Protein jagunal homolog 1 (JAGN1)
The protein contains 183 amino acids for an estimated molecular weight of 21125 Da.
Endoplasmic reticulum transmembrane protein involved in vesicle-mediated transport, which is required for neutrophil function. Required for vesicle-mediated transport; it is however unclear whether it is involved in early secretory pathway or intracellular protein transport. Acts as a regulator of neutrophil function, probably via its role in vesicle-mediated transport: required for defense against fungal pathogens and for granulocyte colony-stimulating factor (GM-CSF) signaling pathway; possibly by regulating glycosylation and/or targeting of proteins contributing to the viability and migration of neutrophils. (updated: March 4, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is predicted to be membranous by TOPCONS.
Biological Process
Cellular response to tunicamycin
Defense response to fungus
Endoplasmic reticulum organization
Exocytosis
Granulocyte colony-stimulating factor signaling pathway
Negative regulation of insulin secretion involved in cellular response to glucose stimulus
Neutrophil differentiation
Neutrophil mediated immunity
Neutrophil migration
Protein transport
Vesicle-mediated transport
Cellular Component
Endoplasmic reticulum
Endoplasmic reticulum membrane
Integral component of membrane
Molecular Function
The reference OMIM entry for this protein is 616012
Jagunal, drosophila, homolog of, 1; jagn1
DESCRIPTION
JAGN1 is an endoplasmic reticulum (ER)-resident protein that functions in the early secretory pathway (Boztug et al., 2014).CLONING
Boztug et al. (2014) cloned and characterized the JAGN1 gene, which was ubiquitously expressed. Immunofluorescence microscopy of HeLa cells detected endogenous and fluorescence-tagged JAGN1 in the ER.GENE STRUCTURE
Boztug et al. (2014) determined that the JAGN1 gene contains 2 exons.MAPPING
Hartz (2014) mapped the JAGN1 gene to chromosome 3p25.3 based on an alignment of the JAGN1 sequence (GenBank GENBANK AF212230) with the genomic sequence (GRCh38). Wirnsberger et al. (2014) stated that mouse Jagn1 maps to chromosome 6.GENE FUNCTION
Using tandem affinity purification, Boztug et al. (2014) found that epitope-tagged JAGN1 interacted with 3 members of the coat protein I (COPI) complex, COPA (601924), COPB2 (606990), and COPG2 (604355), in transfected HEK293 cells. Knockdown of JAGN1 expression via small interfering RNA in HeLa cells expressing GCSFR (CSF3R; 138971), a critical cytokine receptor governing neutrophil differentiation, interfered with STAT3 (102582) phosphorylation upon exposure to recombinant human GCSF (CSF3; 138970).MOLECULAR GENETICS
In 14 patients from 9 families with autosomal recessive severe congenital neutropenia-6 (SCN6; 616022), Boztug et al. (2014) identified 9 different homozygous mutations in the JAGN1 gene (see, e.g., 616012.0001-616012.0005). The mutation in the first family was found by linkage analysis, followed by candidate gene sequencing as well as exome and Sanger sequencing; subsequent mutations were found by direct sequencing of the JAGN1 gene in 74 individuals with SCN. Most of the mutations were missense mutations; 1 patient had a truncating mutation. There were no apparent genotype/phenotype correlations. Bone marrow biopsy showed maturational arrest of granulocytes at the promyelocyte/myelocyte stage. Electron microscopy of patient neutrophils showed an abnormal and enlarged ER with almost complete absence of granules, as well as evidence of increased ER stress. Patient cells showed increased apoptosis compared to control cells. In addition, JAGN1-mutant neutrophils showed abnormal N-glycomic profiles with a marked reduction in the fucosylation of all multiantennary glycans. O-glycosylation patterns were normal. Patients showed a poor response to GCSF treatment, and JAGN1-deficient neutrophils showed decreased amounts of GCSF receptors (CSF3R; 138971), possibly resulting from the N-glycosylation defect. Wirnsberger et al. (2014) found that GMCSF (CSF2; 138960) treatment of bone marrow granulocytes from patients with JAGN1 mutations restored phosphorylation of STAT5 (STAT5A; 601511) and cytotoxicity in response to Candida albicans.ANIMAL MODEL
Wirnsberger et al. (2014) found that knockout of Jagn1 in mice caused lethality around embryonic day 8.5. Mice carrying a hematopoietic lineage-specific deletion of Jagn1, called Jagn1(delta-hem) mice, appeared normal and showed no gross abnormalities in total cellularity or composition of mesenteric lymph nodes, spleen, thymus, or bone marrow. However, Jagn1(delta-hem) mice did not mount an efficient neutrophil-dependent immune response to Candida albicans, resulting in elevated morbidity and mortality and massively increased fungal burdens in all organs tested. Global glycobiome analysis of Jagn1(delta-hem) neutrophils identified marke ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 616012 was added.
Feb. 25, 2016: Protein entry updated
Automatic update: model status changed
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed
Sept. 16, 2015: Protein entry updated
Automatic update: model status changed