ERFE_MOUSE
ID ERFE_MOUSE Reviewed; 340 AA.
AC Q6PGN1; E3VWA0; Q8CE11;
DT 10-JUN-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 103.
DE RecName: Full=Erythroferrone;
DE AltName: Full=Complement C1q tumor necrosis factor-related protein 15;
DE AltName: Full=Myonectin;
DE Flags: Precursor;
GN Name=Erfe; Synonyms=C1qtnf15, Ctrp15, Fam132b;
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], FUNCTION, DIMERIZATION, INTERACTION WITH
RP C1QTNF2; C1QTNF5; C1QTNF10 AND C1QTNF12, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, DEVELOPMENTAL STAGE, INDUCTION, AND GLYCOSYLATION.
RC STRAIN=C57BL/6J;
RX PubMed=22351773; DOI=10.1074/jbc.m111.336834;
RA Seldin M.M., Peterson J.M., Byerly M.S., Wei Z., Wong G.W.;
RT "Myonectin (CTRP15), a novel myokine that links skeletal muscle to systemic
RT lipid homeostasis.";
RL J. Biol. Chem. 287:11968-11980(2012).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Head;
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].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J;
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 FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=24880340; DOI=10.1038/ng.2996;
RA Kautz L., Jung G., Valore E.V., Rivella S., Nemeth E., Ganz T.;
RT "Identification of erythroferrone as an erythroid regulator of iron
RT metabolism.";
RL Nat. Genet. 46:678-684(2014).
CC -!- FUNCTION: Iron-regulatory hormone that acts as an erythroid regulator
CC after hemorrhage: produced by erythroblasts following blood loss and
CC mediates suppression of hepcidin (HAMP) expression in the liver,
CC thereby promoting increased iron absorption and mobilization from
CC stores (PubMed:24880340). Promotes lipid uptake into adipocytes and
CC hepatocytes via transcriptional up-regulation of genes involved in
CC fatty acid uptake (PubMed:22351773). {ECO:0000269|PubMed:22351773,
CC ECO:0000269|PubMed:24880340}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. May form heteromeric complexes
CC with C1QTNF2 and C1QTNF12 and, to a lesser extent, with C1QTNF5 and
CC C1QTNF10. {ECO:0000269|PubMed:22351773}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:22351773,
CC ECO:0000269|PubMed:24880340}.
CC -!- TISSUE SPECIFICITY: Predominantly expressed in skeletal muscle and, at
CC much lower levels, in other tissues, including lung, eye, smooth
CC muscle, heart, brain and kidney. Within skeletal muscles, higher
CC expression levels in soleus as compared with plantaris. Found in blood
CC (at protein level). Following EPO treatment, only expressed in bone
CC marrow and spleen (PubMed:24880340). Females tend to have higher
CC circulating levels than males. Obese mice tend to have lower expression
CC and circulating levels as compared to lean animals.
CC {ECO:0000269|PubMed:22351773, ECO:0000269|PubMed:24880340}.
CC -!- DEVELOPMENTAL STAGE: In the myoblast C2C12 cell line, expression is
CC increased upon differentiation into myotubes.
CC {ECO:0000269|PubMed:22351773}.
CC -!- INDUCTION: Up-regulated by intracellular increase in cAMP levels, such
CC as those elicited by forskolin and epinephrine treatments, and increase
CC in calcium (ionomycine). Up-regulated by exercise in skeletal muscle
CC (at the mRNA level) and blood (at protein level). Drastically down-
CC regulated by fasting. Up-regulated in skeletal muscle by refeeding; the
CC extent of induction by refeeding may be dependent upon the muscle fiber
CC type, being much higher in soleus than in plantaris. Both glucose and
CC lipid are equally potent in this induction, in the absence of any gut-
CC derived hormones. Highly induced within 4 hours of bleeding
CC (PubMed:24880340). {ECO:0000269|PubMed:22351773,
CC ECO:0000269|PubMed:24880340}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:22351773}.
CC -!- DISRUPTION PHENOTYPE: Mice are viable and fertile without any abnormal
CC phenotypic features in normal conditions but show transient hemoglobin
CC deficit after hemorrhage and exhibit a delay in recovery from blood
CC loss. They also fail to suppress hepcidin rapidly.
CC {ECO:0000269|PubMed:24880340}.
CC -!- MISCELLANEOUS: Mice with thalassemia intermedia show high levels of
CC Erfe expression, contributing to the suppression of hepcidin and the
CC systemic iron overload characteristic of thalassemia.
CC {ECO:0000305|PubMed:24880340}.
CC -!- SIMILARITY: Belongs to the adipolin/erythroferrone family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC26362.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; HQ285249; ADP00570.1; -; mRNA.
DR EMBL; AK029264; BAC26362.1; ALT_FRAME; mRNA.
DR EMBL; CH466520; EDL40047.1; -; Genomic_DNA.
DR EMBL; BC056923; AAH56923.1; -; mRNA.
DR CCDS; CCDS48323.1; -.
DR RefSeq; NP_775571.2; NM_173395.2.
DR AlphaFoldDB; Q6PGN1; -.
DR STRING; 10090.ENSMUSP00000084073; -.
DR GlyGen; Q6PGN1; 4 sites.
DR PhosphoSitePlus; Q6PGN1; -.
DR MaxQB; Q6PGN1; -.
DR PaxDb; Q6PGN1; -.
DR PRIDE; Q6PGN1; -.
DR ProteomicsDB; 275469; -.
DR Antibodypedia; 77392; 4 antibodies from 4 providers.
DR DNASU; 227358; -.
DR Ensembl; ENSMUST00000086861; ENSMUSP00000084073; ENSMUSG00000047443.
DR GeneID; 227358; -.
DR KEGG; mmu:227358; -.
DR UCSC; uc007caj.1; mouse.
DR CTD; 151176; -.
DR MGI; MGI:3606476; Erfe.
DR VEuPathDB; HostDB:ENSMUSG00000047443; -.
DR eggNOG; ENOG502RNS4; Eukaryota.
DR GeneTree; ENSGT00940000162100; -.
DR HOGENOM; CLU_057344_1_1_1; -.
DR InParanoid; Q6PGN1; -.
DR OMA; DPRDTWM; -.
DR OrthoDB; 1462460at2759; -.
DR PhylomeDB; Q6PGN1; -.
DR TreeFam; TF331282; -.
DR BioGRID-ORCS; 227358; 2 hits in 70 CRISPR screens.
DR PRO; PR:Q6PGN1; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q6PGN1; protein.
DR Bgee; ENSMUSG00000047443; Expressed in primary oocyte and 44 other tissues.
DR ExpressionAtlas; Q6PGN1; baseline and differential.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0005179; F:hormone activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:MGI.
DR GO; GO:0006879; P:cellular iron ion homeostasis; IMP:UniProtKB.
DR GO; GO:0051649; P:establishment of localization in cell; IDA:MGI.
DR GO; GO:0015908; P:fatty acid transport; IDA:MGI.
DR GO; GO:0045721; P:negative regulation of gluconeogenesis; IBA:GO_Central.
DR GO; GO:2000193; P:positive regulation of fatty acid transport; IDA:MGI.
DR GO; GO:0046326; P:positive regulation of glucose import; IBA:GO_Central.
DR GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0019217; P:regulation of fatty acid metabolic process; IDA:MGI.
DR Gene3D; 2.60.120.40; -; 1.
DR InterPro; IPR001073; C1q_dom.
DR InterPro; IPR008983; Tumour_necrosis_fac-like_dom.
DR SUPFAM; SSF49842; SSF49842; 1.
DR PROSITE; PS50871; C1Q; 1.
PE 1: Evidence at protein level;
KW Disulfide bond; Glycoprotein; Hormone; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..340
FT /note="Erythroferrone"
FT /id="PRO_0000340251"
FT DOMAIN 185..340
FT /note="C1q"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00368"
FT REGION 30..63
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 79..112
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 141..161
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 43..57
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 98..112
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 144..160
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 229
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 281
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 292
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 319
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 36
FT /note="T -> M (in Ref. 2; BAC26362)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 340 AA; 36265 MW; 73E4D31896061E4A CRC64;
MASTRRPVGA RTLLACASLL AAMGLGVPES AEPVGTHARP QPPGAELPAP PANSPPEPTI
AHAHSVDPRD AWMLFVKQSD KGINSKRRSK ARRLKLGLPG PPGPPGPQGP PGPFIPSEVL
LKEFQLLLKG AVRQRESHLE HCTRDLTTPA SGSPSRVPAA QELDSQDPGA LLALLAATLA
QGPRAPRVEA AFHCRLRRDV QVDRRALHEL GIYYLPEVEG AFHRGPGLNL TSGQYTAPVA
GFYALAATLH VALTEQPRKG PTRPRDRLRL LICIQSLCQH NASLETVMGL ENSSELFTIS
VNGVLYLQAG HYTSVFLDNA SGSSLTVRSG SHFSAILLGL
