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Protein

Caspase-9

Gene

Casp9

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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)DescriptionActionsGraphical viewLength
Active sitei275By similarity1
Active sitei325By similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease, Thiol protease
Biological processApoptosis

Enzyme and pathway databases

ReactomeiR-MMU-168638 NOD1/2 Signaling Pathway
R-MMU-198323 AKT phosphorylates targets in the cytosol
R-MMU-418889 via Dependence Receptors in the absence of ligand

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:1277950 Casp9

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_0000421173? – 353Caspase-9 subunit p35By similarity
PropeptideiPRO_00004211721 – ?Sequence analysis
PropeptideiPRO_0000421174354 – 367By similarityAdd BLAST14
ChainiPRO_0000421175368 – 454Caspase-9 subunit p10By similarityAdd BLAST87

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei163Phosphothreonine; by MAPK1By similarity1
Modified residuei191Phosphotyrosine; by ABL11 Publication1
Modified residuei340PhosphoserineBy similarity1
Modified residuei348PhosphoserineBy similarity1

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
PhosphoSitePlusiQ8C3Q9

Expressioni

Gene expression databases

BgeeiENSMUSG00000028914 Expressed in 283 organ(s), highest expression level in blood
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 interactors
DIPiDIP-60482N
IntActiQ8C3Q9, 1 interactor
STRINGi10090.ENSMUSP00000030747

Structurei

3D structure databases

ProteinModelPortaliQ8C3Q9
SMRiQ8C3Q9
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 92CARDPROSITE-ProRule annotationAdd BLAST92

Sequence similaritiesi

Belongs to the peptidase C14A family.Curated

Phylogenomic databases

eggNOGiKOG3573 Eukaryota
ENOG410ZQIE LUCA
GeneTreeiENSGT00760000118912
HOVERGENiHBG059022
InParanoidiQ8C3Q9
KOiK04399
OMAiVFEQWAH
OrthoDBiEOG091G05YD
PhylomeDBiQ8C3Q9
TreeFamiTF102023

Family and domain databases

CDDicd00032 CASc, 1 hit
InterProiView protein in InterPro
IPR001315 CARD
IPR033171 Caspase-9
IPR029030 Caspase-like_dom_sf
IPR033139 Caspase_cys_AS
IPR016129 Caspase_his_AS
IPR011029 DEATH-like_dom_sf
IPR002398 Pept_C14
IPR002138 Pept_C14_p10
IPR001309 Pept_C14_p20
IPR015917 Pept_C14A
PANTHERiPTHR10454 PTHR10454, 1 hit
PTHR10454:SF157 PTHR10454:SF157, 1 hit
PfamiView protein in Pfam
PF00619 CARD, 1 hit
PRINTSiPR00376 IL1BCENZYME
SMARTiView protein in SMART
SM00114 CARD, 1 hit
SM00115 CASc, 1 hit
SUPFAMiSSF47986 SSF47986, 1 hit
SSF52129 SSF52129, 1 hit
PROSITEiView protein in PROSITE
PS50209 CARD, 1 hit
PS01122 CASPASE_CYS, 1 hit
PS01121 CASPASE_HIS, 1 hit
PS50207 CASPASE_P10, 1 hit
PS50208 CASPASE_P20, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A2AS93A2AS93_MOUSE
Caspase 9, isoform CRA_a
Casp9 mCG_19990
405Annotation score:
A2AS92A2AS92_MOUSE
Caspase-9
Casp9
215Annotation score:

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

Similar proteinsi

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
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi198501, 4 interactors
DIPiDIP-60482N
IntActiQ8C3Q9, 1 interactor
STRINGi10090.ENSMUSP00000030747

Protein family/group databases

MEROPSiC14.010

PTM databases

iPTMnetiQ8C3Q9
PhosphoSitePlusiQ8C3Q9

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
OrthoDBiEOG091G05YD
PhylomeDBiQ8C3Q9
TreeFamiTF102023

Enzyme and pathway databases

ReactomeiR-MMU-168638 NOD1/2 Signaling Pathway
R-MMU-198323 AKT phosphorylates targets in the cytosol
R-MMU-418889 via Dependence Receptors in the absence of ligand

Miscellaneous databases

ChiTaRSiCasp9 mouse
PROiPR:Q8C3Q9
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000028914 Expressed in 283 organ(s), highest expression level in blood
ExpressionAtlasiQ8C3Q9 baseline and differential
GenevisibleiQ8C3Q9 MM

Family and domain databases

CDDicd00032 CASc, 1 hit
InterProiView protein in InterPro
IPR001315 CARD
IPR033171 Caspase-9
IPR029030 Caspase-like_dom_sf
IPR033139 Caspase_cys_AS
IPR016129 Caspase_his_AS
IPR011029 DEATH-like_dom_sf
IPR002398 Pept_C14
IPR002138 Pept_C14_p10
IPR001309 Pept_C14_p20
IPR015917 Pept_C14A
PANTHERiPTHR10454 PTHR10454, 1 hit
PTHR10454:SF157 PTHR10454:SF157, 1 hit
PfamiView protein in Pfam
PF00619 CARD, 1 hit
PRINTSiPR00376 IL1BCENZYME
SMARTiView protein in SMART
SM00114 CARD, 1 hit
SM00115 CASc, 1 hit
SUPFAMiSSF47986 SSF47986, 1 hit
SSF52129 SSF52129, 1 hit
PROSITEiView protein in PROSITE
PS50209 CARD, 1 hit
PS01122 CASPASE_CYS, 1 hit
PS01121 CASPASE_HIS, 1 hit
PS50207 CASPASE_P10, 1 hit
PS50208 CASPASE_P20, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCASP9_MOUSE
AccessioniPrimary (citable) accession number: Q8C3Q9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 6, 2013
Last sequence update: March 1, 2003
Last modified: November 7, 2018
This is version 156 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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