Autism susceptibility gene 2 protein (AUTS2)
The protein contains 1259 amino acids for an estimated molecular weight of 138982 Da.
Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility (PubMed:25519132). The PRC1-like complex that contains PCGF5, RNF2, CSNK2B, RYBP and AUTS2 has decreased histone H2A ubiquitination activity, due to the phosphorylation of RNF2 by CSNK2B (PubMed:25519132). As a consequence, the complex mediates transcriptional activation (PubMed:25519132). In the cytoplasm, plays a role in axon and dendrite elongation and in neuronal migration during embryonic brain development. Promotes reorganization of the actin cytoskeleton, lamellipodia formation and neurite elongation via its interaction with RAC guanine nucleotide exchange factors, which then leads to the activation of RAC1 (By similarity). (updated: March 1, 2002)
Protein identification was indicated in the following studies:
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.
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| Variant | Description |
|---|---|
| dbSNP:rs2293507 |
No binding partner found
Biological Process
Actin cytoskeleton reorganization
Axon extension
Dendrite extension
Neuron migration
Positive regulation of histone H3-K4 methylation
Positive regulation of histone H4-K16 acetylation
Positive regulation of lamellipodium assembly
Positive regulation of Rac protein signal transduction
Positive regulation of transcription by RNA polymerase II
The reference OMIM entry for this protein is 607270
Kiaa0442 gene; kiaa0442
Autism susceptibility candidate 2; auts2
CLONING
By sequencing clones obtained from a size-fractionated brain cDNA library, Ishikawa et al. (1997) cloned KIAA0442. The deduced 1,172-amino acid protein shares sequence homology with rat atrophin-1-related protein (RERE; 605226). RT-PCR detected KIAA0442 in all tissues examined, with highest expression in kidney, followed by ovary, prostate, and small intestine. Sultana et al. (2002) studied a monozygotic twin pair concordant for autism (see 209850) and for an identical balanced t(7;20)(q11.2;p11.2) translocation. They identified and characterized a novel gene, which they designated 'AUTS2,' that spans the 7q11.2 breakpoint. The gene is identical to the KIAA0442 gene identified by Ishikawa et al. (1997). The predicted 1,259-amino acid protein contains 2 proline-rich domains and regions that share homology with the dwarfin family consensus sequence and with topoisomerase (see 126420). It has a PY motif, several putative phosphorylation sites and N-myristoylation sites, and 2 putative N-glycosylation sites. The KIAA0442 protein shares 93% amino acid identity with its murine homolog. Northern blot analysis detected strong expression of 7.5- and 8.0-kb transcripts in fetal and adult brain. KIAA0442 was also strongly expressed in skeletal muscle and kidney, with lower levels in placenta, lung, and leukocytes. In fetal brain, KIAA0442 was expressed in frontal, parietal, and temporal lobes, but not in the occipital lobe. Sultana et al. (2002) identified several smaller splice variants of KIAA0442. Beunders et al. (2013) identified a short 3-prime AUTS2 mRNA variant starting in the middle of exon 9. The reading frame of the short transcript is identical to that of the full-length AUTS2 transcript and is predicted to encode a polypeptide of 697 amino acids instead of the 1,259 amino acids of the full-length protein.GENE FUNCTION
Gao et al. (2014) investigated the role of AUTS2 as part of an AUTS2-containing Polycomb repressive complex (PRC1-AUTS2) and in the context of neurodevelopment. In contrast to the canonical role of PRC1 in gene repression, PRC1-AUTS2 activates transcription. Biochemical studies demonstrated that the casein kinase-2 (CK2; see 115440) component of PRC1-AUTS2 neutralizes PRC1 repressive activity, whereas AUTS2-mediated recruitment of p300 (602700) leads to gene activation. Chromatin immunoprecipitation followed by sequencing demonstrated that AUTS2 regulates neuronal gene expression through promoter association. Conditional targeting of Auts2 in the mouse central nervous system (CNS) leads to various developmental defects. Gao et al. (2014) concluded that their findings revealed a natural means of subverting PRC1 activity, linking key epigenetic modulators with neuronal functions and diseases.GENE STRUCTURE
By genomic sequence analysis, Sultana et al. (2002) determined that the KIAA0442 gene spans 1.2 Mb and contains 19 exons.MAPPING
By radiation hybrid analysis, Ishikawa et al. (1997) mapped the KIAA0442 gene to chromosome 7. By FISH, Sultana et al. (2002) mapped the AUTS2 gene to chromosome 7q11.2.MOLECULAR GENETICS
- Intragenic Copy Number Variation in MRD26 By combining the results of diagnostic testing of 49,684 individuals, Beunders et al. (2013) identified 24 microdeletions that affected at least 1 exon of AUTS2, as well as 1 translocation and 1 inversion each with a breakpoint within the AUTS2 locus. The authors then analyzed 16,784 controls from 12 c ... More on the omim web site
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 607270 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).