CASP9_MOUSE
ID CASP9_MOUSE Reviewed; 454 AA.
AC Q8C3Q9;
DT 06-FEB-2013, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Caspase-9;
DE Short=CASP-9;
DE EC=3.4.22.62;
DE AltName: Full=Apoptotic protease Mch-6;
DE AltName: Full=Apoptotic protease-activating factor 3;
DE Short=APAF-3;
DE AltName: Full=ICE-like apoptotic protease 6;
DE Short=ICE-LAP6;
DE Contains:
DE RecName: Full=Caspase-9 subunit p35;
DE Contains:
DE RecName: Full=Caspase-9 subunit p10;
DE Flags: Precursor;
GN Name=Casp9; Synonyms=Mch6;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Lung;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PHOSPHORYLATION AT TYR-191 BY ABL1.
RX PubMed=15657060; DOI=10.1074/jbc.m413787200;
RA Raina D., Pandey P., Ahmad R., Bharti A., Ren J., Kharbanda S.,
RA Weichselbaum R., Kufe D.;
RT "c-Abl tyrosine kinase regulates caspase-9 autocleavage in the apoptotic
RT response to DNA damage.";
RL J. Biol. Chem. 280:11147-11151(2005).
CC -!- FUNCTION: Involved in the activation cascade of caspases responsible
CC for apoptosis execution. Binding of caspase-9 to Apaf-1 leads to
CC activation of the protease which then cleaves and activates caspase-3.
CC Promotes DNA damage-induced apoptosis in a ABL1/c-Abl-dependent manner.
CC Proteolytically cleaves poly(ADP-ribose) polymerase (PARP) (By
CC similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Strict requirement for an Asp residue at position P1 and with
CC a marked preference for His at position P2. It has a preferred
CC cleavage sequence of Leu-Gly-His-Asp-|-Xaa.; EC=3.4.22.62;
CC -!- SUBUNIT: Heterotetramer that consists of two anti-parallel arranged
CC heterodimers, each one formed by a 35 kDa (p35) and a 10 kDa (p10)
CC subunit. Caspase-9 and APAF1 bind to each other via their respective
CC NH2-terminal CED-3 homologous domains in the presence of cytochrome C
CC and ATP. Interacts (inactive form) with EFHD2. Interacts with HAX1.
CC Interacts with BIRC2/c-IAP1, XIAP/BIRC4, BIRC5/survivin, BIRC6/bruce
CC and BIRC7/livin. Interacts with ABL1 (via SH3 domain); the interaction
CC is direct and increased in the response of cells to genotoxic stress
CC and ABL1/c-Abl activation (By similarity). Interacts with BCL2L10 (By
CC similarity). {ECO:0000250, ECO:0000250|UniProtKB:P55211}.
CC -!- PTM: Cleavages at Asp-353 by granzyme B and at Asp-368 by caspase-3
CC generate the two active subunits. Caspase-8 and -10 can also be
CC involved in these processing events (By similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylated at Thr-163 by MAPK1/ERK2. Phosphorylation at Thr-
CC 163 is sufficient to block caspase-9 processing and subsequent caspase-
CC 3 activation (By similarity). Phosphorylation on Tyr-191 by ABL1/c-Abl;
CC occurs in the response of cells to DNA damage. {ECO:0000250,
CC ECO:0000269|PubMed:15657060}.
CC -!- SIMILARITY: Belongs to the peptidase C14A family. {ECO:0000305}.
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DR EMBL; AK085095; BAC39365.1; -; mRNA.
DR EMBL; AL928577; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466615; EDL13399.1; -; Genomic_DNA.
DR EMBL; BC056372; AAH56372.1; -; mRNA.
DR EMBL; BC056447; AAH56447.1; -; mRNA.
DR CCDS; CCDS18883.1; -.
DR RefSeq; NP_056548.2; NM_015733.5.
DR AlphaFoldDB; Q8C3Q9; -.
DR SMR; Q8C3Q9; -.
DR BioGRID; 198501; 6.
DR ComplexPortal; CPX-3801; Caspase-9 complex.
DR ComplexPortal; CPX-3824; Apoptosome.
DR DIP; DIP-60482N; -.
DR IntAct; Q8C3Q9; 1.
DR STRING; 10090.ENSMUSP00000030747; -.
DR MEROPS; C14.010; -.
DR iPTMnet; Q8C3Q9; -.
DR PhosphoSitePlus; Q8C3Q9; -.
DR EPD; Q8C3Q9; -.
DR MaxQB; Q8C3Q9; -.
DR PaxDb; Q8C3Q9; -.
DR PRIDE; Q8C3Q9; -.
DR ProteomicsDB; 279915; -.
DR Antibodypedia; 749; 1874 antibodies from 50 providers.
DR DNASU; 12371; -.
DR Ensembl; ENSMUST00000030747; ENSMUSP00000030747; ENSMUSG00000028914.
DR GeneID; 12371; -.
DR KEGG; mmu:12371; -.
DR UCSC; uc008vpi.2; mouse.
DR CTD; 842; -.
DR MGI; MGI:1277950; Casp9.
DR VEuPathDB; HostDB:ENSMUSG00000028914; -.
DR eggNOG; KOG3573; Eukaryota.
DR GeneTree; ENSGT00940000159698; -.
DR HOGENOM; CLU_036904_5_0_1; -.
DR InParanoid; Q8C3Q9; -.
DR OMA; RYKQIPG; -.
DR OrthoDB; 1092723at2759; -.
DR PhylomeDB; Q8C3Q9; -.
DR TreeFam; TF102023; -.
DR Reactome; R-MMU-111458; Formation of apoptosome.
DR Reactome; R-MMU-111459; Activation of caspases through apoptosome-mediated cleavage.
DR Reactome; R-MMU-168638; NOD1/2 Signaling Pathway.
DR Reactome; R-MMU-198323; AKT phosphorylates targets in the cytosol.
DR Reactome; R-MMU-418889; Caspase activation via Dependence Receptors in the absence of ligand.
DR Reactome; R-MMU-9627069; Regulation of the apoptosome activity.
DR BioGRID-ORCS; 12371; 2 hits in 76 CRISPR screens.
DR ChiTaRS; Casp9; mouse.
DR PRO; PR:Q8C3Q9; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q8C3Q9; protein.
DR Bgee; ENSMUSG00000028914; Expressed in metanephric mesenchyme and 262 other tissues.
DR ExpressionAtlas; Q8C3Q9; baseline and differential.
DR Genevisible; Q8C3Q9; MM.
DR GO; GO:0043293; C:apoptosome; ISO:MGI.
DR GO; GO:0008303; C:caspase complex; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0005739; C:mitochondrion; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IDA:MGI.
DR GO; GO:0097153; F:cysteine-type endopeptidase activity involved in apoptotic process; IBA:GO_Central.
DR GO; GO:0097199; F:cysteine-type endopeptidase activity involved in apoptotic signaling pathway; ISS:UniProtKB.
DR GO; GO:0097200; F:cysteine-type endopeptidase activity involved in execution phase of apoptosis; IBA:GO_Central.
DR GO; GO:0008234; F:cysteine-type peptidase activity; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0008233; F:peptidase activity; IDA:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISS:UniProtKB.
DR GO; GO:0017124; F:SH3 domain binding; ISS:UniProtKB.
DR GO; GO:0097202; P:activation of cysteine-type endopeptidase activity; ISO:MGI.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:MGI.
DR GO; GO:0008635; P:activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c; ISO:MGI.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0006915; P:apoptotic process; IMP:MGI.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IDA:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IMP:MGI.
DR GO; GO:0034644; P:cellular response to UV; ISS:UniProtKB.
DR GO; GO:1904019; P:epithelial cell apoptotic process; IDA:MGI.
DR GO; GO:0044346; P:fibroblast apoptotic process; IDA:MGI.
DR GO; GO:0034349; P:glial cell apoptotic process; IEA:Ensembl.
DR GO; GO:0097193; P:intrinsic apoptotic signaling pathway; IC:ComplexPortal.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; ISS:UniProtKB.
DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; NAS:ParkinsonsUK-UCL.
DR GO; GO:0001822; P:kidney development; IEA:Ensembl.
DR GO; GO:0071887; P:leukocyte apoptotic process; IEA:Ensembl.
DR GO; GO:0051402; P:neuron apoptotic process; IMP:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IMP:MGI.
DR GO; GO:0016485; P:protein processing; ISO:MGI.
DR GO; GO:2001020; P:regulation of response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0046677; P:response to antibiotic; IEA:Ensembl.
DR GO; GO:0032025; P:response to cobalt ion; IEA:Ensembl.
DR GO; GO:0032355; P:response to estradiol; IEA:Ensembl.
DR GO; GO:0002931; P:response to ischemia; IEA:Ensembl.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0014070; P:response to organic cyclic compound; ISO:MGI.
DR GO; GO:0009411; P:response to UV; IMP:MGI.
DR GO; GO:0042770; P:signal transduction in response to DNA damage; ISS:UniProtKB.
DR CDD; cd08326; CARD_CASP9; 1.
DR CDD; cd00032; CASc; 1.
DR Gene3D; 1.10.533.10; -; 1.
DR InterPro; IPR001315; CARD.
DR InterPro; IPR042147; CARD_CASP9.
DR InterPro; IPR033171; Caspase-9.
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; 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:SF157; PTHR10454:SF157; 1.
DR Pfam; PF00619; CARD; 1.
DR PRINTS; PR00376; IL1BCENZYME.
DR SMART; SM00114; CARD; 1.
DR SMART; SM00115; CASc; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR SUPFAM; SSF52129; SSF52129; 1.
DR PROSITE; PS50209; CARD; 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.
PE 1: Evidence at protein level;
KW Apoptosis; Hydrolase; Phosphoprotein; Protease; Reference proteome;
KW Thiol protease; Zymogen.
FT PROPEP 1..?
FT /evidence="ECO:0000255"
FT /id="PRO_0000421172"
FT CHAIN ?..353
FT /note="Caspase-9 subunit p35"
FT /evidence="ECO:0000250"
FT /id="PRO_0000421173"
FT PROPEP 354..367
FT /evidence="ECO:0000250"
FT /id="PRO_0000421174"
FT CHAIN 368..454
FT /note="Caspase-9 subunit p10"
FT /evidence="ECO:0000250"
FT /id="PRO_0000421175"
FT DOMAIN 1..92
FT /note="CARD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00046"
FT ACT_SITE 275
FT /evidence="ECO:0000250"
FT ACT_SITE 325
FT /evidence="ECO:0000250"
FT MOD_RES 163
FT /note="Phosphothreonine; by MAPK1"
FT /evidence="ECO:0000250|UniProtKB:P55211"
FT MOD_RES 191
FT /note="Phosphotyrosine; by ABL1"
FT /evidence="ECO:0000269|PubMed:15657060"
FT MOD_RES 340
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P55211"
FT MOD_RES 348
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P55211"
SQ SEQUENCE 454 AA; 49979 MW; 438A67EA66A6EE78 CRC64;
MDEADRQLLR RCRVRLVSEL QVAELWDALL SRELFTRDMI EDIQQAGSGS RRDQARQLVT
DLETRGRQAL PLFISCLEDT GQGTLASLLQ SGRQAAKQDP EAVKPLDHLV PVVLGPMGLT
AKEQRVVKLD PSQPAVGNLT PVVLGPEELW PARLKPEVLR PETPRPVDIG SGGAHDVCVP
GKIRGHADMA YTLDSDPCGH CLIINNVNFC PSSGLGTRTG SNLDRDKLEH RFRWLRFMVE
VKNDLTAKKM VTALMEMAHR NHRALDCFVV VILSHGCQAS HLQFPGAVYG TDGCSVSIEK
IVNIFNGSGC PSLGGKPKLF FIQACGGEQK DHGFEVACTS SQGRTLDSDS EPDAVPYQEG
PRPLDQLDAV SSLPTPSDIL VSYSTFPGFV SWRDKKSGSW YIETLDGILE QWARSEDLQS
LLLRVANAVS AKGTYKQIPG CFNFLRKKLF FKTS
