Human Gene CASP9 (ENST00000333868.10_7) from GENCODE V47lift37
  Description: caspase 9, transcript variant 5 (from RefSeq NR_102733.2)
Gencode Transcript: ENST00000333868.10_7
Gencode Gene: ENSG00000132906.18_14
Transcript (Including UTRs)
   Position: hg19 chr1:15,817,896-15,850,710 Size: 32,815 Total Exon Count: 9 Strand: -
Coding Region
   Position: hg19 chr1:15,819,438-15,850,695 Size: 31,258 Coding Exon Count: 9 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2024-08-22 23:36:26

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr1:15,817,896-15,850,710)mRNA (may differ from genome)Protein (416 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
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HGNCMalacardsMGIOMIMPubMedReactome
UniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: CASP9_HUMAN
DESCRIPTION: RecName: Full=Caspase-9; Short=CASP-9; EC=3.4.22.62; AltName: Full=Apoptotic protease Mch-6; AltName: Full=Apoptotic protease-activating factor 3; Short=APAF-3; AltName: Full=ICE-like apoptotic protease 6; Short=ICE-LAP6; Contains: RecName: Full=Caspase-9 subunit p35; Contains: RecName: Full=Caspase-9 subunit p10; Flags: Precursor;
FUNCTION: 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. Proteolytically cleaves poly(ADP-ribose) polymerase (PARP).
FUNCTION: Isoform 2 lacks activity is an dominant-negative inhibitor of caspase-9.
CATALYTIC ACTIVITY: 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.
SUBUNIT: 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.
INTERACTION: O14727:APAF1; NbExp=17; IntAct=EBI-516799, EBI-446492; Q96CA5:BIRC7; NbExp=5; IntAct=EBI-516799, EBI-517623; Q13418:ILK; NbExp=2; IntAct=EBI-516799, EBI-747644; P98170:XIAP; NbExp=5; IntAct=EBI-516799, EBI-517127;
TISSUE SPECIFICITY: Ubiquitous, with highest expression in the heart, moderate expression in liver, skeletal muscle, and pancreas. Low levels in all other tissues. Within the heart, specifically expressed in myocytes.
DEVELOPMENTAL STAGE: Expressed at low levels in fetal heart, at moderate levels in neonate heart, and at high levels in adult heart.
PTM: Cleavages at Asp-315 by granzyme B and at Asp-330 by caspase- 3 generate the two active subunits. Caspase-8 and -10 can also be involved in these processing events.
PTM: Phosphorylated at Thr-125 by MAPK1/ERK2. Phosphorylation at Thr-125 is sufficient to block caspase-9 processing and subsequent caspase-3 activation.
SIMILARITY: Belongs to the peptidase C14A family.
SIMILARITY: Contains 1 CARD domain.
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/CASP9ID423ch1p36.html";
WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/casp9/";
WEB RESOURCE: Name=Wikipedia; Note=Caspase-9 entry; URL="http://en.wikipedia.org/wiki/Caspase-9";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: CASP9
Diseases sorted by gene-association score: brain meningioma (15), inflammatory bowel disease 7 (9), varicocele (7), cervical cancer, somatic (7), chronic mountain sickness (6), lung cancer (6), cerebral hypoxia (6), colorectal cancer (6), dystrophinopathies (5), breast adenocarcinoma (5), newcastle disease (5), carbuncle (4), prostate cancer (4), hepatocellular carcinoma (4), breast cancer (3), stomach cancer (2), alzheimer disease (2), pancreatic cancer (2), uveal melanoma (2), multiple myeloma (2), esophageal cancer (2), leukemia, acute promyelocytic, somatic (2), lung cancer susceptibility 3 (1), ovarian cancer, somatic (1), parkinson disease, late-onset (1), gastrointestinal system cancer (1), leukemia, acute myeloid (0)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 20.47 RPKM in Ovary
Total median expression: 253.58 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
3' UTR -504.391542-0.327 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR001315 - CARD
IPR017350 - Caspase_IL-1_beta
IPR011029 - DEATH-like
IPR011600 - Pept_C14_cat
IPR001309 - Pept_C14_ICE_p20
IPR016129 - Pept_C14_ICE_p20_AS
IPR002138 - Pept_C14_p10
IPR002398 - Pept_C14_p45
IPR015917 - Pept_C14_p45_core

Pfam Domains:
PF00619 - Caspase recruitment domain
PF00656 - Caspase domain

SCOP Domains:
47986 - DEATH domain
52129 - Caspase-like

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1JXQ - X-ray MuPIT 1NW9 - X-ray MuPIT 2AR9 - X-ray 3D9T - X-ray MuPIT 3YGS - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P55211
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
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 RGDEnsembl   
      
      

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004197 cysteine-type endopeptidase activity
GO:0005515 protein binding
GO:0008047 enzyme activator activity
GO:0008233 peptidase activity
GO:0008234 cysteine-type peptidase activity
GO:0016787 hydrolase activity
GO:0017124 SH3 domain binding
GO:0019901 protein kinase binding
GO:0042802 identical protein binding
GO:0097200 cysteine-type endopeptidase activity involved in execution phase of apoptosis

Biological Process:
GO:0006508 proteolysis
GO:0006915 apoptotic process
GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0006974 cellular response to DNA damage stimulus
GO:0007568 aging
GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage
GO:0008635 activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c
GO:0009411 response to UV
GO:0014070 response to organic cyclic compound
GO:0030220 platelet formation
GO:0032025 response to cobalt ion
GO:0032355 response to estradiol
GO:0032496 response to lipopolysaccharide
GO:0034349 glial cell apoptotic process
GO:0034644 cellular response to UV
GO:0042770 signal transduction in response to DNA damage
GO:0042981 regulation of apoptotic process
GO:0043065 positive regulation of apoptotic process
GO:0043525 positive regulation of neuron apoptotic process
GO:0046677 response to antibiotic
GO:0071407 cellular response to organic cyclic compound
GO:0071549 cellular response to dexamethasone stimulus
GO:0097192 extrinsic apoptotic signaling pathway in absence of ligand
GO:0097194 execution phase of apoptosis
GO:2001020 regulation of response to DNA damage stimulus

Cellular Component:
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005829 cytosol
GO:0032991 macromolecular complex
GO:0043293 apoptosome


-  Descriptions from all associated GenBank mRNAs
  AB209147 - Homo sapiens mRNA for caspase 9 isoform alpha preproprotein variant protein.
JD513539 - Sequence 494563 from Patent EP1572962.
U60521 - Human protease proMch6 (Mch6) mRNA, complete cds.
BC002452 - Homo sapiens caspase 9, apoptosis-related cysteine peptidase, mRNA (cDNA clone MGC:3054 IMAGE:3343958), complete cds.
BC006463 - Homo sapiens caspase 9, apoptosis-related cysteine peptidase, mRNA (cDNA clone MGC:2105 IMAGE:3542075), complete cds.
JA482043 - Sequence 26 from Patent WO2011072091.
JA482044 - Sequence 27 from Patent WO2011072091.
JE980335 - Sequence 26 from Patent EP2862929.
JE980336 - Sequence 27 from Patent EP2862929.
JD216960 - Sequence 197984 from Patent EP1572962.
AY732490 - Homo sapiens caspase 9 splice variant (CASP9) mRNA, complete cds, alternatively spliced.
JD560882 - Sequence 541906 from Patent EP1572962.
JD307476 - Sequence 288500 from Patent EP1572962.
JD239359 - Sequence 220383 from Patent EP1572962.
JD480651 - Sequence 461675 from Patent EP1572962.
JD503710 - Sequence 484734 from Patent EP1572962.
AB015653 - Homo sapiens mRNA for caspase-9 beta, complete cds.
JD447955 - Sequence 428979 from Patent EP1572962.
AK292111 - Homo sapiens cDNA FLJ75893 complete cds, highly similar to Homo sapiens caspase 9, apoptosis-related cysteine peptidase (CASP9), transcript variant alpha, mRNA.
JD261760 - Sequence 242784 from Patent EP1572962.
JD193492 - Sequence 174516 from Patent EP1572962.
JD274347 - Sequence 255371 from Patent EP1572962.
AK292080 - Homo sapiens cDNA FLJ78720 complete cds, highly similar to Homo sapiens caspase 9, apoptosis-related cysteine peptidase (CASP9), transcript variant alpha, mRNA.
U56390 - Human cysteine protease ICE-LAP6 mRNA, complete cds.
JD419310 - Sequence 400334 from Patent EP1572962.
JD098655 - Sequence 79679 from Patent EP1572962.
JD069337 - Sequence 50361 from Patent EP1572962.
JD044340 - Sequence 25364 from Patent EP1572962.
JD400491 - Sequence 381515 from Patent EP1572962.
AK303743 - Homo sapiens cDNA FLJ57472 complete cds, highly similar to Caspase-9 precursor (EC 3.4.22.-).
JD390383 - Sequence 371407 from Patent EP1572962.
JD384186 - Sequence 365210 from Patent EP1572962.
JD209553 - Sequence 190577 from Patent EP1572962.
JD562525 - Sequence 543549 from Patent EP1572962.
AF093130 - Homo sapiens caspase 9 short isoform (CASP9) mRNA, complete cds.
AB020979 - Homo sapiens mRNA for caspase-9, complete cds.
AF110376 - Homo sapiens caspase-9S precursor, mRNA, complete cds.
AJ781267 - Homo sapiens partial mRNA for caspase-9c protein.
HQ447255 - Synthetic construct Homo sapiens clone IMAGE:100070564; CCSB004596_02 caspase 9, apoptosis-related cysteine peptidase (CASP9) gene, encodes complete protein.
KJ890829 - Synthetic construct Homo sapiens clone ccsbBroadEn_00223 CASP9 gene, encodes complete protein.
BT006911 - Homo sapiens caspase 9, apoptosis-related cysteine protease mRNA, complete cds.
DQ891693 - Synthetic construct clone IMAGE:100004323; FLH180812.01X; RZPDo839G04134D caspase 9, apoptosis-related cysteine peptidase (CASP9) gene, encodes complete protein.
AB590140 - Synthetic construct DNA, clone: pFN21AE1303, Homo sapiens CASP9 gene for caspase 9, apoptosis-related cysteine peptidase, without stop codon, in Flexi system.
CU675417 - Synthetic construct Homo sapiens gateway clone IMAGE:100019296 5' read CASP9 mRNA.
JD494366 - Sequence 475390 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  BioCarta from NCI Cancer Genome Anatomy Project
h_WNVpathway - West Nile Virus
h_chemicalPathway - Apoptotic Signaling in Response to DNA Damage
h_d4gdiPathway - D4-GDI Signaling Pathway
h_mitochondriaPathway - Role of Mitochondria in Apoptotic Signaling
h_tffPathway - Trefoil Factors Initiate Mucosal Healing
h_HivnefPathway - HIV-I Nef: negative effector of Fas and TNF
h_hsp27Pathway - Stress Induction of HSP Regulation
h_caspasePathway - Caspase Cascade in Apoptosis
h_rasPathway - Ras Signaling Pathway
h_aktPathway - AKT Signaling Pathway
h_deathPathway - Induction of apoptosis through DR3 and DR4/5 Death Receptors

Reactome (by CSHL, EBI, and GO)

Protein P55211 (Reactome details) participates in the following event(s):

R-HSA-114256 Cytochrome C:Apaf-1 binds Procaspase-9
R-HSA-198621 AKT phosphorylates caspase-9
R-HSA-2399985 AKT1 E17K mutant phosphorylates caspase-9
R-HSA-114259 Cleavage of Procaspase-9 to Caspase-9
R-HSA-622420 NOD1 induced apoptosis is mediated by RIP2 and CARD8
R-HSA-373700 Caspase-9 binds DCC:DIP13alpha complex
R-HSA-114440 Dissociation of Caspase-9 from SMAC:XIAP:Caspase-9
R-HSA-114361 SMAC binds XIAP:Caspase-9
R-HSA-114252 Cleavage of Procaspase-3 by the apoptosome
R-HSA-114261 Cleavage of Procaspase-7 by the apoptosome
R-HSA-418845 Activation of caspase-3
R-HSA-111458 Formation of apoptosome
R-HSA-198323 AKT phosphorylates targets in the cytosol
R-HSA-5674400 Constitutive Signaling by AKT1 E17K in Cancer
R-HSA-168638 NOD1/2 Signaling Pathway
R-HSA-111461 Cytochrome c-mediated apoptotic response
R-HSA-1257604 PIP3 activates AKT signaling
R-HSA-2219528 PI3K/AKT Signaling in Cancer
R-HSA-418889 Ligand-independent caspase activation via DCC
R-HSA-111464 SMAC-mediated dissociation of IAP:caspase complexes
R-HSA-168643 Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways
R-HSA-111471 Apoptotic factor-mediated response
R-HSA-9006925 Intracellular signaling by second messengers
R-HSA-5663202 Diseases of signal transduction
R-HSA-111463 SMAC binds to IAPs
R-HSA-5357769 Caspase activation via extrinsic apoptotic signalling pathway
R-HSA-111469 SMAC-mediated apoptotic response
R-HSA-168249 Innate Immune System
R-HSA-109606 Intrinsic Pathway for Apoptosis
R-HSA-162582 Signal Transduction
R-HSA-1643685 Disease
R-HSA-111459 Activation of caspases through apoptosome-mediated cleavage
R-HSA-109581 Apoptosis
R-HSA-168256 Immune System
R-HSA-5357801 Programmed Cell Death

-  Other Names for This Gene
  Alternate Gene Symbols: B4E1A3, CASP9_HUMAN, ENST00000333868.1, ENST00000333868.2, ENST00000333868.3, ENST00000333868.4, ENST00000333868.5, ENST00000333868.6, ENST00000333868.7, ENST00000333868.8, ENST00000333868.9, MCH6, NR_102733, O95348, P55211, Q53Y70, Q5JRU9, Q5UGI1, Q92852, Q9BQ62, Q9UEQ3, Q9UIJ8, uc317ttr.1, uc317ttr.2
UCSC ID: ENST00000333868.10_7
RefSeq Accession: NM_001229.5
Protein: P55211 (aka CASP9_HUMAN or ICE9_HUMAN)

-  Gene Model Information
  Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.