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

    Gene ID: 9994, updated on 14-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 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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    NEW Try the new Transcript table

    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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