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    FICD FIC domain protein adenylyltransferase [ Homo sapiens (human) ]

    Gene ID: 11153, updated on 10-Dec-2024

    Summary

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    Official Symbol
    FICDprovided by HGNC
    Official Full Name
    FIC domain protein adenylyltransferaseprovided by HGNC
    Primary source
    HGNC:HGNC:18416
    See related
    Ensembl:ENSG00000198855 MIM:620875; AllianceGenome:HGNC:18416
    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
    HYPE; HIP13; SPG92; UNQ3041
    Summary
    Enables several functions, including AMPylase activity; ATP binding activity; and Hsp70 protein binding activity. Involved in protein adenylylation; regulation of IRE1-mediated unfolded protein response; and response to endoplasmic reticulum stress. Located in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Dec 2024]
    Expression
    Ubiquitous expression in thyroid (RPKM 7.5), testis (RPKM 4.5) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See FICD in Genome Data Viewer
    Location:
    12q23.3
    Exon count:
    3
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (108515277..108521210)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (108484639..108490575)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (108909054..108914987)

    Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:108697351-108697872 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:108699443-108699964 Neighboring gene chemerin chemokine-like receptor 1 Neighboring gene Sharpr-MPRA regulatory region 8395 Neighboring gene Sharpr-MPRA regulatory region 632 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6959 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:108732521-108733144 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4826 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:108739700-108740200 Neighboring gene MPRA-validated peak1933 silencer Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr12:108780158-108781357 Neighboring gene Sharpr-MPRA regulatory region 8786 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr12:108811567-108812766 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr12:108835174-108835930 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr12:108835931-108836688 Neighboring gene MPRA-validated peak1935 silencer Neighboring gene long intergenic non-protein coding RNA 1498 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:108906844-108907029 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6960 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:108910488-108910988 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:108910989-108911489 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr12:108918373-108919572 Neighboring gene MPRA-validated peak1936 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6962 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4827 Neighboring gene spliceosome associated factor 3, U4/U6 recycling protein Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6964 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6963 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6965 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6966 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4828 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6967 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4829 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6968 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6969 Neighboring gene iron-sulfur cluster assembly enzyme

    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. BiP inactivation due to loss of the deAMPylation function of FICD causes a motor neuron disease. Rebelo AP, et al. Genet Med, 2022 Dec. PMID 36136088
    2. Investigation of the Detailed AMPylated Reaction Mechanism for the Huntingtin Yeast-Interacting Protein E Enzyme HYPE. Liu M, et al. Int J Mol Sci, 2021 Jun 29. PMID 34209803, Free PMC Article
    3. Specificity of AMPylation of the human chaperone BiP is mediated by TPR motifs of FICD. Fauser J, et al. Nat Commun, 2021 Apr 23. PMID 33893288, Free PMC Article
    4. A Fluorescence Polarization-Based High-Throughput Screen to Identify the First Small-Molecule Modulators of the Human Adenylyltransferase HYPE/FICD. Camara A, et al. Int J Mol Sci, 2020 Sep 27. PMID 32992526, Free PMC Article
    5. FICD activity and AMPylation remodelling modulate human neurogenesis. Kielkowski P, et al. Nat Commun, 2020 Jan 24. PMID 31980631, Free PMC Article

    See all (25) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Structures of a deAMPylation complex rationalise the switch between antagonistic catalytic activities of FICD.
      Title: Structures of a deAMPylation complex rationalise the switch between antagonistic catalytic activities of FICD.
    2. Investigation of the Detailed AMPylated Reaction Mechanism for the Huntingtin Yeast-Interacting Protein E Enzyme HYPE.
      Title: Investigation of the Detailed AMPylated Reaction Mechanism for the Huntingtin Yeast-Interacting Protein E Enzyme HYPE.
    3. Specificity of AMPylation of the human chaperone BiP is mediated by TPR motifs of FICD.
      Title: Specificity of AMPylation of the human chaperone BiP is mediated by TPR motifs of FICD.
    4. A Fluorescence Polarization-Based High-Throughput Screen to Identify the First Small-Molecule Modulators of the Human Adenylyltransferase HYPE/FICD.
      Title: A Fluorescence Polarization-Based High-Throughput Screen to Identify the First Small-Molecule Modulators of the Human Adenylyltransferase HYPE/FICD.
    5. FICD-dependent AMPylation remodelling accelerates differentiation of neural progenitor cells into mature neurons.
      Title: FICD activity and AMPylation remodelling modulate human neurogenesis.
    6. The single catalytic domain of FICD can release the attached AMP, restoring functionality to BiP.
      Title: FICD acts bifunctionally to AMPylate and de-AMPylate the endoplasmic reticulum chaperone BiP.
    7. We first demonstrate efficient enrichment and fast visualization of potential HYPE substrates in cell lysates by in-gel fluorescence, followed by robust identification via shotgun proteomics on a QExactive mass spectrometer
      Title: Global Profiling of Huntingtin-associated protein E (HYPE)-Mediated AMPylation through a Chemical Proteomic Approach.
    8. HYPE is an unfolded protein response regulator.
      Title: A novel link between Fic (filamentation induced by cAMP)-mediated adenylylation/AMPylation and the unfolded protein response.
    Submit: New GeneRIF Correction

    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

    EBI GWAS Catalog

    Description
    Genome-wide association study identifies three novel susceptibility loci for severe Acne vulgaris.
    EBI GWAS Catalog
    Genome-wide data reveal novel genes for methotrexate response in a large cohort of juvenile idiopathic arthritis cases.
    EBI GWAS Catalog
    Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC5623

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables AMPylase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables ATP binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables Hsp70 protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein adenylylhydrolase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables protein adenylylhydrolase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein homodimerization activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein homodimerization activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables protein-folding chaperone binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in negative regulation of GTPase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in protein adenylylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein deadenylylation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in regulation of IRE1-mediated unfolded protein response IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in response to endoplasmic reticulum stress IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in response to unfolded protein IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in endoplasmic reticulum IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    located_in endoplasmic reticulum membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    protein adenylyltransferase FICD
    Names
    AMPylase
    AMPylator FICD
    FIC domain containing
    FIC domain-containing protein
    HIP-13
    Huntingtin interacting protein E
    adenosine monophosphate-protein transferase FICD
    de-AMPylase FICD
    fic S-phase protein cell division homolog
    huntingtin interactor protein E
    huntingtin yeast partner E
    huntingtin-interacting protein 13
    huntingtin-interacting protein E
    NP_009007.2

    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_007076.3 → NP_009007.2  protein adenylyltransferase FICD

      See identical proteins and their annotated locations for NP_009007.2

      Status: VALIDATED

      Source sequence(s)
      AC010206, AF049611, AK026074, BC001342
      Consensus CDS
      CCDS9116.1
      UniProtKB/Swiss-Prot
      O75406, Q9BVA6
      Related
      ENSP00000446479.1, ENST00000552695.6
      Conserved Domains (4) summary
      COG3177
      Location:227 → 430
      COG3177; Fic family protein [Transcription]
      sd00006
      Location:106 → 134
      TPR; TPR repeat [structural motif]
      pfam02661
      Location:285 → 381
      Fic; Fic/DOC family
      pfam13414
      Location:105 → 171
      TPR_11; TPR repeat

    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_000012.12 Reference GRCh38.p14 Primary Assembly

      Range
      108515277..108521210
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060936.1 Alternate T2T-CHM13v2.0

      Range
      108484639..108490575
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9BVA6.2 GenPept UniProtKB/Swiss-Prot:Q9BVA6

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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