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Protein

Caspase-9

Gene

Casp9

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in the activation cascade of caspases responsible for apoptosis execution. Binding of caspase-9 to Apaf-1 leads to activation of the protease which then cleaves and activates caspase-3. Promotes DNA damage-induced apoptosis in a ABL1/c-Abl-dependent manner. Proteolytically cleaves poly(ADP-ribose) polymerase (PARP) (By similarity).By similarity

Catalytic activityi

Strict requirement for an Asp residue at position P1 and with a marked preference for His at position P2. It has a preferred cleavage sequence of Leu-Gly-His-Asp-|-Xaa.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei275 – 2751By similarity
Active sitei325 – 3251By similarity

GO - Molecular functioni

  • cysteine-type endopeptidase activity Source: MGI
  • peptidase activity Source: MGI
  • protein kinase binding Source: UniProtKB
  • SH3 domain binding Source: UniProtKB

GO - Biological processi

  • activation of cysteine-type endopeptidase activity involved in apoptotic process Source: MGI
  • aging Source: Ensembl
  • apoptotic process Source: MGI
  • cellular response to dexamethasone stimulus Source: UniProtKB
  • cellular response to DNA damage stimulus Source: MGI
  • cellular response to UV Source: UniProtKB
  • glial cell apoptotic process Source: Ensembl
  • intrinsic apoptotic signaling pathway in response to DNA damage Source: UniProtKB
  • intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress Source: ParkinsonsUK-UCL
  • positive regulation of neuron apoptotic process Source: MGI
  • regulation of response to DNA damage stimulus Source: UniProtKB
  • response to antibiotic Source: Ensembl
  • response to cobalt ion Source: Ensembl
  • response to estradiol Source: Ensembl
  • response to lipopolysaccharide Source: Ensembl
  • response to UV Source: MGI
  • signal transduction in response to DNA damage Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Apoptosis

Enzyme and pathway databases

ReactomeiR-MMU-111458. Formation of apoptosome.
R-MMU-111459. Activation of caspases through apoptosome-mediated cleavage.
R-MMU-198323. AKT phosphorylates targets in the cytosol.
R-MMU-418889. Ligand-independent caspase activation via DCC.

Protein family/group databases

MEROPSiC14.010.

Names & Taxonomyi

Protein namesi
Recommended name:
Caspase-9 (EC:3.4.22.62)
Short name:
CASP-9
Alternative name(s):
Apoptotic protease Mch-6
Apoptotic protease-activating factor 3
Short name:
APAF-3
ICE-like apoptotic protease 6
Short name:
ICE-LAP6
Cleaved into the following 2 chains:
Gene namesi
Name:Casp9
Synonyms:Mch6
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:1277950. Casp9.

Subcellular locationi

GO - Cellular componenti

  • apoptosome Source: MGI
  • cytosol Source: MGI
  • mitochondrion Source: Ensembl
  • nucleus Source: MGI
Complete GO annotation...

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini? – 353Caspase-9 subunit p35By similarityPRO_0000421173
Propeptidei1 – ?Sequence analysisPRO_0000421172
Propeptidei354 – 36714By similarityPRO_0000421174Add
BLAST
Chaini368 – 45487Caspase-9 subunit p10By similarityPRO_0000421175Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei163 – 1631Phosphothreonine; by MAPK1By similarity
Modified residuei191 – 1911Phosphotyrosine; by ABL11 Publication
Modified residuei340 – 3401PhosphoserineBy similarity

Post-translational modificationi

Cleavages at Asp-353 by granzyme B and at Asp-368 by caspase-3 generate the two active subunits. Caspase-8 and -10 can also be involved in these processing events (By similarity).By similarity
Phosphorylated at Thr-163 by MAPK1/ERK2. Phosphorylation at Thr-163 is sufficient to block caspase-9 processing and subsequent caspase-3 activation (By similarity). Phosphorylation on Tyr-191 by ABL1/c-Abl; occurs in the response of cells to DNA damage.By similarity1 Publication

Keywords - PTMi

Phosphoprotein, Zymogen

Proteomic databases

EPDiQ8C3Q9.
MaxQBiQ8C3Q9.
PaxDbiQ8C3Q9.
PRIDEiQ8C3Q9.

PTM databases

iPTMnetiQ8C3Q9.

Expressioni

Gene expression databases

BgeeiQ8C3Q9.
ExpressionAtlasiQ8C3Q9. baseline and differential.
GenevisibleiQ8C3Q9. MM.

Interactioni

Subunit structurei

Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 35 kDa (p35) and a 10 kDa (p10) subunit. Caspase-9 and APAF1 bind to each other via their respective NH2-terminal CED-3 homologous domains in the presence of cytochrome C and ATP. Interacts (inactive form) with EFHD2. Interacts with HAX1. Interacts with BIRC2/c-IAP1, XIAP/BIRC4, BIRC5/survivin, BIRC6/bruce and BIRC7/livin. Interacts with ABL1 (via SH3 domain); the interaction is direct and increased in the response of cells to genotoxic stress and ABL1/c-Abl activation (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi198501. 4 interactions.
DIPiDIP-60482N.
STRINGi10090.ENSMUSP00000030747.

Structurei

3D structure databases

ProteinModelPortaliQ8C3Q9.
SMRiQ8C3Q9. Positions 1-95, 183-454.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1 – 9292CARDPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the peptidase C14A family.Curated
Contains 1 CARD domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG3573. Eukaryota.
ENOG410ZQIE. LUCA.
GeneTreeiENSGT00760000118912.
HOVERGENiHBG059022.
InParanoidiQ8C3Q9.
KOiK04399.
OMAiVFEQWAH.
PhylomeDBiQ8C3Q9.
TreeFamiTF102023.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
3.40.50.1460. 1 hit.
InterProiIPR001315. CARD.
IPR033171. Caspase-9.
IPR029030. Caspase-like_dom.
IPR033139. Caspase_cys_AS.
IPR016129. Caspase_his_AS.
IPR011029. DEATH-like_dom.
IPR002138. Pept_C14_p10.
IPR001309. Pept_C14_p20.
IPR015917. Pept_C14A.
IPR017350. Pept_C14A_CASP1-typ.
[Graphical view]
PANTHERiPTHR10454:SF157. PTHR10454:SF157. 1 hit.
PfamiPF00619. CARD. 1 hit.
[Graphical view]
PIRSFiPIRSF038001. Caspase_ICE. 1 hit.
PRINTSiPR00376. IL1BCENZYME.
SMARTiSM00114. CARD. 1 hit.
SM00115. CASc. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF52129. SSF52129. 1 hit.
PROSITEiPS50209. CARD. 1 hit.
PS01122. CASPASE_CYS. 1 hit.
PS01121. CASPASE_HIS. 1 hit.
PS50207. CASPASE_P10. 1 hit.
PS50208. CASPASE_P20. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q8C3Q9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDEADRQLLR RCRVRLVSEL QVAELWDALL SRELFTRDMI EDIQQAGSGS
60 70 80 90 100
RRDQARQLVT DLETRGRQAL PLFISCLEDT GQGTLASLLQ SGRQAAKQDP
110 120 130 140 150
EAVKPLDHLV PVVLGPMGLT AKEQRVVKLD PSQPAVGNLT PVVLGPEELW
160 170 180 190 200
PARLKPEVLR PETPRPVDIG SGGAHDVCVP GKIRGHADMA YTLDSDPCGH
210 220 230 240 250
CLIINNVNFC PSSGLGTRTG SNLDRDKLEH RFRWLRFMVE VKNDLTAKKM
260 270 280 290 300
VTALMEMAHR NHRALDCFVV VILSHGCQAS HLQFPGAVYG TDGCSVSIEK
310 320 330 340 350
IVNIFNGSGC PSLGGKPKLF FIQACGGEQK DHGFEVACTS SQGRTLDSDS
360 370 380 390 400
EPDAVPYQEG PRPLDQLDAV SSLPTPSDIL VSYSTFPGFV SWRDKKSGSW
410 420 430 440 450
YIETLDGILE QWARSEDLQS LLLRVANAVS AKGTYKQIPG CFNFLRKKLF

FKTS
Length:454
Mass (Da):49,979
Last modified:March 1, 2003 - v1
Checksum:i438A67EA66A6EE78
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK085095 mRNA. Translation: BAC39365.1.
AL928577 Genomic DNA. Translation: CAM23134.1.
CH466615 Genomic DNA. Translation: EDL13399.1.
BC056372 mRNA. Translation: AAH56372.1.
BC056447 mRNA. Translation: AAH56447.1.
CCDSiCCDS18883.1.
RefSeqiNP_056548.2. NM_015733.5.
UniGeneiMm.88829.

Genome annotation databases

EnsembliENSMUST00000030747; ENSMUSP00000030747; ENSMUSG00000028914.
GeneIDi12371.
KEGGimmu:12371.
UCSCiuc008vpi.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK085095 mRNA. Translation: BAC39365.1.
AL928577 Genomic DNA. Translation: CAM23134.1.
CH466615 Genomic DNA. Translation: EDL13399.1.
BC056372 mRNA. Translation: AAH56372.1.
BC056447 mRNA. Translation: AAH56447.1.
CCDSiCCDS18883.1.
RefSeqiNP_056548.2. NM_015733.5.
UniGeneiMm.88829.

3D structure databases

ProteinModelPortaliQ8C3Q9.
SMRiQ8C3Q9. Positions 1-95, 183-454.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi198501. 4 interactions.
DIPiDIP-60482N.
STRINGi10090.ENSMUSP00000030747.

Protein family/group databases

MEROPSiC14.010.

PTM databases

iPTMnetiQ8C3Q9.

Proteomic databases

EPDiQ8C3Q9.
MaxQBiQ8C3Q9.
PaxDbiQ8C3Q9.
PRIDEiQ8C3Q9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000030747; ENSMUSP00000030747; ENSMUSG00000028914.
GeneIDi12371.
KEGGimmu:12371.
UCSCiuc008vpi.2. mouse.

Organism-specific databases

CTDi842.
MGIiMGI:1277950. Casp9.

Phylogenomic databases

eggNOGiKOG3573. Eukaryota.
ENOG410ZQIE. LUCA.
GeneTreeiENSGT00760000118912.
HOVERGENiHBG059022.
InParanoidiQ8C3Q9.
KOiK04399.
OMAiVFEQWAH.
PhylomeDBiQ8C3Q9.
TreeFamiTF102023.

Enzyme and pathway databases

ReactomeiR-MMU-111458. Formation of apoptosome.
R-MMU-111459. Activation of caspases through apoptosome-mediated cleavage.
R-MMU-198323. AKT phosphorylates targets in the cytosol.
R-MMU-418889. Ligand-independent caspase activation via DCC.

Miscellaneous databases

ChiTaRSiCasp9. mouse.
PROiQ8C3Q9.
SOURCEiSearch...

Gene expression databases

BgeeiQ8C3Q9.
ExpressionAtlasiQ8C3Q9. baseline and differential.
GenevisibleiQ8C3Q9. MM.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
3.40.50.1460. 1 hit.
InterProiIPR001315. CARD.
IPR033171. Caspase-9.
IPR029030. Caspase-like_dom.
IPR033139. Caspase_cys_AS.
IPR016129. Caspase_his_AS.
IPR011029. DEATH-like_dom.
IPR002138. Pept_C14_p10.
IPR001309. Pept_C14_p20.
IPR015917. Pept_C14A.
IPR017350. Pept_C14A_CASP1-typ.
[Graphical view]
PANTHERiPTHR10454:SF157. PTHR10454:SF157. 1 hit.
PfamiPF00619. CARD. 1 hit.
[Graphical view]
PIRSFiPIRSF038001. Caspase_ICE. 1 hit.
PRINTSiPR00376. IL1BCENZYME.
SMARTiSM00114. CARD. 1 hit.
SM00115. CASc. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF52129. SSF52129. 1 hit.
PROSITEiPS50209. CARD. 1 hit.
PS01122. CASPASE_CYS. 1 hit.
PS01121. CASPASE_HIS. 1 hit.
PS50207. CASPASE_P10. 1 hit.
PS50208. CASPASE_P20. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Lung.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  3. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "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].
    Strain: C57BL/6J.
    Tissue: Brain.
  5. "c-Abl tyrosine kinase regulates caspase-9 autocleavage in the apoptotic response to DNA damage."
    Raina D., Pandey P., Ahmad R., Bharti A., Ren J., Kharbanda S., Weichselbaum R., Kufe D.
    J. Biol. Chem. 280:11147-11151(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT TYR-191 BY ABL1.

Entry informationi

Entry nameiCASP9_MOUSE
AccessioniPrimary (citable) accession number: Q8C3Q9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 6, 2013
Last sequence update: March 1, 2003
Last modified: June 8, 2016
This is version 136 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.