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    SERPINE1 serpin family E member 1 [ Homo sapiens (human) ]

    Gene ID: 5054, updated on 27-Nov-2024

    Summary

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    Official Symbol
    SERPINE1provided by HGNC
    Official Full Name
    serpin family E member 1provided by HGNC
    Primary source
    HGNC:HGNC:8583
    See related
    Ensembl:ENSG00000106366 MIM:173360; AllianceGenome:HGNC:8583
    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
    PAI; PAI1; PAI-1; PLANH1
    Summary
    This gene encodes a member of the serine proteinase inhibitor (serpin) superfamily. This member is the principal inhibitor of tissue plasminogen activator (tPA) and urokinase (uPA), and hence is an inhibitor of fibrinolysis. The protein also functions as a component of innate antiviral immunity. Defects in this gene are the cause of plasminogen activator inhibitor-1 deficiency (PAI-1 deficiency), and high concentrations of the gene product are associated with thrombophilia. [provided by RefSeq, Aug 2020]
    Annotation information
    Note: This gene has been reviewed for its involvement in coronavirus biology, and is involved in immune response or antiviral activity.
    Expression
    Biased expression in gall bladder (RPKM 208.8), placenta (RPKM 164.7) and 7 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See SERPINE1 in Genome Data Viewer
    Location:
    7q22.1
    Exon count:
    9
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (101127104..101139247)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (102449908..102462056)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (100770385..100782528)

    Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene mucin 17, cell surface associated Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:100709117-100709986 Neighboring gene RN7SK pseudogene 54 Neighboring gene H3K27ac hESC enhancer GRCh37_chr7:100727119-100727619 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26398 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:100730454-100731094 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:100731095-100731734 Neighboring gene tripartite motif containing 56 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:100742673-100743380 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:100743381-100744088 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:100751090-100752040 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:100752041-100752991 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:100755193-100755694 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:100760705-100761406 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:100765023-100765642 Neighboring gene H3K27ac hESC enhancer GRCh37_chr7:100766263-100766880 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:100769261-100770040 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:100770821-100771600 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:100771601-100772380 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:100778603-100779104 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:100781393-100782168 Neighboring gene negCOR silencer S6 Neighboring gene Sharpr-MPRA regulatory region 5920 Neighboring gene H3K27ac hESC enhancer GRCh37_chr7:100798163-100798663 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr7:100799642-100800841 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18475 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18476 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18477 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18478 Neighboring gene ReSE screen-validated silencer GRCh37_chr7:100812095-100812265 Neighboring gene adaptor related protein complex 1 subunit sigma 1 Neighboring gene microRNA 4653 Neighboring gene VGF nerve growth factor inducible

    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. High serum level of plasminogen activator inhibitor-1 predicts histological grade of intracerebral gliomas. Iwadate Y, et al. Anticancer Res, 2008 Jan-Feb. PMID 18383878
    2. Type 2 diabetes significantly modulates the cardiovascular risk conferred by the PAI-1 -675 4G/5G polymorphism in angiographied coronary patients. Saely CH, et al. Clin Chim Acta, 2008 Oct. PMID 18619429
    3. Plasminogen activator inhibitor-1 4G/5G gene polymorphism and primary open-angle glaucoma. Mossböck G, et al. Mol Vis, 2008 Jul 4. PMID 18615155, Free PMC Article
    4. Plasminogen activator inhibitor-1 activity and 4G/5G polymorphism in hemodialysis. Trimarchi H, et al. J Vasc Access, 2008 Apr-Jun. PMID 18609532
    5. The relationship of plasminogen activator inhibitor-1 levels to the ST deviation pattern of acute myocardial infarction. Rott D, et al. Cardiology, 2009. PMID 18580060

    See all (1000) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Suppressing Expression of SERPINE1/PAI1 Through Activation of GPER1 Reduces Progression of Vulvar Carcinoma.
      Title: Suppressing Expression of SERPINE1/PAI1 Through Activation of GPER1 Reduces Progression of Vulvar Carcinoma.
    2. Glial-Cell-Line-Derived Neurotrophic Factor Promotes Glioblastoma Cell Migration and Invasion via the SMAD2/3-SERPINE1-Signaling Axis.
      Title: Glial-Cell-Line-Derived Neurotrophic Factor Promotes Glioblastoma Cell Migration and Invasion via the SMAD2/3-SERPINE1-Signaling Axis.
    3. PAI-1 Regulates the Cytoskeleton and Intrinsic Stiffness of Vascular Smooth Muscle Cells.
      Title: PAI-1 Regulates the Cytoskeleton and Intrinsic Stiffness of Vascular Smooth Muscle Cells.
    4. The influence of 4G/5G polymorphism in the plasminogen-activator-inhibitor-1 promoter on COVID-19 severity and endothelial dysfunction.
      Title: The influence of 4G/5G polymorphism in the plasminogen-activator-inhibitor-1 promoter on COVID-19 severity and endothelial dysfunction.
    5. Genetic Polymorphisms of GP1BA, PEAR1, and PAI-1 may be Associated with Serum sIgE and Blood Eosinophil Levels in Chinese Patients with Allergic Diseases.
      Title: Genetic Polymorphisms of GP1BA, PEAR1, and PAI-1 may be Associated with Serum sIgE and Blood Eosinophil Levels in Chinese Patients with Allergic Diseases.
    6. SERPINE1 and MTHFR genetic variants in patients with embolic stroke of undetermined source: links with fibrin clot properties.
      Title: SERPINE1 and MTHFR genetic variants in patients with embolic stroke of undetermined source: links with fibrin clot properties.
    7. PAI-1 mediates acquired resistance to MET-targeted therapy in non-small cell lung cancer.
      Title: PAI-1 mediates acquired resistance to MET-targeted therapy in non-small cell lung cancer.
    8. Plasminogen activator inhibitor-1 promotes immune evasion in tumors by facilitating the expression of programmed cell death-ligand 1.
      Title: Plasminogen activator inhibitor-1 promotes immune evasion in tumors by facilitating the expression of programmed cell death-ligand 1.
    9. Interleukin-1 increases SERPINE1 expression in human granulosa-lutein cell via P50/P52 signaling pathways.
      Title: Interleukin-1 increases SERPINE1 expression in human granulosa-lutein cell via P50/P52 signaling pathways.
    10. Thrombotic risk assessed by PAI-1 in patients with COVID-19: The influence of hyperglycemia and diabetes mellitus.
      Title: Thrombotic risk assessed by PAI-1 in patients with COVID-19: The influence of hyperglycemia and diabetes mellitus.
    Submit: New GeneRIF Correction See all GeneRIFs (1155)

    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

    EBI GWAS Catalog

    Description
    Genome-wide association study for circulating levels of PAI-1 provides novel insights into its regulation.
    EBI GWAS Catalog
    Genome-wide association study for circulating tissue plasminogen activator levels and functional follow-up implicates endothelial STXBP5 and STX2.
    EBI GWAS Catalog

    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
    Pr55(Gag) gag Cellular biotinylated serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 (SERPINE1) protein is incorporated into HIV-1 Gag virus-like particles PubMed
    Tat tat HIV-1 Tat has been shown to activate central nervous system-derived endothelial cells by the upregulation of E-selectin, IL-6 and PAI-1 PubMed
    tat HIV-1 Tat affects the fibrinolytic activity of tumor cell lines derived from BKV/tat-transgenic mice by upregulating/modulating the production of both urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor 1 (PAI-1) PubMed
    Vpr vpr Treatment of human primary astrocytes with HIV-1 Vpr upregulates secretion of IL-6, IL-8, MCP-1, and MIF and downregulates secretion of serpin E1, a serine proteinase inhibitor (known as PAI-1) 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

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables protease binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables serine-type endopeptidase inhibitor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables serine-type endopeptidase inhibitor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables serine-type endopeptidase inhibitor activity TAS
    Traceable Author Statement
    more info
    		  
    enables signaling receptor binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in angiogenesis IEP
    Inferred from Expression Pattern
    more info
    		 PubMed 
    involved_in cellular response to lipopolysaccharide IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in defense response to Gram-negative bacterium IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    involved_in dentinogenesis IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in fibrinolysis TAS
    Traceable Author Statement
    more info
    		  
    involved_in negative regulation of blood coagulation IC
    Inferred by Curator
    more info
    		 PubMed 
    involved_in negative regulation of cell adhesion mediated by integrin IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of cell migration IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of endopeptidase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of endopeptidase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of endothelial cell apoptotic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of extrinsic apoptotic signaling pathway via death domain receptors IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of fibrinolysis IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of fibrinolysis NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in negative regulation of plasminogen activation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of plasminogen activation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of plasminogen activation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of plasminogen activation NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in negative regulation of smooth muscle cell migration IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of smooth muscle cell-matrix adhesion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of vascular wound healing IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of vascular wound healing IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    involved_in negative regulation of wound healing IC
    Inferred by Curator
    more info
    		 PubMed 
    involved_in positive regulation of angiogenesis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of blood coagulation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of inflammatory response IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    involved_in positive regulation of interleukin-8 production IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of leukotriene production involved in inflammatory response IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of monocyte chemotaxis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of odontoblast differentiation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of receptor-mediated endocytosis IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of signaling receptor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in replicative senescence IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    colocalizes_with collagen-containing extracellular matrix HDA PubMed 
    located_in collagen-containing extracellular matrix HDA PubMed 
    located_in collagen-containing extracellular matrix IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in collagen-containing extracellular matrix NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    located_in extracellular exosome IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in extracellular region IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in extracellular region TAS
    Traceable Author Statement
    more info
    		  
    is_active_in extracellular space IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in extracellular space IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of peptidase inhibitor complex IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in platelet alpha granule lumen TAS
    Traceable Author Statement
    more info
    		  
    part_of serine protease inhibitor complex IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    plasminogen activator inhibitor 1
    Names
    endothelial plasminogen activator inhibitor
    serine (or cysteine) proteinase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1
    serpin E1
    serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 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_013213.1 RefSeqGene

      Range
      4992..17169
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_597

    mRNA and Protein(s)

    1. NM_000602.5 → NP_000593.1  plasminogen activator inhibitor 1 isoform 2 precursor

      See identical proteins and their annotated locations for NP_000593.1

      Status: REVIEWED

      Source sequence(s)
      AI752990, BC010860, CN309001, M16006
      Consensus CDS
      CCDS5711.1
      UniProtKB/Swiss-Prot
      B7Z4S0, F8WD53, P05121
      UniProtKB/TrEMBL
      B7Z4X6
      Related
      ENSP00000223095.4, ENST00000223095.5
      Conserved Domains (1) summary
      cd02051
      Location:29 → 402
      serpinE1_PAI-1; serpin family E member 1, plasminogen activator inhibitor-1

    2. NM_001386456.1 → NP_001373385.1  plasminogen activator inhibitor 1 isoform 3

      Status: REVIEWED

      Source sequence(s)
      AC004876
      UniProtKB/TrEMBL
      B7Z4X6
      Conserved Domains (1) summary
      cl38926
      Location:1 → 318
      serpin; SERine Proteinase INhibitors (serpin) family

    3. NM_001386457.1 → NP_001373386.1  plasminogen activator inhibitor 1 isoform 4 precursor

      Status: REVIEWED

      Source sequence(s)
      AC004876
      Conserved Domains (1) summary
      cl38926
      Location:29 → 338
      serpin; SERine Proteinase INhibitors (serpin) family

    4. NM_001386458.1 → NP_001373387.1  plasminogen activator inhibitor 1 isoform 5 precursor

      Status: REVIEWED

      Source sequence(s)
      AC004876
      UniProtKB/TrEMBL
      B7Z4X6
      Conserved Domains (1) summary
      cd02051
      Location:29 → 409
      serpinE1_PAI-1; serpin family E member 1, plasminogen activator inhibitor-1

    5. NM_001386459.1 → NP_001373388.1  plasminogen activator inhibitor 1 isoform 6 precursor

      Status: REVIEWED

      Source sequence(s)
      AC004876
      Conserved Domains (1) summary
      cd02051
      Location:29 → 398
      serpinE1_PAI-1; serpin family E member 1, plasminogen activator inhibitor-1

    6. NM_001386460.1 → NP_001373389.1  plasminogen activator inhibitor 1 isoform 1 precursor

      Status: REVIEWED

      Source sequence(s)
      AC004876
      Conserved Domains (1) summary
      cd02051
      Location:29 → 393
      serpinE1_PAI-1; serpin family E member 1, plasminogen activator inhibitor-1

    7. NM_001386461.1 → NP_001373390.1  plasminogen activator inhibitor 1 isoform 7 precursor

      Status: REVIEWED

      Source sequence(s)
      AC004876
      Conserved Domains (1) summary
      cl38926
      Location:29 → 366
      serpin; SERine Proteinase INhibitors (serpin) family

    8. NM_001386462.1 → NP_001373391.1  plasminogen activator inhibitor 1 isoform 8

      Status: REVIEWED

      Source sequence(s)
      AC004876
      UniProtKB/TrEMBL
      B7Z4X6, B7ZAB0
      Conserved Domains (1) summary
      cl38926
      Location:1 → 335
      serpin; SERine Proteinase INhibitors (serpin) family

    9. NM_001386463.1 → NP_001373392.1  plasminogen activator inhibitor 1 isoform 9 precursor

      Status: REVIEWED

      Source sequence(s)
      AC004876
      UniProtKB/TrEMBL
      B7Z4X6
      Conserved Domains (1) summary
      cd02051
      Location:27 → 400
      serpinE1_PAI-1; serpin family E member 1, plasminogen activator inhibitor-1

    10. NM_001386464.1 → NP_001373393.1  plasminogen activator inhibitor 1 isoform 10 precursor

      Status: REVIEWED

      Source sequence(s)
      AC004876
      Conserved Domains (1) summary
      cd02051
      Location:29 → 390
      serpinE1_PAI-1; serpin family E member 1, plasminogen activator inhibitor-1

    11. NM_001386465.1 → NP_001373394.1  plasminogen activator inhibitor 1 isoform 11 precursor

      Status: REVIEWED

      Source sequence(s)
      AC004876
      UniProtKB/TrEMBL
      B7Z4X6
      Conserved Domains (1) summary
      cd02051
      Location:29 → 407
      serpinE1_PAI-1; serpin family E member 1, plasminogen activator inhibitor-1

    12. NM_001386466.1 → NP_001373395.1  plasminogen activator inhibitor 1 isoform 12 precursor

      Status: REVIEWED

      Source sequence(s)
      AC004876
      UniProtKB/TrEMBL
      B7Z4X6
      Conserved Domains (1) summary
      cd02051
      Location:29 → 410
      serpinE1_PAI-1; serpin family E member 1, plasminogen activator inhibitor-1

    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_000007.14 Reference GRCh38.p14 Primary Assembly

      Range
      101127104..101139247
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060931.1 Alternate T2T-CHM13v2.0

      Range
      102449908..102462056
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_001165413.2: Suppressed sequence

      Description
      NM_001165413.2: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P05121.1 GenPept UniProtKB/Swiss-Prot:P05121

    Gene LinkOut

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

    Other Literature Sources
    Chemical Information
    Medical
    Molecular Biology Databases
    Research Materials
    Tools
    Miscellaneous