O43353 (RIPK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	540 AA.
Sequence status	Complete.
Protein existence	Evidence 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. Once recruited, RIPK2 autophosphorylates and undergoes 'Lys-63'-linked polyubiquitination by E3 ubiquitin ligases 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.7 Ref.9 Ref.11 Ref.17
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subunit structure	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 and NOD2. 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. Ref.9 Ref.10 Ref.11 Ref.14 Ref.20 Ref.21
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. Ref.8 Ref.17 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. Ref.11 Ref.14 Ref.15 Ref.20
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 process	Adaptive immunity Apoptosis Immunity Innate immunity
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
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 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 T cell proliferation Inferred from electronic annotation. Source: Compara 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 Toll 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: Compara cellular response to peptidoglycan Inferred from electronic annotation. Source: Compara defense response to Gram-positive bacterium Inferred from electronic annotation. Source: Compara inflammatory response Traceable author statement Ref.3. Source: ProtInc innate immune response Inferred from sequence or structural similarity. Source: UniProtKB lipopolysaccharide-mediated signaling pathway Inferred from electronic annotation. Source: Compara nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome nucleotide-binding oligomerization domain containing 1 signaling pathway Inferred from electronic annotation. Source: Compara nucleotide-binding oligomerization domain containing 2 signaling pathway Inferred from electronic annotation. Source: Compara nucleotide-binding oligomerization domain containing signaling pathway Traceable author statement. Source: Reactome positive regulation of ERK1 and ERK2 cascade Inferred from electronic annotation. Source: Compara positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from direct assay PubMed 10329646. Source: MGI positive regulation of JNK cascade Inferred from electronic annotation. Source: Compara positive regulation of NF-kappaB transcription factor activity Traceable author statement. Source: Reactome positive regulation of T-helper 1 cell differentiation Inferred from electronic annotation. Source: Compara positive regulation of T-helper 1 type immune response Inferred from electronic annotation. Source: Compara positive regulation of alpha-beta T cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of apoptotic process Inferred from electronic annotation. Source: Compara positive regulation of chemokine production Inferred from electronic annotation. Source: Compara positive regulation of cytokine-mediated signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of immature T cell proliferation Inferred from electronic annotation. Source: Compara 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: Compara 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: Compara positive regulation of interleukin-6 production Inferred from electronic annotation. Source: Compara 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: Compara response to exogenous dsRNA Inferred from electronic annotation. Source: Compara response to interleukin-1 Inferred from electronic annotation. Source: Compara response to interleukin-12 Inferred from electronic annotation. Source: Compara response to interleukin-18 Inferred from electronic annotation. Source: Compara toll-like receptor 1 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
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW CARD domain binding Inferred from direct assay PubMed 10329646. Source: MGI non-membrane spanning protein tyrosine kinase activity Inferred from electronic annotation. Source: EC 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...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BIRC2	Q13490	3	EBI-358522,EBI-514538
BIRC3	Q13489	3	EBI-358522,EBI-517709
MAVS	Q7Z434	3	EBI-358522,EBI-995373

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 540	540	Receptor-interacting serine/threonine-protein kinase 2		PRO_0000086608
Regions
	Domain	18 – 294	277	Protein kinase
	Domain	432 – 524	93	CARD
	Nucleotide binding	24 – 32	9	ATP By similarity
Sites
	Active site	146	1	Proton acceptor
	Binding site	47	1	ATP
Amino acid modifications
	Modified residue	168	1	Phosphoserine Ref.16
	Modified residue	176	1	Phosphoserine; by autocatalysis Ref.8
	Modified residue	363	1	Phosphoserine Ref.12 Ref.16
	Modified residue	393	1	Phosphoserine Ref.16
	Modified residue	474	1	Phosphotyrosine; by autocatalysis
	Modified residue	527	1	Phosphoserine Ref.12 Ref.16
	Modified residue	529	1	Phosphoserine Ref.18
	Modified residue	531	1	Phosphoserine Ref.13
	Modified residue	539	1	Phosphoserine Ref.12 Ref.16
Natural variations
	Alternative sequence	1 – 137	137	Missing in isoform 2.		VSP_013266
	Natural variant	259	1	I → T. Ref.22 Corresponds to variant rs2230801 [ dbSNP | Ensembl ].		VAR_041045
	Natural variant	268	1	L → V. Ref.22 Corresponds to variant rs35004667 [ dbSNP | Ensembl ].		VAR_041046
	Natural variant	313	1	K → N. Ref.22 Corresponds to variant rs35395048 [ dbSNP | Ensembl ].		VAR_041047
Experimental info
	Mutagenesis	47	1	K → A: Abolishes kinase activity. Ref.1 Ref.2
	Mutagenesis	47	1	K → M: Reduces FAS-mediated apoptosis. Ref.1 Ref.2
	Mutagenesis	146	1	D → N: Abolishes kinase activity. Ref.3
	Mutagenesis	209	1	K → R: Complete loss of polyubiquitination. Ref.11
	Mutagenesis	444	1	R → E: Abolishes interaction with NOD1. Ref.9
	Mutagenesis	474	1	Y → F: Decreases interaction with NOD2. Ref.17
	Mutagenesis	483	1	R → E: Abolishes interaction with NOD1. Ref.9
	Mutagenesis	488	1	R → E: Abolishes interaction with NOD1. Ref.9

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1998. Version 2. Checksum: 575A692239505792	FASTA	540	61,195
	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
	Isoform 2 [UniParc]. Checksum: 9F0DE53A01B25EF5	FASTA	403	45,582
	10 20 30 40 50 60 MTPPLLHHDL KTQNILLDNE FHVKIADFGL SKWRMMSLSQ SRSSKSAPEG GTIIYMPPEN 70 80 90 100 110 120 YEPGQKSRAS IKHDIYSYAV ITWEVLSRKQ PFEDVTNPLQ IMYSVSQGHR PVINEESLPY 130 140 150 160 170 180 DIPHRARMIS LIESGWAQNP DERPSFLKCL IELEPVLRTF EEITFLEAVI QLKKTKLQSV 190 200 210 220 230 240 SSAIHLCDKK KMELSLNIPV NHGPQEESCG SSQLHENSGS PETSRSLPAP QDNDFLSRKA 250 260 270 280 290 300 QDCYFMKLHH CPGNHSWDST ISGSQRAAFC DHKTTPCSSA IINPLSTAGN SERLQPGIAQ 310 320 330 340 350 360 QWIQSKREDI VNQMTEACLN QSLDALLSRD LIMKEDYELV STKPTRTSKV RQLLDTTDIQ 370 380 390 400 GEEFAKVIVQ KLKDNKQMGL QPYPEILVVS RSPSLNLLQN KSM

References

	« Hide 'large scale' referencesShow '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. , 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]	"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. , 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].
[6]	"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.
[7]	"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.
[8]	"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: AUTOPHOSPHORYLATION AT SER-176.
[9]	"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.
[10]	"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.
[11]	"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.
[12]	"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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[13]	"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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"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 RIPK2, INTERACTION WITH NOD2.
[15]	"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.
[16]	"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, MASS SPECTROMETRY.
[17]	"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, AUTOPHOSPHORYLATION, MUTAGENESIS OF TYR-474.
[18]	"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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[19]	"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].
[20]	"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.
[21]	"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.
[22]	"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. , 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. AC004003 Genomic DNA. Translation: AAC24561.1. AF117829 Genomic DNA. No translation available. BC004553 mRNA. Translation: AAH04553.1.
IPI	IPI00021917. IPI00554774.
RefSeq	NP_003812.1. NM_003821.5.
UniGene	Hs.103755.
3D structure databases
ProteinModelPortal	O43353.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-27518N.
IntAct	O43353. 8 interactions.
MINT	MINT-90752.
STRING	9606.ENSP00000220751.
PTM databases
PhosphoSite	O43353.
Proteomic databases
PaxDb	O43353.
PRIDE	O43353.
Protocols and materials databases
DNASU	8767.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000220751; ENSP00000220751; ENSG00000104312. ENST00000540020; ENSP00000441623; ENSG00000104312.
GeneID	8767.
KEGG	hsa:8767.
UCSC	uc003yee.3. human.
Organism-specific databases
CTD	8767.
GeneCards	GC08P090769.
HGNC	HGNC:10020. RIPK2.
HPA	HPA015273. HPA016499.
MIM	603455. gene.
neXtProt	NX_O43353.
PharmGKB	PA34395.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000136856.
HOVERGEN	HBG054242.
InParanoid	O43353.
KO	K08846.
OMA	PDVAWPL.
OrthoDB	EOG4VQ9NZ.
Enzyme and pathway databases
BRENDA	2.7.10.2. 2681.
Pathway_Interaction_DB	nfkappabcanonicalpathway. Canonical NF-kappaB pathway. il12_2pathway. IL12-mediated signaling events. p75ntrpathway. p75(NTR)-mediated signaling.
Reactome	REACT_111102. Signal Transduction. REACT_6782. TRAF6 Mediated Induction of proinflammatory cytokines. REACT_6900. Immune System.
Gene expression databases
ArrayExpress	O43353.
Bgee	O43353.
CleanEx	HS_RIPK2.
Genevestigator	O43353.
GermOnline	ENSG00000104312. Homo sapiens.
Family and domain databases
Gene3D	1.10.533.10. 1 hit.
InterPro	IPR001315. CARD. IPR011029. DEATH-like_dom. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017322. Rcpt-int_Ser/Thr_kinase-2. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
Pfam	PF00619. CARD. 1 hit. PF00069. Pkinase. 1 hit. [Graphical view]
PIRSF	PIRSF037921. STPK_RIP2. 1 hit.
SMART	SM00114. CARD. 1 hit. [Graphical view]
SUPFAM	SSF47986. DEATH_like. 1 hit. SSF56112. Kinase_like. 1 hit.
PROSITE	PS50209. CARD. 1 hit. PS00107. PROTEIN_KINASE_ATP. False negative. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	O43353.
ChEMBL	CHEMBL5014.
GenomeRNAi	8767.
NextBio	32880.
SOURCE	Search...

Entry information

Entry name

RIPK2_HUMAN

Accession

Primary (citable) accession number: O43353
Secondary accession number(s): Q6UWF0

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 2, 2002
Last sequence update:	November 1, 1998
Last modified:	May 1, 2013
This is version 144 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.