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Q3SZJ2

- RIPK2_BOVIN

UniProt

Q3SZJ2 - RIPK2_BOVIN

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Protein

Receptor-interacting serine/threonine-protein kinase 2

Gene

RIPK2

Organism
Bos taurus (Bovine)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli

Functioni

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).By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.
ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei47 – 471ATPPROSITE-ProRule annotation
Active sitei146 – 1461Proton acceptor

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi24 – 329ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. non-membrane spanning protein tyrosine kinase activity Source: UniProtKB-EC
  3. protein serine/threonine kinase activity Source: UniProtKB-KW

GO - Biological processi

  1. adaptive immune response Source: UniProtKB
  2. apoptotic process Source: UniProtKB-KW
  3. cellular response to muramyl dipeptide Source: UniProtKB
  4. I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  5. innate immune response Source: UniProtKB
  6. nucleotide-binding oligomerization domain containing 2 signaling pathway Source: UniProtKB
  7. positive regulation of apoptotic process Source: InterPro
  8. positive regulation of interleukin-6 production Source: UniProtKB
  9. positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  10. positive regulation of peptidyl-serine phosphorylation Source: UniProtKB
  11. positive regulation of peptidyl-threonine phosphorylation Source: UniProtKB
  12. positive regulation of peptidyl-tyrosine phosphorylation Source: UniProtKB
  13. positive regulation of tumor necrosis factor production Source: UniProtKB
  14. T cell receptor signaling pathway Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Adaptive immunity, Apoptosis, Immunity, Innate immunity

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiREACT_205423. Downstream TCR signaling.
REACT_207826. Interleukin-1 signaling.
REACT_207897. activated TAK1 mediates p38 MAPK activation.
REACT_211964. JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
REACT_217214. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
REACT_224941. NOD1/2 Signaling Pathway.
REACT_227494. p75NTR recruits signalling complexes.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:RIPK2
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
ProteomesiUP000009136: Chromosome 14

Subcellular locationi

Cytoplasm Curated

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. cytoskeleton Source: UniProtKB
  3. protein complex Source: UniProtKB
  4. vesicle Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 540540Receptor-interacting serine/threonine-protein kinase 2PRO_0000245586Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei168 – 1681PhosphoserineBy similarity
Modified residuei176 – 1761Phosphoserine; by autocatalysisBy similarity
Cross-linki209 – 209Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei363 – 3631PhosphoserineBy similarity
Modified residuei391 – 3911PhosphoserineBy similarity
Modified residuei472 – 4721Phosphotyrosine; by autocatalysisBy similarity
Modified residuei525 – 5251PhosphoserineBy similarity
Modified residuei527 – 5271PhosphoserineBy similarity
Modified residuei529 – 5291PhosphoserineBy similarity
Modified residuei537 – 5371PhosphoserineBy similarity

Post-translational modificationi

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).By similarity

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PRIDEiQ3SZJ2.

Expressioni

Gene expression databases

ExpressionAtlasiQ3SZJ2. baseline.

Interactioni

Subunit structurei

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).By similarity

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000020312.

Structurei

3D structure databases

ProteinModelPortaliQ3SZJ2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini18 – 294277Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini432 – 52493CARDPROSITE-ProRule annotationAdd
BLAST

Domaini

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

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00550000074536.
HOGENOMiHOG000136856.
HOVERGENiHBG054242.
InParanoidiQ3SZJ2.
KOiK08846.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
InterProiIPR001315. 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]
PfamiPF00619. CARD. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
PIRSFiPIRSF037921. STPK_RIP2. 1 hit.
SMARTiSM00114. CARD. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50209. CARD. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q3SZJ2-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MSAEPVCSAL PAIPYHKLAD LRYLSRGASG TVSSARHADW RVQVAVKHLH
60 70 80 90 100
IHSPLLDSER NDVLREAEIL HKARFSYILP ILGICNEPEF LGIVTEYMPN
110 120 130 140 150
GSLNELLHRK IEYPDVPWPL RFRILHEIAL GVNYLHNMNP PLLHHDLKTQ
160 170 180 190 200
NILLDNEFHV KIADFGLSKW RMMSLSQSRS SKSAPEGGTI VYMPPENYEP
210 220 230 240 250
GQKARASVKH DIYSYAIIIW EVLSRKQPFE DVTNPLQIMY SVSQGHRPDT
260 270 280 290 300
NEESLPFDIP HRALMISLIE SGWAQNPDER PSFLKCLIEL EPVLRTFEEI
310 320 330 340 350
TFLEAVIQLK KTKLQNASRT VHLSDKKKRE LSPNIPVNSG PREESCGSSQ
360 370 380 390 400
LHKTSGSPGT SRSLSAPQDK DFLSAKTQDF SALHQCSVNH SRNSDFCVDC
410 420 430 440 450
QVAFCDHRTA PCSLAIVNPL SAEGNSGRFQ PGIAQQWIQS KREDIVSQMT
460 470 480 490 500
EACLNQSLDA LLSRDLIMKE DYELISTKPT RTSKVRQLLD TTDIQGEEFA
510 520 530 540
RVIVQKLKDN KQMGLQPYPE ILVLSQSPSL NFFHNKSHKK
Length:540
Mass (Da):61,106
Last modified:October 11, 2005 - v1
Checksum:i2F54BD72A747970F
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
BC102829 mRNA. Translation: AAI02830.1.
RefSeqiNP_001029782.1. NM_001034610.2.
UniGeneiBt.34596.

Genome annotation databases

EnsembliENSBTAT00000020312; ENSBTAP00000020312; ENSBTAG00000015271.
GeneIDi534407.
KEGGibta:534407.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
BC102829 mRNA. Translation: AAI02830.1 .
RefSeqi NP_001029782.1. NM_001034610.2.
UniGenei Bt.34596.

3D structure databases

ProteinModelPortali Q3SZJ2.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 9913.ENSBTAP00000020312.

Proteomic databases

PRIDEi Q3SZJ2.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSBTAT00000020312 ; ENSBTAP00000020312 ; ENSBTAG00000015271 .
GeneIDi 534407.
KEGGi bta:534407.

Organism-specific databases

CTDi 8767.

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00550000074536.
HOGENOMi HOG000136856.
HOVERGENi HBG054242.
InParanoidi Q3SZJ2.
KOi K08846.

Enzyme and pathway databases

Reactomei REACT_205423. Downstream TCR signaling.
REACT_207826. Interleukin-1 signaling.
REACT_207897. activated TAK1 mediates p38 MAPK activation.
REACT_211964. JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
REACT_217214. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
REACT_224941. NOD1/2 Signaling Pathway.
REACT_227494. p75NTR recruits signalling complexes.

Miscellaneous databases

NextBioi 20876393.

Gene expression databases

ExpressionAtlasi Q3SZJ2. baseline.

Family and domain databases

Gene3Di 1.10.533.10. 1 hit.
InterProi IPR001315. 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 ]
Pfami PF00619. CARD. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view ]
PIRSFi PIRSF037921. STPK_RIP2. 1 hit.
SMARTi SM00114. CARD. 1 hit.
[Graphical view ]
SUPFAMi SSF47986. SSF47986. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEi PS50209. CARD. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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.

Entry informationi

Entry nameiRIPK2_BOVIN
AccessioniPrimary (citable) accession number: Q3SZJ2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 11, 2006
Last sequence update: October 11, 2005
Last modified: October 29, 2014
This is version 83 of the entry and version 1 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

External Data

Dasty 3