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    NBN nibrin [ Homo sapiens (human) ]

    Gene ID: 4683, updated on 10-Dec-2024

    Summary

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    Official Symbol
    NBNprovided by HGNC
    Official Full Name
    nibrinprovided by HGNC
    Primary source
    HGNC:HGNC:7652
    See related
    Ensembl:ENSG00000104320 MIM:602667; AllianceGenome:HGNC:7652
    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
    ATV; NBS; P95; NBS1; AT-V1; AT-V2; hNbs1
    Summary
    Mutations in this gene are associated with Nijmegen breakage syndrome, an autosomal recessive chromosomal instability syndrome characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition. The encoded protein is a member of the MRE11/RAD50 double-strand break repair complex which consists of 5 proteins. This gene product is thought to be involved in DNA double-strand break repair and DNA damage-induced checkpoint activation. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in appendix (RPKM 14.8), thyroid (RPKM 14.2) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See NBN in Genome Data Viewer
    Location:
    8q21.3
    Exon count:
    20
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 8 NC_000008.11 (89933331..89984667, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 8 NC_060932.1 (91056512..91107848, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 8 NC_000008.10 (90945559..90996895, complement)

    Chromosome 8 - NC_000008.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124901974 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:90912677-90913442 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:90913443-90914208 Neighboring gene ReSE screen-validated silencer GRCh37_chr8:90914502-90914800 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19347 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19348 Neighboring gene RNA, U6 small nuclear 925, pseudogene Neighboring gene oxidative stress induced growth inhibitor family member 2 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr8:90959982-90961181 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27608 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:90996459-90997255 Neighboring gene Sharpr-MPRA regulatory region 13813 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19350 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27609 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27610 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27611 Neighboring gene 2,4-dienoyl-CoA reductase 1 Neighboring gene uncharacterized LOC124901976 Neighboring gene calbindin 1

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

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    Related articles in PubMed

    1. Functional variants in NBS1 and cancer risk: evidence from a meta-analysis of 60 publications with 111 individual studies. Gao P, et al. Mutagenesis, 2013 Nov. PMID 24113799
    2. NBN gain is predictive for adverse outcome following image-guided radiotherapy for localized prostate cancer. Berlin A, et al. Oncotarget, 2014 Nov 30. PMID 25415046, Free PMC Article
    3. Nijmegen breakage syndrome fibroblasts expressing the C-terminal truncated NBN(p70) protein undergo p38/MK2-dependent premature senescence. Davis T, et al. Biogerontology, 2015 Feb. PMID 25214013, Free PMC Article
    4. 657del5 mutation of the Nijmegen breakage syndrome gene (NBS1) in the Turkish population. Tekin M, et al. Hum Biol, 2005 Jun. PMID 16392640
    5. NBS1 Glu185Gln polymorphism and susceptibility to urinary system cancer: a meta-analysis. Zhang Y, et al. Tumour Biol, 2014 Nov. PMID 25073514

    See all (591) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. NBS1 lactylation is required for efficient DNA repair and chemotherapy resistance.
      Title: NBS1 lactylation is required for efficient DNA repair and chemotherapy resistance.
    2. Suppression of NBS1 Upregulates CyclinB to Induce Olaparib Sensitivity in Ovarian Cancer.
      Title: Suppression of NBS1 Upregulates CyclinB to Induce Olaparib Sensitivity in Ovarian Cancer.
    3. Simultaneous Nbs1 and p53 inactivation in neural progenitors triggers high-grade gliomas.
      Title: Simultaneous Nbs1 and p53 inactivation in neural progenitors triggers high-grade gliomas.
    4. XRCC3 and NBS1 gene polymorphisms modulate the risk of pre-oral cancer and oral cancer in the North Indian population.
      Title: XRCC3 and NBS1 gene polymorphisms modulate the risk of pre-oral cancer and oral cancer in the North Indian population.
    5. The NBN founder mutation-Evidence for a country specific difference in age at cancer manifestation.
      Title: The NBN founder mutation-Evidence for a country specific difference in age at cancer manifestation.
    6. NBN Pathogenic Germline Variants are Associated with Pan-Cancer Susceptibility and In Vitro DNA Damage Response Defects.
      Title: NBN Pathogenic Germline Variants are Associated with Pan-Cancer Susceptibility and In Vitro DNA Damage Response Defects.
    7. MRN Complex and Cancer Risk: Old Bottles, New Wine.
      Title: MRN Complex and Cancer Risk: Old Bottles, New Wine.
    8. Disruption of NBS1/MRN Complex Formation by E4orf3 Supports NF-kappaB That Licenses E1B55K-Deleted Adenovirus-Infected Cells to Accumulate DNA>4n.
      Title: Disruption of NBS1/MRN Complex Formation by E4orf3 Supports NF-κB That Licenses E1B55K-Deleted Adenovirus-Infected Cells to Accumulate DNA>4n.
    9. Structure of the human ATM kinase and mechanism of Nbs1 binding.
      Title: Structure of the human ATM kinase and mechanism of Nbs1 binding.
    10. Association of germline rare pathogenic mutations in guideline-recommended genes with prostate cancer progression: A meta-analysis.
      Title: Association of germline rare pathogenic mutations in guideline-recommended genes with prostate cancer progression: A meta-analysis.
    Submit: New GeneRIF Correction See all GeneRIFs (312)

    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
    Acute lymphoid leukemia
    MedGen: C0023449 OMIM: 613065 GeneReviews: Not available
    		Compare labs
    Aplastic anemia
    MedGen: C0002874 OMIM: 609135 GeneReviews: Not available
    		Compare labs
    Microcephaly, normal intelligence and immunodeficiency
    MedGen: C0398791 OMIM: 251260 GeneReviews: Nijmegen Breakage Syndrome
    		Compare labs

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp160, precursor env PML, TopBP1, NBS1 or ATM-induced activation of phosphorylation of Chk2 participates in the DNA damage-elicited pro-apoptotic cascade that leads to the demise of Env-elicited syncytia 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

    Clone Names

    • FLJ10155, MGC87362

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables DNA-binding transcription factor binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables chromatin-protein adaptor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables damaged DNA binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    contributes_to damaged DNA binding IC
    Inferred by Curator
    more info
    		 PubMed 
    enables histone binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables phosphorylation-dependent protein binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein serine/threonine kinase activator activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    acts_upstream_of_or_within DNA damage checkpoint signaling IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in DNA damage response, signal transduction by p53 class mediator TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in DNA double-strand break processing IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in DNA double-strand break processing NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in DNA duplex unwinding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in DNA duplex unwinding IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in DNA strand resection involved in replication fork processing IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in DNA strand resection involved in replication fork processing NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in R-loop processing IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in blastocyst growth IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in double-strand break repair IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in double-strand break repair via alternative nonhomologous end joining IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in double-strand break repair via homologous recombination IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in double-strand break repair via homologous recombination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in homologous recombination NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in intrinsic apoptotic signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in isotype switching IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in meiotic cell cycle IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in mitotic G2 DNA damage checkpoint signaling IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in mitotic G2 DNA damage checkpoint signaling IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in mitotic G2/M transition checkpoint NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in negative regulation of telomere capping IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in neuroblast proliferation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in neuromuscular process controlling balance IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of double-strand break repair via homologous recombination ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of protein autophosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of telomere maintenance IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in protection from non-homologous end joining at telomere IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein K63-linked ubiquitination ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in protein localization to site of double-strand break IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of DNA-templated DNA replication initiation TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in regulation of cell cycle TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in t-circle formation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in telomere maintenance IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in telomere maintenance in response to DNA damage IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in telomere maintenance via telomere trimming IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    involved_in telomeric 3' overhang formation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    part_of BRCA1-C complex IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    located_in Golgi apparatus IDA
    Inferred from Direct Assay
    more info
    		  
    part_of Mre11 complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of Mre11 complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of Mre11 complex IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    part_of Mre11 complex TAS
    Traceable Author Statement
    more info
    		 PubMed 
    located_in PML body IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in chromosomal region NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    located_in chromosome, telomeric region HDA PubMed 
    is_active_in chromosome, telomeric region IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in chromosome, telomeric region IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    colocalizes_with chromosome, telomeric region ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in nuclear inclusion body IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleolus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleus NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    located_in replication fork IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in site of double-strand break IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in site of double-strand break IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    nibrin
    Names
    Nijmegen breakage syndrome 1 (nibrin)
    cell cycle regulatory protein p95
    p95 protein of the MRE11/RAD50 complex

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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_008860.1 RefSeqGene

      Range
      4948..56336
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_158

    mRNA and Protein(s)

    1. NM_001024688.3 → NP_001019859.1  nibrin isoform 2

      See identical proteins and their annotated locations for NP_001019859.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) has an additional exon in the 5' region, as compared to variant 1. This results in translation initiation from a downstream AUG codon and an isoform (2) with a shorter N-terminus compared to isoform 1.
      Source sequence(s)
      AF069291, BC040519, BC136802, BX640816
      Consensus CDS
      CCDS43753.1
      UniProtKB/TrEMBL
      A0A0C4DG07, A6H8Y5, A8K1D3, E5RGN7
      Related
      ENSP00000428252.2, ENST00000523444.2
      Conserved Domains (4) summary
      cd00027
      Location:32 → 100
      BRCT; Breast Cancer Suppressor Protein (BRCA1), carboxy-terminal domain. The BRCT domain is found within many DNA damage repair and cell cycle checkpoint proteins. The unique diversity of this domain superfamily allows BRCT modules to interact forming homo ...
      pfam08599
      Location:601 → 663
      Nbs1_C; DNA damage repair protein Nbs1
      pfam16508
      Location:135 → 243
      NIBRIN_BRCT_II; Second BRCT domain on Nijmegen syndrome breakage protein
      cl26761
      Location:420 → 564
      MDN1; Midasin, AAA ATPase with vWA domain, involved in ribosome maturation [Translation, ribosomal structure and biogenesis]

    2. NM_002485.5 → NP_002476.2  nibrin isoform 1

      See identical proteins and their annotated locations for NP_002476.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longer isoform (1).
      Source sequence(s)
      AF069291, BC040519, BC071590, BX640816
      Consensus CDS
      CCDS6249.1
      UniProtKB/Swiss-Prot
      B2R626, B2RNC5, O60672, O60934, Q32NF7, Q53FM6, Q63HR6, Q7LDM2
      UniProtKB/TrEMBL
      A6H8Y5, A8K1D3
      Related
      ENSP00000265433.4, ENST00000265433.8
      Conserved Domains (4) summary
      cd00027
      Location:114 → 182
      BRCT; Breast Cancer Suppressor Protein (BRCA1), carboxy-terminal domain. The BRCT domain is found within many DNA damage repair and cell cycle checkpoint proteins. The unique diversity of this domain superfamily allows BRCT modules to interact forming homo ...
      cd00060
      Location:1 → 109
      FHA; Forkhead associated domain (FHA); found in eukaryotic and prokaryotic proteins. Putative nuclear signalling domain. FHA domains may bind phosphothreonine, phosphoserine and sometimes phosphotyrosine. In eukaryotes, many FHA domain-containing proteins ...
      pfam08599
      Location:683 → 745
      Nbs1_C; DNA damage repair protein Nbs1
      pfam16508
      Location:216 → 325
      NIBRIN_BRCT_II; Second BRCT domain on Nijmegen syndrome breakage protein

    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_000008.11 Reference GRCh38.p14 Primary Assembly

      Range
      89933331..89984667 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_024447163.2 → XP_024302931.1  nibrin isoform X1

      UniProtKB/TrEMBL
      A0A0C4DG07, A6H8Y5, A8K1D3, E5RGN7
      Related
      ENSP00000386924.1, ENST00000409330.5
      Conserved Domains (4) summary
      cd00027
      Location:32 → 100
      BRCT; Breast Cancer Suppressor Protein (BRCA1), carboxy-terminal domain. The BRCT domain is found within many DNA damage repair and cell cycle checkpoint proteins. The unique diversity of this domain superfamily allows BRCT modules to interact forming homo ...
      pfam08599
      Location:601 → 663
      Nbs1_C; DNA damage repair protein Nbs1
      pfam16508
      Location:135 → 243
      NIBRIN_BRCT_II; Second BRCT domain on Nijmegen syndrome breakage protein
      cl26761
      Location:420 → 564
      MDN1; Midasin, AAA ATPase with vWA domain, involved in ribosome maturation [Translation, ribosomal structure and biogenesis]

    2. XM_011517045.2 → XP_011515347.1  nibrin isoform X1

      See identical proteins and their annotated locations for XP_011515347.1

      UniProtKB/TrEMBL
      A0A0C4DG07, A6H8Y5, A8K1D3, E5RGN7
      Related
      ENSP00000429971.2, ENST00000517337.2
      Conserved Domains (4) summary
      cd00027
      Location:32 → 100
      BRCT; Breast Cancer Suppressor Protein (BRCA1), carboxy-terminal domain. The BRCT domain is found within many DNA damage repair and cell cycle checkpoint proteins. The unique diversity of this domain superfamily allows BRCT modules to interact forming homo ...
      pfam08599
      Location:601 → 663
      Nbs1_C; DNA damage repair protein Nbs1
      pfam16508
      Location:135 → 243
      NIBRIN_BRCT_II; Second BRCT domain on Nijmegen syndrome breakage protein
      cl26761
      Location:420 → 564
      MDN1; Midasin, AAA ATPase with vWA domain, involved in ribosome maturation [Translation, ribosomal structure and biogenesis]

    3. XM_047421795.1 → XP_047277751.1  nibrin isoform X3

    4. XM_011517046.2 → XP_011515348.1  nibrin isoform X2

      UniProtKB/TrEMBL
      A0PJ71
      Conserved Domains (3) summary
      cd00027
      Location:114 → 182
      BRCT; Breast Cancer Suppressor Protein (BRCA1), carboxy-terminal domain. The BRCT domain is found within many DNA damage repair and cell cycle checkpoint proteins. The unique diversity of this domain superfamily allows BRCT modules to interact forming homo ...
      cd00060
      Location:1 → 109
      FHA; Forkhead associated domain (FHA); found in eukaryotic and prokaryotic proteins. Putative nuclear signalling domain. FHA domains may bind phosphothreonine, phosphoserine and sometimes phosphotyrosine. In eukaryotes, many FHA domain-containing proteins ...
      pfam16508
      Location:216 → 325
      NIBRIN_BRCT_II; Second BRCT domain on Nijmegen syndrome breakage protein

    5. XM_047421796.1 → XP_047277752.1  nibrin isoform X4

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060932.1 Alternate T2T-CHM13v2.0

      Range
      91056512..91107848 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054360508.1 → XP_054216483.1  nibrin isoform X1

      UniProtKB/TrEMBL
      A0A0C4DG07, A6H8Y5, A8K1D3, E5RGN7

    2. XM_054360510.1 → XP_054216485.1  nibrin isoform X3

    3. XM_054360509.1 → XP_054216484.1  nibrin isoform X2

      UniProtKB/TrEMBL
      A0PJ71

    4. XM_054360511.1 → XP_054216486.1  nibrin isoform X4

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O60934.1 GenPept UniProtKB/Swiss-Prot:O60934

    Gene LinkOut

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

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    Chemical Information
    Medical
    Molecular Biology Databases
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    Miscellaneous