RIPK3 activation protects host against Candida albicans infection.
TAK1 suppresses RIPK1-dependent cell death and is associated with disease progression in melanoma.
Title: TAK1 suppresses RIPK1-dependent cell death and is associated with disease progression in melanoma.
The anticonvulsive Phenhydan((R)) suppresses extrinsic cell death.
Title: The anticonvulsive Phenhydan<sup>®</sup> suppresses extrinsic cell death.

Submit: New GeneRIF Correction See all GeneRIFs (192)

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
A genome-wide association meta-analysis of preschool internalizing problems. GeneReviews: Not available
AUTOINFLAMMATION WITH EPISODIC FEVER AND LYMPHADENOPATHY MedGen: C5394286 OMIM: 618852 GeneReviews: Not available	not available
Immunodeficiency 57 MedGen: C4748212 OMIM: 618108 GeneReviews: Not available	Compare labs

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

Homology

Homologs of the RIPK1 gene: The RIPK1 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 338 organisms have orthologs with human gene RIPK1
Orthologs

Gene Ontology Provided by GOA

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

Process	Evidence Code	Pubs
I-kappaB kinase/NF-kappaB signaling	TAS Traceable Author Statement more info
MyD88-independent toll-like receptor signaling pathway	TAS Traceable Author Statement more info
T cell apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
TRIF-dependent toll-like receptor signaling pathway	TAS Traceable Author Statement more info
activation of JNKK activity	IEA Inferred from Electronic Annotation more info
activation of JUN kinase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
activation of JUN kinase activity	TAS Traceable Author Statement more info	PubMed
activation of cysteine-type endopeptidase activity involved in apoptotic process	TAS Traceable Author Statement more info
amyloid fibril formation	IMP Inferred from Mutant Phenotype more info	PubMed
apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
apoptotic signaling pathway	TAS Traceable Author Statement more info
cell death	IMP Inferred from Mutant Phenotype more info	PubMed
cellular protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
cellular response to hydrogen peroxide	ISS Inferred from Sequence or Structural Similarity more info
cellular response to tumor necrosis factor	IDA Inferred from Direct Assay more info	PubMed
death-inducing signaling complex assembly	TAS Traceable Author Statement more info
extrinsic apoptotic signaling pathway	IDA Inferred from Direct Assay more info	PubMed
extrinsic apoptotic signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
inflammatory response	IEA Inferred from Electronic Annotation more info
necroptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
necroptotic process	ISS Inferred from Sequence or Structural Similarity more info
necroptotic process	TAS Traceable Author Statement more info
necroptotic signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
necroptotic signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of I-kappaB kinase/NF-kappaB signaling	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of extrinsic apoptotic signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of extrinsic apoptotic signaling pathway via death domain receptors	TAS Traceable Author Statement more info
negative regulation of necroptotic process	ISS Inferred from Sequence or Structural Similarity more info
peptidyl-serine autophosphorylation	IDA Inferred from Direct Assay more info	PubMed
peptidyl-serine autophosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of I-kappaB kinase/NF-kappaB signaling	IDA Inferred from Direct Assay more info	PubMed
positive regulation of I-kappaB kinase/NF-kappaB signaling	IEP Inferred from Expression Pattern more info	PubMed
positive regulation of JNK cascade	IDA Inferred from Direct Assay more info	PubMed
positive regulation of NF-kappaB transcription factor activity	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of apoptotic process	IDA Inferred from Direct Assay more info	PubMed
positive regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of extrinsic apoptotic signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of hydrogen peroxide-induced cell death	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of inflammatory response	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of interleukin-6-mediated signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of interleukin-8 production	IDA Inferred from Direct Assay more info	PubMed
positive regulation of macrophage differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of necroptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of necrotic cell death	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of production of miRNAs involved in gene silencing by miRNA	IDA Inferred from Direct Assay more info	PubMed
positive regulation of programmed cell death	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of protein phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of reactive oxygen species metabolic process	TAS Traceable Author Statement more info	PubMed
positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
positive regulation of tumor necrosis factor production	IDA Inferred from Direct Assay more info	PubMed
programmed necrotic cell death	ISS Inferred from Sequence or Structural Similarity more info
protein autophosphorylation	IDA Inferred from Direct Assay more info	PubMed
protein autophosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
protein deubiquitination	TAS Traceable Author Statement more info
regulation of ATP:ADP antiporter activity	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of extrinsic apoptotic signaling pathway via death domain receptors	TAS Traceable Author Statement more info
regulation of tumor necrosis factor-mediated signaling pathway	TAS Traceable Author Statement more info
response to tumor necrosis factor	IMP Inferred from Mutant Phenotype more info	PubMed
ripoptosome assembly	IMP Inferred from Mutant Phenotype more info	PubMed
toll-like receptor 3 signaling pathway	TAS Traceable Author Statement more info
tumor necrosis factor-mediated signaling pathway	IC Inferred by Curator more info	PubMed
tumor necrosis factor-mediated signaling pathway	TAS Traceable Author Statement more info
viral process	IEA Inferred from Electronic Annotation more info

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

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

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

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

Q13546

UniProtKB/TrEMBL

A0A024QZU0

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: Homo sapiens Updated Annotation Release 109.20201120

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

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000006.12 Reference GRCh38.p13 Primary Assembly

Range

3063967..3115187

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017011405.1 → XP_016866894.1 receptor-interacting serine/threonine-protein kinase 1 isoform X1

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_006715237.3 → XP_006715300.2 receptor-interacting serine/threonine-protein kinase 1 isoform X1

Related

ENST00000678084.1

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_017011403.1 → XP_016866892.1 receptor-interacting serine/threonine-protein kinase 1 isoform X2

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_017011404.2 → XP_016866893.1 receptor-interacting serine/threonine-protein kinase 1 isoform X3