RBCC Red Blood Cell Collection

TF [Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Serotransferrin; Transferrin (Beta-1 metal-binding globulin; Siderophilin; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)

hRBCD IPI00022463
IPI00022463 transferrin precursor transferrin precursor membrane n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a 5 extracellular binds RBC n/a found at its expected molecular weight found at molecular weight

UniProt P02787
ID TRFE_HUMAN Reviewed; 698 AA.
AC P02787; O43890; Q1HBA5; Q9NQB8; Q9UHV0;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
read moreDT 30-NOV-2010, sequence version 3.
DT 22-JAN-2014, entry version 180.
DE RecName: Full=Serotransferrin;
DE Short=Transferrin;
DE AltName: Full=Beta-1 metal-binding globulin;
DE AltName: Full=Siderophilin;
DE Flags: Precursor;
GN Name=TF; ORFNames=PRO1400;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS TF*B2; TF*CHI; TF*D1 AND
RP VAL-448.
RX PubMed=6585826; DOI=10.1073/pnas.81.9.2752;
RA Yang F., Lum J.B., McGill J.R., Moore C.M., Naylor S.L.,
RA van Bragt P.H., Baldwin W.D., Bowman B.H.;
RT "Human transferrin: cDNA characterization and chromosomal
RT localization.";
RL Proc. Natl. Acad. Sci. U.S.A. 81:2752-2756(1984).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3678832; DOI=10.1016/0378-1119(87)90163-6;
RA Schaeffer E., Lucero M.A., Jeltsch J.-M., Py M.-C., Levin M.J.,
RA Chambon P., Cohen G.N., Zakin M.M.;
RT "Complete structure of the human transferrin gene. Comparison with
RT analogous chicken gene and human pseudogene.";
RL Gene 56:109-116(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT VAL-448.
RC TISSUE=Liver;
RX PubMed=1809186; DOI=10.1111/j.1749-6632.1991.tb18573.x;
RA Hershberger C.L., Larson J.L., Arnold B., Rosteck P.R. Jr.,
RA Williams P., Dehoff B., Dunn P., O'Neal K.L., Riemen M.W., Tice P.A.;
RT "A cloned gene for human transferrin.";
RL Ann. N. Y. Acad. Sci. 646:140-154(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-448 AND ATRAF
RP PRO-477.
RX PubMed=11110675;
RA Beutler E., Gelbart T., Lee P.L., Trevino R., Fernandez M.A.,
RA Fairbanks V.F.;
RT "Molecular characterization of a case of atransferrinemia.";
RL Blood 96:4071-4074(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ARG-55; SER-277;
RP GLY-296; VAL-448 AND SER-589.
RG SeattleSNPs variation discovery resource;
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT VAL-448.
RG NHLBI resequencing and genotyping service (RS&G;);
RL Submitted (MAY-2006) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R.,
RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J.,
RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT VAL-448.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-448.
RC TISSUE=Brain;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-72 AND 291-300.
RX PubMed=3106157; DOI=10.1016/0378-1119(86)90277-5;
RA Adrian G.S., Korinek B.W., Bowman B.H., Yang F.;
RT "The human transferrin gene: 5' region contains conserved sequences
RT which match the control elements regulated by heavy metals,
RT glucocorticoids and acute phase reaction.";
RL Gene 49:167-175(1986).
RN [11]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-14.
RX PubMed=3786138; DOI=10.1093/nar/14.21.8692;
RA Lucero M.A., Schaeffer E., Cohen G.N., Zakin M.M.;
RT "The 5' region of the human transferrin gene: structure and potential
RT regulatory sites.";
RL Nucleic Acids Res. 14:8692-8692(1986).
RN [12]
RP PROTEIN SEQUENCE OF 20-698, AND VARIANT VAL-448.
RX PubMed=6833213;
RA McGillivray R.T.A., Mendez E., Shewale J.G., Sinha S.K.,
RA Lineback-Zins J., Brew K.;
RT "The primary structure of human serum transferrin. The structures of
RT seven cyanogen bromide fragments and the assembly of the complete
RT structure.";
RL J. Biol. Chem. 258:3543-3553(1983).
RN [13]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 45-72.
RX PubMed=10931525;
RX DOI=10.1002/1097-4547(20000815)61:4<388::AID-JNR5>3.0.CO;2-Q;
RA de Arriba Zerpa G.A., Saleh M.-C., Fernandez P.M., Guillou F.,
RA Espinosa de los Monteros A., de Vellis J., Zakin M.M., Baron B.;
RT "Alternative splicing prevents transferrin secretion during
RT differentiation of a human oligodendrocyte cell line.";
RL J. Neurosci. Res. 61:388-395(2000).
RN [14]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 73-698, AND VARIANT VAL-448.
RX PubMed=3858812; DOI=10.1073/pnas.82.10.3149;
RA Park I., Schaeffer E., Sidoli A., Baralle F.E., Cohen G.N.,
RA Zakin M.M.;
RT "Organization of the human transferrin gene: direct evidence that it
RT originated by gene duplication.";
RL Proc. Natl. Acad. Sci. U.S.A. 82:3149-3153(1985).
RN [15]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 99-698, AND VARIANT VAL-448.
RC TISSUE=Fetal liver;
RA Zhang C., Yu Y., Zhang S., Wei H., Zhou G., Bi J., Zhang Y., Liu M.,
RA He F.;
RT "Functional prediction of the coding sequences of 33 new genes deduced
RT by analysis of cDNA clones from human fetal liver.";
RL Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases.
RN [16]
RP PROTEIN SEQUENCE OF 108-121; 259-273; 332-343; 374-384; 434-452;
RP 454-464; 495-508; 531-541; 577-600 AND 684-696, MASS SPECTROMETRY, AND
RP VARIANT VAL-448.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [17]
RP PROTEIN SEQUENCE OF 263-266; 454-458; 531-538 AND 589-595.
RC TISSUE=Heart;
RX PubMed=7498159; DOI=10.1002/elps.11501601192;
RA Kovalyov L.I., Shishkin S.S., Efimochkin A.S., Kovalyova M.A.,
RA Ershova E.S., Egorov T.A., Musalyamov A.K.;
RT "The major protein expression profile and two-dimensional protein
RT database of human heart.";
RL Electrophoresis 16:1160-1169(1995).
RN [18]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 422-698, AND VARIANT VAL-448.
RX PubMed=6322780; DOI=10.1016/0006-291X(84)91648-6;
RA Uzan G., Frain M., Park I., Besmond C., Maessen G., Trepat J.S.,
RA Zakin M.M., Kahn A.;
RT "Molecular cloning and sequence analysis of cDNA for human
RT transferrin.";
RL Biochem. Biophys. Res. Commun. 119:273-281(1984).
RN [19]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 564-624, AND VARIANTS TF*C2 AND SER-589.
RC TISSUE=Brain;
RX PubMed=9272172; DOI=10.1007/s004390050533;
RA Namekata K., Oyama F., Imagawa M., Ihara Y.;
RT "Human transferrin (Tf): a single mutation at codon 570 determines Tf
RT C1 or Tf C2 variant.";
RL Hum. Genet. 100:457-458(1997).
RN [20]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 564-624.
RA Tsuchida S., Ikemoto S., Kajii E.;
RL Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases.
RN [21]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 636-696.
RX PubMed=2780570; DOI=10.1073/pnas.86.18.7260;
RA Duguid J.R., Bohmont C.W., Liu N.G., Tourtellotte W.W.;
RT "Changes in brain gene expression shared by scrapie and Alzheimer
RT disease.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:7260-7264(1989).
RN [22]
RP DISULFIDE BONDS.
RX PubMed=6953407; DOI=10.1073/pnas.79.8.2504;
RA McGillivray R.T.A., Mendez E., Sinha S.K., Sutton M.R.,
RA Lineback-Zins J., Brew K.;
RT "The complete amino acid sequence of human serum transferrin.";
RL Proc. Natl. Acad. Sci. U.S.A. 79:2504-2508(1982).
RN [23]
RP MUTAGENESIS.
RX PubMed=1932003; DOI=10.1021/bi00109a002;
RA Woodworth R.C., Mason A.B., Funk W.D., McGillivray R.T.A.;
RT "Expression and initial characterization of five site-directed mutants
RT of the N-terminal half-molecule of human transferrin.";
RL Biochemistry 30:10824-10829(1991).
RN [24]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-432 AND ASN-630, AND MASS
RP SPECTROMETRY.
RC TISSUE=Bile;
RX PubMed=15084671; DOI=10.1074/mcp.M400015-MCP200;
RA Kristiansen T.Z., Bunkenborg J., Gronborg M., Molina H.,
RA Thuluvath P.J., Argani P., Goggins M.G., Maitra A., Pandey A.;
RT "A proteomic analysis of human bile.";
RL Mol. Cell. Proteomics 3:715-728(2004).
RN [25]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-432 AND ASN-630, AND MASS
RP SPECTROMETRY.
RC TISSUE=Plasma;
RX PubMed=14760718; DOI=10.1002/pmic.200300556;
RA Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R.;
RT "Screening for N-glycosylated proteins by liquid chromatography mass
RT spectrometry.";
RL Proteomics 4:454-465(2004).
RN [26]
RP GLYCOSYLATION AT ASN-432; ASN-491 AND ASN-630.
RX PubMed=15536627; DOI=10.1002/rcm.1718;
RA Satomi Y., Shimonishi Y., Hase T., Takao T.;
RT "Site-specific carbohydrate profiling of human transferrin by nano-
RT flow liquid chromatography/electrospray ionization mass
RT spectrometry.";
RL Rapid Commun. Mass Spectrom. 18:2983-2988(2004).
RN [27]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-432 AND ASN-630, AND MASS
RP SPECTROMETRY.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E.,
RA Moore R.J., Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [28]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-630, AND MASS
RP SPECTROMETRY.
RC TISSUE=Saliva;
RX PubMed=16740002; DOI=10.1021/pr050492k;
RA Ramachandran P., Boontheung P., Xie Y., Sondej M., Wong D.T.,
RA Loo J.A.;
RT "Identification of N-linked glycoproteins in human saliva by
RT glycoprotein capture and mass spectrometry.";
RL J. Proteome Res. 5:1493-1503(2006).
RN [29]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-432 AND ASN-630, AND MASS
RP SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of
RT multiple enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [30]
RP GLYCOSYLATION AT ASN-630.
RX PubMed=19139490; DOI=10.1074/mcp.M800504-MCP200;
RA Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F.,
RA Zheng Z.B., Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y.,
RA Zhang Y.K., Deng Y.L., Ying W.T., He S.M., Qian X.H.;
RT "A strategy for precise and large scale identification of core
RT fucosylated glycoproteins.";
RL Mol. Cell. Proteomics 8:913-923(2009).
RN [31]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-432 AND ASN-630, STRUCTURE
RP OF CARBOHYDRATES, AND MASS SPECTROMETRY.
RC TISSUE=Cerebrospinal fluid;
RX PubMed=19838169; DOI=10.1038/nmeth.1392;
RA Nilsson J., Rueetschi U., Halim A., Hesse C., Carlsohn E.,
RA Brinkmalm G., Larson G.;
RT "Enrichment of glycopeptides for glycan structure and attachment site
RT identification.";
RL Nat. Methods 6:809-811(2009).
RN [32]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 22-350.
RX PubMed=9609685; DOI=10.1021/bi980355j;
RA Macgillivray R.T.A., Moore S.A., Chen J., Anderson B.F., Baker H.,
RA Luo Y., Bewley M.C., Smith C.A., Murphy M.E.P., Wang Y., Mason A.B.,
RA Woodworth R.C., Brayer G.D., Baker E.N.;
RT "Two high-resolution crystal structures of the recombinant N-lobe of
RT human transferrin reveal a structural change implicated in iron
RT release.";
RL Biochemistry 37:7919-7928(1998).
RN [33]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 22-350.
RX PubMed=9760232; DOI=10.1021/bi9812064;
RA Jeffrey P.D., Bewley M.C., Macgillivray R.T.A., Mason A.B.,
RA Woodworth R.C., Baker E.N.;
RT "Ligand-induced conformational change in transferrins: crystal
RT structure of the open form of the N-terminal half-molecule of human
RT transferrin.";
RL Biochemistry 37:13978-13986(1998).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 23-352.
RX PubMed=10029548; DOI=10.1021/bi9824543;
RA Bewley M.C., Tam B.M., Grewal J., He S., Shewry S., Murphy M.E.P.,
RA Mason A.B., Woodworth R.C., Baker E.N., Macgillivray R.T.A.;
RT "X-ray crystallography and mass spectroscopy reveal that the N-lobe of
RT human transferrin expressed in Pichia pastoris is folded correctly but
RT is glycosylated on serine-32.";
RL Biochemistry 38:2535-2541(1999).
RN [35]
RP VARIANT SER-142.
RX PubMed=9358047; DOI=10.1016/S0378-1119(97)00356-9;
RA Evans P., Kemp J.;
RT "Exon/intron structure of the human transferrin receptor gene.";
RL Gene 199:123-131(1997).
RN [36]
RP VARIANT GLU-646.
RX PubMed=9803271; DOI=10.1046/j.1469-1809.1998.6230271.x;
RA Pang H., Koda Y., Soejima M., Kimura H.;
RT "Identification of a mutation (A1879G) of transferrin from cDNA
RT prepared from peripheral blood cells.";
RL Ann. Hum. Genet. 62:271-274(1998).
RN [37]
RP VARIANTS SER-277; SER-589 AND GLU-671, AND CHARACTERIZATION OF VARIANT
RP SER-277.
RX PubMed=11703331; DOI=10.1046/j.1365-2141.2001.03096.x;
RA Lee P.L., Halloran C., Trevino R., Felitti V., Beutler E.;
RT "Human transferrin G277S mutation: a risk factor for iron deficiency
RT anaemia.";
RL Br. J. Haematol. 115:329-333(2001).
RN [38]
RP VARIANTS SER-277 AND SER-589.
RX PubMed=11702220; DOI=10.1007/s004390100599;
RA Douabin-Gicquel V., Soriano N., Ferran H., Wojcik F., Palierne E.,
RA Tamim S., Jovelin T., McKie A.T., Le Gall J.-Y., David V., Mosser J.;
RT "Identification of 96 single nucleotide polymorphisms in eight genes
RT involved in iron metabolism: efficiency of bioinformatic extraction
RT compared with a systematic sequencing approach.";
RL Hum. Genet. 109:393-401(2001).
RN [39]
RP VARIANT ATRAF ASN-77.
RX PubMed=15466165; DOI=10.1182/blood-2004-05-1751;
RA Knisely A.S., Gelbart T., Beutler E.;
RT "Molecular characterization of a third case of human
RT atransferrinemia.";
RL Blood 104:2607-2607(2004).
RN [40]
RP VARIANT [LARGE SCALE ANALYSIS] VAL-448, AND MASS SPECTROMETRY.
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Transferrins are iron binding transport proteins which
CC can bind two Fe(3+) ions in association with the binding of an
CC anion, usually bicarbonate. It is responsible for the transport of
CC iron from sites of absorption and heme degradation to those of
CC storage and utilization. Serum transferrin may also have a further
CC role in stimulating cell proliferation.
CC -!- SUBUNIT: Monomer.
CC -!- INTERACTION:
CC P01350:GAST; NbExp=5; IntAct=EBI-714319, EBI-3436637;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed by the liver and secreted in plasma.
CC -!- POLYMORPHISM: Different polymorphic variants of transferrin are
CC known. The sequence shown is the predominant electrophoretic
CC variant (C1 or TF*C1).
CC -!- DISEASE: Atransferrinemia (ATRAF) [MIM:209300]: A rare autosomal
CC recessive disorder characterized by abnormal synthesis of
CC transferrin leading to iron overload and microcytic hypochromic
CC anemia. Note=The disease is caused by mutations affecting the gene
CC represented in this entry.
CC -!- SIMILARITY: Belongs to the transferrin family.
CC -!- SIMILARITY: Contains 2 transferrin-like domains.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF22007.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Transferrin entry;
CC URL="http://en.wikipedia.org/wiki/Transferrin";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/tf/";
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DR EMBL; M12530; AAA61140.1; -; mRNA.
DR EMBL; M17611; AAA61147.1; -; Genomic_DNA.
DR EMBL; M17610; AAA61147.1; JOINED; Genomic_DNA.
DR EMBL; M17614; AAA61148.1; -; Genomic_DNA.
DR EMBL; M17612; AAA61148.1; JOINED; Genomic_DNA.
DR EMBL; M17613; AAA61148.1; JOINED; Genomic_DNA.
DR EMBL; S95936; AAB22049.1; -; mRNA.
DR EMBL; AF288144; AAK77664.1; -; Genomic_DNA.
DR EMBL; AF294270; AAK77664.1; JOINED; Genomic_DNA.
DR EMBL; AF294271; AAK77664.1; JOINED; Genomic_DNA.
DR EMBL; AF288139; AAK77664.1; JOINED; Genomic_DNA.
DR EMBL; AF288140; AAK77664.1; JOINED; Genomic_DNA.
DR EMBL; AF288141; AAK77664.1; JOINED; Genomic_DNA.
DR EMBL; AF288142; AAK77664.1; JOINED; Genomic_DNA.
DR EMBL; AF288143; AAK77664.1; JOINED; Genomic_DNA.
DR EMBL; AY308797; AAP45055.1; -; Genomic_DNA.
DR EMBL; DQ525716; ABF47110.1; -; Genomic_DNA.
DR EMBL; AC080128; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC083905; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; CH471052; EAW79167.1; -; Genomic_DNA.
DR EMBL; BC059367; AAH59367.1; -; mRNA.
DR EMBL; M21569; AAA61143.2; -; Genomic_DNA.
DR EMBL; M15673; AAA61143.2; JOINED; Genomic_DNA.
DR EMBL; M21570; AAA61145.1; -; Genomic_DNA.
DR EMBL; X04600; CAA28265.1; -; Genomic_DNA.
DR EMBL; AJ252279; CAB96907.1; -; mRNA.
DR EMBL; M11372; AAA61141.1; -; Genomic_DNA.
DR EMBL; M11361; AAA61141.1; JOINED; Genomic_DNA.
DR EMBL; M11362; AAA61141.1; JOINED; Genomic_DNA.
DR EMBL; M11363; AAA61141.1; JOINED; Genomic_DNA.
DR EMBL; M11364; AAA61141.1; JOINED; Genomic_DNA.
DR EMBL; M11365; AAA61141.1; JOINED; Genomic_DNA.
DR EMBL; M11366; AAA61141.1; JOINED; Genomic_DNA.
DR EMBL; M11367; AAA61141.1; JOINED; Genomic_DNA.
DR EMBL; M11368; AAA61141.1; JOINED; Genomic_DNA.
DR EMBL; M11369; AAA61141.1; JOINED; Genomic_DNA.
DR EMBL; M11370; AAA61141.1; JOINED; Genomic_DNA.
DR EMBL; M11371; AAA61141.1; JOINED; Genomic_DNA.
DR EMBL; AF118063; AAF22007.1; ALT_INIT; mRNA.
DR EMBL; M12525; AAA61142.1; -; mRNA.
DR EMBL; U88581; AAB97880.1; -; mRNA.
DR EMBL; AF058327; AAC63506.1; -; Genomic_DNA.
DR EMBL; M26641; AAA61233.1; -; mRNA.
DR PIR; A20981; TFHUP.
DR RefSeq; NP_001054.1; NM_001063.3.
DR UniGene; Hs.518267; -.
DR PDB; 1A8E; X-ray; 1.60 A; A=22-350.
DR PDB; 1A8F; X-ray; 1.80 A; A=22-350.
DR PDB; 1B3E; X-ray; 2.50 A; A=23-352.
DR PDB; 1BP5; X-ray; 2.20 A; A/B/C/D=20-356.
DR PDB; 1BTJ; X-ray; 3.20 A; A/B=20-356.
DR PDB; 1D3K; X-ray; 1.80 A; A=22-350.
DR PDB; 1D4N; X-ray; 2.00 A; A=22-350.
DR PDB; 1DTG; X-ray; 2.40 A; A=20-353.
DR PDB; 1FQE; X-ray; 1.80 A; A=20-350.
DR PDB; 1FQF; X-ray; 2.10 A; A=20-350.
DR PDB; 1JQF; X-ray; 1.85 A; A=20-353.
DR PDB; 1N7W; X-ray; 2.20 A; A=22-350.
DR PDB; 1N7X; X-ray; 2.10 A; A=20-350.
DR PDB; 1N84; X-ray; 2.05 A; A=20-350.
DR PDB; 1OQG; X-ray; 1.90 A; A=20-354.
DR PDB; 1OQH; X-ray; 2.40 A; A=20-354.
DR PDB; 1RYO; X-ray; 1.20 A; A=20-346.
DR PDB; 1SUV; EM; 7.50 A; C/D=22-350.
DR PDB; 2HAU; X-ray; 2.70 A; A/B=23-698.
DR PDB; 2HAV; X-ray; 2.70 A; A/B=23-698.
DR PDB; 2O7U; X-ray; 2.80 A; A/B/C/D/E/F/G/H/I=20-356.
DR PDB; 2O84; X-ray; 2.60 A; X=20-356.
DR PDB; 3FGS; X-ray; 1.80 A; A=20-356.
DR PDB; 3QYT; X-ray; 2.80 A; A=20-698.
DR PDB; 3S9L; X-ray; 3.22 A; C/D=20-698.
DR PDB; 3S9M; X-ray; 3.32 A; C/D=20-698.
DR PDB; 3S9N; X-ray; 3.25 A; C/D=20-698.
DR PDB; 3SKP; X-ray; 1.70 A; A=358-698.
DR PDB; 3V83; X-ray; 2.10 A; A/B/C/D/E/F=1-698.
DR PDB; 3V89; X-ray; 3.10 A; B=356-698.
DR PDB; 3V8X; X-ray; 2.60 A; B=1-698.
DR PDB; 3VE1; X-ray; 2.96 A; B/D=20-698.
DR PDB; 4H0W; X-ray; 2.40 A; A=20-698.
DR PDBsum; 1A8E; -.
DR PDBsum; 1A8F; -.
DR PDBsum; 1B3E; -.
DR PDBsum; 1BP5; -.
DR PDBsum; 1BTJ; -.
DR PDBsum; 1D3K; -.
DR PDBsum; 1D4N; -.
DR PDBsum; 1DTG; -.
DR PDBsum; 1FQE; -.
DR PDBsum; 1FQF; -.
DR PDBsum; 1JQF; -.
DR PDBsum; 1N7W; -.
DR PDBsum; 1N7X; -.
DR PDBsum; 1N84; -.
DR PDBsum; 1OQG; -.
DR PDBsum; 1OQH; -.
DR PDBsum; 1RYO; -.
DR PDBsum; 1SUV; -.
DR PDBsum; 2HAU; -.
DR PDBsum; 2HAV; -.
DR PDBsum; 2O7U; -.
DR PDBsum; 2O84; -.
DR PDBsum; 3FGS; -.
DR PDBsum; 3QYT; -.
DR PDBsum; 3S9L; -.
DR PDBsum; 3S9M; -.
DR PDBsum; 3S9N; -.
DR PDBsum; 3SKP; -.
DR PDBsum; 3V83; -.
DR PDBsum; 3V89; -.
DR PDBsum; 3V8X; -.
DR PDBsum; 3VE1; -.
DR PDBsum; 4H0W; -.
DR ProteinModelPortal; P02787; -.
DR SMR; P02787; 20-698.
DR DIP; DIP-2738N; -.
DR IntAct; P02787; 33.
DR MINT; MINT-1400694; -.
DR STRING; 9606.ENSP00000264998; -.
DR ChEMBL; CHEMBL4865; -.
DR DrugBank; DB01370; Aluminium.
DR DrugBank; DB01402; Bismuth.
DR DrugBank; DB00893; Iron Dextran.
DR MEROPS; S60.972; -.
DR PhosphoSite; P02787; -.
DR UniCarbKB; P02787; -.
DR DOSAC-COBS-2DPAGE; P02787; -.
DR REPRODUCTION-2DPAGE; IPI00022463; -.
DR REPRODUCTION-2DPAGE; P02787; -.
DR SWISS-2DPAGE; P02787; -.
DR UCD-2DPAGE; P02787; -.
DR PaxDb; P02787; -.
DR PRIDE; P02787; -.
DR Ensembl; ENST00000402696; ENSP00000385834; ENSG00000091513.
DR GeneID; 7018; -.
DR KEGG; hsa:7018; -.
DR UCSC; uc003epu.2; human.
DR CTD; 7018; -.
DR GeneCards; GC03P133464; -.
DR HGNC; HGNC:11740; TF.
DR HPA; CAB009538; -.
DR HPA; HPA001527; -.
DR HPA; HPA005692; -.
DR MIM; 190000; gene.
DR MIM; 209300; phenotype.
DR neXtProt; NX_P02787; -.
DR Orphanet; 1195; Congenital atransferrinemia.
DR PharmGKB; PA36457; -.
DR eggNOG; NOG87503; -.
DR HOGENOM; HOG000252723; -.
DR HOVERGEN; HBG000055; -.
DR InParanoid; P02787; -.
DR KO; K14736; -.
DR OMA; FYYAVAV; -.
DR OrthoDB; EOG7D59N7; -.
DR PhylomeDB; P02787; -.
DR Reactome; REACT_15518; Transmembrane transport of small molecules.
DR Reactome; REACT_604; Hemostasis.
DR ChiTaRS; TF; human.
DR EvolutionaryTrace; P02787; -.
DR GeneWiki; Transferrin; -.
DR GenomeRNAi; 7018; -.
DR NextBio; 27415; -.
DR PMAP-CutDB; P02787; -.
DR PRO; PR:P02787; -.
DR ArrayExpress; P02787; -.
DR Bgee; P02787; -.
DR CleanEx; HS_TF; -.
DR Genevestigator; P02787; -.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0009925; C:basal plasma membrane; IDA:UniProtKB.
DR GO; GO:0005905; C:coated pit; IDA:UniProtKB.
DR GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR GO; GO:0030139; C:endocytic vesicle; IDA:MGI.
DR GO; GO:0010008; C:endosome membrane; TAS:Reactome.
DR GO; GO:0005576; C:extracellular region; NAS:UniProtKB.
DR GO; GO:0005770; C:late endosome; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0055037; C:recycling endosome; IDA:UniProtKB.
DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome.
DR GO; GO:0008199; F:ferric iron binding; IEA:InterPro.
DR GO; GO:0006879; P:cellular iron ion homeostasis; TAS:Reactome.
DR GO; GO:0030168; P:platelet activation; TAS:Reactome.
DR GO; GO:0002576; P:platelet degranulation; TAS:Reactome.
DR GO; GO:0033572; P:transferrin transport; TAS:Reactome.
DR GO; GO:0055085; P:transmembrane transport; TAS:Reactome.
DR InterPro; IPR016357; Transferrin.
DR InterPro; IPR001156; Transferrin_fam.
DR InterPro; IPR018195; Transferrin_Fe_BS.
DR Pfam; PF00405; Transferrin; 2.
DR PIRSF; PIRSF002549; Transferrin; 1.
DR PRINTS; PR00422; TRANSFERRIN.
DR SMART; SM00094; TR_FER; 2.
DR PROSITE; PS00205; TRANSFERRIN_LIKE_1; 1.
DR PROSITE; PS00206; TRANSFERRIN_LIKE_2; 2.
DR PROSITE; PS00207; TRANSFERRIN_LIKE_3; 2.
DR PROSITE; PS51408; TRANSFERRIN_LIKE_4; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Complete proteome; Direct protein sequencing;
KW Disease mutation; Disulfide bond; Glycoprotein; Ion transport; Iron;
KW Iron transport; Metal-binding; Methylation; Polymorphism;
KW Reference proteome; Repeat; Secreted; Signal; Transport.
FT SIGNAL 1 19
FT CHAIN 20 698 Serotransferrin.
FT /FTId=PRO_0000035715.
FT DOMAIN 25 347 Transferrin-like 1.
FT DOMAIN 361 683 Transferrin-like 2.
FT METAL 82 82 Iron 1.
FT METAL 114 114 Iron 1.
FT METAL 207 207 Iron 1.
FT METAL 268 268 Iron 1.
FT METAL 411 411 Iron 2 (By similarity).
FT METAL 445 445 Iron 2 (By similarity).
FT METAL 536 536 Iron 2 (By similarity).
FT METAL 604 604 Iron 2 (By similarity).
FT BINDING 139 139 Carbonate 1.
FT BINDING 143 143 Carbonate 1.
FT BINDING 145 145 Carbonate 1; via amide nitrogen.
FT BINDING 146 146 Carbonate 1; via amide nitrogen.
FT BINDING 471 471 Carbonate 2 (By similarity).
FT BINDING 475 475 Carbonate 2 (By similarity).
FT BINDING 477 477 Carbonate 2; via amide nitrogen (By
FT similarity).
FT BINDING 478 478 Carbonate 2; via amide nitrogen (By
FT similarity).
FT MOD_RES 42 42 Omega-N-methylated arginine (By
FT similarity).
FT CARBOHYD 51 51 O-linked (GalNAc...).
FT /FTId=CAR_000073.
FT CARBOHYD 432 432 N-linked (GlcNAc...) (complex).
FT /FTId=CAR_000074.
FT CARBOHYD 491 491 N-linked (GlcNAc...).
FT CARBOHYD 630 630 N-linked (GlcNAc...) (complex).
FT /FTId=CAR_000075.
FT DISULFID 28 67
FT DISULFID 38 58
FT DISULFID 137 213
FT DISULFID 156 350
FT DISULFID 177 193
FT DISULFID 180 196
FT DISULFID 190 198
FT DISULFID 246 260
FT DISULFID 358 615
FT DISULFID 364 396
FT DISULFID 374 387
FT DISULFID 421 693
FT DISULFID 437 656
FT DISULFID 469 542
FT DISULFID 493 684
FT DISULFID 503 517
FT DISULFID 514 525
FT DISULFID 582 596
FT DISULFID 634 639
FT VARIANT 42 42 R -> L (in dbSNP:rs41298293).
FT /FTId=VAR_034569.
FT VARIANT 55 55 S -> R (in dbSNP:rs8177318).
FT /FTId=VAR_029280.
FT VARIANT 76 76 A -> V (in dbSNP:rs41298977).
FT /FTId=VAR_034570.
FT VARIANT 77 77 D -> N (in ATRAF).
FT /FTId=VAR_038810.
FT VARIANT 142 142 G -> S (in dbSNP:rs1799830).
FT /FTId=VAR_011997.
FT VARIANT 277 277 G -> S (in allele TF*C3; associated with
FT a reduction in total iron binding
FT capacity; risk factor for iron deficiency
FT anemia in menstruating white women;
FT dbSNP:rs1799899).
FT /FTId=VAR_011998.
FT VARIANT 296 296 D -> G (in allele TF*D1;
FT dbSNP:rs8177238).
FT /FTId=VAR_007544.
FT VARIANT 319 319 H -> R (in allele TF*CHI;
FT dbSNP:rs41295774).
FT /FTId=VAR_007545.
FT VARIANT 377 377 W -> C (in dbSNP:rs1804498).
FT /FTId=VAR_011999.
FT VARIANT 448 448 I -> V (in dbSNP:rs2692696).
FT /FTId=VAR_058199.
FT VARIANT 477 477 A -> P (in ATRAF).
FT /FTId=VAR_012997.
FT VARIANT 562 562 G -> V (in dbSNP:rs41296590).
FT /FTId=VAR_034571.
FT VARIANT 589 589 P -> S (in allele TF*C2;
FT dbSNP:rs1049296).
FT /FTId=VAR_012000.
FT VARIANT 645 645 T -> P (in dbSNP:rs1130537).
FT /FTId=VAR_012001.
FT VARIANT 646 646 K -> E (in allele TF*BV).
FT /FTId=VAR_012998.
FT VARIANT 671 671 G -> E (in allele TF*B2;
FT dbSNP:rs121918677).
FT /FTId=VAR_012999.
FT CONFLICT 216 216 D -> N (in Ref. 9; AAH59367).
FT CONFLICT 264 264 Q -> E (in Ref. 12; AA sequence).
FT CONFLICT 329 329 D -> N (in Ref. 12; AA sequence and 14;
FT AAA61141).
FT CONFLICT 351 351 P -> Q (in Ref. 9; AAH59367).
FT CONFLICT 380 381 NS -> SD (in Ref. 12; AA sequence).
FT CONFLICT 436 436 N -> D (in Ref. 12; AA sequence).
FT CONFLICT 558 561 PQNT -> TQNP (in Ref. 12; AA sequence).
FT CONFLICT 591 591 E -> Q (in Ref. 12; AA sequence).
FT CONFLICT 672 672 E -> Q (in Ref. 12; AA sequence).
FT CONFLICT 691 691 E -> G (in Ref. 18; AAA61142).
FT STRAND 24 30
FT HELIX 31 48
FT STRAND 51 54
FT STRAND 55 63
FT HELIX 64 72
FT STRAND 78 81
FT HELIX 83 90
FT TURN 92 94
FT STRAND 97 105
FT STRAND 107 121
FT HELIX 128 130
FT STRAND 136 139
FT TURN 144 147
FT HELIX 148 154
FT HELIX 155 157
FT STRAND 158 160
FT HELIX 165 172
FT STRAND 173 177
FT TURN 183 185
FT HELIX 187 190
FT STRAND 191 193
FT HELIX 194 196
FT STRAND 198 202
FT HELIX 206 215
FT STRAND 220 225
FT HELIX 228 232
FT HELIX 236 239
FT STRAND 242 245
FT TURN 247 249
FT STRAND 251 253
FT HELIX 254 259
FT STRAND 262 266
FT STRAND 269 272
FT STRAND 274 276
FT HELIX 279 293
FT TURN 295 297
FT STRAND 298 300
FT STRAND 310 314
FT STRAND 318 323
FT HELIX 330 334
FT HELIX 336 345
FT TURN 346 348
FT HELIX 354 357
FT STRAND 360 365
FT HELIX 368 380
FT TURN 381 383
FT STRAND 384 389
FT HELIX 393 401
FT STRAND 407 410
FT HELIX 412 420
FT STRAND 424 430
FT HELIX 437 439
FT STRAND 445 452
FT STRAND 455 457
FT HELIX 460 462
FT STRAND 466 471
FT TURN 476 479
FT HELIX 480 485
FT HELIX 487 489
FT HELIX 495 497
FT STRAND 498 503
FT STRAND 509 511
FT HELIX 512 514
FT HELIX 521 523
FT STRAND 531 533
FT HELIX 535 545
FT STRAND 548 553
FT HELIX 556 559
FT TURN 568 572
FT HELIX 575 577
FT STRAND 578 581
FT STRAND 587 589
FT HELIX 590 595
FT STRAND 598 601
FT STRAND 605 608
FT HELIX 610 612
FT HELIX 613 627
FT STRAND 628 630
FT STRAND 635 637
FT STRAND 644 646
FT STRAND 648 650
FT STRAND 656 659
FT HELIX 661 663
FT HELIX 666 669
FT HELIX 672 684
FT HELIX 688 694
SQ SEQUENCE 698 AA; 77064 MW; 9A73B90D8C5671E9 CRC64;
MRLAVGALLV CAVLGLCLAV PDKTVRWCAV SEHEATKCQS FRDHMKSVIP SDGPSVACVK
KASYLDCIRA IAANEADAVT LDAGLVYDAY LAPNNLKPVV AEFYGSKEDP QTFYYAVAVV
KKDSGFQMNQ LRGKKSCHTG LGRSAGWNIP IGLLYCDLPE PRKPLEKAVA NFFSGSCAPC
ADGTDFPQLC QLCPGCGCST LNQYFGYSGA FKCLKDGAGD VAFVKHSTIF ENLANKADRD
QYELLCLDNT RKPVDEYKDC HLAQVPSHTV VARSMGGKED LIWELLNQAQ EHFGKDKSKE
FQLFSSPHGK DLLFKDSAHG FLKVPPRMDA KMYLGYEYVT AIRNLREGTC PEAPTDECKP
VKWCALSHHE RLKCDEWSVN SVGKIECVSA ETTEDCIAKI MNGEADAMSL DGGFVYIAGK
CGLVPVLAEN YNKSDNCEDT PEAGYFAIAV VKKSASDLTW DNLKGKKSCH TAVGRTAGWN
IPMGLLYNKI NHCRFDEFFS EGCAPGSKKD SSLCKLCMGS GLNLCEPNNK EGYYGYTGAF
RCLVEKGDVA FVKHQTVPQN TGGKNPDPWA KNLNEKDYEL LCLDGTRKPV EEYANCHLAR
APNHAVVTRK DKEACVHKIL RQQQHLFGSN VTDCSGNFCL FRSETKDLLF RDDTVCLAKL
HDRNTYEKYL GEEYVKAVGN LRKCSTSSLL EACTFRRP
//

MIM 190000
*RECORD*
*FIELD* NO
190000
*FIELD* TI
*190000 TRANSFERRIN; TF
*FIELD* TX

DESCRIPTION

The TF gene encodes transferrin, a circulating serum protein responsible
read morefor delivering iron to cells (Hershberger et al., 1991).

CLONING

Uzan et al. (1984) isolated a clone corresponding to the human
transferrin gene from a human liver cDNA library. A single major 2.4-kb
mRNA species was identified.

Yang et al. (1984) isolated recombinant plasmids containing human cDNA
encoding TF by screening an adult human liver library with a mixed
oligonucleotide probe. Sequence analysis indicated that 3 areas of the
homologous amino and carboxyl domains were strongly conserved in
evolution.

Bost et al. (1985) identified short regions in the nucleotide and amino
acid sequences of epidermal growth factor (EGF; 131530), interleukin-2
(IL2; 147680), and transferrin that matched short regions in their
respective receptor complements (antisense strand) and their deduced
amino acid sequences. In each case, the region of homology of the
receptor was in sequences external to the cytoplasmic membrane that
might qualify for the ligand binding site.

Hershberger et al. (1991) cloned the human TF gene and determined that
the deduced protein contains 678 residues and 19 disulfide bonds, with a
molecular mass of about 80 kD.

MAPPING

Robson et al. (1966) presented evidence of linkage between the
transferrin locus and the pseudocholinesterase locus E1 (CHE1, BCHE;
177400). Naylor et al. (1980) suggested that the TF-CHE1 linkage group
may be on chromosome 3 in man since aminoacylase (ACY1; 104620) and
beta-galactosidase-1 (GLB1; 611458) are on chromosome 3 in man and on
chromosome 9 in the mouse, and since Tf is closely linked to Acy1 and
Glb1 in the mouse,

By somatic cell hybridization, using a monoclonal antibody to
demonstrate the synthesis of transferrin, Bodmer (1981) assigned
transferrin to chromosome 3. Lactotransferrin (LTF; 150210), found in
milk of many mammals including man, is structurally similar to serum
transferrin and is coded by a gene on chromosome 3p. Interestingly and
perhaps significantly, the gene for the transferrin receptor (TFRC;
190010) is also on chromosome 3q29. Eiberg et al. (1984) found a low
positive lod score at a recombination fraction of about 0.23 for linkage
of TF to heteromorphism at the centromere of chromosome 3. Since CHE1
and A2HS (104210) showed negative lod scores, these are possibly distal
to TF on chromosome 3.

Yang et al. (1984) mapped the TF gene to chromosome 3q21-q25 by in situ
hybridization and analysis of somatic cell hybrids. Huerre et al. (1984)
confirmed these findings.

Through linkage studies in a large Newfoundland kindred segregating for
an inversion, inv(3)(p25q21), McAlpine et al. (1987) determined the
order to be: cen--3q21--TF--CHE1--AHSG (138680)--qter.

By in situ hybridization, Baranov et al. (1987) assigned the TF gene to
3q21. They mapped both the CP (117700) and TF genes to chromosome 9 in
the mouse and chromosome 7 in rats. In rats, they also observed a
concentration of silver grains over chromosome 15 after hybridization
with both CP and TF probes, suggesting the presence of a related
pseudogene cluster on rat chromosome 15 and favoring partial homeology
to rat chromosome 7. Use of a rat CP DNA probe appeared to contradict
synteny of CP and TF in man and suggested the existence of a related DNA
sequence on 15q11-q13.

GENE FUNCTION

Transferrin is the product of an ancient intragenic duplication that led
to homologous carboxyl and amino domains, each of which binds 1 ion of
ferric iron. Transferrin carries iron from the intestine,
reticuloendothelial system, and liver parenchymal cells to all
proliferating cells in the body. It carries iron into cells by
receptor-mediated endocytosis. Iron is dissociated from transferrin in a
nonlysosomal acidic compartment of the cell. Provision of intracellular
iron is required for cell division. After dissociation of iron,
transferrin and its receptor return undegraded to the extracellular
environment and the cell membrane, respectively (Yang et al., 1984; Park
et al., 1985; Bowman et al., 1988).

Sass-Kuhn et al. (1984) identified a heat-stable protein in normal human
serum that promoted the binding of granulocytes to timothy grass pollen.
They concluded that this granulocyte/pollen-binding protein (GPBP) was
identical to transferrin. This novel property of transferrin was
unrelated to iron transport. The authors concluded that transferrin may
have a physiologic role in the removal of certain organic matter.

IGFBP3 (146732) possesses both growth-inhibitory and -potentiating
effects on cells that are independent of IGF action and are mediated
through specific IGFBP3-binding proteins/receptors located at the cell
membrane, cytosol, or nuclear compartments and in the extracellular
matrix. Weinzimer et al. (2001) characterized TF as one of these
IGFBP3-binding proteins. Human serum was fractionated over an IGFBP3
affinity column, and a 70-kD protein was eluted, sequenced, and
identified (through database searching and Western immunoblot) as human
TF. Biosensor interaction analysis confirmed that this interaction is
specific and sensitive, with a high association rate similar to that of
IGF1 (147440), and suggested that binding occurs in the vicinity of the
IGFBP3 nuclear localization site. TF treatment blocked IGFBP3-induced
cell proliferation in bladder smooth muscle cells and IGFBP3-induced
apoptosis in prostate cancer cells.

Iron is essential to life, but poses severe problems because of its
toxicity and the insolubility of hydrated ferric ions at neutral pH. In
animals, transferrins are responsible for the sequestration, transport,
and distribution of free iron. Baker et al. (2003) compared the
structure and function of transferrins with hemopexin (HPX; 142290), a
completely unrelated protein that carries out the same function for
heme. They identified molecular features that contribute to a successful
protein system for iron acquisition, transport, and release. These
include a 2-domain protein structure with flexible hinges that allow
these domains to enclose the bound ligand and provide suitable chemistry
for stable binding and an appropriate trigger for release.

MOLECULAR GENETICS

Transferrin polymorphisms were first demonstrated by Oliver Smithies
(1957, 1958) using starch gel electrophoresis. Welch and Langmead (1990)
stated that more than 30 different genetic TF variants had been
described. TF C (190000.0004), especially TF C1 (Kamboh and Ferrell,
1987), is the predominant form in all investigated populations.

Data on gene frequencies of allelic variants were tabulated by
Roychoudhury and Nei (1988).

Evans et al. (1982) described a transferrin variant that was abnormal in
its iron-binding properties. It was able to bind 2 atoms of iron, but
the iron in the C-terminal binding site was bound abnormally, as judged
by its spectral properties, and dissociated from the protein under
certain conditions. Furthermore, the iron-free C-terminal domain was
relatively unstable. Young et al. (1984) described a variant transferrin
that showed both abnormal iron-binding properties and an abnormal
interaction with the transferrin receptor.

Weidinger et al. (1984) identified and characterized several TF
variants, including a null allele, in a German population.

Pang et al. (1998) showed that peripheral blood cells can be used as a
source for preparation of TF cDNA, as an alternative to human liver, in
the molecular analysis of TF polymorphism.

In a patient with atransferrinemia (209300), Beutler et al. (2000)
identified compound heterozygosity for 2 mutations in the TF gene
(190000.0006 and 190000.0007).

For a discussion of a possible relationship between variation in the TF
gene and serum transferrin as a quantitative trait, see 614193.

HISTORY

Chautard-Freire-Maia (1976) presented evidence that the TF locus was on
chromosome 1 and linked to Rh (111700). However, King et al. (1979) were
unable to confirm these findings. Linkage of HLA and TF was excluded by
Jenkins et al. (1982).

*FIELD* AV
.0001
TRANSFERRIN VARIANT D1
TF, GLY277ASP

Yang et al. (1984) identified the amino acid change in 3 genetic
variants of transferrin: D1 (Wang and Sutton, 1965), chi (Wang et al.,
1967), and B2 (Wang et al., 1966). The variants differed at the
following amino acids: 277 (gly-to-asp), 300 (his-to-arg; 190000.0002),
and 652 (gly-to-glu; 190000.0003). All could be explained by mutational
transitions, G-to-A, A-to-G, and G-to-A, respectively, in the second
nucleotide of each of the 3 codons.

Yang et al. (1984) originally reported this mutation as ASP277GLY,
caused by an A-to-G nucleotide change.

.0002
TRANSFERRIN VARIANT CHI
TF, HIS300ARG

See 190000.0001 and Yang et al. (1984).

.0003
TRANSFERRIN VARIANT B2
TF, GLY652GLU

See 190000.0001 and Yang et al. (1984).

.0004
TRANSFERRIN VARIANT C1/C2
ALZHEIMER DISEASE, SUSCEPTIBILITY TO, INCLUDED
TF, PRO570SER

As the basis of the C1/C2 variation in transferrin as revealed by
isoelectric focusing, Namekata et al. (1997) identified a single base
change in exon 15 of the TF gene. A C-to-T substitution at codon 570
replaced proline (in C1) with serine (in C2). Based on this nucleotide
substitution, Namekata et al. (1997) established PCR-based genotyping
for the TF*C1 and TF*C2 alleles.

Robson et al. (2004) noted that there is evidence that iron may play a
role in the pathology of Alzheimer disease (104300). Thus, genetic
factors that contribute to iron deposition resulting in tissue damage
might exacerbate AD. The authors examined the interaction between the C2
variant of the TF gene and the C282Y allele of the HFE gene
(613609.0001), the most common basis of hemochromatosis, as risk factors
for developing AD. The results showed that each of the 2 variants was
associated with an increased risk of AD only in the presence of the
other. Neither allele alone had any effect. Carriers of both variants
were at 5 times greater risk of AD compared with all others.
Furthermore, carriers of these 2 alleles plus APOE4 (see 107741) were at
still higher risk of AD: of the 14 carriers of the 3 variants identified
in this study, 12 had AD and 2 had mild cognitive impairment. Robson et
al. (2004) concluded that their results indicated that the combination
of TF*C2 and HFE C282Y may lead to an excess of redoxactive iron and the
induction of oxidative stress in neurons, which is exacerbated in
carriers of APOE4. They noted that 4% of northern Europeans carry the 2
iron-related variants and that iron overload is a treatable condition.

.0005
TRANSFERRIN VARIANT Bv
TF, LYS627GLU

Pang et al. (1998) used peripheral blood cells to prepare cDNA for TF.
They found that the TF B variant allele (TF Bv) contains an A-to-G
transition at nucleotide 1879 in the coding region that was predicted to
result in a lys627-to-glu substitution in exon 16.

.0006
ATRANSFERRINEMIA
TF, 10-BP DEL AND 9-BP DUP

In the first reported case of hereditary atransferrinemia (209300) in
the U.S., Beutler et al. (2000) found compound heterozygosity for
mutations in the TF gene: the patient had hypothyroidism, which was
ascribed to iron overload, and was treated monthly with removal of blood
followed by infusion of 500 ml of normal human plasma. The patient's DNA
demonstrated heterozygosity for a 10-bp deletion followed by a 9-bp
insertion of a duplicated sequence; and a G-to-C transversion at cDNA
nucleotide 1429, resulting in an ala477-to-pro substitution
(190000.0007). The latter mutation occurred at a highly conserved site.

.0007
ATRANSFERRINEMIA
TF, ALA477PRO

See 190000.0006 and Beutler et al. (2000).

.0008
RECLASSIFIED - VARIANT OF UNKNOWN SIGNIFICANCE
TF, GLY277SER

This variant, formerly titled IRON DEFICIENCY ANEMIA, SUSCEPTIBILITY TO,
has been reclassified based on the findings of Aisen (2003) and Delanghe
et al. (2005).

In the course of a study to determine whether polymorphisms in
transferrin may affect the severity of hemochromatosis in persons
carrying mutations in the HFE gene (613609), Lee et al. (2001) found
that a common polymorphism in exon 7 of the transferrin gene, a G-to-A
transition at nucleotide 829, resulting in a gly277-to-ser (G277S) amino
acid change, was associated with a reduction in total iron-binding
capacity (TIBC). Although the loss of TIBC did not compromise the iron
status of men and postmenopausal women, it predisposed menstruating
women to iron deficiency anemia. In menstruating white women, iron
deficiency anemia was present in 27% of homozygous ser277 women, 10% of
heterozygous gly277/ser277 women, and 5% of homozygous wildtype
gly277/gly277 women.

To explore the suggestion that the glycine in amino acid position 277 is
important for the maintenance of the biologic activity and/or structure
of transferrin, Aisen (2003) constructed the mutation in the human
transferrin expression vector, verified the construct by DNA sequencing,
and expressed the mutant in the nonglycosylated form of BHK21 cells. He
could demonstrate no difference between the mutant and native
transferrins and concluded that the cause of the iron deficiency
observed in the subjects studied by Lee et al. (2001) should be sought
elsewhere.

In a study of 92 pregnant women followed longitudinally during
pregnancy, Delanghe et al. (2005) found no relationship between
transferrin concentration, iron status, and the G277S variant of the
transferrin gene. They concluded that the G277S polymorphism does not
significantly alter iron metabolism.

.0009
ATRANSFERRINEMIA
TF, GLU375LYS

Hayashi et al. (1993) analyzed transferrin in a family with
atransferrinemia (209300) reported by Goya et al. (1972) and concluded
that the patient and his 2 healthy sibs were compound heterozygotes with
a paternal 'variant' TF allele and a maternal 'null' TF allele.
Asada-Senju et al. (2002) investigated the TF gene of the patient and
his family. They showed that the patient and his father shared a variant
TF gene bearing a G-to-A transition, resulting in a glu375-to-lys
(E375K) substitution in the mature protein. As for the maternal null
allele, no mutation was found in either the coding region or the
exon-intron boundaries, suggesting an abnormality in the transcription
or stability of mRNA of maternal allele origin.

.0010
ATRANSFERRINEMIA
TF, ASP77ASN

In lymphoblastoid cell lines from a patient with atransferrinemia
(209300), her parents, and her healthy brothers, first reported by Cap
et al. (1968), Knisely et al. (2004) identified a 229G-A transition in
exon 3 of the TF gene, resulting in a nonconservative amino acid
substitution, asp77 to asn (D77N). The proband was homozygous for the
D77N mutation; both parents and 1 brother were heterozygous. The proband
came to medical attention at the age of 2 months with severe
hypochromic, microcytic anemia. Atransferrinemia was diagnosed by means
of serum electrophoresis. Serum transferrin concentrations in her
parents, a brother, and a grandfather were approximately half normal
values. Periodic infusions of purified transferrin led to improved
erythropoiesis, although complications attributed to siderosis
developed. The proband, aged 34 years at the time of report, came from a
town of 7,000 inhabitants in a relatively isolated region of west
Slovakia. The disease in this patient was more severe than either of the
2 previously reported cases (Goya et al., 1972; Beutler et al., 2000).

*FIELD* SA
Chautard-Freire-Maia (1977); Dayhoff (1972); Giari et al. (1985);
Kueppers and Harpel (1980); MacGillivray et al. (1982); Parker and
Bearn (1962); Sutherland et al. (1981)
*FIELD* RF
1. Aisen, P.: The G277S mutation in transferrin does not disturb
function. (Letter) Brit. J. Haemat. 121: 674-675, 2003.

2. Asada-Senju, M.; Maeda, T.; Sakata, T.; Hayashi, A.; Suzuki, T.
: Molecular analysis of the transferrin gene in a patient with hereditary
hypotransferrinemia. J. Hum. Genet. 47: 355-359, 2002.

3. Baker, H. M.; Anderson, B. F.; Baker, E. N.: Dealing with iron:
common structural principles in proteins that transport iron and heme. Proc.
Nat. Acad. Sci. 100: 3579-3583, 2003.

4. Baranov, V. S.; Schwartzman, A. L.; Gorbunova, V. N.; Gaitskhoki,
V. S.; Rubtsov, N. B.; Timchenko, N. A.; Neifakh, S. A.: Chromosomal
localization of ceruloplasmin and transferrin genes in laboratory
rats, mice and in man by hybridization with specific DNA probes. Chromosoma 96:
60-66, 1987.

5. Beutler, E.; Gelbart, T.; Lee, P.; Trevino, R.; Fernandez, M. A.;
Fairbanks, V. F.: Molecular characterization of a case of atransferrinemia. Blood 96:
4071-4074, 2000.

6. Bodmer, W. F.: Monoclonal antibodies: their role in human genetics.
(Abstract) Sixth Int. Cong. Hum. Genet., Jerusalem 112 only, 1981.

7. Bost, K. L.; Smith, E. M.; Blalock, J. E.: Regions of complementarity
between the messenger RNAs for epidermal growth factor, transferrin,
interleukin-2 and their respective receptors. Biochem. Biophys. Res.
Commun. 128: 1373-1380, 1985.

8. Bowman, B. H.; Yang, F.; Adrian, G. S.: Transferrin: evolution
and genetic regulation of expression. Adv. Genet. 25: 1-38, 1988.

9. Cap, J.; Lehotska, V.; Mayerova, A.: Kongenitalna atransferinemia
u 11-mesacneho dietata. Cesk. Pediat. 23: 1020-1025, 1968.

10. Chautard-Freire-Maia, E. A.: Probable assignment of the serum
cholinesterase (E1) and transferrin (Tf) loci to chromosome 1 in man. Hum.
Hered. 27: 134-142, 1977.

11. Chautard-Freire-Maia, E. A.: Probable assignment of the E1 and
Tf loci to chromosome 1 in man. Ciencia e Cultura (Brazil) 28 (suppl.):
309-310, 1976.

12. Dayhoff, M. O.: Atlas of Protein Sequence and Structure. Transferrin.
Washington: National Biomedical Research Foundation (pub.) 5: 1972.
P. D310.

13. Delanghe, J.; Verstraelen, H.; Pynaert, I.; Debels, L.; Taes,
Y.; Verhasselt, B.; De Henauw, S.; Temmerman, M.: Human transferrin
G277S mutation and iron deficiency in pregnancy. (Letter) Brit. J.
Haemat. 132: 249-250, 2005.

14. Eiberg, H.; Mohr, J.; Nielsen, L. S.: A2HS: new methods of phenotyping
and analysis of linkage relations: assignment to chromosome 3. (Abstract) Cytogenet.
Cell Genet. 37: 461 only, 1984.

15. Evans, R. W.; Williams, J.; Moreton, K.: A variant of human transferrin
with abnormal properties. Biochem. J. 201: 19-26, 1982.

16. Giari, A.; Weidinger, S.; Domenici, R.; Bargagna, M.: Transferrin
variants in Tuscany (Italy): evidence for two 'new' Tf alleles. Hum.
Genet. 69: 284-286, 1985.

17. Goya, N.; Miyazaki, S.; Kodate, S.; Ushio, B.: A family of congenital
atransferrinemia. Blood 40: 239-245, 1972.

18. Hayashi, A.; Wada, Y.; Suzuki, T.; Shimizu, A.: Studies on familial
hypotransferrinemia: unique clinical course and molecular pathology. Am.
J. Hum. Genet. 53: 201-213, 1993.

19. Hershberger, C. L.; Larson, J. L.; Arnold, B.; Rosteck, P. R.,
Jr.; Williams, P.; DeHoff, B.; Dunn, P.; O'Neal, K. L.; Riemen, M.
W.; Tice, P. A.; Crofts, R.; Ivancic, J.: A cloned gene for human
transferrin. Ann. N. Y. Acad. Sci. 646: 140-154, 1991.

20. Huerre, C.; Uzan, G.; Grzeschik, K. H.; Weil, D.; Levin, M.; Hors-Cayla,
M.-C.; Boue, J.; Kahn, A.; Junien, C.: The structural gene for transferrin
(TF) maps to 3q21-3qter. Ann. Genet. 27: 5-10, 1984.

21. Jenkins, T.; Bothwell, T. H.; Maier, G.; Laidler, A.: Is transferrin
normal in idiopathic haemochromatosis? Brit. J. Haemat. 52: 493-495,
1982.

22. Kamboh, M. I.; Ferrell, R. E.: Human transferrin polymorphism. Hum.
Hered. 37: 65-81, 1987.

23. King, J.; Robson, E. B.; Edwards, V. H.; Cook, P. J. L.; Buckton,
K. E.: Miscellaneous contributions to the mapping of chromosome 1.
(Abstract) Cytogenet. Cell Genet. 25: 172 only, 1979.

24. Knisely, A. S.; Gelbart, T.; Beutler, E.: Molecular characterization
of a third case of human atransferrinemia. (Letter) Blood 104: 2607
only, 2004.

25. Kueppers, F.; Harpel, B. M.: Transferrin C subtypes in US blacks
and whites. Hum. Hered. 30: 376-382, 1980.

26. Lee, P. L.; Halloran, C.; Trevino, R.; Felitti, V.; Beutler, E.
: Human transferrin G277S mutation: a risk factor for iron deficiency
anaemia. Brit. J. Haemat. 115: 329-333, 2001.

27. MacGillivray, R. T. A.; Mendez, E.; Sinha, S. K.; Sutton, M. R.;
Lineback-Zins, J.; Brew, K.: The complete amino acid sequence of
human serum transferrin. Proc. Nat. Acad. Sci. 79: 2504-2508, 1982.

28. McAlpine, P. J.; Allderdice, P. W.; Cox, D. W.; Simpson, N. E.;
McEachran, M.; Komarnicki, L.: The ordering of TF:CHE1:AHSG and their
orientation distal to 3q21. (Abstract) Cytogenet. Cell Genet. 46:
659 only, 1987.

29. Namekata, K.; Oyama, F.; Imagawa, M.; Ihara, Y.: Human transferrin
(Tf): a single mutation at codon 570 determines Tf C1 or Tf C2 variant. Hum.
Genet. 100: 457-458, 1997.

30. Naylor, S. L.; Lalley, P. A.; Elliott, R. W.; Brown, J. A.; Shows,
T. B.: Evidence for homologous regions of human chromosome 3 and
mouse chromosome 9 predicts location of human genes. (Abstract) Am.
J. Hum. Genet. 32: 158A only, 1980.

31. Pang, H.; Koda, Y.; Soejima, M.; Kimura, H.: Identification of
a mutation (A1879G) of transferrin from cDNA prepared from peripheral
blood cells. Ann. Hum. Genet. 62: 271-274, 1998.

32. Park, I.; Schaeffer, E.; Sidoli, A.; Baralle, F. E.; Cohen, G.
N.; Zakin, M. M.: Organization of the human transferrin gene: direct
evidence that it originated by gene duplication. Proc. Nat. Acad.
Sci. 82: 3149-3153, 1985.

33. Parker, W. C.; Bearn, A. G.: Additional genetic variation of
human serum transferrin. Science 137: 854-856, 1962.

34. Robson, E. B.; Sutherland, I.; Harris, H.: Evidence for linkage
between the transferrin locus (TF) and the serum cholinesterase locus
E(1) in man. Ann. Hum. Genet. 29: 325-336, 1966.

35. Robson, K. J. H.; Lehmann, D. J.; Wimhurst, V. L. C.; Livesey,
K. J.; Combrinck, M.; Merryweather-Clarke, A. T.; Warden, D. R.; Smith,
A. D.: Synergy between the C2 allele of transferrin and the C282Y
allele of the haemochromatosis gene (HFE) as risk factors for developing
Alzheimer's disease. J. Med. Genet. 41: 261-265, 2004.

36. Roychoudhury, A. K.; Nei, M.: Human Polymorphic Genes: World
Distribution. New York: Oxford Univ. Press (pub.) 1988.

37. Sass-Kuhn, S. P.; Moqbel, R.; Mackay, J. A.; Cromwell, O.; Kay,
A. B.: Human granulocyte/pollen-binding protein: recognition and
identification as transferrin. J. Clin. Invest. 73: 202-210, 1984.

38. Smithies, O.: Third allele at the serum beta-globulin locus in
humans. Nature 181: 1203-1204, 1958.

39. Smithies, O.: Variants in human serum B-globulins. Nature 180:
1482 only, 1957.

40. Sutherland, R.; Delia, D.; Schneider, C.; Newman, R.; Kemshead,
J.; Greaves, M.: Ubiquitous cell-surface glycoprotein on tumor cells
is proliferation-associated receptor for transferrin. Proc. Nat.
Acad. Sci. 78: 4515-4519, 1981.

41. Uzan, G.; Frain, M.; Park, I.; Besmond, C.; Maessen, G.; Trepat,
J. S.; Zakin, M. M.; Kahn, A.: Molecular cloning and sequence analysis
of cDNA for human transferrin. Biochem. Biophys. Res. Commun. 119:
273-281, 1984.

42. Wang, A.-C.; Sutton, H. E.: Human transferrins C and D(1): chemical
difference in a peptide. Science 149: 435-437, 1965.

43. Wang, A.-C.; Sutton, H. E.; Howard, P. N.: Human transferrins
C and D(Chi): an amino-acid difference. Biochem. Genet. 1: 55-60,
1967.

44. Wang, A.-C.; Sutton, H. E.; Riggs, A.: A chemical difference
between human transferrins B2 and C. Am. J. Hum. Genet. 18: 454-458,
1966.

45. Weidinger, S.; Cleve, H.; Schwarzfischer, F.; Postel, W.; Weser,
J.; Gorg, A.: Transferrin subtypes and variants in Germany; further
evidence for a Tf null allele. Hum. Genet. 66: 356-360, 1984.

46. Weinzimer, S. A.; Gibson, T. B.; Collett-Solberg, P. F.; Khare,
A.; Liu, B.; Cohen, P.: Transferrin is an insulin-like growth factor-binding
protein-3 binding protein. J. Clin. Endocr. Metab. 86: 1806-1813,
2001.

47. Welch, S.; Langmead, L.: A comparison of the structure and properties
of normal human transferrin and a genetic variant of human transferrin. Int.
J. Biochem. 22: 275-282, 1990.

48. Yang, F.; Lum, J. B.; McGill, J. R.; Moore, C. M.; Naylor, S.
L.; van Bragt, P. H.; Baldwin, W. D.; Bowman, B. H.: Human transferrin:
cDNA characterization and chromosomal localization. Proc. Nat. Acad.
Sci. 81: 2752-2756, 1984.

49. Young, S. P.; Bomford, A.; Madden, A. D.; Garratt, R. C.; Williams,
R.; Evans, R. W.: Abnormal in vitro function of a variant human transferrin. Brit.
J. Haemat. 56: 581-587, 1984.

*FIELD* CN
Cassandra L. Kniffin - updated: 2/23/2009
Cassandra L. Kniffin - reorganized: 2/23/2009
Marla J. F. O'Neill - updated: 3/30/2006
Victor A. McKusick - updated: 12/6/2004
Victor A. McKusick - updated: 4/29/2004
Victor A. McKusick - updated: 9/8/2003
Victor A. McKusick - updated: 5/30/2003
Victor A. McKusick - updated: 8/5/2002
Victor A. McKusick - updated: 1/24/2002
John A. Phillips, III - updated: 10/24/2001
Victor A. McKusick - updated: 2/14/2001
Victor A. McKusick - updated: 2/16/1999
Victor A. McKusick - updated: 9/8/1997

*FIELD* CD
Victor A. McKusick: 6/2/1986

*FIELD* ED
alopez: 08/29/2011
carol: 10/21/2010
terry: 4/30/2010
carol: 1/28/2010
carol: 2/25/2009
carol: 2/24/2009
carol: 2/23/2009
ckniffin: 2/3/2009
wwang: 3/31/2006
terry: 3/30/2006
terry: 12/14/2005
joanna: 4/15/2005
tkritzer: 1/24/2005
terry: 12/6/2004
tkritzer: 5/27/2004
tkritzer: 5/19/2004
terry: 4/29/2004
cwells: 9/10/2003
terry: 9/8/2003
tkritzer: 6/5/2003
terry: 5/30/2003
tkritzer: 8/8/2002
tkritzer: 8/7/2002
terry: 8/5/2002
carol: 2/6/2002
mcapotos: 2/4/2002
terry: 1/24/2002
alopez: 10/24/2001
alopez: 7/27/2001
carol: 2/26/2001
cwells: 2/20/2001
terry: 2/14/2001
terry: 6/11/1999
mgross: 2/22/1999
mgross: 2/18/1999
terry: 2/16/1999
jenny: 9/18/1997
terry: 9/8/1997
mimadm: 5/10/1995
davew: 8/5/1994
carol: 5/13/1994
terry: 4/27/1994
warfield: 3/7/1994
supermim: 3/16/1992

MIM 209300
*RECORD*
*FIELD* NO
209300
*FIELD* TI
#209300 ATRANSFERRINEMIA
;;HYPOTRANSFERRINEMIA, FAMILIAL
TRANSFERRIN SERUM LEVEL QUANTITATIVE TRAIT LOCUS 1, INCLUDED; TFQTL1,
read moreINCLUDED
*FIELD* TX
A number sign (#) is used with this entry because atransferrinemia has
been found to be caused by mutation in the structural gene for
transferrin (TF; 190000) on chromosome 3q22.1. Variation in the TF gene
also affects serum transferrin levels.

Variation in the HFE gene (613609.0001) also affects serum transferrin
levels (see TFQTL2, 614193).

DESCRIPTION

Atransferrinemia is characterized by microcytic anemia and by iron
loading. It can be treated effectively by plasma infusions (summary by
Beutler et al., 2000).

CLINICAL FEATURES

Heilmeyer et al. (1961) described total absence of transferrin in a
7-year-old girl whose presenting complaint was severe hypochromic
anemia. Death occurred from heart failure. Severe hemosiderosis of the
heart and liver was found at autopsy. About half-normal levels of
transferrin in both parents supported recessive inheritance (Goya et
al., 1972).

Goya et al. (1972) described a patient with only a trace of transferrin
in the blood by immunologic methods, who responded well to parenteral
administration of transferrin. Hayashi et al. (1993) restudied the
family reported by Goya et al. (1972). The proband showed late onset of
anemia and growth retardation (at age 7 years) and was found to have a
healthy brother and a sister with very low transferrin levels.
Supplementary therapy with apo-TF over a period of 5 years resulted in
gradual disappearance of the anemia and improvement in growth. Severe
deficiency of both TF and haptoglobin were demonstrated by
immunoelectrophoretic studies. Recovery from anemia and the resumption
of growth were dependent, however, only on his TF level. Hayashi et al.
(1993) suggested that TF values less than 10 mg/dl may result in severe
growth retardation and anemia, whereas persons with more than 20 mg/dl
are apparently healthy. They also suggested that coexisting haptoglobin
deficiency may alleviate hemosiderosis. Study by isoelectric focusing
disclosed that there was a small amount of TF variant present in all 3
sibs, and that the variant was produced by an allelic gene derived from
their father. For that reason, Hayashi et al. (1993) suggested that the
condition be termed hypotransferrinemia, that it is a recessive trait,
and that subjects with the recessive phenotype may be compound
heterozygotes of a 'variant' allele and a 'null' allele.

Westerhausen and Meuret (1977) observed an acquired (autoimmune) form of
atransferrinemia.

MAPPING

- Serum Transferrin Quantitative Trait Locus

Benyamin et al. (2009) provided evidence that variation in the TF gene
was associated with serum transferrin levels. A genomewide association
study of 411 adolescent twins and their sibs, all of European descent,
demonstrated that dbSNP rs1830084, located 3-prime to the TF gene, was
significantly associated with serum transferrin levels (p = 1.0 x
10(-9)). A second scan on an independent sample of 459 female
monozygotic twin pairs found an association with dbSNP rs3811647 within
intron 11 of the TF gene (p = 3 x 10(-15)). The second scan also
identified 2 additional and independent SNPs in TF (dbSNP rs1799852 and
dbSNP rs2280673) that were associated with serum transferrin levels. The
known C282Y variant in the HFE gene (613609.0001) was independently
associated with serum transferrin (p = 1.1 x 10(-10)). The 3 TF SNPs
found in the second scan plus the HFE C282Y mutation explained about 40%
of genetic variation in serum transferrin levels (p = 7.8 x 10(-25)).

MOLECULAR GENETICS

Beutler et al. (2000) stated that atransferrinemia had been reported in
only 8 patients in 6 families. They reported the first known case in the
United States and identified mutations in the TF gene
(190000.0006-190000.0007). The patient was a compound heterozygote.

ANIMAL MODEL

Craven et al. (1987) studied hypotransferrinemia in the mouse. The
tissue distribution of iron overload was similar to that in
hemochromatosis; the hypotransferrinemic mice accumulated iron in the
liver and pancreas. The authors suggested that hereditary
hemochromatosis (235200) and congenital atransferrinemia in man are one
and the same disease and that they are associated with subnormal
concentration of plasma apo-transferrin. Inasmuch as the transferrin
locus maps to chromosome 3 and the hemochromatosis locus to chromosome
6, the suggestion that the atransferrinemic mouse is a model of
hemochromatosis cannot be extended to the level of the gene.

*FIELD* SA
Heilmeyer (1966); Heilmeyer et al. (1965)
*FIELD* RF
1. Benyamin, B.; McRae, A. F.; Zhu, G.; Gordon, S.; Henders, A. K.;
Palotie, A.; Peltonen, L.; Martin, N. G.; Montgomery, G. W.; Whitfield,
J. B.; Visscher, P. M.: Variants in TF and HFE explain about 40%
of genetic variation in serum-transferrin levels. Am. J. Hum. Genet. 84:
60-65, 2009.

2. Beutler, E.; Gelbart, T.; Lee, P.; Trevino, R.; Fernandez, M. A.;
Fairbanks, V. F.: Molecular characterization of a case of atransferrinemia. Blood 96:
4071-4074, 2000.

3. Craven, C. M.; Alexander, J.; Eldridge, M.; Kushner, J. P.; Bernstein,
S.; Kaplan, J.: Tissue distribution and clearance kinetics of non-transferrin-bound
iron in the hypotransferrinemic mouse: a rodent model for hemochromatosis. Proc.
Nat. Acad. Sci. 84: 3457-3461, 1987.

4. Goya, N.; Miyazaki, S.; Kodate, S.; Ushio, B.: A family of congenital
atransferrinemia. Blood 40: 239-245, 1972.

5. Hayashi, A.; Wada, Y.; Suzuki, T.; Shimizu, A.: Studies on familial
hypotransferrinemia: unique clinical course and molecular pathology. Am.
J. Hum. Genet. 53: 201-213, 1993.

6. Heilmeyer, L.: Die Atransferrinaemien. Acta Haemat. 36: 40-49,
1966.

7. Heilmeyer, L.; Keller, W.; Vivell, O.; Keiderling, W.; Betke, K.;
Wohler, F.; Schultze, H. E.: Kongenitale Atransferrinaemie bei einem
sieben Jahre alten Kind. Dtsch. Med. Wschr. 86: 1745-1751, 1961.

8. Heilmeyer, L.; Merker, H.; Wetzel, H. P.; Burmeister, P.; Haas,
R.: Atransferrinaemie bei nephrotischem Syndrom. Dtsch. Med. Wschr. 90:
1649-1656, 1965.

9. Westerhausen, M.; Meuret, G.: Transferrin-immune complex disease. Acta
Haemat. 57: 96-101, 1977.

*FIELD* CS

Heme:
Anemia, hypochromic

Lab:
Transferrin absent

Cardiovascular:
Congestive heart failure;
Hemosiderosis, heart

Liver:
Hemosiderosis

Inheritance:
Autosomal recessive

*FIELD* CN
Victor A. McKusick - updated: 2/14/2001

*FIELD* CD
Victor A. McKusick: 6/3/1986

*FIELD* ED
alopez: 09/01/2011
alopez: 9/1/2011
carol: 2/26/2001
cwells: 2/20/2001
terry: 2/14/2001
mimadm: 2/19/1994
carol: 7/21/1993
supermim: 3/16/1992
supermim: 3/20/1990
ddp: 10/26/1989
marie: 3/25/1988