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Q3SZJ2 (RIPK2_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 80. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Receptor-interacting serine/threonine-protein kinase 2

EC=2.7.11.1
Alternative name(s):
Tyrosine-protein kinase RIPK2
EC=2.7.10.2
Gene names
Name:RIPK2
OrganismBos taurus (Bovine) [Reference proteome]
Taxonomic identifier9913 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos

Protein attributes

Sequence length540 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

Serine/threonine/tyrosine kinase that plays an essential role in modulation of innate and adaptive immune responses. Upon stimulation by bacterial peptidoglycans, NOD1 and NOD2 are activated, oligomerize and recruit RIPK2 through CARD-CARD domains. Once recruited, autophosphorylates and undergoes 'Lys-63'-linked polyubiquitination by E3 ubiquitin ligases XIAP, BIRC2 and BIRC3. The polyubiquitinated protein mediates the recruitment of MAP3K7/TAK1 to IKBKG/NEMO and induces 'Lys-63'-linked polyubiquitination of IKBKG/NEMO and subsequent activation of IKBKB/IKKB. In turn, NF-kappa-B is release from NF-kappa-B inhibitors and translocates into the nucleus where it activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. Plays also a role during engagement of the T-cell receptor (TCR) in promoting BCL10 phosphorylation and subsequent NF-kappa-B activation By similarity.

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

Subunit structure

Found in a signaling complex consisting of at least ARHGEF2, NOD2 and RIPK2. Interacts with ARHGEF2. Binds to CFLAR/CLARP and CASP1 via their CARD domains. Binds to BIRC3/c-IAP1 and BIRC2/c-IAP2, TRAF1, TRAF2, TRAF5 and TRAF6. May be a component of both the TNFRSF1A and TNRFSF5/CD40 receptor complex. Interacts with NOD1. Interacts (via CARD domain) with NOD2 (via CARD domain). Interacts with MAP3K4; this interaction sequesters RIPK2 from the NOD2 signaling pathway. Interacts with IKBKG/NEMO. The polyubiquitinated protein interacts with MAP3K7/TAK1. Interacts with XIAP/BIRC4. Interacts with NLRP10. Interacts with CARD9 By similarity.

Subcellular location

Cytoplasm Probable.

Domain

Contains an N-terminal kinase domain and a C-terminal caspase activation and recruitment domain (CARD) that mediates the recruitment of CARD-containing proteins By similarity.

Post-translational modification

Autophosphorylated. Autophosphorylation at Tyr-472 is necessary for effective NOD2 signaling.

Ubiquitinated on Lys-209; undergoes 'Lys-63'-linked polyubiquitination catalyzed by ITCH. Polyubiquitinated with 'Lys-48' and 'Lys-63'-linked chains by BIRC2/c-IAP1 and BIRC3/c-IAP2, leading to activation of NF-kappa-B. Also undergoes 'Met-1'-linked polyubiquitination; the head-to-tail linear polyubiquitination is mediated by the LUBAC complex in response to NOD2 stimulation. Linear polyubiquitination is restricted by FAM105B/otulin, probably to limit NOD2-dependent proinflammatory signaling activation of NF-kappa-B By similarity.

Sequence similarities

Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.

Contains 1 CARD domain.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processAdaptive immunity
Apoptosis
Immunity
Innate immunity
   Cellular componentCytoplasm
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMIsopeptide bond
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processI-kappaB kinase/NF-kappaB signaling

Inferred from sequence or structural similarity. Source: UniProtKB

T cell receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

adaptive immune response

Inferred from sequence or structural similarity. Source: UniProtKB

apoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

cellular response to muramyl dipeptide

Inferred from sequence or structural similarity. Source: UniProtKB

innate immune response

Inferred from sequence or structural similarity. Source: UniProtKB

nucleotide-binding oligomerization domain containing 2 signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of NF-kappaB transcription factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of apoptotic process

Inferred from electronic annotation. Source: InterPro

positive regulation of interleukin-6 production

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of peptidyl-serine phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of peptidyl-threonine phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of peptidyl-tyrosine phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of tumor necrosis factor production

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

cytoskeleton

Inferred from sequence or structural similarity. Source: UniProtKB

protein complex

Inferred from sequence or structural similarity. Source: UniProtKB

vesicle

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

non-membrane spanning protein tyrosine kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

protein serine/threonine kinase activity

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 540540Receptor-interacting serine/threonine-protein kinase 2
PRO_0000245586

Regions

Domain18 – 294277Protein kinase
Domain432 – 52493CARD
Nucleotide binding24 – 329ATP By similarity

Sites

Active site1461Proton acceptor
Binding site471ATP By similarity

Amino acid modifications

Modified residue1681Phosphoserine By similarity
Modified residue1761Phosphoserine; by autocatalysis By similarity
Modified residue3631Phosphoserine By similarity
Modified residue3911Phosphoserine By similarity
Modified residue4721Phosphotyrosine; by autocatalysis By similarity
Modified residue5251Phosphoserine By similarity
Modified residue5271Phosphoserine By similarity
Modified residue5291Phosphoserine By similarity
Modified residue5371Phosphoserine By similarity
Cross-link209Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Sequences

Sequence LengthMass (Da)Tools
Q3SZJ2 [UniParc].

Last modified October 11, 2005. Version 1.
Checksum: 2F54BD72A747970F

FASTA54061,106
        10         20         30         40         50         60 
MSAEPVCSAL PAIPYHKLAD LRYLSRGASG TVSSARHADW RVQVAVKHLH IHSPLLDSER 

        70         80         90        100        110        120 
NDVLREAEIL HKARFSYILP ILGICNEPEF LGIVTEYMPN GSLNELLHRK IEYPDVPWPL 

       130        140        150        160        170        180 
RFRILHEIAL GVNYLHNMNP PLLHHDLKTQ NILLDNEFHV KIADFGLSKW RMMSLSQSRS 

       190        200        210        220        230        240 
SKSAPEGGTI VYMPPENYEP GQKARASVKH DIYSYAIIIW EVLSRKQPFE DVTNPLQIMY 

       250        260        270        280        290        300 
SVSQGHRPDT NEESLPFDIP HRALMISLIE SGWAQNPDER PSFLKCLIEL EPVLRTFEEI 

       310        320        330        340        350        360 
TFLEAVIQLK KTKLQNASRT VHLSDKKKRE LSPNIPVNSG PREESCGSSQ LHKTSGSPGT 

       370        380        390        400        410        420 
SRSLSAPQDK DFLSAKTQDF SALHQCSVNH SRNSDFCVDC QVAFCDHRTA PCSLAIVNPL 

       430        440        450        460        470        480 
SAEGNSGRFQ PGIAQQWIQS KREDIVSQMT EACLNQSLDA LLSRDLIMKE DYELISTKPT 

       490        500        510        520        530        540 
RTSKVRQLLD TTDIQGEEFA RVIVQKLKDN KQMGLQPYPE ILVLSQSPSL NFFHNKSHKK 

« Hide

References

[1]NIH - Mammalian Gene Collection (MGC) project
Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: Crossbred X Angus.
Tissue: Ileum.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
BC102829 mRNA. Translation: AAI02830.1.
RefSeqNP_001029782.1. NM_001034610.2.
UniGeneBt.34596.

3D structure databases

ProteinModelPortalQ3SZJ2.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9913.ENSBTAP00000020312.

Proteomic databases

PRIDEQ3SZJ2.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSBTAT00000020312; ENSBTAP00000020312; ENSBTAG00000015271.
GeneID534407.
KEGGbta:534407.

Organism-specific databases

CTD8767.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00550000074536.
HOGENOMHOG000136856.
HOVERGENHBG054242.
InParanoidQ3SZJ2.
KOK08846.

Family and domain databases

Gene3D1.10.533.10. 1 hit.
InterProIPR001315. CARD.
IPR011029. DEATH-like_dom.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017322. Rcpt-int_Ser/Thr_kinase-2.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00619. CARD. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
PIRSFPIRSF037921. STPK_RIP2. 1 hit.
SMARTSM00114. CARD. 1 hit.
[Graphical view]
SUPFAMSSF47986. SSF47986. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS50209. CARD. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio20876393.

Entry information

Entry nameRIPK2_BOVIN
AccessionPrimary (citable) accession number: Q3SZJ2
Entry history
Integrated into UniProtKB/Swiss-Prot: July 11, 2006
Last sequence update: October 11, 2005
Last modified: April 16, 2014
This is version 80 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families