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   24-JAN-2024, entry version 172.
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.ENSMUSP00000142720; -.
DR   MEROPS; M28.973; -.
DR   GlyCosmos; Q9JKX3; 3 sites, No reported glycans.
DR   GlyGen; Q9JKX3; 3 sites.
DR   iPTMnet; Q9JKX3; -.
DR   PhosphoSitePlus; Q9JKX3; -.
DR   SwissPalm; Q9JKX3; -.
DR   jPOST; Q9JKX3; -.
DR   MaxQB; Q9JKX3; -.
DR   PaxDb; 10090-ENSMUSP00000031729; -.
DR   PeptideAtlas; Q9JKX3; -.
DR   ProteomicsDB; 262893; -. [Q9JKX3-1]
DR   ProteomicsDB; 262894; -. [Q9JKX3-2]
DR   ProteomicsDB; 262895; -. [Q9JKX3-3]
DR   Antibodypedia; 2306; 268 antibodies from 28 providers.
DR   DNASU; 50765; -.
DR   Ensembl; ENSMUST00000031729.13; ENSMUSP00000031729.9; ENSMUSG00000029716.14. [Q9JKX3-1]
DR   Ensembl; ENSMUST00000196471.5; ENSMUSP00000142814.2; ENSMUSG00000029716.14. [Q9JKX3-1]
DR   Ensembl; ENSMUST00000198783.5; ENSMUSP00000142502.2; ENSMUSG00000029716.14. [Q9JKX3-1]
DR   Ensembl; ENSMUST00000198866.5; ENSMUSP00000142720.2; ENSMUSG00000029716.14. [Q9JKX3-1]
DR   Ensembl; ENSMUST00000199054.5; ENSMUSP00000142478.2; ENSMUSG00000029716.14. [Q9JKX3-1]
DR   GeneID; 50765; -.
DR   KEGG; mmu:50765; -.
DR   UCSC; uc009acv.2; mouse. [Q9JKX3-1]
DR   AGR; MGI:1354956; -.
DR   CTD; 7036; -.
DR   MGI; MGI:1354956; Tfr2.
DR   VEuPathDB; HostDB:ENSMUSG00000029716; -.
DR   eggNOG; KOG2195; Eukaryota.
DR   GeneTree; ENSGT01030000234598; -.
DR   InParanoid; Q9JKX3; -.
DR   OMA; QVVFNNH; -.
DR   OrthoDB; 2428249at2759; -.
DR   PhylomeDB; Q9JKX3; -.
DR   TreeFam; TF312981; -.
DR   Reactome; R-MMU-917977; Transferrin endocytosis and recycling.
DR   BioGRID-ORCS; 50765; 1 hit in 79 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 146 other cell types or tissues.
DR   ExpressionAtlas; Q9JKX3; baseline and differential.
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:0016020; C:membrane; ISA:MGI.
DR   GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR   GO; GO:0098794; C:postsynapse; IDA:SynGO.
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:0071281; P:cellular response to iron ion; ISO:MGI.
DR   GO; GO:0140298; P:endocytic iron import into cell; ISO:MGI.
DR   GO; GO:0006879; P:intracellular iron ion homeostasis; ISO:MGI.
DR   GO; GO:0060586; P:multicellular organismal-level 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:0099072; P:regulation of postsynaptic membrane neurotransmitter receptor levels; IDA:SynGO.
DR   GO; GO:0010039; P:response to iron ion; ISO:MGI.
DR   GO; GO:0033572; P:transferrin transport; ISO:MGI.
DR   CDD; cd09848; M28_TfR; 1.
DR   CDD; cd02128; PA_TfR; 1.
DR   Gene3D; 3.50.30.30; -; 1.
DR   Gene3D; 1.20.930.40; Transferrin receptor-like, dimerisation domain; 1.
DR   Gene3D; 3.40.630.10; Zn peptidases; 1.
DR   InterPro; IPR046450; PA_dom_sf.
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; N-ACETYLATED-ALPHA-LINKED ACIDIC DIPEPTIDASE; 1.
DR   PANTHER; PTHR10404:SF33; TRANSFERRIN RECEPTOR PROTEIN 2; 1.
DR   Pfam; PF02225; PA; 1.
DR   Pfam; PF04389; Peptidase_M28; 1.
DR   SUPFAM; SSF52025; PA domain; 1.
DR   SUPFAM; SSF47672; Transferrin receptor-like dimerisation domain; 1.
DR   SUPFAM; SSF53187; Zn-dependent exopeptidases; 1.
DR   Genevisible; Q9JKX3; MM.
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
//