ID KCC2B_HUMAN Reviewed; 666 AA.
AC Q13554; A4D2K0; A4D2K1; A4D2K2; A4D2K3; A4D2K4; A4D2K5; A4D2K6; O95437;
AC O95438; O95599; Q9UGH7; Q9UGH8; Q9UGH9; Q9UNX0; Q9UNX7; Q9UP00; Q9Y5N4;
AC Q9Y6F4;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 31-MAY-2011, sequence version 3.
DT 27-MAR-2024, entry version 227.
DE RecName: Full=Calcium/calmodulin-dependent protein kinase type II subunit beta;
DE Short=CaM kinase II subunit beta;
DE Short=CaMK-II subunit beta;
DE EC=2.7.11.17 {ECO:0000269|PubMed:31930741};
GN Name=CAMK2B; Synonyms=CAM2, CAMK2, CAMKB;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 5; 6 AND 7).
RC TISSUE=Brain;
RX PubMed=10858498; DOI=10.1016/s0014-5793(00)01634-3;
RA Wang P., Wu Y., Zhou T.H., Sun Y., Pei G.;
RT "Identification of alternative splicing variants of the beta subunit of
RT human Ca(2+)/calmodulin-dependent protein kinase II with different
RT activities.";
RL FEBS Lett. 475:107-110(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
RC TISSUE=Skeletal muscle;
RA Leddy J.J., Salih M., Tuana B.S.;
RL Submitted (MAR-1995) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 5).
RC TISSUE=Brain;
RA Li G.Y., Cooper N.G.F.;
RT "Molecular cloning and sequencing of human calcium/calmodulin dependent
RT protein kinase II beta subunit.";
RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 5).
RC TISSUE=Insulinoma;
RX PubMed=10819240; DOI=10.1007/s001250051330;
RA Rochlitz H., Voigt A., Lankat-Buttgereit B., Goeke B., Heimberg H.,
RA Nauck M.A., Schiemann U., Schatz H., Pfeiffer A.F.;
RT "Cloning and quantitative determination of the human Ca2+/calmodulin-
RT dependent protein kinase II (CaMK II) isoforms in human beta cells.";
RL Diabetologia 43:465-473(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Testis, and Thalamus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Lung;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 302-605 (ISOFORM 2).
RX PubMed=9060999; DOI=10.1016/s0167-4889(96)00141-3;
RA Tombes R.M., Krystal G.W.;
RT "Identification of novel human tumor cell-specific CaMK-II variants.";
RL Biochim. Biophys. Acta 1355:281-292(1997).
RN [9]
RP ACTIVITY REGULATION, SUBUNIT, AND AUTOPHOSPHORYLATION.
RX PubMed=14722083; DOI=10.1074/jbc.m313597200;
RA Gaertner T.R., Kolodziej S.J., Wang D., Kobayashi R., Koomen J.M.,
RA Stoops J.K., Waxham M.N.;
RT "Comparative analyses of the three-dimensional structures and enzymatic
RT properties of alpha, beta, gamma and delta isoforms of Ca2+-calmodulin-
RT dependent protein kinase II.";
RL J. Biol. Chem. 279:12484-12494(2004).
RN [10]
RP INTERACTION WITH MPDZ.
RX PubMed=15312654; DOI=10.1016/j.neuron.2004.08.003;
RA Krapivinsky G., Medina I., Krapivinsky L., Gapon S., Clapham D.E.;
RT "SynGAP-MUPP1-CaMKII synaptic complexes regulate p38 MAP kinase activity
RT and NMDA receptor-dependent synaptic AMPA receptor potentiation.";
RL Neuron 43:563-574(2004).
RN [11]
RP FUNCTION IN SKELETAL MUSCLE, PHOSPHORYLATION AT THR-287, FUNCTION IN
RP PHOSPHORYLATION OF PLN, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=16690701; DOI=10.1113/jphysiol.2006.111757;
RA Rose A.J., Kiens B., Richter E.A.;
RT "Ca2+-calmodulin-dependent protein kinase expression and signalling in
RT skeletal muscle during exercise.";
RL J. Physiol. (Lond.) 574:889-903(2006).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [13]
RP SUBCELLULAR LOCATION.
RX PubMed=21529938; DOI=10.1016/j.ceca.2011.02.007;
RA Wayman G.A., Tokumitsu H., Davare M.A., Soderling T.R.;
RT "Analysis of CaM-kinase signaling in cells.";
RL Cell Calcium 50:1-8(2011).
RN [14]
RP REVIEW ON FUNCTION IN SKELETAL MUSCLE.
RX PubMed=15294044; DOI=10.1079/pns2004335;
RA Chin E.R.;
RT "The role of calcium and calcium/calmodulin-dependent kinases in skeletal
RT muscle plasticity and mitochondrial biogenesis.";
RL Proc. Nutr. Soc. 63:279-286(2004).
RN [15]
RP REVIEW ON FUNCTION IN SKELETAL MUSCLE.
RA Sacchetto R., Bovo E., Damiani E.;
RT "The Ca2+-calmodulin dependent protein kinase II system of skeletal muscle
RT sarcoplasmic reticulum.";
RL Basic Appl. Myol. 15:5-17(2005).
RN [16]
RP REVIEW ON FUNCTION IN NEURONAL PLASTICITY.
RX PubMed=18817731; DOI=10.1016/j.neuron.2008.08.021;
RA Wayman G.A., Lee Y.S., Tokumitsu H., Silva A.J., Silva A., Soderling T.R.;
RT "Calmodulin-kinases: modulators of neuronal development and plasticity.";
RL Neuron 59:914-931(2008).
RN [17]
RP REVIEW ON FUNCTION IN NEURONAL PLASTICITY.
RX PubMed=19996366; DOI=10.1152/physiol.00029.2009;
RA Okamoto K., Bosch M., Hayashi Y.;
RT "The roles of CaMKII and F-actin in the structural plasticity of dendritic
RT spines: a potential molecular identity of a synaptic tag?";
RL Physiology (Bethesda) 24:357-366(2009).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-401, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [19]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=31930741; DOI=10.15252/embj.2019102608;
RA Jiang X., Wang X., Ding X., Du M., Li B., Weng X., Zhang J., Li L.,
RA Tian R., Zhu Q., Chen S., Wang L., Liu W., Fang L., Neculai D., Sun Q.;
RT "FAM134B oligomerization drives endoplasmic reticulum membrane scission for
RT ER-phagy.";
RL EMBO J. 39:e102608-e102608(2020).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 11-303 IN COMPLEX WITH INHIBITOR.
RG Structural genomics consortium (SGC);
RT "Crystal structure of human calcium/calmodulin-dependent protein kinase IIb
RT isoform 1 (CAMK2B).";
RL Submitted (DEC-2007) to the PDB data bank.
RN [21]
RP VARIANTS [LARGE SCALE ANALYSIS] LEU-489 AND LYS-510.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
RN [22]
RP INVOLVEMENT IN MRD54, VARIANTS MRD54 29-ARG--GLN-666 DEL; LYS-110; LEU-139;
RP LYS-237 AND GLU-301, CHARACTERIZATION OF VARIANTS MRD54 LYS-110; LEU-139;
RP LYS-237 AND GLU-301, AND FUNCTION.
RX PubMed=29100089; DOI=10.1016/j.ajhg.2017.10.003;
RG Undiagnosed Diseases Network;
RG GEM HUGO;
RG Deciphering Developmental Disorders Study;
RA Kuery S., van Woerden G.M., Besnard T., Proietti Onori M., Latypova X.,
RA Towne M.C., Cho M.T., Prescott T.E., Ploeg M.A., Sanders S.,
RA Stessman H.A.F., Pujol A., Distel B., Robak L.A., Bernstein J.A.,
RA Denomme-Pichon A.S., Lesca G., Sellars E.A., Berg J., Carre W., Busk O.L.,
RA van Bon B.W.M., Waugh J.L., Deardorff M., Hoganson G.E., Bosanko K.B.,
RA Johnson D.S., Dabir T., Holla O.L., Sarkar A., Tveten K., de Bellescize J.,
RA Braathen G.J., Terhal P.A., Grange D.K., van Haeringen A., Lam C.,
RA Mirzaa G., Burton J., Bhoj E.J., Douglas J., Santani A.B., Nesbitt A.I.,
RA Helbig K.L., Andrews M.V., Begtrup A., Tang S., van Gassen K.L.I.,
RA Juusola J., Foss K., Enns G.M., Moog U., Hinderhofer K., Paramasivam N.,
RA Lincoln S., Kusako B.H., Lindenbaum P., Charpentier E., Nowak C.B.,
RA Cherot E., Simonet T., Ruivenkamp C.A.L., Hahn S., Brownstein C.A., Xia F.,
RA Schmitt S., Deb W., Bonneau D., Nizon M., Quinquis D., Chelly J.,
RA Rudolf G., Sanlaville D., Parent P., Gilbert-Dussardier B., Toutain A.,
RA Sutton V.R., Thies J., Peart-Vissers L.E.L.M., Boisseau P., Vincent M.,
RA Grabrucker A.M., Dubourg C., Tan W.H., Verbeek N.E., Granzow M.,
RA Santen G.W.E., Shendure J., Isidor B., Pasquier L., Redon R., Yang Y.,
RA State M.W., Kleefstra T., Cogne B., Petrovski S., Retterer K.,
RA Eichler E.E., Rosenfeld J.A., Agrawal P.B., Bezieau S., Odent S.,
RA Elgersma Y., Mercier S.;
RT "De Novo Mutations in Protein Kinase Genes CAMK2A and CAMK2B Cause
RT Intellectual Disability.";
RL Am. J. Hum. Genet. 101:768-788(2017).
RN [23]
RP INVOLVEMENT IN MRD54, AND VARIANTS MRD54 LEU-213 AND SER-284.
RX PubMed=29560374; DOI=10.1002/acn3.528;
RA Akita T., Aoto K., Kato M., Shiina M., Mutoh H., Nakashima M., Kuki I.,
RA Okazaki S., Magara S., Shiihara T., Yokochi K., Aiba K., Tohyama J.,
RA Ohba C., Miyatake S., Miyake N., Ogata K., Fukuda A., Matsumoto N.,
RA Saitsu H.;
RT "De novo variants in CAMK2A and CAMK2B cause neurodevelopmental
RT disorders.";
RL Ann. Clin. Transl. Neurol. 5:280-296(2018).
CC -!- FUNCTION: Calcium/calmodulin-dependent protein kinase that functions
CC autonomously after Ca(2+)/calmodulin-binding and autophosphorylation,
CC and is involved in dendritic spine and synapse formation, neuronal
CC plasticity and regulation of sarcoplasmic reticulum Ca(2+) transport in
CC skeletal muscle (PubMed:16690701). In neurons, plays an essential
CC structural role in the reorganization of the actin cytoskeleton during
CC plasticity by binding and bundling actin filaments in a kinase-
CC independent manner. This structural function is required for correct
CC targeting of CaMK2A, which acts downstream of NMDAR to promote
CC dendritic spine and synapse formation and maintain synaptic plasticity
CC which enables long-term potentiation (LTP) and hippocampus-dependent
CC learning. In developing hippocampal neurons, promotes arborization of
CC the dendritic tree and in mature neurons, promotes dendritic
CC remodeling. Also regulates the migration of developing neurons
CC (PubMed:29100089). Participates in the modulation of skeletal muscle
CC function in response to exercise (PubMed:16690701). In slow-twitch
CC muscles, is involved in regulation of sarcoplasmic reticulum (SR)
CC Ca(2+) transport and in fast-twitch muscle participates in the control
CC of Ca(2+) release from the SR through phosphorylation of triadin, a
CC ryanodine receptor-coupling factor, and phospholamban (PLN/PLB), an
CC endogenous inhibitor of SERCA2A/ATP2A2. In response to interferon-gamma
CC (IFN-gamma) stimulation, catalyzes phosphorylation of STAT1,
CC stimulating the JAK-STAT signaling pathway (By similarity).
CC Phosphorylates reticulophagy regulator RETREG1 at 'Ser-151' under
CC endoplasmic reticulum stress conditions which enhances RETREG1
CC oligomerization and its membrane scission and reticulophagy activity
CC (PubMed:31930741). {ECO:0000250|UniProtKB:P08413,
CC ECO:0000269|PubMed:16690701, ECO:0000269|PubMed:29100089,
CC ECO:0000269|PubMed:31930741}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.17;
CC Evidence={ECO:0000269|PubMed:31930741};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.17;
CC -!- ACTIVITY REGULATION: Activated by Ca(2+)/calmodulin. Binding of
CC calmodulin results in conformational change that relieves intrasteric
CC autoinhibition and allows autophosphorylation of Thr-287 which turns
CC the kinase in a constitutively active form and confers to the kinase a
CC Ca(2+)-independent activity. {ECO:0000269|PubMed:14722083}.
CC -!- SUBUNIT: CAMK2 is composed of 4 different chains: alpha (CAMK2A), beta
CC (CAMK2B), gamma (CAMK2G), and delta (CAMK2D). The different isoforms
CC assemble into homo- or heteromultimeric holoenzymes composed of 12
CC subunits with two hexameric rings stacked one on top of the other
CC (PubMed:14722083, Ref.20). Interacts with SYNGAP1 and CAMK2N2 (By
CC similarity). Interacts with MPDZ (PubMed:15312654). Interacts with
CC FOXO3 (By similarity). Interacts (when in a kinase inactive state not
CC associated with calmodulin) with ARC; leading to target ARC to inactive
CC synapses (By similarity). Interacts with CAMK2N1; this interaction
CC requires CAMK2B activation by Ca(2+) (By similarity).
CC {ECO:0000250|UniProtKB:P08413, ECO:0000250|UniProtKB:P28652,
CC ECO:0000269|PubMed:14722083, ECO:0000269|PubMed:15312654,
CC ECO:0000269|Ref.20}.
CC -!- INTERACTION:
CC Q13554; O00154: ACOT7; NbExp=3; IntAct=EBI-1058722, EBI-948905;
CC Q13554; Q2VPB7: AP5B1; NbExp=3; IntAct=EBI-1058722, EBI-5917279;
CC Q13554; Q9UQM7: CAMK2A; NbExp=3; IntAct=EBI-1058722, EBI-1383687;
CC Q13554; Q13554: CAMK2B; NbExp=2; IntAct=EBI-1058722, EBI-1058722;
CC Q13554; Q13557: CAMK2D; NbExp=4; IntAct=EBI-1058722, EBI-351018;
CC Q13554; Q8N0U1: FAM171A2; NbExp=3; IntAct=EBI-1058722, EBI-10264767;
CC Q13554; P60412: KRTAP10-11; NbExp=3; IntAct=EBI-1058722, EBI-10217483;
CC Q13554; Q3LI72: KRTAP19-5; NbExp=3; IntAct=EBI-1058722, EBI-1048945;
CC Q13554; Q3SYF9: KRTAP19-7; NbExp=3; IntAct=EBI-1058722, EBI-10241353;
CC Q13554; Q9UI95: MAD2L2; NbExp=3; IntAct=EBI-1058722, EBI-77889;
CC Q13554; Q9BUE0: MED18; NbExp=3; IntAct=EBI-1058722, EBI-394640;
CC Q13554; Q9UBU8: MORF4L1; NbExp=3; IntAct=EBI-1058722, EBI-399246;
CC Q13554; Q9UBU8-2: MORF4L1; NbExp=3; IntAct=EBI-1058722, EBI-10288852;
CC Q13554; Q9Y3B7: MRPL11; NbExp=3; IntAct=EBI-1058722, EBI-5453723;
CC Q13554; Q93100: PHKB; NbExp=3; IntAct=EBI-1058722, EBI-740559;
CC Q13554; Q969H6: POP5; NbExp=3; IntAct=EBI-1058722, EBI-366525;
CC Q13554; P61225: RAP2B; NbExp=3; IntAct=EBI-1058722, EBI-750871;
CC Q13554; O43251: RBFOX2; NbExp=3; IntAct=EBI-1058722, EBI-746056;
CC Q13554; Q93062: RBPMS; NbExp=3; IntAct=EBI-1058722, EBI-740322;
CC Q13554; P62913: RPL11; NbExp=3; IntAct=EBI-1058722, EBI-354380;
CC Q13554; Q9NTN9-3: SEMA4G; NbExp=3; IntAct=EBI-1058722, EBI-9089805;
CC Q13554; Q5W111: SPRYD7; NbExp=3; IntAct=EBI-1058722, EBI-10248098;
CC Q13554; Q8N0Z6: TTC5; NbExp=3; IntAct=EBI-1058722, EBI-9526213;
CC Q13554; B3KWQ7; NbExp=3; IntAct=EBI-1058722, EBI-10175974;
CC Q13554-3; O00154-4: ACOT7; NbExp=3; IntAct=EBI-11523526, EBI-12007918;
CC Q13554-3; P15289: ARSA; NbExp=3; IntAct=EBI-11523526, EBI-2117357;
CC Q13554-3; Q9UQM7: CAMK2A; NbExp=3; IntAct=EBI-11523526, EBI-1383687;
CC Q13554-3; Q13557-8: CAMK2D; NbExp=4; IntAct=EBI-11523526, EBI-11534483;
CC Q13554-3; Q13555-5: CAMK2G; NbExp=3; IntAct=EBI-11523526, EBI-12020154;
CC Q13554-3; Q9NUG4: CCM2L; NbExp=3; IntAct=EBI-11523526, EBI-350645;
CC Q13554-3; Q16543: CDC37; NbExp=3; IntAct=EBI-11523526, EBI-295634;
CC Q13554-3; Q6P1R4: DUS1L; NbExp=3; IntAct=EBI-11523526, EBI-6660325;
CC Q13554-3; O43790: KRT86; NbExp=3; IntAct=EBI-11523526, EBI-9996498;
CC Q13554-3; Q07627: KRTAP1-1; NbExp=3; IntAct=EBI-11523526, EBI-11959885;
CC Q13554-3; Q7Z4W3: KRTAP19-3; NbExp=3; IntAct=EBI-11523526, EBI-12020132;
CC Q13554-3; Q3LI66: KRTAP6-2; NbExp=3; IntAct=EBI-11523526, EBI-11962084;
CC Q13554-3; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-11523526, EBI-16439278;
CC Q13554-3; Q9UBU8-2: MORF4L1; NbExp=3; IntAct=EBI-11523526, EBI-10288852;
CC Q13554-3; Q15014: MORF4L2; NbExp=3; IntAct=EBI-11523526, EBI-399257;
CC Q13554-3; Q9Y3B7: MRPL11; NbExp=3; IntAct=EBI-11523526, EBI-5453723;
CC Q13554-3; Q96T60: PNKP; NbExp=3; IntAct=EBI-11523526, EBI-1045072;
CC Q13554-3; Q9BUI4: POLR3C; NbExp=3; IntAct=EBI-11523526, EBI-5452779;
CC Q13554-3; P61225: RAP2B; NbExp=3; IntAct=EBI-11523526, EBI-750871;
CC Q13554-3; P78317: RNF4; NbExp=3; IntAct=EBI-11523526, EBI-2340927;
CC Q13554-3; O14787-2: TNPO2; NbExp=3; IntAct=EBI-11523526, EBI-12076664;
CC Q13554-3; Q9Y5L0: TNPO3; NbExp=3; IntAct=EBI-11523526, EBI-1042571;
CC Q13554-3; Q8N0Z6: TTC5; NbExp=3; IntAct=EBI-11523526, EBI-9526213;
CC Q13554-3; P26640: VARS1; NbExp=3; IntAct=EBI-11523526, EBI-355765;
CC Q13554-3; A0A0C4DGF1: ZBTB32; NbExp=3; IntAct=EBI-11523526, EBI-10188476;
CC Q13554-3; Q9UJ78-2: ZMYM5; NbExp=3; IntAct=EBI-11523526, EBI-17634549;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:21529938}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000250}. Sarcoplasmic reticulum
CC membrane {ECO:0000269|PubMed:21529938}; Peripheral membrane protein
CC {ECO:0000269|PubMed:21529938}; Cytoplasmic side
CC {ECO:0000269|PubMed:21529938}. Synapse {ECO:0000250|UniProtKB:P08413}.
CC Note=In slow-twitch muscle, evenly distributed between longitudinal SR
CC and junctional SR.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=8;
CC Comment=The variable region of the CAMK2B protein is encoded by at
CC least 7 exons (V1 to V7). Alternative splicing within this region
CC gives rise to CAMK2B isoforms.;
CC Name=4;
CC IsoId=Q13554-1; Sequence=Displayed;
CC Name=1; Synonyms=Beta;
CC IsoId=Q13554-2; Sequence=VSP_004776;
CC Name=2; Synonyms=Beta1, Beta'E;
CC IsoId=Q13554-3; Sequence=VSP_004770, VSP_004771, VSP_004775,
CC VSP_004776;
CC Name=3; Synonyms=Beta2;
CC IsoId=Q13554-4; Sequence=VSP_004770, VSP_004771, VSP_004774,
CC VSP_004776;
CC Name=5; Synonyms=Beta4, BetaE;
CC IsoId=Q13554-5; Sequence=VSP_004770, VSP_004771, VSP_004776;
CC Name=6; Synonyms=Beta6;
CC IsoId=Q13554-6; Sequence=VSP_004773, VSP_004776, VSP_004777;
CC Name=7; Synonyms=Beta7;
CC IsoId=Q13554-7; Sequence=VSP_004770, VSP_004772;
CC Name=8;
CC IsoId=Q13554-8; Sequence=VSP_041219, VSP_004776;
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed in adult and fetal
CC brain. Expression is slightly lower in fetal brain. Expressed in
CC skeletal muscle. {ECO:0000269|PubMed:16690701}.
CC -!- INDUCTION: Activity is induced in skeletal muscle during exercise.
CC {ECO:0000269|PubMed:16690701}.
CC -!- DOMAIN: The CAMK2 protein kinases contain a unique C-terminal subunit
CC association domain responsible for oligomerization.
CC -!- PTM: Autophosphorylation of Thr-287 following activation by
CC Ca(2+)/calmodulin. Phosphorylation of Thr-287 locks the kinase into an
CC activated state. {ECO:0000269|PubMed:14722083,
CC ECO:0000269|PubMed:16690701}.
CC -!- DISEASE: Intellectual developmental disorder, autosomal dominant 54
CC (MRD54) [MIM:617799]: A disorder characterized by significantly below
CC average general intellectual functioning associated with impairments in
CC adaptive behavior and manifested during the developmental period.
CC {ECO:0000269|PubMed:29100089, ECO:0000269|PubMed:29560374}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. CaMK subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC99802.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF078803; AAD42035.1; -; mRNA.
DR EMBL; AF081572; AAD42036.1; -; mRNA.
DR EMBL; AF081924; AAD42037.1; -; mRNA.
DR EMBL; AF083419; AAD42038.1; -; mRNA.
DR EMBL; AF140350; AAD42070.1; -; mRNA.
DR EMBL; U23460; AAC99802.1; ALT_FRAME; mRNA.
DR EMBL; AF112472; AAD03744.1; -; mRNA.
DR EMBL; AF112471; AAD03743.1; -; mRNA.
DR EMBL; AJ252236; CAB65120.1; -; mRNA.
DR EMBL; AJ252237; CAB65121.1; -; mRNA.
DR EMBL; AJ252238; CAB65122.1; -; mRNA.
DR EMBL; AK290148; BAF82837.1; -; mRNA.
DR EMBL; AK315663; BAG38029.1; -; mRNA.
DR EMBL; CH236960; EAL23756.1; -; Genomic_DNA.
DR EMBL; CH236960; EAL23757.1; -; Genomic_DNA.
DR EMBL; CH236960; EAL23758.1; -; Genomic_DNA.
DR EMBL; CH236960; EAL23759.1; -; Genomic_DNA.
DR EMBL; CH236960; EAL23760.1; -; Genomic_DNA.
DR EMBL; CH236960; EAL23761.1; -; Genomic_DNA.
DR EMBL; CH236960; EAL23762.1; -; Genomic_DNA.
DR EMBL; BC019070; AAH19070.1; -; mRNA.
DR EMBL; U50358; AAB16863.1; -; mRNA.
DR CCDS; CCDS43573.1; -. [Q13554-8]
DR CCDS; CCDS5483.1; -. [Q13554-1]
DR CCDS; CCDS5484.1; -. [Q13554-2]
DR CCDS; CCDS5485.1; -. [Q13554-5]
DR CCDS; CCDS5486.1; -. [Q13554-3]
DR CCDS; CCDS5487.1; -. [Q13554-6]
DR CCDS; CCDS5488.1; -. [Q13554-4]
DR CCDS; CCDS5489.1; -. [Q13554-7]
DR RefSeq; NP_001211.3; NM_001220.4. [Q13554-1]
DR RefSeq; NP_001280099.1; NM_001293170.1. [Q13554-2]
DR RefSeq; NP_742075.1; NM_172078.2. [Q13554-2]
DR RefSeq; NP_742076.1; NM_172079.2. [Q13554-5]
DR RefSeq; NP_742077.1; NM_172080.2. [Q13554-8]
DR RefSeq; NP_742078.1; NM_172081.2. [Q13554-3]
DR RefSeq; NP_742079.1; NM_172082.2. [Q13554-6]
DR RefSeq; NP_742080.1; NM_172083.2. [Q13554-4]
DR RefSeq; NP_742081.1; NM_172084.2. [Q13554-7]
DR PDB; 3BHH; X-ray; 2.40 A; A/B/C/D=11-303.
DR PDB; 7URW; X-ray; 3.11 A; A/B/C/D/E/F/G=534-666.
DR PDB; 7URY; X-ray; 2.64 A; A/B/C/D/E/F/G=534-666.
DR PDB; 7URZ; X-ray; 3.45 A; A/B/C/G=534-666.
DR PDBsum; 3BHH; -.
DR PDBsum; 7URW; -.
DR PDBsum; 7URY; -.
DR PDBsum; 7URZ; -.
DR AlphaFoldDB; Q13554; -.
DR SMR; Q13554; -.
DR BioGRID; 107266; 178.
DR DIP; DIP-39770N; -.
DR IntAct; Q13554; 81.
DR MINT; Q13554; -.
DR STRING; 9606.ENSP00000379098; -.
DR BindingDB; Q13554; -.
DR ChEMBL; CHEMBL4121; -.
DR DrugBank; DB07168; [4-({4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]-6-(methylamino)pyrimidin-2-yl}amino)phenyl]acetonitrile.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q13554; -.
DR GuidetoPHARMACOLOGY; 1556; -.
DR GlyCosmos; Q13554; 2 sites, 1 glycan.
DR GlyGen; Q13554; 5 sites, 1 O-linked glycan (5 sites).
DR iPTMnet; Q13554; -.
DR PhosphoSitePlus; Q13554; -.
DR SwissPalm; Q13554; -.
DR BioMuta; CAMK2B; -.
DR DMDM; 334302890; -.
DR EPD; Q13554; -.
DR jPOST; Q13554; -.
DR MassIVE; Q13554; -.
DR MaxQB; Q13554; -.
DR PaxDb; 9606-ENSP00000379098; -.
DR PeptideAtlas; Q13554; -.
DR ProteomicsDB; 59530; -. [Q13554-1]
DR ProteomicsDB; 59531; -. [Q13554-2]
DR ProteomicsDB; 59532; -. [Q13554-3]
DR ProteomicsDB; 59533; -. [Q13554-4]
DR ProteomicsDB; 59534; -. [Q13554-5]
DR ProteomicsDB; 59535; -. [Q13554-6]
DR ProteomicsDB; 59536; -. [Q13554-7]
DR ProteomicsDB; 59537; -. [Q13554-8]
DR Pumba; Q13554; -.
DR Antibodypedia; 3482; 622 antibodies from 38 providers.
DR DNASU; 816; -.
DR Ensembl; ENST00000258682.10; ENSP00000258682.6; ENSG00000058404.21. [Q13554-8]
DR Ensembl; ENST00000346990.8; ENSP00000326518.5; ENSG00000058404.21. [Q13554-7]
DR Ensembl; ENST00000347193.8; ENSP00000326544.6; ENSG00000058404.21. [Q13554-6]
DR Ensembl; ENST00000350811.7; ENSP00000326375.5; ENSG00000058404.21. [Q13554-2]
DR Ensembl; ENST00000353625.8; ENSP00000326427.5; ENSG00000058404.21. [Q13554-4]
DR Ensembl; ENST00000358707.7; ENSP00000351542.3; ENSG00000058404.21. [Q13554-3]
DR Ensembl; ENST00000395747.6; ENSP00000379096.2; ENSG00000058404.21. [Q13554-5]
DR Ensembl; ENST00000395749.7; ENSP00000379098.2; ENSG00000058404.21. [Q13554-1]
DR Ensembl; ENST00000440254.6; ENSP00000397937.2; ENSG00000058404.21. [Q13554-2]
DR Ensembl; ENST00000700285.1; ENSP00000514918.1; ENSG00000058404.21. [Q13554-2]
DR GeneID; 816; -.
DR KEGG; hsa:816; -.
DR MANE-Select; ENST00000395749.7; ENSP00000379098.2; NM_001220.5; NP_001211.3.
DR UCSC; uc003tkp.3; human. [Q13554-1]
DR AGR; HGNC:1461; -.
DR CTD; 816; -.
DR DisGeNET; 816; -.
DR GeneCards; CAMK2B; -.
DR HGNC; HGNC:1461; CAMK2B.
DR HPA; ENSG00000058404; Group enriched (brain, heart muscle, skeletal muscle, tongue).
DR MalaCards; CAMK2B; -.
DR MIM; 607707; gene.
DR MIM; 617799; phenotype.
DR neXtProt; NX_Q13554; -.
DR OpenTargets; ENSG00000058404; -.
DR Orphanet; 178469; Autosomal dominant non-syndromic intellectual disability.
DR PharmGKB; PA91; -.
DR VEuPathDB; HostDB:ENSG00000058404; -.
DR eggNOG; KOG0033; Eukaryota.
DR GeneTree; ENSGT00940000158973; -.
DR HOGENOM; CLU_000288_71_0_1; -.
DR InParanoid; Q13554; -.
DR OMA; DENHHYL; -.
DR OrthoDB; 1121238at2759; -.
DR PhylomeDB; Q13554; -.
DR TreeFam; TF315229; -.
DR BRENDA; 2.7.11.17; 2681.
DR PathwayCommons; Q13554; -.
DR Reactome; R-HSA-111932; CaMK IV-mediated phosphorylation of CREB.
DR Reactome; R-HSA-3371571; HSF1-dependent transactivation.
DR Reactome; R-HSA-399719; Trafficking of AMPA receptors.
DR Reactome; R-HSA-438066; Unblocking of NMDA receptors, glutamate binding and activation.
DR Reactome; R-HSA-442729; CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde.
DR Reactome; R-HSA-442982; Ras activation upon Ca2+ influx through NMDA receptor.
DR Reactome; R-HSA-5576892; Phase 0 - rapid depolarisation.
DR Reactome; R-HSA-5578775; Ion homeostasis.
DR Reactome; R-HSA-5673000; RAF activation.
DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade.
DR Reactome; R-HSA-6802946; Signaling by moderate kinase activity BRAF mutants.
DR Reactome; R-HSA-6802952; Signaling by BRAF and RAF1 fusions.
DR Reactome; R-HSA-6802955; Paradoxical activation of RAF signaling by kinase inactive BRAF.
DR Reactome; R-HSA-877300; Interferon gamma signaling.
DR Reactome; R-HSA-9022692; Regulation of MECP2 expression and activity.
DR Reactome; R-HSA-936837; Ion transport by P-type ATPases.
DR Reactome; R-HSA-9609736; Assembly and cell surface presentation of NMDA receptors.
DR Reactome; R-HSA-9617324; Negative regulation of NMDA receptor-mediated neuronal transmission.
DR Reactome; R-HSA-9620244; Long-term potentiation.
DR Reactome; R-HSA-9649948; Signaling downstream of RAS mutants.
DR Reactome; R-HSA-9656223; Signaling by RAF1 mutants.
DR SignaLink; Q13554; -.
DR SIGNOR; Q13554; -.
DR BioGRID-ORCS; 816; 18 hits in 1181 CRISPR screens.
DR ChiTaRS; CAMK2B; human.
DR EvolutionaryTrace; Q13554; -.
DR GeneWiki; CAMK2B; -.
DR GenomeRNAi; 816; -.
DR Pharos; Q13554; Tchem.
DR PRO; PR:Q13554; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q13554; Protein.
DR Bgee; ENSG00000058404; Expressed in cerebellar cortex and 171 other cell types or tissues.
DR ExpressionAtlas; Q13554; baseline and differential.
DR Genevisible; Q13554; HS.
DR GO; GO:0005954; C:calcium- and calmodulin-dependent protein kinase complex; IDA:BHF-UCL.
DR GO; GO:0005813; C:centrosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030666; C:endocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0045202; C:synapse; IEA:UniProtKB-SubCell.
DR GO; GO:0003779; F:actin binding; IEA:UniProtKB-KW.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0009931; F:calcium-dependent protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; IBA:GO_Central.
DR GO; GO:0004683; F:calmodulin-dependent protein kinase activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:BHF-UCL.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB.
DR GO; GO:0061003; P:positive regulation of dendritic spine morphogenesis; ISS:UniProtKB.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISS:UniProtKB.
DR GO; GO:0090129; P:positive regulation of synapse maturation; ISS:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; TAS:ProtInc.
DR GO; GO:0051924; P:regulation of calcium ion transport; TAS:UniProtKB.
DR GO; GO:0060998; P:regulation of dendritic spine development; TAS:UniProtKB.
DR GO; GO:0048169; P:regulation of long-term neuronal synaptic plasticity; TAS:UniProtKB.
DR GO; GO:2001222; P:regulation of neuron migration; IMP:UniProtKB.
DR GO; GO:0014733; P:regulation of skeletal muscle adaptation; TAS:UniProtKB.
DR GO; GO:0051823; P:regulation of synapse structural plasticity; TAS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR CDD; cd14086; STKc_CaMKII; 1.
DR Gene3D; 3.10.450.50; -; 1.
DR Gene3D; 6.10.140.620; -; 1.
DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR InterPro; IPR013543; Ca/CaM-dep_prot_kinase-assoc.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR032710; NTF2-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR PANTHER; PTHR24347:SF403; CALCIUM_CALMODULIN-DEPENDENT PROTEIN KINASE TYPE II SUBUNIT BETA; 1.
DR PANTHER; PTHR24347; SERINE/THREONINE-PROTEIN KINASE; 1.
DR Pfam; PF08332; CaMKII_AD; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF54427; NTF2-like; 1.
DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Actin-binding; Alternative splicing; ATP-binding;
KW Calmodulin-binding; Cytoplasm; Cytoskeleton; Developmental protein;
KW Differentiation; Intellectual disability; Kinase; Membrane; Neurogenesis;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Sarcoplasmic reticulum; Serine/threonine-protein kinase; Synapse;
KW Transferase.
FT CHAIN 1..666
FT /note="Calcium/calmodulin-dependent protein kinase type II
FT subunit beta"
FT /id="PRO_0000086096"
FT DOMAIN 14..272
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 283..292
FT /note="Autoinhibitory domain"
FT /evidence="ECO:0000250"
FT REGION 291..301
FT /note="Calmodulin-binding"
FT REGION 349..534
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 350..368
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 430..446
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 511..530
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 136
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 20..28
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 43
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 17
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P28652"
FT MOD_RES 287
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:16690701"
FT MOD_RES 306
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 307
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 367
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P08413"
FT MOD_RES 394
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P28652"
FT MOD_RES 397
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P08413"
FT MOD_RES 400
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P28652"
FT MOD_RES 401
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VAR_SEQ 316..340
FT /note="Missing (in isoform 8)"
FT /evidence="ECO:0000305"
FT /id="VSP_041219"
FT VAR_SEQ 316
FT /note="V -> A (in isoform 2, isoform 3, isoform 5 and
FT isoform 7)"
FT /evidence="ECO:0000303|PubMed:10819240,
FT ECO:0000303|PubMed:10858498, ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:9060999,
FT ECO:0000303|Ref.3"
FT /id="VSP_004770"
FT VAR_SEQ 317..533
FT /note="Missing (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:10858498"
FT /id="VSP_004772"
FT VAR_SEQ 317..340
FT /note="Missing (in isoform 2, isoform 3 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:10819240,
FT ECO:0000303|PubMed:10858498, ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:9060999,
FT ECO:0000303|Ref.3"
FT /id="VSP_004771"
FT VAR_SEQ 354..392
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:10819240"
FT /id="VSP_004774"
FT VAR_SEQ 354..377
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:10858498"
FT /id="VSP_004773"
FT VAR_SEQ 379..393
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10819240,
FT ECO:0000303|PubMed:10858498, ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:9060999"
FT /id="VSP_004775"
FT VAR_SEQ 410..533
FT /note="Missing (in isoform 1, isoform 2, isoform 3, isoform
FT 5, isoform 6 and isoform 8)"
FT /evidence="ECO:0000303|PubMed:10819240,
FT ECO:0000303|PubMed:10858498, ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:9060999,
FT ECO:0000303|Ref.3"
FT /id="VSP_004776"
FT VAR_SEQ 559..584
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:10858498"
FT /id="VSP_004777"
FT VARIANT 29..666
FT /note="Missing (in MRD54)"
FT /evidence="ECO:0000269|PubMed:29100089"
FT /id="VAR_080588"
FT VARIANT 110
FT /note="E -> K (in MRD54; decreased protein abundance;
FT increased autophosphorylation; decreased neuronal
FT migration; dbSNP:rs1554402092)"
FT /evidence="ECO:0000269|PubMed:29100089"
FT /id="VAR_080589"
FT VARIANT 139
FT /note="P -> L (in MRD54; decreased protein abundance;
FT increased autophosphorylation; decreased neuronal
FT migration; dbSNP:rs1554389088)"
FT /evidence="ECO:0000269|PubMed:29100089"
FT /id="VAR_080590"
FT VARIANT 213
FT /note="P -> L (in MRD54; dbSNP:rs1554387293)"
FT /evidence="ECO:0000269|PubMed:29560374"
FT /id="VAR_081162"
FT VARIANT 237
FT /note="E -> K (in MRD54; no effect on protein abundance;
FT increased autophosphorylation; decreased neuronal
FT migration; dbSNP:rs1554386687)"
FT /evidence="ECO:0000269|PubMed:29100089"
FT /id="VAR_080591"
FT VARIANT 284
FT /note="R -> S (in MRD54; dbSNP:rs1554385203)"
FT /evidence="ECO:0000269|PubMed:29560374"
FT /id="VAR_081163"
FT VARIANT 301
FT /note="K -> E (in MRD54; no effect on protein abundance;
FT loss of autophosphorylation; changed function in neuronal
FT migration; dbSNP:rs1554385111)"
FT /evidence="ECO:0000269|PubMed:29100089"
FT /id="VAR_080592"
FT VARIANT 489
FT /note="P -> L (in a colorectal adenocarcinoma sample;
FT somatic mutation; dbSNP:rs555460132)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_045581"
FT VARIANT 510
FT /note="E -> K (in dbSNP:rs35452727)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_045582"
FT CONFLICT 68
FT /note="L -> V (in Ref. 3; AAD03744/AAD03743)"
FT /evidence="ECO:0000305"
FT CONFLICT 535
FT /note="K -> N (in Ref. 8; AAB16863)"
FT /evidence="ECO:0000305"
FT STRAND 14..19
FT /evidence="ECO:0007829|PDB:3BHH"
FT STRAND 27..33
FT /evidence="ECO:0007829|PDB:3BHH"
FT TURN 34..36
FT /evidence="ECO:0007829|PDB:3BHH"
FT STRAND 39..46
FT /evidence="ECO:0007829|PDB:3BHH"
FT HELIX 52..67
FT /evidence="ECO:0007829|PDB:3BHH"
FT STRAND 76..81
FT /evidence="ECO:0007829|PDB:3BHH"
FT STRAND 83..91
FT /evidence="ECO:0007829|PDB:3BHH"
FT STRAND 95..97
FT /evidence="ECO:0007829|PDB:3BHH"
FT HELIX 98..102
FT /evidence="ECO:0007829|PDB:3BHH"
FT HELIX 110..129
FT /evidence="ECO:0007829|PDB:3BHH"
FT HELIX 139..141
FT /evidence="ECO:0007829|PDB:3BHH"
FT STRAND 142..145
FT /evidence="ECO:0007829|PDB:3BHH"
FT STRAND 153..155
FT /evidence="ECO:0007829|PDB:3BHH"
FT HELIX 178..180
FT /evidence="ECO:0007829|PDB:3BHH"
FT HELIX 183..186
FT /evidence="ECO:0007829|PDB:3BHH"
FT HELIX 194..209
FT /evidence="ECO:0007829|PDB:3BHH"
FT HELIX 219..228
FT /evidence="ECO:0007829|PDB:3BHH"
FT TURN 235..238
FT /evidence="ECO:0007829|PDB:3BHH"
FT STRAND 239..241
FT /evidence="ECO:0007829|PDB:3BHH"
FT HELIX 243..252
FT /evidence="ECO:0007829|PDB:3BHH"
FT TURN 257..259
FT /evidence="ECO:0007829|PDB:3BHH"
FT HELIX 263..266
FT /evidence="ECO:0007829|PDB:3BHH"
FT HELIX 270..273
FT /evidence="ECO:0007829|PDB:3BHH"
FT HELIX 275..278
FT /evidence="ECO:0007829|PDB:3BHH"
FT HELIX 285..298
FT /evidence="ECO:0007829|PDB:3BHH"
FT HELIX 534..551
FT /evidence="ECO:0007829|PDB:7URY"
FT HELIX 554..560
FT /evidence="ECO:0007829|PDB:7URY"
FT STRAND 561..568
FT /evidence="ECO:0007829|PDB:7URY"
FT HELIX 570..572
FT /evidence="ECO:0007829|PDB:7URY"
FT STRAND 577..580
FT /evidence="ECO:0007829|PDB:7URY"
FT HELIX 581..588
FT /evidence="ECO:0007829|PDB:7URY"
FT HELIX 592..594
FT /evidence="ECO:0007829|PDB:7URY"
FT STRAND 598..609
FT /evidence="ECO:0007829|PDB:7URY"
FT STRAND 611..626
FT /evidence="ECO:0007829|PDB:7URY"
FT STRAND 632..646
FT /evidence="ECO:0007829|PDB:7URY"
FT STRAND 649..659
FT /evidence="ECO:0007829|PDB:7URY"
FT CONFLICT Q13554-3:316
FT /note="A -> V (in Ref. 1; AAD42036)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 666 AA; 72678 MW; 8CACFC3E392C3857 CRC64;
MATTVTCTRF TDEYQLYEDI GKGAFSVVRR CVKLCTGHEY AAKIINTKKL SARDHQKLER
EARICRLLKH SNIVRLHDSI SEEGFHYLVF DLVTGGELFE DIVAREYYSE ADASHCIQQI
LEAVLHCHQM GVVHRDLKPE NLLLASKCKG AAVKLADFGL AIEVQGDQQA WFGFAGTPGY
LSPEVLRKEA YGKPVDIWAC GVILYILLVG YPPFWDEDQH KLYQQIKAGA YDFPSPEWDT
VTPEAKNLIN QMLTINPAKR ITAHEALKHP WVCQRSTVAS MMHRQETVEC LKKFNARRKL
KGAILTTMLA TRNFSVGRQT TAPATMSTAA SGTTMGLVEQ AKSLLNKKAD GVKPQTNSTK
NSAAATSPKG TLPPAALEPQ TTVIHNPVDG IKESSDSANT TIEDEDAKAP RVPDILSSVR
RGSGAPEAEG PLPCPSPAPF SPLPAPSPRI SDILNSVRRG SGTPEAEGPL SAGPPPCLSP
ALLGPLSSPS PRISDILNSV RRGSGTPEAE GPSPVGPPPC PSPTIPGPLP TPSRKQEIIK
TTEQLIEAVN NGDFEAYAKI CDPGLTSFEP EALGNLVEGM DFHRFYFENL LAKNSKPIHT
TILNPHVHVI GEDAACIAYI RLTQYIDGQG RPRTSQSEET RVWHRRDGKW QNVHFHCSGA
PVAPLQ
//
