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 27-MAR-2024, entry version 232. 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 (PubMed:17179159). Is essential for left ventricular remodeling CC responses to myocardial infarction. In pathological myocardial CC remodeling acts downstream of the beta adrenergic receptor signaling CC cascade to regulate key proteins involved in ECC. Regulates Ca(2+) CC influx to myocytes by binding and phosphorylating the L-type Ca(2+) CC channel subunit beta-2 CACNB2. In addition to Ca(2+) channels, can CC target and regulate the cardiac sarcolemmal Na(+) channel Nav1.5/SCN5A CC and the K+ channel Kv4.3/KCND3, which contribute to arrhythmogenesis in CC heart 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 (PubMed:16690701). May participate in the modulation of CC skeletal muscle function in response to exercise, by regulating SR CC Ca(2+) transport through phosphorylation of PLN/PLB and triadin, a CC ryanodine receptor-coupling factor. In response to interferon-gamma CC (IFN-gamma) stimulation, catalyzes phosphorylation of STAT1, CC stimulating the JAK-STAT signaling pathway (By similarity). CC {ECO:0000250|UniProtKB:Q6PHZ2, ECO:0000269|PubMed:16690701, CC 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; P62258: YWHAE; NbExp=2; IntAct=EBI-351018, EBI-356498; 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; 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 CCDS; CCDS93607.1; -. [Q13557-6] DR CCDS; CCDS93609.1; -. [Q13557-3] DR CCDS; CCDS93612.1; -. [Q13557-11] 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. DR RefSeq; XP_011530593.1; XM_011532291.1. 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 PDB; 7ZRP; X-ray; 2.65 A; B/D=294-315. DR PDB; 7ZRQ; X-ray; 1.68 A; B=294-315. DR PDBsum; 2VN9; -. DR PDBsum; 2W2C; -. DR PDBsum; 2WEL; -. DR PDBsum; 3GP2; -. DR PDBsum; 5VLO; -. DR PDBsum; 6AYW; -. DR PDBsum; 7ZRP; -. DR PDBsum; 7ZRQ; -. DR AlphaFoldDB; Q13557; -. DR SMR; Q13557; -. DR BioGRID; 107267; 199. DR CORUM; Q13557; -. DR DIP; DIP-33129N; -. DR IntAct; Q13557; 179. DR MINT; Q13557; -. DR STRING; 9606.ENSP00000425824; -. 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 GlyGen; Q13557; 4 sites, 1 O-linked glycan (4 sites). 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; 9606-ENSP00000339740; -. DR PeptideAtlas; 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 Pumba; Q13557; -. DR Antibodypedia; 15593; 438 antibodies from 35 providers. DR DNASU; 817; -. DR Ensembl; ENST00000296402.9; ENSP00000296402.5; ENSG00000145349.20. [Q13557-8] DR Ensembl; ENST00000342666.9; ENSP00000339740.5; ENSG00000145349.20. [Q13557-1] DR Ensembl; ENST00000379773.6; ENSP00000369098.2; ENSG00000145349.20. [Q13557-8] DR Ensembl; ENST00000394522.7; ENSP00000378030.3; ENSG00000145349.20. [Q13557-10] DR Ensembl; ENST00000394524.7; ENSP00000378032.3; ENSG00000145349.20. [Q13557-12] DR Ensembl; ENST00000508738.5; ENSP00000422566.1; ENSG00000145349.20. [Q13557-9] DR Ensembl; ENST00000515496.5; ENSP00000423482.1; ENSG00000145349.20. [Q13557-3] DR Ensembl; ENST00000683023.1; ENSP00000507073.1; ENSG00000145349.20. [Q13557-1] DR Ensembl; ENST00000699047.1; ENSP00000514099.1; ENSG00000145349.20. [Q13557-6] DR Ensembl; ENST00000699048.1; ENSP00000514100.1; ENSG00000145349.20. [Q13557-11] DR Ensembl; ENST00000699381.1; ENSP00000514346.1; ENSG00000145349.20. [Q13557-6] DR GeneID; 817; -. DR KEGG; hsa:817; -. DR UCSC; uc003ibi.4; human. [Q13557-1] DR AGR; HGNC:1462; -. 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 OrthoDB; 1121238at2759; -. 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; 14 hits in 1185 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 187 other cell types or tissues. DR ExpressionAtlas; Q13557; baseline and differential. 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: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 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:SF365; CALCIUM_CALMODULIN-DEPENDENT PROTEIN KINASE TYPE II SUBUNIT DELTA; 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. DR Genevisible; Q13557; HS. 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 TURN 311..313 FT /evidence="ECO:0007829|PDB:7ZRP" 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 //