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Protein

Receptor-interacting serine/threonine-protein kinase 3

Gene

Ripk3

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Essential for necroptosis, a programmed cell death process in response to death-inducing TNF-alpha family members. Upon induction of necrosis, RIPK3 interacts with, and phosphorylates RIPK1 and MLKL to form a necrosis-inducing complex. RIPK3 binds to and enhances the activity of three metabolic enzymes: GLUL, GLUD1, and PYGL. These metabolic enzymes may eventually stimulate the tricarboxylic acid cycle and oxidative phosphorylation, which could result in enhanced ROS production (By similarity).By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei51ATPPROSITE-ProRule annotation1
Active sitei143Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi28 – 36ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

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

ReactomeiR-RNO-3295583. TRP channels.
R-RNO-5213460. RIPK1-mediated regulated necrosis.

Names & Taxonomyi

Protein namesi
Recommended name:
Receptor-interacting serine/threonine-protein kinase 3 (EC:2.7.11.1)
Alternative name(s):
Homocysteine respondent protein HCYP2
RIP-like protein kinase 3
Receptor-interacting protein 3
Short name:
RIP-3
Gene namesi
Name:Ripk3
Synonyms:Rip3
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 15

Organism-specific databases

RGDi628899. Ripk3.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Mitochondrion

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000866121 – 478Receptor-interacting serine/threonine-protein kinase 3Add BLAST478

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2PhosphoserineBy similarity1
Modified residuei165PhosphoserineBy similarity1
Modified residuei201Phosphoserine; by autocatalysisBy similarity1
Modified residuei228PhosphothreonineBy similarity1
Modified residuei229PhosphoserineBy similarity1
Modified residuei254PhosphothreonineBy similarity1
Modified residuei301PhosphoserineBy similarity1
Modified residuei323PhosphoserineBy similarity1
Modified residuei335PhosphothreonineBy similarity1
Modified residuei350PhosphoserineBy similarity1
Modified residuei369PhosphoserineBy similarity1
Modified residuei380PhosphoserineBy similarity1
Modified residuei392PhosphothreonineBy similarity1
Modified residuei474Omega-N-methylarginineBy similarity1

Post-translational modificationi

RIPK1 and RIPK3 undergo reciprocal auto- and trans-phosphorylation. Phosphorylation of Ser-201 plays a role in the necroptotic function of RIPK3 (By similarity).By similarity
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

Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ9Z2P5.
PRIDEiQ9Z2P5.

PTM databases

iPTMnetiQ9Z2P5.
PhosphoSitePlusiQ9Z2P5.

Expressioni

Gene expression databases

BgeeiENSRNOG00000020465.
GenevisibleiQ9Z2P5. RN.

Interactioni

Subunit structurei

Interacts (via RIP homotypic interaction motif) with RIPK1 (via RIP homotypic interaction motif); this interaction induces RIPK1 phosphorylation and formation of a RIPK1-RIPK3 necroptosis-inducing complex. 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 (By similarity). Interacts with MLKL; the interaction is direct. Binds TRAF2 and is recruited to the TNFR-1 signaling complex. Interacts with PYGL, GLUL and GLUD1; these interactions result in activation of these metabolic enzymes (By similarity). Interacts with BIRC2/c-IAP1, BIRC3/c-IAP2 and XIAP/BIRC4. Interacts with ARHGEF2 (By similarity).By similarity

Protein-protein interaction databases

IntActiQ9Z2P5. 1 interactor.
STRINGi10116.ENSRNOP00000027759.

Structurei

3D structure databases

ProteinModelPortaliQ9Z2P5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini22 – 290Protein kinasePROSITE-ProRule annotationAdd BLAST269

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi437 – 461RIP homotypic interaction motif (RHIM)Add BLAST25

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0192. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00550000074536.
HOGENOMiHOG000035101.
HOVERGENiHBG062538.
InParanoidiQ9Z2P5.
KOiK08847.
OMAiVTKFMEN.
OrthoDBiEOG091G0DXD.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR025735. RHIM_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
PF12721. RHIM. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9Z2P5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSSVKLWLNG ASSISLVGSE ELENLGFVGK GGFGAVFRAR HTAWNLDVAV
60 70 80 90 100
KIVNSKKISR EVKAMVNLRH ENVLLLLGVT ENLEWDYVYG PALVTGFMEN
110 120 130 140 150
GSLSGLLQPS CPRPWPLLCR LLEEVVLGMC YLHSLNPSLL HRDLKPSNVL
160 170 180 190 200
LDPELHAKLA DFGLSTFQGG SQSGSGSGSR DSGGTLAYLA PELLDNDGKA
210 220 230 240 250
SKASDVYSFG VLVWTVLAGR EAEVVDKTSL IRGAVCNRQR RPPLTELPPD
260 270 280 290 300
SPETPGLEGL KELMTHCWSS EPKDRPSFQD CESKTNNVYI LVQDKVDAAV
310 320 330 340 350
SKVKHYLSQY RSSDTKLSAR ESSQKGTEVD CPRETIVYEM LDRLHLEEPS
360 370 380 390 400
GSVPERLTSL TERRGKEASF GHATPAGTSS DTLAGTPQIP HTLPSRGTTP
410 420 430 440 450
RPAFTETPGP DPQRNQGDGR NSNPWYTWNA PNPMTGLQSI VLNNCSEVQI
460 470
GQHNCMSVQP RTAFPKKEPA QFGRGRGW
Length:478
Mass (Da):52,218
Last modified:February 19, 2014 - v3
Checksum:i87C83BFD16287136
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti153P → L in AAD02059 (Ref. 1) Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF036537 mRNA. Translation: AAD02059.2.
AABR06083269 Genomic DNA. No translation available.
CH474049 Genomic DNA. Translation: EDM14285.1.
CH474049 Genomic DNA. Translation: EDM14286.1.
BC158580 mRNA. Translation: AAI58581.1.
RefSeqiNP_647558.1. NM_139342.1.
UniGeneiRn.7110.

Genome annotation databases

EnsembliENSRNOT00000027759; ENSRNOP00000027759; ENSRNOG00000020465.
GeneIDi246240.
KEGGirno:246240.
UCSCiRGD:628899. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF036537 mRNA. Translation: AAD02059.2.
AABR06083269 Genomic DNA. No translation available.
CH474049 Genomic DNA. Translation: EDM14285.1.
CH474049 Genomic DNA. Translation: EDM14286.1.
BC158580 mRNA. Translation: AAI58581.1.
RefSeqiNP_647558.1. NM_139342.1.
UniGeneiRn.7110.

3D structure databases

ProteinModelPortaliQ9Z2P5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ9Z2P5. 1 interactor.
STRINGi10116.ENSRNOP00000027759.

PTM databases

iPTMnetiQ9Z2P5.
PhosphoSitePlusiQ9Z2P5.

Proteomic databases

PaxDbiQ9Z2P5.
PRIDEiQ9Z2P5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000027759; ENSRNOP00000027759; ENSRNOG00000020465.
GeneIDi246240.
KEGGirno:246240.
UCSCiRGD:628899. rat.

Organism-specific databases

CTDi11035.
RGDi628899. Ripk3.

Phylogenomic databases

eggNOGiKOG0192. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00550000074536.
HOGENOMiHOG000035101.
HOVERGENiHBG062538.
InParanoidiQ9Z2P5.
KOiK08847.
OMAiVTKFMEN.
OrthoDBiEOG091G0DXD.

Enzyme and pathway databases

ReactomeiR-RNO-3295583. TRP channels.
R-RNO-5213460. RIPK1-mediated regulated necrosis.

Miscellaneous databases

PROiQ9Z2P5.

Gene expression databases

BgeeiENSRNOG00000020465.
GenevisibleiQ9Z2P5. RN.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR025735. RHIM_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
PF12721. RHIM. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiRIPK3_RAT
AccessioniPrimary (citable) accession number: Q9Z2P5
Secondary accession number(s): B0BMV6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 2, 2002
Last sequence update: February 19, 2014
Last modified: November 2, 2016
This is version 126 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 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.