TFR2_MOUSE
ID TFR2_MOUSE Reviewed; 798 AA.
AC Q9JKX3; Q920I6; Q99MQ9; Q9CPT2;
DT 11-FEB-2002, integrated into UniProtKB/Swiss-Prot.
DT 11-FEB-2002, sequence version 2.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Transferrin receptor protein 2;
DE Short=TfR2;
GN Name=Tfr2; Synonyms=Trfr2;
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] (ISOFORM 1).
RC TISSUE=Embryo;
RX PubMed=10681454; DOI=10.1073/pnas.040548097;
RA Fleming R.E., Migas M.C., Holden C.C., Waheed A., Britton R.S., Tomatsu S.,
RA Bacon B.R., Sly W.S.;
RT "Transferrin receptor 2: continued expression in mouse liver in the face of
RT iron overload and in hereditary hemochromatosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:2214-2219(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Erythroleukemia;
RX PubMed=11535534; DOI=10.1182/blood.v98.6.1949;
RA Kawabata H., Germain R.S., Ikezoe T., Tong X., Green E.M., Gombart A.F.,
RA Koeffler H.P.;
RT "Regulation of expression of murine transferrin receptor 2.";
RL Blood 98:1949-1954(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Liver;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
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 NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-278.
RC STRAIN=129/Sv;
RX PubMed=11239002; DOI=10.1093/nar/29.6.1352;
RA Wilson M.D., Riemer C., Martindale D.W., Schnupf P., Boright A.P.,
RA Cheung T.L., Hardy D.M., Schwartz S., Scherer S.W., Tsui L.-C., Miller W.,
RA Koop B.F.;
RT "Comparative analysis of the gene-dense ACHE/TFR2 region on human
RT chromosome 7q22 with the orthologous region on mouse chromosome 5.";
RL Nucleic Acids Res. 29:1352-1365(2001).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
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: Mediates cellular uptake of transferrin-bound iron in a non-
CC iron dependent manner. May be involved in iron metabolism, hepatocyte
CC function and erythrocyte differentiation.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type II membrane
CC protein.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9JKX3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9JKX3-2; Sequence=VSP_005357, VSP_005358;
CC Name=3;
CC IsoId=Q9JKX3-3; Sequence=VSP_005356;
CC -!- TISSUE SPECIFICITY: Predominantly expressed in liver. Also expressed in
CC kidney, spleen, brain, lung, heart and muscle with very low expression
CC in kidney, muscle and heart.
CC -!- DEVELOPMENTAL STAGE: First expressed between embryo days 8 and 11. In
CC the liver, expression increases during development from embryo day 13
CC to adulthood while, in the spleen, levels remain constant throughout
CC development.
CC -!- INDUCTION: Down-regulated during erythrocyte differentiation.
CC Expression unchanged by cellular iron status.
CC -!- MISCELLANEOUS: [Isoform 2]: Lacks most of the extracellular domain.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the peptidase M28 family. M28B subfamily.
CC {ECO:0000305}.
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DR EMBL; AF222895; AAF37272.1; -; mRNA.
DR EMBL; AF207741; AAL05976.1; -; mRNA.
DR EMBL; AF207742; AAL05977.1; -; Genomic_DNA.
DR EMBL; AK004965; BAB23705.1; -; mRNA.
DR EMBL; AK004848; BAB23614.1; -; mRNA.
DR EMBL; BC013654; AAH13654.1; -; mRNA.
DR EMBL; AF312033; AAK28830.1; -; Genomic_DNA.
DR CCDS; CCDS39333.1; -. [Q9JKX3-1]
DR RefSeq; NP_001276436.1; NM_001289507.1. [Q9JKX3-1]
DR RefSeq; NP_001276438.1; NM_001289509.1. [Q9JKX3-1]
DR RefSeq; NP_001276440.1; NM_001289511.1. [Q9JKX3-1]
DR RefSeq; NP_056614.3; NM_015799.4. [Q9JKX3-1]
DR RefSeq; XP_006504656.1; XM_006504593.3. [Q9JKX3-1]
DR RefSeq; XP_006504657.1; XM_006504594.3. [Q9JKX3-1]
DR RefSeq; XP_011239249.1; XM_011240947.2.
DR AlphaFoldDB; Q9JKX3; -.
DR SMR; Q9JKX3; -.
DR BioGRID; 206097; 2.
DR IntAct; Q9JKX3; 1.
DR MINT; Q9JKX3; -.
DR STRING; 10090.ENSMUSP00000031729; -.
DR MEROPS; M28.973; -.
DR GlyGen; Q9JKX3; 3 sites.
DR iPTMnet; Q9JKX3; -.
DR PhosphoSitePlus; Q9JKX3; -.
DR jPOST; Q9JKX3; -.
DR MaxQB; Q9JKX3; -.
DR PaxDb; Q9JKX3; -.
DR PeptideAtlas; Q9JKX3; -.
DR PRIDE; Q9JKX3; -.
DR ProteomicsDB; 262893; -. [Q9JKX3-1]
DR ProteomicsDB; 262894; -. [Q9JKX3-2]
DR ProteomicsDB; 262895; -. [Q9JKX3-3]
DR Antibodypedia; 2306; 215 antibodies from 28 providers.
DR DNASU; 50765; -.
DR Ensembl; ENSMUST00000031729; ENSMUSP00000031729; ENSMUSG00000029716. [Q9JKX3-1]
DR Ensembl; ENSMUST00000196471; ENSMUSP00000142814; ENSMUSG00000029716. [Q9JKX3-1]
DR Ensembl; ENSMUST00000198783; ENSMUSP00000142502; ENSMUSG00000029716. [Q9JKX3-1]
DR Ensembl; ENSMUST00000198866; ENSMUSP00000142720; ENSMUSG00000029716. [Q9JKX3-1]
DR Ensembl; ENSMUST00000199054; ENSMUSP00000142478; ENSMUSG00000029716. [Q9JKX3-1]
DR GeneID; 50765; -.
DR KEGG; mmu:50765; -.
DR UCSC; uc009acv.2; mouse. [Q9JKX3-1]
DR CTD; 7036; -.
DR MGI; MGI:1354956; Tfr2.
DR VEuPathDB; HostDB:ENSMUSG00000029716; -.
DR eggNOG; KOG2195; Eukaryota.
DR GeneTree; ENSGT01030000234598; -.
DR InParanoid; Q9JKX3; -.
DR OMA; FSQGPHK; -.
DR OrthoDB; 804230at2759; -.
DR PhylomeDB; Q9JKX3; -.
DR TreeFam; TF312981; -.
DR Reactome; R-MMU-917977; Transferrin endocytosis and recycling.
DR BioGRID-ORCS; 50765; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Tfr2; mouse.
DR PRO; PR:Q9JKX3; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q9JKX3; protein.
DR Bgee; ENSMUSG00000029716; Expressed in left lobe of liver and 143 other tissues.
DR ExpressionAtlas; Q9JKX3; baseline and differential.
DR Genevisible; Q9JKX3; MM.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:MGI.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:MGI.
DR GO; GO:1990712; C:HFE-transferrin receptor complex; IDA:BHF-UCL.
DR GO; GO:0016021; C:integral component of membrane; ISA:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:MGI.
DR GO; GO:0039706; F:co-receptor binding; ISO:MGI.
DR GO; GO:0004998; F:transferrin receptor activity; ISO:MGI.
DR GO; GO:0006953; P:acute-phase response; IEA:Ensembl.
DR GO; GO:0006879; P:cellular iron ion homeostasis; TAS:MGI.
DR GO; GO:0071281; P:cellular response to iron ion; ISO:MGI.
DR GO; GO:0140298; P:endocytic iron import into cell; ISO:MGI.
DR GO; GO:0055072; P:iron ion homeostasis; IMP:MGI.
DR GO; GO:0045807; P:positive regulation of endocytosis; ISO:MGI.
DR GO; GO:0090277; P:positive regulation of peptide hormone secretion; ISO:MGI.
DR GO; GO:1903319; P:positive regulation of protein maturation; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0006898; P:receptor-mediated endocytosis; ISO:MGI.
DR GO; GO:0010039; P:response to iron ion; ISO:MGI.
DR GO; GO:0033572; P:transferrin transport; ISO:MGI.
DR CDD; cd02128; PA_TfR; 1.
DR Gene3D; 1.20.930.40; -; 1.
DR InterPro; IPR003137; PA_domain.
DR InterPro; IPR007484; Peptidase_M28.
DR InterPro; IPR039373; Peptidase_M28B.
DR InterPro; IPR036757; TFR-like_dimer_dom_sf.
DR InterPro; IPR037324; TfR1/2_PA.
DR PANTHER; PTHR10404; PTHR10404; 1.
DR Pfam; PF02225; PA; 1.
DR Pfam; PF04389; Peptidase_M28; 1.
DR SUPFAM; SSF47672; SSF47672; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cytoplasm; Disulfide bond;
KW Glycoprotein; Membrane; Receptor; Reference proteome; Signal-anchor;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..798
FT /note="Transferrin receptor protein 2"
FT /id="PRO_0000174137"
FT TOPO_DOM 1..81
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 82..102
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 103..798
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT MOTIF 23..26
FT /note="Endocytosis signal"
FT /evidence="ECO:0000255"
FT CARBOHYD 235
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 334
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 535
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 106
FT /note="Interchain"
FT /evidence="ECO:0000255"
FT DISULFID 109
FT /note="Interchain"
FT /evidence="ECO:0000255"
FT VAR_SEQ 12..93
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:11535534"
FT /id="VSP_005356"
FT VAR_SEQ 237
FT /note="T -> TVRFPGWGAHHVLIG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11535534"
FT /id="VSP_005357"
FT VAR_SEQ 238..798
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11535534"
FT /id="VSP_005358"
FT CONFLICT 25
FT /note="R -> P (in Ref. 2; AAL05977)"
FT /evidence="ECO:0000305"
FT CONFLICT 42
FT /note="G -> V (in Ref. 2; AAL05977 and 5; AAK28830)"
FT /evidence="ECO:0000305"
FT CONFLICT 103
FT /note="R -> P (in Ref. 2; AAL05977)"
FT /evidence="ECO:0000305"
FT CONFLICT 151
FT /note="T -> N (in Ref. 4; AAH13654)"
FT /evidence="ECO:0000305"
FT CONFLICT 248
FT /note="S -> L (in Ref. 2; AAL05976)"
FT /evidence="ECO:0000305"
FT CONFLICT 287
FT /note="A -> V (in Ref. 2; AAL05976)"
FT /evidence="ECO:0000305"
FT CONFLICT 595
FT /note="K -> E (in Ref. 1; AAF37272)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 798 AA; 88402 MW; FA6161FE3FFF2AA4 CRC64;
MEQRWGLLRR VQQWSPRPSQ TIYRRVEGPQ LEHLEEEDRE EGAELPAQFC PMELKGPEHL
GSCPGRSIPI PWAAAGRKAA PYLVLITLLI FTGAFLLGYV AFRGSCQACG DSVLVVDEDV
NPEDSGRTTL YWSDLQAMFL RFLGEGRMED TIRLTSLRER VAGSARMATL VQDILDKLSR
QKLDHVWTDT HYVGLQFPDP AHANTLHWVD ADGSVQEQLP LEDPEVYCPY SATGNATGKL
VYAHYGRSED LQDLKAKGVE LAGSLLLVRV GITSFAQKVA VAQDFGAQGV LIYPDPSDFS
QDPHKPGLSS HQAVYGHVHL GTGDPYTPGF PSFNQTQFPP VESSGLPSIP AQPISADIAD
QLLRKLTGPV APQEWKGHLS GSPYRLGPGP DLRLVVNNHR VSTPISNIFA CIEGFAEPDH
YVVIGAQRDA WGPGAAKSAV GTAILLELVR TFSSMVSNGF RPRRSLLFIS WDGGDFGSVG
ATEWLEGYLS VLHLKAVVYV SLDNSVLGDG KFHAKTSPLL VSLIENILKQ VDSPNHSGQT
LYEQVALTHP SWDAEVIQPL PMDSSAYSFT AFAGVPAVEF SFMEDDRVYP FLHTKEDTYE
NLHKMLRGRL PAVVQAVAQL AGQLLIRLSH DHLLPLDFGR YGDVVLRHIG NLNEFSGDLK
ERGLTLQWVY SARGDYIRAA EKLRKEIYSS ERNDERLMRM YNVRIMRVEF YFLSQYVSPA
DSPFRHIFLG QGDHTLGALV DHLRMLRADG SGAASSRLTA GLGFQESRFR RQLALLTWTL
QGAANALSGD VWNIDNNF
