The Disabled-1 (Dab1) gene encodes a key regulator of Reelin signaling. Reelin is a large glycoprotein secreted by neurons of the developing brain, particularly Cajal-Retzius cells. DAB1 functions downstream of Reln in a signaling pathway that controls cell positioning in the developing brain and during adult neurogenesis. It docks to the intracellular part of the Reelin very low density lipoprotein receptor (VLDLR) and apoE receptor type 2 (ApoER2) and becomes tyrosine-phosphorylated following binding of Reelin to cortical neurons. In mice, mutations of Dab1 and Reelin generate identical phenotypes. In humans, Reelin mutations are associated with brain malformations and mental retardation. In mice, Dab1 mutation results in the scrambler mouse phenotype.
Aprataxin is a protein that in humans is encoded by the APTX gene.
MID1 is a protein that belongs to the Tripartite motif family (TRIM) and is also known as TRIM18. The MID1 gene is located on the short arm of the X chromosome and loss-of-function mutations in this gene are causative of the X-linked form of a rare developmental disease, Opitz G/BBB Syndrome.
The Abelson helper integration site 1 (AHI1) is a protein coding gene that is known for the critical role it plays in brain development. Proper cerebellar and cortical development in the human brain depends heavily on AHI1. The AHI1 gene is prominently expressed in the embryonic hindbrain and forebrain. AHI1 specifically encodes the Jouberin protein and mutations in the expression of the gene is known to cause specific forms of Joubert syndrome. Joubert syndrome is autosomal recessive and is characterized by the brain malformations and mental retardation that AHI1 mutations have the potential to induce. AHI1 has also been associated with schizophrenia and autism due to the role it plays in brain development. An AHI1 heterozygous knockout mouse model was studied by Bernard Lerer and his group at Hadassah Medical Center in Jerusalem to elucidate the correlation between alterations in AHI1 expression and the pathogenesis of neuropsychiatric disorders. The core temperatures and corticosterone secretions of the heterozygous knockout mice after exposure to environmental and visceral stress exhibited extreme repression of autonomic nervous system and hypothalamic-pituitary-adrenal responses. The knockout mice demonstrated an increased resilience to different types of stress and these results lead to a correlation between emotional regulation and neuropsychiatric disorders.
The human gene UBR1 encodes the enzyme ubiquitin-protein ligase E3 component n-recognin 1.
E3 ubiquitin-protein ligase FANCL is an enzyme that in humans is encoded by the FANCL gene.
Ubiquitin-conjugating enzyme E2 H is a protein that in humans is encoded by the UBE2H gene.
Tripartite motif-containing protein 32 is a protein that in humans is encoded by the TRIM32 gene. Since its discovery in 1995, TRIM32 has been shown to be implicated in a number of diverse biological pathways.
Puratrophin-1 is a protein that in humans is encoded by the PLEKHG4 gene.
E3 ubiquitin-protein ligase LRSAM1, previously known as Tsg101-associated ligase (Tal), is an enzyme that in humans is encoded by the LRSAM1 gene.
E3 ubiquitin-protein ligase UBR2 is an enzyme that in humans is encoded by the UBR2 gene.
Nuclear factor 1 B-type is a protein that in humans is encoded by the NFIB gene.
Meckel syndrome, type 1 also known as MKS1 is a protein that in humans is encoded by the MKS1 gene.
Johanson–Blizzard syndrome is a rare, sometimes fatal autosomal recessive multisystem congenital disorder featuring abnormal development of the pancreas, nose and scalp, with intellectual disability, hearing loss and growth failure. It is sometimes described as a form of ectodermal dysplasia.
Cereblon is a protein that in humans is encoded by the CRBN gene. The gene that encodes the cereblon protein is found on the human chromosome 3, on the short arm at position p26.3 from base pair 3,190,676 to base pair 3,221,394. CRBN orthologs are highly conserved from plants to humans.
IQ motif and Sec7 domain 2 is a protein that in humans is encoded by the IQSEC2 gene.
DDB1 and CUL4 associated factor 17 is a protein that in humans is encoded buy the DCAF17 gene.
Potassium channel tetramerisation domain containing 7 is a protein in humans that is encoded by the KCTD7 gene. Alternative splicing results in multiple transcript variants.
Probable E3 ubiquitin-protein ligase HERC3 is an enzyme that in humans is encoded by the HERC3 gene. The gene is a member of the HERC family of ubiquitin ligases and encodes a protein with a HECT domain and an RCC1-like domain (RLD). It binds ubiquitin and hPLIC-1/2 via its HECT domain. Alternatively spiced transcript variants encoding multiple isoforms have been observed, and mutations in this gene have been linked to colorectal and gastric carcinomas. The protein is localized in the cytosol and vesicular-like structures containing β-COP, ARF, and Rab5. Since HERC3 can itself be ubiquitinated and degraded by the proteasome, it likely has roles in both vesicular traffic and ubiquitin-dependent processes.
ATP/GTP binding protein 1 is gene that encodes the protein known as cytosolic carboxypeptidase 1 (CCP1), originally named NNA1. Mice with a naturally occurring mutation of the Agtpbp1 gene are known as pcd mice.
