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    MDFIC MyoD family inhibitor domain containing [ Homo sapiens (human) ]

    Gene ID: 29969, updated on 5-Mar-2024

    Summary

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    Official Symbol
    MDFICprovided by HGNC
    Official Full Name
    MyoD family inhibitor domain containingprovided by HGNC
    Primary source
    HGNC:HGNC:28870
    See related
    Ensembl:ENSG00000135272 MIM:614511; AllianceGenome:HGNC:28870
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    HIC; MDFIC1; LMPHM12
    Summary
    This gene product is a member of a family of proteins characterized by a specific cysteine-rich C-terminal domain, which is involved in transcriptional regulation of viral genome expression. Alternative translation initiation from an upstream non-AUG (GUG), and an in-frame, downstream AUG codon, results in the production of two isoforms, p40 and p32, respectively, which have different subcellular localization; p32 is mainly found in the cytoplasm, whereas p40 is targeted to the nucleolus. Both isoforms have transcriptional regulatory activity that is attributable to the cysteine-rich C-terminal domain. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]
    Expression
    Ubiquitous expression in fat (RPKM 25.2), spleen (RPKM 14.3) and 23 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See MDFIC in Genome Data Viewer
    Location:
    7q31.1-q31.2
    Exon count:
    6
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (114922094..115019917)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (116236858..116334721)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (114562149..114659971)

    Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene forkhead box P2 Neighboring gene VISTA enhancer hs1080 Neighboring gene VISTA enhancer hs222 Neighboring gene RNA, 5S ribosomal pseudogene 238 Neighboring gene VISTA enhancer hs956 Neighboring gene VISTA enhancer hs966 Neighboring gene microRNA 3666 Neighboring gene H3K27ac hESC enhancer GRCh37_chr7:114373209-114373709 Neighboring gene VISTA enhancer hs1192 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr7:114465341-114466180 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18547 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26523 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18548 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18551 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18550 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18549 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr7:114570117-114570666 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18552 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26524 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:114670265-114670880 Neighboring gene long intergenic non-protein coding RNA 1393 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26525 Neighboring gene long intergenic non-protein coding RNA 1392 Neighboring gene Rac family small GTPase 1 pseudogene 6

    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. Human I-mfa domain proteins specifically interact with KSHV LANA and affect its regulation of Wnt signaling-dependent transcription. Kusano S, et al. Biochem Biophys Res Commun, 2010 Jun 4. PMID 20417616
    2. The complex regulation of HIC (Human I-mfa domain containing protein) expression. Reiss-Sklan E, et al. PLoS One, 2009 Jul 7. PMID 19582149, Free PMC Article
    3. Expression profile and differential regulation of the Human I-mfa domain-Containing protein (HIC) gene in immune cells. Gu L, et al. Immunol Lett, 2009 Apr 27. PMID 19428567
    4. The 3'UTR of HIC mRNA improves the production of recombinant proteins in Chinese hamster ovary cells. Liu J, et al. J Biotechnol, 2009 Jan 15. PMID 19041912
    5. HIC gene, a candidate suppressor gene within a minimal region of loss at 7q31.1 in myeloid neoplasms. Cigognini D, et al. Leuk Res, 2007 Apr. PMID 17064770

    See all (26) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. MyoD-family inhibitor proteins act as auxiliary subunits of Piezo channels.
      Title: MyoD-family inhibitor proteins act as auxiliary subunits of Piezo channels.
    2. Pathogenic variants in MDFIC cause recessive central conducting lymphatic anomaly with lymphedema.
      Title: Pathogenic variants in MDFIC cause recessive central conducting lymphatic anomaly with lymphedema.
    3. Opposite Roles of the JMJD1A Interaction Partners MDFI and MDFIC in Colorectal Cancer.
      Title: Opposite Roles of the JMJD1A Interaction Partners MDFI and MDFIC in Colorectal Cancer.
    4. GR directly represses the MDFIC gene, revealing a negative feedback loop by which glucocorticoids limit MDFIC activity. These findings identify a new binding partner for cytoplasmic GR that modulates the receptor transcriptome and contributes to the tissue-specific actions of glucocorticoids.
      Title: Cross-talk between the glucocorticoid receptor and MyoD family inhibitor domain-containing protein provides a new mechanism for generating tissue-specific responses to glucocorticoids.
    5. HIC specifically interacts with HTLV-1 Tax and negatively regulates Tax transactivational activity by altering its subcellular distribution and stability.
      Title: I-mfa domain proteins specifically interact with HTLV-1 Tax and repress its transactivating functions.
    6. We demonstrate that HIC selectively interferes with Rev NLS interaction with importin beta and impedes its nuclear import and function, but does not affect Rev nuclear import mediated by transportin.
      Title: Intermolecular masking of the HIV-1 Rev NLS by the cellular protein HIC: novel insights into the regulation of Rev nuclear import.
    7. These data reveal for the first time that I-mfa domain proteins interact with LANA and negatively regulate LANA-mediated activation of Wnt signaling-dependent transcription by inhibiting the formation of the LANA.GSK-3beta complex.
      Title: Human I-mfa domain proteins specifically interact with KSHV LANA and affect its regulation of Wnt signaling-dependent transcription.
    8. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
      Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
    9. strict regulation of HIC expression at the levels of mRNA stability, translation efficiency and protein stability suggests that expression of the HIC protein and its involvement in the various pathways is required only under specific cellular conditions
      Title: The complex regulation of HIC (Human I-mfa domain containing protein) expression.
    10. This study describes that the immune expression of HIC is cell-specific, dynamic, and identifies the HIC gene as an IL-2 responsive gene.
      Title: Expression profile and differential regulation of the Human I-mfa domain-Containing protein (HIC) gene in immune cells.
    Submit: New GeneRIF Correction See all GeneRIFs (11)

    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

    Associated conditions

    Description Tests
    Lymphatic malformation 12
    MedGen: C5774203 OMIM: 620014 GeneReviews: Not available
    		Compare labs

    EBI GWAS Catalog

    Description
    Combined linkage and association analyses identify a novel locus for obesity near PROX1 in Asians.
    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)

    Genotypes

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Rev rev Downregulation of HIV-1 Rev activity by HIC is dependent on the I-mfa domain in a cell-specific manner PubMed
    rev HIV-1 Rev nuclear import mediated by importin beta is selectively inhibited by competitive excess of HIC in a cell-specific fashion PubMed
    rev HIV-1 Rev and HIC interact directly and form a complex through the I-mfa domain (residues 144-246) of HIC PubMed
    Tat tat I-mfa (inhibitor of MyoD family a) and HIC (human I-mfa-domain-containing) proteins serve as substrates for P-TEFb. Their I-mfa domains bind the activation domain of HIV-1 Tat and inhibit Tat- and P-TEFb-dependent HIV-1 transcription PubMed
    tat HIC binds both HIV-1 Tat and cyclin T1 through its I-mfa domain (amino acids 165-246) and modulates Tat transactivation of the HIV-1 LTR promoter PubMed
    tat HIC binds the NLS domain of HIV-1 Tat located between amino acid residues 48 and 60 of Tat 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

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables DNA-binding transcription factor binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables Tat protein binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables cyclin binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables transcription factor binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in negative regulation of DNA-templated transcription IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of DNA-templated transcription ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in negative regulation of protein import into nucleus ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of DNA-templated transcription IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of viral transcription IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of viral transcription IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of JNK cascade IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of Wnt signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in extracellular region IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in nucleolus IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    myoD family inhibitor domain-containing protein
    Names
    I-mfa domain-containing protein

    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.

    Genomic

    1. NG_029463.2 RefSeqGene

      Range
      5002..102825
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001166345.3 → NP_001159817.1  myoD family inhibitor domain-containing protein isoform p32

      See identical proteins and their annotated locations for NP_001159817.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript. It encodes isoform p32 via the use of a downstream AUG translation initiation codon.
      Source sequence(s)
      AC017003
      Consensus CDS
      CCDS55155.1
      UniProtKB/Swiss-Prot
      Q9P1T6, Q9P1T7
      Related
      ENSP00000377126.1, ENST00000393486.6
      Conserved Domains (1) summary
      pfam15316
      Location:74 → 246
      MDFI; MyoD family inhibitor

    2. NM_001166346.1 → NP_001159818.3  myoD family inhibitor domain-containing protein isoform c

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 3' coding region and 3' UTR, compared to variant 1. The encoded isoform (c) has a distinct and shorter C-terminus, compared to isoform p40.
      Source sequence(s)
      AF054589, CB048531

    3. NM_199072.5 → NP_951038.1  myoD family inhibitor domain-containing protein isoform p40

      See identical proteins and their annotated locations for NP_951038.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript. It encodes the longest isoform (p40) via the use of an upstream non-AUG (GUG) translation initiation codon.
      Source sequence(s)
      AA406528, AC017003, AF054589
      UniProtKB/Swiss-Prot
      Q9P1T7
      UniProtKB/TrEMBL
      A0A087X231
      Conserved Domains (1) summary
      pfam15316
      Location:183 → 355
      MDFI; MyoD family inhibitor

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000007.14 Reference GRCh38.p14 Primary Assembly

      Range
      114922094..115019917
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060931.1 Alternate T2T-CHM13v2.0

      Range
      116236858..116334721
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9P1T7.2 GenPept UniProtKB/Swiss-Prot:Q9P1T7

    Gene LinkOut

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

    Chemical Information
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