KCC2D_HUMAN
ID KCC2D_HUMAN Reviewed; 499 AA.
AC Q13557; A8MVS8; Q52PK4; Q59G21; Q8N553; Q9UGH6; Q9UQE9;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 3.
DT 03-AUG-2022, entry version 223.
DE RecName: Full=Calcium/calmodulin-dependent protein kinase type II subunit delta;
DE Short=CaM kinase II subunit delta;
DE Short=CaMK-II subunit delta;
DE EC=2.7.11.17;
GN Name=CAMK2D; Synonyms=CAMKD;
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] (ISOFORM DELTA 2), ALTERNATIVE SPLICING, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Myocardium;
RX PubMed=10189359; DOI=10.1161/01.res.84.6.713;
RA Hoch B., Meyer R., Hetzer R., Krause E.-G., Karczewski P.;
RT "Identification and expression of delta-isoforms of the multifunctional
RT Ca2+/calmodulin-dependent protein kinase in failing and nonfailing human
RT myocardium.";
RL Circ. Res. 84:713-721(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM DELTA 12).
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM DELTA 10).
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM DELTA 7).
RA Zhou G., Nong W., Li H., Ke R., Li M., Zheng Z., Zhong G., Shen C.,
RA Liang M., Lin L., Yang S.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM DELTA 6).
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-243, AND ALTERNATIVE SPLICING.
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 [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 302-417, AND ALTERNATIVE SPLICING.
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 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 [11]
RP FUNCTION IN PHOSPHORYLATION OF HDAC4.
RX PubMed=17179159; DOI=10.1074/jbc.m604281200;
RA Little G.H., Bai Y., Williams T., Poizat C.;
RT "Nuclear calcium/calmodulin-dependent protein kinase IIdelta preferentially
RT transmits signals to histone deacetylase 4 in cardiac cells.";
RL J. Biol. Chem. 282:7219-7231(2007).
RN [12]
RP REVIEW ON INVOLVEMENT IN EXCITATION-CONTRACTION COUPLING IN HEART.
RX PubMed=17157285; DOI=10.1016/j.cardiores.2006.11.005;
RA Maier L.S., Bers D.M.;
RT "Role of Ca2+/calmodulin-dependent protein kinase (CaMK) in excitation-
RT contraction coupling in the heart.";
RL Cardiovasc. Res. 73:631-640(2007).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=18318008; DOI=10.1002/pmic.200700884;
RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA Zou H., Gu J.;
RT "Large-scale phosphoproteome analysis of human liver tissue by enrichment
RT and fractionation of phosphopeptides with strong anion exchange
RT chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [16]
RP REVIEW ON PHOSPHORYLATION OF RYR2.
RX PubMed=19482609; DOI=10.2741/3591;
RA Currie S.;
RT "Cardiac ryanodine receptor phosphorylation by CaM Kinase II: keeping the
RT balance right.";
RL Front. Biosci. 14:5134-5156(2009).
RN [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-319; SER-404 AND SER-490, CLEAVAGE OF INITIATOR METHIONINE
RP [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE
RP 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 [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [20]
RP REVIEW.
RX PubMed=20673813; DOI=10.1016/j.hrthm.2010.07.029;
RA Mohler P.J., Hund T.J.;
RT "Role of CaMKII in cardiovascular health, disease, and arrhythmia.";
RL Heart Rhythm 8:142-144(2011).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-315; SER-319; SER-330;
RP THR-331 AND THR-337, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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 [23]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 11-335 IN COMPLEX AND INHIBITORS.
RX PubMed=20668654; DOI=10.1371/journal.pbio.1000426;
RA Rellos P., Pike A.C., Niesen F.H., Salah E., Lee W.H., von Delft F.,
RA Knapp S.;
RT "Structure of the CaMKIIdelta/calmodulin complex reveals the molecular
RT mechanism of CaMKII kinase activation.";
RL PLoS Biol. 8:E1000426-E1000426(2010).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (1.46 ANGSTROMS) OF 294-311 IN COMPLEX WITH
RP CALMODULIN.
RA Ng H.L., Alber T.A., Wand A.J.;
RT "Calmodulin bound to peptide from calmodulin kinase II (CaMKII).";
RL Submitted (MAR-2009) to the PDB data bank.
RN [25]
RP VARIANTS [LARGE SCALE ANALYSIS] GLU-167 AND ILE-493.
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).
CC -!- FUNCTION: Calcium/calmodulin-dependent protein kinase involved in the
CC regulation of Ca(2+) homeostatis and excitation-contraction coupling
CC (ECC) in heart by targeting ion channels, transporters and accessory
CC proteins involved in Ca(2+) influx into the myocyte, Ca(2+) release
CC from the sarcoplasmic reticulum (SR), SR Ca(2+) uptake and Na(+) and
CC K(+) channel transport. Targets also transcription factors and
CC signaling molecules to regulate heart function. In its activated form,
CC is involved in the pathogenesis of dilated cardiomyopathy and heart
CC failure. Contributes to cardiac decompensation and heart failure by
CC regulating SR Ca(2+) release via direct phosphorylation of RYR2 Ca(2+)
CC channel on 'Ser-2808'. In the nucleus, phosphorylates the MEF2
CC repressor HDAC4, promoting its nuclear export and binding to 14-3-3
CC protein, and expression of MEF2 and genes involved in the hypertrophic
CC program. Is essential for left ventricular remodeling responses to
CC myocardial infarction. In pathological myocardial remodeling acts
CC downstream of the beta adrenergic receptor signaling cascade to
CC regulate key proteins involved in ECC. Regulates Ca(2+) influx to
CC myocytes by binding and phosphorylating the L-type Ca(2+) channel
CC subunit beta-2 CACNB2. In addition to Ca(2+) channels, can target and
CC regulate the cardiac sarcolemmal Na(+) channel Nav1.5/SCN5A and the K+
CC channel Kv4.3/KCND3, which contribute to arrhythmogenesis in heart
CC failure. Phosphorylates phospholamban (PLN/PLB), an endogenous
CC inhibitor of SERCA2A/ATP2A2, contributing to the enhancement of SR
CC Ca(2+) uptake that may be important in frequency-dependent acceleration
CC of relaxation (FDAR) and maintenance of contractile function during
CC acidosis. May participate in the modulation of skeletal muscle function
CC in response to exercise, by regulating SR Ca(2+) transport through
CC phosphorylation of PLN/PLB and triadin, a ryanodine receptor-coupling
CC factor. {ECO:0000269|PubMed:16690701, ECO:0000269|PubMed:17179159}.
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 -!- 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). Interacts with RRAD and CACNB2 (By similarity).
CC {ECO:0000250, ECO:0000269|PubMed:14722083}.
CC -!- INTERACTION:
CC Q13557; Q8N9N5: BANP; NbExp=4; IntAct=EBI-351018, EBI-744695;
CC Q13557; P62158: CALM3; NbExp=5; IntAct=EBI-351018, EBI-397435;
CC Q13557; Q9UQM7: CAMK2A; NbExp=5; IntAct=EBI-351018, EBI-1383687;
CC Q13557; Q13554: CAMK2B; NbExp=4; IntAct=EBI-351018, EBI-1058722;
CC Q13557; Q13557: CAMK2D; NbExp=5; IntAct=EBI-351018, EBI-351018;
CC Q13557; Q13555: CAMK2G; NbExp=3; IntAct=EBI-351018, EBI-1383465;
CC Q13557; O96015: DNAL4; NbExp=4; IntAct=EBI-351018, EBI-742362;
CC Q13557; Q5JZY3-3: EPHA10; NbExp=3; IntAct=EBI-351018, EBI-10244652;
CC Q13557; P68106: FKBP1B; NbExp=3; IntAct=EBI-351018, EBI-6693977;
CC Q13557; Q53EP0-3: FNDC3B; NbExp=3; IntAct=EBI-351018, EBI-10242151;
CC Q13557; P51116: FXR2; NbExp=3; IntAct=EBI-351018, EBI-740459;
CC Q13557; Q96BY2: MOAP1; NbExp=3; IntAct=EBI-351018, EBI-739825;
CC Q13557; Q9Y3B7: MRPL11; NbExp=5; IntAct=EBI-351018, EBI-5453723;
CC Q13557; Q96PM5: RCHY1; NbExp=2; IntAct=EBI-351018, EBI-947779;
CC Q13557; Q14524: SCN5A; NbExp=16; IntAct=EBI-351018, EBI-726858;
CC Q13557; O14787: TNPO2; NbExp=4; IntAct=EBI-351018, EBI-431907;
CC Q13557; Q8N0Z6: TTC5; NbExp=4; IntAct=EBI-351018, EBI-9526213;
CC Q13557; P61014: Pln; Xeno; NbExp=2; IntAct=EBI-351018, EBI-10148373;
CC Q13557; PRO_0000037311 [P0C6X7]: rep; Xeno; NbExp=4; IntAct=EBI-351018, EBI-25474079;
CC Q13557-8; Q9UQM7: CAMK2A; NbExp=3; IntAct=EBI-11534483, EBI-1383687;
CC Q13557-8; Q13554-3: CAMK2B; NbExp=4; IntAct=EBI-11534483, EBI-11523526;
CC Q13557-8; Q13555-5: CAMK2G; NbExp=3; IntAct=EBI-11534483, EBI-12020154;
CC Q13557-8; A0A0S2Z3P2: ERCC8; NbExp=3; IntAct=EBI-11534483, EBI-16440910;
CC Q13557-8; P78317: RNF4; NbExp=3; IntAct=EBI-11534483, EBI-2340927;
CC Q13557-8; Q9Y5L0: TNPO3; NbExp=3; IntAct=EBI-11534483, EBI-1042571;
CC Q13557-8; Q8N0Z6: TTC5; NbExp=3; IntAct=EBI-11534483, EBI-9526213;
CC Q13557-8; Q7KZS0: UBE2I; NbExp=3; IntAct=EBI-11534483, EBI-10180829;
CC -!- SUBCELLULAR LOCATION: Cell membrane, sarcolemma {ECO:0000305};
CC Peripheral membrane protein {ECO:0000305}; Cytoplasmic side
CC {ECO:0000305}. Sarcoplasmic reticulum membrane {ECO:0000305};
CC Peripheral membrane protein {ECO:0000305}; Cytoplasmic side
CC {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=10;
CC Name=Delta 2;
CC IsoId=Q13557-1; Sequence=Displayed;
CC Name=Delta 3;
CC IsoId=Q13557-3; Sequence=VSP_023096;
CC Name=Delta 4;
CC IsoId=Q13557-4; Sequence=VSP_023097;
CC Name=Delta 6;
CC IsoId=Q13557-8; Sequence=VSP_023099;
CC Name=Delta 7;
CC IsoId=Q13557-9; Sequence=VSP_023096, VSP_023099;
CC Name=Delta 8;
CC IsoId=Q13557-5; Sequence=VSP_023097, VSP_023099;
CC Name=Delta 9;
CC IsoId=Q13557-6; Sequence=VSP_023098;
CC Name=Delta 10;
CC IsoId=Q13557-10; Sequence=VSP_023098, VSP_023099;
CC Name=Delta 11;
CC IsoId=Q13557-11; Sequence=VSP_023095;
CC Name=Delta 12;
CC IsoId=Q13557-12; Sequence=VSP_041820, VSP_023099;
CC -!- TISSUE SPECIFICITY: Expressed in cardiac muscle and skeletal muscle.
CC Isoform Delta 3, isoform Delta 2, isoform Delta 8 and isoform Delta 9
CC are expressed in cardiac muscle. Isoform Delta 11 is expressed in
CC skeletal muscle. {ECO:0000269|PubMed:10189359,
CC 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:16690701}.
CC -!- MISCELLANEOUS: Expression of CAMK2D is significantly increased in
CC patients suffering from dilated cardiomyopathy in PubMed:10189359.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. CaMK subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD92525.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF071569; AAD20442.1; -; mRNA.
DR EMBL; AK055642; BAG51545.1; -; mRNA.
DR EMBL; AB209288; BAD92525.1; ALT_INIT; mRNA.
DR EMBL; AY987011; AAX88806.1; -; mRNA.
DR EMBL; AC004056; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC004168; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC093900; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC107386; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC032784; AAH32784.1; -; mRNA.
DR EMBL; AJ252239; CAB65123.1; -; mRNA.
DR EMBL; U50361; AAB16866.1; -; mRNA.
DR CCDS; CCDS3703.1; -. [Q13557-1]
DR CCDS; CCDS3704.1; -. [Q13557-8]
DR CCDS; CCDS43263.1; -. [Q13557-12]
DR CCDS; CCDS47127.1; -. [Q13557-10]
DR CCDS; CCDS54797.1; -. [Q13557-9]
DR RefSeq; NP_001212.2; NM_001221.3. [Q13557-1]
DR RefSeq; NP_001308495.1; NM_001321566.1. [Q13557-6]
DR RefSeq; NP_001308502.1; NM_001321573.1. [Q13557-11]
DR RefSeq; NP_001308509.1; NM_001321580.1. [Q13557-4]
DR RefSeq; NP_001308518.1; NM_001321589.1. [Q13557-10]
DR RefSeq; NP_742112.1; NM_172114.1. [Q13557-10]
DR RefSeq; NP_742113.1; NM_172115.2. [Q13557-8]
DR RefSeq; NP_742125.1; NM_172127.2. [Q13557-8]
DR RefSeq; NP_742126.1; NM_172128.2. [Q13557-12]
DR RefSeq; NP_742127.1; NM_172129.1. [Q13557-9]
DR RefSeq; XP_011530591.1; XM_011532289.1. [Q13557-3]
DR RefSeq; XP_011530593.1; XM_011532291.1. [Q13557-9]
DR PDB; 2VN9; X-ray; 2.30 A; A/B=11-309.
DR PDB; 2W2C; X-ray; 2.70 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N=334-475.
DR PDB; 2WEL; X-ray; 1.90 A; A=11-335.
DR PDB; 3GP2; X-ray; 1.46 A; B=294-311.
DR PDB; 5VLO; X-ray; 2.05 A; A/B=3-301.
DR PDB; 6AYW; X-ray; 2.05 A; A/B=3-301.
DR PDBsum; 2VN9; -.
DR PDBsum; 2W2C; -.
DR PDBsum; 2WEL; -.
DR PDBsum; 3GP2; -.
DR PDBsum; 5VLO; -.
DR PDBsum; 6AYW; -.
DR AlphaFoldDB; Q13557; -.
DR SMR; Q13557; -.
DR BioGRID; 107267; 142.
DR CORUM; Q13557; -.
DR DIP; DIP-33129N; -.
DR IntAct; Q13557; 173.
DR MINT; Q13557; -.
DR STRING; 9606.ENSP00000339740; -.
DR BindingDB; Q13557; -.
DR ChEMBL; CHEMBL2801; -.
DR DrugBank; DB08039; (3Z)-N,N-DIMETHYL-2-OXO-3-(4,5,6,7-TETRAHYDRO-1H-INDOL-2-YLMETHYLIDENE)-2,3-DIHYDRO-1H-INDOLE-5-SULFONAMIDE.
DR DrugBank; DB07853; 2-[4-[4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]quinazolin-2-yl]iminocyclohexa-2,5-dien-1-yl]acetonitrile.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q13557; -.
DR GuidetoPHARMACOLOGY; 1558; -.
DR iPTMnet; Q13557; -.
DR MetOSite; Q13557; -.
DR PhosphoSitePlus; Q13557; -.
DR SwissPalm; Q13557; -.
DR BioMuta; CAMK2D; -.
DR DMDM; 116242602; -.
DR EPD; Q13557; -.
DR jPOST; Q13557; -.
DR MassIVE; Q13557; -.
DR MaxQB; Q13557; -.
DR PaxDb; Q13557; -.
DR PeptideAtlas; Q13557; -.
DR PRIDE; Q13557; -.
DR ProteomicsDB; 59548; -. [Q13557-1]
DR ProteomicsDB; 59549; -. [Q13557-10]
DR ProteomicsDB; 59550; -. [Q13557-11]
DR ProteomicsDB; 59551; -. [Q13557-12]
DR ProteomicsDB; 59552; -. [Q13557-3]
DR ProteomicsDB; 59553; -. [Q13557-4]
DR ProteomicsDB; 59554; -. [Q13557-5]
DR ProteomicsDB; 59555; -. [Q13557-6]
DR ProteomicsDB; 59556; -. [Q13557-8]
DR ProteomicsDB; 59557; -. [Q13557-9]
DR Antibodypedia; 15593; 348 antibodies from 35 providers.
DR DNASU; 817; -.
DR Ensembl; ENST00000296402.9; ENSP00000296402.5; ENSG00000145349.18. [Q13557-8]
DR Ensembl; ENST00000342666.9; ENSP00000339740.5; ENSG00000145349.18. [Q13557-1]
DR Ensembl; ENST00000379773.6; ENSP00000369098.2; ENSG00000145349.18. [Q13557-8]
DR Ensembl; ENST00000394522.7; ENSP00000378030.3; ENSG00000145349.18. [Q13557-10]
DR Ensembl; ENST00000394524.7; ENSP00000378032.3; ENSG00000145349.18. [Q13557-12]
DR Ensembl; ENST00000508738.5; ENSP00000422566.1; ENSG00000145349.18. [Q13557-9]
DR Ensembl; ENST00000515496.5; ENSP00000423482.1; ENSG00000145349.18. [Q13557-3]
DR Ensembl; ENST00000683023.1; ENSP00000507073.1; ENSG00000145349.18. [Q13557-1]
DR GeneID; 817; -.
DR KEGG; hsa:817; -.
DR UCSC; uc003ibi.4; human. [Q13557-1]
DR CTD; 817; -.
DR DisGeNET; 817; -.
DR GeneCards; CAMK2D; -.
DR HGNC; HGNC:1462; CAMK2D.
DR HPA; ENSG00000145349; Tissue enhanced (heart).
DR MIM; 607708; gene.
DR neXtProt; NX_Q13557; -.
DR OpenTargets; ENSG00000145349; -.
DR PharmGKB; PA92; -.
DR VEuPathDB; HostDB:ENSG00000145349; -.
DR eggNOG; KOG0033; Eukaryota.
DR GeneTree; ENSGT00940000155150; -.
DR HOGENOM; CLU_000288_71_0_1; -.
DR InParanoid; Q13557; -.
DR PhylomeDB; Q13557; -.
DR TreeFam; TF315229; -.
DR BRENDA; 2.7.11.17; 2681.
DR PathwayCommons; Q13557; -.
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-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; Q13557; -.
DR SIGNOR; Q13557; -.
DR BioGRID-ORCS; 817; 13 hits in 1106 CRISPR screens.
DR ChiTaRS; CAMK2D; human.
DR EvolutionaryTrace; Q13557; -.
DR GeneWiki; CAMK2D; -.
DR GenomeRNAi; 817; -.
DR Pharos; Q13557; Tchem.
DR PRO; PR:Q13557; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q13557; protein.
DR Bgee; ENSG00000145349; Expressed in left ventricle myocardium and 185 other tissues.
DR ExpressionAtlas; Q13557; baseline and differential.
DR Genevisible; Q13557; HS.
DR GO; GO:0005954; C:calcium- and calmodulin-dependent protein kinase complex; IDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; ISS:BHF-UCL.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030666; C:endocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; ISS:BHF-UCL.
DR GO; GO:0042383; C:sarcolemma; IEA:UniProtKB-SubCell.
DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; 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; IDA:BHF-UCL.
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:0004674; F:protein serine/threonine kinase activity; IDA:BHF-UCL.
DR GO; GO:0019871; F:sodium channel inhibitor activity; IDA:BHF-UCL.
DR GO; GO:0031432; F:titin binding; IPI:BHF-UCL.
DR GO; GO:0044325; F:transmembrane transporter binding; IPI:BHF-UCL.
DR GO; GO:0086003; P:cardiac muscle cell contraction; ISS:BHF-UCL.
DR GO; GO:0071277; P:cellular response to calcium ion; TAS:BHF-UCL.
DR GO; GO:0032469; P:endoplasmic reticulum calcium ion homeostasis; ISS:BHF-UCL.
DR GO; GO:1902306; P:negative regulation of sodium ion transmembrane transport; IDA:BHF-UCL.
DR GO; GO:2000650; P:negative regulation of sodium ion transmembrane transporter activity; IDA:BHF-UCL.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:BHF-UCL.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:BHF-UCL.
DR GO; GO:0010666; P:positive regulation of cardiac muscle cell apoptotic process; ISS:BHF-UCL.
DR GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; IMP:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:BHF-UCL.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:1902514; P:regulation of calcium ion transmembrane transport via high voltage-gated calcium channel; ISS:BHF-UCL.
DR GO; GO:0098901; P:regulation of cardiac muscle cell action potential; ISS:BHF-UCL.
DR GO; GO:0098909; P:regulation of cardiac muscle cell action potential involved in regulation of contraction; IC:BHF-UCL.
DR GO; GO:0010881; P:regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion; TAS:UniProtKB.
DR GO; GO:0010649; P:regulation of cell communication by electrical coupling; ISS:BHF-UCL.
DR GO; GO:1901844; P:regulation of cell communication by electrical coupling involved in cardiac conduction; IC:BHF-UCL.
DR GO; GO:0001558; P:regulation of cell growth; NAS:UniProtKB.
DR GO; GO:0060341; P:regulation of cellular localization; IMP:UniProtKB.
DR GO; GO:0008016; P:regulation of heart contraction; TAS:UniProtKB.
DR GO; GO:0086091; P:regulation of heart rate by cardiac conduction; IC:BHF-UCL.
DR GO; GO:1901725; P:regulation of histone deacetylase activity; TAS:BHF-UCL.
DR GO; GO:0003254; P:regulation of membrane depolarization; IDA:BHF-UCL.
DR GO; GO:1901897; P:regulation of relaxation of cardiac muscle; IDA:BHF-UCL.
DR GO; GO:0010880; P:regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum; ISS:BHF-UCL.
DR GO; GO:0060314; P:regulation of ryanodine-sensitive calcium-release channel activity; TAS:UniProtKB.
DR GO; GO:0002026; P:regulation of the force of heart contraction; TAS:BHF-UCL.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; TAS:BHF-UCL.
DR GO; GO:0055119; P:relaxation of cardiac muscle; ISS:BHF-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; Acetylation; Alternative splicing; ATP-binding;
KW Calmodulin-binding; Cell membrane; Kinase; Membrane; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Sarcoplasmic reticulum;
KW Serine/threonine-protein kinase; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19369195"
FT CHAIN 2..499
FT /note="Calcium/calmodulin-dependent protein kinase type II
FT subunit delta"
FT /id="PRO_0000086099"
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 /evidence="ECO:0000250"
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 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19369195"
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:0000305"
FT MOD_RES 307
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000305"
FT MOD_RES 315
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 318
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q6PHZ2"
FT MOD_RES 319
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 330
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 331
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 333
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6PHZ2"
FT MOD_RES 336
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q6PHZ2"
FT MOD_RES 337
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 404
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 490
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 494
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6PHZ2"
FT VAR_SEQ 328
FT /note="K -> KKRKSSSSVQMMEPQTTVIHNPDGNK (in isoform Delta
FT 11)"
FT /evidence="ECO:0000305"
FT /id="VSP_023095"
FT VAR_SEQ 328
FT /note="K -> KKRKSSSSVQMM (in isoform Delta 3 and isoform
FT Delta 7)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_023096"
FT VAR_SEQ 328
FT /note="K -> KINNKANVVTSPKENIPTPAL (in isoform Delta 4 and
FT isoform Delta 8)"
FT /evidence="ECO:0000305"
FT /id="VSP_023097"
FT VAR_SEQ 329
FT /note="E -> EPQTTVIHNPDGNKE (in isoform Delta 9 and isoform
FT Delta 10)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_023098"
FT VAR_SEQ 478
FT /note="K -> N (in isoform Delta 12)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_041820"
FT VAR_SEQ 479..499
FT /note="Missing (in isoform Delta 6, isoform Delta 7,
FT isoform Delta 8, isoform Delta 10 and isoform Delta 12)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|Ref.3,
FT ECO:0000303|Ref.4"
FT /id="VSP_023099"
FT VARIANT 167
FT /note="D -> E (in dbSNP:rs35367671)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040602"
FT VARIANT 463
FT /note="Q -> E (in dbSNP:rs1053668)"
FT /id="VAR_028196"
FT VARIANT 493
FT /note="T -> I (in dbSNP:rs35765784)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040603"
FT CONFLICT 39
FT /note="E -> G (in Ref. 1; AAD20442)"
FT /evidence="ECO:0000305"
FT CONFLICT 272
FT /note="I -> T (in Ref. 4; AAX88806)"
FT /evidence="ECO:0000305"
FT HELIX 10..13
FT /evidence="ECO:0007829|PDB:2WEL"
FT STRAND 14..23
FT /evidence="ECO:0007829|PDB:2WEL"
FT STRAND 26..33
FT /evidence="ECO:0007829|PDB:2WEL"
FT TURN 34..36
FT /evidence="ECO:0007829|PDB:2WEL"
FT STRAND 39..46
FT /evidence="ECO:0007829|PDB:2WEL"
FT HELIX 47..49
FT /evidence="ECO:0007829|PDB:2WEL"
FT HELIX 52..67
FT /evidence="ECO:0007829|PDB:2WEL"
FT STRAND 76..82
FT /evidence="ECO:0007829|PDB:2WEL"
FT STRAND 85..90
FT /evidence="ECO:0007829|PDB:2WEL"
FT HELIX 98..105
FT /evidence="ECO:0007829|PDB:2WEL"
FT HELIX 110..129
FT /evidence="ECO:0007829|PDB:2WEL"
FT HELIX 139..141
FT /evidence="ECO:0007829|PDB:2WEL"
FT STRAND 142..148
FT /evidence="ECO:0007829|PDB:2WEL"
FT STRAND 153..155
FT /evidence="ECO:0007829|PDB:2WEL"
FT HELIX 158..160
FT /evidence="ECO:0007829|PDB:2WEL"
FT HELIX 178..180
FT /evidence="ECO:0007829|PDB:2WEL"
FT HELIX 183..186
FT /evidence="ECO:0007829|PDB:2WEL"
FT HELIX 194..209
FT /evidence="ECO:0007829|PDB:2WEL"
FT HELIX 219..228
FT /evidence="ECO:0007829|PDB:2WEL"
FT TURN 235..240
FT /evidence="ECO:0007829|PDB:2WEL"
FT HELIX 243..252
FT /evidence="ECO:0007829|PDB:2WEL"
FT TURN 257..259
FT /evidence="ECO:0007829|PDB:2WEL"
FT HELIX 263..266
FT /evidence="ECO:0007829|PDB:2WEL"
FT HELIX 270..273
FT /evidence="ECO:0007829|PDB:2WEL"
FT HELIX 275..278
FT /evidence="ECO:0007829|PDB:5VLO"
FT HELIX 296..310
FT /evidence="ECO:0007829|PDB:3GP2"
FT HELIX 340..363
FT /evidence="ECO:0007829|PDB:2W2C"
FT HELIX 366..372
FT /evidence="ECO:0007829|PDB:2W2C"
FT STRAND 373..380
FT /evidence="ECO:0007829|PDB:2W2C"
FT HELIX 382..384
FT /evidence="ECO:0007829|PDB:2W2C"
FT STRAND 389..392
FT /evidence="ECO:0007829|PDB:2W2C"
FT HELIX 393..401
FT /evidence="ECO:0007829|PDB:2W2C"
FT STRAND 410..421
FT /evidence="ECO:0007829|PDB:2W2C"
FT STRAND 426..438
FT /evidence="ECO:0007829|PDB:2W2C"
FT STRAND 444..458
FT /evidence="ECO:0007829|PDB:2W2C"
FT STRAND 461..470
FT /evidence="ECO:0007829|PDB:2W2C"
SQ SEQUENCE 499 AA; 56369 MW; 62999FBAB98120CE CRC64;
MASTTTCTRF TDEYQLFEEL GKGAFSVVRR CMKIPTGQEY AAKIINTKKL SARDHQKLER
EARICRLLKH PNIVRLHDSI SEEGFHYLVF DLVTGGELFE DIVAREYYSE ADASHCIQQI
LESVNHCHLN GIVHRDLKPE NLLLASKSKG AAVKLADFGL AIEVQGDQQA WFGFAGTPGY
LSPEVLRKDP YGKPVDMWAC GVILYILLVG YPPFWDEDQH RLYQQIKAGA YDFPSPEWDT
VTPEAKDLIN KMLTINPAKR ITASEALKHP WICQRSTVAS MMHRQETVDC LKKFNARRKL
KGAILTTMLA TRNFSAAKSL LKKPDGVKES TESSNTTIED EDVKARKQEI IKVTEQLIEA
INNGDFEAYT KICDPGLTAF EPEALGNLVE GMDFHRFYFE NALSKSNKPI HTIILNPHVH
LVGDDAACIA YIRLTQYMDG SGMPKTMQSE ETRVWHRRDG KWQNVHFHRS GSPTVPIKPP
CIPNGKENFS GGTSLWQNI
