ID CSKP_HUMAN Reviewed; 926 AA. AC O14936; A6NES1; B7ZKY0; O43215; Q17RI4; Q59HA0; Q5VT16; Q5VT17; AC Q5VT18; Q5VT19; Q66T42; Q9BYH6; Q9NYB2; Q9NYB3; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 17-APR-2007, sequence version 3. DT 05-SEP-2012, entry version 143. DE RecName: Full=Peripheral plasma membrane protein CASK; DE Short=hCASK; DE EC=2.7.11.1; DE AltName: Full=Calcium/calmodulin-dependent serine protein kinase; DE AltName: Full=Protein lin-2 homolog; GN Name=CASK; Synonyms=LIN2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND INTERACTION WITH SDC2 AND RP EPB41. RC TISSUE=Brain, Liver, and Lung; RX MEDLINE=98327121; PubMed=9660868; DOI=10.1083/jcb.142.1.129; RA Cohen A.R., Woods D.F., Marfatia S.M., Walther Z., Chishti A.H., RA Anderson J.M.; RT "Human CASK/LIN-2 binds syndecan-2 and protein 4.1 and localizes to RT the basolateral membrane of epithelial cells."; RL J. Cell Biol. 142:129-138(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). RA Zha D., Hu G.; RT "The human homolog of the rat CASK, Drosophila Camguk and C.elegans RT Lin-2 genes."; RL Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5). RC TISSUE=Kidney; RA Ding L., Saijo K., Kawai K., Akaza H., Ugai H., Yokoyama K.K., RA Ohno T.; RT "Putative alternative splicing form of human CASK mRNA (partial RT codes)."; RL Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC TISSUE=Colon carcinoma; RA Yan Y., Merlin D.; RT "Caco2-BBE calcium/calmodulin-dependent serine protein kinase."; RL Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S., RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., RA Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., RA Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., RA Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., RA Williams G., Williams L., Williamson A., Williamson H., Wilming L., RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., RA Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., RA Gibbs R.A., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 5-926 (ISOFORM 2). RC TISSUE=Brain; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 173-926 (ISOFORM 1), NUCLEOTIDE SEQUENCE RP [MRNA] OF 27-926 (ISOFORM 3), AND TISSUE SPECIFICITY. RC TISSUE=Fetus; RX MEDLINE=20458875; PubMed=11003712; DOI=10.1007/s003350010170; RA Stevenson D., Laverty H.G., Wenwieser S., Douglas M., Wilson J.B.; RT "Mapping and expression analysis of the human CASK gene."; RL Mamm. Genome 11:934-937(2000). RN [9] RP INTERACTION WITH KIRREL3. RX PubMed=19012874; DOI=10.1016/j.ajhg.2008.10.020; RA Bhalla K., Luo Y., Buchan T., Beachem M.A., Guzauskas G.F., Ladd S., RA Bratcher S.J., Schroer R.J., Balsamo J., DuPont B.R., Lilien J., RA Srivastava A.K.; RT "Alterations in CDH15 and KIRREL3 in patients with mild to severe RT intellectual disability."; RL Am. J. Hum. Genet. 83:703-713(2008). RN [10] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 489-572. RX MEDLINE=98206299; PubMed=9546224; DOI=10.1038/nsb0498-317; RA Daniels D.L., Cohen A.R., Anderson J.M., Bruenger A.T.; RT "Crystal structure of the hCASK PDZ domain reveals the structural RT basis of class II PDZ domain target recognition."; RL Nat. Struct. Biol. 5:317-325(1998). RN [11] RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 1-337 IN COMPLEX WITH AMP, RP COFACTOR, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, RP PHOSPHORYLATION OF NRXN1, AND AUTOPHOSPHORYLATION AT SER-151 AND RP SER-155. RX PubMed=18423203; DOI=10.1016/j.cell.2008.02.036; RA Mukherjee K., Sharma M., Urlaub H., Bourenkov G.P., Jahn R., RA Suedhof T.C., Wahl M.C.; RT "CASK functions as a Mg2+-independent neurexin kinase."; RL Cell 133:328-339(2008). RN [12] RP VARIANT [LARGE SCALE ANALYSIS] VAL-96. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E., RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., RA Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). RN [13] RP INVOLVEMENT IN MICPCH SYNDROME. RX PubMed=19165920; DOI=10.1038/ng.194; RA Najm J., Horn D., Wimplinger I., Golden J.A., Chizhikov V.V., Sudi J., RA Christian S.L., Ullmann R., Kuechler A., Haas C.A., Flubacher A., RA Charnas L.R., Uyanik G., Frank U., Klopocki E., Dobyns W.B., RA Kutsche K.; RT "Mutations of CASK cause an X-linked brain malformation phenotype with RT microcephaly and hypoplasia of the brainstem and cerebellum."; RL Nat. Genet. 40:1065-1067(2008). RN [14] RP ERRATUM. RA Najm J., Horn D., Wimplinger I., Golden J.A., Chizhikov V.V., Sudi J., RA Christian S.L., Ullmann R., Kuechler A., Haas C.A., Flubacher A., RA Charnas L.R., Uyanik G., Frank U., Klopocki E., Dobyns W.B., RA Kutsche K.; RL Nat. Genet. 40:1384-1384(2008). RN [15] RP VARIANT FGS4 LEU-28, AND CHARACTERIZATION OF VARIANT FGS4 LEU-28. RX PubMed=19200522; DOI=10.1016/j.ajhg.2008.12.018; RA Piluso G., D'Amico F., Saccone V., Bismuto E., Rotundo I.L., RA Di Domenico M., Aurino S., Schwartz C.E., Neri G., Nigro V.; RT "A missense mutation in CASK causes FG syndrome in an Italian RT family."; RL Am. J. Hum. Genet. 84:162-177(2009). RN [16] RP VARIANTS [LARGE SCALE ANALYSIS] MRXCASK HIS-268; SER-396 AND GLY-710. RX PubMed=19377476; DOI=10.1038/ng.367; RA Tarpey P.S., Smith R., Pleasance E., Whibley A., Edkins S., Hardy C., RA O'Meara S., Latimer C., Dicks E., Menzies A., Stephens P., Blow M., RA Greenman C., Xue Y., Tyler-Smith C., Thompson D., Gray K., Andrews J., RA Barthorpe S., Buck G., Cole J., Dunmore R., Jones D., Maddison M., RA Mironenko T., Turner R., Turrell K., Varian J., West S., Widaa S., RA Wray P., Teague J., Butler A., Jenkinson A., Jia M., Richardson D., RA Shepherd R., Wooster R., Tejada M.I., Martinez F., Carvill G., RA Goliath R., de Brouwer A.P., van Bokhoven H., Van Esch H., Chelly J., RA Raynaud M., Ropers H.H., Abidi F.E., Srivastava A.K., Cox J., Luo Y., RA Mallya U., Moon J., Parnau J., Mohammed S., Tolmie J.L., RA Shoubridge C., Corbett M., Gardner A., Haan E., Rujirabanjerd S., RA Shaw M., Vandeleur L., Fullston T., Easton D.F., Boyle J., RA Partington M., Hackett A., Field M., Skinner C., Stevenson R.E., RA Bobrow M., Turner G., Schwartz C.E., Gecz J., Raymond F.L., RA Futreal P.A., Stratton M.R.; RT "A systematic, large-scale resequencing screen of X-chromosome coding RT exons in mental retardation."; RL Nat. Genet. 41:535-543(2009). CC -!- FUNCTION: Multidomain scaffolding protein with a role in synaptic CC transmembrane protein anchoring and ion channel trafficking. CC Contributes to neural development and regulation of gene CC expression via interaction with the transcription factor TRB1. CC Binds to cell-surface proteins, including amyloid precursor CC protein, neurexins and syndecans. May mediate a link between the CC extracellular matrix and the actin cytoskeleton via its CC interaction with syndecan and with the actin/spectrin-binding CC protein 4.1. CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC -!- COFACTOR: Unlike other protein kinases, does not require a CC divalent cation such as magnesium for catalytic activity. CC -!- ENZYME REGULATION: Differs from archetypal CaMK members in that CC the kinase domain exhibits a constitutively active conformation CC and the autoinhibitory region does not engage in direct contact CC with the ATP-binding cleft, although it still binds Ca(2+)/CAM. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=563 uM for ATP; CC Note=Kinetics of autophosphorylation assay were measured, rather CC than phosphorylation of an exogenous substrate; CC -!- SUBUNIT: Binds WHRN and NRXN1 cytosolic tail. Interacts with CC CASKIN1, APBA1, LIN7(A/B/C) and L27 domain of DLG1 and isoform 2 CC of DLG4 (By similarity). CASK and LIN7 form two mutually exclusive CC tripartite complexes with APBA1 or CASKIN1 (By similarity). CC Interacts with FCHSD2. Interacts with TSPYL2. Part of a complex CC containing CASK, TRB1 and TSPYL2 (By similarity). Identified in a CC complex with ACTN4, IQGAP1, MAGI2, NPHS1, SPTAN1 and SPTBN1 (By CC similarity). Interacts with KIRREL3. CC -!- INTERACTION: CC P41134:ID1; NbExp=3; IntAct=EBI-1215506, EBI-1215527; CC Q63373:Nrxn1 (xeno); NbExp=3; IntAct=EBI-1215506, EBI-1780696; CC Q9Y2J0:RPH3A; NbExp=3; IntAct=EBI-1215506, EBI-1216802; CC P34741:SDC2; NbExp=2; IntAct=EBI-1215506, EBI-1172957; CC -!- SUBCELLULAR LOCATION: Nucleus (By similarity). Cytoplasm (By CC similarity). Cell membrane; Peripheral membrane protein (By CC similarity). CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=6; CC Name=1; CC IsoId=O14936-1; Sequence=Displayed; CC Name=2; CC IsoId=O14936-2; Sequence=VSP_024426; CC Name=3; CC IsoId=O14936-3; Sequence=VSP_024422, VSP_024424; CC Name=4; CC IsoId=O14936-4; Sequence=VSP_024424, VSP_024426; CC Name=5; CC IsoId=O14936-5; Sequence=VSP_024421, VSP_024423, VSP_024424; CC Name=6; CC IsoId=O14936-6; Sequence=VSP_024425, VSP_024426; CC Note=Gene prediction confirmed by EST data; CC -!- TISSUE SPECIFICITY: Ubiquitous. Expression is significantly CC greater in brain relative to kidney, lung, and liver and in fetal CC brain and kidney relative to lung and liver. CC -!- DOMAIN: The first L27 domain binds DLG1 and the second L27 domain CC probably binds LIN7 (By similarity). CC -!- DOMAIN: The protein kinase domain mediates the interaction with CC FCHSD2. CC -!- DISEASE: Defects in CASK are the cause of mental retardation X- CC linked CASK-related (MRXCASK) [MIM:300749]. Mental retardation is CC characterized by significantly below average general intellectual CC functioning associated with impairments in adaptative behavior and CC manifested during the developmental period. Patients with mental CC retardation X-linked CASK-related can manifest a severe phenotype CC consisting of severe intellectual deficit, congenital or postnatal CC microcephaly, disproportionate brainstem and cerebellar hypoplasia CC (MICPCH Syndrome). A milder phenotype consists of mental CC retardation alone or associated with nystagmus. CC -!- DISEASE: Defects in CASK are the cause of FG syndrome type 4 CC (FGS4) [MIM:300422]. FG syndrome (FGS) is an X-linked disorder CC characterized by mental retardation, relative macrocephaly, CC hypotonia and constipation. CC -!- SIMILARITY: In the N-terminal section; belongs to the protein CC kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK CC subfamily. CC -!- SIMILARITY: Belongs to the MAGUK family. CC -!- SIMILARITY: Contains 1 guanylate kinase-like domain. CC -!- SIMILARITY: Contains 2 L27 domains. CC -!- SIMILARITY: Contains 1 PDZ (DHR) domain. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC -!- SIMILARITY: Contains 1 SH3 domain. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF032119; AAB88125.1; -; mRNA. DR EMBL; AF035582; AAB88198.1; -; mRNA. DR EMBL; AB039327; BAB12252.2; -; mRNA. DR EMBL; AY705392; AAU10527.1; -; mRNA. DR EMBL; AL627402; CAH71237.1; -; Genomic_DNA. DR EMBL; AL158144; CAH71237.1; JOINED; Genomic_DNA. DR EMBL; AL353691; CAH71237.1; JOINED; Genomic_DNA. DR EMBL; AL445239; CAH71237.1; JOINED; Genomic_DNA. DR EMBL; AL603754; CAH71237.1; JOINED; Genomic_DNA. DR EMBL; AL627402; CAH71238.1; -; Genomic_DNA. DR EMBL; AL158144; CAH71238.1; JOINED; Genomic_DNA. DR EMBL; AL353691; CAH71238.1; JOINED; Genomic_DNA. DR EMBL; AL445239; CAH71238.1; JOINED; Genomic_DNA. DR EMBL; AL603754; CAH71238.1; JOINED; Genomic_DNA. DR EMBL; AL627402; CAH71239.1; -; Genomic_DNA. DR EMBL; AL158144; CAH71239.1; JOINED; Genomic_DNA. DR EMBL; AL353691; CAH71239.1; JOINED; Genomic_DNA. DR EMBL; AL445239; CAH71239.1; JOINED; Genomic_DNA. DR EMBL; AL603754; CAH71239.1; JOINED; Genomic_DNA. DR EMBL; AL627402; CAH71240.1; -; Genomic_DNA. DR EMBL; AL158144; CAH71240.1; JOINED; Genomic_DNA. DR EMBL; AL353691; CAH71240.1; JOINED; Genomic_DNA. DR EMBL; AL445239; CAH71240.1; JOINED; Genomic_DNA. DR EMBL; AL603754; CAH71240.1; JOINED; Genomic_DNA. DR EMBL; AL445239; CAI41092.1; -; Genomic_DNA. DR EMBL; AL158144; CAI41092.1; JOINED; Genomic_DNA. DR EMBL; AL353691; CAI41092.1; JOINED; Genomic_DNA. DR EMBL; AL603754; CAI41092.1; JOINED; Genomic_DNA. DR EMBL; AL627402; CAI41092.1; JOINED; Genomic_DNA. DR EMBL; AL445239; CAI41093.1; -; Genomic_DNA. DR EMBL; AL158144; CAI41093.1; JOINED; Genomic_DNA. DR EMBL; AL353691; CAI41093.1; JOINED; Genomic_DNA. DR EMBL; AL603754; CAI41093.1; JOINED; Genomic_DNA. DR EMBL; AL627402; CAI41093.1; JOINED; Genomic_DNA. DR EMBL; AL445239; CAI41094.1; -; Genomic_DNA. DR EMBL; AL158144; CAI41094.1; JOINED; Genomic_DNA. DR EMBL; AL353691; CAI41094.1; JOINED; Genomic_DNA. DR EMBL; AL603754; CAI41094.1; JOINED; Genomic_DNA. DR EMBL; AL627402; CAI41094.1; JOINED; Genomic_DNA. DR EMBL; AL445239; CAI41095.1; -; Genomic_DNA. DR EMBL; AL158144; CAI41095.1; JOINED; Genomic_DNA. DR EMBL; AL353691; CAI41095.1; JOINED; Genomic_DNA. DR EMBL; AL603754; CAI41095.1; JOINED; Genomic_DNA. DR EMBL; AL627402; CAI41095.1; JOINED; Genomic_DNA. DR EMBL; AL603754; CAI41634.1; -; Genomic_DNA. DR EMBL; AL158144; CAI41634.1; JOINED; Genomic_DNA. DR EMBL; AL353691; CAI41634.1; JOINED; Genomic_DNA. DR EMBL; AL445239; CAI41634.1; JOINED; Genomic_DNA. DR EMBL; AL627402; CAI41634.1; JOINED; Genomic_DNA. DR EMBL; AL603754; CAI41635.1; -; Genomic_DNA. DR EMBL; AL158144; CAI41635.1; JOINED; Genomic_DNA. DR EMBL; AL353691; CAI41635.1; JOINED; Genomic_DNA. DR EMBL; AL445239; CAI41635.1; JOINED; Genomic_DNA. DR EMBL; AL627402; CAI41635.1; JOINED; Genomic_DNA. DR EMBL; AL603754; CAI41636.1; -; Genomic_DNA. DR EMBL; AL158144; CAI41636.1; JOINED; Genomic_DNA. DR EMBL; AL353691; CAI41636.1; JOINED; Genomic_DNA. DR EMBL; AL445239; CAI41636.1; JOINED; Genomic_DNA. DR EMBL; AL627402; CAI41636.1; JOINED; Genomic_DNA. DR EMBL; AL603754; CAI41637.1; -; Genomic_DNA. DR EMBL; AL158144; CAI41637.1; JOINED; Genomic_DNA. DR EMBL; AL353691; CAI41637.1; JOINED; Genomic_DNA. DR EMBL; AL445239; CAI41637.1; JOINED; Genomic_DNA. DR EMBL; AL627402; CAI41637.1; JOINED; Genomic_DNA. DR EMBL; AL353691; CAI42244.1; -; Genomic_DNA. DR EMBL; AL158144; CAI42244.1; JOINED; Genomic_DNA. DR EMBL; AL445239; CAI42244.1; JOINED; Genomic_DNA. DR EMBL; AL603754; CAI42244.1; JOINED; Genomic_DNA. DR EMBL; AL627402; CAI42244.1; JOINED; Genomic_DNA. DR EMBL; AL353691; CAI42245.1; -; Genomic_DNA. DR EMBL; AL158144; CAI42245.1; JOINED; Genomic_DNA. DR EMBL; AL445239; CAI42245.1; JOINED; Genomic_DNA. DR EMBL; AL603754; CAI42245.1; JOINED; Genomic_DNA. DR EMBL; AL627402; CAI42245.1; JOINED; Genomic_DNA. DR EMBL; AL353691; CAI42246.1; -; Genomic_DNA. DR EMBL; AL158144; CAI42246.1; JOINED; Genomic_DNA. DR EMBL; AL445239; CAI42246.1; JOINED; Genomic_DNA. DR EMBL; AL603754; CAI42246.1; JOINED; Genomic_DNA. DR EMBL; AL627402; CAI42246.1; JOINED; Genomic_DNA. DR EMBL; AL353691; CAI42247.1; -; Genomic_DNA. DR EMBL; AL158144; CAI42247.1; JOINED; Genomic_DNA. DR EMBL; AL445239; CAI42247.1; JOINED; Genomic_DNA. DR EMBL; AL603754; CAI42247.1; JOINED; Genomic_DNA. DR EMBL; AL627402; CAI42247.1; JOINED; Genomic_DNA. DR EMBL; AL158144; CAI42762.1; -; Genomic_DNA. DR EMBL; AL353691; CAI42762.1; JOINED; Genomic_DNA. DR EMBL; AL445239; CAI42762.1; JOINED; Genomic_DNA. DR EMBL; AL603754; CAI42762.1; JOINED; Genomic_DNA. DR EMBL; AL627402; CAI42762.1; JOINED; Genomic_DNA. DR EMBL; AL158144; CAI42763.1; -; Genomic_DNA. DR EMBL; AL353691; CAI42763.1; JOINED; Genomic_DNA. DR EMBL; AL445239; CAI42763.1; JOINED; Genomic_DNA. DR EMBL; AL603754; CAI42763.1; JOINED; Genomic_DNA. DR EMBL; AL627402; CAI42763.1; JOINED; Genomic_DNA. DR EMBL; AL158144; CAI42764.1; -; Genomic_DNA. DR EMBL; AL353691; CAI42764.1; JOINED; Genomic_DNA. DR EMBL; AL445239; CAI42764.1; JOINED; Genomic_DNA. DR EMBL; AL603754; CAI42764.1; JOINED; Genomic_DNA. DR EMBL; AL627402; CAI42764.1; JOINED; Genomic_DNA. DR EMBL; AL158144; CAI42765.1; -; Genomic_DNA. DR EMBL; AL353691; CAI42765.1; JOINED; Genomic_DNA. DR EMBL; AL445239; CAI42765.1; JOINED; Genomic_DNA. DR EMBL; AL603754; CAI42765.1; JOINED; Genomic_DNA. DR EMBL; AL627402; CAI42765.1; JOINED; Genomic_DNA. DR EMBL; BC117311; AAI17312.1; -; mRNA. DR EMBL; BC143454; AAI43455.1; -; mRNA. DR EMBL; AB208859; BAD92096.1; -; mRNA. DR EMBL; AF262404; AAF72666.1; -; mRNA. DR EMBL; AF262405; AAF72667.1; -; mRNA. DR IPI; IPI00514301; -. DR IPI; IPI00555605; -. DR IPI; IPI00641315; -. DR IPI; IPI00646452; -. DR IPI; IPI00877929; -. DR IPI; IPI00937304; -. DR RefSeq; NP_001119526.1; NM_001126054.2. DR RefSeq; NP_001119527.1; NM_001126055.2. DR RefSeq; NP_003679.2; NM_003688.3. DR UniGene; Hs.495984; -. DR PDB; 1KGD; X-ray; 1.31 A; A=739-909. DR PDB; 1KWA; X-ray; 1.93 A; A/B=489-572. DR PDB; 1ZL8; NMR; -; B=403-456. DR PDB; 3C0G; X-ray; 2.19 A; A/B=1-337. DR PDB; 3C0H; X-ray; 2.30 A; A/B=1-337. DR PDB; 3C0I; X-ray; 1.85 A; A=1-337. DR PDB; 3MFR; X-ray; 2.00 A; A=1-337. DR PDB; 3MFS; X-ray; 2.10 A; A=1-337. DR PDB; 3MFT; X-ray; 2.20 A; A=1-337. DR PDB; 3MFU; X-ray; 2.30 A; A=1-337. DR PDB; 3TAC; X-ray; 2.20 A; A=1-345. DR PDBsum; 1KGD; -. DR PDBsum; 1KWA; -. DR PDBsum; 1ZL8; -. DR PDBsum; 3C0G; -. DR PDBsum; 3C0H; -. DR PDBsum; 3C0I; -. DR PDBsum; 3MFR; -. DR PDBsum; 3MFS; -. DR PDBsum; 3MFT; -. DR PDBsum; 3MFU; -. DR PDBsum; 3TAC; -. DR ProteinModelPortal; O14936; -. DR SMR; O14936; 5-324, 339-458, 487-572, 615-923. DR DIP; DIP-38727N; -. DR IntAct; O14936; 25. DR MINT; MINT-102444; -. DR STRING; O14936; -. DR PhosphoSite; O14936; -. DR PRIDE; O14936; -. DR DNASU; 8573; -. DR Ensembl; ENST00000378158; ENSP00000367400; ENSG00000147044. DR Ensembl; ENST00000378163; ENSP00000367405; ENSG00000147044. DR Ensembl; ENST00000378166; ENSP00000367408; ENSG00000147044. DR Ensembl; ENST00000421587; ENSP00000400526; ENSG00000147044. DR Ensembl; ENST00000442742; ENSP00000398007; ENSG00000147044. DR GeneID; 8573; -. DR KEGG; hsa:8573; -. DR UCSC; uc004dfk.4; human. DR UCSC; uc004dfl.4; human. DR UCSC; uc004dfm.4; human. DR UCSC; uc004dfn.4; human. DR CTD; 8573; -. DR GeneCards; GC0XM041374; -. DR HGNC; HGNC:1497; CASK. DR HPA; CAB001949; -. DR HPA; HPA023857; -. DR MIM; 300172; gene. DR MIM; 300422; phenotype. DR MIM; 300749; phenotype. DR neXtProt; NX_O14936; -. DR PharmGKB; PA26081; -. DR eggNOG; COG0515; -. DR GeneTree; ENSGT00560000077048; -. DR HOVERGEN; HBG001858; -. DR KO; K06103; -. DR OMA; AIELVCT; -. DR BRENDA; 2.7.11.1; 2681. DR Pathway_Interaction_DB; syndecan_1_pathway; Syndecan-1-mediated signaling events. DR Pathway_Interaction_DB; syndecan_2_pathway; Syndecan-2-mediated signaling events. DR Pathway_Interaction_DB; syndecan_3_pathway; Syndecan-3-mediated signaling events. DR Reactome; REACT_111155; Cell-Cell communication. DR EvolutionaryTrace; O14936; -. DR GenomeRNAi; 8573; -. DR NextBio; 32157; -. DR ArrayExpress; O14936; -. DR Bgee; O14936; -. DR CleanEx; HS_CASK; -. DR Genevestigator; O14936; -. DR GermOnline; ENSG00000147044; Homo sapiens. DR GO; GO:0015629; C:actin cytoskeleton; TAS:ProtInc. DR GO; GO:0005911; C:cell-cell junction; IDA:BHF-UCL. DR GO; GO:0060170; C:cilium membrane; ISS:BHF-UCL. DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL. DR GO; GO:0005652; C:nuclear lamina; IDA:BHF-UCL. DR GO; GO:0016363; C:nuclear matrix; IDA:BHF-UCL. DR GO; GO:0005730; C:nucleolus; IDA:BHF-UCL. DR GO; GO:0042734; C:presynaptic membrane; ISS:BHF-UCL. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004385; F:guanylate kinase activity; TAS:ProtInc. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW. DR GO; GO:0007155; P:cell adhesion; TAS:ProtInc. DR GO; GO:0001953; P:negative regulation of cell-matrix adhesion; IMP:BHF-UCL. DR GO; GO:0090288; P:negative regulation of cellular response to growth factor stimulus; IMP:BHF-UCL. DR GO; GO:0010839; P:negative regulation of keratinocyte proliferation; IMP:BHF-UCL. DR GO; GO:0061045; P:negative regulation of wound healing; IMP:BHF-UCL. DR InterPro; IPR008144; Guanylate_kin. DR InterPro; IPR008145; Guanylate_kin/L-typ_Ca_channel. DR InterPro; IPR020590; Guanylate_kinase_CS. DR InterPro; IPR011009; Kinase-like_dom. DR InterPro; IPR004172; L27. DR InterPro; IPR014775; L27_C. DR InterPro; IPR001478; PDZ. DR InterPro; IPR000719; Prot_kinase_cat_dom. DR InterPro; IPR002290; Ser/Thr_dual-sp_kinase_dom. DR InterPro; IPR011511; SH3_2. DR InterPro; IPR001452; SH3_domain. DR Pfam; PF00625; Guanylate_kin; 1. DR Pfam; PF02828; L27; 2. DR Pfam; PF00595; PDZ; 1. DR Pfam; PF00069; Pkinase; 1. DR Pfam; PF07653; SH3_2; 1. DR SMART; SM00072; GuKc; 1. DR SMART; SM00569; L27; 2. DR SMART; SM00228; PDZ; 1. DR SMART; SM00220; S_TKc; 1. DR SMART; SM00326; SH3; 1. DR SUPFAM; SSF56112; Kinase_like; 1. DR SUPFAM; SSF50156; PDZ; 1. DR SUPFAM; SSF50044; SH3; 1. DR PROSITE; PS00856; GUANYLATE_KINASE_1; 1. DR PROSITE; PS50052; GUANYLATE_KINASE_2; 1. DR PROSITE; PS51022; L27; 2. DR PROSITE; PS50106; PDZ; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; FALSE_NEG. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; FALSE_NEG. DR PROSITE; PS50002; SH3; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Calmodulin-binding; KW Cell membrane; Complete proteome; Cytoplasm; Disease mutation; Kinase; KW Membrane; Mental retardation; Nucleotide-binding; Nucleus; KW Phosphoprotein; Polymorphism; Reference proteome; Repeat; KW Serine/threonine-protein kinase; SH3 domain; Transferase. FT CHAIN 1 926 Peripheral plasma membrane protein CASK. FT /FTId=PRO_0000094568. FT DOMAIN 12 276 Protein kinase. FT DOMAIN 343 398 L27 1. FT DOMAIN 402 455 L27 2. FT DOMAIN 489 564 PDZ. FT DOMAIN 615 682 SH3. FT DOMAIN 739 911 Guanylate kinase-like. FT NP_BIND 18 26 ATP (By similarity). FT REGION 305 315 Calmodulin-binding. FT ACT_SITE 141 141 By similarity. FT BINDING 41 41 ATP (By similarity). FT MOD_RES 151 151 Phosphoserine; by autocatalysis. FT MOD_RES 155 155 Phosphoserine; by autocatalysis. FT MOD_RES 571 571 Phosphotyrosine (By similarity). FT VAR_SEQ 1 385 Missing (in isoform 5). FT /FTId=VSP_024421. FT VAR_SEQ 340 345 Missing (in isoform 3). FT /FTId=VSP_024422. FT VAR_SEQ 386 386 L -> M (in isoform 5). FT /FTId=VSP_024423. FT VAR_SEQ 580 602 Missing (in isoform 3, isoform 4 and FT isoform 5). FT /FTId=VSP_024424. FT VAR_SEQ 603 614 Missing (in isoform 6). FT /FTId=VSP_024425. FT VAR_SEQ 719 723 Missing (in isoform 2, isoform 4 and FT isoform 6). FT /FTId=VSP_024426. FT VARIANT 28 28 R -> L (in FGS4; does not reveal FT significant alterations induced by the FT mutation substitution; causes a partial FT skipping of exon 2 of the protein). FT /FTId=VAR_058719. FT VARIANT 96 96 G -> V (in a lung large cell carcinoma FT sample; somatic mutation). FT /FTId=VAR_041956. FT VARIANT 268 268 Y -> H (in MRXCASK). FT /FTId=VAR_062996. FT VARIANT 396 396 P -> S (in MRXCASK). FT /FTId=VAR_062997. FT VARIANT 710 710 D -> G (in MRXCASK). FT /FTId=VAR_062998. FT CONFLICT 401 401 P -> L (in Ref. 2; AAB88198). FT CONFLICT 479 479 D -> G (in Ref. 1; AAB88125, 3; BAB12252, FT 4; AAU10527 and 8; AAF72666/AAF72667). FT CONFLICT 675 675 P -> S (in Ref. 1; AAB88125 and 4; FT AAU10527). FT CONFLICT 780 780 K -> R (in Ref. 1; AAB88125 and 4; FT AAU10527). FT HELIX 8 11 FT STRAND 12 20 FT STRAND 22 31 FT TURN 32 34 FT STRAND 37 44 FT HELIX 45 49 FT STRAND 51 53 FT HELIX 56 68 FT STRAND 77 83 FT STRAND 86 92 FT HELIX 99 108 FT HELIX 115 134 FT HELIX 144 146 FT STRAND 147 149 FT STRAND 151 153 FT STRAND 158 160 FT HELIX 163 165 FT STRAND 171 173 FT HELIX 183 185 FT HELIX 188 191 FT HELIX 199 214 FT HELIX 223 232 FT HELIX 239 242 FT HELIX 247 256 FT TURN 261 263 FT HELIX 267 271 FT HELIX 274 277 FT HELIX 279 282 FT HELIX 289 302 FT TURN 304 306 FT HELIX 309 312 FT HELIX 404 416 FT HELIX 423 431 FT HELIX 437 450 FT STRAND 489 495 FT STRAND 497 499 FT STRAND 503 506 FT HELIX 510 512 FT STRAND 513 518 FT HELIX 523 527 FT STRAND 535 539 FT HELIX 544 546 FT HELIX 549 558 FT STRAND 561 568 FT STRAND 741 745 FT HELIX 752 762 FT TURN 764 766 FT TURN 784 786 FT HELIX 793 801 FT STRAND 805 811 FT STRAND 814 819 FT HELIX 820 828 FT STRAND 832 836 FT HELIX 839 841 FT HELIX 842 845 FT TURN 848 850 FT STRAND 852 858 FT HELIX 870 886 FT HELIX 887 889 FT STRAND 891 895 FT HELIX 899 909 SQ SEQUENCE 926 AA; 105123 MW; 6C02008CE52728BA CRC64; MADDDVLFED VYELCEVIGK GPFSVVRRCI NRETGQQFAV KIVDVAKFTS SPGLSTEDLK REASICHMLK HPHIVELLET YSSDGMLYMV FEFMDGADLC FEIVKRADAG FVYSEAVASH YMRQILEALR YCHDNNIIHR DVKPHCVLLA SKENSAPVKL GGFGVAIQLG ESGLVAGGRV GTPHFMAPEV VKREPYGKPV DVWGCGVILF ILLSGCLPFY GTKERLFEGI IKGKYKMNPR QWSHISESAK DLVRRMLMLD PAERITVYEA LNHPWLKERD RYAYKIHLPE TVEQLRKFNA RRKLKGAVLA AVSSHKFNSF YGDPPEELPD FSEDPTSSGL LAAERAVSQV LDSLEEIHAL TDCSEKDLDF LHSVFQDQHL HTLLDLYDKI NTKSSPQIRN PPSDAVQRAK EVLEEISCYP ENNDAKELKR ILTQPHFMAL LQTHDVVAHE VYSDEALRVT PPPTSPYLNG DSPESANGDM DMENVTRVRL VQFQKNTDEP MGITLKMNEL NHCIVARIMH GGMIHRQGTL HVGDEIREIN GISVANQTVE QLQKMLREMR GSITFKIVPS YRTQSSSCER DSPSTSRQSP ANGHSSTNNS VSDLPSTTQP KGRQIYVRAQ FEYDPAKDDL IPCKEAGIRF RVGDIIQIIS KDDHNWWQGK LENSKNGTAG LIPSPELQEW RVACIAMEKT KQEQQASCTW FGKKKKQYKD KYLAKHNAVF DQLDLVTYEE VVKLPAFKRK TLVLLGAHGV GRRHIKNTLI TKHPDRFAYP IPHTTRPPKK DEENGKNYYF VSHDQMMQDI SNNEYLEYGS HEDAMYGTKL ETIRKIHEQG LIAILDVEPQ ALKVLRTAEF APFVVFIAAP TITPGLNEDE SLQRLQKESD ILQRTYAHYF DLTIINNEID ETIRHLEEAV ELVCTAPQWV PVSWVY //