FNDC4_MOUSE
ID FNDC4_MOUSE Reviewed; 231 AA.
AC Q3TR08; Q810E5; Q9CYY4;
DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Fibronectin type III domain-containing protein 4;
DE AltName: Full=Fibronectin type III repeat-containing protein 1;
DE Flags: Precursor;
GN Name=Fndc4; Synonyms=Fnmp1, Frcp1;
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 [GENOMIC DNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RC STRAIN=129;
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 [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 FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION BY INFLAMMATION.
RX PubMed=27066907; DOI=10.1038/ncomms11314;
RA Bosma M., Gerling M., Pasto J., Georgiadi A., Graham E., Shilkova O.,
RA Iwata Y., Almer S., Soederman J., Toftgaard R., Wermeling F.,
RA Bostroem E.A., Bostroem P.A.;
RT "FNDC4 acts as an anti-inflammatory factor on macrophages and improves
RT colitis in mice.";
RL Nat. Commun. 7:11314-11314(2016).
CC -!- FUNCTION: Acts as an anti-inflammatory factor in the intestine and
CC colon. Binds to and acts on macrophages to down-regulate pro-
CC inflammatory gene expression. Affects key macrophage functions,
CC including phagocytosis, by down-regulating many key pathways for
CC macrophage activation, partly via by STAT3 activation and signaling.
CC May be required to dampen the immunological response in colitis.
CC {ECO:0000269|PubMed:27066907}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000305}. Secreted {ECO:0000269|PubMed:27066907}.
CC Note=The N-terminus is probably cleaved to release a secreted
CC extracellular portion of the protein. {ECO:0000269|PubMed:27066907}.
CC -!- TISSUE SPECIFICITY: Highly expressed in adult liver and brain tissues.
CC {ECO:0000269|PubMed:12384288}.
CC -!- DEVELOPMENTAL STAGE: During embryo development, expressed in the brain.
CC {ECO:0000269|PubMed:12384288}.
CC -!- INDUCTION: Up-regulated in the context of tissue inflammation.
CC {ECO:0000269|PubMed:27066907}.
CC -!- MISCELLANEOUS: Therapeutic delivery of FNDC4 reduces the disease
CC severity of chemical-induced colitis in mice.
CC {ECO:0000269|PubMed:27066907}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAO85424.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF466728; AAO85424.1; ALT_INIT; Genomic_DNA.
DR EMBL; AK013203; BAB28710.2; -; mRNA.
DR EMBL; AK163183; BAE37223.1; -; mRNA.
DR CCDS; CCDS19181.1; -.
DR RefSeq; NP_071869.2; NM_022424.5.
DR RefSeq; XP_006504107.1; XM_006504044.2.
DR AlphaFoldDB; Q3TR08; -.
DR SMR; Q3TR08; -.
DR STRING; 10090.ENSMUSP00000127404; -.
DR GlyGen; Q3TR08; 2 sites.
DR iPTMnet; Q3TR08; -.
DR PhosphoSitePlus; Q3TR08; -.
DR PaxDb; Q3TR08; -.
DR PRIDE; Q3TR08; -.
DR ProteomicsDB; 267607; -.
DR Antibodypedia; 28574; 287 antibodies from 22 providers.
DR DNASU; 64339; -.
DR Ensembl; ENSMUST00000041266; ENSMUSP00000047185; ENSMUSG00000038552.
DR Ensembl; ENSMUST00000172435; ENSMUSP00000127404; ENSMUSG00000038552.
DR GeneID; 64339; -.
DR KEGG; mmu:64339; -.
DR UCSC; uc008wyd.1; mouse.
DR CTD; 64838; -.
DR MGI; MGI:1917195; Fndc4.
DR VEuPathDB; HostDB:ENSMUSG00000038552; -.
DR eggNOG; ENOG502QQ99; Eukaryota.
DR GeneTree; ENSGT00390000004923; -.
DR HOGENOM; CLU_089166_0_0_1; -.
DR InParanoid; Q3TR08; -.
DR OMA; PMGARQK; -.
DR OrthoDB; 1198350at2759; -.
DR PhylomeDB; Q3TR08; -.
DR TreeFam; TF325415; -.
DR BioGRID-ORCS; 64339; 3 hits in 71 CRISPR screens.
DR ChiTaRS; Fndc4; mouse.
DR PRO; PR:Q3TR08; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q3TR08; protein.
DR Bgee; ENSMUSG00000038552; Expressed in motor neuron and 198 other tissues.
DR ExpressionAtlas; Q3TR08; baseline and differential.
DR Genevisible; Q3TR08; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IDA:UniProtKB.
DR GO; GO:0071559; P:response to transforming growth factor beta; IEA:Ensembl.
DR CDD; cd00063; FN3; 1.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR003961; FN3_dom.
DR InterPro; IPR036116; FN3_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR Pfam; PF00041; fn3; 1.
DR SMART; SM00060; FN3; 1.
DR SUPFAM; SSF49265; SSF49265; 1.
DR PROSITE; PS50853; FN3; 1.
PE 2: Evidence at transcript level;
KW Glycoprotein; Membrane; Reference proteome; Secreted; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..40
FT /evidence="ECO:0000255"
FT CHAIN 41..231
FT /note="Fibronectin type III domain-containing protein 4"
FT /id="PRO_0000271380"
FT TOPO_DOM 41..163
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 164..184
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 185..231
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 43..136
FT /note="Fibronectin type-III"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT REGION 118..156
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 193..231
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 211..231
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 48
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 143
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 126
FT /note="G -> A (in Ref. 1; BAB28710)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 231 AA; 24933 MW; ABCC097E5251F14A CRC64;
MPLAPPANSV ETMASLMPLS PYLSPTVLLL VSCDLGFVRA DRPPSPVNVT VTHLRANSAT
VSWDVPEGNI VIGYSISQQR QNGPGQRVIR EVNTTTRACA LWGLAEDSDY TVQVRSIGLR
GESPPGPRVH FRTLKGSDRL PSNSSSPGDI TVEGLDGERP LQTGEVVIIV VVLLMWAAVI
GLFCRQYDII KDNDSNNNPK EKGKGPEQSP QGRPVGTTRQ KKSPSINTID V
