|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
2
|
|
pubmed:dateCreated |
2000-7-20
|
|
pubmed:databankReference |
|
|
pubmed:abstractText |
We showed recently that the yeast mitochondrial intermediate peptidase (YMIP polypeptide; gene symbol, OCT1) promotes mitochondrial iron uptake by catalyzing the maturation of iron-utilizing proteins and exacerbates the mitochondrial iron accumulation that results from loss of yeast frataxin, a mitochondrial protein required for mitochondrial iron efflux. This suggests that the human MIP (HMIP polypeptide; gene symbol MIPEP) may be one of the loci predicted to influence the clinical manifestations of Friedreich's ataxia (FRDA), an autosomal recessive neurodegenerative disease caused by lack of human frataxin. To begin to test this hypothesis, we have characterized HMIP at the functional and genomic levels. We show that HMIP can complement a yeast knock-out mutant lacking YMIP, demonstrating that HMIP and YMIP are functional homologues. The MIPEP gene spans 57 kb and consists of 19 exons that correlate with the functional domains of HMIP. Primer extension analysis has identified a major transcript of the MIPEP gene expressed differentially and predominantly in tissues with high oxygen consumption, while sequence analysis of approximately 2 kb of 5'-flanking DNA has revealed putative Mt1/3/4, NF-kappaB, and AP-1 elements that may regulate MIPEP expression in these tissues. Using a new polymorphic (CA)(n) repeat in intron 4, MIPEP has been genetically mapped within a 7-cM interval between markers D13S283 and D13S217 on 13q12. This work provides the basis for molecular analysis of MIPEP in FRDA and possibly other neurodegenerative diseases.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Apr
|
|
pubmed:issn |
0888-7543
|
|
pubmed:author |
|
|
pubmed:copyrightInfo |
Copyright 2000 Academic Press.
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
15
|
|
pubmed:volume |
65
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
104-12
|
|
pubmed:dateRevised |
2010-11-18
|
|
pubmed:meshHeading |
pubmed-meshheading:10783257-Base Sequence,
pubmed-meshheading:10783257-Cell Division,
pubmed-meshheading:10783257-Chromosomes, Human, Pair 13,
pubmed-meshheading:10783257-Contig Mapping,
pubmed-meshheading:10783257-DNA, Fungal,
pubmed-meshheading:10783257-Family Health,
pubmed-meshheading:10783257-Fungal Proteins,
pubmed-meshheading:10783257-Genetic Complementation Test,
pubmed-meshheading:10783257-Genetic Linkage,
pubmed-meshheading:10783257-Humans,
pubmed-meshheading:10783257-Iron-Binding Proteins,
pubmed-meshheading:10783257-Metalloendopeptidases,
pubmed-meshheading:10783257-Molecular Sequence Data,
pubmed-meshheading:10783257-Phosphotransferases (Alcohol Group Acceptor),
pubmed-meshheading:10783257-Promoter Regions, Genetic,
pubmed-meshheading:10783257-Repetitive Sequences, Nucleic Acid,
pubmed-meshheading:10783257-Sequence Analysis, DNA,
pubmed-meshheading:10783257-Sequence Homology, Nucleic Acid,
pubmed-meshheading:10783257-Transcription, Genetic,
pubmed-meshheading:10783257-Yeasts
|
|
pubmed:year |
2000
|
|
pubmed:articleTitle |
Functional and genomic analysis of the human mitochondrial intermediate peptidase, a putative protein partner of frataxin.
|
|
pubmed:affiliation |
Department of Pediatric and Adolescent Medicine, Mayo Clinic and Foundation, 200 First Street SW, Rochester, Minnesota, 55905, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
|
