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Protein

Receptor-interacting serine/threonine-protein kinase 1

Gene

RIPK1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.4 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.1 Publication

Enzyme regulationi

Inhibited by necrostatins, including necrostatin-1, necrostatin-3 and necrostatin-4.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei49ATPPROSITE-ProRule annotation1
Active sitei138Proton acceptorPROSITE-ProRule annotation1

Regions

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

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • death domain binding Source: BHF-UCL
  • death receptor binding Source: BHF-UCL
  • identical protein binding Source: IntAct
  • protein complex binding Source: UniProtKB
  • protein kinase activity Source: UniProtKB
  • protein serine/threonine kinase activity Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB

GO - Biological processi

  • activation of cysteine-type endopeptidase activity involved in apoptotic process Source: Reactome
  • activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway Source: Reactome
  • activation of JUN kinase activity Source: BHF-UCL
  • amyloid fibril formation Source: UniProtKB
  • apoptotic process Source: UniProtKB
  • apoptotic signaling pathway Source: Reactome
  • cellular protein catabolic process Source: UniProtKB
  • cellular response to growth factor stimulus Source: Ensembl
  • cellular response to tumor necrosis factor Source: UniProtKB
  • death-inducing signaling complex assembly Source: Reactome
  • extrinsic apoptotic signaling pathway Source: BHF-UCL
  • I-kappaB kinase/NF-kappaB signaling Source: Reactome
  • necroptotic process Source: UniProtKB
  • necroptotic signaling pathway Source: UniProtKB
  • negative regulation of extrinsic apoptotic signaling pathway Source: UniProtKB
  • negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: Ensembl
  • negative regulation of extrinsic apoptotic signaling pathway via death domain receptors Source: Reactome
  • negative regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • peptidyl-serine autophosphorylation Source: UniProtKB
  • positive regulation of apoptotic process Source: UniProtKB
  • positive regulation of extrinsic apoptotic signaling pathway Source: UniProtKB
  • positive regulation of hydrogen peroxide-induced cell death Source: BHF-UCL
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • positive regulation of interleukin-8 production Source: BHF-UCL
  • positive regulation of JNK cascade Source: UniProtKB
  • positive regulation of macrophage differentiation Source: UniProtKB
  • positive regulation of necroptotic process Source: UniProtKB
  • positive regulation of necrotic cell death Source: BHF-UCL
  • positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • positive regulation of programmed cell death Source: UniProtKB
  • positive regulation of protein phosphorylation Source: UniProtKB
  • positive regulation of reactive oxygen species metabolic process Source: BHF-UCL
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • positive regulation of tumor necrosis factor production Source: BHF-UCL
  • protein autophosphorylation Source: BHF-UCL
  • protein heterooligomerization Source: UniProtKB
  • protein homooligomerization Source: UniProtKB
  • regulation of ATP:ADP antiporter activity Source: BHF-UCL
  • regulation of extrinsic apoptotic signaling pathway via death domain receptors Source: Reactome
  • regulation of necrotic cell death Source: Reactome
  • regulation of tumor necrosis factor-mediated signaling pathway Source: Reactome
  • response to tumor necrosis factor Source: BHF-UCL
  • ripoptosome assembly Source: UniProtKB
  • ripoptosome assembly involved in necroptotic process Source: Ensembl
  • T cell apoptotic process Source: UniProtKB
  • TRIF-dependent toll-like receptor signaling pathway Source: Reactome
  • tumor necrosis factor-mediated signaling pathway Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Necrosis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS06304-MONOMER.
BRENDAi2.7.10.2. 2681.
ReactomeiR-HSA-140534. Ligand-dependent caspase activation.
R-HSA-1810476. RIP-mediated NFkB activation via ZBP1.
R-HSA-2562578. TRIF-mediated programmed cell death.
R-HSA-3295583. TRP channels.
R-HSA-3371378. Regulation by c-FLIP.
R-HSA-5213460. RIPK1-mediated regulated necrosis.
R-HSA-5218900. CASP8 activity is inhibited.
R-HSA-5357786. TNFR1-induced proapoptotic signaling.
R-HSA-5357905. Regulation of TNFR1 signaling.
R-HSA-5357956. TNFR1-induced NFkappaB signaling pathway.
R-HSA-5675482. Regulation of necroptotic cell death.
R-HSA-5689880. Ub-specific processing proteases.
R-HSA-5689896. Ovarian tumor domain proteases.
R-HSA-69416. Dimerization of procaspase-8.
R-HSA-75893. TNF signaling.
R-HSA-933543. NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10.
R-HSA-937041. IKK complex recruitment mediated by RIP1.
SignaLinkiQ13546.
SIGNORiQ13546.

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:RIP, RIP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:10019. RIPK1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: HPA
  • cytosol Source: Reactome
  • death-inducing signaling complex Source: BHF-UCL
  • membrane raft Source: Ensembl
  • mitochondrion Source: BHF-UCL
  • receptor complex Source: BHF-UCL
  • ripoptosome Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi45K → A: Abolishes kinase activity. 1 Publication1
Mutagenesisi161S → A: Decreases RIPK1 kinase activity. 1 Publication1
Mutagenesisi161S → E: No effect on RIPK1 autophosphorylation. 1 Publication1
Mutagenesisi324D → K: Abolishes cleavage by caspase-8. 1 Publication1
Mutagenesisi377K → R: Abolishes RIP-mediated NF-Kappa-B activation. 1 Publication1

Organism-specific databases

DisGeNETi8737.
OpenTargetsiENSG00000137275.
PharmGKBiPA34394.

Chemistry databases

ChEMBLiCHEMBL5464.
GuidetoPHARMACOLOGYi2189.

Polymorphism and mutation databases

BioMutaiRIPK1.
DMDMi60393639.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000866061 – 671Receptor-interacting serine/threonine-protein kinase 1Add BLAST671

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei6Phosphoserine1 Publication1
Modified residuei20Phosphoserine; by autocatalysisSequence analysis1
Modified residuei25Phosphoserine1 Publication1
Modified residuei161Phosphoserine; by RIPK3 and autocatalysisSequence analysis1
Modified residuei166Phosphoserine; by autocatalysisSequence analysis1
Modified residuei303Phosphoserine1 Publication1
Modified residuei320PhosphoserineCombined sources1 Publication1
Modified residuei333Phosphoserine1 Publication1
Modified residuei384PhosphotyrosineCombined sources1

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.1 Publication
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.2 Publications
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.6 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei324 – 325Cleavage; by caspase-82

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ13546.
MaxQBiQ13546.
PaxDbiQ13546.
PeptideAtlasiQ13546.
PRIDEiQ13546.

PTM databases

iPTMnetiQ13546.
PhosphoSitePlusiQ13546.

Miscellaneous databases

PMAP-CutDBQ13546.

Expressioni

Gene expression databases

BgeeiENSG00000137275.
CleanExiHS_RIPK1.
ExpressionAtlasiQ13546. baseline and differential.
GenevisibleiQ13546. HS.

Organism-specific databases

HPAiCAB010302.
HPA015257.

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 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 with ZBP1 (By similarity). Interacts with BIRC2/c-IAP1, BIRC3/c-IAP2 and XIAP/BIRC4. Upon TNF-induced necrosis, forms in complex with PGAM5, RIPK3 and MLKL. Interacts (via kinase domain) with DAB2IP (via Ras-GAP domain); the interaction occurs in a TNF-alpha-dependent manner. Interacts with ARHGEF2. Interacts (via protein kinase domain) with RFFL; involved in RIPK1 ubiquitination. Interacts with RNF34; involved in RIPK1 ubiquitination. Interacts with TICAM1 and this interaction is enhanced in the presence of WDFY1 (PubMed:25736436).By similarity20 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself8EBI-358507,EBI-358507
ANXA1P040835EBI-358507,EBI-354007
BIRC2Q134903EBI-358507,EBI-514538
BIRC3Q134893EBI-358507,EBI-517709
CASP10Q928512EBI-358507,EBI-495095
CASP8Q1479024EBI-358507,EBI-78060
CCDC50Q8IVM02EBI-358507,EBI-723996
CSNK1A1P487295EBI-358507,EBI-1383726
FADDQ131589EBI-358507,EBI-494804
IKBKGQ9Y6K97EBI-358507,EBI-81279
PYCARDQ9ULZ32EBI-358507,EBI-751215
RIPK3Q9Y57226EBI-358507,EBI-298250
Ripk3Q9QZL02EBI-358507,EBI-2367423From a different organism.
TNFRSF1AP194386EBI-358507,EBI-299451
TRAF1Q130775EBI-358507,EBI-359224
TRAF2Q129336EBI-358507,EBI-355744
UL39U5TQE93EBI-358507,EBI-11894787From a different organism.
USP4Q131074EBI-358507,EBI-723290

GO - Molecular functioni

  • death domain binding Source: BHF-UCL
  • death receptor binding Source: BHF-UCL
  • identical protein binding Source: IntAct
  • protein complex binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi114274. 79 interactors.
DIPiDIP-433N.
IntActiQ13546. 38 interactors.
MINTiMINT-128219.
STRINGi9606.ENSP00000259808.

Chemistry databases

BindingDBiQ13546.

Structurei

Secondary structure

1671
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi14 – 16Combined sources3
Beta strandi17 – 19Combined sources3
Beta strandi20 – 22Combined sources3
Turni26 – 28Combined sources3
Beta strandi30 – 36Combined sources7
Turni37 – 39Combined sources3
Beta strandi40 – 51Combined sources12
Helixi54 – 56Combined sources3
Helixi57 – 68Combined sources12
Beta strandi78 – 84Combined sources7
Beta strandi87 – 93Combined sources7
Helixi100 – 104Combined sources5
Beta strandi106 – 108Combined sources3
Helixi112 – 131Combined sources20
Helixi141 – 143Combined sources3
Beta strandi144 – 146Combined sources3
Beta strandi152 – 154Combined sources3
Helixi163 – 168Combined sources6
Beta strandi171 – 173Combined sources3
Helixi190 – 192Combined sources3
Helixi195 – 197Combined sources3
Beta strandi201 – 203Combined sources3
Helixi207 – 223Combined sources17
Helixi234 – 242Combined sources9
Helixi249 – 251Combined sources3
Helixi258 – 267Combined sources10
Helixi272 – 274Combined sources3
Helixi278 – 292Combined sources15
Helixi294 – 296Combined sources3
Helixi297 – 309Combined sources13
Turni310 – 312Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4ITHX-ray2.25A/B1-294[»]
4ITIX-ray2.86A/B1-294[»]
4ITJX-ray1.80A/B1-294[»]
4NEUX-ray2.57A/B1-324[»]
5HX6X-ray2.23A/B1-294[»]
ProteinModelPortaliQ13546.
SMRiQ13546.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini17 – 289Protein kinasePROSITE-ProRule annotationAdd BLAST273
Domaini583 – 669DeathPROSITE-ProRule annotationAdd BLAST87

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni290 – 582Interaction with SQSTM11 PublicationAdd BLAST293

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi531 – 547RIP homotypic interaction motif (RHIM)Add BLAST17

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi411 – 414Poly-Arg4

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.1 Publication

Sequence similaritiesi

Contains 1 death domain.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0192. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00550000074536.
HOGENOMiHOG000010270.
HOVERGENiHBG055612.
InParanoidiQ13546.
KOiK02861.
OMAiVVKRMQS.
OrthoDBiEOG091G0479.
PhylomeDBiQ13546.
TreeFamiTF106506.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
InterProiIPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR025735. RHIM_dom.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00531. Death. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF12721. RHIM. 1 hit.
[Graphical view]
PRINTSiPR00109. TYRKINASE.
SMARTiSM00005. DEATH. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50017. DEATH_DOMAIN. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q13546-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MQPDMSLNVI KMKSSDFLES AELDSGGFGK VSLCFHRTQG LMIMKTVYKG
60 70 80 90 100
PNCIEHNEAL LEEAKMMNRL RHSRVVKLLG VIIEEGKYSL VMEYMEKGNL
110 120 130 140 150
MHVLKAEMST PLSVKGRIIL EIIEGMCYLH GKGVIHKDLK PENILVDNDF
160 170 180 190 200
HIKIADLGLA SFKMWSKLNN EEHNELREVD GTAKKNGGTL YYMAPEHLND
210 220 230 240 250
VNAKPTEKSD VYSFAVVLWA IFANKEPYEN AICEQQLIMC IKSGNRPDVD
260 270 280 290 300
DITEYCPREI ISLMKLCWEA NPEARPTFPG IEEKFRPFYL SQLEESVEED
310 320 330 340 350
VKSLKKEYSN ENAVVKRMQS LQLDCVAVPS SRSNSATEQP GSLHSSQGLG
360 370 380 390 400
MGPVEESWFA PSLEHPQEEN EPSLQSKLQD EANYHLYGSR MDRQTKQQPR
410 420 430 440 450
QNVAYNREEE RRRRVSHDPF AQQRPYENFQ NTEGKGTAYS SAASHGNAVH
460 470 480 490 500
QPSGLTSQPQ VLYQNNGLYS SHGFGTRPLD PGTAGPRVWY RPIPSHMPSL
510 520 530 540 550
HNIPVPETNY LGNTPTMPFS SLPPTDESIK YTIYNSTGIQ IGAYNYMEIG
560 570 580 590 600
GTSSSLLDST NTNFKEEPAA KYQAIFDNTT SLTDKHLDPI RENLGKHWKN
610 620 630 640 650
CARKLGFTQS QIDEIDHDYE RDGLKEKVYQ MLQKWVMREG IKGATVGKLA
660 670
QALHQCSRID LLSSLIYVSQ N
Length:671
Mass (Da):75,931
Last modified:February 1, 2005 - v3
Checksum:i976E2428D525A9B2
GO
Isoform 2 (identifier: Q13546-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     108-153: Missing.

Note: No experimental confirmation available.
Show »
Length:625
Mass (Da):70,733
Checksum:i4D3780FB4A93FDB1
GO

Sequence cautioni

The sequence BAG65471 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti258R → I in BAG36858 (PubMed:14702039).Curated1
Sequence conflicti286R → S in BAG36858 (PubMed:14702039).Curated1
Sequence conflicti514T → S in AAC50137 (PubMed:7538908).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04103964A → V in a colorectal adenocarcinoma sample; somatic mutation. 1 PublicationCorresponds to variant rs774996232dbSNPEnsembl.1
Natural variantiVAR_04104081V → I in a colorectal adenocarcinoma sample; somatic mutation. 1 PublicationCorresponds to variant rs758268804dbSNPEnsembl.1
Natural variantiVAR_041041220A → V in a colorectal adenocarcinoma sample; somatic mutation. 1 PublicationCorresponds to variant rs759012409dbSNPEnsembl.1
Natural variantiVAR_021109234E → K.1 PublicationCorresponds to variant rs17548383dbSNPEnsembl.1
Natural variantiVAR_041042404A → S.1 PublicationCorresponds to variant rs34872409dbSNPEnsembl.1
Natural variantiVAR_058285438A → V.3 PublicationsCorresponds to variant rs3173519dbSNPEnsembl.1
Natural variantiVAR_041043443A → V.1 PublicationCorresponds to variant rs35722193dbSNPEnsembl.1
Natural variantiVAR_041044569A → V.1 PublicationCorresponds to variant rs55861377dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_037690108 – 153Missing in isoform 2. 1 PublicationAdd BLAST46

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U50062 mRNA. Translation: AAC32232.1.
AK314176 mRNA. Translation: BAG36858.1.
AK304701 mRNA. Translation: BAG65471.1. Different initiation.
AY682848 Genomic DNA. Translation: AAT74626.1.
AL031963 Genomic DNA. Translation: CAD70625.1.
BC126254 mRNA. Translation: AAI26255.1.
BC126256 mRNA. Translation: AAI26257.1.
AB208926 mRNA. Translation: BAD92163.1.
U25994 mRNA. Translation: AAC50137.1.
CCDSiCCDS4482.1. [Q13546-1]
PIRiT09479.
RefSeqiNP_001303990.1. NM_001317061.1.
NP_003795.2. NM_003804.4. [Q13546-1]
XP_005249514.2. XM_005249457.3. [Q13546-1]
UniGeneiHs.519842.

Genome annotation databases

EnsembliENST00000259808; ENSP00000259808; ENSG00000137275. [Q13546-1]
ENST00000380409; ENSP00000369773; ENSG00000137275. [Q13546-1]
GeneIDi8737.
KEGGihsa:8737.
UCSCiuc003mux.4. human. [Q13546-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U50062 mRNA. Translation: AAC32232.1.
AK314176 mRNA. Translation: BAG36858.1.
AK304701 mRNA. Translation: BAG65471.1. Different initiation.
AY682848 Genomic DNA. Translation: AAT74626.1.
AL031963 Genomic DNA. Translation: CAD70625.1.
BC126254 mRNA. Translation: AAI26255.1.
BC126256 mRNA. Translation: AAI26257.1.
AB208926 mRNA. Translation: BAD92163.1.
U25994 mRNA. Translation: AAC50137.1.
CCDSiCCDS4482.1. [Q13546-1]
PIRiT09479.
RefSeqiNP_001303990.1. NM_001317061.1.
NP_003795.2. NM_003804.4. [Q13546-1]
XP_005249514.2. XM_005249457.3. [Q13546-1]
UniGeneiHs.519842.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4ITHX-ray2.25A/B1-294[»]
4ITIX-ray2.86A/B1-294[»]
4ITJX-ray1.80A/B1-294[»]
4NEUX-ray2.57A/B1-324[»]
5HX6X-ray2.23A/B1-294[»]
ProteinModelPortaliQ13546.
SMRiQ13546.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114274. 79 interactors.
DIPiDIP-433N.
IntActiQ13546. 38 interactors.
MINTiMINT-128219.
STRINGi9606.ENSP00000259808.

Chemistry databases

BindingDBiQ13546.
ChEMBLiCHEMBL5464.
GuidetoPHARMACOLOGYi2189.

PTM databases

iPTMnetiQ13546.
PhosphoSitePlusiQ13546.

Polymorphism and mutation databases

BioMutaiRIPK1.
DMDMi60393639.

Proteomic databases

EPDiQ13546.
MaxQBiQ13546.
PaxDbiQ13546.
PeptideAtlasiQ13546.
PRIDEiQ13546.

Protocols and materials databases

DNASUi8737.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000259808; ENSP00000259808; ENSG00000137275. [Q13546-1]
ENST00000380409; ENSP00000369773; ENSG00000137275. [Q13546-1]
GeneIDi8737.
KEGGihsa:8737.
UCSCiuc003mux.4. human. [Q13546-1]

Organism-specific databases

CTDi8737.
DisGeNETi8737.
GeneCardsiRIPK1.
HGNCiHGNC:10019. RIPK1.
HPAiCAB010302.
HPA015257.
MIMi603453. gene.
neXtProtiNX_Q13546.
OpenTargetsiENSG00000137275.
PharmGKBiPA34394.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0192. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00550000074536.
HOGENOMiHOG000010270.
HOVERGENiHBG055612.
InParanoidiQ13546.
KOiK02861.
OMAiVVKRMQS.
OrthoDBiEOG091G0479.
PhylomeDBiQ13546.
TreeFamiTF106506.

Enzyme and pathway databases

BioCyciZFISH:HS06304-MONOMER.
BRENDAi2.7.10.2. 2681.
ReactomeiR-HSA-140534. Ligand-dependent caspase activation.
R-HSA-1810476. RIP-mediated NFkB activation via ZBP1.
R-HSA-2562578. TRIF-mediated programmed cell death.
R-HSA-3295583. TRP channels.
R-HSA-3371378. Regulation by c-FLIP.
R-HSA-5213460. RIPK1-mediated regulated necrosis.
R-HSA-5218900. CASP8 activity is inhibited.
R-HSA-5357786. TNFR1-induced proapoptotic signaling.
R-HSA-5357905. Regulation of TNFR1 signaling.
R-HSA-5357956. TNFR1-induced NFkappaB signaling pathway.
R-HSA-5675482. Regulation of necroptotic cell death.
R-HSA-5689880. Ub-specific processing proteases.
R-HSA-5689896. Ovarian tumor domain proteases.
R-HSA-69416. Dimerization of procaspase-8.
R-HSA-75893. TNF signaling.
R-HSA-933543. NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10.
R-HSA-937041. IKK complex recruitment mediated by RIP1.
SignaLinkiQ13546.
SIGNORiQ13546.

Miscellaneous databases

ChiTaRSiRIPK1. human.
GeneWikiiRIPK1.
GenomeRNAii8737.
PMAP-CutDBQ13546.
PROiQ13546.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000137275.
CleanExiHS_RIPK1.
ExpressionAtlasiQ13546. baseline and differential.
GenevisibleiQ13546. HS.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
InterProiIPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR025735. RHIM_dom.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00531. Death. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF12721. RHIM. 1 hit.
[Graphical view]
PRINTSiPR00109. TYRKINASE.
SMARTiSM00005. DEATH. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50017. DEATH_DOMAIN. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiRIPK1_HUMAN
AccessioniPrimary (citable) accession number: Q13546
Secondary accession number(s): A0AV89
, B2RAG1, B4E3F9, Q13180, Q59H33
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: February 1, 2005
Last modified: November 30, 2016
This is version 182 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.