CASP8_RAT
ID CASP8_RAT Reviewed; 482 AA.
AC Q9JHX4;
DT 01-APR-2015, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Caspase-8 {ECO:0000303|PubMed:10197541, ECO:0000303|Ref.2};
DE Short=CASP-8 {ECO:0000303|PubMed:10197541};
DE EC=3.4.22.61 {ECO:0000250|UniProtKB:O89110};
DE Contains:
DE RecName: Full=Caspase-8 subunit p18 {ECO:0000250|UniProtKB:Q14790};
DE Contains:
DE RecName: Full=Caspase-8 subunit p10 {ECO:0000250|UniProtKB:Q14790};
DE Flags: Precursor;
GN Name=Casp8 {ECO:0000303|PubMed:10197541, ECO:0000312|RGD:620945};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley;
RA Itoh T., Itoh A., Pleasure D.;
RL Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Cerebellum;
RA Cao G., Graham S.H., Chen D., Chen J.;
RT "Molecular cloning and characterization of rat caspase-8: Its implication
RT in delayed neuronal cell death after ischemia.";
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=10197541; DOI=10.1016/s0896-6273(00)80716-3;
RA Sanchez I., Xu C.J., Juo P., Kakizaka A., Blenis J., Yuan J.;
RT "Caspase-8 is required for cell death induced by expanded polyglutamine
RT repeats.";
RL Neuron 22:623-633(1999).
RN [6]
RP INTERACTION WITH NOL3.
RX PubMed=15383280; DOI=10.1016/j.molcel.2004.08.020;
RA Nam Y.J., Mani K., Ashton A.W., Peng C.F., Krishnamurthy B., Hayakawa Y.,
RA Lee P., Korsmeyer S.J., Kitsis R.N.;
RT "Inhibition of both the extrinsic and intrinsic death pathways through
RT nonhomotypic death-fold interactions.";
RL Mol. Cell 15:901-912(2004).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Thiol protease that plays a key role in programmed cell death
CC by acting as a molecular switch for apoptosis, necroptosis and
CC pyroptosis, and is required to prevent tissue damage during embryonic
CC development and adulthood (By similarity). Initiator protease that
CC induces extrinsic apoptosis by mediating cleavage and activation of
CC effector caspases responsible for the TNFRSF6/FAS mediated and TNFRSF1A
CC induced cell death (PubMed:10197541). Cleaves and activates effector
CC caspases CASP3, CASP4, CASP6, CASP7, CASP9 and CASP10 (By similarity).
CC Binding to the adapter molecule FADD recruits it to either receptor
CC TNFRSF6/FAS mediated or TNFRSF1A (PubMed:10197541). The resulting
CC aggregate called death-inducing signaling complex (DISC) performs CASP8
CC proteolytic activation (By similarity). The active dimeric enzyme is
CC then liberated from the DISC and free to activate downstream apoptotic
CC proteases (By similarity). Proteolytic fragments of the N-terminal
CC propeptide (termed CAP3, CAP5 and CAP6) are likely retained in the DISC
CC (By similarity). In addition to extrinsic apoptosis, also acts as a
CC negative regulator of necroptosis: acts by cleaving RIPK1 at 'Asp-325',
CC which is crucial to inhibit RIPK1 kinase activity, limiting TNF-induced
CC apoptosis, necroptosis and inflammatory response (By similarity). Also
CC able to initiate pyroptosis by mediating cleavage and activation of
CC gasdermin-D (GSDMD): GSDMD cleavage promoting release of the N-terminal
CC moiety (Gasdermin-D, N-terminal) that binds to membranes and forms
CC pores, triggering pyroptosis (By similarity). Initiates pyroptosis
CC following inactivation of MAP3K7/TAK1 (By similarity). Also acts as a
CC regulator of innate immunity by mediating cleavage and inactivation of
CC N4BP1 downstream of TLR3 or TLR4, thereby promoting cytokine production
CC (By similarity). May participate in the Granzyme B (GZMB) cell death
CC pathways (By similarity). Cleaves PARP1 (By similarity).
CC {ECO:0000250|UniProtKB:O89110, ECO:0000250|UniProtKB:Q14790,
CC ECO:0000269|PubMed:10197541}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Strict requirement for Asp at position P1 and has a preferred
CC cleavage sequence of (Leu/Asp/Val)-Glu-Thr-Asp-|-(Gly/Ser/Ala).;
CC EC=3.4.22.61; Evidence={ECO:0000250|UniProtKB:O89110};
CC -!- ACTIVITY REGULATION: CASP8 activity is restricted by RIPK1.
CC {ECO:0000250|UniProtKB:O89110}.
CC -!- SUBUNIT: Heterotetramer that consists of two anti-parallel arranged
CC heterodimers, each one formed by a 18 kDa (p18) and a 10 kDa (p10)
CC subunit (By similarity). Interacts with FADD, CFLAR and PEA15 (By
CC similarity). Interacts with RFFL and RNF34; negatively regulate CASP8
CC through proteasomal degradation (By similarity). Interacts with
CC TNFAIP8L2 (By similarity). Interacts with CASP8AP2 (By similarity).
CC Interacts with NOL3; decreases CASP8 activity in a mitochondria
CC localization- and phosphorylation-dependent manner and this interaction
CC is dissociated by calcium (PubMed:15383280). Interacts with UBR2 (By
CC similarity). Interacts with RIPK1 (By similarity). Interacts with
CC stimulated TNFRSF10B; this interaction is followed by CASP8 proteolytic
CC cleavage and activation (By similarity). Component of the AIM2
CC PANoptosome complex, a multiprotein complex that drives inflammatory
CC cell death (PANoptosis) (By similarity). {ECO:0000250|UniProtKB:O89110,
CC ECO:0000250|UniProtKB:Q14790, ECO:0000269|PubMed:15383280}.
CC -!- INTERACTION:
CC Q9JHX4; Q8R2E7: Fadd; NbExp=2; IntAct=EBI-4326675, EBI-4326723;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10197541}. Nucleus
CC {ECO:0000269|PubMed:10197541}.
CC -!- PTM: Generation of the subunits requires association with the death-
CC inducing signaling complex (DISC), whereas additional processing is
CC likely due to the autocatalytic activity of the activated protease.
CC GZMB and CASP10 can be involved in these processing events (By
CC similarity). {ECO:0000250|UniProtKB:Q14790}.
CC -!- PTM: Phosphorylation on Ser-389 during mitosis by CDK1 inhibits
CC activation by proteolysis and prevents apoptosis. This phosphorylation
CC occurs in cancer cell lines, as well as in primary breast tissues and
CC lymphocytes (By similarity). {ECO:0000250|UniProtKB:Q14790}.
CC -!- SIMILARITY: Belongs to the peptidase C14A family. {ECO:0000305}.
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DR EMBL; AF279308; AAF87778.1; -; mRNA.
DR EMBL; AF288372; AAK83055.1; -; mRNA.
DR EMBL; AABR06060567; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06060568; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH473965; EDL98978.1; -; Genomic_DNA.
DR EMBL; CH473965; EDL98979.1; -; Genomic_DNA.
DR RefSeq; NP_071613.1; NM_022277.1.
DR RefSeq; XP_006245077.1; XM_006245015.3.
DR AlphaFoldDB; Q9JHX4; -.
DR SMR; Q9JHX4; -.
DR IntAct; Q9JHX4; 2.
DR STRING; 10116.ENSRNOP00000016613; -.
DR MEROPS; C14.009; -.
DR iPTMnet; Q9JHX4; -.
DR PhosphoSitePlus; Q9JHX4; -.
DR PaxDb; Q9JHX4; -.
DR PRIDE; Q9JHX4; -.
DR Ensembl; ENSRNOT00000016613; ENSRNOP00000016613; ENSRNOG00000012331.
DR GeneID; 64044; -.
DR KEGG; rno:64044; -.
DR UCSC; RGD:620945; rat.
DR CTD; 841; -.
DR RGD; 620945; Casp8.
DR eggNOG; KOG3573; Eukaryota.
DR GeneTree; ENSGT00940000160319; -.
DR HOGENOM; CLU_036904_4_2_1; -.
DR InParanoid; Q9JHX4; -.
DR OMA; VYRMESK; -.
DR OrthoDB; 939331at2759; -.
DR PhylomeDB; Q9JHX4; -.
DR TreeFam; TF102023; -.
DR BRENDA; 3.4.22.61; 5301.
DR Reactome; R-RNO-111465; Apoptotic cleavage of cellular proteins.
DR Reactome; R-RNO-168638; NOD1/2 Signaling Pathway.
DR Reactome; R-RNO-264870; Caspase-mediated cleavage of cytoskeletal proteins.
DR Reactome; R-RNO-3371378; Regulation by c-FLIP.
DR Reactome; R-RNO-5218900; CASP8 activity is inhibited.
DR Reactome; R-RNO-5357905; Regulation of TNFR1 signaling.
DR Reactome; R-RNO-5660668; CLEC7A/inflammasome pathway.
DR Reactome; R-RNO-5675482; Regulation of necroptotic cell death.
DR Reactome; R-RNO-69416; Dimerization of procaspase-8.
DR Reactome; R-RNO-75108; Activation, myristolyation of BID and translocation to mitochondria.
DR Reactome; R-RNO-75153; Apoptotic execution phase.
DR Reactome; R-RNO-75157; FasL/ CD95L signaling.
DR Reactome; R-RNO-75158; TRAIL signaling.
DR PRO; PR:Q9JHX4; -.
DR Proteomes; UP000002494; Chromosome 9.
DR Proteomes; UP000234681; Chromosome 9.
DR Bgee; ENSRNOG00000012331; Expressed in thymus and 18 other tissues.
DR Genevisible; Q9JHX4; RN.
DR GO; GO:0008303; C:caspase complex; ISO:RGD.
DR GO; GO:0031265; C:CD95 death-inducing signaling complex; IDA:RGD.
DR GO; GO:0044297; C:cell body; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0031264; C:death-inducing signaling complex; IDA:RGD.
DR GO; GO:0045121; C:membrane raft; IDA:RGD.
DR GO; GO:0043005; C:neuron projection; IDA:RGD.
DR GO; GO:0030690; C:Noc1p-Noc2p complex; ISO:RGD.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0097342; C:ripoptosome; ISS:UniProtKB.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IDA:RGD.
DR GO; GO:0097153; F:cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
DR GO; GO:0097199; F:cysteine-type endopeptidase activity involved in apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0097200; F:cysteine-type endopeptidase activity involved in execution phase of apoptosis; IBA:GO_Central.
DR GO; GO:0035877; F:death effector domain binding; ISO:RGD.
DR GO; GO:0005123; F:death receptor binding; IPI:RGD.
DR GO; GO:0004175; F:endopeptidase activity; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0008233; F:peptidase activity; ISO:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:RGD.
DR GO; GO:0097110; F:scaffold protein binding; ISO:RGD.
DR GO; GO:0005164; F:tumor necrosis factor receptor binding; IPI:RGD.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR GO; GO:0097202; P:activation of cysteine-type endopeptidase activity; ISO:RGD.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:RGD.
DR GO; GO:0001525; P:angiogenesis; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IMP:RGD.
DR GO; GO:0097190; P:apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; ISO:RGD.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IEP:RGD.
DR GO; GO:0097194; P:execution phase of apoptosis; ISS:UniProtKB.
DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; ISS:UniProtKB.
DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; ISO:RGD.
DR GO; GO:0007507; P:heart development; ISS:UniProtKB.
DR GO; GO:0097284; P:hepatocyte apoptotic process; ISO:RGD.
DR GO; GO:0030225; P:macrophage differentiation; ISO:RGD.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; ISO:RGD.
DR GO; GO:0060546; P:negative regulation of necroptotic process; ISS:UniProtKB.
DR GO; GO:0001841; P:neural tube formation; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISO:RGD.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; ISO:RGD.
DR GO; GO:0045651; P:positive regulation of macrophage differentiation; ISO:RGD.
DR GO; GO:1901216; P:positive regulation of neuron death; IMP:RGD.
DR GO; GO:0045862; P:positive regulation of proteolysis; ISO:RGD.
DR GO; GO:0016485; P:protein processing; IDA:RGD.
DR GO; GO:0006508; P:proteolysis; ISO:RGD.
DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; ISS:UniProtKB.
DR GO; GO:0070269; P:pyroptosis; ISS:UniProtKB.
DR GO; GO:2001233; P:regulation of apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0001817; P:regulation of cytokine production; ISS:UniProtKB.
DR GO; GO:0045088; P:regulation of innate immune response; ISS:UniProtKB.
DR GO; GO:0070243; P:regulation of thymocyte apoptotic process; ISO:RGD.
DR GO; GO:0046677; P:response to antibiotic; IEP:RGD.
DR GO; GO:0032025; P:response to cobalt ion; IEP:RGD.
DR GO; GO:0009409; P:response to cold; IEP:RGD.
DR GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR GO; GO:0045471; P:response to ethanol; IDA:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0034612; P:response to tumor necrosis factor; ISO:RGD.
DR GO; GO:0097264; P:self proteolysis; ISS:UniProtKB.
DR GO; GO:0036462; P:TRAIL-activated apoptotic signaling pathway; ISO:RGD.
DR CDD; cd00032; CASc; 1.
DR Gene3D; 1.10.533.10; -; 2.
DR InterPro; IPR033170; Caspase-8.
DR InterPro; IPR029030; Caspase-like_dom_sf.
DR InterPro; IPR033139; Caspase_cys_AS.
DR InterPro; IPR016129; Caspase_his_AS.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR001875; DED_dom.
DR InterPro; IPR002398; Pept_C14.
DR InterPro; IPR002138; Pept_C14_p10.
DR InterPro; IPR001309; Pept_C14_p20.
DR InterPro; IPR015917; Pept_C14A.
DR PANTHER; PTHR10454; PTHR10454; 1.
DR PANTHER; PTHR10454:SF162; PTHR10454:SF162; 1.
DR Pfam; PF01335; DED; 2.
DR PRINTS; PR00376; IL1BCENZYME.
DR SMART; SM00115; CASc; 1.
DR SMART; SM00031; DED; 2.
DR SUPFAM; SSF47986; SSF47986; 2.
DR SUPFAM; SSF52129; SSF52129; 1.
DR PROSITE; PS01122; CASPASE_CYS; 1.
DR PROSITE; PS01121; CASPASE_HIS; 1.
DR PROSITE; PS50207; CASPASE_P10; 1.
DR PROSITE; PS50208; CASPASE_P20; 1.
DR PROSITE; PS50168; DED; 2.
PE 1: Evidence at protein level;
KW Apoptosis; Cytoplasm; Hydrolase; Nucleus; Phosphoprotein; Protease;
KW Reference proteome; Repeat; Thiol protease; Zymogen.
FT PROPEP 1..218
FT /evidence="ECO:0000250|UniProtKB:Q14790"
FT /id="PRO_0000432425"
FT CHAIN 219..378
FT /note="Caspase-8 subunit p18"
FT /evidence="ECO:0000250|UniProtKB:Q14790"
FT /id="PRO_0000432426"
FT PROPEP 379..388
FT /evidence="ECO:0000250|UniProtKB:Q14790"
FT /id="PRO_0000432427"
FT CHAIN 389..482
FT /note="Caspase-8 subunit p10"
FT /evidence="ECO:0000250|UniProtKB:Q14790"
FT /id="PRO_0000432428"
FT DOMAIN 2..80
FT /note="DED 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00065"
FT DOMAIN 100..177
FT /note="DED 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00065"
FT ACT_SITE 319
FT /evidence="ECO:0000250|UniProtKB:Q14790"
FT ACT_SITE 362
FT /evidence="ECO:0000250|UniProtKB:Q14790"
FT SITE 218..219
FT /note="Cleavage; by autocatalytic cleavage"
FT /evidence="ECO:0000250|UniProtKB:Q14790"
FT SITE 376..377
FT /note="Cleavage; by CASP6"
FT /evidence="ECO:0000250|UniProtKB:Q14790"
FT SITE 388..389
FT /note="Cleavage; by autocatalytic cleavage"
FT /evidence="ECO:0000250|UniProtKB:Q14790"
FT MOD_RES 188
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O89110"
FT MOD_RES 213
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O89110"
FT MOD_RES 336
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q14790"
FT MOD_RES 390
FT /note="Phosphoserine; by CDK1"
FT /evidence="ECO:0000250|UniProtKB:Q14790"
SQ SEQUENCE 482 AA; 55339 MW; 82B4A29330C53264 CRC64;
MDFHSCLYDI AERLGNEELA ALKFLCLDHI PQKKQESIND VLVLFQRLQE EGMLEEDNLS
FLKELLFHIS RRDLLSRVLK SSPEEMVREL QVLGKAQVSA YRVMLFKLSE DMDKEDLKSF
KFLLITEIPK CKLQDNSSLL DIFVEMEKRT ILAENNLVTL KSICFRVNRS LLGRIDDYER
SSTERRMSTE GGEELPVSVL DEVTIKMQDM WDSPGEQESE SLNSDNVYQM KSKPRGYCLI
FNNNNFSKAR EDIPKLSNMR DRKGTNYDEE ALSKTFKELH FEIVSFSDCT ASQIHEVLVS
YQSKDHKGKD CFICCILSHG DKGIVYGTDG KEASIYELTS YFTGSKCPSL AGKPKIFFIQ
ACQGNNFQKA VPVPDETGLE QEHVLEEDSS SYKNYIPDEA DFLLGMATVK NCVSYRDPTR
GTWYIQSLCQ SLRERCPRGE DILSILTGVN YDVSNKDNPR NMGKQMPQPI FTLRKKLFFP
PN
