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CASP8AP2 caspase 8 associated protein 2 [ Homo sapiens (human) ]

Gene ID: 9994, updated on 27-Nov-2024

Summary

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Official Symbol
CASP8AP2provided by HGNC
Official Full Name
caspase 8 associated protein 2provided by HGNC
Primary source
HGNC:HGNC:1510
See related
Ensembl:ENSG00000118412 MIM:606880; AllianceGenome:HGNC:1510
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
CED-4; FLASH; RIP25
Summary
This protein is highly similar to FLASH, a mouse apoptotic protein identified by its interaction with the death-effector domain (DED) of caspase 8. Studies of FLASH protein suggested that this protein may be a component of the death-inducing signaling complex that includes Fas receptor, Fas-binding adapter FADD, and caspase 8, and plays a regulatory role in Fas-mediated apoptosis. Alternative splicing results in multiple transcript variants encoding the same protein.[provided by RefSeq, Nov 2008]
Annotation information
Annotation category: suggests misassembly
Annotation category: partial on reference assembly
Expression
Ubiquitous expression in lymph node (RPKM 5.6), testis (RPKM 4.6) and 25 other tissues See more
Orthologs
mouse all
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Genomic context

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See CASP8AP2 in Genome Data Viewer
Location:
6q15
Exon count:
10
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (89829880..89874436)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (91029094..91086157)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (90539599..90584155)

Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene midasin AAA ATPase 1 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr6:90526731-90527350 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr6:90527351-90527970 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:90527971-90528590 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:90529211-90529830 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:90529831-90530450 Neighboring gene small nucleolar RNA U13 Neighboring gene PIMREG pseudogene 3 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17396 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24832 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:90596851-90597424 Neighboring gene ribosomal protein L22 pseudogene 14 Neighboring gene G protein pathway suppressor 1 pseudogene

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Systems-wide RNAi analysis of CASP8AP2/FLASH shows transcriptional deregulation of the replication-dependent histone genes and extensive effects on the transcriptome of colorectal cancer cells. Hummon AB, et al. Mol Cancer, 2012 Jan 4. PMID 22216762, Free PMC Article
  2. FLASH is required for the endonucleolytic cleavage of histone pre-mRNAs but is dispensable for the 5' exonucleolytic degradation of the downstream cleavage product. Yang XC, et al. Mol Cell Biol, 2011 Apr. PMID 21245389, Free PMC Article
  3. Hypermethylation of two CpG sites upstream of CASP8AP2 promoter influences gene expression and treatment outcome in childhood acute lymphoblastic leukemia. Li ZG, et al. Leuk Res, 2013 Oct. PMID 23953914
  4. SUMO modification regulates the transcriptional activity of FLASH. Alm-Kristiansen AH, et al. Biochem Biophys Res Commun, 2009 Sep 25. PMID 19615980
  5. The N-terminal domains of FLASH and Lsm11 form a 2:1 heterotrimer for histone pre-mRNA 3'-end processing. Aik WS, et al. PLoS One, 2017. PMID 29020104, Free PMC Article

See all (91) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Interaction of E2F3a and CASP8AP2 Regulates Histone Expression and Chemosensitivity of Leukemic Cells.
    Title: Interaction of E2F3a and CASP8AP2 Regulates Histone Expression and Chemosensitivity of Leukemic Cells.
  2. CRISPRi screening identifies CASP8AP2 as an essential viability factor in lung cancer controlling tumor cell death via the AP-1 pathway.
    Title: CRISPRi screening identifies CASP8AP2 as an essential viability factor in lung cancer controlling tumor cell death via the AP-1 pathway.
  3. Interaction between CASP8AP2 and ZEB2-CtBP2 Regulates the Expression of LEF1.
    Title: Interaction between CASP8AP2 and ZEB2-CtBP2 Regulates the Expression of LEF1.
  4. Knockout of the caspase 8-associated protein 2 gene improves recombinant protein expression in HEK293 cells through up-regulation of the cyclin-dependent kinase inhibitor 2A gene.
    Title: Knockout of the caspase 8-associated protein 2 gene improves recombinant protein expression in HEK293 cells through up-regulation of the cyclin-dependent kinase inhibitor 2A gene.
  5. Low expression of CTBP2 and CASP8AP2 predicts risk of relapse in childhood B-cell precursor acute lymphoblastic leukemia: a retrospective cohort study.
    Title: Low expression of CTBP2 and CASP8AP2 predicts risk of relapse in childhood B-cell precursor acute lymphoblastic leukemia: a retrospective cohort study.
  6. Structural Analysis of the SANT/Myb Domain of FLASH and YARP Proteins and Their Complex with the C-Terminal Fragment of NPAT by NMR Spectroscopy and Computer Simulations.
    Title: Structural Analysis of the SANT/Myb Domain of FLASH and YARP Proteins and Their Complex with the C-Terminal Fragment of NPAT by NMR Spectroscopy and Computer Simulations.
  7. Here, we assembled core U7 snRNP bound to FLASH from recombinant components and analyzed its appearance by electron microscopy and ability to support histone pre-mRNA processing in the presence of polyadenylation factors from nuclear extracts
    Title: Composition and processing activity of a semi-recombinant holo U7 snRNP.
  8. FLASH plays two roles in 3' end processing of histone pre-mRNAs: It interacts with Lsm11 to form a docking platform for the polyadenylation factors, and it cooperates with SLBP to recruit U7 snRNP to histone pre-mRNA.
    Title: U7 snRNP is recruited to histone pre-mRNA in a FLASH-dependent manner by two separate regions of the stem-loop binding protein.
  9. FLASH is required for embryogenesis, but not for cell proliferation or differentiation in embryonic stem cells.
    Title: FLASH/casp8ap2 is indispensable for early embryogenesis but dispensable for proliferation and differentiation of ES cells.
  10. Our results indicate that the APAF1, BAX, and FLASH genes not only harbor frameshift mutations but also demonstrate mutational ITH, which together might play a role in the tumorigenesis of CRC with MSI-H by affecting the apoptosis of cancer cells.
    Title: Regional Bias of Intratumoral Genetic Heterogeneity of Apoptosis-Related Genes BAX, APAF1, and FLASH in Colon Cancers with High Microsatellite Instability.
Submit: New GeneRIF Correction See all GeneRIFs (41)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See Variation Viewer (GRCh37.p13)

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env HIV-1 gp120 upregulates the expression of caspase 8 associated protein 2 (CASP8AP2) in human B cells PubMed
Vpr vpr Overexpression of CASP8AP2 is induced by HIV-1 Vpr in the transfected 293T cells PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ11208, KIAA1315

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables SUMO polymer binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables cysteine-type endopeptidase activator activity involved in apoptotic process ISS
Inferred from Sequence or Structural Similarity
more info
  
enables death receptor binding TAS
Traceable Author Statement
more info
 PubMed 
enables peptidase activator activity involved in apoptotic process ISS
Inferred from Sequence or Structural Similarity
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables transcription corepressor activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables transcription corepressor activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in Fas signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in Fas signaling pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in apoptotic signaling pathway TAS
Traceable Author Statement
more info
 PubMed 
involved_in cellular response to mechanical stimulus IEP
Inferred from Expression Pattern
more info
 PubMed 
involved_in extrinsic apoptotic signaling pathway via death domain receptors IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in extrinsic apoptotic signaling pathway via death domain receptors IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in extrinsic apoptotic signaling pathway via death domain receptors ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in negative regulation of DNA-templated transcription IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of cysteine-type endopeptidase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of cysteine-type endopeptidase activity ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in signal transduction TAS
Traceable Author Statement
more info
 PubMed 
Component Evidence Code Pubs
is_active_in PML body IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in PML body IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytoplasm ISS
Inferred from Sequence or Structural Similarity
more info
 PubMed 
is_active_in mitochondrion IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in mitochondrion IDA
Inferred from Direct Assay
more info
 PubMed 
located_in nucleoplasm TAS
Traceable Author Statement
more info
  
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 
located_in nucleus ISS
Inferred from Sequence or Structural Similarity
more info
 PubMed 

General protein information

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Preferred Names
CASP8-associated protein 2
Names
FLASH homolog RIP25
FLICE associated huge
FLICE-associated huge protein
human FLASH

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001137667.2 → NP_001131139.1  CASP8-associated protein 2

    See identical proteins and their annotated locations for NP_001131139.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR, compared to variant 1.
    Source sequence(s)
    AF164678, AL353692, BC132828
    UniProtKB/Swiss-Prot
    A2RUB7, E1P553, Q6PH76, Q7LCQ7, Q86YD9, Q9NUQ4, Q9NZV9, Q9P2N1, Q9UKL3, Q9Y563
    UniProtKB/TrEMBL
    A7E2C0
    Conserved Domains (1) summary
    cd12202
    Location:1916 → 1980
    CASP8AP2; Caspase 8-associated protein 2 myb-like domain

  2. NM_001137668.2 → NP_001131140.1  CASP8-associated protein 2

    See identical proteins and their annotated locations for NP_001131140.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR, compared to variant 1.
    Source sequence(s)
    AF154415, AF164678, AL353692
    UniProtKB/Swiss-Prot
    A2RUB7, E1P553, Q6PH76, Q7LCQ7, Q86YD9, Q9NUQ4, Q9NZV9, Q9P2N1, Q9UKL3, Q9Y563
    UniProtKB/TrEMBL
    A7E2C0
    Conserved Domains (1) summary
    cd12202
    Location:1916 → 1980
    CASP8AP2; Caspase 8-associated protein 2 myb-like domain

  3. NM_012115.4 → NP_036247.1  CASP8-associated protein 2

    See identical proteins and their annotated locations for NP_036247.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) represents the longest transcript.
    Source sequence(s)
    AF154415, AF164678, AL353692
    UniProtKB/Swiss-Prot
    A2RUB7, E1P553, Q6PH76, Q7LCQ7, Q86YD9, Q9NUQ4, Q9NZV9, Q9P2N1, Q9UKL3, Q9Y563
    UniProtKB/TrEMBL
    A7E2C0
    Related
    ENSP00000478179.2, ENST00000551025.4
    Conserved Domains (1) summary
    cd12202
    Location:1916 → 1980
    CASP8AP2; Caspase 8-associated protein 2 myb-like domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000006.12 Reference GRCh38.p14 Primary Assembly

    Range
    89829880..89874436
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p14 PATCHES

Genomic

  1. NW_017363815.1 Reference GRCh38.p14 PATCHES

    Range
    13399..72124
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054332069.1 → XP_054188044.1  CASP8-associated protein 2 isoform X3

  2. XM_054332078.1 → XP_054188053.1  CASP8-associated protein 2 isoform X4

  3. XM_054332061.1 → XP_054188036.1  CASP8-associated protein 2 isoform X2

  4. XM_054332077.1 → XP_054188052.1  CASP8-associated protein 2 isoform X4

  5. XM_054332079.1 → XP_054188054.1  CASP8-associated protein 2 isoform X2

  6. XM_054332062.1 → XP_054188037.1  CASP8-associated protein 2 isoform X3

  7. XM_054332073.1 → XP_054188048.1  CASP8-associated protein 2 isoform X3

  8. XM_054332071.1 → XP_054188046.1  CASP8-associated protein 2 isoform X3

  9. XM_054332067.1 → XP_054188042.1  CASP8-associated protein 2 isoform X3

  10. XM_054332074.1 → XP_054188049.1  CASP8-associated protein 2 isoform X1

    UniProtKB/Swiss-Prot
    A2RUB7, E1P553, Q6PH76, Q7LCQ7, Q86YD9, Q9NUQ4, Q9NZV9, Q9P2N1, Q9UKL3, Q9Y563

  11. XM_054332076.1 → XP_054188051.1  CASP8-associated protein 2 isoform X1

    UniProtKB/Swiss-Prot
    A2RUB7, E1P553, Q6PH76, Q7LCQ7, Q86YD9, Q9NUQ4, Q9NZV9, Q9P2N1, Q9UKL3, Q9Y563

  12. XM_054332072.1 → XP_054188047.1  CASP8-associated protein 2 isoform X3

  13. XM_054332070.1 → XP_054188045.1  CASP8-associated protein 2 isoform X3

  14. XM_054332063.1 → XP_054188038.1  CASP8-associated protein 2 isoform X3

  15. XM_054332075.1 → XP_054188050.1  CASP8-associated protein 2 isoform X1

    UniProtKB/Swiss-Prot
    A2RUB7, E1P553, Q6PH76, Q7LCQ7, Q86YD9, Q9NUQ4, Q9NZV9, Q9P2N1, Q9UKL3, Q9Y563

  16. XM_054332065.1 → XP_054188040.1  CASP8-associated protein 2 isoform X3

  17. XM_054332064.1 → XP_054188039.1  CASP8-associated protein 2 isoform X3

  18. XM_054332068.1 → XP_054188043.1  CASP8-associated protein 2 isoform X3

  19. XM_054332066.1 → XP_054188041.1  CASP8-associated protein 2 isoform X3

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060930.1 Alternate T2T-CHM13v2.0

    Range
    91029094..91086157
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054356913.1 → XP_054212888.1  CASP8-associated protein 2 isoform X6

  2. XM_054356922.1 → XP_054212897.1  CASP8-associated protein 2 isoform X7

  3. XM_054356906.1 → XP_054212881.1  CASP8-associated protein 2 isoform X5

  4. XM_054356921.1 → XP_054212896.1  CASP8-associated protein 2 isoform X7

  5. XM_054356923.1 → XP_054212898.1  CASP8-associated protein 2 isoform X5

  6. XM_054356907.1 → XP_054212882.1  CASP8-associated protein 2 isoform X6

  7. XM_054356917.1 → XP_054212892.1  CASP8-associated protein 2 isoform X6

  8. XM_054356915.1 → XP_054212890.1  CASP8-associated protein 2 isoform X6

  9. XM_054356911.1 → XP_054212886.1  CASP8-associated protein 2 isoform X6

  10. XM_054356918.1 → XP_054212893.1  CASP8-associated protein 2 isoform X1

    UniProtKB/Swiss-Prot
    A2RUB7, E1P553, Q6PH76, Q7LCQ7, Q86YD9, Q9NUQ4, Q9NZV9, Q9P2N1, Q9UKL3, Q9Y563

  11. XM_054356920.1 → XP_054212895.1  CASP8-associated protein 2 isoform X1

    UniProtKB/Swiss-Prot
    A2RUB7, E1P553, Q6PH76, Q7LCQ7, Q86YD9, Q9NUQ4, Q9NZV9, Q9P2N1, Q9UKL3, Q9Y563

  12. XM_054356916.1 → XP_054212891.1  CASP8-associated protein 2 isoform X6

  13. XM_054356914.1 → XP_054212889.1  CASP8-associated protein 2 isoform X6

  14. XM_054356908.1 → XP_054212883.1  CASP8-associated protein 2 isoform X6

  15. XM_054356919.1 → XP_054212894.1  CASP8-associated protein 2 isoform X1

    UniProtKB/Swiss-Prot
    A2RUB7, E1P553, Q6PH76, Q7LCQ7, Q86YD9, Q9NUQ4, Q9NZV9, Q9P2N1, Q9UKL3, Q9Y563

  16. XM_054356910.1 → XP_054212885.1  CASP8-associated protein 2 isoform X6

  17. XM_054356909.1 → XP_054212884.1  CASP8-associated protein 2 isoform X6

  18. XM_054356912.1 → XP_054212887.1  CASP8-associated protein 2 isoform X6

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9UKL3.1 GenPept UniProtKB/Swiss-Prot:Q9UKL3

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