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O43353 (RIPK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 157. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·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):
CARD-containing interleukin-1 beta-converting enzyme-associated kinase
Short name=CARD-containing IL-1 beta ICE-kinase
RIP-like-interacting CLARP kinase
Receptor-interacting protein 2
Short name=RIP-2
Tyrosine-protein kinase RIPK2
EC=2.7.10.2
Gene names
Name:RIPK2
Synonyms:CARDIAK, RICK, RIP2
ORF Names:UNQ277/PRO314/PRO34092
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length540 AA.
Sequence statusComplete.
Protein existenceEvidence at protein 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. Contributes to the tyrosine phosphorylation of the guanine exchange factor ARHGEF2 through Src tyrosine kinase leading to NF-kappaB activation by NOD2. Once recruited, RIPK2 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 released 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. Ref.8 Ref.10 Ref.12 Ref.18 Ref.23

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; the interaction mediates tyrosine phosphorylation of RIPK2 by Src kinase CSK. 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. Ref.10 Ref.11 Ref.12 Ref.15 Ref.21 Ref.22 Ref.23

Subcellular location

Cytoplasm Probable.

Tissue specificity

Detected in heart, brain, placenta, lung, peripheral blood leukocytes, spleen, kidney, testis, prostate, pancreas and lymph node.

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.

Post-translational modification

Autophosphorylated. Autophosphorylation at Tyr-474 is necessary for effective NOD2 signaling. Phosphorylated. Phosphorylation at Tyr-381 by Src kinase CSK occurs in a ARHGEF2-dependent manner and is required for NOD2-dependent innate immune activation. Ref.9 Ref.18 Ref.23

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. Ref.12 Ref.15 Ref.16 Ref.21 Ref.24

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
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMIsopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processI-kappaB kinase/NF-kappaB signaling

Inferred from sequence or structural similarity. Source: UniProtKB

JNK cascade

Traceable author statement. Source: Reactome

MyD88-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

MyD88-independent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

T cell proliferation

Inferred from electronic annotation. Source: Ensembl

T cell receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

TRIF-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

activation of MAPK activity

Traceable author statement. Source: Reactome

adaptive immune response

Inferred from sequence or structural similarity. Source: UniProtKB

apoptotic process

Traceable author statement Ref.2. Source: ProtInc

cellular response to lipoteichoic acid

Inferred from electronic annotation. Source: Ensembl

cellular response to muramyl dipeptide

Inferred from direct assay Ref.23. Source: UniProtKB

cellular response to peptidoglycan

Inferred from electronic annotation. Source: Ensembl

defense response to Gram-positive bacterium

Inferred from electronic annotation. Source: Ensembl

inflammatory response

Traceable author statement Ref.3. Source: ProtInc

innate immune response

Inferred from direct assay Ref.24. Source: UniProtKB

lipopolysaccharide-mediated signaling pathway

Inferred from electronic annotation. Source: Ensembl

negative regulation of apoptotic process

Traceable author statement. Source: Reactome

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway

Traceable author statement. Source: Reactome

nucleotide-binding oligomerization domain containing 1 signaling pathway

Inferred from electronic annotation. Source: Ensembl

nucleotide-binding oligomerization domain containing 2 signaling pathway

Inferred from direct assay Ref.24. Source: UniProtKB

nucleotide-binding oligomerization domain containing signaling pathway

Traceable author statement. Source: Reactome

positive regulation of ERK1 and ERK2 cascade

Inferred from electronic annotation. Source: Ensembl

positive regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from direct assay PubMed 10329646. Source: MGI

positive regulation of JNK cascade

Inferred from electronic annotation. Source: Ensembl

positive regulation of NF-kappaB transcription factor activity

Inferred from mutant phenotype Ref.23Ref.21. Source: UniProtKB

positive regulation of T-helper 1 cell differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of T-helper 1 type immune response

Inferred from electronic annotation. Source: Ensembl

positive regulation of alpha-beta T cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of chemokine production

Inferred from electronic annotation. Source: Ensembl

positive regulation of cytokine-mediated signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of immature T cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of interferon-alpha production

Non-traceable author statement PubMed 22412986. Source: BHF-UCL

positive regulation of interferon-beta production

Non-traceable author statement PubMed 22412986. Source: BHF-UCL

positive regulation of interferon-gamma production

Inferred from electronic annotation. Source: Ensembl

positive regulation of interleukin-12 production

Non-traceable author statement PubMed 22412986. Source: BHF-UCL

positive regulation of interleukin-2 production

Inferred from electronic annotation. Source: Ensembl

positive regulation of interleukin-6 production

Inferred from electronic annotation. Source: Ensembl

positive regulation of peptidyl-serine phosphorylation

Inferred from direct assay Ref.23. Source: UniProtKB

positive regulation of peptidyl-threonine phosphorylation

Inferred from direct assay Ref.23. Source: UniProtKB

positive regulation of peptidyl-tyrosine phosphorylation

Inferred from direct assay Ref.23. Source: UniProtKB

positive regulation of protein ubiquitination

Inferred from mutant phenotype PubMed 15620648. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Non-traceable author statement PubMed 22412986. Source: BHF-UCL

positive regulation of tumor necrosis factor production

Inferred from electronic annotation. Source: Ensembl

response to exogenous dsRNA

Inferred from electronic annotation. Source: Ensembl

response to interleukin-1

Inferred from electronic annotation. Source: Ensembl

response to interleukin-12

Inferred from electronic annotation. Source: Ensembl

response to interleukin-18

Inferred from electronic annotation. Source: Ensembl

signal transduction

Traceable author statement Ref.2. Source: ProtInc

stress-activated MAPK cascade

Traceable author statement. Source: Reactome

toll-like receptor 10 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 2 signaling pathway

Inferred from direct assay PubMed 11894098. Source: MGI

toll-like receptor 3 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 4 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 5 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 9 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR1:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR6:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

   Cellular_componentcytoplasm

Inferred from direct assay Ref.23. Source: UniProtKB

cytoskeleton

Inferred from direct assay Ref.23. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

protein complex

Inferred from direct assay Ref.23. Source: UniProtKB

vesicle

Inferred from direct assay Ref.23. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

CARD domain binding

Inferred from physical interaction PubMed 11087742. Source: UniProtKB

LIM domain binding

Inferred from physical interaction PubMed 15657077. Source: UniProtKB

non-membrane spanning protein tyrosine kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

protein binding

Inferred from physical interaction Ref.23. Source: UniProtKB

protein homodimerization activity

Inferred from direct assay PubMed 19337385. Source: BHF-UCL

protein serine/threonine kinase activity

Traceable author statement Ref.2. Source: ProtInc

signal transducer activity

Traceable author statement Ref.2. Source: ProtInc

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O43353-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: O43353-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-137: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 540540Receptor-interacting serine/threonine-protein kinase 2
PRO_0000086608

Regions

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

Sites

Active site1461Proton acceptor
Binding site471ATP

Amino acid modifications

Modified residue1681Phosphoserine Ref.17
Modified residue1761Phosphoserine; by autocatalysis Ref.9
Modified residue3631Phosphoserine Ref.13 Ref.17
Modified residue3811Phosphotyrosine; by CSK Ref.23
Modified residue3931Phosphoserine Ref.17
Modified residue4741Phosphotyrosine; by autocatalysis Ref.18
Modified residue5271Phosphoserine Ref.13 Ref.17
Modified residue5291Phosphoserine Ref.19
Modified residue5311Phosphoserine Ref.14
Modified residue5391Phosphoserine Ref.13 Ref.17
Cross-link209Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.12

Natural variations

Alternative sequence1 – 137137Missing in isoform 2.
VSP_013266
Natural variant2591I → T. Ref.25
Corresponds to variant rs2230801 [ dbSNP | Ensembl ].
VAR_041045
Natural variant2681L → V. Ref.25
Corresponds to variant rs35004667 [ dbSNP | Ensembl ].
VAR_041046
Natural variant3131K → N. Ref.25
Corresponds to variant rs35395048 [ dbSNP | Ensembl ].
VAR_041047

Experimental info

Mutagenesis471K → A: Abolishes kinase activity. Ref.1 Ref.2
Mutagenesis471K → M: Reduces FAS-mediated apoptosis. Ref.1 Ref.2
Mutagenesis1461D → N: Abolishes kinase activity. Ref.3
Mutagenesis2091K → R: Complete loss of polyubiquitination. Ref.12
Mutagenesis3811Y → A: Prevents phosphorylation. Reduces serine and threonine phosphorylation of ARHGEF2.
Mutagenesis4441R → E: Abolishes interaction with NOD1. Ref.10
Mutagenesis4741Y → F: Decreases interaction with NOD2. Ref.18
Mutagenesis4831R → E: Abolishes interaction with NOD1. Ref.10
Mutagenesis4881R → E: Abolishes interaction with NOD1. Ref.10
Sequence conflict2711S → G in BAH13484. Ref.5
Sequence conflict5141Q → R in BAH13484. Ref.5

Secondary structure

................................................ 540
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1998. Version 2.
Checksum: 575A692239505792

FASTA54061,195
        10         20         30         40         50         60 
MNGEAICSAL PTIPYHKLAD LRYLSRGASG TVSSARHADW RVQVAVKHLH IHTPLLDSER 

        70         80         90        100        110        120 
KDVLREAEIL HKARFSYILP ILGICNEPEF LGIVTEYMPN GSLNELLHRK TEYPDVAWPL 

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

       190        200        210        220        230        240 
SKSAPEGGTI IYMPPENYEP GQKSRASIKH DIYSYAVITW EVLSRKQPFE DVTNPLQIMY 

       250        260        270        280        290        300 
SVSQGHRPVI NEESLPYDIP HRARMISLIE SGWAQNPDER PSFLKCLIEL EPVLRTFEEI 

       310        320        330        340        350        360 
TFLEAVIQLK KTKLQSVSSA IHLCDKKKME LSLNIPVNHG PQEESCGSSQ LHENSGSPET 

       370        380        390        400        410        420 
SRSLPAPQDN DFLSRKAQDC YFMKLHHCPG NHSWDSTISG SQRAAFCDHK TTPCSSAIIN 

       430        440        450        460        470        480 
PLSTAGNSER LQPGIAQQWI QSKREDIVNQ MTEACLNQSL DALLSRDLIM KEDYELVSTK 

       490        500        510        520        530        540 
PTRTSKVRQL LDTTDIQGEE FAKVIVQKLK DNKQMGLQPY PEILVVSRSP SLNLLQNKSM 

« Hide

Isoform 2 [UniParc].

Checksum: 9F0DE53A01B25EF5
Show »

FASTA40345,582

References

« Hide 'large scale' references
[1]"RICK, a novel protein kinase containing a caspase recruitment domain, interacts with CLARP and regulates CD95-mediated apoptosis."
Inohara N., del Peso L., Koseki T., Chen S., Nunez G.
J. Biol. Chem. 273:12296-12300(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), MUTAGENESIS OF LYS-47.
[2]"RIP2 is a novel NF-kappaB-activating and cell death-inducing kinase."
McCarthy J.V., Ni J., Dixit V.M.
J. Biol. Chem. 273:16968-16975(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), MUTAGENESIS OF LYS-47.
Tissue: Endothelial cell.
[3]"Identification of CARDIAK, a RIP-like kinase that associates with caspase-1."
Thome M., Hofmann K., Burns K., Martinon F., Bodmer J.-L., Mattmann C., Tschopp J.
Curr. Biol. 8:885-888(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), MUTAGENESIS OF ASP-146.
Tissue: Pancreatic adenocarcinoma.
[4]"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. expand/collapse author list , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.
Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Synovium.
[6]"DNA sequence and analysis of human chromosome 8."
Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. expand/collapse author list , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S.
Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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] (ISOFORM 1).
Tissue: Skin.
[8]"Rip2 participates in Bcl10 signaling and T-cell receptor-mediated NF-kappaB activation."
Ruefli-Brasse A.A., Lee W.P., Hurst S., Dixit V.M.
J. Biol. Chem. 279:1570-1574(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"Identification of a regulatory autophosphorylation site in the serine-threonine kinase RIP2."
Dorsch M., Wang A., Cheng H., Lu C., Bielecki A., Charron K., Clauser K., Ren H., Polakiewicz R.D., Parsons T., Li P., Ocain T., Xu Y.
Cell. Signal. 18:2223-2229(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-176.
[10]"Solution structure of NOD1 CARD and mutational analysis of its interaction with the CARD of downstream kinase RICK."
Manon F., Favier A., Nunez G., Simorre J.P., Cusack S.
J. Mol. Biol. 365:160-174(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH NOD1, MUTAGENESIS OF ARG-444; ARG-483 AND ARG-488.
[11]"MEKK4 sequesters RIP2 to dictate NOD2 signal specificity."
Clark N.M., Marinis J.M., Cobb B.A., Abbott D.W.
Curr. Biol. 18:1402-1408(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MAP3K4.
[12]"A critical role of RICK/RIP2 polyubiquitination in Nod-induced NF-kappaB activation."
Hasegawa M., Fujimoto Y., Lucas P.C., Nakano H., Fukase K., Nunez G., Inohara N.
EMBO J. 27:373-383(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH IKBKG/NEMO AND MAP3K7/TAK1, FUNCTION, UBIQUITINATION AT LYS-209, MUTAGENESIS OF LYS-209.
[13]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-363; SER-527 AND SER-539, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[14]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-531, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[15]"ITCH K63-ubiquitinates the NOD2 binding protein, RIP2, to influence inflammatory signaling pathways."
Tao M., Scacheri P.C., Marinis J.M., Harhaj E.W., Matesic L.E., Abbott D.W.
Curr. Biol. 19:1255-1263(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION BY ITCH, INTERACTION WITH NOD2.
[16]"Cellular inhibitors of apoptosis cIAP1 and cIAP2 are required for innate immunity signaling by the pattern recognition receptors NOD1 and NOD2."
Bertrand M.J., Doiron K., Labbe K., Korneluk R.G., Barker P.A., Saleh M.
Immunity 30:789-801(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION BY BIRC2 AND BIRC3.
[17]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-168; SER-363; SER-393; SER-527 AND SER-539, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[18]"Inhibition of RIP2's tyrosine kinase activity limits NOD2-driven cytokine responses."
Tigno-Aranjuez J.T., Asara J.M., Abbott D.W.
Genes Dev. 24:2666-2677(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION AT TYR-474, MUTAGENESIS OF TYR-474.
[19]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-529, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[20]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[21]"cIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4)."
Bertrand M.J., Lippens S., Staes A., Gilbert B., Roelandt R., De Medts J., Gevaert K., Declercq W., Vandenabeele P.
PLoS ONE 6:E22356-E22356(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION BY BIRC2/C-IAP1 AND BIRC3/C-IAP2, INTERACTION WITH BIRC2/C-IAP1; BIRC3/C-IAP2 AND XIAP/BIRC4.
[22]"NLRP10 enhances Shigella-induced pro-inflammatory responses."
Lautz K., Damm A., Menning M., Wenger J., Adam A.C., Zigrino P., Kremmer E., Kufer T.A.
Cell. Microbiol. 14:1568-1583(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NLRP10.
[23]"Control of NOD2 and Rip2-dependent innate immune activation by GEF-H1."
Zhao Y., Alonso C., Ballester I., Song J.H., Chang S.Y., Guleng B., Arihiro S., Murray P.J., Xavier R., Kobayashi K.S., Reinecker H.C.
Inflamm. Bowel Dis. 18:603-612(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, IDENTIFICATION IN A COMPLEX WITH ARHGEF2 AND NOD2, INTERACTION WITH ARHGEF2 AND NOD2, PHOSPHORYLATION AT TYR-381.
[24]"OTULIN restricts Met1-linked ubiquitination to control innate immune signaling."
Fiil B.K., Damgaard R.B., Wagner S.A., Keusekotten K., Fritsch M., Bekker-Jensen S., Mailand N., Choudhary C., Komander D., Gyrd-Hansen M.
Mol. Cell 50:818-830(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION, DEUBIQUITINATION.
[25]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] THR-259; VAL-268 AND ASN-313.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF027706 mRNA. Translation: AAC34970.1.
AF078530 mRNA. Translation: AAC27722.1.
AF064824 mRNA. Translation: AAC25668.1.
AY358813 mRNA. Translation: AAQ89172.1.
AY358814 mRNA. Translation: AAQ89173.1.
AK301448 mRNA. Translation: BAH13484.1.
AC004003 Genomic DNA. Translation: AAC24561.1.
AF117829 Genomic DNA. No translation available.
BC004553 mRNA. Translation: AAH04553.1.
CCDSCCDS6247.1. [O43353-1]
RefSeqNP_003812.1. NM_003821.5. [O43353-1]
XP_005251149.1. XM_005251092.2. [O43353-2]
UniGeneHs.103755.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4C8BX-ray2.75A/B8-317[»]
ProteinModelPortalO43353.
SMRO43353. Positions 9-316.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114300. 39 interactions.
DIPDIP-27518N.
IntActO43353. 11 interactions.
MINTMINT-90752.
STRING9606.ENSP00000220751.

Chemistry

BindingDBO43353.
ChEMBLCHEMBL5014.
GuidetoPHARMACOLOGY2190.

PTM databases

PhosphoSiteO43353.

Proteomic databases

MaxQBO43353.
PaxDbO43353.
PRIDEO43353.

Protocols and materials databases

DNASU8767.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000220751; ENSP00000220751; ENSG00000104312. [O43353-1]
ENST00000540020; ENSP00000441623; ENSG00000104312. [O43353-2]
GeneID8767.
KEGGhsa:8767.
UCSCuc003yee.3. human. [O43353-1]

Organism-specific databases

CTD8767.
GeneCardsGC08P090769.
HGNCHGNC:10020. RIPK2.
HPAHPA015273.
HPA016499.
MIM603455. gene.
neXtProtNX_O43353.
PharmGKBPA34395.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000136856.
HOVERGENHBG054242.
InParanoidO43353.
KOK08846.
OMAYPDVAWP.
OrthoDBEOG78H3SS.
PhylomeDBO43353.
TreeFamTF106506.

Enzyme and pathway databases

BRENDA2.7.10.2. 2681.
ReactomeREACT_111102. Signal Transduction.
REACT_6782. TRAF6 Mediated Induction of proinflammatory cytokines.
REACT_6900. Immune System.
SignaLinkO43353.

Gene expression databases

ArrayExpressO43353.
BgeeO43353.
CleanExHS_RIPK2.
GenevestigatorO43353.

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

GeneWikiRIPK2.
GenomeRNAi8767.
NextBio32880.
PROO43353.
SOURCESearch...

Entry information

Entry nameRIPK2_HUMAN
AccessionPrimary (citable) accession number: O43353
Secondary accession number(s): B7Z748, Q6UWF0
Entry history
Integrated into UniProtKB/Swiss-Prot: May 2, 2002
Last sequence update: November 1, 1998
Last modified: July 9, 2014
This is version 157 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM