Aivojen valkea aine ja atraktiinigeeni ATRN(20p13) , T2DM, obesitas ja monosyyttien DPPT-L.

https://link.springer.com/article/10.1007%2Fs10048-017-0515-7
2017 Abstract

Hypomyelinating leukodystrophies are a group of neurodevelopmental disorders that affect proper formation of the myelin sheath in the central nervous system. They are characterized by developmental delay, hypotonia, spasticity, and variable intellectual disability. We used whole exome analysis to study the molecular basis of hypomyelinating leukodystrophy in two sibs from a consanguineous family. A homozygous mutation, c.3068+5G>A, was identified in the ATRN gene, with the consequent insertion of an intronic sequence into the patients’ cDNA and a predicted premature termination of the ATRN polypeptide. ATRN encodes Attractin, which was previously shown to play a critical role in central myelination. Several spontaneous ATRN rodent mutants exhibited impaired myelination which was attributed to oxidative stress and accelerated apoptosis. ATRN can now be added to the growing list of genes associated with hypomyelinating leukodystrophy. The disease seems to be confined to the CNS; however, given the young age of our patients, longer follow-up may be required. Keywords

Attractin Hypomyelination Leukodystrophy 


Lisätietoa tästä geenistä PubMed Gene lähteestä:
 https://www.ncbi.nlm.nih.gov/gene/8455

Also known as MGCA; DPPT-L

Summary This gene encodes both membrane-bound and secreted protein isoforms. A membrane-bound isoform exhibits sequence similarity with the mouse mahogany protein, a receptor involved in controlling obesity. A secreted isoform is involved in the initial immune cell clustering during inflammatory responses that may regulate the chemotactic activity of chemokines. [provided by RefSeq, Apr 2016]

Expression Ubiquitous expression in duodenum (RPKM 20.8), thyroid (RPKM 17.2) and 25 other tissues

 (Kelch-domeenit voi laskea jaksoista ,joissa on GG----Y----W motiivi.

 

1. NM_001207047.3 → NP_001193976.1  attractin isoform 4
   
   Status: REVIEWED

   Description

   Transcript Variant: This variant (4) uses an alternate splice junction at the 3' end of the first exon and differs in the 3' UTR and coding region compared to variant 1. The resulting isoform (4) has distinct N- and C-termini compared to isoform 1. Unlike isoform 1, which is membrane-bound, isoform 4 is secreted.

   Source sequence(s)

   AK293010, AK302730, AL132773, BC101705, DA368237

   UniProtKB/Swiss-Prot

   O75882

   UniProtKB/TrEMBL

   B4DZ36

   Conserved Domains (7) summary

   cd03597
   Location:672 → 804

   (ALP)CLECT_attractin_like: C-type lectin-like domain (CTLD) of the type found in human and mouse attractin (AtrN) and attractin-like protein (ALP). CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. Mouse AtrN (the product of the mahogany gene) has been shown to bind Agouti protein and to function in agouti-induced pigmentation and obesity. Mutations in AtrN have also been shown to cause spongiform encephalopathy and hypomyelination in rats and hamsters. The cytoplasmic region of mouse ALP has been shown to binds to melanocortin receptor (MCR4). Signaling through MCR4 plays a role in appetite suppression. Attractin may have therapeutic potential in the treatment of obesity. Human attractin (hAtrN) has been shown to be expressed on activated T cells and released extracellularly. The circulating serum attractin induces the spreading of monocytes that become the focus of the clustering of non-proliferating T cells.

   cd00041
   Location:23 → 131

   CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.

   cd00055
   Location:946 → 991

   EGF_Lam; Laminin-type epidermal growth factor-like domain; laminins are the major noncollagenous components of basement membranes that mediate cell adhesion, growth migration, and differentiation; the laminin-type epidermal growth factor-like module occurs in ...

   sd00038
   Location:385 → 434

   Kelch; KELCH repeat [structural motif]

   pfam01437
   Location:816 → 867

   PSI; Plexin repeat

   pfam13415
   Location:234 → 284

   Kelch_3; Galactose oxidase, central domain

   pfam13854
   Location:274 → 312

   Kelch_5; Kelch motif
   
   
   
   

   REFERENCE   3  (residues 1 to 1156)
     AUTHORS   Laudes M, Oberhauser F, Schulte DM, Schilbach K, Freude S,
               Bilkovski R, Schulz O, Faust M and Krone W.
     TITLE     Dipeptidyl-peptidase 4 and attractin expression is increased in
               circulating blood monocytes of obese human subjects
     JOURNAL   Exp. Clin. Endocrinol. Diabetes 118 (8), 473-477 (2010)
      PUBMED   20198559
     REMARK    GeneRIF: The levels of both dipeptidyl-peptidase 4 and attractin in
               circulating monocytes were significantly higher in obese subjects
               as compared with levels in lean controls or in subjects with type 2
               diabetes.

   Atraktiinivajeen merkitys. Tutkimuskoe-eläimeltä:)

   https://www.ncbi.nlm.nih.gov/pubmed/19931230 

   Brain Res. 2010 Feb 2;1312:145-55. doi: 10.1016/j.brainres.2009.11.027. Epub 2009 Nov 18.

   Abnormal myelinogenesis both in the white and gray matter of the attractin-deficient mv rat.
   

   Izawa T¹, Yamate J, Franklin RJ, Kuwamura M.1

   Laboratory of Veterinary Pathology, Osaka Prefecture University, Rinku Orai-Kita, Izumisano, Osaka 598-8531, Japan.

   Abstract

   The myelin vacuolation (mv) rat exhibits hypomyelination and vacuole formation in the myelin throughout the CNS, caused by a null mutation in the attractin gene. Myelin alterations in the spinal cord of mv rats progress during postnatal development and are more prominent in the white matter. In contrast, microglial activation is confined to the gray matter of mv rats. We here investigate the distribution and expression patterns of major CNS myelin proteins in the spinal cord of mv rats during the development of the myelin lesions. Immunohistochemical and Western blot analyses demonstrated a considerable reduction in the expression of major CNS myelin proteins both in the white and gray matter of mv rats, which was consistent with the morphological alterations of myelin sheaths. Real-time PCR analysis revealed a significant decrease in expression of proteolipid protein (PLP) mRNA both in the white and gray matter of mv rats. However, there was no significant difference between control and mv rats in the cell number of PLP mRNA-positive oligodendrocytes either in the white or gray matter, suggesting an impairment of myelin protein production by oligodendrocytes. Our results indicate that myelinogenesis but not oligodendrogenesis is severely altered both in the white and gray matter of mv rats.
   

   (c) 2009 Elsevier B.V. All rights reserved.

   PMID:

   19931230

   DOI:

   10.1016/j.brainres.2009.11.027