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    XIAP X-linked inhibitor of apoptosis [ Homo sapiens (human) ]

    Gene ID: 331, updated on 14-Nov-2024

    Summary

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    Official Symbol
    XIAPprovided by HGNC
    Official Full Name
    X-linked inhibitor of apoptosisprovided by HGNC
    Primary source
    HGNC:HGNC:592
    See related
    Ensembl:ENSG00000101966 MIM:300079; AllianceGenome:HGNC:592
    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
    API3; ILP1; MIHA; XLP2; BIRC4; IAP-3; hIAP3; hIAP-3
    Summary
    This gene encodes a protein that belongs to a family of apoptotic suppressor proteins. Members of this family share a conserved motif termed, baculovirus IAP repeat, which is necessary for their anti-apoptotic function. This protein functions through binding to tumor necrosis factor receptor-associated factors TRAF1 and TRAF2 and inhibits apoptosis induced by menadione, a potent inducer of free radicals, and interleukin 1-beta converting enzyme. This protein also inhibits at least two members of the caspase family of cell-death proteases, caspase-3 and caspase-7. Mutations in this gene are the cause of X-linked lymphoproliferative syndrome. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 2 and 11.[provided by RefSeq, Feb 2011]
    Expression
    Ubiquitous expression in thyroid (RPKM 10.5), colon (RPKM 8.6) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See XIAP in Genome Data Viewer
    Location:
    Xq25
    Exon count:
    10
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (123859708..123913972)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (122170108..122224373)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (122993558..123047822)

    Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene coiled-coil-helix-coiled-coil-helix domain containing 2 pseudogene 1 Neighboring gene RNA, 7SL, cytoplasmic 190, pseudogene Neighboring gene H3K27ac hESC enhancers GRCh37_chrX:122992768-122993708 and GRCh37_chrX:122993709-122994650 Neighboring gene RNA, U6 small nuclear 122, pseudogene Neighboring gene PARD6B pseudogene 1 Neighboring gene NANOG hESC enhancer GRCh37_chrX:123057919-123058420 Neighboring gene H3K27ac hESC enhancer GRCh37_chrX:123093522-123094437 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29912 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20972 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29913 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29914 Neighboring gene STAG2 antisense RNA 1 Neighboring gene ReSE screen-validated silencer GRCh37_chrX:123120781-123120983 Neighboring gene STAG2 cohesin complex component Neighboring gene MPRA-validated peak7422 silencer Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chrX:123261133-123261790 Neighboring gene small nucleolar RNA U13

    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. XIAP and P-glycoprotein co-expression is related to imatinib resistance in chronic myeloid leukemia cells. Silva KL, et al. Leuk Res, 2013 Oct. PMID 23891189
    2. Analysis of Genes Associated With Monogenic Primary Immunodeficiency Identifies Rare Variants in XIAP in Patients With Crohn's Disease. Amininejad L, et al. Gastroenterology, 2018 Jun. PMID 29501442
    3. XIAP Regulation by MNK Links MAPK and NFÎşB Signaling to Determine an Aggressive Breast Cancer Phenotype. Evans MK, et al. Cancer Res, 2018 Apr 1. PMID 29351901, Free PMC Article
    4. Over-expression of X-linked inhibitor of apoptosis protein modulates multiple aspects of neuronal Ca2+ signaling. Grant J, et al. Neurochem Res, 2013 Apr. PMID 23397285
    5. X-linked inhibitor of apoptosis single nucleotide polymorphisms and copy number variation are not risk factors for asthma. Roscioli E, et al. Respirology, 2013 May. PMID 23418891

    See all (660) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Interleukin-1-mediated hyperinflammation in XIAP deficiency is associated with defective autophagy.
      Title: Interleukin-1-mediated hyperinflammation in XIAP deficiency is associated with defective autophagy.
    2. Systematic analysis of PANoptosis-related genes identifies XIAP as a functional oncogene in breast cancer.
      Title: Systematic analysis of PANoptosis-related genes identifies XIAP as a functional oncogene in breast cancer.
    3. Understanding the molecular mechanism of pathogenic variants of BIR2 domain in XIAP-deficient inflammatory bowel disease.
      Title: Understanding the molecular mechanism of pathogenic variants of BIR2 domain in XIAP-deficient inflammatory bowel disease.
    4. Ehrlichia Notch signaling induction promotes XIAP stability and inhibits apoptosis.
      Title: Ehrlichia Notch signaling induction promotes XIAP stability and inhibits apoptosis.
    5. Nicotine promotes renal interstitial fibrosis via upregulation of XIAP in an alpha7-nAChR-dependent manner.
      Title: Nicotine promotes renal interstitial fibrosis via upregulation of XIAP in an alpha7-nAChR-dependent manner.
    6. Caspase-8-driven apoptotic and pyroptotic crosstalk causes cell death and IL-1beta release in X-linked inhibitor of apoptosis (XIAP) deficiency.
      Title: Caspase-8-driven apoptotic and pyroptotic crosstalk causes cell death and IL-1β release in X-linked inhibitor of apoptosis (XIAP) deficiency.
    7. XIAP and PHB1 Regulate Anoikis through Competitive Binding to TRAF6.
      Title: XIAP and PHB1 Regulate Anoikis through Competitive Binding to TRAF6.
    8. Caspase-3, Caspase-8 and XIAP Gene Expression in the Placenta: Exploring the Causes of Spontaneous Preterm Labour.
      Title: Caspase-3, Caspase-8 and XIAP Gene Expression in the Placenta: Exploring the Causes of Spontaneous Preterm Labour.
    9. X-linked inhibitor of apoptosis protein (XIAP) predicts disease-free survival in BRAFV600E mutant papillary thyroid carcinoma in middle eastern patients.
      Title: X-linked inhibitor of apoptosis protein (XIAP) predicts disease-free survival in BRAFV600E mutant papillary thyroid carcinoma in middle eastern patients.
    10. miR-515-5p suppresses trophoblast cell invasion and proliferation through XIAP regulation in preeclampsia.
      Title: miR-515-5p suppresses trophoblast cell invasion and proliferation through XIAP regulation in preeclampsia.
    Submit: New GeneRIF Correction See all GeneRIFs (447)

    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

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    No evidence available (Last evaluated 2022-07-27)

    ClinGen Genome Curation Page
    Haploinsufficency

    Sufficient evidence for dosage pathogenicity (Last evaluated 2022-07-27)

    ClinGen Genome Curation PagePubMed

    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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    Replication interactions

    Interaction Pubs
    Knockdown of X-linked inhibitor of apoptosis (XIAP; BIRC4) by siRNA inhibits the early stages of HIV-1 replication in 293T cells infected with VSV-G pseudotyped HIV-1 PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Nef nef Recombinant HIV-1 Nef increases expression of antiapoptotic proteins BCL2, AKT1, and XIAP in THP-1 cells and primary blood macrophages 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

    • FLJ26913

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables cysteine-type endopeptidase inhibitor activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables cysteine-type endopeptidase inhibitor activity involved in apoptotic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables cysteine-type endopeptidase inhibitor activity involved in apoptotic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables endopeptidase regulator activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    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 protein serine/threonine kinase binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables ubiquitin protein ligase activity EXP
    Inferred from Experiment
    more info
    		 PubMed 
    enables ubiquitin protein ligase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables ubiquitin protein ligase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables ubiquitin protein ligase activity TAS
    Traceable Author Statement
    more info
    		  
    enables ubiquitin-protein transferase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables ubiquitin-protein transferase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in DNA damage response IEP
    Inferred from Expression Pattern
    more info
    		 PubMed 
    involved_in Wnt signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in copper ion homeostasis TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in defense response to bacterium IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in inhibition of cysteine-type endopeptidase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of apoptotic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of apoptotic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of apoptotic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of cysteine-type endopeptidase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of tumor necrosis factor-mediated signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in neuron apoptotic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in nucleotide-binding oligomerization domain containing 1 signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in nucleotide-binding oligomerization domain containing 2 signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of JNK cascade IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of canonical NF-kappaB signal transduction IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of canonical Wnt signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of canonical Wnt signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of protein linear polyubiquitination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of protein ubiquitination IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of protein ubiquitination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of type I interferon production IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein K63-linked ubiquitination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of BMP signaling pathway TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in regulation of apoptosis involved in tissue homeostasis IEA
    Inferred from Electronic Annotation
    more info
    		  
    acts_upstream_of_negative_effect regulation of apoptotic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of cell cycle IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of cell population proliferation TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in regulation of inflammatory response TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in regulation of innate immune response TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in regulation of nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in response to lipopolysaccharide IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in cytoplasm IC
    Inferred by Curator
    more info
    		 PubMed 
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    E3 ubiquitin-protein ligase XIAP
    Names
    IAP-like protein 1
    RING-type E3 ubiquitin transferase XIAP
    X-linked IAP
    X-linked inhibitor of apoptosis, E3 ubiquitin protein ligase
    baculoviral IAP repeat-containing protein 4
    inhibitor of apoptosis protein 3
    NP_001158.2
    NP_001191330.1
    NP_001365519.1
    NP_001365520.1
    NP_001365521.1

    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_007264.1 RefSeqGene

      Range
      4615..58782
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_19

    mRNA and Protein(s)

    1. NM_001167.4 → NP_001158.2  E3 ubiquitin-protein ligase XIAP

      See identical proteins and their annotated locations for NP_001158.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript. Both variants 1 and 2 encode the same protein.
      Source sequence(s)
      AL121601, DA316362, DB113777, H09548, U32974
      Consensus CDS
      CCDS14606.1
      UniProtKB/Swiss-Prot
      D3DTF2, P98170, Q9NQ14
      UniProtKB/TrEMBL
      B2R9R2
      Related
      ENSP00000360242.3, ENST00000371199.8
      Conserved Domains (4) summary
      smart00238
      Location:162 → 232
      BIR; Baculoviral inhibition of apoptosis protein repeat
      cd00022
      Location:28 → 95
      BIR; Baculoviral inhibition of apoptosis protein repeat domain; Found in inhibitors of apoptosis proteins (IAPs) and other proteins. In higher eukaryotes, BIR domains inhibit apoptosis by acting as direct inhibitors of the caspase family of protease enzymes. ...
      cd14395
      Location:370 → 419
      UBA_BIRC4_8; UBA domain found in E3 ubiquitin-protein ligase XIAP, baculoviral IAP repeat-containing protein 8 (BIRC8) and similar proteins
      cd16714
      Location:436 → 497
      RING-HC_BIRC4_8; RING finger, HC subclass, found in E3 ubiquitin-protein ligase XIAP, baculoviral IAP repeat-containing protein 8 (BIRC8) and similar proteins

    2. NM_001204401.2 → NP_001191330.1  E3 ubiquitin-protein ligase XIAP

      See identical proteins and their annotated locations for NP_001191330.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Both variants 1 and 2 encode the same protein.
      Source sequence(s)
      AK313883, AL121601, H09548
      Consensus CDS
      CCDS14606.1
      UniProtKB/Swiss-Prot
      D3DTF2, P98170, Q9NQ14
      UniProtKB/TrEMBL
      B2R9R2
      Conserved Domains (4) summary
      smart00238
      Location:162 → 232
      BIR; Baculoviral inhibition of apoptosis protein repeat
      cd00022
      Location:28 → 95
      BIR; Baculoviral inhibition of apoptosis protein repeat domain; Found in inhibitors of apoptosis proteins (IAPs) and other proteins. In higher eukaryotes, BIR domains inhibit apoptosis by acting as direct inhibitors of the caspase family of protease enzymes. ...
      cd14395
      Location:370 → 419
      UBA_BIRC4_8; UBA domain found in E3 ubiquitin-protein ligase XIAP, baculoviral IAP repeat-containing protein 8 (BIRC8) and similar proteins
      cd16714
      Location:436 → 497
      RING-HC_BIRC4_8; RING finger, HC subclass, found in E3 ubiquitin-protein ligase XIAP, baculoviral IAP repeat-containing protein 8 (BIRC8) and similar proteins

    3. NM_001378590.1 → NP_001365519.1  E3 ubiquitin-protein ligase XIAP

      Status: REVIEWED

      Source sequence(s)
      AL121601, AL591583
      Consensus CDS
      CCDS14606.1
      UniProtKB/Swiss-Prot
      D3DTF2, P98170, Q9NQ14
      UniProtKB/TrEMBL
      B2R9R2
      Related
      ENSP00000347858.3, ENST00000355640.3
      Conserved Domains (4) summary
      smart00238
      Location:162 → 232
      BIR; Baculoviral inhibition of apoptosis protein repeat
      cd00022
      Location:28 → 95
      BIR; Baculoviral inhibition of apoptosis protein repeat domain; Found in inhibitors of apoptosis proteins (IAPs) and other proteins. In higher eukaryotes, BIR domains inhibit apoptosis by acting as direct inhibitors of the caspase family of protease enzymes. ...
      cd14395
      Location:370 → 419
      UBA_BIRC4_8; UBA domain found in E3 ubiquitin-protein ligase XIAP, baculoviral IAP repeat-containing protein 8 (BIRC8) and similar proteins
      cd16714
      Location:436 → 497
      RING-HC_BIRC4_8; RING finger, HC subclass, found in E3 ubiquitin-protein ligase XIAP, baculoviral IAP repeat-containing protein 8 (BIRC8) and similar proteins

    4. NM_001378591.1 → NP_001365520.1  E3 ubiquitin-protein ligase XIAP

      Status: REVIEWED

      Source sequence(s)
      AL121601, AL591583
      Consensus CDS
      CCDS14606.1
      UniProtKB/Swiss-Prot
      D3DTF2, P98170, Q9NQ14
      UniProtKB/TrEMBL
      B2R9R2
      Related
      ENSP00000405529.2, ENST00000422098.6
      Conserved Domains (4) summary
      smart00238
      Location:162 → 232
      BIR; Baculoviral inhibition of apoptosis protein repeat
      cd00022
      Location:28 → 95
      BIR; Baculoviral inhibition of apoptosis protein repeat domain; Found in inhibitors of apoptosis proteins (IAPs) and other proteins. In higher eukaryotes, BIR domains inhibit apoptosis by acting as direct inhibitors of the caspase family of protease enzymes. ...
      cd14395
      Location:370 → 419
      UBA_BIRC4_8; UBA domain found in E3 ubiquitin-protein ligase XIAP, baculoviral IAP repeat-containing protein 8 (BIRC8) and similar proteins
      cd16714
      Location:436 → 497
      RING-HC_BIRC4_8; RING finger, HC subclass, found in E3 ubiquitin-protein ligase XIAP, baculoviral IAP repeat-containing protein 8 (BIRC8) and similar proteins

    5. NM_001378592.1 → NP_001365521.1  E3 ubiquitin-protein ligase XIAP

      Status: REVIEWED

      Source sequence(s)
      AL121601, AL591583
      Consensus CDS
      CCDS14606.1
      UniProtKB/Swiss-Prot
      D3DTF2, P98170, Q9NQ14
      UniProtKB/TrEMBL
      B2R9R2
      Conserved Domains (4) summary
      smart00238
      Location:162 → 232
      BIR; Baculoviral inhibition of apoptosis protein repeat
      cd00022
      Location:28 → 95
      BIR; Baculoviral inhibition of apoptosis protein repeat domain; Found in inhibitors of apoptosis proteins (IAPs) and other proteins. In higher eukaryotes, BIR domains inhibit apoptosis by acting as direct inhibitors of the caspase family of protease enzymes. ...
      cd14395
      Location:370 → 419
      UBA_BIRC4_8; UBA domain found in E3 ubiquitin-protein ligase XIAP, baculoviral IAP repeat-containing protein 8 (BIRC8) and similar proteins
      cd16714
      Location:436 → 497
      RING-HC_BIRC4_8; RING finger, HC subclass, found in E3 ubiquitin-protein ligase XIAP, baculoviral IAP repeat-containing protein 8 (BIRC8) and similar proteins

    RNA

    1. NR_037916.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an exon compared to variant 1. This variant is represented as non-coding because it lacks a large portion of the coding region, including the translational start codon, found in variant 1.
      Source sequence(s)
      AK309704, AL121601, AL591583, DA316362, H09548

    2. NR_165803.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL121601, AL591583

    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_000023.11 Reference GRCh38.p14 Primary Assembly

      Range
      123859708..123913972
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060947.1 Alternate T2T-CHM13v2.0

      Range
      122170108..122224373
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P98170.2 GenPept UniProtKB/Swiss-Prot:P98170

    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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