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    ZCCHC4 zinc finger CCHC-type containing 4 [ Homo sapiens (human) ]

    Gene ID: 29063, updated on 30-Oct-2024

    Summary

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    Official Symbol
    ZCCHC4provided by HGNC
    Official Full Name
    zinc finger CCHC-type containing 4provided by HGNC
    Primary source
    HGNC:HGNC:22917
    See related
    Ensembl:ENSG00000168228 MIM:611792; AllianceGenome:HGNC:22917
    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
    ZGRF4; HSPC052
    Summary
    Enables S-adenosyl-L-methionine binding activity; rRNA (adenine-N6-)-methyltransferase activity; and zinc ion binding activity. Involved in positive regulation of translation and rRNA methylation. Located in cytoplasm and nucleolus. [provided by Alliance of Genome Resources, Oct 2024]
    Expression
    Ubiquitous expression in testis (RPKM 1.4), ovary (RPKM 1.3) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See ZCCHC4 in Genome Data Viewer
    Location:
    4p15.2
    Exon count:
    15
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (25312774..25370383)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (25294601..25352222)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (25314396..25372005)

    Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124900916 Neighboring gene phosphatidylinositol 4-kinase type 2 beta Neighboring gene uncharacterized LOC124900685 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21373 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21374 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:25314050-25314926 Neighboring gene uncharacterized LOC124900686 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21376 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21377 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15324 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21378 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21379 Neighboring gene anaphase promoting complex subunit 4 Neighboring gene uncharacterized LOC105374536 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15325 Neighboring gene H3K27ac hESC enhancer GRCh37_chr4:25451941-25452758 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr4:25458193-25458692

    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. The epigenetic downregulation of LncGHRLOS mediated by RNA m6A methylase ZCCHC4 promotes colorectal cancer tumorigenesis. Chen K, et al. J Exp Clin Cancer Res, 2024 Feb 7. PMID 38326863, Free PMC Article
    2. RNA-binding protein ZCCHC4 promotes human cancer chemoresistance by disrupting DNA-damage-induced apoptosis. Zhu H, et al. Signal Transduct Target Ther, 2022 Jul 20. PMID 35853866, Free PMC Article
    3. ZCCHC4 Promotes Osteosarcoma Progression by Upregulating ITGB1. Luo L, et al. Crit Rev Eukaryot Gene Expr, 2023. PMID 37606162
    4. N(6-)Methyladenosine methyltransferase ZCCHC4 mediates ribosomal RNA methylation. Ma H, et al. Nat Chem Biol, 2019 Jan. PMID 30531910, Free PMC Article
    5. Structure and regulation of ZCCHC4 in m(6)A-methylation of 28S rRNA. Ren W, et al. Nat Commun, 2019 Nov 6. PMID 31695039, Free PMC Article

    See all (22) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The epigenetic downregulation of LncGHRLOS mediated by RNA m6A methylase ZCCHC4 promotes colorectal cancer tumorigenesis.
      Title: The epigenetic downregulation of LncGHRLOS mediated by RNA m6A methylase ZCCHC4 promotes colorectal cancer tumorigenesis.
    2. ZCCHC4 Promotes Osteosarcoma Progression by Upregulating ITGB1.
      Title: ZCCHC4 Promotes Osteosarcoma Progression by Upregulating ITGB1.
    3. RNA-binding protein ZCCHC4 promotes human cancer chemoresistance by disrupting DNA-damage-induced apoptosis.
      Title: RNA-binding protein ZCCHC4 promotes human cancer chemoresistance by disrupting DNA-damage-induced apoptosis.
    4. In summary, we establish ZCCHC4 as the enzyme responsible for m6A modification of human 28S rRNA, and demonstrate its functional significance in mRNA translation.
      Title: The human methyltransferase ZCCHC4 catalyses N6-methyladenosine modification of 28S ribosomal RNA.
    5. 3.1 A-resolution crystal structure of human CCHC zinc finger-containing protein ZCCHC4, a 28S rRNA-specific m(6)A methyltransferase, bound to S-adenosyl-L-homocysteine. Mutational and enzymatic analyses further substantiate the molecular basis for ZCCHC4-RNA recognition and a role of the stem-loop structure within substrate in governing the substrate specificity.
      Title: Structure and regulation of ZCCHC4 in m(6)A-methylation of 28S rRNA.
    6. ZCCHC4 protein is overexpressed in hepatocellular carcinoma tumors.ZCCHC4 is an m6A RNA methyltransferase.
      Title: N(6-)Methyladenosine methyltransferase ZCCHC4 mediates ribosomal RNA methylation.
    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

    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

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC21108

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables S-adenosyl-L-methionine binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables nucleic acid binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables rRNA (adenine-N6-)-methyltransferase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables rRNA (adenine-N6-)-methyltransferase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables zinc ion binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in positive regulation of translation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in rRNA methylation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in rRNA methylation 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 cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in nucleolus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nucleolus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    rRNA N6-adenosine-methyltransferase ZCCHC4
    Names
    DHHC domain-containing zinc finger protein
    zinc finger CCHC domain-containing protein 4
    zinc finger, CCHC domain containing 4
    zinc finger, GRF-type containing 4

    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_001318148.2 → NP_001305077.1  rRNA N6-adenosine-methyltransferase ZCCHC4 isoform 2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) lacks several exons and includes an alternate 3' terminal exon, compared to variant 1. It encodes isoform 2 which is shorter and has a distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AC108218, AK309675, BG719159, CA952098
      Conserved Domains (2) summary
      pfam06839
      Location:38 → 82
      zf-GRF; GRF zinc finger
      pfam10237
      Location:172 → 329
      N6-adenineMlase; Probable N6-adenine methyltransferase

    2. NM_024936.3 → NP_079212.2  rRNA N6-adenosine-methyltransferase ZCCHC4 isoform 1

      See identical proteins and their annotated locations for NP_079212.2

      Status: VALIDATED

      Description
      Transcript Variant: Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AK026677, AY629351, BG719159
      Consensus CDS
      CCDS43218.1
      UniProtKB/Swiss-Prot
      B2RXF6, B4DRD8, B7ZW20, Q5IW78, Q96AN7, Q9H5U6
      Related
      ENSP00000303468.4, ENST00000302874.9
      Conserved Domains (3) summary
      pfam06839
      Location:38 → 82
      zf-GRF; GRF zinc finger
      pfam10237
      Location:172 → 329
      N6-adenineMlase; Probable N6-adenine methyltransferase
      cl19890
      Location:409 → 438
      zf-DHHC; DHHC palmitoyltransferase

    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_000004.12 Reference GRCh38.p14 Primary Assembly

      Range
      25312774..25370383
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011513835.3 → XP_011512137.1  rRNA N6-adenosine-methyltransferase ZCCHC4 isoform X1

      Conserved Domains (3) summary
      pfam06839
      Location:38 → 82
      zf-GRF; GRF zinc finger
      pfam10237
      Location:166 → 294
      N6-adenineMlase; Probable N6-adenine methyltransferase
      cl19890
      Location:424 → 453
      DHHC; DHHC palmitoyltransferase

    2. XM_017008129.3 → XP_016863618.1  rRNA N6-adenosine-methyltransferase ZCCHC4 isoform X2

      Conserved Domains (3) summary
      pfam06839
      Location:38 → 82
      zf-GRF; GRF zinc finger
      pfam10237
      Location:166 → 256
      N6-adenineMlase; Probable N6-adenine methyltransferase
      cl19890
      Location:325 → 354
      DHHC; DHHC palmitoyltransferase

    RNA

    1. XR_925324.4 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060928.1 Alternate T2T-CHM13v2.0

      Range
      25294601..25352222
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054349836.1 → XP_054205811.1  rRNA N6-adenosine-methyltransferase ZCCHC4 isoform X1

    2. XM_054349837.1 → XP_054205812.1  rRNA N6-adenosine-methyltransferase ZCCHC4 isoform X2

    RNA

    1. XR_008486972.1 RNA Sequence

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_014150.1: Suppressed sequence

      Description
      NM_014150.1: This RefSeq record was removed by NCBI staff. Contact info@ncbi.nlm.nih.gov for further information.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9H5U6.3 GenPept UniProtKB/Swiss-Prot:Q9H5U6

    Gene LinkOut

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

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