CoChat
Sign Up
Cited by 827Iron Metabolism and DisordersNeurological diseases and metabolismHemoglobinopathies and Related Disorders

The DOI matches its Crossref record; 27 of the 28 references it cites were found in a registry or an index.

The hemochromatosis gene product complexes with the transferrin receptor and lowers its affinity for ligand binding

Open access
Feder, John N., Penny, David M., Irrinki, Alivelu, Lee, Vince K., Lebrón, José A., Watson, Nicole, Tsuchihashi, Zenta, Sigal, Elliott, Bjorkman, Pamela J., Schatzman, Randall C.·1998·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.95.4.1472PMC PMC19050
Open this paper in CoChat — free account

Abstract

We recently reported the positional cloning of a candidate gene for hereditary hemochromatosis called HFE . The gene product, a member of the major histocompatibility complex class I-like family, was found to have a mutation, Cys-282 → Tyr (C282Y), in 85% of patient chromosomes. This mutation eliminates the ability of HFE to associate with β 2 -microglobulin (β 2 m) and prevents cell-surface expression. A second mutation that has no effect on β 2 m association, H63D, was found in eight out of nine patients heterozygous for the C282Y mutant. In this report, we demonstrate in cultured 293 cells overexpressing wild-type or mutant HFE proteins that both the wild-type and H63D HFE proteins form stable complexes with the transferrin receptor (TfR). The C282Y mutation nearly completely prevents the association of the mutant HFE protein with the TfR. Studies on cell-associated transferrin at 37°C suggest that the overexpressed wild-type HFE protein decreases the affinity of the TfR for transferrin. The overexpressed H63D protein does not have this effect, providing the first direct evidence for a functional consequence of the H63D mutation. Addition of soluble wild-type HFE/β 2 m heterodimers to cultured cells also decreased the apparent affinity of the TfR for its ligand under steady-state conditions, both in 293 cells and in HeLa cells. Furthermore, at 4°C, the added soluble complex of HFE/β 2 m inhibited binding of transferrin to HeLa cell TfR in a concentration-dependent manner. Scatchard plots of these data indicate that the added heterodimer substantially reduced the affinity of TfR for transferrin. These results establish a molecular link between HFE and a key protein involved in iron transport, the TfR, and raise the possibility that alterations in this regulatory mechanism may play a role in the pathogenesis of hereditary hemochromatosis.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1073/pnas.95.4.1472

Cites

27 of 27 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

1 of the 28 references couldn’t be matched to a known paper.

Research works printed but not linked: 2

  1. T H Bothwell, R W Charlton, A G Motulsky The Metabolic and Molecular Basis of Inherited Disease, eds C R Scriver, A L Beaudet, W S Sly, D Valle (McGraw-Hill, New York), pp. 2237–2269 (1995).
  2. C R Bebbingtion, C G G Hentschel DNA Cloning: A Practical Approach., ed D M Glover (IRL, Oxford), pp. 163–188 (1987).

Cited by

Sorted by citations

See all 827

Related

See all

Metadata

Authors
Feder, J. N., Penny, D. M., Irrinki, A., Lee, V. K., Lebrón, J. A., Watson, N., Tsuchihashi, Z., Sigal, E., Bjorkman, P. J., & Schatzman, R. C.
Affiliations
  • California Institute of Technology (US)
  • Progenitor, Inc. (formerly Mercator Genetics, Inc.), 4040 Campbell Avenue, Menlo Park, CA 94025; and Division of Biology 156-29 and Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
1998-02-17
Volume
95
Issue
4
Pages
1472-1477
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.95.4.1472
PMC
PMC19050
OpenAlex
W2141937988
Cited by
827
References
28
Citations by year
2026: 3 · 2025: 4 · 2024: 4 · 2023: 9 · 2022: 7 · 2021: 7 · 2020: 14 · 2019: 7 · 2018: 10 · 2017: 16 · 2016: 24 · 2015: 21 · 2014: 18 · 2013: 28 · 2012: 26
FWCI
51.51
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • CaltechAUTHORS (California Institute of Technology) (submittedVersion)
Topics
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
  • Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
  • Health Sciences › Medicine › Genetics (clinical) › Hemoglobinopathies and Related Disorders
Keywords
hereditary hemochromatosis, HFE gene, transferrin receptor, C282Y mutation, H63D mutation, beta2-microglobulin, protein complex formation, iron transport, pathogenesis
MeSH terms
Hemochromatosis Protein, Amino Acid Sequence, beta 2-Microglobulin, Hemochromatosis, HLA Antigens, Humans, Ligands, Membrane Proteins, Precipitin Tests, Protein Binding, Receptors, Transferrin, Structure-Activity Relationship, Transfection, Transferrin, Histocompatibility Antigens Class I, Point Mutation, Dimerization

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review