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    FNDC5 fibronectin type III domain containing 5 [ Homo sapiens (human) ]

    Gene ID: 252995, updated on 22-Apr-2024

    Summary

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    Official Symbol
    FNDC5provided by HGNC
    Official Full Name
    fibronectin type III domain containing 5provided by HGNC
    Primary source
    HGNC:HGNC:20240
    See related
    Ensembl:ENSG00000160097 MIM:611906; AllianceGenome:HGNC:20240
    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
    FRCP2; irisin
    Summary
    This gene encodes a secreted protein that is released from muscle cells during exercise. The encoded protein may participate in the development of brown fat. Translation of the precursor protein initiates at a non-AUG start codon at a position that is conserved as an AUG start codon in other organisms. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2013]
    Expression
    Biased expression in heart (RPKM 13.5), liver (RPKM 8.6) and 10 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See FNDC5 in Genome Data Viewer
    Location:
    1p35.1
    Exon count:
    7
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (32862268..32872484, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (32722061..32732277, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (33327869..33338085, complement)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 608 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:33219766-33220279 Neighboring gene NHS like 3 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:33225004-33225886 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:33225887-33226770 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:33227405-33227625 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:33231243-33232135 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:33232136-33233029 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:33235076-33235991 Neighboring gene Sharpr-MPRA regulatory region 15696 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_6796 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr1:33251929-33253128 Neighboring gene tyrosyl-tRNA synthetase 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 697 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:33269619-33270293 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:33270294-33270967 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:33275934-33276570 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:33276571-33277206 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:33282071-33282572 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:33282573-33283072 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_6822 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 699 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 700 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 701 Neighboring gene S100P binding protein Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_6850 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_6868 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:33333351-33333852 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:33338281-33339137 Neighboring gene uncharacterized LOC105378631 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_6918 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 609 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 610 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_6924 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 611 Neighboring gene hippocalcin Neighboring gene transmembrane protein 54

    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. Irisin acts through its integrin receptor in a two-step process involving extracellular Hsp90α. A M, et al. Mol Cell, 2023 Jun 1. PMID 37267907, Free PMC Article
    2. Irisin as a Novel Biomarker of Subclinical Atherosclerosis in Severe Obesity. Carmona-Maurici J, et al. Int J Mol Sci, 2023 May 3. PMID 37175880, Free PMC Article
    3. Serum irisin levels and osteoporosis in patients with advanced chronic kidney disease and renal transplant recipients. Demir C, et al. Int Urol Nephrol, 2023 Jul. PMID 36773217, Free PMC Article
    4. Characterization of advanced glycation end products and aggregates of irisin: Multispectroscopic and microscopic approaches. Waseem R, et al. J Cell Biochem, 2023 Jan. PMID 36502526
    5. The serum irisin response to prolonged physical activity in temperate and hot environments in older men with hypertension or type 2 diabetes. McCormick JJ, et al. J Therm Biol, 2022 Dec. PMID 36462879

    See all (328) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The emerging roles of irisin in vascular calcification.
      Title: The emerging roles of irisin in vascular calcification.
    2. Relationship of irisin with disease severity and dopamine uptake in Parkinson's disease patients.
      Title: Relationship of irisin with disease severity and dopamine uptake in Parkinson's disease patients.
    3. Role of irisin and myostatin on sarcopenia in malnourished patients diagnosed with GLIM criteria.
      Title: Role of irisin and myostatin on sarcopenia in malnourished patients diagnosed with GLIM criteria.
    4. The Role of FNDC5/Irisin in Cardiovascular Disease.
      Title: The Role of FNDC5/Irisin in Cardiovascular Disease.
    5. The association of serum irisin with anthropometric, metabolic, and bone parameters in obese children and adolescents.
      Title: The association of serum irisin with anthropometric, metabolic, and bone parameters in obese children and adolescents.
    6. Relationship between Serum Irisin Level, All-Cause Mortality, and Cardiovascular Mortality in Peritoneal Dialysis Patients.
      Title: Relationship between Serum Irisin Level, All-Cause Mortality, and Cardiovascular Mortality in Peritoneal Dialysis Patients.
    7. MiR-143-3p/FNDC5 axis: a novel regulator of insulin sensitivity.
      Title: MiR-143-3p/FNDC5 axis: a novel regulator of insulin sensitivity.
    8. The role of irisin in kidney diseases.
      Title: The role of irisin in kidney diseases.
    9. Serum irisin levels are negatively associated with blood pressure in dialysis patients.
      Title: Serum irisin levels are negatively associated with blood pressure in dialysis patients.
    10. Relationships between circulating irisin levels, cardiorespiratory fitness, and cardiometabolic risk: a cross-sectional study in Japanese adults.
      Title: Relationships between circulating irisin levels, cardiorespiratory fitness, and cardiometabolic risk: a cross-sectional study in Japanese adults.
    Submit: New GeneRIF Correction See all GeneRIFs (330)

    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

    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 hormone activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables molecular_function ND
    No biological Data available
    more info
    		  
    Process Evidence Code Pubs
    involved_in biological_process ND
    No biological Data available
    more info
    		  
    involved_in positive regulation of brown fat cell differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in response to muscle activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in signal transduction IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in endoplasmic reticulum ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in extracellular region ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in peroxisomal membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in plasma membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  

    General protein information

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    Preferred Names
    fibronectin type III domain-containing protein 5
    Names
    fibronectin type III repeat-containing protein 2

    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_001171940.2 → NP_001165411.2  fibronectin type III domain-containing protein 5 isoform 3 preproprotein

      See identical proteins and their annotated locations for NP_001165411.2

      Status: REVIEWED

      Source sequence(s)
      AC114493
      UniProtKB/TrEMBL
      A0A0A0MRR6
      Conserved Domains (2) summary
      cd00063
      Location:34 → 124
      FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...
      pfam16066
      Location:149 → 172
      DUF4808; Domain of unknown function (DUF4808)

    2. NM_001171941.3 → NP_001165412.1  fibronectin type III domain-containing protein 5 isoform 1

      See identical proteins and their annotated locations for NP_001165412.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the shortest isoform (1).
      Source sequence(s)
      AC114493, BC033123, BC062297, CV815003, DA393478
      Consensus CDS
      CCDS65483.1
      UniProtKB/Swiss-Prot
      Q8NAU1
      Related
      ENSP00000476320.1, ENST00000496770.1
      Conserved Domains (2) summary
      cd00063
      Location:5 → 49
      FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...
      pfam16066
      Location:76 → 109
      DUF4808; Domain of unknown function (DUF4808)

    3. NM_153756.3 → NP_715637.2  fibronectin type III domain-containing protein 5 isoform 2 preproprotein

      See identical proteins and their annotated locations for NP_715637.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) contains multiple differences in the UTRs and coding region, compared to variant 1. It initiates translation from an alternate "AUA" start codon that is conserved as an "AUG" start codon in orthologs. The encoded isoform (2) is longer and has distinct N- and C-termini, compared to isoform 1.
      Source sequence(s)
      AC114493, AK092102, BC033123, BE502835
      Consensus CDS
      CCDS369.2
      UniProtKB/Swiss-Prot
      A6NMC9, D3DPQ6, Q6P6D9, Q7Z676, Q8NAU1
      UniProtKB/TrEMBL
      A0A0A0MRR6
      Related
      ENSP00000362570.5, ENST00000373471.9
      Conserved Domains (2) summary
      cd00063
      Location:34 → 124
      FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...
      pfam16066
      Location:151 → 184
      DUF4808; Domain of unknown function (DUF4808)

    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_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      32862268..32872484 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      32722061..32732277 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8NAU1.3 GenPept UniProtKB/Swiss-Prot:Q8NAU1

    Gene LinkOut

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

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