Receptor-interacting serine/threonine-protein kinase 3

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Q9QZL0 (RIPK3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 106. History...

Clusters with 100%, 90%, 50% identity |

Documents (3) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Receptor-interacting serine/threonine-protein kinase 3
EC=2.7.11.1

Alternative name(s):
RIP-like protein kinase 3
Receptor-interacting protein 3
Short name=RIP-3
Short name=mRIP3

Gene names

Name:	Ripk3
Synonyms:	Rip3

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	486 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Essential for programmed necrosis in response to death-inducing TNF-alpha family members. Upon induction of necrosis, RIPK3 interacts with, and phosphorylates RIPK1 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. Ref.3
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	Inhibited by necrostatin-1 By similarity.
Subunit structure	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. Binds TRAF2 and is recruited to the TNFR-1 signaling complex By similarity. Interacts with PYGL, GLUL and GLUD1; these interactions result in activation of these metabolic enzymes. Interacts (via RIP homotypic interaction motif) with murid herpesvirus 1 viral inhibitor of RIP activation; this interaction disrupts RIP3-RIP1 interactions characteristic of TNF-alpha induced necroptosis, thereby suppressing this death pathway. Interacts with BIRC2/c-IAP1, BIRC3/c-IAP2 and XIAP/BIRC4 By similarity. Ref.2 Ref.3
Subcellular location	Cytoplasm Probable. Cell membrane. Mitochondrion Potential.
Tissue specificity	Expressed in embryo and in adult spleen, liver, testis, heart, brain and lung.
Post-translational modification	RIPK1 and RIPK3 undergo reciprocal auto- and trans-phosphorylation. Phosphorylation of Ser-204 plays a role in the necroptotic function of RIPK3 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.
Sequence similarities	Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Host-virus interaction Necrosis
Cellular component	Cell membrane Cytoplasm Membrane Mitochondrion
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	I-kappaB kinase/NF-kappaB cascade Inferred from direct assay Ref.1. Source: MGI induction of apoptosis Inferred from direct assay Ref.1. Source: MGI positive regulation of necroptosis Inferred from mutant phenotype PubMed 21052097. Source: UniProtKB positive regulation of reactive oxygen species metabolic process Inferred from mutant phenotype PubMed 21052097. Source: UniProtKB virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	intracellular Inferred from direct assay Ref.1. Source: MGI mitochondrion Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW NF-kappaB-inducing kinase activity Inferred from direct assay Ref.1. Source: MGI
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Ripk1	Q60855	6	EBI-2367423,EBI-529119

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 486

486

Receptor-interacting serine/threonine-protein kinase 3

PRO_0000086611

Regions

Domain

22 – 292

271

Protein kinase

Nucleotide binding

28 – 36

ATP By similarity

Motif

440 – 461

RIP homotypic interaction motif (RHIM)

Compositional bias

352 – 438

Pro-rich

Sites

Active site

143

Proton acceptor Probable

Binding site

ATP Probable

Amino acid modifications

Modified residue

171

Phosphoserine; by autocatalysis Potential

Modified residue

204

Phosphoserine; by autocatalysis By similarity

Experimental info

Mutagenesis

K → A: Complete loss of induced necrosis.

Mutagenesis

143

D → N: No autophosphorylation. Ref.1

Mutagenesis

459 – 462

PPRT → AAAA: Complete loss of induced necrosis.

Sequences

Sequence

Length

Mass (Da)

Tools

Q9QZL0 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: DD264E69187D3436
Show »

FASTA

486

53,337

        10         20         30         40         50         60 
MSSVKLWPTG ASAVPLVSRE ELKKLEFVGK GGFGVVFRAH HRTWNHDVAV KIVNSKKISW 

        70         80         90        100        110        120 
EVKAMVNLRN ENVLLLLGVT EDLQWDFVSG QALVTRFMEN GSLAGLLQPE CPRPWPLLCR 

       130        140        150        160        170        180 
LLQEVVLGMC YLHSLDPPLL HRDLKPSNIL LDPELHAKLA DFGLSTFQGG SQSGSGSGSG 

       190        200        210        220        230        240 
SRDSGGTLAY LDPELLFKVN LKASKASDVY SFGILVWAVL AGREAELVDK TSLIRETVCD 

       250        260        270        280        290        300 
RQSRPPLTEL PPGSPETPGL EKLKELMIHC WGSQSENRPS FQDCEPKTNE VYNLVKDKVD 

       310        320        330        340        350        360 
AAVSEVKHYL SQHRSSGRNL SAREPSQRGT EMDCPRETMV SKMLDRLHLE EPSGPVPGKC 

       370        380        390        400        410        420 
PERQAQDTSV GPATPARTSS DPVAGTPQIP HTLPFRGTTP GPVFTETPGP HPQRNQGDGR 

       430        440        450        460        470        480 
HGTPWYPWTP PNPMTGPPAL VFNNCSEVQI GNYNSLVAPP RTTASSSAKY DQAQFGRGRG 


WQPFHK

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References

[1]	"Mouse receptor interacting protein 3 does not contain a caspase-recruiting or a death domain but induces apoptosis and activates NF-kappaB." Pazdernik N.J., Donner D.B., Goebl M.G., Harrington M.A. Mol. Cell. Biol. 19:6500-6508(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS OF ASP-143. Tissue: Embryo.
[2]	"Cytomegalovirus M45 cell death suppression requires receptor-interacting protein (RIP) homotypic interaction motif (RHIM)-dependent interaction with RIP1." Upton J.W., Kaiser W.J., Mocarski E.S. J. Biol. Chem. 283:16966-16970(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MURID HERPESVIRUS 1 VIRAL INHIBITOR OF RIP ACTIVATION.
[3]	"DAI/ZBP1 recruits RIP1 and RIP3 through RIP homotypic interaction motifs to activate NF-kappaB." Rebsamen M., Heinz L.X., Meylan E., Michallet M.C., Schroder K., Hofmann K., Vazquez J., Benedict C.A., Tschopp J. EMBO Rep. 10:916-922(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH ZBP1.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF178953 mRNA. Translation: AAF03133.1.
IPI	IPI00137560.
UniGene	Mm.46612.
3D structure databases
ProteinModelPortal	Q9QZL0.
SMR	Q9QZL0. Positions 25-297.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-54883N.
IntAct	Q9QZL0. 6 interactions.
PTM databases
PhosphoSite	Q9QZL0.
Proteomic databases
PaxDb	Q9QZL0.
PRIDE	Q9QZL0.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Organism-specific databases
MGI	MGI:2154952. Ripk3.
Phylogenomic databases
eggNOG	NOG274817.
HOGENOM	HOG000035101.
HOVERGEN	HBG062538.
InParanoid	Q9QZL0.
OrthoDB	EOG40CHHC.
Gene expression databases
CleanEx	MM_RIPK3.
Genevestigator	Q9QZL0.
GermOnline	ENSMUSG00000022221. Mus musculus.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR025735. RHIM_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. PF12721. RHIM. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
SOURCE	Search...

Entry information

Entry name

RIPK3_MOUSE

Accession

Primary (citable) accession number: Q9QZL0

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 2, 2002
Last sequence update:	May 1, 2000
Last modified:	May 1, 2013
This is version 106 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents