Human Gene CASK (ENST00000645566.1) from GENCODE V44
Description: Homo sapiens calcium/calmodulin dependent serine protein kinase (CASK), transcript variant 1, mRNA. (from RefSeq NM_003688) RefSeq Summary (NM_003688): 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, intellectual disability and microcephaly with pontine and cerebellar hypoplasia, and a form of X-linked intellectual disability. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]. Gencode Transcript: ENST00000645566.1 Gencode Gene: ENSG00000147044.23 Transcript (Including UTRs) Position: hg38 chrX:41,519,211-41,923,015 Size: 403,805 Total Exon Count: 27 Strand: - Coding Region Position: hg38 chrX:41,520,420-41,922,988 Size: 402,569 Coding Exon Count: 27
ID:CSKP_HUMAN DESCRIPTION: RecName: Full=Peripheral plasma membrane protein CASK; Short=hCASK; EC=2.7.11.1; AltName: Full=Calcium/calmodulin-dependent serine protein kinase; AltName: Full=Protein lin-2 homolog; FUNCTION: Multidomain scaffolding protein with a role in synaptic transmembrane protein anchoring and ion channel trafficking. Contributes to neural development and regulation of gene expression via interaction with the transcription factor TRB1. Binds to cell-surface proteins, including amyloid precursor protein, neurexins and syndecans. May mediate a link between the extracellular matrix and the actin cytoskeleton via its interaction with syndecan and with the actin/spectrin-binding protein 4.1. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. COFACTOR: Unlike other protein kinases, does not require a divalent cation such as magnesium for catalytic activity. ENZYME REGULATION: 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. BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=563 uM for ATP; Note=Kinetics of autophosphorylation assay were measured, rather than phosphorylation of an exogenous substrate; SUBUNIT: 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. INTERACTION: P41134:ID1; NbExp=3; IntAct=EBI-1215506, EBI-1215527; Q63373:Nrxn1 (xeno); NbExp=3; IntAct=EBI-1215506, EBI-1780696; Q9Y2J0:RPH3A; NbExp=3; IntAct=EBI-1215506, EBI-1216802; P34741:SDC2; NbExp=2; IntAct=EBI-1215506, EBI-1172957; SUBCELLULAR LOCATION: Nucleus (By similarity). Cytoplasm (By similarity). Cell membrane; Peripheral membrane protein (By similarity). TISSUE SPECIFICITY: Ubiquitous. Expression is significantly greater in brain relative to kidney, lung, and liver and in fetal brain and kidney relative to lung and liver. DOMAIN: The first L27 domain binds DLG1 and the second L27 domain probably binds LIN7 (By similarity). DOMAIN: The protein kinase domain mediates the interaction with FCHSD2. DISEASE: Defects in CASK are the cause of mental retardation X- linked CASK-related (MRXCASK) [MIM:300749]. Mental retardation is characterized by significantly below average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period. Patients with mental retardation X-linked CASK-related can manifest a severe phenotype consisting of severe intellectual deficit, congenital or postnatal microcephaly, disproportionate brainstem and cerebellar hypoplasia (MICPCH Syndrome). A milder phenotype consists of mental retardation alone or associated with nystagmus. DISEASE: Defects in CASK are the cause of FG syndrome type 4 (FGS4) [MIM:300422]. FG syndrome (FGS) is an X-linked disorder characterized by mental retardation, relative macrocephaly, hypotonia and constipation. SIMILARITY: In the N-terminal section; belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily. SIMILARITY: Belongs to the MAGUK family. SIMILARITY: Contains 1 guanylate kinase-like domain. SIMILARITY: Contains 2 L27 domains. SIMILARITY: Contains 1 PDZ (DHR) domain. SIMILARITY: Contains 1 protein kinase domain. SIMILARITY: Contains 1 SH3 domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on O14936
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.