ID ANK3_HUMAN Reviewed; 4377 AA. AC Q12955; B1AQT2; B4DIL1; E9PE32; Q13484; Q5CZH9; Q5VXD5; Q7Z3G4; Q9H0P5; DT 11-JUL-2002, integrated into UniProtKB/Swiss-Prot. DT 01-SEP-2009, sequence version 3. DT 10-FEB-2021, entry version 201. DE RecName: Full=Ankyrin-3 {ECO:0000303|PubMed:7836469}; DE Short=ANK-3 {ECO:0000303|PubMed:7836469}; DE AltName: Full=Ankyrin-G {ECO:0000303|PubMed:7836469}; GN Name=ANK3 {ECO:0000312|HGNC:HGNC:494}; 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 1), AND TISSUE SPECIFICITY. RC TISSUE=Brain stem; RX PubMed=7836469; DOI=10.1074/jbc.270.5.2352; RA Kordeli E., Lambert S., Bennett V.; RT "AnkyrinG. A new ankyrin gene with neural-specific isoforms localized at RT the axonal initial segment and node of Ranvier."; RL J. Biol. Chem. 270:2352-2359(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), FUNCTION (ISOFORM 5), AND RP SUBCELLULAR LOCATION (ISOFORM 5). RC TISSUE=Kidney; RX PubMed=8666667; DOI=10.1083/jcb.133.4.819; RA Devarajan P., Stabach P.R., Mann A.S., Ardito T., Kashgarian M., RA Morrow J.S.; RT "Identification of a small cytoplasmic ankyrin (AnkG119) in the kidney and RT muscle that binds beta I sigma spectrin and associates with the Golgi RT apparatus."; RL J. Cell Biol. 133:819-830(1996). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). RC TISSUE=Kidney; RX PubMed=11230166; DOI=10.1101/gr.gr1547r; RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B., RA Klein M., Poustka A.; RT "Towards a catalog of human genes and proteins: sequencing and analysis of RT 500 novel complete protein coding human cDNAs."; RL Genome Res. 11:422-435(2001). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Hippocampus; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Cervix, and Fetal kidney; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164054; DOI=10.1038/nature02462; RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P., RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 10."; RL Nature 429:375-381(2004). RN [7] RP INTERACTION WITH SCN5A. RX PubMed=15579534; DOI=10.1073/pnas.0403711101; RA Mohler P.J., Rivolta I., Napolitano C., LeMaillet G., Lambert S., RA Priori S.G., Bennett V.; RT "Nav1.5 E1053K mutation causing Brugada syndrome blocks binding to ankyrin- RT G and expression of Nav1.5 on the surface of cardiomyocytes."; RL Proc. Natl. Acad. Sci. U.S.A. 101:17533-17538(2004). RN [8] RP INTERACTION WITH RHBG. RX PubMed=15611082; DOI=10.1074/jbc.m413351200; RA Lopez C., Metral S., Eladari D., Drevensek S., Gane P., Chambrey R., RA Bennett V., Cartron J.-P., Le Van Kim C., Colin Y.; RT "The ammonium transporter RhBG: requirement of a tyrosine-based signal and RT ankyrin-G for basolateral targeting and membrane anchorage in polarized RT kidney epithelial cells."; RL J. Biol. Chem. 280:8221-8228(2005). RN [9] 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 [10] RP INTERACTION WITH PLEC AND FLNC, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, RP AND DEVELOPMENTAL STAGE. RX PubMed=21223964; DOI=10.1016/j.yexcr.2011.01.002; RA Maiweilidan Y., Klauza I., Kordeli E.; RT "Novel interactions of ankyrins-G at the costameres: the muscle-specific RT Obscurin/Titin-Binding-related Domain (OTBD) binds plectin and filamin C."; RL Exp. Cell Res. 317:724-736(2011). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-39; SER-847; SER-1445 AND RP SER-4298, AND 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 [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1459; SER-4298 AND SER-4350, RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-4229; SER-4290 AND SER-4298, RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1632 AND SER-1658 (ISOFORM RP 2), PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1625 AND SER-1651 RP (ISOFORM 3), PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-765 AND SER-791 RP (ISOFORM 4), PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-468 (ISOFORM 5), RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [14] RP INTERACTION WITH KCNA1. RX PubMed=23903368; DOI=10.1038/ki.2013.280; RA San-Cristobal P., Lainez S., Dimke H., de Graaf M.J., Hoenderop J.G., RA Bindels R.J.; RT "Ankyrin-3 is a novel binding partner of the voltage-gated potassium RT channel Kv1.1 implicated in renal magnesium handling."; RL Kidney Int. 85:94-102(2014). RN [15] RP INTERACTION WITH IQCJ-SCHIP1 AND SCHIP1. RX PubMed=25950943; DOI=10.1111/jnc.13158; RA Papandreou M.J., Vacher H., Fache M.P., Klingler E., Rueda-Boroni F., RA Ferracci G., Debarnot C., Piperoglou C., Garcia Del Cano G., Goutebroze L., RA Dargent B.; RT "CK2-regulated schwannomin-interacting protein IQCJ-SCHIP-1 association RT with AnkG contributes to the maintenance of the axon initial segment."; RL J. Neurochem. 134:527-537(2015). RN [16] RP VARIANT HIS-968. RX PubMed=25966638; DOI=10.1038/ejhg.2015.91; RA Tham E., Eklund E.A., Hammarsjoe A., Bengtson P., Geiberger S., RA Lagerstedt-Robinson K., Malmgren H., Nilsson D., Grigelionis G., Conner P., RA Lindgren P., Lindstrand A., Wedell A., Albaage M., Zielinska K., RA Nordgren A., Papadogiannakis N., Nishimura G., Grigelioniene G.; RT "A novel phenotype in N-glycosylation disorders: Gillessen-Kaesbach- RT Nishimura skeletal dysplasia due to pathogenic variants in ALG9."; RL Eur. J. Hum. Genet. 24:198-207(2016). RN [17] RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 4088-4199. RX PubMed=25307106; DOI=10.1002/prot.24702; RA Liu Y., Zhang Y., Wang J.H.; RT "Crystal structure of human Ankyrin G death domain."; RL Proteins 82:3476-3482(2014). RN [18] RP VARIANTS ALA-1569; MET-3720 AND PRO-4255, AND POSSIBLE INVOLVEMENT IN RP SUSCEPTIBILITY TO AUTISM. RX PubMed=22865819; DOI=10.1002/humu.22174; RA Bi C., Wu J., Jiang T., Liu Q., Cai W., Yu P., Cai T., Zhao M., Jiang Y.H., RA Sun Z.S.; RT "Mutations of ANK3 identified by exome sequencing are associated with RT autism susceptibility."; RL Hum. Mutat. 33:1635-1638(2012). RN [19] RP INVOLVEMENT IN MRT37. RX PubMed=23390136; DOI=10.1093/hmg/ddt043; RA Iqbal Z., Vandeweyer G., van der Voet M., Waryah A.M., Zahoor M.Y., RA Besseling J.A., Roca L.T., Vulto-van Silfhout A.T., Nijhof B., Kramer J.M., RA Van der Aa N., Ansar M., Peeters H., Helsmoortel C., Gilissen C., RA Vissers L.E., Veltman J.A., de Brouwer A.P., Frank Kooy R., Riazuddin S., RA Schenck A., van Bokhoven H., Rooms L.; RT "Homozygous and heterozygous disruptions of ANK3: at the crossroads of RT neurodevelopmental and psychiatric disorders."; RL Hum. Mol. Genet. 22:1960-1970(2013). CC -!- FUNCTION: In skeletal muscle, required for costamere localization of CC DMD and betaDAG1 (By similarity). Membrane-cytoskeleton linker. May CC participate in the maintenance/targeting of ion channels and cell CC adhesion molecules at the nodes of Ranvier and axonal initial segments. CC Regulates KCNA1 channel activity in function of dietary Mg(2+) levels, CC and thereby contributes to the regulation of renal Mg(2+) reabsorption CC (PubMed:23903368). {ECO:0000250, ECO:0000269|PubMed:17974005}. CC -!- FUNCTION: [Isoform 5]: May be part of a Golgi-specific membrane CC cytoskeleton in association with beta-spectrin. CC {ECO:0000305|PubMed:17974005}. CC -!- SUBUNIT: Directly interacts with DMD and betaDAG1. This interaction CC does not interfere with binding between DMD and betaDAG1. It is also CC required for DMD and betaDAG1 retention at costameres (By similarity). CC Interacts (via N-terminal ANK repeats) with SCHIP1 isoform 5 (via C- CC terminus); this interaction is required for the localization at axon CC initial segments (AISs) and nodes of Ranvier (NRs) (By similarity). May CC be a constituent of a NFASC/NRCAM/ankyrin G complex. Interacts with CC RHBG (PubMed:15611082). Interacts with PLEC and FLNC (PubMed:21223964). CC Interacts with KCNA1; this inhibits channel activity (PubMed:23903368). CC Interacts (via ANK repeats) with IQCJ-SCHIP1; required for IQCJ-SCHIP1 CC localization at axon initial segments (AIS) and nodes of Ranvier CC (PubMed:25950943). Interacts with SCHIP1 (PubMed:25950943). Interacts CC with SCN5A (PubMed:15579534). {ECO:0000250|UniProtKB:G5E8K5, CC ECO:0000269|PubMed:15579534, ECO:0000269|PubMed:15611082, CC ECO:0000269|PubMed:21223964, ECO:0000269|PubMed:23903368, CC ECO:0000269|PubMed:25950943}. CC -!- INTERACTION: CC Q12955; O00203-1: AP3B1; NbExp=2; IntAct=EBI-2691178, EBI-15816315; CC Q12955; Q15796: SMAD2; NbExp=2; IntAct=EBI-2691178, EBI-1040141; CC Q12955-5; Q15742: NAB2; NbExp=3; IntAct=EBI-12154305, EBI-8641936; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton CC {ECO:0000269|PubMed:21223964}. Cell projection, axon CC {ECO:0000250|UniProtKB:O70511}. Cell membrane, sarcolemma CC {ECO:0000269|PubMed:21223964}. Cell junction, synapse, postsynaptic CC cell membrane {ECO:0000250|UniProtKB:O70511}. Lysosome CC {ECO:0000250|UniProtKB:G5E8K5}. Cell membrane, sarcolemma, T-tubule CC {ECO:0000250|UniProtKB:O70511}. Note=In skeletal muscle, localized at CC costameres and neuromuscular junctions. In macrophages, associated with CC lysosomes. {ECO:0000250|UniProtKB:G5E8K5, CC ECO:0000250|UniProtKB:O70511}. CC -!- SUBCELLULAR LOCATION: [Isoform 5]: Cytoplasm, cytoskeleton CC {ECO:0000269|PubMed:8666667}. Golgi apparatus CC {ECO:0000269|PubMed:8666667}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1; CC IsoId=Q12955-3; Sequence=Displayed; CC Name=2; CC IsoId=Q12955-4; Sequence=VSP_044349, VSP_044350, VSP_044351, CC VSP_044352, VSP_044353, VSP_044354; CC Name=3; CC IsoId=Q12955-5; Sequence=VSP_044348, VSP_044351, VSP_044352, CC VSP_044353, VSP_044354; CC Name=4; CC IsoId=Q12955-6; Sequence=VSP_046885, VSP_046886, VSP_044351, CC VSP_044352, VSP_044353, VSP_044354; CC Name=5; Synonyms=AnkG119, Golgi ankyrin; CC IsoId=Q12955-7; Sequence=VSP_053753, VSP_053754, VSP_053755, CC VSP_053756, VSP_053757, VSP_044351, CC VSP_053758, VSP_053759; CC -!- TISSUE SPECIFICITY: Expressed in brain, neurons, muscles and other CC tissues. {ECO:0000269|PubMed:21223964, ECO:0000269|PubMed:7836469}. CC -!- DEVELOPMENTAL STAGE: Up-regulated during muscle cell differentiation. CC {ECO:0000269|PubMed:21223964}. CC -!- DOMAIN: The tandem configuration of the two ZU5 and the UPA domains CC forms a structural supramodule termed ZZU. ZU5-1 mediates interaction CC with beta-spectrin, and the ZU5-1/UPA interface is required for CC ankyrin's function other than binding to spectrin (By similarity). CC {ECO:0000250}. CC -!- DISEASE: Note=Genetic variations in ANK3 may be associated with autism CC spectrum disorders susceptibility. {ECO:0000269|PubMed:22865819}. CC -!- DISEASE: Mental retardation, autosomal recessive 37 (MRT37) CC [MIM:615493]: A disorder characterized by significantly below average CC general intellectual functioning associated with impairments in CC adaptive behavior and manifested during the developmental period. MRT37 CC patients manifest delayed global development with speech delay, CC hypotonia, spasticity, and a sleep disorder. Severe behavioral CC abnormalities include aggression, hyperactivity, and grinding of the CC teeth. Note=The disease is caused by variants affecting the gene CC represented in this entry. A homozygous deletion in ANK3 predicted to CC result in frameshift and premature truncation, has been shown to be the CC cause of moderate intellectual disability, an ADHD-like phenotype and CC behavioral problems in a consanguineous family (PubMed:23390136). CC {ECO:0000269|PubMed:23390136}. CC -!- MISCELLANEOUS: [Isoform 5]: Avidly binds beta spectrin. {ECO:0000305}. CC -!- SEQUENCE CAUTION: [Isoform 4]: CC Sequence=CAB66645.1; Type=Frameshift; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Ankyrin entry; CC URL="https://en.wikipedia.org/wiki/Ankyrin"; 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; U13616; AAA64834.1; -; mRNA. DR EMBL; U43965; AAB08437.1; -; mRNA. DR EMBL; AL136710; CAB66645.1; ALT_FRAME; mRNA. DR EMBL; AK295661; BAG58523.1; -; mRNA. DR EMBL; BX537917; CAD97900.2; -; mRNA. DR EMBL; BX648574; CAI56716.1; -; mRNA. DR EMBL; AC022390; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC023904; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL359267; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL359377; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL391707; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL592430; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL607065; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS55711.1; -. [Q12955-4] DR CCDS; CCDS55712.1; -. [Q12955-5] DR CCDS; CCDS7258.1; -. [Q12955-3] DR CCDS; CCDS7259.1; -. [Q12955-6] DR PIR; A55575; A55575. DR RefSeq; NP_001140.2; NM_001149.3. [Q12955-6] DR RefSeq; NP_001191332.1; NM_001204403.1. [Q12955-5] DR RefSeq; NP_001191333.1; NM_001204404.1. [Q12955-4] DR RefSeq; NP_066267.2; NM_020987.4. [Q12955-3] DR PDB; 4O6X; X-ray; 2.10 A; A/B=4088-4199. DR PDBsum; 4O6X; -. DR SMR; Q12955; -. DR BioGRID; 106785; 59. DR CORUM; Q12955; -. DR DIP; DIP-49017N; -. DR ELM; Q12955; -. DR IntAct; Q12955; 41. DR MINT; Q12955; -. DR STRING; 9606.ENSP00000280772; -. DR iPTMnet; Q12955; -. DR PhosphoSitePlus; Q12955; -. DR SwissPalm; Q12955; -. DR BioMuta; ANK3; -. DR DMDM; 257051061; -. DR EPD; Q12955; -. DR jPOST; Q12955; -. DR MassIVE; Q12955; -. DR MaxQB; Q12955; -. DR PaxDb; Q12955; -. DR PeptideAtlas; Q12955; -. DR PRIDE; Q12955; -. DR ProteomicsDB; 19802; -. DR ProteomicsDB; 3339; -. DR ProteomicsDB; 59048; -. [Q12955-3] DR ABCD; Q12955; 6 sequenced antibodies. DR Antibodypedia; 4197; 265 antibodies. DR DNASU; 288; -. DR Ensembl; ENST00000280772; ENSP00000280772; ENSG00000151150. [Q12955-3] DR Ensembl; ENST00000355288; ENSP00000347436; ENSG00000151150. [Q12955-6] DR Ensembl; ENST00000373827; ENSP00000362933; ENSG00000151150. [Q12955-5] DR Ensembl; ENST00000503366; ENSP00000425236; ENSG00000151150. [Q12955-4] DR GeneID; 288; -. DR KEGG; hsa:288; -. DR UCSC; uc001jkw.4; human. [Q12955-3] DR CTD; 288; -. DR DisGeNET; 288; -. DR GeneCards; ANK3; -. DR HGNC; HGNC:494; ANK3. DR HPA; ENSG00000151150; Tissue enhanced (brain, parathyroid gland). DR MalaCards; ANK3; -. DR MIM; 600465; gene. DR MIM; 615493; phenotype. DR neXtProt; NX_Q12955; -. DR OpenTargets; ENSG00000151150; -. DR Orphanet; 356996; ANK3-related intellectual disability-sleep disturbance syndrome. DR PharmGKB; PA24800; -. DR VEuPathDB; HostDB:ENSG00000151150.20; -. DR eggNOG; KOG4177; Eukaryota. DR GeneTree; ENSGT00940000154939; -. DR HOGENOM; CLU_000134_29_1_1; -. DR InParanoid; Q12955; -. DR OMA; MPDYFSE; -. DR OrthoDB; 1011028at2759; -. DR PhylomeDB; Q12955; -. DR TreeFam; TF351263; -. DR PathwayCommons; Q12955; -. DR Reactome; R-HSA-445095; Interaction between L1 and Ankyrins. DR Reactome; R-HSA-6807878; COPI-mediated anterograde transport. DR BioGRID-ORCS; 288; 4 hits in 886 CRISPR screens. DR ChiTaRS; ANK3; human. DR GeneWiki; ANK3; -. DR GenomeRNAi; 288; -. DR Pharos; Q12955; Tbio. DR PRO; PR:Q12955; -. DR Proteomes; UP000005640; Chromosome 10. DR RNAct; Q12955; protein. DR Bgee; ENSG00000151150; Expressed in substantia nigra and 246 other tissues. DR ExpressionAtlas; Q12955; baseline and differential. DR Genevisible; Q12955; HS. DR GO; GO:0043194; C:axon initial segment; IDA:CAFA. DR GO; GO:0009925; C:basal plasma membrane; IDA:BHF-UCL. DR GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB. DR GO; GO:0009986; C:cell surface; ISS:BHF-UCL. DR GO; GO:0043034; C:costamere; TAS:BHF-UCL. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0030425; C:dendrite; ISS:BHF-UCL. DR GO; GO:0005783; C:endoplasmic reticulum; TAS:ProtInc. DR GO; GO:0005794; C:Golgi apparatus; TAS:ProtInc. DR GO; GO:0014704; C:intercalated disc; ISS:BHF-UCL. DR GO; GO:0016328; C:lateral plasma membrane; IDA:BHF-UCL. DR GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell. DR GO; GO:0031594; C:neuromuscular junction; ISS:BHF-UCL. DR GO; GO:0043005; C:neuron projection; ISS:BHF-UCL. DR GO; GO:0033268; C:node of Ranvier; ISS:ARUK-UCL. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0045211; C:postsynaptic membrane; ISS:BHF-UCL. DR GO; GO:0042383; C:sarcolemma; IDA:BHF-UCL. DR GO; GO:0016529; C:sarcoplasmic reticulum; ISS:BHF-UCL. DR GO; GO:0014731; C:spectrin-associated cytoskeleton; ISS:BHF-UCL. DR GO; GO:0030315; C:T-tubule; ISS:BHF-UCL. DR GO; GO:0030018; C:Z disc; ISS:BHF-UCL. DR GO; GO:0045296; F:cadherin binding; ISS:BHF-UCL. DR GO; GO:0008093; F:cytoskeletal anchor activity; IBA:GO_Central. DR GO; GO:0008092; F:cytoskeletal protein binding; ISS:BHF-UCL. DR GO; GO:0044325; F:ion channel binding; ISS:BHF-UCL. DR GO; GO:0030674; F:protein-macromolecule adaptor activity; ISS:BHF-UCL. DR GO; GO:0030507; F:spectrin binding; ISS:BHF-UCL. DR GO; GO:0005200; F:structural constituent of cytoskeleton; IMP:BHF-UCL. DR GO; GO:0007409; P:axonogenesis; ISS:BHF-UCL. DR GO; GO:0071286; P:cellular response to magnesium ion; ISS:UniProtKB. DR GO; GO:0006888; P:endoplasmic reticulum to Golgi vesicle-mediated transport; TAS:Reactome. DR GO; GO:0045184; P:establishment of protein localization; IMP:UniProtKB. DR GO; GO:0043001; P:Golgi to plasma membrane protein transport; IMP:BHF-UCL. DR GO; GO:0010960; P:magnesium ion homeostasis; ISS:UniProtKB. DR GO; GO:0072660; P:maintenance of protein location in plasma membrane; IGI:BHF-UCL. DR GO; GO:0071709; P:membrane assembly; IMP:BHF-UCL. DR GO; GO:0000281; P:mitotic cytokinesis; IMP:BHF-UCL. DR GO; GO:1902260; P:negative regulation of delayed rectifier potassium channel activity; ISS:UniProtKB. DR GO; GO:0007528; P:neuromuscular junction development; ISS:BHF-UCL. DR GO; GO:0019228; P:neuronal action potential; ISS:BHF-UCL. DR GO; GO:0007009; P:plasma membrane organization; IMP:BHF-UCL. DR GO; GO:2001259; P:positive regulation of cation channel activity; ISS:BHF-UCL. DR GO; GO:0010650; P:positive regulation of cell communication by electrical coupling; ISS:BHF-UCL. DR GO; GO:0010628; P:positive regulation of gene expression; ISS:BHF-UCL. DR GO; GO:0034112; P:positive regulation of homotypic cell-cell adhesion; ISS:BHF-UCL. DR GO; GO:1900827; P:positive regulation of membrane depolarization during cardiac muscle cell action potential; ISS:BHF-UCL. DR GO; GO:0045838; P:positive regulation of membrane potential; ISS:BHF-UCL. DR GO; GO:0090314; P:positive regulation of protein targeting to membrane; ISS:BHF-UCL. DR GO; GO:2000651; P:positive regulation of sodium ion transmembrane transporter activity; ISS:BHF-UCL. DR GO; GO:0010765; P:positive regulation of sodium ion transport; ISS:BHF-UCL. DR GO; GO:0099612; P:protein localization to axon; ISS:UniProtKB. DR GO; GO:0072659; P:protein localization to plasma membrane; IMP:BHF-UCL. DR GO; GO:0043266; P:regulation of potassium ion transport; ISS:BHF-UCL. DR GO; GO:0007165; P:signal transduction; IEA:InterPro. DR CDD; cd08803; Death_ank3; 1. DR Gene3D; 1.25.40.20; -; 3. DR InterPro; IPR037971; Ank3_Death. DR InterPro; IPR002110; Ankyrin_rpt. DR InterPro; IPR020683; Ankyrin_rpt-contain_dom. DR InterPro; IPR036770; Ankyrin_rpt-contain_sf. DR InterPro; IPR040745; Ankyrin_UPA. DR InterPro; IPR011029; DEATH-like_dom_sf. DR InterPro; IPR000488; Death_domain. DR InterPro; IPR000906; ZU5_dom. DR Pfam; PF00023; Ank; 1. DR Pfam; PF12796; Ank_2; 7. DR Pfam; PF13606; Ank_3; 1. DR Pfam; PF00531; Death; 1. DR Pfam; PF17809; UPA_2; 1. DR Pfam; PF00791; ZU5; 1. DR PRINTS; PR01415; ANKYRIN. DR SMART; SM00248; ANK; 22. DR SMART; SM00005; DEATH; 1. DR SMART; SM00218; ZU5; 1. DR SUPFAM; SSF47986; SSF47986; 1. DR SUPFAM; SSF48403; SSF48403; 3. DR PROSITE; PS50297; ANK_REP_REGION; 1. DR PROSITE; PS50088; ANK_REPEAT; 21. DR PROSITE; PS50017; DEATH_DOMAIN; 1. DR PROSITE; PS51145; ZU5; 2. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ANK repeat; Autism spectrum disorder; KW Cell junction; Cell membrane; Cell projection; Cytoplasm; Cytoskeleton; KW Golgi apparatus; Lysosome; Membrane; Mental retardation; Phosphoprotein; KW Postsynaptic cell membrane; Reference proteome; Repeat; Synapse. FT CHAIN 1..4377 FT /note="Ankyrin-3" FT /id="PRO_0000066886" FT REPEAT 73..102 FT /note="ANK 1" FT REPEAT 106..135 FT /note="ANK 2" FT REPEAT 139..168 FT /note="ANK 3" FT REPEAT 172..201 FT /note="ANK 4" FT REPEAT 203..230 FT /note="ANK 5" FT REPEAT 234..263 FT /note="ANK 6" FT REPEAT 267..296 FT /note="ANK 7" FT REPEAT 300..329 FT /note="ANK 8" FT REPEAT 333..362 FT /note="ANK 9" FT REPEAT 366..395 FT /note="ANK 10" FT REPEAT 399..428 FT /note="ANK 11" FT REPEAT 432..461 FT /note="ANK 12" FT REPEAT 465..494 FT /note="ANK 13" FT REPEAT 498..527 FT /note="ANK 14" FT REPEAT 531..560 FT /note="ANK 15" FT REPEAT 564..593 FT /note="ANK 16" FT REPEAT 597..626 FT /note="ANK 17" FT REPEAT 630..659 FT /note="ANK 18" FT REPEAT 663..692 FT /note="ANK 19" FT REPEAT 696..725 FT /note="ANK 20" FT REPEAT 729..758 FT /note="ANK 21" FT REPEAT 762..791 FT /note="ANK 22" FT REPEAT 795..825 FT /note="ANK 23" FT DOMAIN 984..1139 FT /note="ZU5 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00485" FT DOMAIN 1141..1288 FT /note="ZU5 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00485" FT DOMAIN 4090..4174 FT /note="Death" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00064" FT REGION 1273..1407 FT /note="UPA domain" FT /evidence="ECO:0000250" FT COMPBIAS 1519..1898 FT /note="Ser-rich" FT COMPBIAS 2247..2250 FT /note="Poly-Thr" FT COMPBIAS 2393..2396 FT /note="Poly-Glu" FT COMPBIAS 3205..3211 FT /note="Poly-Glu" FT COMPBIAS 3255..3259 FT /note="Poly-Pro" FT COMPBIAS 3482..3487 FT /note="Poly-Ser" FT COMPBIAS 3785..3791 FT /note="Poly-Asn" FT COMPBIAS 3957..3981 FT /note="Thr-rich" FT MOD_RES 39 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:21406692" FT MOD_RES 623 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O70511" FT MOD_RES 847 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:21406692" FT MOD_RES 861 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O70511" FT MOD_RES 867 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:G5E8K5" FT MOD_RES 913 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O70511" FT MOD_RES 916 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O70511" FT MOD_RES 922 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:G5E8K5" FT MOD_RES 957 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O70511" FT MOD_RES 959 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O70511" FT MOD_RES 1113 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:G5E8K5" FT MOD_RES 1445 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:21406692" FT MOD_RES 1459 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:23186163" FT MOD_RES 1470 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:G5E8K5" FT MOD_RES 1622 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:G5E8K5" FT MOD_RES 1625 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:G5E8K5" FT MOD_RES 1984 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O70511" FT MOD_RES 2111 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O70511" FT MOD_RES 2123 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O70511" FT MOD_RES 2126 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O70511" FT MOD_RES 4211 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:G5E8K5" FT MOD_RES 4229 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:24275569" FT MOD_RES 4290 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:24275569" FT MOD_RES 4298 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:21406692, FT ECO:0000244|PubMed:23186163, ECO:0000244|PubMed:24275569" FT MOD_RES 4350 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:23186163" FT VAR_SEQ 1..866 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:11230166" FT /id="VSP_046885" FT VAR_SEQ 1..37 FT /note="MAHAASQLKKNRDLEINAEEEPEKKRKHRKRSRDRKK -> MASSASSSPAG FT TEDSAPAQGGFGSDYSRSSR (in isoform 3)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_044348" FT VAR_SEQ 1..36 FT /note="MAHAASQLKKNRDLEINAEEEPEKKRKHRKRSRDRK -> MSEEPKEKNAKP FT AHRKRKG (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_044349" FT VAR_SEQ 1..6 FT /note="MAHAAS -> MNLRCD (in isoform 5)" FT /evidence="ECO:0000303|PubMed:8666667" FT /id="VSP_053753" FT VAR_SEQ 7..385 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:8666667" FT /id="VSP_053754" FT VAR_SEQ 850..870 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:8666667" FT /id="VSP_053755" FT VAR_SEQ 867..872 FT /note="SDVEEG -> MALPQS (in isoform 4)" FT /evidence="ECO:0000303|PubMed:11230166" FT /id="VSP_046886" FT VAR_SEQ 872 FT /note="G -> GNRCTWYKIPKVQEFTVKS (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_044350" FT VAR_SEQ 913..918 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:8666667" FT /id="VSP_053756" FT VAR_SEQ 1036..1043 FT /note="MVEGEGLA -> HGERRGIS (in isoform 5)" FT /evidence="ECO:0000303|PubMed:8666667" FT /id="VSP_053757" FT VAR_SEQ 1442..1450 FT /note="Missing (in isoform 2, isoform 3, isoform 4 and FT isoform 5)" FT /evidence="ECO:0000303|PubMed:11230166, FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:17974005, FT ECO:0000303|PubMed:8666667" FT /id="VSP_044351" FT VAR_SEQ 1478..4081 FT /note="Missing (in isoform 2, isoform 3 and isoform 4)" FT /evidence="ECO:0000303|PubMed:11230166, FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:17974005" FT /id="VSP_044352" FT VAR_SEQ 1478..1880 FT /note="IERSTGATRSLPTTYSYKPFFSTRPYQSWTTAPITVPGPAKSGFTSLSSSSS FT NTPSASPLKSIWSVSTPSPIKSTLGASTTSSVKSISDVASPIRSFRTMSSPIKTVVSQS FT PYNIQVSSGTLARAPAVTEATPLKGLASNSTFSSRTSPVTTAGSLLERSSITMTPPASP FT KSNINMYSSSLPFKSIITSAAPLISSPLKSVVSPVKSAVDVISSAKITMASSLSSPVKQ FT MPGHAEVALVNGSISPLKYPSSSTLINGCKATATLQEKISSATNSVSSVVSAATDTVEK FT VFSTTTAMPFSPLRSYVSAAPSAFQSLRTPSASALYTSLGSSISATTSSVTSSIITVPV FT YSVVNVLPEPALKKLPDSNSFTKSAAALLSPIKTLTTETHPQPHFSRTSSPVKSSL -> FT TSCTVKVRKSQLKEVCKHSIEYFKGISGETLKLVDRLSEEEKKMQSELSDEEESTSRNT FT SLSETSRGGQPSVTTKSARDKKTEAAPLKSKSEKAGSEKRSSRRTGPQSPCERTDIRMA FT IVADHLGLSWTELARELNFSVDEINQIRVENPNSLISQSFMLLKKWVTRDGKNATTDAL FT TSVLTKINRIDIVTLLEGPIFDYGNISGTRSFADENNVFHDPVDGWQNETSSGNLESCA FT QARRVTGGLLDRLDDSPDQCRDSITSYLKGEAGKFEANGSHTEITPEAKTKSYFPESQN FT DVGKQSTKETLKPKIHGSGHVEEPASPLAAYQKSLEETSKLSKLIIEETKPCVPVSMKK FT MSRTSPADGKPRLSLHEEEGSSGSEQKQGEGFKVKTKKEIRHVEKKSHS (in FT isoform 5)" FT /evidence="ECO:0000303|PubMed:8666667" FT /id="VSP_053758" FT VAR_SEQ 1881..4377 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:8666667" FT /id="VSP_053759" FT VAR_SEQ 4082 FT /note="G -> S (in isoform 2, isoform 3 and isoform 4)" FT /evidence="ECO:0000303|PubMed:11230166, FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:17974005" FT /id="VSP_044353" FT VAR_SEQ 4199 FT /note="G -> GYPSLQVELETPTGLHYTPPTPFQQDDYFSDISSIESPLRTPSRLSD FT GLVPSQGNIEHSADGPPVVTAEDASLEDSKLEDSVPLTEMPEAVDVDESQLENVCLS FT (in isoform 2, isoform 3 and isoform 4)" FT /evidence="ECO:0000303|PubMed:11230166, FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:17974005" FT /id="VSP_044354" FT VARIANT 968 FT /note="D -> H (found in a patient with Gillessen-Kaesbach- FT Nishimura syndrome; unknown pathological significance; FT dbSNP:rs730882195)" FT /evidence="ECO:0000269|PubMed:25966638" FT /id="VAR_077912" FT VARIANT 1569 FT /note="S -> A (found in a patient with autism; unknown FT pathological significance; dbSNP:rs375050420)" FT /evidence="ECO:0000269|PubMed:22865819" FT /id="VAR_068702" FT VARIANT 2318 FT /note="K -> R (in dbSNP:rs59021407)" FT /id="VAR_061013" FT VARIANT 2885 FT /note="H -> Q (in dbSNP:rs11599164)" FT /id="VAR_059115" FT VARIANT 2996 FT /note="Q -> H (in dbSNP:rs41274672)" FT /id="VAR_061014" FT VARIANT 3117 FT /note="I -> V (in dbSNP:rs28932171)" FT /id="VAR_059116" FT VARIANT 3123 FT /note="K -> R (in dbSNP:rs10821668)" FT /id="VAR_059117" FT VARIANT 3720 FT /note="T -> M (found in a patient with autism; unknown FT pathological significance; dbSNP:rs201547988)" FT /evidence="ECO:0000269|PubMed:22865819" FT /id="VAR_068703" FT VARIANT 4255 FT /note="T -> P (found in a patient with autism; unknown FT pathological significance; dbSNP:rs769573528)" FT /evidence="ECO:0000269|PubMed:22865819" FT /id="VAR_068704" FT VARIANT 4257 FT /note="I -> V (in dbSNP:rs12261793)" FT /id="VAR_054333" FT CONFLICT 197 FT /note="T -> A (in Ref. 5; CAI56716)" FT /evidence="ECO:0000305" FT CONFLICT 222 FT /note="L -> P (in Ref. 5; CAD97900)" FT /evidence="ECO:0000305" FT CONFLICT 327 FT /note="I -> V (in Ref. 5; CAD97900)" FT /evidence="ECO:0000305" FT CONFLICT 338 FT /note="L -> W (in Ref. 4; BAG58523)" FT /evidence="ECO:0000305" FT CONFLICT 523 FT /note="A -> T (in Ref. 5; CAD97900)" FT /evidence="ECO:0000305" FT CONFLICT 578 FT /note="L -> P (in Ref. 5; CAI56716)" FT /evidence="ECO:0000305" FT CONFLICT 921 FT /note="R -> G (in Ref. 3; CAB66645)" FT /evidence="ECO:0000305" FT CONFLICT 977 FT /note="S -> P (in Ref. 3; CAB66645)" FT /evidence="ECO:0000305" FT CONFLICT 1237 FT /note="D -> G (in Ref. 5; CAI56716)" FT /evidence="ECO:0000305" FT CONFLICT 1418 FT /note="P -> R (in Ref. 1; AAA64834)" FT /evidence="ECO:0000305" FT CONFLICT 1455 FT /note="D -> E (in Ref. 4; BAG58523)" FT /evidence="ECO:0000305" FT CONFLICT 1574 FT /note="F -> L (in Ref. 1; AAA64834)" FT /evidence="ECO:0000305" FT CONFLICT 1685 FT /note="A -> R (in Ref. 1; AAA64834)" FT /evidence="ECO:0000305" FT CONFLICT 1726 FT /note="P -> A (in Ref. 1; AAA64834)" FT /evidence="ECO:0000305" FT CONFLICT 2062..2063 FT /note="ER -> GG (in Ref. 1; AAA64834)" FT /evidence="ECO:0000305" FT CONFLICT 2146 FT /note="S -> T (in Ref. 1; AAA64834)" FT /evidence="ECO:0000305" FT CONFLICT 3919 FT /note="H -> P (in Ref. 1; AAA64834)" FT /evidence="ECO:0000305" FT CONFLICT 4137 FT /note="L -> F (in Ref. 3; CAB66645)" FT /evidence="ECO:0000305" FT HELIX 4089..4101 FT /evidence="ECO:0000244|PDB:4O6X" FT HELIX 4102..4104 FT /evidence="ECO:0000244|PDB:4O6X" FT HELIX 4105..4111 FT /evidence="ECO:0000244|PDB:4O6X" FT HELIX 4116..4125 FT /evidence="ECO:0000244|PDB:4O6X" FT HELIX 4130..4145 FT /evidence="ECO:0000244|PDB:4O6X" FT HELIX 4146..4148 FT /evidence="ECO:0000244|PDB:4O6X" FT HELIX 4151..4160 FT /evidence="ECO:0000244|PDB:4O6X" FT HELIX 4164..4171 FT /evidence="ECO:0000244|PDB:4O6X" FT HELIX 4173..4178 FT /evidence="ECO:0000244|PDB:4O6X" FT MOD_RES Q12955-4:1632 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:24275569" FT MOD_RES Q12955-4:1658 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:24275569" FT MOD_RES Q12955-5:1625 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:24275569" FT MOD_RES Q12955-5:1651 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:24275569" FT MOD_RES Q12955-6:765 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:24275569" FT MOD_RES Q12955-6:791 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:24275569" FT MOD_RES Q12955-7:468 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:24275569" SQ SEQUENCE 4377 AA; 480410 MW; F6F9FABD09F15C13 CRC64; MAHAASQLKK NRDLEINAEE EPEKKRKHRK RSRDRKKKSD ANASYLRAAR AGHLEKALDY IKNGVDINIC NQNGLNALHL ASKEGHVEVV SELLQREANV DAATKKGNTA LHIASLAGQA EVVKVLVTNG ANVNAQSQNG FTPLYMAAQE NHLEVVKFLL DNGASQSLAT EDGFTPLAVA LQQGHDQVVS LLLENDTKGK VRLPALHIAA RKDDTKAAAL LLQNDNNADV ESKSGFTPLH IAAHYGNINV ATLLLNRAAA VDFTARNDIT PLHVASKRGN ANMVKLLLDR GAKIDAKTRD GLTPLHCGAR SGHEQVVEML LDRAAPILSK TKNGLSPLHM ATQGDHLNCV QLLLQHNVPV DDVTNDYLTA LHVAAHCGHY KVAKVLLDKK ANPNAKALNG FTPLHIACKK NRIKVMELLL KHGASIQAVT ESGLTPIHVA AFMGHVNIVS QLMHHGASPN TTNVRGETAL HMAARSGQAE VVRYLVQDGA QVEAKAKDDQ TPLHISARLG KADIVQQLLQ QGASPNAATT SGYTPLHLSA REGHEDVAAF LLDHGASLSI TTKKGFTPLH VAAKYGKLEV ANLLLQKSAS PDAAGKSGLT PLHVAAHYDN QKVALLLLDQ GASPHAAAKN GYTPLHIAAK KNQMDIATTL LEYGADANAV TRQGIASVHL AAQEGHVDMV SLLLGRNANV NLSNKSGLTP LHLAAQEDRV NVAEVLVNQG AHVDAQTKMG YTPLHVGCHY GNIKIVNFLL QHSAKVNAKT KNGYTPLHQA AQQGHTHIIN VLLQNNASPN ELTVNGNTAL GIARRLGYIS VVDTLKIVTE ETMTTTTVTE KHKMNVPETM NEVLDMSDDE VRKANAPEML SDGEYISDVE EGEDAMTGDT DKYLGPQDLK ELGDDSLPAE GYMGFSLGAR SASLRSFSSD RSYTLNRSSY ARDSMMIEEL LVPSKEQHLT FTREFDSDSL RHYSWAADTL DNVNLVSSPI HSGFLVSFMV DARGGSMRGS RHHGMRIIIP PRKCTAPTRI TCRLVKRHKL ANPPPMVEGE GLASRLVEMG PAGAQFLGPV IVEIPHFGSM RGKERELIVL RSENGETWKE HQFDSKNEDL TELLNGMDEE LDSPEELGKK RICRIITKDF PQYFAVVSRI KQESNQIGPE GGILSSTTVP LVQASFPEGA LTKRIRVGLQ AQPVPDEIVK KILGNKATFS PIVTVEPRRR KFHKPITMTI PVPPPSGEGV SNGYKGDTTP NLRLLCSITG GTSPAQWEDI TGTTPLTFIK DCVSFTTNVS ARFWLADCHQ VLETVGLATQ LYRELICVPY MAKFVVFAKM NDPVESSLRC FCMTDDKVDK TLEQQENFEE VARSKDIEVL EGKPIYVDCY GNLAPLTKGG QQLVFNFYSF KENRLPFSIK IRDTSQEPCG RLSFLKEPKT TKGLPQTAVC NLNITLPAHK KETESDQDDE IEKTDRRQSF ASLALRKRYS YLTEPGMIER STGATRSLPT TYSYKPFFST RPYQSWTTAP ITVPGPAKSG FTSLSSSSSN TPSASPLKSI WSVSTPSPIK STLGASTTSS VKSISDVASP IRSFRTMSSP IKTVVSQSPY NIQVSSGTLA RAPAVTEATP LKGLASNSTF SSRTSPVTTA GSLLERSSIT MTPPASPKSN INMYSSSLPF KSIITSAAPL ISSPLKSVVS PVKSAVDVIS SAKITMASSL SSPVKQMPGH AEVALVNGSI SPLKYPSSST LINGCKATAT LQEKISSATN SVSSVVSAAT DTVEKVFSTT TAMPFSPLRS YVSAAPSAFQ SLRTPSASAL YTSLGSSISA TTSSVTSSII TVPVYSVVNV LPEPALKKLP DSNSFTKSAA ALLSPIKTLT TETHPQPHFS RTSSPVKSSL FLAPSALKLS TPSSLSSSQE ILKDVAEMKE DLMRMTAILQ TDVPEEKPFQ PELPKEGRID DEEPFKIVEK VKEDLVKVSE ILKKDVCVDN KGSPKSPKSD KGHSPEDDWI EFSSEEIREA RQQAAASQSP SLPERVQVKA KAASEKDYNL TKVIDYLTND IGSSSLTNLK YKFEDAKKDG EERQKRVLKP AIALQEHKLK MPPASMRTST SEKELCKMAD SFFGTDTILE SPDDFSQHDQ DKSPLSDSGF ETRSEKTPSA PQSAESTGPK PLFHEVPIPP VITETRTEVV HVIRSYDPSA GDVPQTQPEE PVSPKPSPTF MELEPKPTTS SIKEKVKAFQ MKASSEEDDH NRVLSKGMRV KEETHITTTT RMVYHSPPGG EGASERIEET MSVHDIMKAF QSGRDPSKEL AGLFEHKSAV SPDVHKSAAE TSAQHAEKDN QMKPKLERII EVHIEKGNQA EPTEVIIRET KKHPEKEMYV YQKDLSRGDI NLKDFLPEKH DAFPCSEEQG QQEEEELTAE ESLPSYLESS RVNTPVSQEE DSRPSSAQLI SDDSYKTLKL LSQHSIEYHD DELSELRGES YRFAEKMLLS EKLDVSHSDT EESVTDHAGP PSSELQGSDK RSREKIATAP KKEILSKIYK DVSENGVGKV SKDEHFDKVT VLHYSGNVSS PKHAMWMRFT EDRLDRGREK LIYEDRVDRT VKEAEEKLTE VSQFFRDKTE KLNDELQSPE KKARPKNGKE YSSQSPTSSS PEKVLLTELL ASNDEWVKAR QHGPDGQGFP KAEEKAPSLP SSPEKMVLSQ QTEDSKSTVE AKGSISQSKA PDGPQSGFQL KQSKLSSIRL KFEQGTHAKS KDMSQEDRKS DGQSRIPVKK IQESKLPVYQ VFAREKQQKA IDLPDESVSV QKDFMVLKTK DEHAQSNEIV VNDSGSDNVK KQRTEMSSKA MPDSFSEQQA KDLACHITSD LATRGPWDKK VFRTWESSGA TNNKSQKEKL SHVLVHDVRE NHIGHPESKS VDQKNEFMSV TERERKLLTN GSLSEIKEMT VKSPSKKVLY REYVVKEGDH PGGLLDQPSR RSESSAVSHI PVRVADERRM LSSNIPDGFC EQSAFPKHEL SQKLSQSSMS KETVETQHFN SIEDEKVTYS EISKVSKHQS YVGLCPPLEE TETSPTKSPD SLEFSPGKES PSSDVFDHSP IDGLEKLAPL AQTEGGKEIK TLPVYVSFVQ VGKQYEKEIQ QGGVKKIISQ ECKTVQETRG TFYTTRQQKQ PPSPQGSPED DTLEQVSFLD SSGKSPLTPE TPSSEEVSYE FTSKTPDSLI AYIPGKPSPI PEVSEESEEE EQAKSTSLKQ TTVEETAVER EMPNDVSKDS NQRPKNNRVA YIEFPPPPPL DADQIESDKK HHYLPEKEVD MIEVNLQDEH DKYQLAEPVI RVQPPSPVPP GADVSDSSDD ESIYQPVPVK KYTFKLKEVD DEQKEKPKAS AEKASNQKEL ESNGSGKDNE FGLGLDSPQN EIAQNGNNDQ SITECSIATT AEFSHDTDAT EIDSLDGYDL QDEDDGLTES DSKLPIQAME IKKDIWNTEG ILKPADRSFS QSKLEVIEEE GKVGPDEDKP PSKSSSSEKT PDKTDQKSGA QFFTLEGRHP DRSVFPDTYF SYKVDEEFAT PFKTVATKGL DFDPWSNNRG DDEVFDSKSR EDETKPFGLA VEDRSPATTP DTTPARTPTD ESTPTSEPNP FPFHEGKMFE MTRSGAIDMS KRDFVEERLQ FFQIGEHTSE GKSGDQGEGD KSMVTATPQP QSGDTTVETN LERNVETPTV EPNPSIPTSG ECQEGTSSSG SLEKSAAATN TSKVDPKLRT PIKMGISAST MTMKKEGPGE ITDKIEAVMT SCQGLENETI TMISNTANSQ MGVRPHEKHD FQKDNFNNNN NLDSSTIQTD NIMSNIVLTE HSAPTCTTEK DNPVKVSSGK KTGVLQGHCV RDKQKVLGEQ QKTKELIGIR QKSKLPIKAT SPKDTFPPNH MSNTKASKMK QVSQSEKTKA LTTSSCVDVK SRIPVKNTHR DNIIAVRKAC ATQKQGQPEK GKAKQLPSKL PVKVRSTCVT TTTTTATTTT TTTTTTTTSC TVKVRKSQLK EVCKHSIEYF KGISGETLKL VDRLSEEEKK MQSELSDEEE STSRNTSLSE TSRGGQPSVT TKSARDKKTE AAPLKSKSEK AGSEKRSSRR TGPQSPCERT DIRMAIVADH LGLSWTELAR ELNFSVDEIN QIRVENPNSL ISQSFMLLKK WVTRDGKNAT TDALTSVLTK INRIDIVTLL EGPIFDYGNI SGTRSFADEN NVFHDPVDGW QNETSSGNLE SCAQARRVTG GLLDRLDDSP DQCRDSITSY LKGEAGKFEA NGSHTEITPE AKTKSYFPES QNDVGKQSTK ETLKPKIHGS GHVEEPASPL AAYQKSLEET SKLIIEETKP CVPVSMKKMS RTSPADGKPR LSLHEEEGSS GSEQKQGEGF KVKTKKEIRH VEKKSHS //