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Q9UP52 (TFR2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 119. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Transferrin receptor protein 2

Short name=TfR2
Gene names
Name:TFR2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length801 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Mediates cellular uptake of transferrin-bound iron in a non-iron dependent manner. May be involved in iron metabolism, hepatocyte function and erythrocyte differentiation.

Subunit structure

Homodimer.

Subcellular location

Cell membrane; Single-pass type II membrane protein.

Isoform Beta: Cytoplasm Probable. Note: Lacks the transmembrane domain. Probably intracellular.

Tissue specificity

Predominantly expressed in liver. While the alpha form is also expressed in spleen, lung, muscle, prostate and peripheral blood mononuclear cells, the beta form is expressed in all tissues tested, albeit weakly.

Involvement in disease

Hemochromatosis 3 (HFE3) [MIM:604250]: A disorder of iron metabolism characterized by iron overload. Excess iron is deposited in a variety of organs leading to their failure, and resulting in serious illnesses including cirrhosis, hepatomas, diabetes, cardiomyopathy, arthritis, and hypogonadotropic hypogonadism. Severe effects of the disease usually do not appear until after decades of progressive iron loading.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Ref.9 Ref.10 Ref.12

Miscellaneous

The variant Lys-172 found in hereditary hemochromatosis type III affects the putative initiation codon of the beta isoform thuspreventing its translation.

Sequence similarities

Belongs to the peptidase M28 family. M28B subfamily.

Sequence caution

The sequence BAA91153.1 differs from that shown. Reason: Erroneous initiation.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform Alpha (identifier: Q9UP52-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform Beta (identifier: Q9UP52-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-171: Missing.
Isoform Gamma (identifier: Q9UP52-3)

The sequence of this isoform differs from the canonical sequence as follows:
     343-369: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 801801Transferrin receptor protein 2
PRO_0000174136

Regions

Topological domain1 – 8383Cytoplasmic Potential
Transmembrane84 – 10421Helical; Signal-anchor for type II membrane protein; Potential
Topological domain105 – 801697Extracellular Potential
Motif23 – 264Endocytosis signal Potential

Amino acid modifications

Glycosylation2401N-linked (GlcNAc...) Potential
Glycosylation3391N-linked (GlcNAc...) Ref.8
Glycosylation5401N-linked (GlcNAc...) Potential
Glycosylation7541N-linked (GlcNAc...) Ref.8
Disulfide bond108Interchain Potential
Disulfide bond111Interchain Potential

Natural variations

Alternative sequence1 – 171171Missing in isoform Beta.
VSP_005354
Alternative sequence343 – 36927Missing in isoform Gamma.
VSP_005355
Natural variant221V → I in HFE3. Ref.12
VAR_042515
Natural variant1721M → K in HFE3. Ref.9
VAR_012738
Natural variant2301D → E.
Corresponds to variant rs41303465 [ dbSNP | Ensembl ].
VAR_034122
Natural variant2381I → M.
Corresponds to variant rs34242818 [ dbSNP | Ensembl ].
VAR_034123
Natural variant4551R → Q Hereditary hemochromatosis modifier. Ref.11
Corresponds to variant rs41303501 [ dbSNP | Ensembl ].
VAR_042516
Natural variant6901Q → P in HFE3. Ref.10
VAR_042517
Natural variant7521R → H.
Corresponds to variant rs41295942 [ dbSNP | Ensembl ].
VAR_034124

Experimental info

Sequence conflict7121R → RIPLSAQV Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform Alpha [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: D3D3082BA835413A

FASTA80188,755
        10         20         30         40         50         60 
MERLWGLFQR AQQLSPRSSQ TVYQRVEGPR KGHLEEEEED GEEGAETLAH FCPMELRGPE 

        70         80         90        100        110        120 
PLGSRPRQPN LIPWAAAGRR AAPYLVLTAL LIFTGAFLLG YVAFRGSCQA CGDSVLVVSE 

       130        140        150        160        170        180 
DVNYEPDLDF HQGRLYWSDL QAMFLQFLGE GRLEDTIRQT SLRERVAGSA GMAALTQDIR 

       190        200        210        220        230        240 
AALSRQKLDH VWTDTHYVGL QFPDPAHPNT LHWVDEAGKV GEQLPLEDPD VYCPYSAIGN 

       250        260        270        280        290        300 
VTGELVYAHY GRPEDLQDLR ARGVDPVGRL LLVRVGVISF AQKVTNAQDF GAQGVLIYPE 

       310        320        330        340        350        360 
PADFSQDPPK PSLSSQQAVY GHVHLGTGDP YTPGFPSFNQ TQFPPVASSG LPSIPAQPIS 

       370        380        390        400        410        420 
ADIASRLLRK LKGPVAPQEW QGSLLGSPYH LGPGPRLRLV VNNHRTSTPI NNIFGCIEGR 

       430        440        450        460        470        480 
SEPDHYVVIG AQRDAWGPGA AKSAVGTAIL LELVRTFSSM VSNGFRPRRS LLFISWDGGD 

       490        500        510        520        530        540 
FGSVGSTEWL EGYLSVLHLK AVVYVSLDNA VLGDDKFHAK TSPLLTSLIE SVLKQVDSPN 

       550        560        570        580        590        600 
HSGQTLYEQV VFTNPSWDAE VIRPLPMDSS AYSFTAFVGV PAVEFSFMED DQAYPFLHTK 

       610        620        630        640        650        660 
EDTYENLHKV LQGRLPAVAQ AVAQLAGQLL IRLSHDRLLP LDFGRYGDVV LRHIGNLNEF 

       670        680        690        700        710        720 
SGDLKARGLT LQWVYSARGD YIRAAEKLRQ EIYSSEERDE RLTRMYNVRI MRVEFYFLSQ 

       730        740        750        760        770        780 
YVSPADSPFR HIFMGRGDHT LGALLDHLRL LRSNSSGTPG ATSSTGFQES RFRRQLALLT 

       790        800 
WTLQGAANAL SGDVWNIDNN F 

« Hide

Isoform Beta [UniParc].

Checksum: 267F164C1D1DEEAE
Show »

FASTA63069,618
Isoform Gamma [UniParc].

Checksum: 09A2662EFC77C9A0
Show »

FASTA77486,012

References

« Hide 'large scale' references
[1]"Molecular cloning of transferrin receptor 2: a new member of the transferrin receptor-like family."
Kawabata H., Yang R., Hirama T., Vuong P.T., Kawano S., Gombart A.F., Koeffler H.P.
J. Biol. Chem. 274:20826-20832(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA AND BETA).
Tissue: Erythroleukemia and Myeloid leukemia cell.
[2]"Large-scale sequencing of two regions in human chromosome 7q22: analysis of 650 kb of genomic sequence around the EPO and CUTL1 loci reveals 17 genes."
Gloeckner G., Scherer S., Schattevoy R., Boright A.P., Weber J., Tsui L.-C., Rosenthal A.
Genome Res. 8:1060-1073(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM GAMMA).
[3]NHLBI resequencing and genotyping service (RS&G)
Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"The DNA sequence of human chromosome 7."
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. expand/collapse author list , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-158 AND 370-801.
Tissue: Carcinoma and Embryo.
[7]"The gene TFR2 is mutated in a new type of haemochromatosis mapping to 7q22."
Camaschella C., Roetto A., Cali A., De Gobbi M., Garozzo G., Carella M., Majorano N., Totaro A., Gasparini P.
Nat. Genet. 25:14-15(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: DISEASE.
[8]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-339 AND ASN-754.
Tissue: Liver.
[9]"New mutations inactivating transferrin 2 in hemochromatosis type 3."
Roetto A., Totaro A., Piperno A., Piga A., Longo F., Garozzo G., Cali A., De Gobbi M., Gasparini P., Camaschella C.
Blood 97:2555-2560(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HFE3 LYS-172.
[10]"Transferrin receptor 2 (TfR2) and HFE mutational analysis in non-C282Y iron overload: identification of a novel TfR2 mutation."
Mattman A., Huntsman D., Lockitch G., Langlois S., Buskard N., Ralston D., Butterfield Y., Rodrigues P., Jones S., Porto G., Marra M., De Sousa M., Vatcher G.
Blood 100:1075-1077(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HFE3 PRO-690.
[11]"Mutation analysis of transferrin-receptor 2 in patients with atypical hemochromatosis."
Hofmann W.-K., Tong X.-J., Ajioka R.S., Kushner J.P., Koeffler H.P.
Blood 100:1099-1100(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GLN-455.
[12]"Identification of new mutations of the HFE, hepcidin, and transferrin receptor 2 genes by denaturing HPLC analysis of individuals with biochemical indications of iron overload."
Biasiotto G., Belloli S., Ruggeri G., Zanella I., Gerardi G., Corrado M., Gobbi E., Albertini A., Arosio P.
Clin. Chem. 49:1981-1988(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HFE3 ILE-22.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF067864 mRNA. Translation: AAD45561.1.
AF053356 Genomic DNA. Translation: AAC78796.1.
DQ496110 Genomic DNA. Translation: ABF47099.1.
AC099394 Genomic DNA. No translation available.
BC142630 mRNA. Translation: AAI42631.1.
AK022002 mRNA. Translation: BAB13951.1.
AK000421 mRNA. Translation: BAA91153.1. Different initiation.
RefSeqNP_001193784.1. NM_001206855.1.
NP_003218.2. NM_003227.3.
XP_005250610.1. XM_005250553.2.
UniGeneHs.544932.

3D structure databases

ProteinModelPortalQ9UP52.
SMRQ9UP52. Positions 134-799.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112894. 6 interactions.
IntActQ9UP52. 1 interaction.
STRING9606.ENSP00000223051.

Protein family/group databases

MEROPSM28.973.

PTM databases

PhosphoSiteQ9UP52.

Polymorphism databases

DMDM20140912.

Proteomic databases

PaxDbQ9UP52.
PRIDEQ9UP52.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000223051; ENSP00000223051; ENSG00000106327. [Q9UP52-1]
ENST00000462107; ENSP00000420525; ENSG00000106327. [Q9UP52-1]
ENST00000544242; ENSP00000443656; ENSG00000106327.
GeneID7036.
KEGGhsa:7036.
UCSCuc003uvu.1. human. [Q9UP52-1]
uc010lhc.1. human. [Q9UP52-2]

Organism-specific databases

CTD7036.
GeneCardsGC07M100218.
HGNCHGNC:11762. TFR2.
HPACAB016255.
HPA011937.
MIM604250. phenotype.
604720. gene.
neXtProtNX_Q9UP52.
Orphanet225123. Hemochromatosis type 3.
PharmGKBPA36477.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG74799.
HOGENOMHOG000124067.
HOVERGENHBG023177.
InParanoidQ9UP52.
OMALFISWDG.
OrthoDBEOG780RKW.
PhylomeDBQ9UP52.
TreeFamTF312981.

Gene expression databases

ArrayExpressQ9UP52.
BgeeQ9UP52.
CleanExHS_TFR2.
GenevestigatorQ9UP52.

Family and domain databases

Gene3D1.20.930.40. 1 hit.
InterProIPR007484. Peptidase_M28.
IPR003137. Protease-assoc_domain.
IPR007365. TFR-like_dimer_dom.
[Graphical view]
PfamPF02225. PA. 1 hit.
PF04389. Peptidase_M28. 1 hit.
PF04253. TFR_dimer. 1 hit.
[Graphical view]
SUPFAMSSF47672. SSF47672. 1 hit.
ProtoNetSearch...

Other

GeneWikiTFR2.
GenomeRNAi7036.
NextBio27489.
PROQ9UP52.
SOURCESearch...

Entry information

Entry nameTFR2_HUMAN
AccessionPrimary (citable) accession number: Q9UP52
Secondary accession number(s): A6NGM7 expand/collapse secondary AC list , O75422, Q1HE13, Q9HA99, Q9NX67
Entry history
Integrated into UniProtKB/Swiss-Prot: February 11, 2002
Last sequence update: May 1, 2000
Last modified: April 16, 2014
This is version 119 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM