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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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei51 – 511ATPPROSITE-ProRule annotation
Active sitei143 – 1431Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi28 – 369ATPPROSITE-ProRule annotation

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)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 478478Receptor-interacting serine/threonine-protein kinase 3PRO_0000086612Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21PhosphoserineBy similarity
Modified residuei165 – 1651PhosphoserineBy similarity
Modified residuei201 – 2011Phosphoserine; by autocatalysisBy similarity
Modified residuei228 – 2281PhosphothreonineBy similarity
Modified residuei229 – 2291PhosphoserineBy similarity
Modified residuei254 – 2541PhosphothreonineBy similarity
Modified residuei301 – 3011PhosphoserineBy similarity
Modified residuei323 – 3231PhosphoserineBy similarity
Modified residuei335 – 3351PhosphothreonineBy similarity
Modified residuei350 – 3501PhosphoserineBy similarity
Modified residuei369 – 3691PhosphoserineBy similarity
Modified residuei380 – 3801PhosphoserineBy similarity
Modified residuei392 – 3921PhosphothreonineBy similarity

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

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ9Z2P5.
PeptideAtlasiQ9Z2P5.
PRIDEiQ9Z2P5.

PTM databases

iPTMnetiQ9Z2P5.
PhosphoSiteiQ9Z2P5.

Expressioni

Gene expression databases

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 interaction.
STRINGi10116.ENSRNOP00000027759.

Structurei

3D structure databases

ProteinModelPortaliQ9Z2P5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini22 – 290269Protein kinasePROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi437 – 46125RIP homotypic interaction motif (RHIM)Add
BLAST

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0192. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00550000074536.
HOGENOMiHOG000035101.
HOVERGENiHBG062538.
InParanoidiQ9Z2P5.
KOiK08847.
OMAiVTKFMEN.
OrthoDBiEOG7Q2N5T.

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti153 – 1531P → L in AAD02059 (Ref. 1) Curated

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.
XP_006251990.1. XM_006251928.2.
XP_008768883.1. XM_008770661.1.
XP_008768884.1. XM_008770662.1.
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.
XP_006251990.1. XM_006251928.2.
XP_008768883.1. XM_008770661.1.
XP_008768884.1. XM_008770662.1.
UniGeneiRn.7110.

3D structure databases

ProteinModelPortaliQ9Z2P5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ9Z2P5. 1 interaction.
STRINGi10116.ENSRNOP00000027759.

PTM databases

iPTMnetiQ9Z2P5.
PhosphoSiteiQ9Z2P5.

Proteomic databases

PaxDbiQ9Z2P5.
PeptideAtlasiQ9Z2P5.
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.
OrthoDBiEOG7Q2N5T.

Enzyme and pathway databases

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

Miscellaneous databases

PROiQ9Z2P5.

Gene expression databases

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...

Publicationsi

« Hide 'large scale' publications
  1. "A homocysteine-respondent gene cloned from WKY VSMCs by differential display."
    Chen K.H., Tang J.
    Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Wistar Kyoto.
  2. "Genome sequence of the Brown Norway rat yields insights into mammalian evolution."
    Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., Morgan M.
    , Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S., Collins F.S.
    Nature 428:493-521(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: Brown Norway.
  3. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Spleen.
  5. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
    Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
    Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

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: July 6, 2016
This is version 124 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.