NDLI: ATP6AP1 deficiency causes an immunodeficiency with hepatopathy, cognitive impairment and abnormal protein glycosylation

Content Provider	PubMed Central
Author	Jansen, Eric J. R. Timal, Sharita Ryan, Margret Angel, Ashikov Scherpenzeel, Monique Van Graham, Laurie A. Mandel, Hanna Alexander, Hoischen Iancu, Theodore C. Raymond, Kimiyo Steenbergen, Gerry Gilissen, Christian Karin, Huijben Bakel, Nick H. M. Van Maeda, Yusuke Rodenburg, Richard J. Adamowicz, Maciej Ellen, Crushell Koenen, Hans Adams, Darius Julia, Vodopiutz Greber-platzer, Susanne Müller, Thomas Gregor, Dueckers Morava, Eva Sykut-cegielska, Jolanta Martens, Gerard J. M. Wevers, Ron A. Niehues, Tim Huynen, Martijn A. Veltman, Joris A. Stevens, Tom H. Lefeber, Dirk J.
Copyright Year	2016
Abstract	The V-ATPase is the main regulator of intra-organellar acidification. Assembly of this complex has extensively been studied in yeast, while limited knowledge exists for man. We identified 11 male patients with hemizygous missense mutations in ATP6AP1, encoding accessory protein Ac45 of the V-ATPase. Homology detection at the level of sequence profiles indicated Ac45 as the long-sought human homologue of yeast V-ATPase assembly factor Voa1. Processed wild-type Ac45, but not its disease mutants, restored V-ATPase-dependent growth in Voa1 mutant yeast. Patients display an immunodeficiency phenotype associated with hypogammaglobulinemia, hepatopathy and a spectrum of neurocognitive abnormalities. Ac45 in human brain is present as the common, processed ∼40-kDa form, while liver shows a 62-kDa intact protein, and B-cells a 50-kDa isoform. Our work unmasks Ac45 as the functional ortholog of yeast V-ATPase assembly factor Voa1 and reveals a novel link of tissue-specific V-ATPase assembly with immunoglobulin production and cognitive function.
Related Links	http://dx.doi.org/10.1038/ncomms11600
Starting Page	11600
File Format	PDF
ISSN	20411723
e-ISSN	20411723
Journal	Nature Communications
Volume Number	7
Language	English
Publisher	Nature Publishing Group
Publisher Date	2016-05-01
Access Restriction	Open
Rights Holder	Nature Publishing Group
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Physics and Astronomy(all) Chemistry(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Chemistry Physics and Astronomy Biochemistry, Genetics and Molecular Biology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Genetic deficiency of the mitochondrial protein PGAM5 causes a Parkinson’s-like movement disorder

Spartan deficiency causes genomic instability and progeroid phenotypes

Biallelic loss-of-function mutation in NIK causes a primary immunodeficiency with multifaceted aberrant lymphoid immunity

GRK6 deficiency in mice causes autoimmune disease due to impaired apoptotic cell clearance

Glycine decarboxylase deficiency causes neural tube defects and features of non-ketotic hyperglycinemia in mice

Dynamic interplay between catalytic and lectin domains of GalNAc-transferases modulates protein O-glycosylation

Regulation of protein glycosylation and sorting by the Golgi matrix proteins GRASP55/65

Loss of the RNA-binding protein TACO1 causes late-onset mitochondrial dysfunction in mice

Double-sieving-defective aminoacyl-tRNA synthetase causes protein mistranslation and affects cellular physiology and development

ATP6AP1 deficiency causes an immunodeficiency with hepatopathy, cognitive impairment and abnormal protein glycosylation

Similar Documents

Genetic deficiency of the mitochondrial protein PGAM5 causes a Parkinson’s-like movement disorder

Spartan deficiency causes genomic instability and progeroid phenotypes

Biallelic loss-of-function mutation in NIK causes a primary immunodeficiency with multifaceted aberrant lymphoid immunity

GRK6 deficiency in mice causes autoimmune disease due to impaired apoptotic cell clearance

Glycine decarboxylase deficiency causes neural tube defects and features of non-ketotic hyperglycinemia in mice

Dynamic interplay between catalytic and lectin domains of GalNAc-transferases modulates protein O-glycosylation

Regulation of protein glycosylation and sorting by the Golgi matrix proteins GRASP55/65

Loss of the RNA-binding protein TACO1 causes late-onset mitochondrial dysfunction in mice

Double-sieving-defective aminoacyl-tRNA synthetase causes protein mistranslation and affects cellular physiology and development

ATP6AP1 deficiency causes an immunodeficiency with hepatopathy, cognitive impairment and abnormal protein glycosylation