Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2007-9-5
pubmed:abstractText
The molecular basis of the erythrocytosis group of red cell disorders is incompletely defined. Some cases are due to dysregulation of erythropoietin (Epo) synthesis. The hypoxia inducible transcription factor (HIF) tightly regulates Epo synthesis. HIF in turn is regulated through its alpha subunit, which under normoxic conditions is hydroxylated on specific prolines and targeted for degradation by the von Hippel Lindau (VHL) protein. Several mutations in VHL have been reported in erythrocytosis, but only 1 mutation in the HIF prolyl hydroxylase PHD2 (prolyl hydroxylase domain protein 2) has been described. Here, we report a novel PHD2 mutation, Arg371His, which causes decreased HIF binding, HIF hydroxylase, and HIF inhibitory activities. In the tertiary structure of PHD2, Arg371 lies close to the previously described Pro317Arg mutation site. These findings substantiate PHD2 as a critical enzyme controlling HIF and therefore Epo in humans, and furthermore suggest the location of an active site groove in PHD2 that binds HIF.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/17579185-11358837, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579185-11504942, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579185-12181324, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579185-12393546, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579185-12653567, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579185-12702509, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579185-15304631, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579185-15642664, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579185-15952883, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579185-16029446, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579185-16210343, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579185-16407130, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579185-16503548, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579185-16687917, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579185-16782814, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579185-17228556, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579185-17267906, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579185-8506290, http://linkedlifedata.com/resource/pubmed/commentcorrection/17579185-9488636
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
110
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2193-6
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
A novel erythrocytosis-associated PHD2 mutation suggests the location of a HIF binding groove.
pubmed:affiliation
Department of Haematology, Belfast City Hospital, Belfast, United Kingdom. melanie.percy@belfasttrust.hscni.net
pubmed:publicationType
Journal Article, Case Reports, Research Support, N.I.H., Extramural