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    ZRANB3 zinc finger RANBP2-type containing 3 [ Homo sapiens (human) ]

    Gene ID: 84083, updated on 10-Dec-2024

    Summary

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    Official Symbol
    ZRANB3provided by HGNC
    Official Full Name
    zinc finger RANBP2-type containing 3provided by HGNC
    Primary source
    HGNC:HGNC:25249
    See related
    Ensembl:ENSG00000121988 MIM:615655; AllianceGenome:HGNC:25249
    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
    AH2; 4933425L19Rik
    Summary
    Enables ATP-dependent DNA/DNA annealing activity; DNA endonuclease activity; and K63-linked polyubiquitin modification-dependent protein binding activity. Involved in several processes, including DNA metabolic process; DNA rewinding; and negative regulation of DNA recombination. Located in nuclear replication fork and nucleoplasm. [provided by Alliance of Genome Resources, Dec 2024]
    Expression
    Broad expression in testis (RPKM 1.8), thyroid (RPKM 0.8) and 24 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See ZRANB3 in Genome Data Viewer
    Location:
    2q21.3
    Exon count:
    23
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (135196969..135531218, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (135637447..135971741, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (135954539..136288788, complement)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene small nucleolar RNA U13 Neighboring gene RAB3 GTPase activating protein catalytic subunit 1 Neighboring gene HNF4 motif-containing MPRA enhancer 203 Neighboring gene small nucleolar RNA, H/ACA box 40B Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr2:135970274-135970798 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:135980911-135981075 Neighboring gene uncharacterized LOC124906077 Neighboring gene MPRA-validated peak3875 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16571 Neighboring gene Sharpr-MPRA regulatory region 5980 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16572 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11981 Neighboring gene G3BP1 pseudogene 1 Neighboring gene R3H domain containing 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16573 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16574 Neighboring gene uncharacterized LOC124907893 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16575 Neighboring gene RNA, U6 small nuclear 512, pseudogene Neighboring gene microRNA 128-1

    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. Identification of a Substrate Recognition Domain in the Replication Stress Response Protein Zinc Finger Ran-binding Domain-containing Protein 3 (ZRANB3). Badu-Nkansah A, et al. J Biol Chem, 2016 Apr 8. PMID 26884333, Free PMC Article
    2. Structural insights into the function of ZRANB3 in replication stress response. Sebesta M, et al. Nat Commun, 2017 Jun 16. PMID 28621305, Free PMC Article
    3. Annealing helicase 2 (AH2), a DNA-rewinding motor with an HNH motif. Yusufzai T, et al. Proc Natl Acad Sci U S A, 2010 Dec 7. PMID 21078962, Free PMC Article
    4. Nuclear RNR-α antagonizes cell proliferation by directly inhibiting ZRANB3. Fu Y, et al. Nat Chem Biol, 2018 Oct. PMID 30150681, Free PMC Article
    5. Replication Fork Slowing and Reversal upon DNA Damage Require PCNA Polyubiquitination and ZRANB3 DNA Translocase Activity. Vujanovic M, et al. Mol Cell, 2017 Sep 7. PMID 28886337, Free PMC Article

    See all (38) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. RFWD3 promotes ZRANB3 recruitment to regulate the remodeling of stalled replication forks.
      Title: RFWD3 promotes ZRANB3 recruitment to regulate the remodeling of stalled replication forks.
    2. Time for remodeling: SNF2-family DNA translocases in replication fork metabolism and human disease.
      Title: Time for remodeling: SNF2-family DNA translocases in replication fork metabolism and human disease.
    3. ZRANB3 is an African-specific type 2 diabetes locus associated with beta-cell mass and insulin response.
      Title: ZRANB3 is an African-specific type 2 diabetes locus associated with beta-cell mass and insulin response.
    4. Nuclear RNR-alpha antagonizes cell proliferation by directly inhibiting ZRANB3
      Title: Nuclear RNR-α antagonizes cell proliferation by directly inhibiting ZRANB3.
    5. PCNA and ATP-dependency serve as a multi-layered regulatory mechanism that modulates ZRANB3 activity at replication forks.
      Title: Structural insights into the function of ZRANB3 in replication stress response.
    6. A large number of SNF2 family, DNA and ATP-dependent motor proteins are needed during transcription, DNA replication, and DNA repair to manipulate protein-DNA interactions and change DNA structure. SMARCAL1, ZRANB3, and HLTF are three related members of this family with specialized functions that maintain genome stability during DNA replication. [review]
      Title: Functions of SMARCAL1, ZRANB3, and HLTF in maintaining genome stability.
    7. depletion of SMARCAL1, a SNF2-family DNA translocase that remodels stalled forks, restores replication fork stability and reduces the formation of replication stress-induced DNA breaks and chromosomal aberrations in BRCA1/2-deficient cells. In addition to SMARCAL1, other SNF2-family fork remodelers, including ZRANB3 and HLTF, cause nascent DNA degradation and genomic instability
      Title: Restoration of Replication Fork Stability in BRCA1- and BRCA2-Deficient Cells by Inactivation of SNF2-Family Fork Remodelers.
    8. Damage-induced fork reversal in mammalian cells requires PCNA ubiquitination, UBC13, and K63-linked polyubiquitin chains, previously involved in error-free damage tolerance. Fork reversal in vivo also requires ZRANB3 translocase activity and its interaction with polyubiquitinated PCNA, pinpointing ZRANB3 as a key effector of error-free DNA damage tolerance.
      Title: Replication Fork Slowing and Reversal upon DNA Damage Require PCNA Polyubiquitination and ZRANB3 DNA Translocase Activity.
    9. Here is described a substrate recognition domain within ZRANB3 that is needed for it to recognize forked DNA structures, hydrolyze ATP, catalyze fork remodeling, and act as a structure-specific endonuclease.
      Title: Identification of a Substrate Recognition Domain in the Replication Stress Response Protein Zinc Finger Ran-binding Domain-containing Protein 3 (ZRANB3).
    10. AH2 is recruited to stalled replication forks and that cells depleted of AH2 are hypersensitive to replication stresses.
      Title: The HARP-like domain-containing protein AH2/ZRANB3 binds to PCNA and participates in cellular response to replication stress.
    Submit: New GeneRIF Correction See all GeneRIFs (14)

    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)

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC75012, MGC105033

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables ATP-dependent DNA/DNA annealing activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables DNA endonuclease activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables DNA endonuclease activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    NOT enables DNA helicase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables K63-linked polyubiquitin modification-dependent protein binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables zinc ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in DNA damage response IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in DNA repair IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in DNA repair IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in DNA rewinding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of DNA recombination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in replication fork processing IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in replication fork processing IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in replication fork reversal IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in response to UV IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in nuclear replication fork IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nuclear replication fork IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  

    General protein information

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    Preferred Names
    DNA annealing helicase and endonuclease ZRANB3
    Names
    annealing helicase 2
    zinc finger Ran-binding domain-containing protein 3
    zinc finger, RAN-binding domain containing 3

    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_001286568.2 → NP_001273497.1  DNA annealing helicase and endonuclease ZRANB3 isoform 2

      See identical proteins and their annotated locations for NP_001273497.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR and uses an alternate splice site in the central coding region compared to variant 1. The encoded isoform (2) is shorter than isoform 1.
      Source sequence(s)
      AC017031, AI670931, BX647838
      Consensus CDS
      CCDS67963.1
      UniProtKB/Swiss-Prot
      Q5FWF4
      Related
      ENSP00000383979.1, ENST00000401392.5
      Conserved Domains (6) summary
      cd00046
      Location:55 → 190
      DEXDc; DEAD-like helicases superfamily. A diverse family of proteins involved in ATP-dependent RNA or DNA unwinding. This domain contains the ATP-binding region.
      cd00085
      Location:1009 → 1047
      HNHc; HNH nucleases; HNH endonuclease signature which is found in viral, prokaryotic, and eukaryotic proteins. The alignment includes members of the large group of homing endonucleases, yeast intron 1 protein, MutS, as well as bacterial colicins, pyocins, and ...
      sd00029
      Location:625 → 644
      zf-RanBP2; RanBP2-type Zn finger [structural motif]
      pfam00176
      Location:40 → 316
      SNF2_N; SNF2 family N-terminal domain
      pfam00271
      Location:330 → 435
      Helicase_C; Helicase conserved C-terminal domain
      pfam00641
      Location:625 → 647
      zf-RanBP; Zn-finger in Ran binding protein and others

    2. NM_001286569.1 → NP_001273498.1  DNA annealing helicase and endonuclease ZRANB3 isoform 3

      See identical proteins and their annotated locations for NP_001273498.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR which results in the use of a downstream start codon compared to variant 1. The encoded isoform (3) has a shorter N-terminus compared to isoform 1.
      Source sequence(s)
      AC016742, AC017031, AC064850, AI670931, AL833322
      Consensus CDS
      CCDS74580.1
      UniProtKB/TrEMBL
      F5GYN7
      Related
      ENSP00000441320.2, ENST00000536680.5
      Conserved Domains (3) summary
      cd00085
      Location:557 → 595
      HNHc; HNH nucleases; HNH endonuclease signature which is found in viral, prokaryotic, and eukaryotic proteins. The alignment includes members of the large group of homing endonucleases, yeast intron 1 protein, MutS, as well as bacterial colicins, pyocins, and ...
      sd00029
      Location:171 → 190
      zf-RanBP2; RanBP2-type Zn finger [structural motif]
      pfam00641
      Location:171 → 193
      zf-RanBP; Zn-finger in Ran binding protein and others

    3. NM_032143.4 → NP_115519.2  DNA annealing helicase and endonuclease ZRANB3 isoform 1

      See identical proteins and their annotated locations for NP_115519.2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform 1.
      Source sequence(s)
      AC017031, AI670931, BC089429
      Consensus CDS
      CCDS46419.1
      UniProtKB/Swiss-Prot
      B3KYA1, B4E375, B5MDI3, D3DP76, E9PBP0, Q53SM1, Q5FWF4, Q6P2C4, Q8N1P4, Q9H0E8
      Related
      ENSP00000264159.6, ENST00000264159.11
      Conserved Domains (6) summary
      cd00046
      Location:55 → 190
      DEXDc; DEAD-like helicases superfamily. A diverse family of proteins involved in ATP-dependent RNA or DNA unwinding. This domain contains the ATP-binding region.
      cd00085
      Location:1011 → 1049
      HNHc; HNH nucleases; HNH endonuclease signature which is found in viral, prokaryotic, and eukaryotic proteins. The alignment includes members of the large group of homing endonucleases, yeast intron 1 protein, MutS, as well as bacterial colicins, pyocins, and ...
      sd00029
      Location:625 → 644
      zf-RanBP2; RanBP2-type Zn finger [structural motif]
      pfam00176
      Location:40 → 316
      SNF2_N; SNF2 family N-terminal domain
      pfam00271
      Location:330 → 435
      Helicase_C; Helicase conserved C-terminal domain
      pfam00641
      Location:625 → 647
      zf-RanBP; Zn-finger in Ran binding protein and others

    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_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      135196969..135531218 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      135637447..135971741 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q5FWF4.2 GenPept UniProtKB/Swiss-Prot:Q5FWF4

    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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