ID ANKL2_DROME Reviewed; 1174 AA. AC Q8MQX9; Q0KHR1; Q9VX44; X2JCC5; DT 17-JUN-2020, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2002, sequence version 1. DT 24-JAN-2024, entry version 154. DE RecName: Full=Ankyrin repeat and LEM domain-containing protein 2 homolog {ECO:0000312|FlyBase:FBgn0028343}; GN Name=Ankle2 {ECO:0000312|FlyBase:FBgn0028343}; GN Synonyms=l(1)G0222 {ECO:0000312|FlyBase:FBgn0028343}, GN l(1)G0316 {ECO:0000312|FlyBase:FBgn0028343}; GN ORFNames=CG8465 {ECO:0000312|FlyBase:FBgn0028343}; OS Drosophila melanogaster (Fruit fly). OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota; OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea; OC Drosophilidae; Drosophila; Sophophora. OX NCBI_TaxID=7227 {ECO:0000312|Proteomes:UP000000803}; RN [1] {ECO:0000312|Proteomes:UP000000803} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803}; RX PubMed=10731132; DOI=10.1126/science.287.5461.2185; RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C., RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., RA Venter J.C.; RT "The genome sequence of Drosophila melanogaster."; RL Science 287:2185-2195(2000). RN [2] {ECO:0000312|Proteomes:UP000000803} RP GENOME REANNOTATION. RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803}; RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083; RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A., RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.; RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic RT review."; RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002). RN [3] {ECO:0000312|EMBL:AAM52753.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM D). RC TISSUE=Embryo {ECO:0000312|EMBL:AAM52753.1}; RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080; RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A., RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M., RA Celniker S.E.; RT "A Drosophila full-length cDNA resource."; RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002). RN [4] {ECO:0000305} RP FUNCTION, AND MUTAGENESIS OF LEU-326. RX PubMed=25259927; DOI=10.1016/j.cell.2014.09.002; RA Yamamoto S., Jaiswal M., Charng W.L., Gambin T., Karaca E., Mirzaa G., RA Wiszniewski W., Sandoval H., Haelterman N.A., Xiong B., Zhang K., Bayat V., RA David G., Li T., Chen K., Gala U., Harel T., Pehlivan D., Penney S., RA Vissers L.E., de Ligt J., Jhangiani S.N., Xie Y., Tsang S.H., Parman Y., RA Sivaci M., Battaloglu E., Muzny D., Wan Y.W., Liu Z., Lin-Moore A.T., RA Clark R.D., Curry C.J., Link N., Schulze K.L., Boerwinkle E., Dobyns W.B., RA Allikmets R., Gibbs R.A., Chen R., Lupski J.R., Wangler M.F., Bellen H.J.; RT "A drosophila genetic resource of mutants to study mechanisms underlying RT human genetic diseases."; RL Cell 159:200-214(2014). RN [5] {ECO:0000305} RP FUNCTION, AND MUTAGENESIS OF LEU-326. RX PubMed=30550790; DOI=10.1016/j.cell.2018.11.028; RA Shah P.S., Link N., Jang G.M., Sharp P.P., Zhu T., Swaney D.L., RA Johnson J.R., Von Dollen J., Ramage H.R., Satkamp L., Newton B., RA Huettenhain R., Petit M.J., Baum T., Everitt A., Laufman O., Tassetto M., RA Shales M., Stevenson E., Iglesias G.N., Shokat L., Tripathi S., RA Balasubramaniam V., Webb L.G., Aguirre S., Willsey A.J., Garcia-Sastre A., RA Pollard K.S., Cherry S., Gamarnik A.V., Marazzi I., Taunton J., RA Fernandez-Sesma A., Bellen H.J., Andino R., Krogan N.J.; RT "Comparative Flavivirus-Host Protein Interaction Mapping Reveals Mechanisms RT of Dengue and Zika Virus Pathogenesis."; RL Cell 175:1931-1945(2018). RN [6] {ECO:0000305} RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND DISRUPTION RP PHENOTYPE. RX PubMed=31735666; DOI=10.1016/j.devcel.2019.10.009; RA Link N., Chung H., Jolly A., Withers M., Tepe B., Arenkiel B.R., Shah P.S., RA Krogan N.J., Aydin H., Geckinli B.B., Tos T., Isikay S., Tuysuz B., RA Mochida G.H., Thomas A.X., Clark R.D., Mirzaa G.M., Lupski J.R., RA Bellen H.J.; RT "Mutations in ANKLE2, a ZIKA Virus Target, Disrupt an Asymmetric Cell RT Division Pathway in Drosophila Neuroblasts to Cause Microcephaly."; RL Dev. Cell 51:713-729.e6(2019). CC -!- FUNCTION: Involved in brain development probably by regulating CC asymmetric division of neuroblasts (PubMed:31735666, PubMed:30550790, CC PubMed:25259927). Regulates neuroblast asymmetric cell division by CC controlling asymmetric protein localization of Mira, Baz, Par-6 and CC aPKC, and spindle alignment (PubMed:31735666). Also, regulates the CC localization of kinase Ball during mitosis, specifically maintaining CC Ball in the nucleus during interphase (PubMed:31735666). Required for CC proper ER and nuclear envelope morphology in neuroblasts CC (PubMed:31735666). {ECO:0000269|PubMed:25259927, CC ECO:0000269|PubMed:30550790, ECO:0000269|PubMed:31735666}. CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum CC {ECO:0000269|PubMed:31735666}. Nucleus envelope CC {ECO:0000269|PubMed:31735666}. Cytoplasm {ECO:0000269|PubMed:31735666}. CC Note=In neuroblasts, recruited to the nuclear envelope at the CC initiation of mitosis and remains associated with it until the CC beginning of cytokinesis. {ECO:0000269|PubMed:31735666}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=D {ECO:0000312|FlyBase:FBgn0028343}; Synonyms=E CC {ECO:0000312|FlyBase:FBgn0028343}; CC IsoId=Q8MQX9-1; Sequence=Displayed; CC Name=F {ECO:0000312|FlyBase:FBgn0028343}; CC IsoId=Q8MQX9-2; Sequence=VSP_060611; CC Name=G {ECO:0000312|FlyBase:FBgn0028343}; CC IsoId=Q8MQX9-3; Sequence=VSP_060612; CC -!- DEVELOPMENTAL STAGE: Expressed in embryo, wing disk and eye disk. CC Broadly expressed in 3rd instar larval brain, including neuroblasts, CC ganglion mother cells, and neurons. {ECO:0000269|PubMed:31735666}. CC -!- DISRUPTION PHENOTYPE: Animals die as third instar larvae, are smaller CC than wild-type and show very severely reduced brain volume CC (PubMed:31735666). Complete disruption of brain morphology, especially CC the optic lobe, in 3rd instar larvae (PubMed:31735666). CC {ECO:0000269|PubMed:31735666}. CC -!- SIMILARITY: Belongs to the ANKLE2 family. {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; AE014298; AAF48735.2; -; Genomic_DNA. DR EMBL; AE014298; AAF48736.2; -; Genomic_DNA. DR EMBL; AE014298; AAF48737.2; -; Genomic_DNA. DR EMBL; AE014298; AHN59845.1; -; Genomic_DNA. DR EMBL; AY122241; AAM52753.1; -; mRNA. DR RefSeq; NP_001285375.1; NM_001298446.1. [Q8MQX9-3] DR RefSeq; NP_573221.2; NM_132993.3. [Q8MQX9-1] DR RefSeq; NP_728082.2; NM_167569.2. [Q8MQX9-1] DR RefSeq; NP_728083.2; NM_167570.2. [Q8MQX9-2] DR AlphaFoldDB; Q8MQX9; -. DR SMR; Q8MQX9; -. DR IntAct; Q8MQX9; 1. DR STRING; 7227.FBpp0290628; -. DR PaxDb; 7227-FBpp0290627; -. DR DNASU; 32732; -. DR EnsemblMetazoa; FBtr0301413; FBpp0290627; FBgn0028343. [Q8MQX9-1] DR EnsemblMetazoa; FBtr0301414; FBpp0290628; FBgn0028343. [Q8MQX9-1] DR EnsemblMetazoa; FBtr0301415; FBpp0290629; FBgn0028343. [Q8MQX9-2] DR EnsemblMetazoa; FBtr0340625; FBpp0309489; FBgn0028343. [Q8MQX9-3] DR GeneID; 32732; -. DR KEGG; dme:Dmel_CG8465; -. DR UCSC; CG8465-RA; d. melanogaster. DR UCSC; CG8465-RC; d. melanogaster. DR AGR; FB:FBgn0028343; -. DR CTD; 23141; -. DR FlyBase; FBgn0028343; Ankle2. DR VEuPathDB; VectorBase:FBgn0028343; -. DR eggNOG; ENOG502QQ4Z; Eukaryota. DR GeneTree; ENSGT00390000016767; -. DR HOGENOM; CLU_277464_0_0_1; -. DR InParanoid; Q8MQX9; -. DR OMA; VWENPRF; -. DR OrthoDB; 5402020at2759; -. DR PhylomeDB; Q8MQX9; -. DR Reactome; R-DME-2995383; Initiation of Nuclear Envelope (NE) Reformation. DR BioGRID-ORCS; 32732; 1 hit in 1 CRISPR screen. DR GenomeRNAi; 32732; -. DR PRO; PR:Q8MQX9; -. DR Proteomes; UP000000803; Chromosome X. DR Bgee; FBgn0028343; Expressed in egg cell and 26 other cell types or tissues. DR ExpressionAtlas; Q8MQX9; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0012505; C:endomembrane system; HDA:FlyBase. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0005635; C:nuclear envelope; IDA:UniProtKB. DR GO; GO:0051721; F:protein phosphatase 2A binding; IBA:GO_Central. DR GO; GO:0055059; P:asymmetric neuroblast division; IMP:UniProtKB. DR GO; GO:0045167; P:asymmetric protein localization involved in cell fate determination; IMP:UniProtKB. DR GO; GO:0000902; P:cell morphogenesis; IMP:FlyBase. DR GO; GO:0007029; P:endoplasmic reticulum organization; IMP:UniProtKB. DR GO; GO:0042326; P:negative regulation of phosphorylation; IBA:GO_Central. DR GO; GO:0031468; P:nuclear membrane reassembly; IMP:UniProtKB. DR GO; GO:0035307; P:positive regulation of protein dephosphorylation; IBA:GO_Central. DR GO; GO:0051653; P:spindle localization; IMP:UniProtKB. DR Gene3D; 1.25.40.20; Ankyrin repeat-containing domain; 1. DR InterPro; IPR002110; Ankyrin_rpt. DR InterPro; IPR036770; Ankyrin_rpt-contain_sf. DR PANTHER; PTHR12349; ANKYRIN REPEAT AND LEM DOMAIN-CONTAINING PROTEIN 2; 1. DR PANTHER; PTHR12349:SF4; ANKYRIN REPEAT AND LEM DOMAIN-CONTAINING PROTEIN 2; 1. DR Pfam; PF00023; Ank; 1. DR SMART; SM00248; ANK; 2. DR SUPFAM; SSF48403; Ankyrin repeat; 1. DR PROSITE; PS50297; ANK_REP_REGION; 1. DR PROSITE; PS50088; ANK_REPEAT; 1. PE 1: Evidence at protein level; KW Alternative splicing; ANK repeat; Cell cycle; Cell division; Cytoplasm; KW Endoplasmic reticulum; Neurogenesis; Nucleus; Reference proteome. FT CHAIN 1..1174 FT /note="Ankyrin repeat and LEM domain-containing protein 2 FT homolog" FT /id="PRO_0000450384" FT REPEAT 338..367 FT /note="ANK" FT /evidence="ECO:0000255" FT REGION 37..74 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 141..230 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 519..543 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 961..981 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 37..65 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 144..221 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 521..543 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 961..979 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT VAR_SEQ 2..78 FT /note="STYFGVYIPTSKAGCFEGSVSQCIGSIAAVNIKPSNPASGSASVASGSPSGS FT AASVQTGNADDGSAATKYEDPDYPP -> PTHQHCHRHDGAA (in isoform F)" FT /evidence="ECO:0000305" FT /id="VSP_060611" FT VAR_SEQ 1040..1044 FT /note="Missing (in isoform G)" FT /evidence="ECO:0000305" FT /id="VSP_060612" FT MUTAGEN 326 FT /note="L->H: Pupal lethality at temperatures above 22 FT degrees Celsius. Larvae initially have normal brain sizes, FT but later in the third larval stage, the brain is smaller FT than in wild-type counterparts." FT /evidence="ECO:0000269|PubMed:25259927, FT ECO:0000269|PubMed:30550790" SQ SEQUENCE 1174 AA; 129082 MW; DF2A7F18FF7BD44C CRC64; MSTYFGVYIP TSKAGCFEGS VSQCIGSIAA VNIKPSNPAS GSASVASGSP SGSAASVQTG NADDGSAATK YEDPDYPPDS PLWLIFTEKS KALDILRHYK EARLREFPNL EQAESYVQFG FESIEALKRF CKAKPESKPI PIISGSGYKS SPTSTDNSCS SSPTGNGSGF IIPLGSNSSM SNLLLSDSPT SSPSSSSNVI ANGRQQQMQQ QQQQQPQQPD VSGEGPPFRA PTKQELVEFR KQIEGGHIDR VKRIIWENPR FLISSGDTPT SLKEGCRYNA MHICAQVNKA RIAQLLLKTI SDREFTQLYV GKKGSGKMCA ALNISLLDYY LNMPDKGRGE TPLHFAAKNG HVAMVEVLVS YPECKSLRNH EGKEPKEIIC LRNANATHVT IKKLELLLYD PHFVPVLRSQ SNTLPPKVGQ PFSPKDPPNL QHKADDYEGL SVDLAISALA GPMSREKAMN FYRRWKTPPR VSNNVMSPLA GSPFSSPVKV TPSKSIFDRS AGNSSPVHSG RRVLFSPLAE ATSSPKPTKN VPNGTNECEH NNNNVKPVYP LEFPATPIRK MKPDLFMAYR NNNSFDSPSL ADDSQILDMS LSRSLNASLN DSFRERHIKN TDIEKGLEVV GRQLARQEQL EWREYWDFLD SFLDIGTTEG LARLEAYFLE KTEQQADKSE TVWNFAHLHQ YFDSMAGEQQ QQLRKDKNEA AGATSPSAGV MTPYTCVEKS LQVFAKRITK TLINKIGNMV SINDTLLCEL KRLKSLIVSF KDDARFISVD FSKVHSRIAH LVASYVTHSQ EVSVAMRLQL LQMLRSLRQL LADERGREQH LGCVCASLLL MLEQAPTSAV HLPDTLKTEE LCCAAWETEQ CCACLWDANL SRKTSRRKRT KSLRAAAVVQ SQGQLQDTSG STGSSALHAS LGVGSTSLGA SRVVASASKD AWRRQQSDDE DYDSDEQVIF FDCTNVTLPY GSSSEDEENF RTPPQSLSPG ISMDLEPRYE LFIFGNEPTK RDLDVLNALS NVDIDKETLP HVYAWKTAME SYSCAEMNLF PSPRNVKVQK PEPWYSGTSS SHNSQPLLHP KRLLATPKLN AVVSGRRGSG PLTAPVTPRL ARTPSAASIQ VASETNGESV GTAVTPASPI LSFAALTAAT QSFQTPLNKV RGLFSQYRDQ RSYNEGDTPL GNRN //