FNDC5_MOUSE
ID FNDC5_MOUSE Reviewed; 209 AA.
AC Q8K4Z2; Q9DB97;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Fibronectin type III domain-containing protein 5;
DE AltName: Full=Fibronectin type III repeat-containing protein 2;
DE AltName: Full=Peroxisomal protein;
DE Short=PeP;
DE Contains:
DE RecName: Full=Irisin;
DE Flags: Precursor;
GN Name=Fndc5; Synonyms=Frcp2, Pep;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RC STRAIN=BALB/cJ; TISSUE=Heart;
RX PubMed=12112469; DOI=10.1002/dvdy.10099;
RA Ferrer-Martinez A., Ruiz-Lozano P., Chien K.R.;
RT "Mouse PeP: a novel peroxisomal protein linked to myoblast differentiation
RT and development.";
RL Dev. Dyn. 224:154-167(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Cerebellum;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PROTEIN SEQUENCE OF 133-140, FUNCTION, INDUCTION, GLYCOSYLATION,
RP SUBCELLULAR LOCATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=22237023; DOI=10.1038/nature10777;
RA Bostrom P., Wu J., Jedrychowski M.P., Korde A., Ye L., Lo J.C.,
RA Rasbach K.A., Bostrom E.A., Choi J.H., Long J.Z., Kajimura S.,
RA Zingaretti M.C., Vind B.F., Tu H., Cinti S., Hojlund K., Gygi S.P.,
RA Spiegelman B.M.;
RT "A PGC1-alpha-dependent myokine that drives brown-fat-like development of
RT white fat and thermogenesis.";
RL Nature 481:463-468(2012).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=12384288; DOI=10.1016/s0378-1119(02)00828-4;
RA Teufel A., Malik N., Mukhopadhyay M., Westphal H.;
RT "Frcp1 and Frcp2, two novel fibronectin type III repeat containing genes.";
RL Gene 297:79-83(2002).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: [Irisin]: Mediates beneficial effects of muscular exercise.
CC Induces browning of white adipose tissue by stimulating UCP1
CC expression, at least in part, via the nuclear receptor PPARA.
CC {ECO:0000269|PubMed:22237023}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane
CC protein. Peroxisome membrane; Single-pass type I membrane protein.
CC Secreted. Note=Imported in peroxisomes through the PEX5 receptor
CC pathway.
CC -!- SUBCELLULAR LOCATION: [Irisin]: Secreted. Note=Detected in the blood of
CC individuals subjected to endurance exercise.
CC -!- TISSUE SPECIFICITY: In adult, it is highly expressed in skeletal
CC muscle, heart and brain. {ECO:0000269|PubMed:12112469,
CC ECO:0000269|PubMed:12384288}.
CC -!- DEVELOPMENTAL STAGE: During embryonic development, it is detected
CC almost exclusively in the skeletal muscle, and at lower level in brain.
CC In skeletal muscle, it is induced after myoblast differentiation, when
CC myotube formation is promoted. {ECO:0000269|PubMed:12112469}.
CC -!- INDUCTION: Up-regulated by muscular exercise. This effect can be
CC mediated, at least partly, by PPARGC1A. {ECO:0000269|PubMed:22237023}.
CC -!- PTM: The extracellular domain is cleaved and released from the cell
CC membrane.
CC -!- PTM: N-Glycosylated. {ECO:0000269|PubMed:22237023}.
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DR EMBL; AJ401376; CAC82194.1; -; mRNA.
DR EMBL; AK005096; BAB23815.1; -; mRNA.
DR EMBL; AL606977; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC109183; AAI09184.1; -; mRNA.
DR EMBL; BC109184; AAI09185.1; -; mRNA.
DR CCDS; CCDS18683.1; -.
DR RefSeq; NP_081678.1; NM_027402.4.
DR AlphaFoldDB; Q8K4Z2; -.
DR SMR; Q8K4Z2; -.
DR BioGRID; 239035; 1440.
DR IntAct; Q8K4Z2; 1.
DR MINT; Q8K4Z2; -.
DR STRING; 10090.ENSMUSP00000099660; -.
DR GlyGen; Q8K4Z2; 2 sites.
DR iPTMnet; Q8K4Z2; -.
DR PhosphoSitePlus; Q8K4Z2; -.
DR PaxDb; Q8K4Z2; -.
DR PRIDE; Q8K4Z2; -.
DR ProteomicsDB; 271778; -.
DR Antibodypedia; 54866; 207 antibodies from 28 providers.
DR DNASU; 384061; -.
DR Ensembl; ENSMUST00000102600; ENSMUSP00000099660; ENSMUSG00000001334.
DR GeneID; 384061; -.
DR KEGG; mmu:384061; -.
DR UCSC; uc008uwe.1; mouse.
DR CTD; 252995; -.
DR MGI; MGI:1917614; Fndc5.
DR VEuPathDB; HostDB:ENSMUSG00000001334; -.
DR eggNOG; ENOG502QQCU; Eukaryota.
DR GeneTree; ENSGT00390000004923; -.
DR HOGENOM; CLU_089166_1_0_1; -.
DR InParanoid; Q8K4Z2; -.
DR OMA; TTHSCAL; -.
DR OrthoDB; 1198350at2759; -.
DR PhylomeDB; Q8K4Z2; -.
DR TreeFam; TF325415; -.
DR BioGRID-ORCS; 384061; 2 hits in 74 CRISPR screens.
DR ChiTaRS; Fndc5; mouse.
DR PRO; PR:Q8K4Z2; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q8K4Z2; protein.
DR Bgee; ENSMUSG00000001334; Expressed in interventricular septum and 179 other tissues.
DR Genevisible; Q8K4Z2; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005778; C:peroxisomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005179; F:hormone activity; IEA:UniProtKB-KW.
DR GO; GO:0090336; P:positive regulation of brown fat cell differentiation; IDA:UniProtKB.
DR GO; GO:0014850; P:response to muscle activity; IDA:UniProtKB.
DR CDD; cd00063; FN3; 1.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR003961; FN3_dom.
DR InterPro; IPR036116; FN3_sf.
DR InterPro; IPR032073; FNDC5_C.
DR InterPro; IPR013783; Ig-like_fold.
DR Pfam; PF16066; DUF4808; 1.
DR Pfam; PF00041; fn3; 1.
DR SMART; SM00060; FN3; 1.
DR SUPFAM; SSF49265; SSF49265; 1.
DR PROSITE; PS50853; FN3; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Direct protein sequencing; Glycoprotein; Hormone; Membrane;
KW Peroxisome; Reference proteome; Secreted; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..28
FT /evidence="ECO:0000255"
FT CHAIN 29..209
FT /note="Fibronectin type III domain-containing protein 5"
FT /id="PRO_0000328972"
FT CHAIN 29..140
FT /note="Irisin"
FT /id="PRO_0000415858"
FT TOPO_DOM 29..149
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 150..170
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 171..209
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 33..124
FT /note="Fibronectin type-III"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT REGION 179..209
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 207..209
FT /note="Microbody targeting signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 179..193
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 36
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305|PubMed:22237023"
FT CARBOHYD 81
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305|PubMed:22237023"
FT CONFLICT 13..14
FT /note="AL -> VV (in Ref. 2; BAB23815)"
FT /evidence="ECO:0000305"
FT CONFLICT 64
FT /note="I -> L (in Ref. 2; BAB23815)"
FT /evidence="ECO:0000305"
FT CONFLICT 124
FT /note="E -> A (in Ref. 2; BAB23815)"
FT /evidence="ECO:0000305"
FT CONFLICT 130
FT /note="S -> P (in Ref. 2; BAB23815)"
FT /evidence="ECO:0000305"
FT CONFLICT 158
FT /note="V -> C (in Ref. 2; BAB23815)"
FT /evidence="ECO:0000305"
FT CONFLICT 171
FT /note="R -> A (in Ref. 2; BAB23815)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 209 AA; 23321 MW; 86A33DE8E4616507 CRC64;
MPPGPCAWPP RAALRLWLGC VCFALVQADS PSAPVNVTVR HLKANSAVVS WDVLEDEVVI
GFAISQQKKD VRMLRFIQEV NTTTRSCALW DLEEDTEYIV HVQAISIQGQ SPASEPVLFK
TPREAEKMAS KNKDEVTMKE MGRNQQLRTG EVLIIVVVLF MWAGVIALFC RQYDIIKDNE
PNNNKEKTKS ASETSTPEHQ GGGLLRSKI
