LOCUS       NP_001341859             671 aa            linear   PRI 11-FEB-2025
DEFINITION  receptor-interacting serine/threonine-protein kinase 1 isoform 1
            [Homo sapiens].
ACCESSION   NP_001341859 XP_005249514
VERSION     NP_001341859.1
DBSOURCE    REFSEQ: accession NM_001354930.2
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 671)
  AUTHORS   Mannion,J., Gifford,V., Bellenie,B., Fernando,W., Ramos Garcia,L.,
            Wilson,R., John,S.W., Udainiya,S., Patin,E.C., Tiu,C., Smith,A.,
            Goicoechea,M., Craxton,A., Moraes de Vasconcelos,N., Guppy,N.,
            Cheung,K.J., Cundy,N.J., Pierrat,O., Brennan,A., Roumeliotis,T.I.,
            Benstead-Hume,G., Alexander,J., Muirhead,G., Layzell,S., Lyu,W.,
            Roulstone,V., Allen,M., Baldock,H., Legrand,A., Gabel,F.,
            Serrano-Aparicio,N., Starling,C., Guo,H., Upton,J., Gyrd-Hansen,M.,
            MacFarlane,M., Seddon,B., Raynaud,F., Roxanis,I., Harrington,K.,
            Haider,S., Choudhary,J.S., Hoelder,S., Tenev,T. and Meier,P.
  TITLE     A RIPK1-specific PROTAC degrader achieves potent antitumor activity
            by enhancing immunogenic cell death
  JOURNAL   Immunity 57 (7), 1514-1532 (2024)
   PUBMED   38788712
  REMARK    GeneRIF: A RIPK1-specific PROTAC degrader achieves potent antitumor
            activity by enhancing immunogenic cell death.
REFERENCE   2  (residues 1 to 671)
  AUTHORS   Jin,X., Zhang,Y., Zhou,Y., Luo,Y., Han,X., Gao,Y., Yu,H., Duan,Y.,
            Shi,L., Wu,Y. and Li,Y.
  TITLE     Sirt1 Deficiency Promotes Age-Related AF Through Enhancing Atrial
            Necroptosis by Activation of RIPK1 Acetylation
  JOURNAL   Circ Arrhythm Electrophysiol 17 (7), e012452 (2024)
   PUBMED   39012929
  REMARK    GeneRIF: Sirt1 Deficiency Promotes Age-Related AF Through Enhancing
            Atrial Necroptosis by Activation of RIPK1 Acetylation.
REFERENCE   3  (residues 1 to 671)
  AUTHORS   Yang,M., Wei,Y., He,X. and Xia,C.
  TITLE     The deubiquitinating protein OTUD6B promotes lung adenocarcinoma
            progression by stabilizing RIPK1
  JOURNAL   Biol Direct 19 (1), 46 (2024)
   PUBMED   38880876
  REMARK    GeneRIF: The deubiquitinating protein OTUD6B promotes lung
            adenocarcinoma progression by stabilizing RIPK1.
            Publication Status: Online-Only
REFERENCE   4  (residues 1 to 671)
  AUTHORS   Damhofer,H., Tatar,T., Southgate,B., Scarneo,S., Agger,K.,
            Shlyueva,D., Uhrbom,L., Morrison,G.M., Hughes,P.F., Haystead,T.,
            Pollard,S.M. and Helin,K.
  TITLE     TAK1 inhibition leads to RIPK1-dependent apoptosis in
            immune-activated cancers
  JOURNAL   Cell Death Dis 15 (4), 273 (2024)
   PUBMED   38632238
  REMARK    GeneRIF: TAK1 inhibition leads to RIPK1-dependent apoptosis in
            immune-activated cancers.
            Publication Status: Online-Only
REFERENCE   5  (residues 1 to 671)
  AUTHORS   Lee,Y.M. and Vucic,D.
  TITLE     The role of autophagy in RIP1 mediated cell death and intestinal
            inflammation
  JOURNAL   Adv Immunol 163, 1-20 (2024)
   PUBMED   39271257
  REMARK    GeneRIF: The role of autophagy in RIP1 mediated cell death and
            intestinal inflammation.
            Review article
REFERENCE   6  (residues 1 to 671)
  AUTHORS   Silke,J., Rickard,J.A. and Gerlic,M.
  TITLE     The diverse role of RIP kinases in necroptosis and inflammation
  JOURNAL   Nat Immunol 16 (7), 689-697 (2015)
   PUBMED   26086143
  REMARK    GeneRIF: Studies indicate that RIP kinases RIPK1 and RIPK3 directly
            regulate inflammatory signaling.
            Review article
            Erratum:[Nat Immunol. 2015 Aug;16(8):889. doi:
            10.1038/ni0815-889b.. PMID: 26194288]
REFERENCE   7  (residues 1 to 671)
  AUTHORS   Takeuchi,M., Rothe,M. and Goeddel,D.V.
  TITLE     Anatomy of TRAF2. Distinct domains for nuclear factor-kappaB
            activation and association with tumor necrosis factor signaling
            proteins
  JOURNAL   J Biol Chem 271 (33), 19935-19942 (1996)
   PUBMED   8702708
REFERENCE   8  (residues 1 to 671)
  AUTHORS   Hsu,H., Huang,J., Shu,H.B., Baichwal,V. and Goeddel,D.V.
  TITLE     TNF-dependent recruitment of the protein kinase RIP to the TNF
            receptor-1 signaling complex
  JOURNAL   Immunity 4 (4), 387-396 (1996)
   PUBMED   8612133
REFERENCE   9  (residues 1 to 671)
  AUTHORS   Hsu,H., Xiong,J. and Goeddel,D.V.
  TITLE     The TNF receptor 1-associated protein TRADD signals cell death and
            NF-kappa B activation
  JOURNAL   Cell 81 (4), 495-504 (1995)
   PUBMED   7758105
REFERENCE   10 (residues 1 to 671)
  AUTHORS   Stanger,B.Z., Leder,P., Lee,T.H., Kim,E. and Seed,B.
  TITLE     RIP: a novel protein containing a death domain that interacts with
            Fas/APO-1 (CD95) in yeast and causes cell death
  JOURNAL   Cell 81 (4), 513-523 (1995)
   PUBMED   7538908
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL031963.40.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Aug 30, 2017 this sequence version replaced XP_005249514.2.
            
            Summary: This gene encodes a member of the receptor-interacting
            protein (RIP) family of serine/threonine protein kinases. The
            encoded protein plays a role in inflammation and cell death in
            response to tissue damage, pathogen recognition, and as part of
            developmental regulation. RIPK1/RIPK3 kinase-mediated necrosis is
            referred to as necroptosis. Genetic disruption of this gene in mice
            results in death shortly after birth. [provided by RefSeq, Aug
            2017].
            
            Sequence Note: The RefSeq transcript and protein were derived from
            genomic sequence to make the sequence consistent with the reference
            genome assembly. The genomic coordinates used for the transcript
            record were based on alignments.
            
            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 :: SRR1803611.265177.1,
                                           SRR1660803.229431.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000259808.9/ ENSP00000259808.3
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..671
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="6"
                     /map="6p25.2"
     Protein         1..671
                     /product="receptor-interacting serine/threonine-protein
                     kinase 1 isoform 1"
                     /EC_number="2.7.11.1"
                     /note="receptor-interacting serine/threonine-protein
                     kinase 1; serine/threonine-protein kinase RIP; cell death
                     protein RIP; receptor-interacting protein 1; receptor
                     (TNFRSF)-interacting serine-threonine kinase 1;
                     receptor-interacting protein kinase 1"
                     /calculated_mol_wt=75800
     Site            6
                     /site_type="phosphorylation"
                     /note="Phosphoserine, by IKKA and IKKB.
                     /evidence=ECO:0000269|PubMed:18408713; propagated from
                     UniProtKB/Swiss-Prot (Q13546.3)"
     Site            20
                     /site_type="phosphorylation"
                     /note="Phosphoserine, by autocatalysis.
                     /evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (Q13546.3)"
     Region          23..290
                     /region_name="STKc_RIP1"
                     /note="Catalytic domain of the Serine/Threonine kinase,
                     Receptor Interacting Protein 1; cd14027"
                     /db_xref="CDD:270929"
     Site            order(23..27,31,43,45,76,92..95,99,101,138,140,142..143,
                     145,156,159,188..191)
                     /site_type="active"
                     /db_xref="CDD:270929"
     Site            order(23..27,31,43,45,76,92..95,99,138,140,142..143,145,
                     156)
                     /site_type="other"
                     /note="ATP binding site [chemical binding]"
                     /db_xref="CDD:270929"
     Site            25
                     /site_type="phosphorylation"
                     /note="Phosphoserine, by IKKA and IKKB.
                     /evidence=ECO:0000269|PubMed:18408713,
                     ECO:0000269|PubMed:30988283; propagated from
                     UniProtKB/Swiss-Prot (Q13546.3)"
     Site            order(27,99,101,138,140,142,159,188..191)
                     /site_type="other"
                     /note="polypeptide substrate binding site [polypeptide
                     binding]"
                     /db_xref="CDD:270929"
     Site            order(45,64,67..68,70,75..76,78,90,92,129,134,136,
                     154..157,159,161..162,165)
                     /site_type="other"
                     /note="Necrostatin binding site [chemical binding]"
                     /db_xref="CDD:270929"
     Site            155..191
                     /site_type="other"
                     /note="activation loop (A-loop)"
                     /db_xref="CDD:270929"
     Site            161
                     /site_type="phosphorylation"
                     /note="Phosphoserine, by RIPK3 and autocatalysis.
                     /evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (Q13546.3)"
     Site            166
                     /site_type="phosphorylation"
                     /note="Phosphoserine, by autocatalysis.
                     /evidence=ECO:0000255, ECO:0000269|PubMed:29440439,
                     ECO:0000269|PubMed:31827280; propagated from
                     UniProtKB/Swiss-Prot (Q13546.3)"
     Region          290..582
                     /region_name="Interaction with SQSTM1.
                     /evidence=ECO:0000269|PubMed:10356400"
                     /note="propagated from UniProtKB/Swiss-Prot (Q13546.3)"
     Site            303
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0000269|PubMed:18408713; propagated from
                     UniProtKB/Swiss-Prot (Q13546.3)"
     Site            320
                     /site_type="phosphorylation"
                     /note="Phosphoserine, by MAP3K7.
                     /evidence=ECO:0000269|PubMed:18408713,
                     ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163;
                     propagated from UniProtKB/Swiss-Prot (Q13546.3)"
     Site            324..325
                     /site_type="cleavage"
                     /note="Cleavage, by CASP8.
                     /evidence=ECO:0000269|PubMed:10521396,
                     ECO:0000269|PubMed:31827280, ECO:0000269|PubMed:31827281;
                     propagated from UniProtKB/Swiss-Prot (Q13546.3)"
     Region          331..354
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (Q13546.3)"
     Site            331
                     /site_type="phosphorylation"
                     /note="Phosphoserine, by MAP3K7.
                     /evidence=ECO:0000250|UniProtKB:Q60855; propagated from
                     UniProtKB/Swiss-Prot (Q13546.3)"
     Site            333
                     /site_type="phosphorylation"
                     /note="Phosphoserine, by MAP3K7.
                     /evidence=ECO:0000269|PubMed:18408713; propagated from
                     UniProtKB/Swiss-Prot (Q13546.3)"
     Site            384
                     /site_type="phosphorylation"
                     /note="Phosphotyrosine.
                     /evidence=ECO:0007744|PubMed:15144186; propagated from
                     UniProtKB/Swiss-Prot (Q13546.3)"
     Region          389..455
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (Q13546.3)"
     Region          531..547
                     /region_name="RIP homotypic interaction motif (RHIM).
                     /evidence=ECO:0000269|PubMed:11734559,
                     ECO:0000269|PubMed:29681455"
                     /note="propagated from UniProtKB/Swiss-Prot (Q13546.3)"
     Region          583..668
                     /region_name="Death_RIP1"
                     /note="Death Domain of Receptor-Interacting Protein 1;
                     cd08777"
                     /db_xref="CDD:260048"
     Site            603
                     /site_type="glycosylation"
                     /note="(Microbial infection) N-beta-linked (GlcNAc)
                     arginine. /evidence=ECO:0000269|PubMed:30979585,
                     ECO:0000305|PubMed:23955153, ECO:0007744|PDB:6AC5;
                     propagated from UniProtKB/Swiss-Prot (Q13546.3)"
     CDS             1..671
                     /gene="RIPK1"
                     /gene_synonym="AIEFL; IMD57; RIP; RIP-1; RIP1"
                     /coded_by="NM_001354930.2:229..2244"
                     /note="isoform 1 is encoded by transcript variant 3"
                     /db_xref="CCDS:CCDS4482.1"
                     /db_xref="GeneID:8737"
                     /db_xref="HGNC:HGNC:10019"
                     /db_xref="MIM:603453"
ORIGIN      
        1 mqpdmslnvi kmkssdfles aeldsggfgk vslcfhrtqg lmimktvykg pnciehneal
       61 leeakmmnrl rhsrvvkllg viieegkysl vmeymekgnl mhvlkaemst plsvkgriil
      121 eiiegmcylh gkgvihkdlk penilvdndf hikiadlgla sfkmwsklnn eehnelrevd
      181 gtakknggtl yymapehlnd vnakpteksd vysfavvlwa ifankepyen aiceqqlimc
      241 iksgnrpdvd diteycprei islmklcwea npearptfpg ieekfrpfyl sqleesveed
      301 vkslkkeysn enavvkrmqs lqldcvavps srsnsateqp gslhssqglg mgpveeswfa
      361 pslehpqeen epslqsklqd eanyhlygsr mdrqtkqqpr qnvaynreee rrrrvshdpf
      421 aqqrpyenfq ntegkgtays saashgnavh qpsgltsqpq vlyqnnglys shgfgtrpld
      481 pgtagprvwy rpipshmpsl hnipvpetny lgntptmpfs slpptdesik ytiynstgiq
      541 igaynymeig gtssslldst ntnfkeepaa kyqaifdntt sltdkhldpi renlgkhwkn
      601 carklgftqs qideidhdye rdglkekvyq mlqkwvmreg ikgatvgkla qalhqcsrid
      661 llssliyvsq n
//
