Tänään katson PAX6 geenistä tietoa. PAX 6 proteiinin hajoittaa TRIM11(E3 ubikitiiniliaasi).

PAX6 (11p13) ,

Paired box protein Pax-6

https://www.genecards.org/cgi-bin/carddisp.pl?gene=PAX6&keywords=PAX6

This gene encodes paired box protein Pax-6, one of many human homologs of the Drosophila melanogaster gene prd. In addition to a conserved paired box domain, a hallmark feature of this gene family, the encoded protein also contains a homeobox domain. Both domains are known to bind DNA and function as regulators of gene transcription. Activity of this protein is key in the development of neural tissues, particularly the eye. This gene is regulated by multiple enhancers located up to hundreds of kilobases distant from this locus. Mutations in this gene or in the enhancer regions can cause ocular disorders such as aniridia and Peter's anomaly. Use of alternate promoters and alternative splicing results in multiple transcript variants encoding different isoforms. Interestingly, inclusion of a particular alternate coding exon has been shown to increase the length of the paired box domain and alter its DNA binding specificity. Consequently, isoforms that carry the shorter paired box domain regulate a different set of genes compared to the isoforms carrying the longer paired box domain. [provided by RefSeq, Mar 2019]

GeneCards Summary for PAX6 Gene: PAX6 (Paired Box 6) is a Protein Coding gene. Diseases associated with PAX6 include Coloboma Of Optic Nerve and Optic Nerve Hypoplasia, Bilateral. Among its related pathways are Incretin synthesis, secretion, and inactivation and Regulation of beta-cell development. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and chromatin binding. An important paralog of this gene is PAX7.

UniProtKB/Swiss-Prot Summary for PAX6 Gene;

Transcription factor with important functions in the development of the eye, nose, central nervous system and pancreas. Required for the differentiation of pancreatic islet alpha cells (By similarity). Competes with PAX4 in binding to a common element in the glucagon, insulin and somatostatin promoters. Regulates specification of the ventral neuron subtypes by establishing the correct progenitor domains (By similarity). Acts as a transcriptional repressor of NFATC1-mediated gene expression (By similarity). ( PAX6_HUMAN,P26367 )

Size: 422 amino acids Molecular mass: 46683 Da

Quaternary structure: 

Interacts with MAF and MAFB (By similarity).

• Interacts with TRIM11; this interaction leads to ubiquitination and proteasomal degradation, as well as inhibition of transactivation, possibly in part by preventing PAX6 binding to consensus DNA sequences (By similarity).
  Interacts with TLE6/GRG6 (By similarity).

 (Etsin lisätietoa PAX6 proteiineista) 

 LISÄTIETO: 

. 2005 Aug 12;6:43. doi: 10.1186/1471-2156-6-43. A screen for proteins that interact with PAX6: C-terminal mutations disrupt interaction with HOMER3, DNCL1 and TRIM11 https://pubmed.ncbi.nlm.nih.gov/?term=DNCL1 Abstract Background: The PAX6 protein is a transcriptional regulator with a key role in ocular and neurological development. Individuals with heterozygous loss-of-function mutations in the PAX6 gene have malformations of the eye and brain. Little is known about the interactions of PAX6 with other proteins, so we carried out a systematic screen for proteins that interact with PAX6. Results: We used bioinformatics techniques to characterise a highly conserved peptide at the C-terminus of the PAX6 protein. Yeast two-hybrid library screens were then carried out to identify brain-expressed proteins that interact with the C-terminal peptide and with the entire PAX6 proline-serine-threonine-rich domain. Three novel PAX6-interacting proteins were identified: the post-synaptic density (PSD) protein HOMER3, the dynein subunit DNCL1, and the tripartite motif protein TRIM11. Three C-terminal PAX6 mutations, previously identified in patients with eye malformations, all reduced or abolished the interactions.

 TRIM 11  (RNF92)  E3 ubiquitin-protein ligase TRIM 11  (Alias RING finger 92).  468 aminohappoa.

Protein Domains for TRIM11 Gene

InterPro: ConA-like_dom_sZnf_RING/FYVE/PHD , Znf_RING  Znf_RING_CS B30.2/SPR        Blocks: Zn-finger, RING,  B-box zinc finger signature , Butyrophylin C-terminal DUF signature SPRY-associated domain.

https://www.genecards.org/cgi-bin/carddisp.pl?gene=TRIM11&keywords=TRIM11 The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. This protein localizes to the nucleus and the cytoplasm. Its function has not been identified. [provided by RefSeq, Jul 2008]

GeneCards Summary for TRIM11 Gene. TRIM11 (Tripartite Motif Containing 11) is a Protein Coding gene. Among its related pathways are Class I MHC mediated antigen processing and presentation and Innate Immune System. Gene Ontology (GO) annotations related to this gene include ligase activity and ubiquitin-protein transferase activity. An important paralog of this gene is TRIM17.

UniProtKB/Swiss-Prot Summary for TRIM11 Gene. E3 ubiquitin-protein ligase that promotes the degradation of insoluble ubiquitinated proteins, including insoluble PAX6, poly-Gln repeat expanded HTT and poly-Ala repeat expanded ARX. Mediates PAX6 ubiquitination leading to proteasomal degradation, thereby modulating cortical neurogenesis. May also inhibit PAX6 transcriptional activity, possibly in part by preventing the binding of PAX6 to its consensus sequences. May contribute to the regulation of the intracellular level of HN (humanin) or HN-containing proteins through the proteasomal degradation pathway. Mediates MED15 ubiquitination leading to proteasomal degradation. May contribute to the innate restriction of retroviruses. Upon overexpression, reduces HIV-1 and murine leukemia virus infectivity, by suppressing viral gene expression. Antiviral activity depends on a functional E3 ubiquitin-protein ligase domain. May regulate TRIM5 turnover via the proteasome pathway, thus counteracting the TRIM5-mediated cross-species restriction of retroviral infection at early stages of the retroviral life cycle. ( TRI11_HUMAN,Q96F44 )

(  Toista tietä etsin lisätietoa HOMER proteiinista   ja DYNLL1 (entinen DNCL1 ).

HOMER3 geeni (19p13.11), Neuronal Immediate Early Gene , Recommended name: Homer protein homolog 3

https://www.genecards.org/cgi-bin/carddisp.pl?gene=HOMER3&keywords=HOMER3

 This gene encodes a member of the HOMER family of postsynaptic density scaffolding proteins that share a similar domain structure consisting of an N-terminal Enabled/vasodilator-stimulated phosphoprotein homology 1 domain which mediates protein-protein interactions, and a carboxy-terminal coiled-coil domain and two leucine zipper motifs that are involved in self-oligomerization. The encoded protein binds numerous other proteins including group I metabotropic glutamate receptors, inositol 1,4,5-trisphosphate receptors and amyloid precursor proteins and has been implicated in diverse biological functions such as neuronal signaling, T-cell activation and trafficking of amyloid beta peptides. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Mar 2009]

GeneCards Summary for HOMER3 Gene  HOMER3 (Homer Scaffold Protein 3) is a Protein Coding gene. Diseases associated with HOMER3 include Keratoconus and Deafness, Autosomal Dominant 68. Among its related pathways are Protein-protein interactions at synapses and Transmission across Chemical Synapses. Gene Ontology (GO) annotations related to this gene include protein domain specific binding and G protein-coupled glutamate receptor binding. An important paralog of this gene is HOMER1.

UniProtKB/Swiss-Prot Summary for HOMER3 GenePostsynaptic density scaffolding protein. Binds and cross-links cytoplasmic regions of GRM1, GRM5, ITPR1, DNM3, RYR1, RYR2, SHANK1 and SHANK3. By physically linking GRM1 and GRM5 with ER-associated ITPR1 receptors, it aids the coupling of surface receptors to intracellular calcium release. Isoforms can be differently regulated and may play an important role in maintaining the plasticity at glutamatergic synapses. Negatively regulates T cell activation by inhibiting the calcineurin-NFAT pathway. Acts by competing with calcineurin/PPP3CA for NFAT protein binding, hence preventing NFAT activation by PPP3CA (PubMed:18218901). ( HOME3_HUMAN,Q9NSC5 ) 

 DNCL1 geeni (12q24.31),  Recommended name: Dynein light chain 1, cytoplasmic

 https://www.genecards.org/cgi-bin/carddisp.pl?gene=DYNLL1&keywords=DNCL1 Cytoplasmic dyneins are large enzyme complexes with a molecular mass of about 1,200 kD. They contain two force-producing heads formed primarily from dynein heavy chains, and stalks linking the heads to a basal domain, which contains a varying number of accessory intermediate chains. The complex is involved in intracellular transport and motility. The protein described in this record is a light chain and exists as part of this complex but also physically interacts with and inhibits the activity of neuronal nitric oxide synthase. Binding of this protein destabilizes the neuronal nitric oxide synthase dimer, a conformation necessary for activity, and it may regulate numerous biologic processes through its effects on nitric oxide synthase activity. Alternate transcriptional splice variants have been characterized. [provided by RefSeq, Jul 2008]

GeneCards Summary for DYNLL1 Gene.  DYNLL1 (Dynein Light Chain LC8-Type 1) is a Protein Coding gene. Diseases associated with DYNLL1 include Prostate Carcinoma In Situ and Breast Adenoid Cystic Carcinoma. Among its related pathways are Loss of Nlp from mitotic centrosomes and EML4 and NUDC in mitotic spindle formation. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and protein domain specific binding. An important paralog of this gene is DYNLL2.

UniProtKB/Swiss-Prot Summary for DYNLL1 Gene. Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. May play a role in changing or maintaining the spatial distribution of cytoskeletal structures. ( DYL1_HUMAN,P63167 )Binds and inhibits the catalytic activity of neuronal nitric oxide synthase. ( DYL1_HUMAN,P63167 )Promotes transactivation functions of ESR1 and plays a role in the nuclear localization of ESR1. ( DYL1_HUMAN,P63167 ) Regulates apoptotic activities of BCL2L11 by sequestering it to microtubules. Upon apoptotic stimuli the BCL2L11-DYNLL1 complex dissociates from cytoplasmic dynein and translocates to mitochondria and sequesters BCL2 thus neutralizing its antiapoptotic activity. ( DYL1_HUMAN,P63167 )