LOCUS       NP_003812                540 aa            linear   PRI 12-JUN-2025
DEFINITION  receptor-interacting serine/threonine-protein kinase 2 isoform 1
            [Homo sapiens].
ACCESSION   NP_003812
VERSION     NP_003812.1
DBSOURCE    REFSEQ: accession NM_003821.6
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 540)
  AUTHORS   Goncharov,T., Komuves,L.G., Kist,M., Castellanos,E.R., Witt,A.,
            Fedorova,A.V., Izrael-Tomasevic,A., Yu,K., Keir,M., Matsumoto,M.L.
            and Vucic,D.
  TITLE     Simultaneous substrate and ubiquitin modification recognition by
            bispecific antibodies enables detection of ubiquitinated RIP1 and
            RIP2
  JOURNAL   Sci Signal 17 (819), eabn1101 (2024)
   PUBMED   38227684
  REMARK    GeneRIF: Simultaneous substrate and ubiquitin modification
            recognition by bispecific antibodies enables detection of
            ubiquitinated RIP1 and RIP2.
REFERENCE   2  (residues 1 to 540)
  AUTHORS   Lee,J., Sim,K.M., Kang,M., Oh,H.J., Choi,H.J., Kim,Y.E., Pack,C.G.,
            Kim,K., Kim,K.M., Oh,S.H., Kim,I. and Chang,I.
  TITLE     Understanding the molecular mechanism of pathogenic variants of
            BIR2 domain in XIAP-deficient inflammatory bowel disease
  JOURNAL   Sci Rep 14 (1), 853 (2024)
   PUBMED   38191507
  REMARK    Publication Status: Online-Only
REFERENCE   3  (residues 1 to 540)
  AUTHORS   Zheng,S., Li,Y., Song,X., Wu,M., Yu,L., Huang,G., Liu,T., Zhang,L.,
            Shang,M., Zhu,Q., Gao,C., Chen,L. and Liu,H.
  TITLE     OTUD1 ameliorates cerebral ischemic injury through inhibiting
            inflammation by disrupting K63-linked deubiquitination of RIP2
  JOURNAL   J Neuroinflammation 20 (1), 281 (2023)
   PUBMED   38012669
  REMARK    Publication Status: Online-Only
REFERENCE   4  (residues 1 to 540)
  AUTHORS   Hezinger,L., Bauer,S., Ellwanger,K., Piotrowsky,A., Biber,F.,
            Venturelli,S. and Kufer,T.A.
  TITLE     NOD1 cooperates with HAX-1 to promote cell migration in a RIPK2-
            and NF-kB-independent manner
  JOURNAL   FEBS J 290 (22), 5295-5312 (2023)
   PUBMED   37488967
  REMARK    GeneRIF: NOD1 cooperates with HAX-1 to promote cell migration in a
            RIPK2- and NF-kB-independent manner.
REFERENCE   5  (residues 1 to 540)
  AUTHORS   Cui,K., Wang,X., Han,C., Liu,S. and Hu,Y.
  TITLE     Mechanism of Human Cytomegalovirus-Induced Epithelial-Mesenchymal
            Transition in Glioma Cells via the Upregulation of RIP2 Expression
  JOURNAL   Biol Pharm Bull 46 (11), 1506-1511 (2023)
   PUBMED   37914353
  REMARK    GeneRIF: Mechanism of Human Cytomegalovirus-Induced
            Epithelial-Mesenchymal Transition in Glioma Cells via the
            Upregulation of RIP2 Expression.
REFERENCE   6  (residues 1 to 540)
  AUTHORS   Thome,M., Hofmann,K., Burns,K., Martinon,F., Bodmer,J.L.,
            Mattmann,C. and Tschopp,J.
  TITLE     Identification of CARDIAK, a RIP-like kinase that associates with
            caspase-1
  JOURNAL   Curr Biol 8 (15), 885-888 (1998)
   PUBMED   9705938
REFERENCE   7  (residues 1 to 540)
  AUTHORS   McCarthy,J.V., Ni,J. and Dixit,V.M.
  TITLE     RIP2 is a novel NF-kappaB-activating and cell death-inducing kinase
  JOURNAL   J Biol Chem 273 (27), 16968-16975 (1998)
   PUBMED   9642260
REFERENCE   8  (residues 1 to 540)
  AUTHORS   Inohara,N., del Peso,L., Koseki,T., Chen,S. and Nunez,G.
  TITLE     RICK, a novel protein kinase containing a caspase recruitment
            domain, interacts with CLARP and regulates CD95-mediated apoptosis
  JOURNAL   J Biol Chem 273 (20), 12296-12300 (1998)
   PUBMED   9575181
  REMARK    Erratum:[J Biol Chem 1998 Jul 17;273(29):18675]
REFERENCE   9  (residues 1 to 540)
  AUTHORS   Mercurio,F., Zhu,H., Murray,B.W., Shevchenko,A., Bennett,B.L.,
            Li,J., Young,D.B., Barbosa,M., Mann,M., Manning,A. and Rao,A.
  TITLE     IKK-1 and IKK-2: cytokine-activated IkappaB kinases essential for
            NF-kappaB activation
  JOURNAL   Science 278 (5339), 860-866 (1997)
   PUBMED   9346484
REFERENCE   10 (residues 1 to 540)
  AUTHORS   Kunsch,C., Ruben,S.M. and Rosen,C.A.
  TITLE     Selection of optimal kappa B/Rel DNA-binding motifs: interaction of
            both subunits of NF-kappa B with DNA is required for
            transcriptional activation
  JOURNAL   Mol Cell Biol 12 (10), 4412-4421 (1992)
   PUBMED   1406630
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AY358814.1 and AI824070.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            Summary: This gene encodes a member of the receptor-interacting
            protein (RIP) family of serine/threonine protein kinases. The
            encoded protein contains a C-terminal caspase activation and
            recruitment domain (CARD), and is a component of signaling
            complexes in both the innate and adaptive immune pathways. It is a
            potent activator of NF-kappaB and inducer of apoptosis in response
            to various stimuli. [provided by RefSeq, Jul 2008].
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: AY358814.1, SRR1660807.150538.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000220751.5/ ENSP00000220751.4
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..540
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="8"
                     /map="8q21.3"
     Protein         1..540
                     /product="receptor-interacting serine/threonine-protein
                     kinase 2 isoform 1"
                     /EC_number="2.7.11.1"
                     /EC_number="2.7.10.2"
                     /note="receptor-interacting protein (RIP)-like interacting
                     caspase-like apoptosis regulatory protein (CLARP) kinase;
                     CARD-containing interleukin-1 beta-converting enzyme
                     (ICE)-associated kinase; growth-inhibiting gene 30;
                     CARD-carrying kinase; receptor-interacting
                     serine/threonine-protein kinase 2; RIP-2;
                     receptor-interacting protein 2; CARD-containing IL-1 beta
                     ICE-kinase; tyrosine-protein kinase RIPK2"
                     /calculated_mol_wt=61064
     Region          20..303
                     /region_name="STKc_RIP2"
                     /note="Catalytic domain of the Serine/Threonine kinase,
                     Receptor Interacting Protein 2; cd14026"
                     /db_xref="CDD:270928"
     Site            order(24..28,32,45,47,79,95..98,102,104,146,148,150..151,
                     153,164,167,188..191)
                     /site_type="active"
                     /db_xref="CDD:270928"
     Site            order(24..28,32,45,47,79,95..98,102,146,148,150..151,153,
                     164)
                     /site_type="other"
                     /note="ATP binding site [chemical binding]"
                     /db_xref="CDD:270928"
     Site            order(28,102,104,146,148,150,167,188..191)
                     /site_type="other"
                     /note="polypeptide substrate binding site [polypeptide
                     binding]"
                     /db_xref="CDD:270928"
     Region          65..73
                     /region_name="Helix alphaC.
                     /evidence=ECO:0000269|PubMed:28545134"
                     /note="propagated from UniProtKB/Swiss-Prot (O43353.2)"
     Site            149
                     /site_type="acetylation"
                     /note="(Microbial infection) O-acetylthreonine, by
                     Yersinia YopJ. /evidence=ECO:0000269|PubMed:22520462;
                     propagated from UniProtKB/Swiss-Prot (O43353.2)"
     Site            163..191
                     /site_type="other"
                     /note="activation loop (A-loop)"
                     /db_xref="CDD:270928"
     Region          167..193
                     /region_name="Activation segment (AS).
                     /evidence=ECO:0000269|PubMed:28545134"
                     /note="propagated from UniProtKB/Swiss-Prot (O43353.2)"
     Site            168
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:19369195; propagated from
                     UniProtKB/Swiss-Prot (O43353.2)"
     Site            174
                     /site_type="acetylation"
                     /note="(Microbial infection) O-acetylserine, by Yersinia
                     YopJ. /evidence=ECO:0000269|PubMed:22520462; propagated
                     from UniProtKB/Swiss-Prot (O43353.2)"
     Site            174
                     /site_type="phosphorylation"
                     /note="Phosphoserine, alternate.
                     /evidence=ECO:0000269|PubMed:28545134; propagated from
                     UniProtKB/Swiss-Prot (O43353.2)"
     Site            176
                     /site_type="acetylation"
                     /note="(Microbial infection) O-acetylserine, by Yersinia
                     YopJ, alternate. /evidence=ECO:0000269|PubMed:22520462;
                     propagated from UniProtKB/Swiss-Prot (O43353.2)"
     Site            176
                     /site_type="phosphorylation"
                     /note="Phosphoserine, by autocatalysis and LRRK2,
                     alternate. /evidence=ECO:0000269|PubMed:16824733,
                     ECO:0000269|PubMed:27830463, ECO:0000269|PubMed:28545134;
                     propagated from UniProtKB/Swiss-Prot (O43353.2)"
     Site            178
                     /site_type="acetylation"
                     /note="(Microbial infection) O-acetylserine, by Yersinia
                     YopJ. /evidence=ECO:0000269|PubMed:22520462; propagated
                     from UniProtKB/Swiss-Prot (O43353.2)"
     Site            178
                     /site_type="phosphorylation"
                     /note="Phosphoserine, alternate.
                     /evidence=ECO:0000269|PubMed:28545134; propagated from
                     UniProtKB/Swiss-Prot (O43353.2)"
     Site            180
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0000269|PubMed:28545134; propagated from
                     UniProtKB/Swiss-Prot (O43353.2)"
     Site            181
                     /site_type="acetylation"
                     /note="(Microbial infection) O-acetylserine, by Yersinia
                     YopJ. /evidence=ECO:0000269|PubMed:22520462; propagated
                     from UniProtKB/Swiss-Prot (O43353.2)"
     Site            181
                     /site_type="phosphorylation"
                     /note="Phosphoserine, alternate.
                     /evidence=ECO:0000269|PubMed:28545134; propagated from
                     UniProtKB/Swiss-Prot (O43353.2)"
     Site            183
                     /site_type="acetylation"
                     /note="(Microbial infection) O-acetylserine, by Yersinia
                     YopJ. /evidence=ECO:0000269|PubMed:22520462; propagated
                     from UniProtKB/Swiss-Prot (O43353.2)"
     Site            189
                     /site_type="acetylation"
                     /note="(Microbial infection) O-acetylthreonine, by
                     Yersinia YopJ. /evidence=ECO:0000269|PubMed:22520462;
                     propagated from UniProtKB/Swiss-Prot (O43353.2)"
     Region          338..369
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (O43353.2)"
     Site            363
                     /site_type="acetylation"
                     /note="(Microbial infection) O-acetylserine, by Yersinia
                     YopJ. /evidence=ECO:0000269|PubMed:22520462; propagated
                     from UniProtKB/Swiss-Prot (O43353.2)"
     Site            363
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:18691976,
                     ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:23186163;
                     propagated from UniProtKB/Swiss-Prot (O43353.2)"
     Site            381
                     /site_type="phosphorylation"
                     /note="Phosphotyrosine, by CSK.
                     /evidence=ECO:0000269|PubMed:21887730; propagated from
                     UniProtKB/Swiss-Prot (O43353.2)"
     Site            393
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:19369195; propagated from
                     UniProtKB/Swiss-Prot (O43353.2)"
     Site            397
                     /site_type="acetylation"
                     /note="(Microbial infection) O-acetylthreonine, by
                     Yersinia YopJ. /evidence=ECO:0000269|PubMed:22520462;
                     propagated from UniProtKB/Swiss-Prot (O43353.2)"
     Site            423
                     /site_type="acetylation"
                     /note="(Microbial infection) O-acetylserine, by Yersinia
                     YopJ. /evidence=ECO:0000269|PubMed:22520462; propagated
                     from UniProtKB/Swiss-Prot (O43353.2)"
     Region          438..524
                     /region_name="CARD_RIP2_CARD3"
                     /note="Caspase activation and recruitment domain of
                     Receptor Interacting Protein 2; cd08786"
                     /db_xref="CDD:176764"
     Site            474
                     /site_type="phosphorylation"
                     /note="Phosphotyrosine, by autocatalysis.
                     /evidence=ECO:0000269|PubMed:21123652; propagated from
                     UniProtKB/Swiss-Prot (O43353.2)"
     Site            527
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:18691976,
                     ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:23186163;
                     propagated from UniProtKB/Swiss-Prot (O43353.2)"
     Site            529
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:20068231,
                     ECO:0007744|PubMed:23186163; propagated from
                     UniProtKB/Swiss-Prot (O43353.2)"
     Site            531
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:18669648,
                     ECO:0007744|PubMed:23186163; propagated from
                     UniProtKB/Swiss-Prot (O43353.2)"
     Site            539
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:18691976,
                     ECO:0007744|PubMed:19369195; propagated from
                     UniProtKB/Swiss-Prot (O43353.2)"
     CDS             1..540
                     /gene="RIPK2"
                     /gene_synonym="CARD3; CARDIAK; CCK; GIG30; RICK; RIP2"
                     /coded_by="NM_003821.6:246..1868"
                     /note="isoform 1 is encoded by transcript variant 1"
                     /db_xref="CCDS:CCDS6247.1"
                     /db_xref="GeneID:8767"
                     /db_xref="HGNC:HGNC:10020"
                     /db_xref="MIM:603455"
ORIGIN      
        1 mngeaicsal ptipyhklad lrylsrgasg tvssarhadw rvqvavkhlh ihtplldser
       61 kdvlreaeil hkarfsyilp ilgicnepef lgivteympn gslnellhrk teypdvawpl
      121 rfrilheial gvnylhnmtp pllhhdlktq nilldnefhv kiadfglskw rmmslsqsrs
      181 sksapeggti iymppenyep gqksrasikh diysyavitw evlsrkqpfe dvtnplqimy
      241 svsqghrpvi neeslpydip hrarmislie sgwaqnpder psflkcliel epvlrtfeei
      301 tfleaviqlk ktklqsvssa ihlcdkkkme lslnipvnhg pqeescgssq lhensgspet
      361 srslpapqdn dflsrkaqdc yfmklhhcpg nhswdstisg sqraafcdhk ttpcssaiin
      421 plstagnser lqpgiaqqwi qskredivnq mteaclnqsl dallsrdlim kedyelvstk
      481 ptrtskvrql ldttdiqgee fakvivqklk dnkqmglqpy peilvvsrsp slnllqnksm
//
