Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Receptor-interacting serine/threonine-protein kinase 1

Gene

Ripk1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Serine-threonine kinase which transduces inflammatory and cell-death signals (programmed necrosis) following death receptors ligation, activation of pathogen recognition receptors (PRRs), and DNA damage. Upon activation of TNFR1 by the TNF-alpha family cytokines, TRADD and TRAF2 are recruited to the receptor. Phosphorylates DAB2IP at 'Ser-728' in a TNF-alpha-dependent manner, and thereby activates the MAP3K5-JNK apoptotic cascade. Ubiquitination by TRAF2 via 'Lys-63'-link chains acts as a critical enhancer of communication with downstream signal transducers in the mitogen-activated protein kinase pathway and the NF-kappa-B pathway, which in turn mediate downstream events including the activation of genes encoding inflammatory molecules. Polyubiquitinated protein binds to IKBKG/NEMO, the regulatory subunit of the IKK complex, a critical event for NF-kappa-B activation. Interaction with other cellular RHIM-containing adapters initiates gene activation and cell death. RIPK1 and RIPK3 association, in particular, forms a necrosis-inducing complex (By similarity). Interacts with ARHGEF2 (By similarity).By similarity2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

Inhibited by necrostatin-1.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei46ATPPROSITE-ProRule annotation1
Active sitei138Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi23 – 31ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

  • activation of JUN kinase activity Source: GO_Central
  • amyloid fibril formation Source: UniProtKB
  • apoptotic process Source: UniProtKB
  • cellular protein catabolic process Source: UniProtKB
  • cellular response to growth factor stimulus Source: UniProtKB
  • cellular response to tumor necrosis factor Source: UniProtKB
  • extrinsic apoptotic signaling pathway Source: MGI
  • necroptotic process Source: MGI
  • necroptotic signaling pathway Source: UniProtKB
  • negative regulation of extrinsic apoptotic signaling pathway Source: MGI
  • negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: UniProtKB
  • negative regulation of I-kappaB kinase/NF-kappaB signaling Source: MGI
  • peptidyl-serine autophosphorylation Source: UniProtKB
  • positive regulation of apoptotic process Source: UniProtKB
  • positive regulation of extrinsic apoptotic signaling pathway Source: MGI
  • positive regulation of hydrogen peroxide-induced cell death Source: MGI
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: MGI
  • positive regulation of interleukin-8 production Source: MGI
  • positive regulation of JNK cascade Source: UniProtKB
  • positive regulation of macrophage differentiation Source: MGI
  • positive regulation of MAPK cascade Source: UniProtKB
  • positive regulation of necroptotic process Source: MGI
  • positive regulation of necrotic cell death Source: MGI
  • positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • positive regulation of phosphorylation Source: UniProtKB
  • positive regulation of programmed cell death Source: MGI
  • positive regulation of protein phosphorylation Source: UniProtKB
  • positive regulation of transcription by RNA polymerase II Source: UniProtKB
  • positive regulation of tumor necrosis factor production Source: MGI
  • protein autophosphorylation Source: MGI
  • protein heterooligomerization Source: UniProtKB
  • protein homooligomerization Source: UniProtKB
  • regulation of ATP:ADP antiporter activity Source: MGI
  • regulation of reactive oxygen species metabolic process Source: MGI
  • response to tumor necrosis factor Source: MGI
  • ripoptosome assembly Source: UniProtKB
  • ripoptosome assembly involved in necroptotic process Source: MGI
  • T cell apoptotic process Source: UniProtKB
  • viral process Source: UniProtKB-KW

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processHost-virus interaction, Necrosis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.2 3474
ReactomeiR-MMU-140534 Ligand-dependent caspase activation
R-MMU-2562578 TRIF-mediated programmed cell death
R-MMU-3295583 TRP channels
R-MMU-3371378 Regulation by c-FLIP
R-MMU-5213460 RIPK1-mediated regulated necrosis
R-MMU-5218900 CASP8 activity is inhibited
R-MMU-5357786 TNFR1-induced proapoptotic signaling
R-MMU-5357905 Regulation of TNFR1 signaling
R-MMU-5357956 TNFR1-induced NFkappaB signaling pathway
R-MMU-5689880 Ub-specific processing proteases
R-MMU-5689896 Ovarian tumor domain proteases
R-MMU-69416 Dimerization of procaspase-8
R-MMU-75893 TNF signaling
R-MMU-937041 IKK complex recruitment mediated by RIP1

Names & Taxonomyi

Protein namesi
Recommended name:
Receptor-interacting serine/threonine-protein kinase 1 (EC:2.7.11.1)
Alternative name(s):
Cell death protein RIP
Receptor-interacting protein 1
Short name:
RIP-1
Serine/threonine-protein kinase RIP
Gene namesi
Name:Ripk1
Synonyms:Rinp, Rip
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 13

Organism-specific databases

MGIiMGI:108212 Ripk1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL3784911

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000866071 – 656Receptor-interacting serine/threonine-protein kinase 1Add BLAST656

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei6PhosphoserineBy similarity1
Modified residuei25PhosphoserineBy similarity1
Modified residuei161Phosphoserine; by RIPK3 and autocatalysisSequence analysis1
Modified residuei166Phosphoserine; by autocatalysisSequence analysis1
Modified residuei304PhosphoserineBy similarity1
Modified residuei313PhosphoserineCombined sources1
Modified residuei321PhosphoserineCombined sources1
Modified residuei334PhosphoserineBy similarity1
Modified residuei383PhosphotyrosineBy similarity1

Post-translational modificationi

Proteolytically cleaved by caspase-8 during TNF-induced apoptosis. Cleavage abolishes NF-kappa-B activation and enhances pro-apoptotic signaling through the TRADD-FADD interaction (By similarity).By similarity
RIPK1 and RIPK3 undergo reciprocal auto- and trans-phosphorylation. Phosphorylation of Ser-161 by RIPK3 is necessary for the formation of the necroptosis-inducing complex (By similarity).By similarity
Ubiquitinated by 'Lys-11'-, 'Lys-48'-, 'Lys-63'- and linear-linked type ubiquitin. Polyubiquitination with 'Lys-63'-linked chains by TRAF2 induces association with the IKK complex. Deubiquitination of 'Lys-63'-linked chains and polyubiquitination with 'Lys-48'-linked chains by TNFAIP3 leads to RIPK1 proteasomal degradation and consequently down-regulates TNF-alpha-induced NFkappa-B signaling. 'Lys-48'-linked polyubiquitination by RFFL or RNF34 also promotes proteasomal degradation and negatively regulates TNF-alpha-induced NFkappa-B signaling. Linear polyubiquitinated; the head-to-tail polyubiquitination is mediated by the LUBAC complex. LPS-mediated activation of NF-kappa-B. Also ubiquitinated with 'Lys-11'-linked chains. Polyubiquitinated with 'Lys-48' and 'Lys-63'-linked chains by BIRC2/c-IAP1 and BIRC3/c-IAP2, leading to activation of NF-kappa-B.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ60855
MaxQBiQ60855
PaxDbiQ60855
PeptideAtlasiQ60855
PRIDEiQ60855

PTM databases

iPTMnetiQ60855
PhosphoSitePlusiQ60855

Expressioni

Tissue specificityi

Found at low levels in all tissues.

Inductioni

In concanavalin A-treated splenocytes.

Gene expression databases

BgeeiENSMUSG00000021408
ExpressionAtlasiQ60855 baseline and differential
GenevisibleiQ60855 MM

Interactioni

Subunit structurei

Interacts (via RIP homotypic interaction motif) with RIPK3 (via RIP homotypic interaction motif). Upon TNF-induced necrosis, the RIPK1-RIPK3 dimer further interacts with PGAM5 and MLKL; the formation of this complex leads to PGAM5 phosphorylation and increase in PGAM5 phosphatase activity. Interacts (via kinase domain) with DAB2IP (via Ras-GAP domain); the interaction occurs in a TNF-alpha-dependent manner (By similarity). Interacts (via the death domain) with TNFRSF6 (via the death domain) and TRADD (via the death domain). Is recruited by TRADD to TNFRSF1A in a TNF-dependent process. Binds RNF216, EGFR, IKBKG, TRAF1, TRAF2 and TRAF3. Interacts with BNLF1. Interacts with SQSTM1 upon TNF-alpha stimulation. May interact with MAVS/IPS1. Interacts with ZFAND5. Interacts with RBCK1 (By similarity). Interacts (via RIP homotypic interaction motif) with murid herpesvirus 1 viral inhibitor of RIP activation; this interaction inhibits RIPK1 ubiquitination. Interacts with BIRC2/c-IAP1, BIRC3/c-IAP2 and XIAP/BIRC4 (By similarity). Interacts with ARHGEF2 (By similarity). Interacts (via protein kinase domain) with RFFL; involved in RIPK1 ubiquitination (By similarity). Interacts with RNF34; involved in RIPK1 ubiquitination (By similarity). Interacts with ZBP1. Interacts with TICAM1 and this interaction is enhanced in the presence of WDFY1 (By similarity).By similarity1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi202896, 18 interactors
DIPiDIP-34962N
IntActiQ60855, 24 interactors
MINTiQ60855
STRINGi10090.ENSMUSP00000021844

Chemistry databases

BindingDBiQ60855

Structurei

3D structure databases

ProteinModelPortaliQ60855
SMRiQ60855
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini17 – 290Protein kinasePROSITE-ProRule annotationAdd BLAST274
Domaini568 – 654DeathPROSITE-ProRule annotationAdd BLAST87

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni291 – 567Interaction with SQSTM1Add BLAST277

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi520 – 536RIP homotypic interaction motif (RHIM)Add BLAST17

Domaini

Contains a C-terminal death domain (DD) that engages other DD-containing proteins as well as a central (intermediate) region important for NF-kB activation and RHIM-dependent signaling.

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0192 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00550000074536
HOGENOMiHOG000010270
HOVERGENiHBG055612
InParanoidiQ60855
KOiK02861
OMAiVMEYMEK
OrthoDBiEOG091G0479
PhylomeDBiQ60855
TreeFamiTF106506

Family and domain databases

CDDicd08777 Death_RIP1, 1 hit
InterProiView protein in InterPro
IPR011029 DEATH-like_dom_sf
IPR000488 Death_domain
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR025735 RHIM_dom
IPR037934 RIP1_Death
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00531 Death, 1 hit
PF07714 Pkinase_Tyr, 1 hit
PF12721 RHIM, 1 hit
PRINTSiPR00109 TYRKINASE
SMARTiView protein in SMART
SM00005 DEATH, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF47986 SSF47986, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50017 DEATH_DOMAIN, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequencei

Sequence statusi: Complete.

Q60855-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQPDMSLDNI KMASSDLLEK TDLDSGGFGK VSLCYHRSHG FVILKKVYTG
60 70 80 90 100
PNRAEYNEVL LEEGKMMHRL RHSRVVKLLG IIIEEGNYSL VMEYMEKGNL
110 120 130 140 150
MHVLKTQIDV PLSLKGRIIV EAIEGMCYLH DKGVIHKDLK PENILVDRDF
160 170 180 190 200
HIKIADLGVA SFKTWSKLTK EKDNKQKEVS STTKKNNGGT LYYMAPEHLN
210 220 230 240 250
DINAKPTEKS DVYSFGIVLW AIFAKKEPYE NVICTEQFVI CIKSGNRPNV
260 270 280 290 300
EEILEYCPRE IISLMERCWQ AIPEDRPTFL GIEEEFRPFY LSHFEEYVEE
310 320 330 340 350
DVASLKKEYP DQSPVLQRMF SLQHDCVPLP PSRSNSEQPG SLHSSQGLQM
360 370 380 390 400
GPVEESWFSS SPEYPQDEND RSVQAKLQEE ASYHAFGIFA EKQTKPQPRQ
410 420 430 440 450
NEAYNREEER KRRVSHDPFA QQRARENIKS AGARGHSDPS TTSRGIAVQQ
460 470 480 490 500
LSWPATQTVW NNGLYNQHGF GTTGTGVWYP PNLSQMYSTY KTPVPETNIP
510 520 530 540 550
GSTPTMPYFS GPVADDLIKY TIFNSSGIQI GNHNYMDVGL NSQPPNNTCK
560 570 580 590 600
EESTSRHQAI FDNTTSLTDE HLNPIRENLG RQWKNCARKL GFTESQIDEI
610 620 630 640 650
DHDYERDGLK EKVYQMLQKW LMREGTKGAT VGKLAQALHQ CCRIDLLNHL

IRASQS
Length:656
Mass (Da):74,854
Last modified:November 1, 1997 - v1
Checksum:iABB350B523879933
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti66M → K in BAC27194 (PubMed:16141072).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti473T → I. 1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U25995 mRNA Translation: AAB60487.1
AK030959 mRNA Translation: BAC27194.1
AK156803 mRNA Translation: BAE33860.1
BC050905 mRNA Translation: AAH50905.2
BC054542 mRNA Translation: AAH54542.1
BC058162 mRNA Translation: AAH58162.1
CCDSiCCDS26443.1
PIRiI49299
RefSeqiNP_033094.3, NM_009068.3
XP_006516670.1, XM_006516607.3
XP_006516672.1, XM_006516609.3
UniGeneiMm.374799

Genome annotation databases

EnsembliENSMUST00000021844; ENSMUSP00000021844; ENSMUSG00000021408
ENSMUST00000167374; ENSMUSP00000129831; ENSMUSG00000021408
GeneIDi19766
KEGGimmu:19766
UCSCiuc007qax.1 mouse

Similar proteinsi

Entry informationi

Entry nameiRIPK1_MOUSE
AccessioniPrimary (citable) accession number: Q60855
Secondary accession number(s): Q3U0J3, Q8CD90
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: May 23, 2018
This is version 180 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health