{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q8NAU1","secondaryAccessions":["A0AA34QVI5","A6NMC9","D3DPQ6","Q6P6D9","Q7Z676"],"uniProtkbId":"FNDC5_HUMAN","entryAudit":{"firstPublicDate":"2008-04-08","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2025-02-05","entryVersion":168,"sequenceVersion":4},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"Fibronectin type III domain-containing protein 5"}},"alternativeNames":[{"fullName":{"value":"Fibronectin type III repeat-containing protein 2"}}],"contains":[{"recommendedName":{"fullName":{"value":"Irisin"}}}],"flag":"Precursor"},"genes":[{"geneName":{"value":"FNDC5"},"synonyms":[{"value":"FRCP2"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8K4Z2"}],"value":"Mediates beneficial effects of muscular exercise. Induces browning of white adipose tissue by stimulating UCP1 expression, at least in part, via the nuclear receptor PPARA"}],"commentType":"FUNCTION","molecule":"Irisin"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24114836"}],"value":"Dimer; may exist in other oligomeric forms"}],"commentType":"SUBUNIT","molecule":"Irisin"},{"commentType":"SUBCELLULAR LOCATION","molecule":"Fibronectin type III domain-containing protein 5","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8K4Z2"}],"value":"Imported into peroxisomes through the PEX5 receptor pathway"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22237023"}],"value":"Cell membrane","id":"SL-0039"},"topology":{"evidences":[{"evidenceCode":"ECO:0000255"}],"value":"Single-pass membrane protein","id":"SL-9904"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8K4Z2"}],"value":"Peroxisome membrane","id":"SL-0203"},"topology":{"evidences":[{"evidenceCode":"ECO:0000255"}],"value":"Single-pass membrane protein","id":"SL-9904"}}]},{"commentType":"SUBCELLULAR LOCATION","molecule":"Irisin","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22237023"}],"value":"Detected in plasma following endurance exercise"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22237023"}],"value":"Secreted","id":"SL-0243"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative promoter usage","Alternative splicing"],"isoforms":[{"name":{"value":"1"},"isoformIds":["Q8NAU1-5"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"2"},"isoformIds":["Q8NAU1-2"],"sequenceIds":["VSP_062500","VSP_062501"],"isoformSequenceStatus":"Described"},{"name":{"value":"3"},"isoformIds":["Q8NAU1-3"],"sequenceIds":["VSP_062499","VSP_062502"],"isoformSequenceStatus":"Described"},{"name":{"value":"4"},"isoformIds":["Q8NAU1-4"],"sequenceIds":["VSP_062499"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24040023"}],"value":"Widely expressed, with highest levels in heart. Very low expression, if any, in colon, pancreas and spleen"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22237023"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24040023"}],"value":"Up-regulated twofold by muscular exercise at the mRNA and protein level; this effect has been suggested to be mediated by PPARGC1A (PubMed:22237023). However, up-regulation at the mRNA level upon exercise could not be reproduced in another study (PubMed:24040023)"}],"commentType":"INDUCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26278051"}],"value":"Present in sedentary individuals with significantly increased levels in individuals undergoing aerobic interval training"}],"commentType":"INDUCTION","molecule":"Irisin"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24114836"}],"value":"Fibronectin type-III domain is capable of forming a continuous intersubunit beta-sheet dimer; dimerization may thereby play a role in cell-cell adhesion or signaling"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8K4Z2"}],"value":"The extracellular domain is cleaved and released from the cell membrane"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8K4Z2"}],"value":"N-Glycosylated"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38471509"}],"value":"Produced by alternative promoter usage"}],"commentType":"MISCELLANEOUS","molecule":"Isoform 1"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Produced by alternative splicing of isoform 1"}],"commentType":"MISCELLANEOUS","molecule":"Isoform 2"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Produced by alternative promoter usage and alternative splicing"}],"commentType":"MISCELLANEOUS","molecule":"Isoform 3"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Produced by alternative promoter usage"}],"commentType":"MISCELLANEOUS","molecule":"Isoform 4"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22237023"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26278051"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38471509"},{"evidenceCode":"ECO:0000305"}],"value":"There has been some uncertainty over the initiator of the protein. Some transcript evidence points to Met-124 as the start but, in this short version of the protein, the irisin peptide is severely truncated. But Western blot analysis suggests the presence of a full-length irisin peptide in human (PubMed:22237023, PubMed:26278051). An alternative upstream initiation codon was proposed which is conserved across most mammals but this corresponds to an ATA codon in human and translation from this start site in human has not been confirmed. A further alternative to the putative N-terminal ATA codon as the initiation site is provided by an upstream transcription start site which allows use of a highly conserved AUG initiation codon and is likely to represent the true initiator of the protein (PubMed:38471509)"}],"commentType":"CAUTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24040023"},{"evidenceCode":"ECO:0000305"}],"value":"Contrary to mouse, was shown to have no involvement in the beneficial effects of muscular exercise nor in the induction of browning of human white adipose tissue (PubMed:24040023). However, this may be due to the construct used which did not start from the upstream AUG transcription start site"}],"commentType":"CAUTION"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":260,"modifier":"EXACT"}},"description":"Fibronectin type III domain-containing protein 5","featureId":"PRO_0000328971"},{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":191,"modifier":"EXACT"}},"description":"Irisin","featureId":"PRO_0000415857"},{"type":"Transmembrane","location":{"start":{"value":201,"modifier":"EXACT"},"end":{"value":221,"modifier":"EXACT"}},"description":"Helical","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Domain","location":{"start":{"value":84,"modifier":"EXACT"},"end":{"value":175,"modifier":"EXACT"}},"description":"Fibronectin type-III","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00316"}]},{"type":"Region","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":56,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Region","location":{"start":{"value":230,"modifier":"EXACT"},"end":{"value":260,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Motif","location":{"start":{"value":258,"modifier":"EXACT"},"end":{"value":260,"modifier":"EXACT"}},"description":"Microbody targeting signal","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Compositional bias","location":{"start":{"value":10,"modifier":"EXACT"},"end":{"value":28,"modifier":"EXACT"}},"description":"Basic and acidic residues","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Compositional bias","location":{"start":{"value":29,"modifier":"EXACT"},"end":{"value":56,"modifier":"EXACT"}},"description":"Low complexity","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Compositional bias","location":{"start":{"value":230,"modifier":"EXACT"},"end":{"value":241,"modifier":"EXACT"}},"description":"Basic and acidic residues","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Compositional bias","location":{"start":{"value":251,"modifier":"EXACT"},"end":{"value":260,"modifier":"EXACT"}},"description":"Gly residues","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Site","location":{"start":{"value":126,"modifier":"EXACT"},"end":{"value":126,"modifier":"EXACT"}},"description":"Required for dimerization","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24114836"}]},{"type":"Glycosylation","location":{"start":{"value":87,"modifier":"EXACT"},"end":{"value":87,"modifier":"EXACT"}},"description":"N-linked (GlcNAc...) asparagine","evidences":[{"evidenceCode":"ECO:0000255"}],"featureId":""},{"type":"Glycosylation","location":{"start":{"value":132,"modifier":"EXACT"},"end":{"value":132,"modifier":"EXACT"}},"description":"N-linked (GlcNAc...) asparagine","evidences":[{"evidenceCode":"ECO:0000255"}],"featureId":""},{"type":"Alternative sequence","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":123,"modifier":"EXACT"}},"description":"in isoform 3 and isoform 4","evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"14702039"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"15489334"}],"featureId":"VSP_062499","alternativeSequence":{}},{"type":"Alternative sequence","location":{"start":{"value":228,"modifier":"EXACT"},"end":{"value":229,"modifier":"EXACT"}},"description":"in isoform 2","evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"17974005"}],"featureId":"VSP_062500","alternativeSequence":{"originalSequence":"KD","alternativeSequences":["EA"]}},{"type":"Alternative sequence","location":{"start":{"value":230,"modifier":"EXACT"},"end":{"value":260,"modifier":"EXACT"}},"description":"in isoform 2","evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"17974005"}],"featureId":"VSP_062501","alternativeSequence":{}},{"type":"Alternative sequence","location":{"start":{"value":260,"modifier":"EXACT"},"end":{"value":260,"modifier":"EXACT"}},"description":"in isoform 3","evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"15489334"}],"featureId":"VSP_062502","alternativeSequence":{"originalSequence":"I","alternativeSequences":["VRARPGPGWATLCLMLW"]}},{"type":"Mutagenesis","location":{"start":{"value":126,"modifier":"EXACT"},"end":{"value":126,"modifier":"EXACT"}},"description":"Abolishes dimerization; probably prevents inter-subunit salt bridge formation.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24114836"}],"alternativeSequence":{"originalSequence":"R","alternativeSequences":["E"]}},{"type":"Helix","location":{"start":{"value":82,"modifier":"EXACT"},"end":{"value":85,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"4LSD"}]},{"type":"Beta strand","location":{"start":{"value":86,"modifier":"EXACT"},"end":{"value":92,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"4LSD"}]},{"type":"Beta strand","location":{"start":{"value":98,"modifier":"EXACT"},"end":{"value":103,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"4LSD"}]},{"type":"Turn","location":{"start":{"value":107,"modifier":"EXACT"},"end":{"value":109,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"4LSD"}]},{"type":"Beta strand","location":{"start":{"value":110,"modifier":"EXACT"},"end":{"value":121,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"4LSD"}]},{"type":"Beta strand","location":{"start":{"value":125,"modifier":"EXACT"},"end":{"value":132,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"4LSD"}]},{"type":"Beta strand","location":{"start":{"value":137,"modifier":"EXACT"},"end":{"value":140,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"4LSD"}]},{"type":"Beta strand","location":{"start":{"value":148,"modifier":"EXACT"},"end":{"value":159,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"4LSD"}]},{"type":"Helix","location":{"start":{"value":162,"modifier":"EXACT"},"end":{"value":164,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"4LSD"}]},{"type":"Beta strand","location":{"start":{"value":168,"modifier":"EXACT"},"end":{"value":171,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"4LSD"}]},{"type":"Helix","location":{"start":{"value":174,"modifier":"EXACT"},"end":{"value":176,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"4LSD"}]}],"keywords":[{"id":"KW-0002","category":"Technical term","name":"3D-structure"},{"id":"KW-0877","category":"Coding sequence diversity","name":"Alternative promoter usage"},{"id":"KW-0025","category":"Coding sequence diversity","name":"Alternative splicing"},{"id":"KW-1003","category":"Cellular component","name":"Cell membrane"},{"id":"KW-0325","category":"PTM","name":"Glycoprotein"},{"id":"KW-0372","category":"Molecular function","name":"Hormone"},{"id":"KW-0472","category":"Cellular component","name":"Membrane"},{"id":"KW-0576","category":"Cellular component","name":"Peroxisome"},{"id":"KW-1267","category":"Technical term","name":"Proteomics identification"},{"id":"KW-1185","category":"Technical term","name":"Reference proteome"},{"id":"KW-0964","category":"Cellular component","name":"Secreted"},{"id":"KW-0812","category":"Domain","name":"Transmembrane"},{"id":"KW-1133","category":"Domain","name":"Transmembrane helix"}],"references":[{"referenceNumber":1,"citation":{"id":"14702039","citationType":"journal article","authors":["Ota T.","Suzuki Y.","Nishikawa T.","Otsuki T.","Sugiyama T.","Irie R.","Wakamatsu A.","Hayashi K.","Sato H.","Nagai K.","Kimura K.","Makita H.","Sekine M.","Obayashi M.","Nishi T.","Shibahara T.","Tanaka T.","Ishii S.","Yamamoto J.","Saito K.","Kawai Y.","Isono Y.","Nakamura Y.","Nagahari K.","Murakami K.","Yasuda T.","Iwayanagi T.","Wagatsuma M.","Shiratori A.","Sudo H.","Hosoiri T.","Kaku Y.","Kodaira H.","Kondo H.","Sugawara M.","Takahashi M.","Kanda K.","Yokoi T.","Furuya T.","Kikkawa E.","Omura Y.","Abe K.","Kamihara K.","Katsuta N.","Sato K.","Tanikawa M.","Yamazaki M.","Ninomiya K.","Ishibashi T.","Yamashita H.","Murakawa K.","Fujimori K.","Tanai H.","Kimata M.","Watanabe M.","Hiraoka S.","Chiba Y.","Ishida S.","Ono Y.","Takiguchi S.","Watanabe S.","Yosida M.","Hotuta T.","Kusano J.","Kanehori K.","Takahashi-Fujii A.","Hara H.","Tanase T.-O.","Nomura Y.","Togiya S.","Komai F.","Hara R.","Takeuchi K.","Arita M.","Imose N.","Musashino K.","Yuuki H.","Oshima A.","Sasaki N.","Aotsuka S.","Yoshikawa Y.","Matsunawa H.","Ichihara T.","Shiohata N.","Sano S.","Moriya S.","Momiyama H.","Satoh N.","Takami S.","Terashima Y.","Suzuki O.","Nakagawa S.","Senoh A.","Mizoguchi H.","Goto Y.","Shimizu F.","Wakebe H.","Hishigaki H.","Watanabe T.","Sugiyama A.","Takemoto M.","Kawakami B.","Yamazaki M.","Watanabe K.","Kumagai A.","Itakura S.","Fukuzumi Y.","Fujimori Y.","Komiyama M.","Tashiro H.","Tanigami A.","Fujiwara T.","Ono T.","Yamada K.","Fujii Y.","Ozaki K.","Hirao M.","Ohmori Y.","Kawabata A.","Hikiji T.","Kobatake N.","Inagaki H.","Ikema Y.","Okamoto S.","Okitani R.","Kawakami T.","Noguchi S.","Itoh T.","Shigeta K.","Senba T.","Matsumura K.","Nakajima Y.","Mizuno T.","Morinaga M.","Sasaki M.","Togashi T.","Oyama M.","Hata H.","Watanabe M.","Komatsu T.","Mizushima-Sugano J.","Satoh T.","Shirai Y.","Takahashi Y.","Nakagawa K.","Okumura K.","Nagase T.","Nomura N.","Kikuchi H.","Masuho Y.","Yamashita R.","Nakai K.","Yada T.","Nakamura Y.","Ohara O.","Isogai T.","Sugano S."],"citationCrossReferences":[{"database":"PubMed","id":"14702039"},{"database":"DOI","id":"10.1038/ng1285"}],"title":"Complete sequencing and characterization of 21,243 full-length human cDNAs.","publicationDate":"2004","journal":"Nat. Genet.","firstPage":"40","lastPage":"45","volume":"36"},"referencePositions":["NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4)"]},{"referenceNumber":2,"citation":{"id":"16710414","citationType":"journal article","authors":["Gregory S.G.","Barlow K.F.","McLay K.E.","Kaul R.","Swarbreck D.","Dunham A.","Scott C.E.","Howe K.L.","Woodfine K.","Spencer C.C.A.","Jones M.C.","Gillson C.","Searle S.","Zhou Y.","Kokocinski F.","McDonald L.","Evans R.","Phillips K.","Atkinson A.","Cooper R.","Jones C.","Hall R.E.","Andrews T.D.","Lloyd C.","Ainscough R.","Almeida J.P.","Ambrose K.D.","Anderson F.","Andrew R.W.","Ashwell R.I.S.","Aubin K.","Babbage A.K.","Bagguley C.L.","Bailey J.","Beasley H.","Bethel G.","Bird C.P.","Bray-Allen S.","Brown J.Y.","Brown A.J.","Buckley D.","Burton J.","Bye J.","Carder C.","Chapman J.C.","Clark S.Y.","Clarke G.","Clee C.","Cobley V.","Collier R.E.","Corby N.","Coville G.J.","Davies J.","Deadman R.","Dunn M.","Earthrowl M.","Ellington A.G.","Errington H.","Frankish A.","Frankland J.","French L.","Garner P.","Garnett J.","Gay L.","Ghori M.R.J.","Gibson R.","Gilby L.M.","Gillett W.","Glithero R.J.","Grafham D.V.","Griffiths C.","Griffiths-Jones S.","Grocock R.","Hammond S.","Harrison E.S.I.","Hart E.","Haugen E.","Heath P.D.","Holmes S.","Holt K.","Howden P.J.","Hunt A.R.","Hunt S.E.","Hunter G.","Isherwood J.","James R.","Johnson C.","Johnson D.","Joy A.","Kay M.","Kershaw J.K.","Kibukawa M.","Kimberley A.M.","King A.","Knights A.J.","Lad H.","Laird G.","Lawlor S.","Leongamornlert D.A.","Lloyd D.M.","Loveland J.","Lovell J.","Lush M.J.","Lyne R.","Martin S.","Mashreghi-Mohammadi M.","Matthews L.","Matthews N.S.W.","McLaren S.","Milne S.","Mistry S.","Moore M.J.F.","Nickerson T.","O'Dell C.N.","Oliver K.","Palmeiri A.","Palmer S.A.","Parker A.","Patel D.","Pearce A.V.","Peck A.I.","Pelan S.","Phelps K.","Phillimore B.J.","Plumb R.","Rajan J.","Raymond C.","Rouse G.","Saenphimmachak C.","Sehra H.K.","Sheridan E.","Shownkeen R.","Sims S.","Skuce C.D.","Smith M.","Steward C.","Subramanian S.","Sycamore N.","Tracey A.","Tromans A.","Van Helmond Z.","Wall M.","Wallis J.M.","White S.","Whitehead S.L.","Wilkinson J.E.","Willey D.L.","Williams H.","Wilming L.","Wray P.W.","Wu Z.","Coulson A.","Vaudin M.","Sulston J.E.","Durbin R.M.","Hubbard T.","Wooster R.","Dunham I.","Carter N.P.","McVean G.","Ross M.T.","Harrow J.","Olson M.V.","Beck S.","Rogers J.","Bentley D.R."],"citationCrossReferences":[{"database":"PubMed","id":"16710414"},{"database":"DOI","id":"10.1038/nature04727"}],"title":"The DNA sequence and biological annotation of human chromosome 1.","publicationDate":"2006","journal":"Nature","firstPage":"315","lastPage":"321","volume":"441"},"referencePositions":["NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]"]},{"referenceNumber":3,"citation":{"id":"CI-5GBD0VIIJ7C63","citationType":"submission","authors":["Mural R.J.","Istrail S.","Sutton G.G.","Florea L.","Halpern A.L.","Mobarry C.M.","Lippert R.","Walenz B.","Shatkay H.","Dew I.","Miller J.R.","Flanigan M.J.","Edwards N.J.","Bolanos R.","Fasulo D.","Halldorsson B.V.","Hannenhalli S.","Turner R.","Yooseph S.","Lu F.","Nusskern D.R.","Shue B.C.","Zheng X.H.","Zhong F.","Delcher A.L.","Huson D.H.","Kravitz S.A.","Mouchard L.","Reinert K.","Remington K.A.","Clark A.G.","Waterman M.S.","Eichler E.E.","Adams M.D.","Hunkapiller M.W.","Myers E.W.","Venter J.C."],"publicationDate":"SEP-2005","submissionDatabase":"EMBL/GenBank/DDBJ databases"},"referencePositions":["NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]"]},{"referenceNumber":4,"citation":{"id":"15489334","citationType":"journal article","authoringGroup":["The MGC Project Team"],"citationCrossReferences":[{"database":"PubMed","id":"15489334"},{"database":"DOI","id":"10.1101/gr.2596504"}],"title":"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).","publicationDate":"2004","journal":"Genome Res.","firstPage":"2121","lastPage":"2127","volume":"14"},"referencePositions":["NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3)"],"referenceComments":[{"value":"Brain","type":"TISSUE"}]},{"referenceNumber":5,"citation":{"id":"CI-826L453UMJGU6","citationType":"submission","authoringGroup":["The Cancer Genome Anatomy Project (CGAP) at the National Cancer Institute"],"publicationDate":"NOV-2000","submissionDatabase":"EMBL/GenBank/DDBJ databases"},"referencePositions":["NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 27-181 (ISOFORM 1)"]},{"referenceNumber":6,"citation":{"id":"17974005","citationType":"journal article","authors":["Bechtel S.","Rosenfelder H.","Duda A.","Schmidt C.P.","Ernst U.","Wellenreuther R.","Mehrle A.","Schuster C.","Bahr A.","Bloecker H.","Heubner D.","Hoerlein A.","Michel G.","Wedler H.","Koehrer K.","Ottenwaelder B.","Poustka A.","Wiemann S.","Schupp I."],"citationCrossReferences":[{"database":"PubMed","id":"17974005"},{"database":"DOI","id":"10.1186/1471-2164-8-399"}],"title":"The full-ORF clone resource of the German cDNA consortium.","publicationDate":"2007","journal":"BMC Genomics","firstPage":"399","lastPage":"399","volume":"8"},"referencePositions":["NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 68-260 (ISOFORM 2)"],"referenceComments":[{"value":"Fetal liver","type":"TISSUE"}]},{"referenceNumber":7,"citation":{"id":"22237023","citationType":"journal article","authors":["Bostrom P.","Wu J.","Jedrychowski M.P.","Korde A.","Ye L.","Lo J.C.","Rasbach K.A.","Bostrom E.A.","Choi J.H.","Long J.Z.","Kajimura S.","Zingaretti M.C.","Vind B.F.","Tu H.","Cinti S.","Hojlund K.","Gygi S.P.","Spiegelman B.M."],"citationCrossReferences":[{"database":"PubMed","id":"22237023"},{"database":"DOI","id":"10.1038/nature10777"}],"title":"A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis.","publicationDate":"2012","journal":"Nature","firstPage":"463","lastPage":"468","volume":"481"},"referencePositions":["INDUCTION","SUBCELLULAR LOCATION"]},{"referenceNumber":8,"citation":{"id":"24040023","citationType":"journal article","authors":["Raschke S.","Elsen M.","Gassenhuber H.","Sommerfeld M.","Schwahn U.","Brockmann B.","Jung R.","Wisloff U.","Tjonna A.E.","Raastad T.","Hallen J.","Norheim F.","Drevon C.A.","Romacho T.","Eckardt K.","Eckel J."],"citationCrossReferences":[{"database":"PubMed","id":"24040023"},{"database":"DOI","id":"10.1371/journal.pone.0073680"}],"title":"Evidence against a Beneficial Effect of Irisin in Humans.","publicationDate":"2013","journal":"PLoS ONE","firstPage":"E73680","lastPage":"E73680","volume":"8"},"referencePositions":["INDUCTION","TISSUE SPECIFICITY"]},{"referenceNumber":9,"citation":{"id":"26278051","citationType":"journal article","authors":["Jedrychowski M.P.","Wrann C.D.","Paulo J.A.","Gerber K.K.","Szpyt J.","Robinson M.M.","Nair K.S.","Gygi S.P.","Spiegelman B.M."],"citationCrossReferences":[{"database":"PubMed","id":"26278051"},{"database":"DOI","id":"10.1016/j.cmet.2015.08.001"}],"title":"Detection and Quantitation of Circulating Human Irisin by Tandem Mass Spectrometry.","publicationDate":"2015","journal":"Cell Metab.","firstPage":"734","lastPage":"740","volume":"22"},"referencePositions":["IDENTIFICATION OF IRISIN","INDUCTION"]},{"referenceNumber":10,"citation":{"id":"38471509","citationType":"journal article","authors":["Witmer N.H.","Linzer C.R.","Boudreau R.L."],"citationCrossReferences":[{"database":"PubMed","id":"38471509"},{"database":"DOI","id":"10.1016/j.cmet.2024.02.008"}],"title":"Fndc5 is translated from an upstream ATG start codon and cleaved to produce irisin myokine precursor protein in humans and mice.","publicationDate":"2024","journal":"Cell Metab.","firstPage":"0","lastPage":"0","volume":"0"},"referencePositions":["ALTERNATIVE PROMOTER USAGE (ISOFORM 1)"]},{"referenceNumber":11,"citation":{"id":"24114836","citationType":"journal article","authors":["Schumacher M.A.","Chinnam N.","Ohashi T.","Shah R.S.","Erickson H.P."],"citationCrossReferences":[{"database":"PubMed","id":"24114836"},{"database":"DOI","id":"10.1074/jbc.m113.516641"}],"title":"The structure of irisin reveals a novel intersubunit beta-sheet fibronectin type III (FNIII) dimer: implications for receptor activation.","publicationDate":"2013","journal":"J. Biol. Chem.","firstPage":"33738","lastPage":"33744","volume":"288"},"referencePositions":["X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 81-177","SUBUNIT","MUTAGENESIS OF ARG-126"],"evidences":[{"evidenceCode":"ECO:0007744","source":"PDB","id":"4LSD"}]}],"uniProtKBCrossReferences":[{"database":"EMBL","id":"AK092102","properties":[{"key":"ProteinId","value":"BAC03806.1"},{"key":"Status","value":"-"},{"key":"MoleculeType","value":"mRNA"}]},{"database":"EMBL","id":"AC114493","properties":[{"key":"ProteinId","value":"-"},{"key":"Status","value":"NOT_ANNOTATED_CDS"},{"key":"MoleculeType","value":"Genomic_DNA"}]},{"database":"EMBL","id":"CH471059","properties":[{"key":"ProteinId","value":"EAX07499.1"},{"key":"Status","value":"-"},{"key":"MoleculeType","value":"Genomic_DNA"}]},{"database":"EMBL","id":"CH471059","properties":[{"key":"ProteinId","value":"EAX07502.1"},{"key":"Status","value":"-"},{"key":"MoleculeType","value":"Genomic_DNA"}]},{"database":"EMBL","id":"CH471059","properties":[{"key":"ProteinId","value":"EAX07500.1"},{"key":"Status","value":"-"},{"key":"MoleculeType","value":"Genomic_DNA"}]},{"database":"EMBL","id":"BC062297","properties":[{"key":"ProteinId","value":"AAH62297.1"},{"key":"Status","value":"-"},{"key":"MoleculeType","value":"mRNA"}]},{"database":"EMBL","id":"BX537781","properties":[{"key":"ProteinId","value":"CAD97840.1"},{"key":"Status","value":"-"},{"key":"MoleculeType","value":"mRNA"}]},{"database":"EMBL","id":"BF221649","properties":[{"key":"ProteinId","value":"-"},{"key":"Status","value":"NOT_ANNOTATED_CDS"},{"key":"MoleculeType","value":"mRNA"}]},{"database":"CCDS","id":"CCDS65483.1","properties":[{"key":"Description","value":"-"}],"isoformId":"Q8NAU1-3"},{"database":"RefSeq","id":"NP_001165411.2","properties":[{"key":"NucleotideSequenceId","value":"NM_001171940.2"}]},{"database":"RefSeq","id":"NP_001165412.1","properties":[{"key":"NucleotideSequenceId","value":"NM_001171941.3"}],"isoformId":"Q8NAU1-3"},{"database":"RefSeq","id":"NP_001428612.1","properties":[{"key":"NucleotideSequenceId","value":"NM_001441683.1"}],"isoformId":"Q8NAU1-5"},{"database":"PDB","id":"4LSD","properties":[{"key":"Method","value":"X-ray"},{"key":"Resolution","value":"2.28 A"},{"key":"Chains","value":"A/B/C/D/E/F/G/H=81-178"}]},{"database":"PDBsum","id":"4LSD","properties":[{"key":"Description","value":"-"}]},{"database":"AlphaFoldDB","id":"Q8NAU1","properties":[{"key":"Description","value":"-"}]},{"database":"SMR","id":"Q8NAU1","properties":[{"key":"Description","value":"-"}]},{"database":"BioGRID","id":"128948","properties":[{"key":"Interactions","value":"173"}]},{"database":"FunCoup","id":"Q8NAU1","properties":[{"key":"Number of interactors","value":"461"}]},{"database":"IntAct","id":"Q8NAU1","properties":[{"key":"Interactions","value":"126"}]},{"database":"STRING","id":"9606.ENSP00000362570","properties":[{"key":"Description","value":"-"}]},{"database":"GlyCosmos","id":"Q8NAU1","properties":[{"key":"glycosylation","value":"2 sites, No reported glycans"}]},{"database":"GlyGen","id":"Q8NAU1","properties":[{"key":"glycosylation","value":"2 sites"}]},{"database":"iPTMnet","id":"Q8NAU1","properties":[{"key":"Description","value":"-"}]},{"database":"PhosphoSitePlus","id":"Q8NAU1","properties":[{"key":"Description","value":"-"}]},{"database":"BioMuta","id":"FNDC5","properties":[{"key":"Description","value":"-"}]},{"database":"DMDM","id":"403314395","properties":[{"key":"Description","value":"-"}]},{"database":"MassIVE","id":"Q8NAU1","properties":[{"key":"Description","value":"-"}]},{"database":"PaxDb","id":"9606-ENSP00000362570","properties":[{"key":"Description","value":"-"}]},{"database":"PeptideAtlas","id":"Q8NAU1","properties":[{"key":"Description","value":"-"}]},{"database":"ProteomicsDB","id":"72701","properties":[{"key":"Description","value":"-"}],"isoformId":"Q8NAU1-2"},{"database":"ProteomicsDB","id":"72702","properties":[{"key":"Description","value":"-"}],"isoformId":"Q8NAU1-3"},{"database":"ProteomicsDB","id":"72703","properties":[{"key":"Description","value":"-"}],"isoformId":"Q8NAU1-4"},{"database":"Antibodypedia","id":"54866","properties":[{"key":"antibodies","value":"227 antibodies from 31 providers"}]},{"database":"DNASU","id":"252995","properties":[{"key":"Description","value":"-"}]},{"database":"Ensembl","id":"ENST00000496770.1","properties":[{"key":"ProteinId","value":"ENSP00000476320.1"},{"key":"GeneId","value":"ENSG00000160097.21"}],"isoformId":"Q8NAU1-3"},{"database":"Ensembl","id":"ENST00000710568.1","properties":[{"key":"ProteinId","value":"ENSP00000518350.1"},{"key":"GeneId","value":"ENSG00000160097.21"}],"isoformId":"Q8NAU1-5"},{"database":"GeneID","id":"252995","properties":[{"key":"Description","value":"-"}]},{"database":"KEGG","id":"hsa:252995","properties":[{"key":"Description","value":"-"}]},{"database":"UCSC","id":"uc001bwg.5","properties":[{"key":"OrganismName","value":"human"}],"isoformId":"Q8NAU1-5"},{"database":"AGR","id":"HGNC:20240","properties":[{"key":"Description","value":"-"}]},{"database":"ClinPGx","id":"PA134924607","properties":[{"key":"Description","value":"-"}]},{"database":"CTD","id":"252995","properties":[{"key":"Description","value":"-"}]},{"database":"DisGeNET","id":"252995","properties":[{"key":"Description","value":"-"}]},{"database":"GeneCards","id":"FNDC5","properties":[{"key":"Description","value":"-"}]},{"database":"HGNC","id":"HGNC:20240","properties":[{"key":"GeneName","value":"FNDC5"}]},{"database":"HPA","id":"ENSG00000160097","properties":[{"key":"ExpressionPatterns","value":"Group enriched (skeletal muscle, tongue)"}]},{"database":"MIM","id":"611906","properties":[{"key":"Type","value":"gene"}]},{"database":"OpenTargets","id":"ENSG00000160097","properties":[{"key":"Description","value":"-"}]},{"database":"VEuPathDB","id":"HostDB:ENSG00000160097","properties":[{"key":"Description","value":"-"}]},{"database":"eggNOG","id":"ENOG502QQCU","properties":[{"key":"ToxonomicScope","value":"Eukaryota"}]},{"database":"GeneTree","id":"ENSGT00390000004923","properties":[{"key":"Description","value":"-"}]},{"database":"HOGENOM","id":"CLU_089166_2_0_1","properties":[{"key":"Description","value":"-"}]},{"database":"InParanoid","id":"Q8NAU1","properties":[{"key":"Description","value":"-"}]},{"database":"OMA","id":"YFSCASL","properties":[{"key":"Fingerprint","value":"-"}]},{"database":"OrthoDB","id":"5843172at2759","properties":[{"key":"Description","value":"-"}]},{"database":"PAN-GO","id":"Q8NAU1","properties":[{"key":"Number of GO annotations","value":"3 GO annotations based on evolutionary models"}]},{"database":"PathwayCommons","id":"Q8NAU1","properties":[{"key":"Description","value":"-"}]},{"database":"SignaLink","id":"Q8NAU1","properties":[{"key":"Description","value":"-"}]},{"database":"Agora","id":"ENSG00000160097","properties":[{"key":"NominatedTarget","value":"-"}]},{"database":"BioGRID-ORCS","id":"252995","properties":[{"key":"hits","value":"5 hits in 968 CRISPR screens"}]},{"database":"ChiTaRS","id":"FNDC5","properties":[{"key":"OrganismName","value":"human"}]},{"database":"EvolutionaryTrace","id":"Q8NAU1","properties":[{"key":"Description","value":"-"}]},{"database":"GenomeRNAi","id":"252995","properties":[{"key":"Description","value":"-"}]},{"database":"Pharos","id":"Q8NAU1","properties":[{"key":"DevelopmentLevel","value":"Tbio"}]},{"database":"PRO","id":"PR:Q8NAU1","properties":[{"key":"Description","value":"-"}]},{"database":"Proteomes","id":"UP000005640","properties":[{"key":"Component","value":"Chromosome 1"}]},{"database":"RNAct","id":"Q8NAU1","properties":[{"key":"moleculeType","value":"protein"}]},{"database":"Bgee","id":"ENSG00000160097","properties":[{"key":"ExpressionPatterns","value":"Expressed in skeletal muscle tissue of biceps brachii and 142 other cell types or tissues"}]},{"database":"ExpressionAtlas","id":"Q8NAU1","properties":[{"key":"ExpressionPatterns","value":"baseline and differential"}]},{"database":"GO","id":"GO:0005783","properties":[{"key":"GoTerm","value":"C:endoplasmic reticulum"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0005576","properties":[{"key":"GoTerm","value":"C:extracellular region"},{"key":"GoEvidenceType","value":"EXP:UniProtKB"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22237023"}]},{"database":"GO","id":"GO:0005778","properties":[{"key":"GoTerm","value":"C:peroxisomal membrane"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0005886","properties":[{"key":"GoTerm","value":"C:plasma membrane"},{"key":"GoEvidenceType","value":"EXP:UniProtKB"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22237023"}]},{"database":"GO","id":"GO:0090336","properties":[{"key":"GoTerm","value":"P:positive regulation of brown fat cell differentiation"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0014850","properties":[{"key":"GoTerm","value":"P:response to muscle activity"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"CDD","id":"cd00063","properties":[{"key":"EntryName","value":"FN3"},{"key":"MatchStatus","value":"1"}]},{"database":"FunFam","id":"2.60.40.10:FF:000117","properties":[{"key":"EntryName","value":"Fibronectin type III domain containing 5"},{"key":"MatchStatus","value":"1"}]},{"database":"Gene3D","id":"2.60.40.10","properties":[{"key":"EntryName","value":"Immunoglobulins"},{"key":"MatchStatus","value":"1"}]},{"database":"InterPro","id":"IPR003961","properties":[{"key":"EntryName","value":"FN3_dom"}]},{"database":"InterPro","id":"IPR036116","properties":[{"key":"EntryName","value":"FN3_sf"}]},{"database":"InterPro","id":"IPR052120","properties":[{"key":"EntryName","value":"FNDC_type_III_4/5"}]},{"database":"InterPro","id":"IPR013783","properties":[{"key":"EntryName","value":"Ig-like_fold"}]},{"database":"PANTHER","id":"PTHR14470","properties":[{"key":"EntryName","value":"FIBRONECTIN TYPE III DOMAIN-CONTAINING PROTEIN"},{"key":"MatchStatus","value":"1"}]},{"database":"PANTHER","id":"PTHR14470:SF1","properties":[{"key":"EntryName","value":"FIBRONECTIN TYPE III DOMAIN-CONTAINING PROTEIN 5"},{"key":"MatchStatus","value":"1"}]},{"database":"Pfam","id":"PF00041","properties":[{"key":"EntryName","value":"fn3"},{"key":"MatchStatus","value":"1"}]},{"database":"SMART","id":"SM00060","properties":[{"key":"EntryName","value":"FN3"},{"key":"MatchStatus","value":"1"}]},{"database":"SUPFAM","id":"SSF49265","properties":[{"key":"EntryName","value":"Fibronectin type III"},{"key":"MatchStatus","value":"1"}]},{"database":"PROSITE","id":"PS50853","properties":[{"key":"EntryName","value":"FN3"},{"key":"MatchStatus","value":"1"}]}],"sequence":{"value":"MQAARGGAGRPERPGRPGRGPERERERPPGAGAASPCAAPGLPAGGATIHPGSPSAWPPRARAALRLWLGCVCFALVQADSPSAPVNVTVRHLKANSAVVSWDVLEDEVVIGFAISQQKKDVRMLRFIQEVNTTTRSCALWDLEEDTEYIVHVQAISIQGQSPASEPVLFKTPREAEKMASKNKDEVTMKEMGRNQQLRTGEVLIIVVVLFMWAGVIALFCRQYDIIKDNEPNNNKEKTKSASETSTPEHQGGGLLRSKI","length":260,"molWeight":28283,"crc64":"2277491F742547A6","md5":"CAC9C3024DC6DAC9358FBAE260B594E6"},"extraAttributes":{"countByCommentType":{"FUNCTION":1,"SUBUNIT":1,"SUBCELLULAR LOCATION":2,"ALTERNATIVE PRODUCTS":4,"TISSUE SPECIFICITY":1,"INDUCTION":2,"DOMAIN":1,"PTM":2,"MISCELLANEOUS":4,"CAUTION":2},"countByFeatureType":{"Chain":2,"Transmembrane":1,"Domain":1,"Region":2,"Motif":1,"Compositional bias":4,"Site":1,"Glycosylation":2,"Alternative sequence":4,"Mutagenesis":1,"Helix":3,"Beta strand":7,"Turn":1},"uniParcId":"UPI002644BF5A"}}