Résumé du gène: This gene encodes a calcium/calmodulin-dependent serine protein kinase. The encoded protein is a MAGUK (membrane-associated guanylate kinase) protein family member. These proteins are scaffold proteins and the encoded protein is located at synapses in the brain. Mutations in this gene are associated with FG syndrome 4, mental retardation and microcephaly with pontine and cerebellar hypoplasia, and a form of X-linked mental retardation. Multiple transcript variants encoding different isoforms have been found for this geneGeneral information above from NCBI
Activité catalytique: ATP + a protein = ADP + a phosphoprotein.
Cofacteur: Unlike other protein kinases, does not require a divalent cation such as magnesium for catalytic activity.
Régulation enzymatique: Differs from archetypal CaMK members in that the kinase domain exhibits a constitutively active conformation and the autoinhibitory region does not engage in direct contact with the ATP-binding cleft, although it still binds Ca(2+)/CAM.
Structure de sous-unités: Binds WHRN and NRXN1 cytosolic tail. Interacts with CASKIN1, APBA1, LIN7(A/B/C) and L27 domain of DLG1 and isoform 2 of DLG4 (By similarity). CASK and LIN7 form two mutually exclusive tripartite complexes with APBA1 or CASKIN1 (By similarity). Interacts with FCHSD2. Interacts with TSPYL2. Part of a complex containing CASK, TRB1 and TSPYL2 (By similarity). Identified in a complex with ACTN4, IQGAP1, MAGI2, NPHS1, SPTAN1 and SPTBN1 (By similarity). Interacts with KIRREL3.
Domaine: The first L27 domain binds DLG1 and the second L27 domain probably binds LIN7 (By similarity).
The protein kinase domain mediates the interaction with FCHSD2.
Localisation subcellulaire: Nucleus (By similarity). Cytoplasm (By similarity). Cell membrane; Peripheral membrane protein (By similarity).
Spécificité tissulaire: Ubiquitous. Expression is significantly greater in brain relative to kidney, lung, and liver and in fetal brain and kidney relative to lung and liver.
Implication dans la maladie: Mental retardation and microcephaly with pontine and cerebellar hypoplasia (MICPCH) [MIM:300749]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period. Affected individuals can manifest a severe phenotype consisting of severe intellectual deficit, congenital or postnatal microcephaly, disproportionate brainstem and cerebellar hypoplasia. A milder phenotype consists of mental retardation alone or associated with nystagmus. Note=The disease is caused by mutations affecting the gene represented in this entry.
FG syndrome 4 (FGS4) [MIM:300422]: FG syndrome (FGS) is an X-linked disorder characterized by mental retardation, relative macrocephaly, hypotonia and constipation. Note=The disease is caused by mutations affecting the gene represented in this entry.
Similarité de séquence: In the N-terminal section; belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily.
Belongs to the MAGUK family.
Contains 1 guanylate kinase-like domain.
Contains 2 L27 domains.
Contains 1 PDZ (DHR) domain.
Contains 1 protein kinase domain.
Contains 1 SH3 domain.C
General information above from UniProt