O14936 · CSKP_HUMAN
- ProteinPeripheral plasma membrane protein CASK
- GeneCASK
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids926 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Multidomain scaffolding Mg2+-independent protein kinase that catalyzes the phosphotransfer from ATP to proteins such as NRXN1, and plays a role in synaptic transmembrane protein anchoring and ion channel trafficking (PubMed:18423203).
Contributes to neural development and regulation of gene expression via interaction with the transcription factor TBR1. 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. Component of the LIN-10-LIN-2-LIN-7 complex, which associates with the motor protein KIF17 to transport vesicles containing N-methyl-D-aspartate (NMDA) receptor subunit NR2B along microtubules (By similarity).
Contributes to neural development and regulation of gene expression via interaction with the transcription factor TBR1. 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. Component of the LIN-10-LIN-2-LIN-7 complex, which associates with the motor protein KIF17 to transport vesicles containing N-methyl-D-aspartate (NMDA) receptor subunit NR2B along microtubules (By similarity).
Catalytic activity
- ATP + L-seryl-[protein] = ADP + H+ + O-phospho-L-seryl-[protein]This reaction proceeds in the forward direction.
Cofactor
Note: Unlike other protein kinases, does not require a divalent cation such as magnesium for catalytic activity.
Activity 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 Ca2+/CAM.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
563 μM | ATP | |||||
748.7 μM | ATP (when NRXN1 is phosphorylated) |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
4.9 nmol/min/mmol |
Kinetics of autophosphorylation assay were measured, rather than phosphorylation of an exogenous substrate.
Features
Showing features for binding site, active site.
GO annotations
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended namePeripheral plasma membrane protein CASK
- EC number
- Short nameshCASK
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionO14936
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Peripheral membrane protein
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Intellectual developmental disorder with microcephaly and pontine and cerebellar hypoplasia (MICPCH)
- Note
- DescriptionA disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive 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 intellectual disability alone or associated with nystagmus.
- See alsoMIM:300749
Natural variants in MICPCH
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_062996 | 268 | Y>H | in MICPCH; dbSNP:rs137852817 | |
VAR_062997 | 396 | P>S | in MICPCH; dbSNP:rs137852820 | |
VAR_062998 | 710 | D>G | in MICPCH; dbSNP:rs137852818 |
FG syndrome 4 (FGS4)
- Note
- DescriptionFG syndrome (FGS) is an X-linked disorder characterized by intellectual disability, relative macrocephaly, hypotonia and constipation.
- See alsoMIM:300422
Natural variants in FGS4
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_058719 | 28 | R>L | in FGS4; does not reveal significant alterations induced by the mutation substitution; causes a partial skipping of exon 2 of the protein; dbSNP:rs137852816 |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_078710 | 19-926 | found in a patient with epilepsy and pontocerebellar hypoplasia; likely pathogenic | |||
Sequence: Missing | ||||||
Natural variant | VAR_058719 | 28 | in FGS4; does not reveal significant alterations induced by the mutation substitution; causes a partial skipping of exon 2 of the protein; dbSNP:rs137852816 | |||
Sequence: R → L | ||||||
Natural variant | VAR_041956 | 96 | in a lung large cell carcinoma sample; somatic mutation | |||
Sequence: G → V | ||||||
Natural variant | VAR_062996 | 268 | in MICPCH; dbSNP:rs137852817 | |||
Sequence: Y → H | ||||||
Natural variant | VAR_062997 | 396 | in MICPCH; dbSNP:rs137852820 | |||
Sequence: P → S | ||||||
Natural variant | VAR_062998 | 710 | in MICPCH; dbSNP:rs137852818 | |||
Sequence: D → G |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 718 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000094568 | 1-926 | UniProt | Peripheral plasma membrane protein CASK | |||
Sequence: MADDDVLFEDVYELCEVIGKGPFSVVRRCINRETGQQFAVKIVDVAKFTSSPGLSTEDLKREASICHMLKHPHIVELLETYSSDGMLYMVFEFMDGADLCFEIVKRADAGFVYSEAVASHYMRQILEALRYCHDNNIIHRDVKPHCVLLASKENSAPVKLGGFGVAIQLGESGLVAGGRVGTPHFMAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAERITVYEALNHPWLKERDRYAYKIHLPETVEQLRKFNARRKLKGAVLAAVSSHKFNSFYGDPPEELPDFSEDPTSSGLLAAERAVSQVLDSLEEIHALTDCSEKDLDFLHSVFQDQHLHTLLDLYDKINTKSSPQIRNPPSDAVQRAKEVLEEISCYPENNDAKELKRILTQPHFMALLQTHDVVAHEVYSDEALRVTPPPTSPYLNGDSPESANGDMDMENVTRVRLVQFQKNTDEPMGITLKMNELNHCIVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREMRGSITFKIVPSYRTQSSSCERDSPSTSRQSPANGHSSTNNSVSDLPSTTQPKGRQIYVRAQFEYDPAKDDLIPCKEAGIRFRVGDIIQIISKDDHNWWQGKLENSKNGTAGLIPSPELQEWRVACIAMEKTKQEQQASCTWFGKKKKQYKDKYLAKHNAVFDQLDLVTYEEVVKLPAFKRKTLVLLGAHGVGRRHIKNTLITKHPDRFAYPIPHTTRPPKKDEENGKNYYFVSHDQMMQDISNNEYLEYGSHEDAMYGTKLETIRKIHEQGLIAILDVEPQALKVLRTAEFAPFVVFIAAPTITPGLNEDESLQRLQKESDILQRTYAHYFDLTIINNEIDETIRHLEEAVELVCTAPQWVPVSWVY | |||||||
Modified residue | 51 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 51 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 55 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 151 | UniProt | Phosphoserine; by autocatalysis | ||||
Sequence: S | |||||||
Modified residue | 155 | UniProt | Phosphoserine; by autocatalysis | ||||
Sequence: S | |||||||
Modified residue | 182 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 192 | UniProt | In isoform O14936-5; Phosphoserine | ||||
Sequence: K | |||||||
Modified residue | 313 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 313 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 314 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 395 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 562 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 571 | UniProt | In isoform O14936-3; Phosphoserine | ||||
Sequence: Y | |||||||
Modified residue | 577 | UniProt | In isoform O14936-4; Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 582 | PRIDE | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
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.
Gene expression databases
Organism-specific databases
Interaction
Subunit
CASK and LIN7 form two mutually exclusive tripartite complexes with APBA1 or CASKIN1 (By similarity).
Component of the brain-specific heterotrimeric complex (LIN-10-LIN-2-LIN-7 complex) composed of at least APBA1, CASK, and LIN7, which associates with the motor protein KIF17 to transport vesicles along microtubules (By similarity).
Forms a heterotrimeric complex with DLG1 and LIN7B via their L27 domains (By similarity).
Identified in a complex with ACTN4, IQGAP1, MAGI2, NPHS1, SPTAN1 and SPTBN1 (By similarity).
Part of a complex containing CASK, TBR1 and TSPYL2 (By similarity).
Interacts with WHRN (By similarity).
Interacts (via the PDZ, SH3 and guanylate kinase-like domains) with NRXN1 (via C-terminus) (By similarity).
Interacts with CASKIN1, APBA1, LIN7(A/B/C) and L27 domain of DLG1 and isoform 2 of DLG4 (By similarity).
Interacts with FCHSD2 (By similarity).
Interacts with KIRREL3 (PubMed:19012874).
Interacts with TBR1 (By similarity).
Interacts with TSPYL2 (By similarity).
Component of the brain-specific heterotrimeric complex (LIN-10-LIN-2-LIN-7 complex) composed of at least APBA1, CASK, and LIN7, which associates with the motor protein KIF17 to transport vesicles along microtubules (By similarity).
Forms a heterotrimeric complex with DLG1 and LIN7B via their L27 domains (By similarity).
Identified in a complex with ACTN4, IQGAP1, MAGI2, NPHS1, SPTAN1 and SPTBN1 (By similarity).
Part of a complex containing CASK, TBR1 and TSPYL2 (By similarity).
Interacts with WHRN (By similarity).
Interacts (via the PDZ, SH3 and guanylate kinase-like domains) with NRXN1 (via C-terminus) (By similarity).
Interacts with CASKIN1, APBA1, LIN7(A/B/C) and L27 domain of DLG1 and isoform 2 of DLG4 (By similarity).
Interacts with FCHSD2 (By similarity).
Interacts with KIRREL3 (PubMed:19012874).
Interacts with TBR1 (By similarity).
Interacts with TSPYL2 (By similarity).
Binary interactions
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 12-276 | Protein kinase | ||||
Sequence: YELCEVIGKGPFSVVRRCINRETGQQFAVKIVDVAKFTSSPGLSTEDLKREASICHMLKHPHIVELLETYSSDGMLYMVFEFMDGADLCFEIVKRADAGFVYSEAVASHYMRQILEALRYCHDNNIIHRDVKPHCVLLASKENSAPVKLGGFGVAIQLGESGLVAGGRVGTPHFMAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKERLFEGIIKGKYKMNPRQWSHISESAKDLVRRMLMLDPAERITVYEALNHPWL | ||||||
Region | 305-315 | Calmodulin-binding | ||||
Sequence: KGAVLAAVSSH | ||||||
Domain | 343-398 | L27 1 | ||||
Sequence: AERAVSQVLDSLEEIHALTDCSEKDLDFLHSVFQDQHLHTLLDLYDKINTKSSPQI | ||||||
Domain | 402-455 | L27 2 | ||||
Sequence: PSDAVQRAKEVLEEISCYPENNDAKELKRILTQPHFMALLQTHDVVAHEVYSDE | ||||||
Region | 482-909 | Required for interaction with NRXN1 (via C-terminal tail) | ||||
Sequence: MENVTRVRLVQFQKNTDEPMGITLKMNELNHCIVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREMRGSITFKIVPSYRTQSSSCERDSPSTSRQSPANGHSSTNNSVSDLPSTTQPKGRQIYVRAQFEYDPAKDDLIPCKEAGIRFRVGDIIQIISKDDHNWWQGKLENSKNGTAGLIPSPELQEWRVACIAMEKTKQEQQASCTWFGKKKKQYKDKYLAKHNAVFDQLDLVTYEEVVKLPAFKRKTLVLLGAHGVGRRHIKNTLITKHPDRFAYPIPHTTRPPKKDEENGKNYYFVSHDQMMQDISNNEYLEYGSHEDAMYGTKLETIRKIHEQGLIAILDVEPQALKVLRTAEFAPFVVFIAAPTITPGLNEDESLQRLQKESDILQRTYAHYFDLTIINNEIDETIRHLEEA | ||||||
Domain | 489-564 | PDZ | ||||
Sequence: RLVQFQKNTDEPMGITLKMNELNHCIVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREMRGSIT | ||||||
Region | 574-610 | Disordered | ||||
Sequence: QSSSCERDSPSTSRQSPANGHSSTNNSVSDLPSTTQP | ||||||
Domain | 612-682 | SH3 | ||||
Sequence: GRQIYVRAQFEYDPAKDDLIPCKEAGIRFRVGDIIQIISKDDHNWWQGKLENSKNGTAGLIPSPELQEWRV | ||||||
Domain | 739-911 | Guanylate kinase-like | ||||
Sequence: RKTLVLLGAHGVGRRHIKNTLITKHPDRFAYPIPHTTRPPKKDEENGKNYYFVSHDQMMQDISNNEYLEYGSHEDAMYGTKLETIRKIHEQGLIAILDVEPQALKVLRTAEFAPFVVFIAAPTITPGLNEDESLQRLQKESDILQRTYAHYFDLTIINNEIDETIRHLEEAVE |
Domain
The first L27 domain binds DLG1 and the second L27 domain probably binds LIN7.
The protein kinase domain mediates the interaction with FCHSD2.
Sequence similarities
In the N-terminal section; belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily.
Belongs to the MAGUK family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 6 isoforms produced by Alternative splicing.
O14936-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length926
- Mass (Da)105,123
- Last updated2007-04-17 v3
- Checksum6C02008CE52728BA
O14936-2
- Name2
- Differences from canonical
- 719-723: Missing
O14936-3
- Name3
O14936-4
- Name4
O14936-5
- Name5
O14936-6
- Name6
Computationally mapped potential isoform sequences
There are 16 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A2R8Y7X6 | A0A2R8Y7X6_HUMAN | CASK | 193 | ||
A0A2R8Y472 | A0A2R8Y472_HUMAN | CASK | 68 | ||
A0A2R8Y3B3 | A0A2R8Y3B3_HUMAN | CASK | 394 | ||
A0A2R8Y6D8 | A0A2R8Y6D8_HUMAN | CASK | 109 | ||
A0A2R8Y6F8 | A0A2R8Y6F8_HUMAN | CASK | 700 | ||
A0A2R8Y4K4 | A0A2R8Y4K4_HUMAN | CASK | 140 | ||
A0A7I2RJN6 | A0A7I2RJN6_HUMAN | CASK | 903 | ||
A0A2R8YE77 | A0A2R8YE77_HUMAN | CASK | 920 | ||
A0A2R8YGH2 | A0A2R8YGH2_HUMAN | CASK | 132 | ||
A0A2R8YFN5 | A0A2R8YFN5_HUMAN | CASK | 904 | ||
A0A2R8YEK3 | A0A2R8YEK3_HUMAN | CASK | 955 | ||
A0A2R8YEJ7 | A0A2R8YEJ7_HUMAN | CASK | 366 | ||
A0A2U3TZN6 | A0A2U3TZN6_HUMAN | CASK | 880 | ||
A0A2U3TZM1 | A0A2U3TZM1_HUMAN | CASK | 908 | ||
A0A2U3TZM4 | A0A2U3TZM4_HUMAN | CASK | 892 | ||
Q5JS79 | Q5JS79_HUMAN | CASK | 927 |
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_024421 | 1-385 | in isoform 5 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_024422 | 340-345 | in isoform 3 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_024423 | 386 | in isoform 5 | |||
Sequence: L → M | ||||||
Sequence conflict | 401 | in Ref. 2; AAB88198 | ||||
Sequence: P → L | ||||||
Sequence conflict | 479 | in Ref. 1; AAB88125, 3; BAB12252, 4; AAU10527 and 8; AAF72666/AAF72667 | ||||
Sequence: D → G | ||||||
Alternative sequence | VSP_024424 | 580-602 | in isoform 3, isoform 4 and isoform 5 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_024425 | 603-614 | in isoform 6 | |||
Sequence: Missing | ||||||
Sequence conflict | 675 | in Ref. 1; AAB88125 and 4; AAU10527 | ||||
Sequence: P → S | ||||||
Alternative sequence | VSP_024426 | 719-723 | in isoform 2, isoform 4 and isoform 6 | |||
Sequence: Missing | ||||||
Sequence conflict | 780 | in Ref. 1; AAB88125 and 4; AAU10527 | ||||
Sequence: K → R |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF032119 EMBL· GenBank· DDBJ | AAB88125.1 EMBL· GenBank· DDBJ | mRNA | ||
AF035582 EMBL· GenBank· DDBJ | AAB88198.1 EMBL· GenBank· DDBJ | mRNA | ||
AB039327 EMBL· GenBank· DDBJ | BAB12252.2 EMBL· GenBank· DDBJ | mRNA | ||
AY705392 EMBL· GenBank· DDBJ | AAU10527.1 EMBL· GenBank· DDBJ | mRNA | ||
AL158144 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL353691 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL445239 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL603754 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL627402 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC117311 EMBL· GenBank· DDBJ | AAI17312.1 EMBL· GenBank· DDBJ | mRNA | ||
BC143454 EMBL· GenBank· DDBJ | AAI43455.1 EMBL· GenBank· DDBJ | mRNA | ||
AB208859 EMBL· GenBank· DDBJ | BAD92096.1 EMBL· GenBank· DDBJ | mRNA | ||
AF262404 EMBL· GenBank· DDBJ | AAF72666.1 EMBL· GenBank· DDBJ | mRNA | ||
AF262405 EMBL· GenBank· DDBJ | AAF72667.1 EMBL· GenBank· DDBJ | mRNA |