Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Q3SZJ2

- RIPK2_BOVIN

UniProt

Q3SZJ2 - RIPK2_BOVIN

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
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 82 (01 Oct 2014)
      Sequence version 1 (11 Oct 2005)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    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

    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

    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.

    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

    MSAEPVCSAL PAIPYHKLAD LRYLSRGASG TVSSARHADW RVQVAVKHLH    50
    IHSPLLDSER NDVLREAEIL HKARFSYILP ILGICNEPEF LGIVTEYMPN 100
    GSLNELLHRK IEYPDVPWPL RFRILHEIAL GVNYLHNMNP PLLHHDLKTQ 150
    NILLDNEFHV KIADFGLSKW RMMSLSQSRS SKSAPEGGTI VYMPPENYEP 200
    GQKARASVKH DIYSYAIIIW EVLSRKQPFE DVTNPLQIMY SVSQGHRPDT 250
    NEESLPFDIP HRALMISLIE SGWAQNPDER PSFLKCLIEL EPVLRTFEEI 300
    TFLEAVIQLK KTKLQNASRT VHLSDKKKRE LSPNIPVNSG PREESCGSSQ 350
    LHKTSGSPGT SRSLSAPQDK DFLSAKTQDF SALHQCSVNH SRNSDFCVDC 400
    QVAFCDHRTA PCSLAIVNPL SAEGNSGRFQ PGIAQQWIQS KREDIVSQMT 450
    EACLNQSLDA LLSRDLIMKE DYELISTKPT RTSKVRQLLD TTDIQGEEFA 500
    RVIVQKLKDN KQMGLQPYPE ILVLSQSPSL NFFHNKSHKK 540
    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.

    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 1, 2014
    This is version 82 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