HAKAI_DROME
ID HAKAI_DROME Reviewed; 473 AA.
AC M9PBE2; Q86NQ9; Q8INV9; Q8INW0; Q95RE3; Q9VIT1;
DT 20-JUN-2018, integrated into UniProtKB/Swiss-Prot.
DT 26-JUN-2013, sequence version 1.
DT 03-AUG-2022, entry version 66.
DE RecName: Full=E3 ubiquitin-protein ligase Hakai {ECO:0000305};
DE EC=2.3.2.27 {ECO:0000250|UniProtKB:Q9JIY2};
GN Name=Hakai {ECO:0000312|FlyBase:FBgn0032812};
GN ORFNames=CG10263 {ECO:0000312|FlyBase:FBgn0032812};
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;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
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]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
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]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RC STRAIN=Berkeley; TISSUE=Embryo;
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]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM C).
RC STRAIN=Berkeley; TISSUE=Embryo;
RA Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J., Champe M.,
RA Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E., George R.,
RA Gonzalez M., Guarin H., Kronmiller B., Li P., Liao G., Miranda A.,
RA Mungall C.J., Nunoo J., Pacleb J., Paragas V., Park S., Patel S.,
RA Phouanenavong S., Wan K., Yu C., Lewis S.E., Rubin G.M., Celniker S.;
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, PATHWAY, INTERACTION WITH SHG, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=19682089; DOI=10.1111/j.1365-2443.2009.01335.x;
RA Kaido M., Wada H., Shindo M., Hayashi S.;
RT "Essential requirement for RING finger E3 ubiquitin ligase Hakai in early
RT embryonic development of Drosophila.";
RL Genes Cells 14:1067-1077(2009).
RN [6]
RP FUNCTION, AND IDENTIFICATION IN THE WMM COMPLEX.
RX PubMed=29535189; DOI=10.1101/gad.309146.117;
RA Knuckles P., Lence T., Haussmann I.U., Jacob D., Kreim N., Carl S.H.,
RA Masiello I., Hares T., Villasenor R., Hess D., Andrade-Navarro M.A.,
RA Biggiogera M., Helm M., Soller M., Buehler M., Roignant J.Y.;
RT "Zc3h13/Flacc is required for adenosine methylation by bridging the mRNA-
RT binding factor Rbm15/Spenito to the m6A machinery component Wtap/Fl(2)d.";
RL Genes Dev. 32:415-429(2018).
CC -!- FUNCTION: E3 ubiquitin-protein ligase required during early development
CC (PubMed:19682089). E3 ubiquitin-protein ligases mediate ubiquitination
CC of target proteins (PubMed:19682089). Required for epithelial integrity
CC and midgut morphogenesis (PubMed:19682089). Associated component of the
CC WMM complex, a complex that mediates N6-methyladenosine (m6A)
CC methylation of RNAs, a modification that plays a role in the efficiency
CC of mRNA splicing and RNA processing (PubMed:29535189). Its function in
CC the WMM complex is unknown (PubMed:29535189).
CC {ECO:0000250|UniProtKB:Q75N03, ECO:0000250|UniProtKB:Q9JIY2,
CC ECO:0000269|PubMed:19682089, ECO:0000305|PubMed:29535189}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000250|UniProtKB:Q9JIY2};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:19682089}.
CC -!- SUBUNIT: Component of the WMM complex, a N6-methyltransferase complex
CC composed of a catalytic subcomplex, named MAC, and of an associated
CC subcomplex, named MACOM (PubMed:29535189). The MAC subcomplex is
CC composed of Ime4/Mettl3 and Mettl14 (PubMed:29535189). The MACOM
CC subcomplex is composed of fl(2)d, Flacc/Xio, Hakai, vir, and, in some
CC cases of nito (PubMed:29535189). Interacts with shg/DE-cadherin
CC (PubMed:19682089). {ECO:0000269|PubMed:19682089,
CC ECO:0000269|PubMed:29535189}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. Cell membrane
CC {ECO:0000305|PubMed:19682089}. Cytoplasmic vesicle
CC {ECO:0000305|PubMed:19682089}. Cytoplasm, perinuclear region
CC {ECO:0000305|PubMed:19682089}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=F;
CC IsoId=M9PBE2-1; Sequence=Displayed;
CC Name=E;
CC IsoId=M9PBE2-2; Sequence=VSP_059629;
CC Name=C;
CC IsoId=M9PBE2-3; Sequence=VSP_059630, VSP_059631;
CC Name=A;
CC IsoId=M9PBE2-4; Sequence=VSP_059629, VSP_059630, VSP_059631;
CC -!- DEVELOPMENTAL STAGE: High levels of maternal transcripts in blastoderm
CC stage embryos are observed. {ECO:0000269|PubMed:19682089}.
CC -!- DISRUPTION PHENOTYPE: Lethality during larval stages. Maternal mutants
CC show a variety of defects in epithelial integrity, including stochastic
CC loss of shg/DE-cadherin expression, as well as defects in cell
CC specification and cell migration. {ECO:0000269|PubMed:19682089}.
CC -!- SIMILARITY: Belongs to the Hakai family. {ECO:0000305}.
CC -!- CAUTION: The subcellular locations reported need confirmation
CC (PubMed:19682089). Components of the WMM complex are known to localize
CC in the nucleus, and it is also the case for the CBLL1/HAKAI protein in
CC vertebrates. It is therefore likely that this protein mainly localizes
CC in the nucleus. {ECO:0000269|PubMed:19682089, ECO:0000305}.
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DR EMBL; AE014134; AAF53834.2; -; Genomic_DNA.
DR EMBL; AE014134; AAN11054.3; -; Genomic_DNA.
DR EMBL; AE014134; AAN11055.1; -; Genomic_DNA.
DR EMBL; AE014134; AGB93128.1; -; Genomic_DNA.
DR EMBL; AY061441; AAL28989.1; -; mRNA.
DR EMBL; BT003776; AAO41457.1; -; mRNA.
DR RefSeq; NP_001260593.1; NM_001273664.1. [M9PBE2-1]
DR RefSeq; NP_609993.1; NM_136149.3. [M9PBE2-4]
DR RefSeq; NP_724217.1; NM_165312.2. [M9PBE2-3]
DR RefSeq; NP_788075.2; NM_176061.3. [M9PBE2-2]
DR AlphaFoldDB; M9PBE2; -.
DR SMR; M9PBE2; -.
DR DIP; DIP-17106N; -.
DR IntAct; M9PBE2; 6.
DR STRING; 7227.FBpp0303688; -.
DR PaxDb; M9PBE2; -.
DR DNASU; 35256; -.
DR EnsemblMetazoa; FBtr0081263; FBpp0080804; FBgn0032812. [M9PBE2-4]
DR EnsemblMetazoa; FBtr0081264; FBpp0080805; FBgn0032812. [M9PBE2-3]
DR EnsemblMetazoa; FBtr0331245; FBpp0303687; FBgn0032812. [M9PBE2-2]
DR EnsemblMetazoa; FBtr0331246; FBpp0303688; FBgn0032812. [M9PBE2-1]
DR GeneID; 35256; -.
DR KEGG; dme:Dmel_CG10263; -.
DR UCSC; CG10263-RA; d. melanogaster.
DR CTD; 35256; -.
DR FlyBase; FBgn0032812; Hakai.
DR VEuPathDB; VectorBase:FBgn0032812; -.
DR eggNOG; KOG2932; Eukaryota.
DR GeneTree; ENSGT00510000047522; -.
DR HOGENOM; CLU_674894_0_0_1; -.
DR OMA; MESDISQ; -.
DR OrthoDB; 847454at2759; -.
DR Reactome; R-DME-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; M9PBE2; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 35256; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 35256; -.
DR PRO; PR:M9PBE2; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0032812; Expressed in secondary oocyte and 23 other tissues.
DR ExpressionAtlas; M9PBE2; baseline and differential.
DR Genevisible; Q8INW0; DM.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:FlyBase.
DR GO; GO:0005829; C:cytosol; IDA:FlyBase.
DR GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:FlyBase.
DR GO; GO:0005886; C:plasma membrane; IDA:FlyBase.
DR GO; GO:0036396; C:RNA N6-methyladenosine methyltransferase complex; IDA:UniProtKB.
DR GO; GO:0045296; F:cadherin binding; IPI:FlyBase.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:FlyBase.
DR GO; GO:0008270; F:zinc ion binding; ISM:FlyBase.
DR GO; GO:0007015; P:actin filament organization; IMP:FlyBase.
DR GO; GO:0040003; P:chitin-based cuticle development; IMP:FlyBase.
DR GO; GO:0007391; P:dorsal closure; IMP:FlyBase.
DR GO; GO:0007427; P:epithelial cell migration, open tracheal system; IMP:FlyBase.
DR GO; GO:0060429; P:epithelium development; IMP:FlyBase.
DR GO; GO:0030237; P:female sex determination; IMP:FlyBase.
DR GO; GO:0008258; P:head involution; IMP:FlyBase.
DR GO; GO:0007494; P:midgut development; IMP:FlyBase.
DR GO; GO:0080009; P:mRNA methylation; IMP:FlyBase.
DR GO; GO:0016567; P:protein ubiquitination; IDA:FlyBase.
DR GO; GO:0000381; P:regulation of alternative mRNA splicing, via spliceosome; IMP:FlyBase.
DR GO; GO:0030155; P:regulation of cell adhesion; IBA:GO_Central.
DR GO; GO:0035282; P:segmentation; IMP:FlyBase.
DR CDD; cd16508; RING-HC_HAKAI_like; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR040380; HAKAI-like_RING-HC.
DR InterPro; IPR040383; HAKAI/CBLL2.
DR InterPro; IPR041042; Znf_Hakai.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR PANTHER; PTHR13480; PTHR13480; 1.
DR Pfam; PF18408; zf_Hakai; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cytoplasm; Cytoplasmic vesicle;
KW Developmental protein; Membrane; Metal-binding; Nucleus;
KW Reference proteome; Transferase; Ubl conjugation pathway; Zinc;
KW Zinc-finger.
FT CHAIN 1..473
FT /note="E3 ubiquitin-protein ligase Hakai"
FT /id="PRO_0000444614"
FT ZN_FING 180..217
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 1..37
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 417..473
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 12..27
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 456..473
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 122..131
FT /note="TISLSLARAV -> I (in isoform E and isoform A)"
FT /id="VSP_059629"
FT VAR_SEQ 305..311
FT /note="LSESSVP -> ASGSYGS (in isoform C and isoform A)"
FT /id="VSP_059630"
FT VAR_SEQ 312..473
FT /note="Missing (in isoform C and isoform A)"
FT /id="VSP_059631"
FT CONFLICT 27
FT /note="R -> H (in Ref. 4; AAO41457)"
FT /evidence="ECO:0000305"
FT CONFLICT 85
FT /note="P -> S (in Ref. 4; AAO41457)"
FT /evidence="ECO:0000305"
FT CONFLICT 234
FT /note="C -> S (in Ref. 4; AAO41457)"
FT /evidence="ECO:0000305"
FT CONFLICT 243
FT /note="S -> R (in Ref. 4; AAO41457)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 473 AA; 49261 MW; DE68D6E39E2DC120 CRC64;
MDTEEVKRGR GRGRGTRARG RGRGRGRGRG KKIDDSSIAD AAALAASSCA ALEDSPGRLD
ASEDSVMQEL DKDGELETPG ALEEPLPHGA LGAVAASGNM TPATQQPQVL QQVPPPVMSQ
TTISLSLARA VDMEADISQL EAPTFTTLSR GPPEPMLRLK WNHKVSLIGE KVLNPMIHCC
DQCDKPILVY GRMIPCKHVF CLKCARAEPI KSCPRCTDKV LRVEQSGLGT VFMCTHGGSR
YGSSGCRRTY LSQRDLQAHI NHRHVAPQPP PLQPQPQLSA MAEQPKMTDL GGVGLGLELH
KQRKLSESSV PISVSASIAS RPVLSRLPLT GGVGNIGSIG SIPPPGSAAA AQNAIHGGHS
TLTLANLTRI NNANAQECHQ GKASLHHTLK KGTPHQSESV ADASYYSSVL ASFGSAAGNP
GSGPPGGGAT AAAQPANPSG SHSAVGPGAL IGGSTDAPTG GSSGNWQQSQ YYR
