ACTN2_HUMAN
ID ACTN2_HUMAN Reviewed; 894 AA.
AC P35609; B1ANE4; B2RCS5; Q86TF4; Q86TI8;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 231.
DE RecName: Full=Alpha-actinin-2;
DE AltName: Full=Alpha-actinin skeletal muscle isoform 2;
DE AltName: Full=F-actin cross-linking protein;
GN Name=ACTN2;
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 [GENOMIC DNA / MRNA] (ISOFORM 1).
RC TISSUE=Skeletal muscle;
RX PubMed=1339456; DOI=10.1016/s0021-9258(19)50420-3;
RA Beggs A.H., Byers T.J., Knoll J.H.M., Boyce F.M., Bruns G.A.P.,
RA Kunkel L.M.;
RT "Cloning and characterization of two human skeletal muscle alpha-actinin
RT genes located on chromosomes 1 and 11.";
RL J. Biol. Chem. 267:9281-9288(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10548523; DOI=10.1006/bbrc.1999.1661;
RA Tiso N., Majetti M., Stanchi F., Rampazzo A., Zimbello R., Nava A.,
RA Danieli G.A.;
RT "Fine mapping and genomic structure of ACTN2, the human gene coding for the
RT sarcomeric isoform of alpha-actinin-2, expressed in skeletal and cardiac
RT muscle.";
RL Biochem. Biophys. Res. Commun. 265:256-259(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=PNS;
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 INTERACTION WITH LDB3.
RX PubMed=10427098; DOI=10.1083/jcb.146.2.465;
RA Faulkner G., Pallavicini A., Formentin E., Comelli A., Ievolella C.,
RA Trevisan S., Bortoletto G., Scannapieco P., Salamon M., Mouly V., Valle G.,
RA Lanfranchi G.;
RT "ZASP: a new Z-band alternatively spliced PDZ-motif protein.";
RL J. Cell Biol. 146:465-475(1999).
RN [8]
RP INTERACTION WITH MYOZ1.
RX PubMed=10984498; DOI=10.1074/jbc.m007493200;
RA Faulkner G., Pallavicini A., Comelli A., Salamon M., Bortoletto G.,
RA Ievolella C., Trevisan S., Kojic' S., Dalla Vecchia F., Laveder P.,
RA Valle G., Lanfranchi G.;
RT "FATZ, a filamin-, actinin-, and telethonin-binding protein of the Z-disc
RT of skeletal muscle.";
RL J. Biol. Chem. 275:41234-41242(2000).
RN [9]
RP INTERACTION WITH MYOZ1 AND MYOZ2.
RX PubMed=11114196; DOI=10.1073/pnas.260501097;
RA Frey N., Richardson J.A., Olson E.N.;
RT "Calsarcins, a novel family of sarcomeric calcineurin-binding proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:14632-14637(2000).
RN [10]
RP INTERACTION WITH MYOZ1, AND SUBCELLULAR LOCATION.
RX PubMed=11171996; DOI=10.1073/pnas.98.4.1595;
RA Takada F., Vander Woude D.L., Tong H.-Q., Thompson T.G., Watkins S.C.,
RA Kunkel L.M., Beggs A.H.;
RT "Myozenin: an alpha-actinin- and gamma-filamin-binding protein of skeletal
RT muscle Z lines.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:1595-1600(2001).
RN [11]
RP INTERACTION WITH MYOZ3.
RX PubMed=11842093; DOI=10.1074/jbc.m200712200;
RA Frey N., Olson E.N.;
RT "Calsarcin-3, a novel skeletal muscle-specific member of the calsarcin
RT family, interacts with multiple Z-disc proteins.";
RL J. Biol. Chem. 277:13998-14004(2002).
RN [12]
RP INTERACTION WITH PARVB.
RX PubMed=15159419; DOI=10.1083/jcb.200308141;
RA Yamaji S., Suzuki A., Kanamori H., Mishima W., Yoshimi R., Takasaki H.,
RA Takabayashi M., Fujimaki K., Fujisawa S., Ohno S., Ishigatsubo Y.;
RT "Affixin interacts with alpha-actinin and mediates integrin signaling for
RT reorganization of F-actin induced by initial cell-substrate interaction.";
RL J. Cell Biol. 165:539-551(2004).
RN [13]
RP INTERACTION WITH XIRP2.
RX PubMed=17046827; DOI=10.1074/jbc.m603244200;
RA Huang H.-T., Brand O.M., Mathew M., Ignatiou C., Ewen E.P., McCalmon S.A.,
RA Naya F.J.;
RT "Myomaxin is a novel transcriptional target of MEF2A that encodes a Xin-
RT related alpha-actinin-interacting protein.";
RL J. Biol. Chem. 281:39370-39379(2006).
RN [14]
RP INTERACTION WITH SYNPO2.
RX PubMed=20554076; DOI=10.1016/j.ejcb.2010.04.004;
RA Linnemann A., van der Ven P.F., Vakeel P., Albinus B., Simonis D.,
RA Bendas G., Schenk J.A., Micheel B., Kley R.A., Fuerst D.O.;
RT "The sarcomeric Z-disc component myopodin is a multiadapter protein that
RT interacts with filamin and alpha-actinin.";
RL Eur. J. Cell Biol. 89:681-692(2010).
RN [15]
RP INTERACTION WITH DST, AND SUBCELLULAR LOCATION.
RX PubMed=19932097; DOI=10.1016/j.yexcr.2009.11.010;
RA Steiner-Champliaud M.F., Schneider Y., Favre B., Paulhe F.,
RA Praetzel-Wunder S., Faulkner G., Konieczny P., Raith M., Wiche G.,
RA Adebola A., Liem R.K., Langbein L., Sonnenberg A., Fontao L., Borradori L.;
RT "BPAG1 isoform-b: complex distribution pattern in striated and heart muscle
RT and association with plectin and alpha-actinin.";
RL Exp. Cell Res. 316:297-313(2010).
RN [16]
RP UBIQUITINATION BY FBXL22.
RX PubMed=22972877; DOI=10.1161/circresaha.112.271007;
RA Spaich S., Will R.D., Just S., Spaich S., Kuhn C., Frank D., Berger I.M.,
RA Wiemann S., Korn B., Koegl M., Backs J., Katus H.A., Rottbauer W., Frey N.;
RT "F-box and leucine-rich repeat protein 22 is a cardiac-enriched F-box
RT protein that regulates sarcomeric protein turnover and is essential for
RT maintenance of contractile function in vivo.";
RL Circ. Res. 111:1504-1516(2012).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 391-637.
RX PubMed=10481917; DOI=10.1016/s0092-8674(00)81981-9;
RA Djinovic-Carugo K., Young P., Gautel M., Saraste M.;
RT "Structure of the alpha-actinin rod: molecular basis for cross-linking of
RT actin filaments.";
RL Cell 98:537-546(1999).
RN [18]
RP STRUCTURE BY NMR OF 823-894 IN COMPLEX WITH A TITIN Z-REPEAT.
RX PubMed=11573089; DOI=10.1038/nsb1001-853;
RA Atkinson R.A., Joseph C., Kelly G., Muskett F.W., Frenkiel T.A.,
RA Nietlispach D., Pastore A.;
RT "Ca2+-independent binding of an EF-hand domain to a novel motif in the
RT alpha-actinin-titin complex.";
RL Nat. Struct. Biol. 8:853-857(2001).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 274-746.
RX PubMed=11470434; DOI=10.1016/s0969-2126(01)00619-0;
RA Ylanne J., Scheffzek K., Young P., Saraste M.;
RT "Crystal structure of the alpha-actinin rod reveals an extensive torsional
RT twist.";
RL Structure 9:597-604(2001).
RN [20]
RP VARIANT CMD1AA ARG-9, AND VARIANT VAL-604.
RX PubMed=14567970; DOI=10.1016/s1096-7192(03)00142-2;
RA Mohapatra B., Jimenez S., Lin J.H., Bowles K.R., Coveler K.J., Marx J.G.,
RA Chrisco M.A., Murphy R.T., Lurie P.R., Schwartz R.J., Elliott P.M.,
RA Vatta M., McKenna W., Towbin J.A., Bowles N.E.;
RT "Mutations in the muscle LIM protein and alpha-actinin-2 genes in dilated
RT cardiomyopathy and endocardial fibroelastosis.";
RL Mol. Genet. Metab. 80:207-215(2003).
RN [21]
RP VARIANTS CMH23 THR-119; MET-495; ALA-583 AND GLY-628.
RX PubMed=20022194; DOI=10.1016/j.jacc.2009.11.016;
RA Chiu C., Bagnall R.D., Ingles J., Yeates L., Kennerson M., Donald J.A.,
RA Jormakka M., Lind J.M., Semsarian C.;
RT "Mutations in alpha-actinin-2 cause hypertrophic cardiomyopathy: a genome-
RT wide analysis.";
RL J. Am. Coll. Cardiol. 55:1127-1135(2010).
RN [22]
RP VARIANT CMD1AA THR-119.
RX PubMed=25224718; DOI=10.1186/s12881-014-0099-0;
RA Bagnall R.D., Molloy L.K., Kalman J.M., Semsarian C.;
RT "Exome sequencing identifies a mutation in the ACTN2 gene in a family with
RT idiopathic ventricular fibrillation, left ventricular noncompaction, and
RT sudden death.";
RL BMC Med. Genet. 15:99-99(2014).
RN [23]
RP VARIANT CMH23 THR-228.
RX PubMed=25173926; DOI=10.1161/circgenetics.113.000486;
RA Girolami F., Iascone M., Tomberli B., Bardi S., Benelli M., Marseglia G.,
RA Pescucci C., Pezzoli L., Sana M.E., Basso C., Marziliano N., Merlini P.A.,
RA Fornaro A., Cecchi F., Torricelli F., Olivotto I.;
RT "Novel alpha-actinin 2 variant associated with familial hypertrophic
RT cardiomyopathy and juvenile atrial arrhythmias: a massively parallel
RT sequencing study.";
RL Circ. Cardiovasc. Genet. 7:741-750(2014).
RN [24]
RP VARIANTS MYOCOZ ARG-727 AND 732-ALA--ILE-742 DEL, INVOLVEMENT IN MYOCOZ,
RP AND SUBCELLULAR LOCATION.
RX PubMed=30701273; DOI=10.1007/s00401-019-01963-8;
RA Lornage X., Romero N.B., Grosgogeat C.A., Malfatti E., Donkervoort S.,
RA Marchetti M.M., Neuhaus S.B., Foley A.R., Labasse C., Schneider R.,
RA Carlier R.Y., Chao K.R., Medne L., Deleuze J.F., Orlikowski D.,
RA Boennemann C.G., Gupta V.A., Fardeau M., Boehm J., Laporte J.;
RT "ACTN2 mutations cause 'Multiple structured Core Disease' (MsCD).";
RL Acta Neuropathol. 137:501-519(2019).
RN [25]
RP VARIANTS MPD6 PRO-131 AND ARG-487, AND INVOLVEMENT IN MPD6.
RX PubMed=30900782; DOI=10.1002/ana.25470;
RA Savarese M., Palmio J., Poza J.J., Weinberg J., Olive M., Cobo A.M.,
RA Vihola A., Jonson P.H., Sarparanta J., Garcia-Bragado F., Urtizberea J.A.,
RA Hackman P., Udd B.;
RT "Actininopathy: A new muscular dystrophy caused by ACTN2 dominant
RT mutations.";
RL Ann. Neurol. 85:899-906(2019).
CC -!- FUNCTION: F-actin cross-linking protein which is thought to anchor
CC actin to a variety of intracellular structures. This is a bundling
CC protein.
CC -!- SUBUNIT: Homodimer; antiparallel. Also forms heterodimers with ACTN3.
CC Interacts with ADAM12, MYOZ1, MYOZ2 and MYOZ3. Interacts via its C-
CC terminal region with the LDB3 PDZ domain. Interacts with XIRP2.
CC Interacts with DST isoform 1 (via N-terminus). Interacts with PARVB.
CC Interacts with SYNPO2. {ECO:0000269|PubMed:10427098,
CC ECO:0000269|PubMed:10984498, ECO:0000269|PubMed:11114196,
CC ECO:0000269|PubMed:11171996, ECO:0000269|PubMed:11842093,
CC ECO:0000269|PubMed:15159419, ECO:0000269|PubMed:17046827,
CC ECO:0000269|PubMed:19932097}.
CC -!- INTERACTION:
CC P35609; P12814: ACTN1; NbExp=3; IntAct=EBI-77797, EBI-351710;
CC P35609; P35609: ACTN2; NbExp=11; IntAct=EBI-77797, EBI-77797;
CC P35609; P03950: ANG; NbExp=4; IntAct=EBI-77797, EBI-525291;
CC P35609; O43827: ANGPTL7; NbExp=3; IntAct=EBI-77797, EBI-12698369;
CC P35609; P05496: ATP5MC1; NbExp=3; IntAct=EBI-77797, EBI-10194585;
CC P35609; Q92934: BAD; NbExp=3; IntAct=EBI-77797, EBI-700771;
CC P35609; Q5PSV4: BRMS1L; NbExp=7; IntAct=EBI-77797, EBI-5666615;
CC P35609; P26842: CD27; NbExp=3; IntAct=EBI-77797, EBI-520729;
CC P35609; Q8WXI8: CLEC4D; NbExp=3; IntAct=EBI-77797, EBI-12703404;
CC P35609; Q8NE01: CNNM3; NbExp=3; IntAct=EBI-77797, EBI-741032;
CC P35609; P29373: CRABP2; NbExp=3; IntAct=EBI-77797, EBI-10204806;
CC P35609; P78560: CRADD; NbExp=3; IntAct=EBI-77797, EBI-520375;
CC P35609; P50461: CSRP3; NbExp=4; IntAct=EBI-77797, EBI-5658719;
CC P35609; Q9NRI5: DISC1; NbExp=4; IntAct=EBI-77797, EBI-529989;
CC P35609; Q8WW35: DYNLT2B; NbExp=3; IntAct=EBI-77797, EBI-2692044;
CC P35609; Q9Y247: FAM50B; NbExp=3; IntAct=EBI-77797, EBI-742802;
CC P35609; P23771: GATA3; NbExp=3; IntAct=EBI-77797, EBI-6664760;
CC P35609; Q7Z5G4: GOLGA7; NbExp=3; IntAct=EBI-77797, EBI-4403685;
CC P35609; P30711: GSTT1; NbExp=3; IntAct=EBI-77797, EBI-8770084;
CC P35609; P62805: H4C9; NbExp=3; IntAct=EBI-77797, EBI-302023;
CC P35609; P28222: HTR1B; NbExp=3; IntAct=EBI-77797, EBI-1056863;
CC P35609; Q8IYT4: KATNAL2; NbExp=3; IntAct=EBI-77797, EBI-1044332;
CC P35609; P22460: KCNA5; NbExp=6; IntAct=EBI-77797, EBI-6426121;
CC P35609; Q9H2S1: KCNN2; NbExp=3; IntAct=EBI-77797, EBI-6658875;
CC P35609; Q8IVT4: MGC50722; NbExp=3; IntAct=EBI-77797, EBI-14086479;
CC P35609; Q8IY33: MICALL2; NbExp=7; IntAct=EBI-77797, EBI-2555563;
CC P35609; P00540: MOS; NbExp=3; IntAct=EBI-77797, EBI-1757866;
CC P35609; Q7Z7H8: MRPL10; NbExp=3; IntAct=EBI-77797, EBI-723524;
CC P35609; A0A0S2Z4Y0: MYOT; NbExp=3; IntAct=EBI-77797, EBI-16430371;
CC P35609; Q9UBF9: MYOT; NbExp=3; IntAct=EBI-77797, EBI-296701;
CC P35609; Q9NPC6: MYOZ2; NbExp=13; IntAct=EBI-77797, EBI-746712;
CC P35609; Q6ZUT1: NKAPD1; NbExp=3; IntAct=EBI-77797, EBI-3920396;
CC P35609; Q86VF7: NRAP; NbExp=2; IntAct=EBI-77797, EBI-5660292;
CC P35609; Q96HA8: NTAQ1; NbExp=3; IntAct=EBI-77797, EBI-741158;
CC P35609; A8MYP8: ODF3B; NbExp=3; IntAct=EBI-77797, EBI-12010090;
CC P35609; Q53GG5: PDLIM3; NbExp=6; IntAct=EBI-77797, EBI-5658852;
CC P35609; Q53GG5-2: PDLIM3; NbExp=3; IntAct=EBI-77797, EBI-12702438;
CC P35609; P62140: PPP1CB; NbExp=3; IntAct=EBI-77797, EBI-352350;
CC P35609; P25786: PSMA1; NbExp=3; IntAct=EBI-77797, EBI-359352;
CC P35609; P47897: QARS1; NbExp=3; IntAct=EBI-77797, EBI-347462;
CC P35609; P63244: RACK1; NbExp=3; IntAct=EBI-77797, EBI-296739;
CC P35609; O95059: RPP14; NbExp=3; IntAct=EBI-77797, EBI-366542;
CC P35609; Q14D33: RTP5; NbExp=7; IntAct=EBI-77797, EBI-10217913;
CC P35609; Q8IYX7: SAXO1; NbExp=7; IntAct=EBI-77797, EBI-3957636;
CC P35609; O95863: SNAI1; NbExp=7; IntAct=EBI-77797, EBI-1045459;
CC P35609; P23497: SP100; NbExp=6; IntAct=EBI-77797, EBI-751145;
CC P35609; P23497-2: SP100; NbExp=3; IntAct=EBI-77797, EBI-6589365;
CC P35609; Q15506: SPA17; NbExp=3; IntAct=EBI-77797, EBI-1377865;
CC P35609; P49458: SRP9; NbExp=3; IntAct=EBI-77797, EBI-350743;
CC P35609; Q9H987-2: SYNPO2L; NbExp=3; IntAct=EBI-77797, EBI-12082116;
CC P35609; Q9H0E2: TOLLIP; NbExp=3; IntAct=EBI-77797, EBI-74615;
CC P35609; Q8WZ42: TTN; NbExp=16; IntAct=EBI-77797, EBI-681210;
CC P35609; O75604: USP2; NbExp=3; IntAct=EBI-77797, EBI-743272;
CC P35609; J3KMY6: ZC2HC1C; NbExp=3; IntAct=EBI-77797, EBI-11990572;
CC P35609; Q53FD0-2: ZC2HC1C; NbExp=3; IntAct=EBI-77797, EBI-14104088;
CC P35609; O60232: ZNRD2; NbExp=3; IntAct=EBI-77797, EBI-741415;
CC P35609; Q61824: Adam12; Xeno; NbExp=3; IntAct=EBI-77797, EBI-77785;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, myofibril, sarcomere, Z line
CC {ECO:0000269|PubMed:11171996, ECO:0000269|PubMed:19932097,
CC ECO:0000269|PubMed:30701273}. Note=Colocalizes with MYOZ1 and FLNC at
CC the Z-lines of skeletal muscle.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P35609-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P35609-2; Sequence=VSP_054923;
CC -!- TISSUE SPECIFICITY: Expressed in both skeletal and cardiac muscle.
CC -!- PTM: Ubiquitinated by FBXL22, leading to proteasomal degradation.
CC {ECO:0000269|PubMed:22972877}.
CC -!- DISEASE: Cardiomyopathy, familial hypertrophic 23, with or without left
CC ventricular non-compaction (CMH23) [MIM:612158]: A hereditary heart
CC disorder characterized by ventricular hypertrophy, which is usually
CC asymmetric and often involves the interventricular septum. The symptoms
CC include dyspnea, syncope, collapse, palpitations, and chest pain. They
CC can be readily provoked by exercise. The disorder has inter- and
CC intrafamilial variability ranging from benign to malignant forms with
CC high risk of cardiac failure and sudden cardiac death.
CC {ECO:0000269|PubMed:20022194, ECO:0000269|PubMed:25173926}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Cardiomyopathy, dilated 1AA, with or without left ventricular
CC non-compaction (CMD1AA) [MIM:612158]: A disorder characterized by
CC ventricular dilation and impaired systolic function, resulting in
CC congestive heart failure and arrhythmia. Patients are at risk of
CC premature death. {ECO:0000269|PubMed:14567970,
CC ECO:0000269|PubMed:25224718}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Myopathy, congenital, with structured cores and Z-line
CC abnormalities (MYOCOZ) [MIM:618654]: An autosomal dominant muscular
CC disorder characterized by progressive early-onset muscle weakness, gait
CC difficulties, loss of ambulation, and respiratory insufficiency.
CC Morphological and ultrastructural analyses of muscle biopsies reveal
CC type 1 fiber predominance, multiple structured cores forming a circular
CC arrangement beneath the sarcolemma, and jagged Z-lines.
CC {ECO:0000269|PubMed:30701273}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Myopathy, distal, 6, adult onset, autosomal dominant (MPD6)
CC [MIM:618655]: An autosomal dominant muscular disorder characterized by
CC adult onset of asymmetric distal muscle weakness, primarily affecting
CC the lower limbs and resulting in gait difficulties. Some patients
CC develop involvement of proximal and upper limb muscles.
CC {ECO:0000269|PubMed:30900782}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the alpha-actinin family. {ECO:0000305}.
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DR EMBL; M86406; AAA51583.1; -; mRNA.
DR EMBL; M86804; AAA51584.1; -; Genomic_DNA.
DR EMBL; AJ249756; CAB61269.1; -; Genomic_DNA.
DR EMBL; AJ249757; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249758; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249759; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249760; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249761; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249762; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249763; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249764; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249765; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249766; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249767; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249768; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249769; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249770; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249771; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249772; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249773; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249774; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249775; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249776; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AK315250; BAG37672.1; -; mRNA.
DR EMBL; AL359185; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL359921; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471098; EAW70064.1; -; Genomic_DNA.
DR EMBL; CH471098; EAW70065.1; -; Genomic_DNA.
DR EMBL; BC047901; AAH47901.2; -; mRNA.
DR EMBL; BC051770; AAH51770.2; -; mRNA.
DR CCDS; CCDS1613.1; -. [P35609-1]
DR CCDS; CCDS60455.1; -. [P35609-2]
DR PIR; A40199; FAHUA2.
DR RefSeq; NP_001094.1; NM_001103.3. [P35609-1]
DR RefSeq; NP_001265272.1; NM_001278343.1. [P35609-2]
DR RefSeq; NP_001265273.1; NM_001278344.1.
DR PDB; 1H8B; NMR; -; A=822-894.
DR PDB; 1HCI; X-ray; 2.80 A; A/B=274-746.
DR PDB; 1QUU; X-ray; 2.50 A; A=391-637.
DR PDB; 4D1E; X-ray; 3.50 A; A=19-894.
DR PDB; 5A36; X-ray; 2.00 A; A/B=19-266.
DR PDB; 5A37; X-ray; 1.88 A; A/B=19-266.
DR PDB; 5A38; X-ray; 1.90 A; A/B=19-266.
DR PDB; 5A4B; X-ray; 2.01 A; A/B=19-266.
DR PDB; 6SWT; X-ray; 1.20 A; A=19-270.
DR PDB; 6TS3; X-ray; 1.28 A; A/B=825-894.
DR PDB; 7A8T; X-ray; 2.69 A; A=274-746.
DR PDB; 7A8U; X-ray; 3.80 A; A=274-746.
DR PDBsum; 1H8B; -.
DR PDBsum; 1HCI; -.
DR PDBsum; 1QUU; -.
DR PDBsum; 4D1E; -.
DR PDBsum; 5A36; -.
DR PDBsum; 5A37; -.
DR PDBsum; 5A38; -.
DR PDBsum; 5A4B; -.
DR PDBsum; 6SWT; -.
DR PDBsum; 6TS3; -.
DR PDBsum; 7A8T; -.
DR PDBsum; 7A8U; -.
DR AlphaFoldDB; P35609; -.
DR BMRB; P35609; -.
DR SASBDB; P35609; -.
DR SMR; P35609; -.
DR BioGRID; 106603; 137.
DR DIP; DIP-383N; -.
DR IntAct; P35609; 98.
DR MINT; P35609; -.
DR STRING; 9606.ENSP00000443495; -.
DR TCDB; 8.A.66.1.3; the dystrophin (dystrophin) family.
DR GlyGen; P35609; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; P35609; -.
DR MetOSite; P35609; -.
DR PhosphoSitePlus; P35609; -.
DR SwissPalm; P35609; -.
DR BioMuta; ACTN2; -.
DR DMDM; 543742; -.
DR EPD; P35609; -.
DR jPOST; P35609; -.
DR MassIVE; P35609; -.
DR MaxQB; P35609; -.
DR PaxDb; P35609; -.
DR PeptideAtlas; P35609; -.
DR PRIDE; P35609; -.
DR ProteomicsDB; 3424; -.
DR ProteomicsDB; 55100; -. [P35609-1]
DR Antibodypedia; 1323; 405 antibodies from 39 providers.
DR DNASU; 88; -.
DR Ensembl; ENST00000366578.6; ENSP00000355537.4; ENSG00000077522.15. [P35609-1]
DR Ensembl; ENST00000542672.6; ENSP00000443495.1; ENSG00000077522.15. [P35609-2]
DR GeneID; 88; -.
DR KEGG; hsa:88; -.
DR MANE-Select; ENST00000366578.6; ENSP00000355537.4; NM_001103.4; NP_001094.1.
DR UCSC; uc001hyf.4; human. [P35609-1]
DR CTD; 88; -.
DR DisGeNET; 88; -.
DR GeneCards; ACTN2; -.
DR GeneReviews; ACTN2; -.
DR HGNC; HGNC:164; ACTN2.
DR HPA; ENSG00000077522; Group enriched (heart muscle, skeletal muscle, tongue).
DR MalaCards; ACTN2; -.
DR MIM; 102573; gene.
DR MIM; 612158; phenotype.
DR MIM; 618654; phenotype.
DR MIM; 618655; phenotype.
DR neXtProt; NX_P35609; -.
DR OpenTargets; ENSG00000077522; -.
DR Orphanet; 154; Familial isolated dilated cardiomyopathy.
DR Orphanet; 155; NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy.
DR PharmGKB; PA25; -.
DR VEuPathDB; HostDB:ENSG00000077522; -.
DR eggNOG; KOG0035; Eukaryota.
DR GeneTree; ENSGT00940000153968; -.
DR HOGENOM; CLU_005217_1_1_1; -.
DR InParanoid; P35609; -.
DR OMA; IMILVDP; -.
DR OrthoDB; 543832at2759; -.
DR PhylomeDB; P35609; -.
DR TreeFam; TF352676; -.
DR PathwayCommons; P35609; -.
DR Reactome; R-HSA-114608; Platelet degranulation.
DR Reactome; R-HSA-373753; Nephrin family interactions.
DR Reactome; R-HSA-390522; Striated Muscle Contraction.
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-5673001; RAF/MAP kinase cascade.
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 SignaLink; P35609; -.
DR BioGRID-ORCS; 88; 16 hits in 1068 CRISPR screens.
DR ChiTaRS; ACTN2; human.
DR EvolutionaryTrace; P35609; -.
DR GeneWiki; Actinin,_alpha_2; -.
DR GenomeRNAi; 88; -.
DR Pharos; P35609; Tbio.
DR PRO; PR:P35609; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P35609; protein.
DR Bgee; ENSG00000077522; Expressed in skeletal muscle tissue of rectus abdominis and 154 other tissues.
DR ExpressionAtlas; P35609; baseline and differential.
DR Genevisible; P35609; HS.
DR GO; GO:0005884; C:actin filament; TAS:ProtInc.
DR GO; GO:0030054; C:cell junction; IBA:GO_Central.
DR GO; GO:0042995; C:cell projection; IBA:GO_Central.
DR GO; GO:0030864; C:cortical actin cytoskeleton; IBA:GO_Central.
DR GO; GO:0005856; C:cytoskeleton; NAS:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0043197; C:dendritic spine; TAS:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0030175; C:filopodium; IDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; IMP:UniProtKB.
DR GO; GO:0031093; C:platelet alpha granule lumen; TAS:Reactome.
DR GO; GO:0031143; C:pseudopodium; TAS:UniProtKB.
DR GO; GO:0030018; C:Z disc; IDA:UniProtKB.
DR GO; GO:0051015; F:actin filament binding; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0008092; F:cytoskeletal protein binding; IDA:UniProtKB.
DR GO; GO:0051373; F:FATZ binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:UniProtKB.
DR GO; GO:0005178; F:integrin binding; TAS:UniProtKB.
DR GO; GO:0030274; F:LIM domain binding; IEA:Ensembl.
DR GO; GO:0030374; F:nuclear receptor coactivator activity; IEA:Ensembl.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IDA:UniProtKB.
DR GO; GO:0019904; F:protein domain specific binding; IPI:UniProtKB.
DR GO; GO:0008307; F:structural constituent of muscle; TAS:ProtInc.
DR GO; GO:0031432; F:titin binding; IPI:BHF-UCL.
DR GO; GO:0070080; F:titin Z domain binding; IMP:UniProtKB.
DR GO; GO:0044325; F:transmembrane transporter binding; IPI:UniProtKB.
DR GO; GO:0030036; P:actin cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0051695; P:actin filament uncapping; IMP:UniProtKB.
DR GO; GO:0055013; P:cardiac muscle cell development; IEA:Ensembl.
DR GO; GO:0007155; P:cell adhesion; TAS:UniProtKB.
DR GO; GO:0048041; P:focal adhesion assembly; IMP:UniProtKB.
DR GO; GO:0030035; P:microspike assembly; IDA:UniProtKB.
DR GO; GO:0055001; P:muscle cell development; IBA:GO_Central.
DR GO; GO:1901017; P:negative regulation of potassium ion transmembrane transporter activity; IMP:BHF-UCL.
DR GO; GO:0043267; P:negative regulation of potassium ion transport; IMP:BHF-UCL.
DR GO; GO:2000009; P:negative regulation of protein localization to cell surface; IMP:BHF-UCL.
DR GO; GO:0086097; P:phospholipase C-activating angiotensin-activated signaling pathway; IMP:UniProtKB.
DR GO; GO:2001259; P:positive regulation of cation channel activity; IMP:UniProtKB.
DR GO; GO:2001137; P:positive regulation of endocytic recycling; IMP:UniProtKB.
DR GO; GO:1901018; P:positive regulation of potassium ion transmembrane transporter activity; IDA:BHF-UCL.
DR GO; GO:0043268; P:positive regulation of potassium ion transport; IDA:BHF-UCL.
DR GO; GO:0072659; P:protein localization to plasma membrane; IMP:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; NAS:UniProtKB.
DR GO; GO:0042391; P:regulation of membrane potential; IMP:BHF-UCL.
DR GO; GO:0045214; P:sarcomere organization; IMP:UniProtKB.
DR CDD; cd00014; CH; 2.
DR CDD; cd00051; EFh; 1.
DR CDD; cd00176; SPEC; 1.
DR Gene3D; 1.10.418.10; -; 2.
DR InterPro; IPR001589; Actinin_actin-bd_CS.
DR InterPro; IPR001715; CH-domain.
DR InterPro; IPR036872; CH_dom_sf.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR014837; EF-hand_Ca_insen.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR018159; Spectrin/alpha-actinin.
DR InterPro; IPR002017; Spectrin_repeat.
DR Pfam; PF00307; CH; 2.
DR Pfam; PF08726; EFhand_Ca_insen; 1.
DR Pfam; PF00435; Spectrin; 4.
DR SMART; SM00033; CH; 2.
DR SMART; SM00054; EFh; 2.
DR SMART; SM00150; SPEC; 3.
DR SUPFAM; SSF47473; SSF47473; 1.
DR SUPFAM; SSF47576; SSF47576; 1.
DR PROSITE; PS00019; ACTININ_1; 1.
DR PROSITE; PS00020; ACTININ_2; 1.
DR PROSITE; PS50021; CH; 2.
DR PROSITE; PS50222; EF_HAND_2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Actin-binding; Alternative splicing; Calcium; Cardiomyopathy;
KW Cytoplasm; Disease variant; Metal-binding; Phosphoprotein;
KW Reference proteome; Repeat; Ubl conjugation.
FT CHAIN 1..894
FT /note="Alpha-actinin-2"
FT /id="PRO_0000073435"
FT DOMAIN 38..142
FT /note="Calponin-homology (CH) 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00044"
FT DOMAIN 151..257
FT /note="Calponin-homology (CH) 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00044"
FT REPEAT 281..391
FT /note="Spectrin 1"
FT REPEAT 401..506
FT /note="Spectrin 2"
FT REPEAT 516..627
FT /note="Spectrin 3"
FT REPEAT 637..740
FT /note="Spectrin 4"
FT DOMAIN 753..788
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 789..824
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 1..254
FT /note="Actin-binding"
FT BINDING 766
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000305"
FT BINDING 770
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000305"
FT BINDING 777
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000305"
FT BINDING 802
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 804
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 808
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT MOD_RES 237
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9JI91"
FT VAR_SEQ 234..261
FT /note="IVNTPKPDERAIMTYVSCFYHAFAGAEQ -> LVYTARPDERAIMTYVSCYY
FT HAFAGAQK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054923"
FT VARIANT 9
FT /note="Q -> R (in CMD1AA; dbSNP:rs121434525)"
FT /evidence="ECO:0000269|PubMed:14567970"
FT /id="VAR_054628"
FT VARIANT 119
FT /note="A -> T (in CMH23 and CMD1AA; dbSNP:rs727502886)"
FT /evidence="ECO:0000269|PubMed:20022194,
FT ECO:0000269|PubMed:25224718"
FT /id="VAR_071970"
FT VARIANT 131
FT /note="L -> P (in MPD6; unknown pathological significance;
FT dbSNP:rs1572114611)"
FT /evidence="ECO:0000269|PubMed:30900782"
FT /id="VAR_083364"
FT VARIANT 228
FT /note="M -> T (in CMH23; dbSNP:rs786205144)"
FT /evidence="ECO:0000269|PubMed:25173926"
FT /id="VAR_074292"
FT VARIANT 487
FT /note="C -> R (in MPD6; dbSNP:rs1572140109)"
FT /evidence="ECO:0000269|PubMed:30900782"
FT /id="VAR_083365"
FT VARIANT 495
FT /note="T -> M (in CMH23; dbSNP:rs200248944)"
FT /evidence="ECO:0000269|PubMed:20022194"
FT /id="VAR_071971"
FT VARIANT 583
FT /note="E -> A (in CMH23; dbSNP:rs200631005)"
FT /evidence="ECO:0000269|PubMed:20022194"
FT /id="VAR_071972"
FT VARIANT 604
FT /note="M -> V (in dbSNP:rs35997569)"
FT /evidence="ECO:0000269|PubMed:14567970"
FT /id="VAR_033487"
FT VARIANT 628
FT /note="E -> G (in CMH23; dbSNP:rs786204951)"
FT /evidence="ECO:0000269|PubMed:20022194"
FT /id="VAR_071973"
FT VARIANT 727
FT /note="L -> R (in MYOCOZ; dbSNP:rs1572148902)"
FT /evidence="ECO:0000269|PubMed:30701273"
FT /id="VAR_083366"
FT VARIANT 732..742
FT /note="Missing (in MYOCOZ; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:30701273"
FT /id="VAR_083367"
FT HELIX 21..29
FT /evidence="ECO:0007829|PDB:5A36"
FT HELIX 32..52
FT /evidence="ECO:0007829|PDB:6SWT"
FT HELIX 53..55
FT /evidence="ECO:0007829|PDB:6SWT"
FT TURN 62..68
FT /evidence="ECO:0007829|PDB:6SWT"
FT HELIX 70..80
FT /evidence="ECO:0007829|PDB:6SWT"
FT STRAND 90..92
FT /evidence="ECO:0007829|PDB:5A36"
FT HELIX 93..109
FT /evidence="ECO:0007829|PDB:6SWT"
FT HELIX 119..123
FT /evidence="ECO:0007829|PDB:6SWT"
FT HELIX 127..142
FT /evidence="ECO:0007829|PDB:6SWT"
FT TURN 143..145
FT /evidence="ECO:0007829|PDB:6SWT"
FT HELIX 153..165
FT /evidence="ECO:0007829|PDB:6SWT"
FT STRAND 175..177
FT /evidence="ECO:0007829|PDB:6SWT"
FT HELIX 178..180
FT /evidence="ECO:0007829|PDB:6SWT"
FT HELIX 184..193
FT /evidence="ECO:0007829|PDB:6SWT"
FT TURN 195..197
FT /evidence="ECO:0007829|PDB:6SWT"
FT HELIX 200..202
FT /evidence="ECO:0007829|PDB:6SWT"
FT HELIX 208..222
FT /evidence="ECO:0007829|PDB:6SWT"
FT HELIX 231..236
FT /evidence="ECO:0007829|PDB:6SWT"
FT STRAND 237..239
FT /evidence="ECO:0007829|PDB:6SWT"
FT HELIX 242..256
FT /evidence="ECO:0007829|PDB:6SWT"
FT HELIX 274..277
FT /evidence="ECO:0007829|PDB:7A8T"
FT HELIX 280..304
FT /evidence="ECO:0007829|PDB:7A8T"
FT HELIX 313..328
FT /evidence="ECO:0007829|PDB:7A8T"
FT HELIX 331..354
FT /evidence="ECO:0007829|PDB:7A8T"
FT HELIX 364..366
FT /evidence="ECO:0007829|PDB:1HCI"
FT HELIX 368..383
FT /evidence="ECO:0007829|PDB:7A8T"
FT STRAND 389..392
FT /evidence="ECO:0007829|PDB:4D1E"
FT HELIX 393..416
FT /evidence="ECO:0007829|PDB:1QUU"
FT TURN 417..419
FT /evidence="ECO:0007829|PDB:1QUU"
FT HELIX 420..425
FT /evidence="ECO:0007829|PDB:1QUU"
FT HELIX 428..431
FT /evidence="ECO:0007829|PDB:7A8T"
FT HELIX 434..470
FT /evidence="ECO:0007829|PDB:1QUU"
FT HELIX 476..536
FT /evidence="ECO:0007829|PDB:1QUU"
FT TURN 537..540
FT /evidence="ECO:0007829|PDB:1QUU"
FT TURN 548..550
FT /evidence="ECO:0007829|PDB:1QUU"
FT HELIX 551..562
FT /evidence="ECO:0007829|PDB:1QUU"
FT HELIX 564..588
FT /evidence="ECO:0007829|PDB:1QUU"
FT HELIX 604..632
FT /evidence="ECO:0007829|PDB:1QUU"
FT TURN 666..669
FT /evidence="ECO:0007829|PDB:1HCI"
FT HELIX 671..704
FT /evidence="ECO:0007829|PDB:7A8T"
FT HELIX 717..745
FT /evidence="ECO:0007829|PDB:7A8T"
FT HELIX 753..762
FT /evidence="ECO:0007829|PDB:4D1E"
FT STRAND 767..770
FT /evidence="ECO:0007829|PDB:4D1E"
FT HELIX 777..784
FT /evidence="ECO:0007829|PDB:4D1E"
FT HELIX 794..799
FT /evidence="ECO:0007829|PDB:4D1E"
FT HELIX 812..820
FT /evidence="ECO:0007829|PDB:4D1E"
FT HELIX 825..838
FT /evidence="ECO:0007829|PDB:6TS3"
FT TURN 839..841
FT /evidence="ECO:0007829|PDB:6TS3"
FT STRAND 843..845
FT /evidence="ECO:0007829|PDB:6TS3"
FT HELIX 847..853
FT /evidence="ECO:0007829|PDB:6TS3"
FT HELIX 856..865
FT /evidence="ECO:0007829|PDB:6TS3"
FT STRAND 871..873
FT /evidence="ECO:0007829|PDB:4D1E"
FT HELIX 881..889
FT /evidence="ECO:0007829|PDB:6TS3"
SQ SEQUENCE 894 AA; 103854 MW; 7F612C1C3B3E2299 CRC64;
MNQIEPGVQY NYVYDEDEYM IQEEEWDRDL LLDPAWEKQQ RKTFTAWCNS HLRKAGTQIE
NIEEDFRNGL KLMLLLEVIS GERLPKPDRG KMRFHKIANV NKALDYIASK GVKLVSIGAE
EIVDGNVKMT LGMIWTIILR FAIQDISVEE TSAKEGLLLW CQRKTAPYRN VNIQNFHTSW
KDGLGLCALI HRHRPDLIDY SKLNKDDPIG NINLAMEIAE KHLDIPKMLD AEDIVNTPKP
DERAIMTYVS CFYHAFAGAE QAETAANRIC KVLAVNQENE RLMEEYERLA SELLEWIRRT
IPWLENRTPE KTMQAMQKKL EDFRDYRRKH KPPKVQEKCQ LEINFNTLQT KLRISNRPAF
MPSEGKMVSD IAGAWQRLEQ AEKGYEEWLL NEIRRLERLE HLAEKFRQKA STHETWAYGK
EQILLQKDYE SASLTEVRAL LRKHEAFESD LAAHQDRVEQ IAAIAQELNE LDYHDAVNVN
DRCQKICDQW DRLGTLTQKR REALERMEKL LETIDQLHLE FAKRAAPFNN WMEGAMEDLQ
DMFIVHSIEE IQSLITAHEQ FKATLPEADG ERQSIMAIQN EVEKVIQSYN IRISSSNPYS
TVTMDELRTK WDKVKQLVPI RDQSLQEELA RQHANERLRR QFAAQANAIG PWIQNKMEEI
ARSSIQITGA LEDQMNQLKQ YEHNIINYKN NIDKLEGDHQ LIQEALVFDN KHTNYTMEHI
RVGWELLLTT IARTINEVET QILTRDAKGI TQEQMNEFRA SFNHFDRRKN GLMDHEDFRA
CLISMGYDLG EAEFARIMTL VDPNGQGTVT FQSFIDFMTR ETADTDTAEQ VIASFRILAS
DKPYILAEEL RRELPPDQAQ YCIKRMPAYS GPGSVPGALD YAAFSSALYG ESDL
