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    WRNIP1 WRN helicase interacting protein 1 [ Homo sapiens (human) ]

    Gene ID: 56897, updated on 5-May-2024

    Summary

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    Official Symbol
    WRNIP1provided by HGNC
    Official Full Name
    WRN helicase interacting protein 1provided by HGNC
    Primary source
    HGNC:HGNC:20876
    See related
    Ensembl:ENSG00000124535 MIM:608196; AllianceGenome:HGNC:20876
    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
    WHIP; FAP93; CFAP93; bA420G6.2
    Summary
    Werner's syndrome is a rare autosomal recessive disorder characterized by accelerated aging that is caused by defects in the Werner syndrome ATP-dependent helicase gene (WRN). The protein encoded by this gene interacts with the exonuclease-containing N-terminal portion of the Werner protein. This protein has a ubiquitin-binding zinc-finger domain in the N-terminus, an ATPase domain, and two leucine zipper motifs in the C-terminus. It has sequence similarity to replication factor C family proteins and is conserved from E. coli to human. This protein likely accumulates at sites of DNA damage by interacting with polyubiquinated proteins and also binds to DNA polymerase delta and increases the initiation frequency of DNA polymerase delta-mediated DNA synthesis. This protein also interacts with nucleoporins at nuclear pore complexes. Two transcript variants encoding different isoforms have been isolated for this gene. [provided by RefSeq, Jul 2012]
    Expression
    Ubiquitous expression in thyroid (RPKM 15.6), placenta (RPKM 14.5) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    6p25.2
    Exon count:
    8
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (2765393..2786952)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (2631255..2653114)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (2765627..2787186)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene long intergenic non-protein coding RNA 1600 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr6:2639651-2640166 Neighboring gene long intergenic non-protein coding RNA 2521 Neighboring gene NANOG hESC enhancer GRCh37_chr6:2665381-2665947 Neighboring gene myosin light chain kinase family member 4 Neighboring gene uncharacterized LOC124901240 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23872 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:2734004-2734694 Neighboring gene Sharpr-MPRA regulatory region 12436 Neighboring gene Sharpr-MPRA regulatory region 3200 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:2764192-2765071 Neighboring gene Sharpr-MPRA regulatory region 3960 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16830 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16831 Neighboring gene uncharacterized LOC124901241 Neighboring gene Sharpr-MPRA regulatory region 6984 Neighboring gene ReSE screen-validated silencer GRCh37_chr6:2798034-2798138 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:2802330-2802830 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr6:2809907-2811106 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16832 Neighboring gene serpin family B member 1

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Bibliography

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    Related articles in PubMed

    1. WRNIP1 Is Recruited to DNA Interstrand Crosslinks and Promotes Repair. Socha A, et al. Cell Rep, 2020 Jul 7. PMID 32640220, Free PMC Article
    2. WRNIP1 protects stalled forks from degradation and promotes fork restart after replication stress. Leuzzi G, et al. EMBO J, 2016 Jul 1. PMID 27242363, Free PMC Article
    3. WRNIP1 accumulates at laser light irradiated sites rapidly via its ubiquitin-binding zinc finger domain and independently from its ATPase domain. Nomura H, et al. Biochem Biophys Res Commun, 2012 Jan 27. PMID 22209848
    4. R-Loop-Associated Genomic Instability and Implication of WRN and WRNIP1. Marabitti V, et al. Int J Mol Sci, 2022 Jan 28. PMID 35163467, Free PMC Article
    5. miR-22 enhances the radiosensitivity of small-cell lung cancer by targeting the WRNIP1. Jiang W, et al. J Cell Biochem, 2019 Oct. PMID 31190355, Free PMC Article

    See all (108) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. WRNIP1 prevents transcription-associated genomic instability.
      Title: WRNIP1 prevents transcription-associated genomic instability.
    2. AXL/WRNIP1 Mediates Replication Stress Response and Promotes Therapy Resistance and Metachronous Metastasis in HER2+ Breast Cancer.
      Title: AXL/WRNIP1 Mediates Replication Stress Response and Promotes Therapy Resistance and Metachronous Metastasis in HER2+ Breast Cancer.
    3. Discovering the nuclear localization signal of Werner Helicase Interacting Protein 1.
      Title: Discovering the nuclear localization signal of Werner Helicase Interacting Protein 1.
    4. Functional Domain Mapping of Werner Interacting Protein 1 (WRNIP1).
      Title: Functional Domain Mapping of Werner Interacting Protein 1 (WRNIP1).
    5. R-Loop-Associated Genomic Instability and Implication of WRN and WRNIP1.
      Title: R-Loop-Associated Genomic Instability and Implication of WRN and WRNIP1.
    6. WRNIP1 Is Recruited to DNA Interstrand Crosslinks and Promotes Repair.
      Title: WRNIP1 Is Recruited to DNA Interstrand Crosslinks and Promotes Repair.
    7. miR-22 enhances the radiosensitivity of small-cell lung cancer by targeting the WRNIP1.
      Title: miR-22 enhances the radiosensitivity of small-cell lung cancer by targeting the WRNIP1.
    8. The WRNIP1-mediated reduction in the amount of PrimPol was suppressed by treatment of the cells with proteasome inhibitors, suggesting that WRNIP1 is involved in the degradation of PrimPol via the proteasome.
      Title: WRNIP1 Controls the Amount of PrimPol.
    9. findings define the WHIP-TRIM14-PPP6C mitochondrial signalosome required for RIG-I-mediated innate antiviral immunity.
      Title: Assembly of the WHIP-TRIM14-PPP6C Mitochondrial Complex Promotes RIG-I-Mediated Antiviral Signaling.
    10. WRNIP1 connects PCNA monoubiquitination with ATMIN/ATM to activate ATM signalling in response to replication stress and contribute to the maintenance of genomic stability.
      Title: RAD18, WRNIP1 and ATMIN promote ATM signalling in response to replication stress.
    Submit: New GeneRIF Correction See all GeneRIFs (19)

    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

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Tat tat Depletion of Werner helicase interacting protein 1 (WRNIP1) by siRNA enhances HIV-1 Tat activation of HIV-1 LTR, which is not the results of increased Tat expression and release of CDK9/CCNT1 from 7SK snRNP, and activation of NF-kappaB PubMed

    Go to the HIV-1, Human Interaction Database

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ22526

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables ATP hydrolysis activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables DNA binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables enzyme activator activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables single-stranded DNA helicase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in DNA duplex unwinding IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in DNA synthesis involved in DNA repair IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in DNA synthesis involved in DNA repair IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in DNA-templated DNA replication IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in innate immune response IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of DNA-templated DNA replication initiation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    colocalizes_with chromosome, telomeric region IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in membrane HDA PubMed 
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    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
    		  
    located_in perinuclear region of cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    ATPase WRNIP1
    Names
    Werner helicase interacting protein 1
    putative helicase RUVBL
    NP_064520.2
    NP_569079.1
    XP_005249289.1
    XP_016866549.1
    XP_047275034.1
    XP_054211912.1
    XP_054211913.1
    XP_054211914.1

    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_020135.3 → NP_064520.2  ATPase WRNIP1 isoform 1

      See identical proteins and their annotated locations for NP_064520.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longer isoform (1).
      Source sequence(s)
      AL139092
      Consensus CDS
      CCDS4475.1
      UniProtKB/Swiss-Prot
      B2RDB0, Q53EP6, Q59ET8, Q5W0E2, Q5W0E4, Q8WV26, Q96S55, Q9H681, Q9NRJ6
      UniProtKB/TrEMBL
      B3KT25
      Related
      ENSP00000370150.4, ENST00000380773.9
      Conserved Domains (3) summary
      smart00734
      Location:17 → 40
      ZnF_Rad18; Rad18-like CCHC zinc finger
      COG5432
      Location:18 → 83
      RAD18; RING-finger-containing E3 ubiquitin ligase [Signal transduction mechanisms]
      PRK13342
      Location:226 → 661
      PRK13342; recombination factor protein RarA; Reviewed

    2. NM_130395.3 → NP_569079.1  ATPase WRNIP1 isoform 2

      See identical proteins and their annotated locations for NP_569079.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) utilizes a different acceptor splice site for an internal coding exon, compared to transcript variant 1. This variant maintains the same reading frame but encodes an isoform (2) which is 25 aa shorter than isoform 1.
      Source sequence(s)
      AK315047, AL139092, BC018923
      Consensus CDS
      CCDS4476.1
      UniProtKB/TrEMBL
      B3KT25
      Related
      ENSP00000370148.4, ENST00000380771.8
      Conserved Domains (3) summary
      smart00734
      Location:17 → 40
      ZnF_Rad18; Rad18-like CCHC zinc finger
      PRK13342
      Location:226 → 636
      PRK13342; recombination factor protein RarA; Reviewed
      cl28410
      Location:18 → 83
      RAD18; RING-finger-containing E3 ubiquitin ligase [Signal transduction mechanisms]

    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_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      2765393..2786952
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047419078.1 → XP_047275034.1  ATPase WRNIP1 isoform X3

    2. XM_005249232.4 → XP_005249289.1  ATPase WRNIP1 isoform X2

      Conserved Domains (3) summary
      cd00009
      Location:246 → 376
      AAA; The AAA+ (ATPases Associated with a wide variety of cellular Activities) superfamily represents an ancient group of ATPases belonging to the ASCE (for additional strand, catalytic E) division of the P-loop NTPase fold. The ASCE division also includes ABC, ...
      smart00734
      Location:17 → 40
      ZnF_Rad18; Rad18-like CCHC zinc finger
      smart00382
      Location:263 → 380
      AAA; ATPases associated with a variety of cellular activities

    3. XM_017011060.2 → XP_016866549.1  ATPase WRNIP1 isoform X1

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      2631255..2653114
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054355939.1 → XP_054211914.1  ATPase WRNIP1 isoform X3

    2. XM_054355938.1 → XP_054211913.1  ATPase WRNIP1 isoform X2

    3. XM_054355937.1 → XP_054211912.1  ATPase WRNIP1 isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q96S55.2 GenPept UniProtKB/Swiss-Prot:Q96S55

    Gene LinkOut

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

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