ANKL2_DROME
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 03-AUG-2022, entry version 149.
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}.
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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.FBpp0290627; -.
DR PaxDb; Q8MQX9; -.
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 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; PHVHAWK; -.
DR OrthoDB; 567264at2759; -.
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 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; -; 1.
DR InterPro; IPR035007; ANKLE2.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR PANTHER; PTHR12349:SF4; PTHR12349:SF4; 1.
DR Pfam; PF13637; Ank_4; 1.
DR SMART; SM00248; ANK; 2.
DR SUPFAM; SSF48403; SSF48403; 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
