KCC2A_HUMAN
ID KCC2A_HUMAN Reviewed; 478 AA.
AC Q9UQM7; Q9UL21; Q9Y2H4; Q9Y352;
DT 16-APR-2002, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 203.
DE RecName: Full=Calcium/calmodulin-dependent protein kinase type II subunit alpha;
DE Short=CaM kinase II subunit alpha;
DE Short=CaMK-II subunit alpha;
DE EC=2.7.11.17 {ECO:0000269|PubMed:23805378};
GN Name=CAMK2A; Synonyms=CAMKA, KIAA0968;
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 A AND B).
RC TISSUE=Brain;
RA Li G.Y., Cooper N.G.F.;
RT "Human calcium/calmodulin-dependent protein kinase II: cDNA cloning and
RT gene analysis.";
RL Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=10231032; DOI=10.1093/dnares/6.1.63;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:63-70(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [4]
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 [5]
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 [6]
RP FUNCTION, CATALYTIC ACTIVITY, AND COFACTOR.
RX PubMed=23805378; DOI=10.7554/elife.00518;
RA Tao L., Xie Q., Ding Y.H., Li S.T., Peng S., Zhang Y.P., Tan D., Yuan Z.,
RA Dong M.Q.;
RT "CAMKII and Calcineurin regulate the lifespan of Caenorhabditis elegans
RT through the FOXO transcription factor DAF-16.";
RL Elife 2:E00518-E00518(2013).
RN [7]
RP FUNCTION, INTERACTION WITH CACNB2; GRIN2B; GRM5; LRRC7 AND SHANK3,
RP SUBCELLULAR LOCATION, AND CHARACTERIZATION OF VARIANT MRD53 VAL-183.
RX PubMed=28130356; DOI=10.1523/jneurosci.2068-16.2017;
RA Stephenson J.R., Wang X., Perfitt T.L., Parrish W.P., Shonesy B.C.,
RA Marks C.R., Mortlock D.P., Nakagawa T., Sutcliffe J.S., Colbran R.J.;
RT "Mutation Disrupts Dendritic Morphology and Synaptic Transmission, and
RT Causes ASD-Related Behaviors.";
RL J. Neurosci. 37:2216-2233(2017).
RN [8]
RP VARIANT MRD53 ALA-138.
RX PubMed=25533962; DOI=10.1038/nature14135;
RG Deciphering Developmental Disorders Study;
RT "Large-scale discovery of novel genetic causes of developmental
RT disorders.";
RL Nature 519:223-228(2015).
RN [9]
RP INVOLVEMENT IN MRD53, VARIANTS MRD53 SER-98; ASP-109; VAL-112; VAL-183;
RP LEU-212; LEU-235; ARG-282 AND PRO-286, CHARACTERIZATION OF VARIANTS MRD53
RP ALA-98; ASP-109; ALA-138; VAL-183; LEU-212; LEU-235; ARG-282 AND PRO-286,
RP FUNCTION, AND MUTAGENESIS OF LYS-42 AND THR-286.
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 [10]
RP INVOLVEMENT IN MRD53, VARIANTS MRD53 GLN-212 AND LEU-235, AND
RP CHARACTERIZATION OF VARIANTS MRD53 GLN-212 AND LEU-235.
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).
RN [11]
RP INVOLVEMENT IN MRT63, SUBUNIT, VARIANT MRT63 TYR-466, CHARACTERIZATION OF
RP VARIANT MRT63 TYR-466, AND MUTAGENESIS OF 466-HIS--HIS-478.
RX PubMed=29784083; DOI=10.7554/elife.32451;
RA Chia P.H., Zhong F.L., Niwa S., Bonnard C., Utami K.H., Zeng R., Lee H.,
RA Eskin A., Nelson S.F., Xie W.H., Al-Tawalbeh S., El-Khateeb M., Shboul M.,
RA Pouladi M.A., Al-Raqad M., Reversade B.;
RT "A homozygous loss-of-function CAMK2A mutation causes growth delay,
RT frequent seizures and severe intellectual disability.";
RL Elife 7:0-0(2018).
CC -!- FUNCTION: Calcium/calmodulin-dependent protein kinase that functions
CC autonomously after Ca(2+)/calmodulin-binding and autophosphorylation,
CC and is involved in synaptic plasticity, neurotransmitter release and
CC long-term potentiation. Member of the NMDAR signaling complex in
CC excitatory synapses, it regulates NMDAR-dependent potentiation of the
CC AMPAR and therefore excitatory synaptic transmission (By similarity).
CC Regulates dendritic spine development (PubMed:28130356). Also regulates
CC the migration of developing neurons (PubMed:29100089). Phosphorylates
CC the transcription factor FOXO3 to activate its transcriptional activity
CC (PubMed:23805378). Acts as a negative regulator of 2-
CC arachidonoylglycerol (2-AG)-mediated synaptic signaling via modulation
CC of DAGLA activity (By similarity). {ECO:0000250|UniProtKB:P11275,
CC ECO:0000250|UniProtKB:P11798, ECO:0000269|PubMed:23805378,
CC ECO:0000269|PubMed:28130356, ECO:0000269|PubMed:29100089}.
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:23805378};
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; Evidence={ECO:0000269|PubMed:23805378};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:23805378};
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-286 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: There are 4 genes encoding calcium/calmodulin-dependent
CC protein kinase type II chains: CAMK2A, CAMK2B, CAMK2G and CAMK2D. The
CC corresponding proteins assemble into homo- or heteromultimeric
CC holoenzymes composed of 12 subunits with two hexameric rings stacked
CC one on top of the other (PubMed:14722083, PubMed:29784083). Interacts
CC with BAALC. Interacts with MPDZ. Interacts with SYN1. Interacts with
CC CAMK2N2. Interacts with SYNGAP1. Interacts with SYNPO2 (By similarity).
CC Interacts with SHANK3 (PubMed:28130356). Interacts with GRIN2B
CC (PubMed:28130356). Interacts with CACNB2 (PubMed:28130356). Interacts
CC with LRRC7 (PubMed:28130356). Interacts with GRM5 (PubMed:28130356).
CC Interacts with DAGLA (via C-terminal); this interaction is enhanced by
CC autophosphorylation of CAMK2A at Thr-286 (By similarity). Interacts
CC with CAMK2N1; this interaction requires CAMK2A activation by Ca(2+) (By
CC similarity). {ECO:0000250|UniProtKB:P11275,
CC ECO:0000250|UniProtKB:P11798, ECO:0000269|PubMed:14722083,
CC ECO:0000269|PubMed:28130356, ECO:0000269|PubMed:29784083}.
CC -!- INTERACTION:
CC Q9UQM7; P68133: ACTA1; NbExp=3; IntAct=EBI-1383687, EBI-367510;
CC Q9UQM7; P31749: AKT1; NbExp=3; IntAct=EBI-1383687, EBI-296087;
CC Q9UQM7; Q92870-2: APBB2; NbExp=3; IntAct=EBI-1383687, EBI-21535880;
CC Q9UQM7; P05067: APP; NbExp=3; IntAct=EBI-1383687, EBI-77613;
CC Q9UQM7; Q03989: ARID5A; NbExp=3; IntAct=EBI-1383687, EBI-948603;
CC Q9UQM7; P13637: ATP1A3; NbExp=3; IntAct=EBI-1383687, EBI-948169;
CC Q9UQM7; P23560-2: BDNF; NbExp=3; IntAct=EBI-1383687, EBI-12275524;
CC Q9UQM7; Q6P1W5: C1orf94; NbExp=3; IntAct=EBI-1383687, EBI-946029;
CC Q9UQM7; P62158: CALM3; NbExp=2; IntAct=EBI-1383687, EBI-397435;
CC Q9UQM7; Q9UQM7: CAMK2A; NbExp=2; IntAct=EBI-1383687, EBI-1383687;
CC Q9UQM7; Q13554: CAMK2B; NbExp=3; IntAct=EBI-1383687, EBI-1058722;
CC Q9UQM7; Q13554-3: CAMK2B; NbExp=3; IntAct=EBI-1383687, EBI-11523526;
CC Q9UQM7; Q13557: CAMK2D; NbExp=5; IntAct=EBI-1383687, EBI-351018;
CC Q9UQM7; Q13557-8: CAMK2D; NbExp=3; IntAct=EBI-1383687, EBI-11534483;
CC Q9UQM7; Q13555-5: CAMK2G; NbExp=3; IntAct=EBI-1383687, EBI-12020154;
CC Q9UQM7; P35520: CBS; NbExp=3; IntAct=EBI-1383687, EBI-740135;
CC Q9UQM7; Q16543: CDC37; NbExp=5; IntAct=EBI-1383687, EBI-295634;
CC Q9UQM7; Q15038: DAZAP2; NbExp=3; IntAct=EBI-1383687, EBI-724310;
CC Q9UQM7; Q92567-2: FAM168A; NbExp=3; IntAct=EBI-1383687, EBI-11978259;
CC Q9UQM7; A1KXE4-2: FAM168B; NbExp=3; IntAct=EBI-1383687, EBI-12193763;
CC Q9UQM7; P04406: GAPDH; NbExp=3; IntAct=EBI-1383687, EBI-354056;
CC Q9UQM7; Q8IW92: GLB1L2; NbExp=3; IntAct=EBI-1383687, EBI-11954377;
CC Q9UQM7; Q13224: GRIN2B; NbExp=3; IntAct=EBI-1383687, EBI-2256942;
CC Q9UQM7; P07900: HSP90AA1; NbExp=5; IntAct=EBI-1383687, EBI-296047;
CC Q9UQM7; P08238: HSP90AB1; NbExp=3; IntAct=EBI-1383687, EBI-352572;
CC Q9UQM7; O43820: HYAL3; NbExp=3; IntAct=EBI-1383687, EBI-3913399;
CC Q9UQM7; O95678: KRT75; NbExp=3; IntAct=EBI-1383687, EBI-2949715;
CC Q9UQM7; Q01546: KRT76; NbExp=3; IntAct=EBI-1383687, EBI-2952745;
CC Q9UQM7; Q3LI76: KRTAP15-1; NbExp=3; IntAct=EBI-1383687, EBI-11992140;
CC Q9UQM7; Q7Z4W3: KRTAP19-3; NbExp=3; IntAct=EBI-1383687, EBI-12020132;
CC Q9UQM7; Q3LI72: KRTAP19-5; NbExp=3; IntAct=EBI-1383687, EBI-1048945;
CC Q9UQM7; Q3SYF9: KRTAP19-7; NbExp=3; IntAct=EBI-1383687, EBI-10241353;
CC Q9UQM7; A1A580: KRTAP23-1; NbExp=3; IntAct=EBI-1383687, EBI-10171734;
CC Q9UQM7; Q3LI64: KRTAP6-1; NbExp=3; IntAct=EBI-1383687, EBI-12111050;
CC Q9UQM7; Q3LI66: KRTAP6-2; NbExp=3; IntAct=EBI-1383687, EBI-11962084;
CC Q9UQM7; Q8IUC2: KRTAP8-1; NbExp=3; IntAct=EBI-1383687, EBI-10261141;
CC Q9UQM7; Q14847-2: LASP1; NbExp=3; IntAct=EBI-1383687, EBI-9088686;
CC Q9UQM7; Q96PV6: LENG8; NbExp=3; IntAct=EBI-1383687, EBI-739546;
CC Q9UQM7; Q13387-4: MAPK8IP2; NbExp=3; IntAct=EBI-1383687, EBI-12345753;
CC Q9UQM7; Q9Y3B7: MRPL11; NbExp=3; IntAct=EBI-1383687, EBI-5453723;
CC Q9UQM7; P41271-2: NBL1; NbExp=3; IntAct=EBI-1383687, EBI-12135485;
CC Q9UQM7; Q96HA8: NTAQ1; NbExp=3; IntAct=EBI-1383687, EBI-741158;
CC Q9UQM7; P16284: PECAM1; NbExp=3; IntAct=EBI-1383687, EBI-716404;
CC Q9UQM7; P27986-2: PIK3R1; NbExp=3; IntAct=EBI-1383687, EBI-9090282;
CC Q9UQM7; O14494: PLPP1; NbExp=3; IntAct=EBI-1383687, EBI-2865290;
CC Q9UQM7; P00491: PNP; NbExp=3; IntAct=EBI-1383687, EBI-712238;
CC Q9UQM7; P05771-2: PRKCB; NbExp=3; IntAct=EBI-1383687, EBI-5774511;
CC Q9UQM7; P20339: RAB5A; NbExp=3; IntAct=EBI-1383687, EBI-399437;
CC Q9UQM7; Q86SE5-3: RALYL; NbExp=3; IntAct=EBI-1383687, EBI-11526555;
CC Q9UQM7; O43251-10: RBFOX2; NbExp=3; IntAct=EBI-1383687, EBI-11963050;
CC Q9UQM7; A0AV96: RBM47; NbExp=3; IntAct=EBI-1383687, EBI-2823850;
CC Q9UQM7; Q93062-3: RBPMS; NbExp=3; IntAct=EBI-1383687, EBI-740343;
CC Q9UQM7; Q6ZRY4: RBPMS2; NbExp=3; IntAct=EBI-1383687, EBI-11987469;
CC Q9UQM7; Q9BQY4: RHOXF2; NbExp=3; IntAct=EBI-1383687, EBI-372094;
CC Q9UQM7; P04271: S100B; NbExp=3; IntAct=EBI-1383687, EBI-458391;
CC Q9UQM7; P29353-7: SHC1; NbExp=3; IntAct=EBI-1383687, EBI-9691288;
CC Q9UQM7; P84022: SMAD3; NbExp=3; IntAct=EBI-1383687, EBI-347161;
CC Q9UQM7; P35711-4: SOX5; NbExp=3; IntAct=EBI-1383687, EBI-11954419;
CC Q9UQM7; Q9UNE7: STUB1; NbExp=3; IntAct=EBI-1383687, EBI-357085;
CC Q9UQM7; P51687: SUOX; NbExp=3; IntAct=EBI-1383687, EBI-3921347;
CC Q9UQM7; Q9NYJ8: TAB2; NbExp=3; IntAct=EBI-1383687, EBI-358708;
CC Q9UQM7; Q9Y4C2-2: TCAF1; NbExp=3; IntAct=EBI-1383687, EBI-11974855;
CC Q9UQM7; Q96LM6: TEX37; NbExp=3; IntAct=EBI-1383687, EBI-743976;
CC Q9UQM7; Q7Z6R9: TFAP2D; NbExp=3; IntAct=EBI-1383687, EBI-11952651;
CC Q9UQM7; Q01085-2: TIAL1; NbExp=3; IntAct=EBI-1383687, EBI-11064654;
CC Q9UQM7; O60784-2: TOM1; NbExp=3; IntAct=EBI-1383687, EBI-12117154;
CC Q9UQM7; Q969E8: TSR2; NbExp=3; IntAct=EBI-1383687, EBI-746981;
CC Q9UQM7; Q8N0Z6: TTC5; NbExp=3; IntAct=EBI-1383687, EBI-9526213;
CC Q9UQM7; P61086: UBE2K; NbExp=3; IntAct=EBI-1383687, EBI-473850;
CC Q9UQM7; P13051-2: UNG; NbExp=3; IntAct=EBI-1383687, EBI-25834258;
CC Q9UQM7; Q9BVJ6: UTP14A; NbExp=3; IntAct=EBI-1383687, EBI-473284;
CC Q9UQM7; P26640: VARS1; NbExp=3; IntAct=EBI-1383687, EBI-355765;
CC Q9UQM7; P08670: VIM; NbExp=3; IntAct=EBI-1383687, EBI-353844;
CC Q9UQM7; Q9UBQ0-2: VPS29; NbExp=3; IntAct=EBI-1383687, EBI-11141397;
CC Q9UQM7; A0A0C4DGF1: ZBTB32; NbExp=3; IntAct=EBI-1383687, EBI-10188476;
CC -!- SUBCELLULAR LOCATION: Synapse {ECO:0000250|UniProtKB:P11275}.
CC Postsynaptic density {ECO:0000250|UniProtKB:P11275}. Cell projection,
CC dendritic spine {ECO:0000269|PubMed:28130356}. Cell projection,
CC dendrite {ECO:0000269|PubMed:28130356}. Note=Postsynaptic lipid rafts.
CC {ECO:0000250|UniProtKB:P11275}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=A;
CC IsoId=Q9UQM7-1; Sequence=Displayed;
CC Name=B;
CC IsoId=Q9UQM7-2; Sequence=VSP_004766;
CC -!- PTM: Autophosphorylation of Thr-286 following activation by
CC Ca(2+)/calmodulin. Phosphorylation of Thr-286 locks the kinase into an
CC activated state. {ECO:0000269|PubMed:14722083}.
CC -!- PTM: Palmitoylated. Probably palmitoylated by ZDHHC3 and ZDHHC7.
CC {ECO:0000250|UniProtKB:P11275}.
CC -!- DISEASE: Intellectual developmental disorder, autosomal dominant 53
CC (MRD53) [MIM:617798]: 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:25533962, ECO:0000269|PubMed:28130356,
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 -!- DISEASE: Intellectual developmental disorder, autosomal recessive 63
CC (MRT63) [MIM:618095]: A disorder characterized by significantly below
CC average general intellectual functioning associated with impairments in
CC adaptive behavior and manifested during the developmental period. MRT63
CC patients manifest global developmental delay, severe intellectual
CC disability, and seizures. {ECO:0000269|PubMed:29784083}. 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=BAA76812.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF145710; AAD30558.1; -; mRNA.
DR EMBL; AF145711; AAD30559.1; -; mRNA.
DR EMBL; AB023185; BAA76812.1; ALT_INIT; mRNA.
DR EMBL; AC011372; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS43386.1; -. [Q9UQM7-1]
DR CCDS; CCDS43387.1; -. [Q9UQM7-2]
DR RefSeq; NP_741960.1; NM_171825.2. [Q9UQM7-1]
DR PDB; 2VZ6; X-ray; 2.30 A; A/B=13-302.
DR PDB; 3SOA; X-ray; 3.55 A; A=1-474.
DR PDB; 5IG3; X-ray; 2.75 A; A/B/C/D/E/F=345-475.
DR PDB; 6OF8; X-ray; 2.10 A; A/B/C/D/E/F/G=345-475.
DR PDB; 6VZK; X-ray; 2.55 A; A=7-274.
DR PDB; 6W4O; EM; 4.80 A; A/B/C/D/E/F/G/I/J/K/L/M/O=7-478.
DR PDB; 6W4P; EM; 6.60 A; A/B/C/D/E/F/G/H/I/J/K/L/M=7-478.
DR PDB; 6X5G; X-ray; 1.85 A; A=7-274.
DR PDB; 6X5Q; X-ray; 2.14 A; A=7-274.
DR PDB; 7KL0; X-ray; 2.40 A; A/B=7-274.
DR PDB; 7KL1; X-ray; 2.40 A; A/B=7-274.
DR PDB; 7KL2; X-ray; 2.56 A; A=7-274.
DR PDB; 7REC; X-ray; 2.20 A; A/B/C/D/E/F/G=345-475.
DR PDB; 7UIQ; X-ray; 3.11 A; A/B=7-274.
DR PDB; 7UIR; X-ray; 3.10 A; A/B=7-274.
DR PDB; 7UIS; X-ray; 2.58 A; A=7-274.
DR PDB; 7UJP; X-ray; 2.56 A; A/B=7-274.
DR PDB; 7UJQ; X-ray; 2.25 A; A/B=7-274.
DR PDB; 7UJR; X-ray; 1.95 A; A=7-274.
DR PDB; 7UJS; X-ray; 2.75 A; A=7-274.
DR PDB; 7UJT; X-ray; 2.10 A; A=7-274.
DR PDBsum; 2VZ6; -.
DR PDBsum; 3SOA; -.
DR PDBsum; 5IG3; -.
DR PDBsum; 6OF8; -.
DR PDBsum; 6VZK; -.
DR PDBsum; 6W4O; -.
DR PDBsum; 6W4P; -.
DR PDBsum; 6X5G; -.
DR PDBsum; 6X5Q; -.
DR PDBsum; 7KL0; -.
DR PDBsum; 7KL1; -.
DR PDBsum; 7KL2; -.
DR PDBsum; 7REC; -.
DR PDBsum; 7UIQ; -.
DR PDBsum; 7UIR; -.
DR PDBsum; 7UIS; -.
DR PDBsum; 7UJP; -.
DR PDBsum; 7UJQ; -.
DR PDBsum; 7UJR; -.
DR PDBsum; 7UJS; -.
DR PDBsum; 7UJT; -.
DR AlphaFoldDB; Q9UQM7; -.
DR SMR; Q9UQM7; -.
DR BioGRID; 107265; 198.
DR CORUM; Q9UQM7; -.
DR DIP; DIP-39705N; -.
DR IntAct; Q9UQM7; 149.
DR MINT; Q9UQM7; -.
DR STRING; 9606.ENSP00000381412; -.
DR BindingDB; Q9UQM7; -.
DR ChEMBL; CHEMBL4147; -.
DR DrugBank; DB07766; (2Z,3E)-2,3'-biindole-2',3(1H,1'H)-dione 3-{O-[(3R)-3,4-dihydroxybutyl]oxime}.
DR DrugBank; DB04447; 1,4-Dithiothreitol.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB04119; Hexatantalum Dodecabromide.
DR DrugCentral; Q9UQM7; -.
DR GlyGen; Q9UQM7; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9UQM7; -.
DR PhosphoSitePlus; Q9UQM7; -.
DR BioMuta; CAMK2A; -.
DR DMDM; 296434552; -.
DR jPOST; Q9UQM7; -.
DR MassIVE; Q9UQM7; -.
DR MaxQB; Q9UQM7; -.
DR PaxDb; Q9UQM7; -.
DR PeptideAtlas; Q9UQM7; -.
DR PRIDE; Q9UQM7; -.
DR ProteomicsDB; 85559; -. [Q9UQM7-1]
DR ProteomicsDB; 85560; -. [Q9UQM7-2]
DR Antibodypedia; 3814; 903 antibodies from 52 providers.
DR DNASU; 815; -.
DR Ensembl; ENST00000348628.11; ENSP00000261793.8; ENSG00000070808.17. [Q9UQM7-1]
DR Ensembl; ENST00000671881.1; ENSP00000500386.1; ENSG00000070808.17. [Q9UQM7-2]
DR Ensembl; ENST00000672479.1; ENSP00000500642.1; ENSG00000070808.17. [Q9UQM7-1]
DR Ensembl; ENST00000682786.1; ENSP00000507199.1; ENSG00000070808.17. [Q9UQM7-2]
DR GeneID; 815; -.
DR KEGG; hsa:815; -.
DR MANE-Select; ENST00000671881.1; ENSP00000500386.1; NM_015981.4; NP_057065.2. [Q9UQM7-2]
DR UCSC; uc003lrt.3; human. [Q9UQM7-1]
DR CTD; 815; -.
DR DisGeNET; 815; -.
DR GeneCards; CAMK2A; -.
DR HGNC; HGNC:1460; CAMK2A.
DR HPA; ENSG00000070808; Tissue enriched (brain).
DR MalaCards; CAMK2A; -.
DR MIM; 114078; gene.
DR MIM; 617798; phenotype.
DR MIM; 618095; phenotype.
DR neXtProt; NX_Q9UQM7; -.
DR OpenTargets; ENSG00000070808; -.
DR Orphanet; 178469; Autosomal dominant non-syndromic intellectual disability.
DR PharmGKB; PA90; -.
DR VEuPathDB; HostDB:ENSG00000070808; -.
DR eggNOG; KOG0033; Eukaryota.
DR GeneTree; ENSGT00940000155150; -.
DR HOGENOM; CLU_000288_71_0_1; -.
DR InParanoid; Q9UQM7; -.
DR OMA; SEETCIW; -.
DR PhylomeDB; Q9UQM7; -.
DR TreeFam; TF315229; -.
DR BRENDA; 2.7.11.17; 2681.
DR PathwayCommons; Q9UQM7; -.
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-4086398; Ca2+ pathway.
DR Reactome; R-HSA-438066; Unblocking of NMDA receptors, glutamate binding and activation.
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; Q9UQM7; -.
DR SIGNOR; Q9UQM7; -.
DR BioGRID-ORCS; 815; 13 hits in 1103 CRISPR screens.
DR ChiTaRS; CAMK2A; human.
DR EvolutionaryTrace; Q9UQM7; -.
DR GeneWiki; CAMK2A; -.
DR GenomeRNAi; 815; -.
DR Pharos; Q9UQM7; Tchem.
DR PRO; PR:Q9UQM7; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q9UQM7; protein.
DR Bgee; ENSG00000070808; Expressed in amygdala and 144 other tissues.
DR ExpressionAtlas; Q9UQM7; baseline and differential.
DR Genevisible; Q9UQM7; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005954; C:calcium- and calmodulin-dependent protein kinase complex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0043197; C:dendritic spine; IDA:UniProtKB.
DR GO; GO:0030666; C:endocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; ISS:ParkinsonsUK-UCL.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005516; F:calmodulin binding; IPI:BHF-UCL.
DR GO; GO:0004683; F:calmodulin-dependent protein kinase activity; IBA:GO_Central.
DR GO; GO:0035254; F:glutamate receptor binding; ISS:ParkinsonsUK-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0016301; F:kinase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0038166; P:angiotensin-activated signaling pathway; IDA:UniProtKB.
DR GO; GO:0006816; P:calcium ion transport; ISS:ParkinsonsUK-UCL.
DR GO; GO:0060996; P:dendritic spine development; IMP:UniProtKB.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; ISS:ParkinsonsUK-UCL.
DR GO; GO:0051346; P:negative regulation of hydrolase activity; ISS:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISS:ParkinsonsUK-UCL.
DR GO; GO:1990443; P:peptidyl-threonine autophosphorylation; IMP:UniProtKB.
DR GO; GO:0051928; P:positive regulation of calcium ion transport; ISS:ParkinsonsUK-UCL.
DR GO; GO:0010666; P:positive regulation of cardiac muscle cell apoptotic process; ISS:ParkinsonsUK-UCL.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:ParkinsonsUK-UCL.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:2000124; P:regulation of endocannabinoid signaling pathway; ISS:UniProtKB.
DR GO; GO:1902108; P:regulation of mitochondrial membrane permeability involved in apoptotic process; ISS:ParkinsonsUK-UCL.
DR GO; GO:2001222; P:regulation of neuron migration; IMP:UniProtKB.
DR GO; GO:0048168; P:regulation of neuronal synaptic plasticity; ISS:ParkinsonsUK-UCL.
DR GO; GO:0046928; P:regulation of neurotransmitter secretion; ISS:ParkinsonsUK-UCL.
DR GO; GO:0002931; P:response to ischemia; ISS:ParkinsonsUK-UCL.
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 Pfam; PF08332; CaMKII_AD; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF54427; SSF54427; 1.
DR SUPFAM; SSF56112; SSF56112; 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; Alternative splicing; ATP-binding; Calmodulin-binding;
KW Cell projection; Disease variant; Intellectual disability; Kinase;
KW Lipoprotein; Magnesium; Metal-binding; Nucleotide-binding; Palmitate;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Synapse; Transferase.
FT CHAIN 1..478
FT /note="Calcium/calmodulin-dependent protein kinase type II
FT subunit alpha"
FT /id="PRO_0000086091"
FT DOMAIN 13..271
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 290..300
FT /note="Calmodulin-binding"
FT REGION 310..320
FT /note="Interaction with BAALC"
FT /evidence="ECO:0000250"
FT REGION 314..341
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 322..341
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 135
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 19..27
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 42
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 13
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P11798"
FT MOD_RES 257
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11275"
FT MOD_RES 286
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P11275"
FT MOD_RES 330
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11798"
FT MOD_RES 331
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11798"
FT MOD_RES 333
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11798"
FT MOD_RES 336
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P11798"
FT MOD_RES 337
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P11798"
FT MOD_RES 404
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11798"
FT VAR_SEQ 328
FT /note="K -> KKRKSSSSVQLM (in isoform B)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_004766"
FT VARIANT 98
FT /note="F -> S (in MRD53; no effect on protein abundance;
FT decreased autophosphorylation; decreased neuronal
FT migration; dbSNP:rs1554122526)"
FT /evidence="ECO:0000269|PubMed:29100089"
FT /id="VAR_080579"
FT VARIANT 109
FT /note="E -> D (in MRD53; no effect on protein abundance;
FT increased autophosphorylation; decreased neuronal
FT migration)"
FT /evidence="ECO:0000269|PubMed:29100089"
FT /id="VAR_080580"
FT VARIANT 112
FT /note="A -> V (in MRD53; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:29100089"
FT /id="VAR_080581"
FT VARIANT 138
FT /note="P -> A (in MRD53; unknown pathological significance;
FT no effect on protein abundance; no effect on
FT autophosphorylation; no effect on neuronal migration)"
FT /evidence="ECO:0000269|PubMed:25533962,
FT ECO:0000269|PubMed:29100089"
FT /id="VAR_080582"
FT VARIANT 183
FT /note="E -> V (in MRD53; increased ubiquitin-mediated
FT proteasomal degradation with a dominant negative effect on
FT wild-type protein; decreased localization to dendritic
FT spines; no effect on holoenzyme assembly; loss of
FT interaction with SHANK3; loss of interaction with GRIN2B;
FT loss of interaction with CACNB2; loss of interaction with
FT LRRC7; loss of interaction with GRM5; decreased protein
FT serine/threonine kinase activity with a dominant negative
FT effect on wild-type protein; decreased autophosphorylation;
FT changed dendritic spine development; decreased neuronal
FT migration; dbSNP:rs1554122129)"
FT /evidence="ECO:0000269|PubMed:28130356,
FT ECO:0000269|PubMed:29100089"
FT /id="VAR_080583"
FT VARIANT 212
FT /note="P -> L (in MRD53; unknown pathological significance;
FT no effect on protein abundance; no effect on
FT autophosphorylation; no effect on neuronal migration;
FT dbSNP:rs926027867)"
FT /evidence="ECO:0000269|PubMed:29100089"
FT /id="VAR_080584"
FT VARIANT 212
FT /note="P -> Q (in MRD53; increased basal
FT autophosphorylation)"
FT /evidence="ECO:0000269|PubMed:29560374"
FT /id="VAR_081160"
FT VARIANT 235
FT /note="P -> L (in MRD53; unknown pathological significance;
FT no effect on protein abundance; no effect on
FT autophosphorylation; no effect on neuronal migration;
FT dbSNP:rs864309606)"
FT /evidence="ECO:0000269|PubMed:29100089,
FT ECO:0000269|PubMed:29560374"
FT /id="VAR_080585"
FT VARIANT 282
FT /note="H -> R (in MRD53; decreased protein abundance;
FT increased autophosphorylation; decreased neuronal
FT migration; dbSNP:rs1554121875)"
FT /evidence="ECO:0000269|PubMed:29100089"
FT /id="VAR_080586"
FT VARIANT 286
FT /note="T -> P (in MRD53; no effect on protein abundance;
FT loss of autophosphorylation; loss of neuronal migration;
FT dbSNP:rs1554121872)"
FT /evidence="ECO:0000269|PubMed:29100089"
FT /id="VAR_080587"
FT VARIANT 466
FT /note="H -> Y (in MRT63; decreased oligomerization;
FT dbSNP:rs1554119274)"
FT /evidence="ECO:0000269|PubMed:29784083"
FT /id="VAR_081161"
FT MUTAGEN 42
FT /note="K->R: No effect on protein stability or degradation.
FT No effect on neuronal migration; when associated with P-
FT 286."
FT /evidence="ECO:0000269|PubMed:29100089"
FT MUTAGEN 286
FT /note="T->A: No effect on neuronal migration."
FT /evidence="ECO:0000269|PubMed:29100089"
FT MUTAGEN 286
FT /note="T->D: Loss of neuronal migration."
FT /evidence="ECO:0000269|PubMed:29100089"
FT MUTAGEN 286
FT /note="T->P: No effect on neuronal migration; when
FT associated with R-42."
FT /evidence="ECO:0000269|PubMed:29100089"
FT MUTAGEN 466..478
FT /note="Missing: Loss of oligomerization."
FT /evidence="ECO:0000269|PubMed:29784083"
FT CONFLICT 365
FT /note="D -> G (in Ref. 1; AAD30558/AAD30559)"
FT /evidence="ECO:0000305"
FT HELIX 8..12
FT /evidence="ECO:0007829|PDB:6X5G"
FT STRAND 13..21
FT /evidence="ECO:0007829|PDB:6X5G"
FT STRAND 26..32
FT /evidence="ECO:0007829|PDB:6X5G"
FT HELIX 33..35
FT /evidence="ECO:0007829|PDB:6X5G"
FT STRAND 37..45
FT /evidence="ECO:0007829|PDB:6X5G"
FT HELIX 46..48
FT /evidence="ECO:0007829|PDB:6X5G"
FT HELIX 51..66
FT /evidence="ECO:0007829|PDB:6X5G"
FT STRAND 75..81
FT /evidence="ECO:0007829|PDB:6X5G"
FT STRAND 84..89
FT /evidence="ECO:0007829|PDB:6X5G"
FT HELIX 97..104
FT /evidence="ECO:0007829|PDB:6X5G"
FT HELIX 109..128
FT /evidence="ECO:0007829|PDB:6X5G"
FT HELIX 138..140
FT /evidence="ECO:0007829|PDB:6X5G"
FT STRAND 141..144
FT /evidence="ECO:0007829|PDB:6X5G"
FT STRAND 152..154
FT /evidence="ECO:0007829|PDB:6X5G"
FT HELIX 157..159
FT /evidence="ECO:0007829|PDB:6X5G"
FT HELIX 177..179
FT /evidence="ECO:0007829|PDB:6X5G"
FT HELIX 182..186
FT /evidence="ECO:0007829|PDB:6X5G"
FT HELIX 193..208
FT /evidence="ECO:0007829|PDB:6X5G"
FT HELIX 218..227
FT /evidence="ECO:0007829|PDB:6X5G"
FT HELIX 236..239
FT /evidence="ECO:0007829|PDB:6X5G"
FT HELIX 242..251
FT /evidence="ECO:0007829|PDB:6X5G"
FT TURN 256..258
FT /evidence="ECO:0007829|PDB:6X5G"
FT HELIX 262..266
FT /evidence="ECO:0007829|PDB:6X5G"
FT HELIX 269..272
FT /evidence="ECO:0007829|PDB:6X5G"
FT HELIX 274..277
FT /evidence="ECO:0007829|PDB:2VZ6"
FT HELIX 284..298
FT /evidence="ECO:0007829|PDB:2VZ6"
FT HELIX 347..362
FT /evidence="ECO:0007829|PDB:6OF8"
FT HELIX 366..372
FT /evidence="ECO:0007829|PDB:6OF8"
FT STRAND 373..380
FT /evidence="ECO:0007829|PDB:6OF8"
FT HELIX 382..384
FT /evidence="ECO:0007829|PDB:6OF8"
FT STRAND 388..392
FT /evidence="ECO:0007829|PDB:6OF8"
FT HELIX 393..401
FT /evidence="ECO:0007829|PDB:6OF8"
FT TURN 402..406
FT /evidence="ECO:0007829|PDB:6OF8"
FT STRAND 410..422
FT /evidence="ECO:0007829|PDB:6OF8"
FT TURN 423..425
FT /evidence="ECO:0007829|PDB:6OF8"
FT STRAND 426..438
FT /evidence="ECO:0007829|PDB:6OF8"
FT STRAND 440..442
FT /evidence="ECO:0007829|PDB:5IG3"
FT STRAND 444..458
FT /evidence="ECO:0007829|PDB:6OF8"
FT STRAND 461..471
FT /evidence="ECO:0007829|PDB:6OF8"
SQ SEQUENCE 478 AA; 54088 MW; 208143A311BA9262 CRC64;
MATITCTRFT EEYQLFEELG KGAFSVVRRC VKVLAGQEYA AKIINTKKLS ARDHQKLERE
ARICRLLKHP NIVRLHDSIS EEGHHYLIFD LVTGGELFED IVAREYYSEA DASHCIQQIL
EAVLHCHQMG VVHRDLKPEN LLLASKLKGA AVKLADFGLA IEVEGEQQAW FGFAGTPGYL
SPEVLRKDPY GKPVDLWACG VILYILLVGY PPFWDEDQHR LYQQIKAGAY DFPSPEWDTV
TPEAKDLINK MLTINPSKRI TAAEALKHPW ISHRSTVASC MHRQETVDCL KKFNARRKLK
GAILTTMLAT RNFSGGKSGG NKKSDGVKES SESTNTTIED EDTKVRKQEI IKVTEQLIEA
ISNGDFESYT KMCDPGMTAF EPEALGNLVE GLDFHRFYFE NLWSRNSKPV HTTILNPHIH
LMGDESACIA YIRITQYLDA GGIPRTAQSE ETRVWHRRDG KWQIVHFHRS GAPSVLPH
