Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Transferrin receptor protein 2

Gene

TFR2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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

GO - Molecular functioni

  • co-receptor binding Source: BHF-UCL
  • glycoprotein binding Source: BHF-UCL
  • transferrin receptor activity Source: UniProtKB

GO - Biological processi

  • acute-phase response Source: Ensembl
  • cellular iron ion homeostasis Source: UniProtKB
  • cellular response to iron ion Source: BHF-UCL
  • ferrous iron import into cell Source: BHF-UCL
  • iron ion homeostasis Source: BHF-UCL
  • iron ion transport Source: UniProtKB
  • positive regulation of endocytosis Source: BHF-UCL
  • positive regulation of peptide hormone secretion Source: BHF-UCL
  • positive regulation of protein maturation Source: BHF-UCL
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • receptor-mediated endocytosis Source: BHF-UCL
  • response to iron ion Source: BHF-UCL
  • transferrin transport Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Enzyme and pathway databases

BioCyciZFISH:ENSG00000106327-MONOMER.

Protein family/group databases

MEROPSiM28.973.

Names & Taxonomyi

Protein namesi
Recommended name:
Transferrin receptor protein 2
Short name:
TfR2
Gene namesi
Name:TFR2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:11762. TFR2.

Subcellular locationi

Isoform Beta :
  • Cytoplasm Curated

  • Note: Lacks the transmembrane domain. Probably intracellular.

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 83CytoplasmicSequence analysisAdd BLAST83
Transmembranei84 – 104Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini105 – 801ExtracellularSequence analysisAdd BLAST697

GO - Cellular componenti

  • cytoplasmic vesicle Source: BHF-UCL
  • external side of plasma membrane Source: BHF-UCL
  • HFE-transferrin receptor complex Source: BHF-UCL
  • integral component of plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Involvement in diseasei

Hemochromatosis 3 (HFE3)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:604250
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04251522V → I in HFE3. 1 PublicationCorresponds to variant rs80338876dbSNPEnsembl.1
Natural variantiVAR_012738172M → K in HFE3. 1 PublicationCorresponds to variant rs80338879dbSNPEnsembl.1
Natural variantiVAR_042517690Q → P in HFE3. 1 PublicationCorresponds to variant rs80338889dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi7036.
MalaCardsiTFR2.
MIMi604250. phenotype.
OpenTargetsiENSG00000106327.
Orphaneti225123. Hemochromatosis type 3.
PharmGKBiPA36477.

Chemistry databases

DrugBankiDB05260. Gallium nitrate.

Polymorphism and mutation databases

BioMutaiTFR2.
DMDMi20140912.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001741361 – 801Transferrin receptor protein 2Add BLAST801

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi108InterchainSequence analysis
Disulfide bondi111InterchainSequence analysis
Glycosylationi240N-linked (GlcNAc...)Sequence analysis1
Glycosylationi339N-linked (GlcNAc...)1 Publication1
Glycosylationi540N-linked (GlcNAc...)Sequence analysis1
Glycosylationi754N-linked (GlcNAc...)1 Publication1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ9UP52.
PeptideAtlasiQ9UP52.
PRIDEiQ9UP52.

PTM databases

iPTMnetiQ9UP52.
PhosphoSitePlusiQ9UP52.

Expressioni

Tissue specificityi

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.

Gene expression databases

BgeeiENSG00000106327.
CleanExiHS_TFR2.
ExpressionAtlasiQ9UP52. baseline and differential.
GenevisibleiQ9UP52. HS.

Organism-specific databases

HPAiCAB016255.
HPA011937.

Interactioni

Subunit structurei

Homodimer.

GO - Molecular functioni

  • co-receptor binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi112894. 10 interactors.
IntActiQ9UP52. 1 interactor.
STRINGi9606.ENSP00000223051.

Structurei

3D structure databases

ProteinModelPortaliQ9UP52.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi23 – 26Endocytosis signalSequence analysis4

Sequence similaritiesi

Belongs to the peptidase M28 family. M28B subfamily.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2195. Eukaryota.
COG2234. LUCA.
GeneTreeiENSGT00550000074421.
HOGENOMiHOG000124067.
HOVERGENiHBG023177.
InParanoidiQ9UP52.
OMAiLFISWDG.
OrthoDBiEOG091G02ZM.
PhylomeDBiQ9UP52.
TreeFamiTF312981.

Family and domain databases

Gene3Di1.20.930.40. 1 hit.
InterProiIPR003137. PA_domain.
IPR007484. Peptidase_M28.
IPR007365. TFR-like_dimer_dom.
[Graphical view]
PfamiPF02225. PA. 1 hit.
PF04389. Peptidase_M28. 1 hit.
[Graphical view]
SUPFAMiSSF47672. SSF47672. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Alpha (identifier: Q9UP52-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MERLWGLFQR AQQLSPRSSQ TVYQRVEGPR KGHLEEEEED GEEGAETLAH
60 70 80 90 100
FCPMELRGPE PLGSRPRQPN LIPWAAAGRR AAPYLVLTAL LIFTGAFLLG
110 120 130 140 150
YVAFRGSCQA CGDSVLVVSE DVNYEPDLDF HQGRLYWSDL QAMFLQFLGE
160 170 180 190 200
GRLEDTIRQT SLRERVAGSA GMAALTQDIR AALSRQKLDH VWTDTHYVGL
210 220 230 240 250
QFPDPAHPNT LHWVDEAGKV GEQLPLEDPD VYCPYSAIGN VTGELVYAHY
260 270 280 290 300
GRPEDLQDLR ARGVDPVGRL LLVRVGVISF AQKVTNAQDF GAQGVLIYPE
310 320 330 340 350
PADFSQDPPK PSLSSQQAVY GHVHLGTGDP YTPGFPSFNQ TQFPPVASSG
360 370 380 390 400
LPSIPAQPIS ADIASRLLRK LKGPVAPQEW QGSLLGSPYH LGPGPRLRLV
410 420 430 440 450
VNNHRTSTPI NNIFGCIEGR SEPDHYVVIG AQRDAWGPGA AKSAVGTAIL
460 470 480 490 500
LELVRTFSSM VSNGFRPRRS LLFISWDGGD FGSVGSTEWL EGYLSVLHLK
510 520 530 540 550
AVVYVSLDNA VLGDDKFHAK TSPLLTSLIE SVLKQVDSPN HSGQTLYEQV
560 570 580 590 600
VFTNPSWDAE VIRPLPMDSS AYSFTAFVGV PAVEFSFMED DQAYPFLHTK
610 620 630 640 650
EDTYENLHKV LQGRLPAVAQ AVAQLAGQLL IRLSHDRLLP LDFGRYGDVV
660 670 680 690 700
LRHIGNLNEF SGDLKARGLT LQWVYSARGD YIRAAEKLRQ EIYSSEERDE
710 720 730 740 750
RLTRMYNVRI MRVEFYFLSQ YVSPADSPFR HIFMGRGDHT LGALLDHLRL
760 770 780 790 800
LRSNSSGTPG ATSSTGFQES RFRRQLALLT WTLQGAANAL SGDVWNIDNN

F
Length:801
Mass (Da):88,755
Last modified:May 1, 2000 - v1
Checksum:iD3D3082BA835413A
GO
Isoform Beta (identifier: Q9UP52-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-171: Missing.

Show »
Length:630
Mass (Da):69,618
Checksum:i267F164C1D1DEEAE
GO
Isoform Gamma (identifier: Q9UP52-3) [UniParc]FASTAAdd to basket

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

Show »
Length:774
Mass (Da):86,012
Checksum:i09A2662EFC77C9A0
GO

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti712R → RIPLSAQV (PubMed:9799793).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04251522V → I in HFE3. 1 PublicationCorresponds to variant rs80338876dbSNPEnsembl.1
Natural variantiVAR_012738172M → K in HFE3. 1 PublicationCorresponds to variant rs80338879dbSNPEnsembl.1
Natural variantiVAR_034122230D → E.Corresponds to variant rs41303465dbSNPEnsembl.1
Natural variantiVAR_034123238I → M.Corresponds to variant rs34242818dbSNPEnsembl.1
Natural variantiVAR_042516455R → Q Hereditary hemochromatosis modifier. 1 PublicationCorresponds to variant rs41303501dbSNPEnsembl.1
Natural variantiVAR_042517690Q → P in HFE3. 1 PublicationCorresponds to variant rs80338889dbSNPEnsembl.1
Natural variantiVAR_034124752R → H.Corresponds to variant rs41295942dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0053541 – 171Missing in isoform Beta. 1 PublicationAdd BLAST171
Alternative sequenceiVSP_005355343 – 369Missing in isoform Gamma. CuratedAdd BLAST27

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS34707.1. [Q9UP52-1]
RefSeqiNP_001193784.1. NM_001206855.1. [Q9UP52-2]
NP_003218.2. NM_003227.3. [Q9UP52-1]
XP_005250610.1. XM_005250553.4. [Q9UP52-1]
XP_016868062.1. XM_017012573.1. [Q9UP52-1]
UniGeneiHs.544932.

Genome annotation databases

EnsembliENST00000223051; ENSP00000223051; ENSG00000106327. [Q9UP52-1]
ENST00000462107; ENSP00000420525; ENSG00000106327. [Q9UP52-1]
GeneIDi7036.
KEGGihsa:7036.
UCSCiuc003uvv.2. human. [Q9UP52-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS34707.1. [Q9UP52-1]
RefSeqiNP_001193784.1. NM_001206855.1. [Q9UP52-2]
NP_003218.2. NM_003227.3. [Q9UP52-1]
XP_005250610.1. XM_005250553.4. [Q9UP52-1]
XP_016868062.1. XM_017012573.1. [Q9UP52-1]
UniGeneiHs.544932.

3D structure databases

ProteinModelPortaliQ9UP52.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112894. 10 interactors.
IntActiQ9UP52. 1 interactor.
STRINGi9606.ENSP00000223051.

Chemistry databases

DrugBankiDB05260. Gallium nitrate.

Protein family/group databases

MEROPSiM28.973.

PTM databases

iPTMnetiQ9UP52.
PhosphoSitePlusiQ9UP52.

Polymorphism and mutation databases

BioMutaiTFR2.
DMDMi20140912.

Proteomic databases

PaxDbiQ9UP52.
PeptideAtlasiQ9UP52.
PRIDEiQ9UP52.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000223051; ENSP00000223051; ENSG00000106327. [Q9UP52-1]
ENST00000462107; ENSP00000420525; ENSG00000106327. [Q9UP52-1]
GeneIDi7036.
KEGGihsa:7036.
UCSCiuc003uvv.2. human. [Q9UP52-1]

Organism-specific databases

CTDi7036.
DisGeNETi7036.
GeneCardsiTFR2.
GeneReviewsiTFR2.
HGNCiHGNC:11762. TFR2.
HPAiCAB016255.
HPA011937.
MalaCardsiTFR2.
MIMi604250. phenotype.
604720. gene.
neXtProtiNX_Q9UP52.
OpenTargetsiENSG00000106327.
Orphaneti225123. Hemochromatosis type 3.
PharmGKBiPA36477.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2195. Eukaryota.
COG2234. LUCA.
GeneTreeiENSGT00550000074421.
HOGENOMiHOG000124067.
HOVERGENiHBG023177.
InParanoidiQ9UP52.
OMAiLFISWDG.
OrthoDBiEOG091G02ZM.
PhylomeDBiQ9UP52.
TreeFamiTF312981.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000106327-MONOMER.

Miscellaneous databases

GeneWikiiTFR2.
GenomeRNAii7036.
PROiQ9UP52.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000106327.
CleanExiHS_TFR2.
ExpressionAtlasiQ9UP52. baseline and differential.
GenevisibleiQ9UP52. HS.

Family and domain databases

Gene3Di1.20.930.40. 1 hit.
InterProiIPR003137. PA_domain.
IPR007484. Peptidase_M28.
IPR007365. TFR-like_dimer_dom.
[Graphical view]
PfamiPF02225. PA. 1 hit.
PF04389. Peptidase_M28. 1 hit.
[Graphical view]
SUPFAMiSSF47672. SSF47672. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiTFR2_HUMAN
AccessioniPrimary (citable) accession number: Q9UP52
Secondary accession number(s): A6NGM7
, O75422, Q1HE13, Q9HA99, Q9NX67
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 11, 2002
Last sequence update: May 1, 2000
Last modified: November 2, 2016
This is version 139 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Miscellaneous

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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Peptidase families
    Classification of peptidase families and list of entries
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.