HIW_DROME
ID HIW_DROME Reviewed; 5233 AA.
AC Q9NB71; Q8MZ36; Q9VXZ5;
DT 21-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 21-JUN-2005, sequence version 2.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=E3 ubiquitin-protein ligase highwire {ECO:0000303|PubMed:10839352};
DE EC=2.3.2.33 {ECO:0000250|UniProtKB:O75592};
DE AltName: Full=Protein pam/highwire/rpm-1;
GN Name=hiw {ECO:0000303|PubMed:10839352, ECO:0000312|FlyBase:FBgn0030600};
GN ORFNames=CG32592;
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] {ECO:0000305, ECO:0000312|EMBL:AAF76150.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND DISRUPTION PHENOTYPE.
RC STRAIN=Canton-S {ECO:0000312|EMBL:AAF76150.1};
RX PubMed=10839352; DOI=10.1016/s0896-6273(00)81166-6;
RA Wan H.I., DiAntonio A., Fetter R.D., Bergstrom K., Strauss R.,
RA Goodman C.S.;
RT "Highwire regulates synaptic growth in Drosophila.";
RL Neuron 26:313-329(2000).
RN [2] {ECO:0000312|EMBL:AAF48411.2}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000269|PubMed:10731132};
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 [3] {ECO:0000305, ECO:0000312|EMBL:AAF48411.2}
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 [4] {ECO:0000305, ECO:0000312|EMBL:AAM29381.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 4083-5233.
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAM29381.1};
RC TISSUE=Larva {ECO:0000269|PubMed:12537569}, and
RC Pupae {ECO:0000269|PubMed:12537569};
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 [5]
RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH FSN, INTERACTION WITH FSN, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=17697379; DOI=10.1186/1749-8104-2-16;
RA Wu C., Daniels R.W., DiAntonio A.;
RT "DFsn collaborates with Highwire to down-regulate the Wallenda/DLK kinase
RT and restrain synaptic terminal growth.";
RL Neural Dev. 2:16-16(2007).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-213 AND SER-216, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Embryo;
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
RN [7]
RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH FSN AND RAE1, INTERACTION WITH
RP RAE1, TISSUE SPECIFICITY, IDENTIFICATION BY MASS SPECTROMETRY, AND
RP MUTAGENESIS OF 1-MET--GLU-2419; 1-MET--HIS-4083; 671-THR--ARG-1011;
RP 1012-VAL-VAL-1014; 1266-ARG--TYR-2146; 2885-ALA--PHE-5233;
RP 3800-PHE--SER-4039; CYS-5038 AND CYS-5041.
RX PubMed=21874015; DOI=10.1038/nn.2922;
RA Tian X., Li J., Valakh V., DiAntonio A., Wu C.;
RT "Drosophila Rae1 controls the abundance of the ubiquitin ligase Highwire in
RT post-mitotic neurons.";
RL Nat. Neurosci. 14:1267-1275(2011).
CC -!- FUNCTION: Atypical E3 ubiquitin-protein ligase which specifically
CC mediates ubiquitination of threonine and serine residues on target
CC proteins, instead of ubiquitinating lysine residues (By similarity).
CC Shows esterification activity towards both threonine and serine, with a
CC preference for threonine, and acts via two essential catalytic cysteine
CC residues that relay ubiquitin to its substrate via thioester
CC intermediates (By similarity). Required in the presynaptic motoneuron
CC to down-regulate the levels of wnd and restrain synaptic terminal
CC growth at the neuromuscular junction (NMJ) together with Rae1 and Fsn
CC (PubMed:10839352, PubMed:21874015, PubMed:17697379).
CC {ECO:0000250|UniProtKB:O75592, ECO:0000269|PubMed:10839352,
CC ECO:0000269|PubMed:17697379, ECO:0000269|PubMed:21874015}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine +
CC [acceptor protein]-L-threonine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + [acceptor protein]-3-O-ubiquitinyl-L-threonine.;
CC EC=2.3.2.33; Evidence={ECO:0000250|UniProtKB:O75592};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:O75592}.
CC -!- SUBUNIT: Component of an E3 ubiquitin ligase complex composed of hiw,
CC Rae1 and Fsn (PubMed:17697379, PubMed:21874015). Interacts with Rae1;
CC the interaction with Rae1 may protect hiw from autophagy-mediated
CC degradation (PubMed:21874015). {ECO:0000269|PubMed:17697379,
CC ECO:0000269|PubMed:21874015}.
CC -!- SUBCELLULAR LOCATION: Synapse {ECO:0000269|PubMed:10839352}. Cell
CC projection, axon {ECO:0000269|PubMed:10839352}.
CC -!- TISSUE SPECIFICITY: Express throughout the nervous system
CC (PubMed:10839352, PubMed:21874015). Stage 13 embryos show expression in
CC the central nervous system (CNS) at the longitudinal axon tracts around
CC which the synaptic neuropil forms (PubMed:10839352). Expression outside
CC the CNS starts at stage 16 in presynaptic terminals at the periactive
CC zone which surround the active zone (PubMed:10839352). Expression at
CC neuromuscular junctions (NMJ) and in the CNS is also seen in third
CC instar larvae (at protein level) (PubMed:10839352).
CC {ECO:0000269|PubMed:10839352, ECO:0000269|PubMed:21874015}.
CC -!- DOMAIN: The PHR domains are compact beta-sandwich folds composed of 11
CC antiparallel strands and decorated with conserved apical loops. They
CC are likely to play a structural role and mediate interactions with
CC substrates or partners (By similarity). {ECO:0000250|UniProtKB:Q7TPH6}.
CC -!- DOMAIN: The tandem cysteine domain region confers threonine specificity
CC and contains the two essential catalytic cysteine residues that relay
CC ubiquitin. It binds four zinc ions in a C5HC7HC2 configuration.
CC {ECO:0000250|UniProtKB:O75592}.
CC -!- DISRUPTION PHENOTYPE: Flies display NMJ synapses that grow exuberantly
CC and are expanded in both the number of boutons and in the extent and
CC length of branches. {ECO:0000269|PubMed:10839352}.
CC -!- SIMILARITY: Belongs to the RING-Cys relay (RCR) family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF48411.2; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=AAM29381.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF262977; AAF76150.1; -; mRNA.
DR EMBL; AE014298; AAF48411.2; ALT_SEQ; Genomic_DNA.
DR EMBL; AY113376; AAM29381.1; ALT_INIT; mRNA.
DR RefSeq; NP_001285258.1; NM_001298329.1.
DR RefSeq; NP_511159.3; NM_078604.4.
DR SMR; Q9NB71; -.
DR BioGRID; 58787; 28.
DR IntAct; Q9NB71; 3.
DR STRING; 7227.FBpp0073787; -.
DR iPTMnet; Q9NB71; -.
DR PaxDb; Q9NB71; -.
DR PRIDE; Q9NB71; -.
DR EnsemblMetazoa; FBtr0073970; FBpp0073787; FBgn0030600.
DR EnsemblMetazoa; FBtr0346087; FBpp0311921; FBgn0030600.
DR GeneID; 32429; -.
DR KEGG; dme:Dmel_CG32592; -.
DR UCSC; CG32592-RA; d. melanogaster.
DR CTD; 32429; -.
DR FlyBase; FBgn0030600; hiw.
DR VEuPathDB; VectorBase:FBgn0030600; -.
DR eggNOG; KOG1428; Eukaryota.
DR HOGENOM; CLU_000063_0_0_1; -.
DR InParanoid; Q9NB71; -.
DR OMA; NKLCILD; -.
DR OrthoDB; 215263at2759; -.
DR PhylomeDB; Q9NB71; -.
DR SignaLink; Q9NB71; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 32429; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 32429; -.
DR PRO; PR:Q9NB71; -.
DR Proteomes; UP000000803; Chromosome X.
DR Bgee; FBgn0030600; Expressed in brain and 11 other tissues.
DR ExpressionAtlas; Q9NB71; baseline and differential.
DR Genevisible; Q9NB71; DM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:FlyBase.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:FlyBase.
DR GO; GO:0045202; C:synapse; IEA:UniProtKB-SubCell.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISS:FlyBase.
DR GO; GO:0008270; F:zinc ion binding; ISM:FlyBase.
DR GO; GO:0007628; P:adult walking behavior; NAS:FlyBase.
DR GO; GO:0006914; P:autophagy; IDA:FlyBase.
DR GO; GO:0007411; P:axon guidance; IBA:GO_Central.
DR GO; GO:0040011; P:locomotion; NAS:FlyBase.
DR GO; GO:0007616; P:long-term memory; IMP:FlyBase.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; IGI:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0045886; P:negative regulation of synaptic assembly at neuromuscular junction; IMP:UniProtKB.
DR GO; GO:1900075; P:positive regulation of neuromuscular synaptic transmission; IMP:FlyBase.
DR GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0008582; P:regulation of synaptic assembly at neuromuscular junction; IMP:FlyBase.
DR GO; GO:2000331; P:regulation of terminal button organization; IMP:FlyBase.
DR GO; GO:0048678; P:response to axon injury; IMP:FlyBase.
DR GO; GO:0050808; P:synapse organization; IDA:FlyBase.
DR Gene3D; 2.130.10.30; -; 2.
DR Gene3D; 2.60.120.820; -; 2.
DR Gene3D; 2.60.40.10; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR004939; APC_su10/DOC_dom.
DR InterPro; IPR017868; Filamin/ABP280_repeat-like.
DR InterPro; IPR008979; Galactose-bd-like_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR014756; Ig_E-set.
DR InterPro; IPR012983; PHR.
DR InterPro; IPR038648; PHR_sf.
DR InterPro; IPR009091; RCC1/BLIP-II.
DR InterPro; IPR000408; Reg_chr_condens.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF08005; PHR; 2.
DR Pfam; PF00415; RCC1; 1.
DR PRINTS; PR00633; RCCNDNSATION.
DR SMART; SM01337; APC10; 1.
DR SMART; SM00184; RING; 2.
DR SUPFAM; SSF49785; SSF49785; 1.
DR SUPFAM; SSF50985; SSF50985; 1.
DR SUPFAM; SSF81296; SSF81296; 1.
DR PROSITE; PS51284; DOC; 1.
DR PROSITE; PS50194; FILAMIN_REPEAT; 1.
DR PROSITE; PS00626; RCC1_2; 2.
DR PROSITE; PS50012; RCC1_3; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Cell projection; Metal-binding; Phosphoprotein; Reference proteome; Repeat;
KW Synapse; Transcription; Transcription regulation; Transferase;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..5233
FT /note="E3 ubiquitin-protein ligase highwire"
FT /id="PRO_0000055971"
FT REPEAT 615..666
FT /note="RCC1 1"
FT /evidence="ECO:0000255"
FT REPEAT 669..724
FT /note="RCC1 2"
FT /evidence="ECO:0000255"
FT REPEAT 768..818
FT /note="RCC1 3"
FT /evidence="ECO:0000255"
FT REPEAT 931..983
FT /note="RCC1 4"
FT /evidence="ECO:0000255"
FT REPEAT 984..1033
FT /note="RCC1 5"
FT /evidence="ECO:0000255"
FT REPEAT 1035..1084
FT /note="RCC1 6"
FT /evidence="ECO:0000255"
FT REPEAT 2906..3000
FT /note="Filamin"
FT /evidence="ECO:0000255"
FT DOMAIN 4195..4374
FT /note="DOC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00614"
FT ZN_FING 4991..5042
FT /note="RING-type; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 197..230
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 680..700
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 900..950
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1051..1109
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1287..1327
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1436..1587
FT /note="PHR domain 1"
FT /evidence="ECO:0000269|PubMed:21874015"
FT REGION 1681..1718
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2014..2169
FT /note="PHR domain 2"
FT /evidence="ECO:0000269|PubMed:21874015"
FT REGION 2329..2353
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2580..2604
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2885..4082
FT /note="Required for interaction with Rae1"
FT /evidence="ECO:0000269|PubMed:21874015"
FT REGION 3005..3024
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3117..3210
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3277..3333
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3348..3378
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3551..3587
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3901..3936
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 4633..4655
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 4680..4702
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 5096..5231
FT /note="Tandem cysteine domain"
FT /evidence="ECO:0000250|UniProtKB:O75592"
FT COMPBIAS 681..700
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1681..1715
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2330..2353
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3177..3192
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3193..3208
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3282..3319
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3348..3373
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3563..3587
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3909..3934
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 4633..4654
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 5115
FT /evidence="ECO:0000250|UniProtKB:O75592"
FT ACT_SITE 5165
FT /evidence="ECO:0000250|UniProtKB:O75592"
FT BINDING 4991
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O75592"
FT BINDING 4994
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O75592"
FT BINDING 5009
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O75592"
FT BINDING 5011
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O75592"
FT BINDING 5014
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O75592"
FT BINDING 5017
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O75592"
FT BINDING 5038
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O75592"
FT BINDING 5041
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O75592"
FT BINDING 5101
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:O75592"
FT BINDING 5104
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:O75592"
FT BINDING 5130
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:O75592"
FT BINDING 5133
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:O75592"
FT BINDING 5142
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:O75592"
FT BINDING 5145
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:O75592"
FT BINDING 5154
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000250|UniProtKB:O75592"
FT BINDING 5157
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000250|UniProtKB:O75592"
FT BINDING 5158
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="6"
FT /evidence="ECO:0000250|UniProtKB:O75592"
FT BINDING 5172
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000250|UniProtKB:O75592"
FT BINDING 5175
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000250|UniProtKB:O75592"
FT BINDING 5193
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="6"
FT /evidence="ECO:0000250|UniProtKB:O75592"
FT BINDING 5207
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="6"
FT /evidence="ECO:0000250|UniProtKB:O75592"
FT BINDING 5213
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="6"
FT /evidence="ECO:0000250|UniProtKB:O75592"
FT BINDING 5224
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:O75592"
FT BINDING 5227
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:O75592"
FT SITE 5166
FT /note="Important for catalysis"
FT /evidence="ECO:0000250|UniProtKB:O75592"
FT SITE 5171
FT /note="Important for catalysis"
FT /evidence="ECO:0000250|UniProtKB:O75592"
FT SITE 5179
FT /note="Important for catalysis"
FT /evidence="ECO:0000250|UniProtKB:O75592"
FT MOD_RES 213
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 216
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MUTAGEN 1..4083
FT /note="Missing: Loss of binding to Rae1 and unable to
FT rescue synaptic terminal overgrowth in mutants."
FT /evidence="ECO:0000269|PubMed:21874015"
FT MUTAGEN 1..2419
FT /note="Missing: Unable to rescue synaptic terminal
FT overgrowth in mutants but has no effect on binding to
FT Rae1."
FT /evidence="ECO:0000269|PubMed:21874015"
FT MUTAGEN 671..1011
FT /note="Missing: Unable to rescue synaptic terminal
FT overgrowth in mutants but has no effect on binding to Rae1;
FT when associated with 1012-E--E-1014."
FT /evidence="ECO:0000269|PubMed:21874015"
FT MUTAGEN 1012..1014
FT /note="VQV->ELE: Unable to rescue synaptic terminal
FT overgrowth in mutants but has no effect on binding to Rae1;
FT when associated with 671-T--R-1011 DEL."
FT /evidence="ECO:0000269|PubMed:21874015"
FT MUTAGEN 1266..2146
FT /note="Missing: Unable to rescue synaptic terminal
FT overgrowth in mutants but has no effect on binding to
FT Rae1."
FT /evidence="ECO:0000269|PubMed:21874015"
FT MUTAGEN 2885..5233
FT /note="Missing: Loss of binding to Rae1 and unable to
FT rescue synaptic terminal overgrowth in mutants."
FT /evidence="ECO:0000269|PubMed:21874015"
FT MUTAGEN 3800..4039
FT /note="Missing: Unable to rescue synaptic terminal
FT overgrowth in mutants but has no effect on binding to
FT Rae1."
FT /evidence="ECO:0000269|PubMed:21874015"
FT MUTAGEN 5038
FT /note="C->S: Unable to rescue synaptic terminal overgrowth
FT in mutants but has no effect on binding to Rae1; when
FT associated with S-5041."
FT /evidence="ECO:0000269|PubMed:21874015"
FT MUTAGEN 5041
FT /note="C->S: Unable to rescue synaptic terminal overgrowth
FT in mutants but has no effect on binding to Rae1; when
FT associated with S-5038."
FT /evidence="ECO:0000269|PubMed:21874015"
FT CONFLICT 137
FT /note="N -> D (in Ref. 1; AAF76150)"
FT /evidence="ECO:0000305"
FT CONFLICT 604
FT /note="C -> R (in Ref. 1; AAF76150)"
FT /evidence="ECO:0000305"
FT CONFLICT 1620
FT /note="F -> S (in Ref. 1; AAF76150)"
FT /evidence="ECO:0000305"
FT CONFLICT 4652
FT /note="G -> E (in Ref. 1; AAF76150)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 5233 AA; 565631 MW; E5220FFDC91A58E7 CRC64;
MVGLLNPLKY GDHFYELYTN STRRKMQHDR KVLTKRKSRK DKSAAAMAAA AAAAVLEGNA
GAGGLVNPLD PPLVKEQLMI LPSFPVAHIE LDPNASKFAV FSAIRSTVLE AETRYSLFQE
GGAPSGQSGS NQKKWSNNVN SACCMMCAHS CMISNLLDCS CHAHMAMHGA VGPGNAGPGG
PVGVLVDGRI PAPVPVVVGG PGLPAEKRPR RDSANSDADS DTEEPTEREP VYATVPLIVG
AGLRSLFELI ADARHVHPLL CTKALKALLD VIQGQQPESF KLEPEELINP LYDLLLDLAT
MPAALNSATG AEANWSAMAC AALLGLCIAR GDTGKMLKAI AAMLMTPRQL SAQIVQLPVV
LATLQHTVIS AALNKPTRPD FHSHGVPHNS LIDEFPVKLP PLSTGAPITS PAMACDGVFV
YLLYGGTLLK IGTGFGGSYK GHIYAQNEDF SHERSAWLGY SGGQLYFRRT CRRSAGDQLQ
MVGLDTLAIK AMSPLSMLHM REGLNYVLFT DDDSLHAICS NRDDTLVVKK LNLYHNSYNI
DPPPFELPLQ LARKKFRTLG YAAFEDELLN QYQIQRIQSA HNSFEPKLPA PCRDADVDVM
GMACGKEFGL VRASNGRVYY YGKSAALGLK CVGRTPTLKL TELVISKAAN IVHVAVGHDG
IHALLVNDDG TVFFAGTARR GEDGDSSKNR RQPKAVKPKK MTKIDGHVVV HAACNNGTSA
FVTKTGKLIM YGKDTAHCDA MGFVSELLEQ HVTKVALGKA HCVALNAKGQ LFSFGLNNKG
QCGRIFNKLQ PVKDVPPFAS SSTAAACFAS LLPLDKRLKL DFSTLCDYDD HNLVQGQCRV
CVICRECTGY NVSCVSALNV PLDQRLAGSI CPCGHGDAGC AKCGLCAACI ALQDSDEAKT
ELKPPPSDVQ QRQQRSKTLI MRRKERKGEL ETGAAGGGAA TPTDLDKDPP RVAPLAPQLL
QLTSSSPVVQ VACGLHHTVV LTLAGEVYTF GSNQYGQLGS GDLQPVSGPV RVQVPGAISQ
VAAGSNHTVL LTSKGMVYTF GNYQKGQLGR LPSDYGLKPP PQDDDSPVGA GSDGGAGGSP
TVAPVGMPGP ERSQSPANVQ PSGSKEMPPL LPVLTQRQKF LWNCSPGAVF GLGPCYGKKV
TWIGANGDQT FIKIDESLIT AQMLPKMHVV ANKKTILLIP SIPLSFHTLS INRRDGSCTA
HYRGQTNFVK LMQAQPEQQQ PEINSNLDVA VTPVADSPAH ASTSSLLAAL TGTATAGVPI
NEQMSRSMHE ARNQIFEEQL PEVGSSAAAA AVAAPGTPVS AGSVPRSRRG GKQGTSSPEP
IPSPPQLAFT MDPTYNVLWV FDGAARKLRC HNVVASDIND SDANAATYRS LLSPELSLPD
RVDSRVARSQ ASLNLLACLD ILTSAQDNIP GCFEQPLLKQ TQQTAETQAG EFQVVNRFDN
FGGGWGYSGH SVEAIRFSAD TDIVICGFGM FGGRGEYSCK LKLFDLGGDG GGYEKEGILI
SETKEVPYEC GARSKHHILL PKPVSAVAGR WYLVWARIAG PSSDCGSCGQ ASVTTEDQVV
FSFKSSKKAN NGTDVNSGQI PAILYRLVTQ DCKQTPAQMD ADPVQRISRA FANSVSRECF
ESLVVLLSWS WDCFKLQLRE ERDRSRPLQL QQSLQYLGYV IKSCLRLLRK YTIEIYPQRN
SSTSVATGGG SNAAHGSGVV TTAKSVQSKP NKDKNTPRVV GNAGVMAKYF GDPSTSVAPA
MISSASSGGA PSTSASAAVA PGSGTPVTRK TNMENIQLAE CIGNVRALLI GIFCDDIFKD
IATDEGYELS LEILDECHLS FVACFDAFYP TSSLKWNCLC DLLAQMDRGA LHSRLLSAIL
AGLCSPSVKL RATFSLLSAA GNERQSIISP SDNSGLPMLS STDAHPYPVL VEQMIYRTQQ
EKSDFLSNSW TFKDVLVRLL DIIASPIRSR IEAIYSRSLG SLGYPGGKDC VNQGLIDNCC
HLLARVLAEI VYQTAMGEYD KLFMPPRTLH STGARFARCD VSRTWNTGNF GPDAIAFAVD
RPGVAIAGAM VYSGSGSYDY QLELLYDNTA DLQPQHKWET LESVSGSYDQ DAVHNDLAEI
KFDHPVHIKE NARYALRLCS QGARTCSGDA GMPAVRGPCG AQFHFYACDL SFNGTTPARG
QLPCILYYST PMKQDGHSAS GRTGDGSNVA THLEDRIMLL GPHEVSTRDT ALQIAADITK
KCTELLILAR NAMAASCSPS DNSSNHTQTI DSEHNITPIE EHMDINWANN SRTAALPTAI
DPQLSTARDL GKRIESFSKG LMETLKFDKR STNPFEMEIE IGATEVEESA DLRNGQSQSV
SQSQSQSQSV PINGNERTAD FEFAEQSAQQ SMPQHLHSDS EEAPLEVAGM AAGGGVSVAD
GSGGVAGVGS QAAAVQLLEV FNLAASNMFH TLLPLVYAHI ANLACSDPKS SVQILGLIKE
ILPHIAALNQ LHVSKDQRQP EPAIFATQTS GSGNSNSSST TSNHYCVVES DHPYKSASIS
SYRVEFPPCV QWLTIEFDPQ CGTAQLEDYL LLSIPMRPAS QAPPVPHVDD YLEQADNNVN
GAGDRRRNTG GGIAGSGAAP NTHQRSASVQ LTMASCCRSP GCGNAPGSAA APSSMPLRSQ
DPNDREWIVV KKFNTASTWL HNVLILPGNC VEFSLETASL YAQDPHNNRY GFKCLVVGYD
NPTSINASNS CLIRLEQELA YLGGMCSANL MKKELNLPDD KDVEDMSGIE ETINTHHTLL
SKGFALSEPQ LTVHQALESY LPIGSQSNER QFLKDFISGA PGSSGARLAA WLQPESRLDP
NKCELNTITE PLRYGWPSQV TVTIRDQYGD AVLVPELKVE IKAIPTGSGP NGSATGTGTS
CTSVAEVSAP GPNLWMRRAS RDTWGWGGMA PPPRINYEPT VKDKMVFKAI TFMKPYANYS
FEELRYASPV QTRVTELLNA KDMEDGTFSV QWTPSSVGAY CLAVTIDGIP LEEVYRVDVK
EGILPPPTQR NSAQRRPQAP SKLRRFQARH SSGLRIRSHP TLQSEQVGVV RVGGVISFID
EIENDDGVWL RLSTESIRQH CTMGWYPTEA WCLQFNQHLA RMLLQPVTDK EVNPVRKGVG
AEEDVEEQPP VTPSASGEAS PEPEPDPSPV LSPAKTKPGR FLSGHQSTNP FLYPAKHADL
AEREAQVQEE REKEEEQVDD EDADDREPEQ EALPAVELLP AHIGSAIAGV VGGGAIKLQA
LQKWFKGDAV DGPQPLTPSH SPPLAGVSVR ELVRAMGGQD SPRGNGNRSQ QEQDPEFSLA
SMRRPNYSAS QTAALLSTPK HTPKRSAVVA SETSGLEDEL SLLQITTTTT GQGEQQSELQ
LATTSTASSA SKRNPMGPIK RAMPPSFAES IRAVFAALLW HEGVVHDAMA CASFLKFHPG
LPKEGATVVT RRGESGDPRL QLSREQKAQQ RHSVEVANAG NYLNIRPSTL ETLTKSGNCS
LHNRSKYRKN LLSGGGGAIN SGDDTAQKLQ ALPEMVSVLP PALRCLVYLW EQICSGCVQI
VQSNALEQRE PRLLSPGSRD LNGDADTEGK EGKNSDQASA GEKDLGRKCK RKKKDDGSWC
EICELFLPMP VTYHMRIAHP GCGKSAKGKG YNSVGIFCEG WAGNCGEGGK GASSWFLMCD
PCRDRYLASC RSANNINSAA RQLESSAAEG NELNLFGVKS TTLIANAEVY TTMRENATFL
LELCSSSSSA SGAAGSLAAT SSSSKRSPQQ MSVVAMPVVI EHQLGNSDLK PSTSRCSRMA
RLSGSKFCPG VGSGAFRKSF VGGPPTAPEN VWLAPESFAC LECLGTAGHE DLPYEMFGLG
PNSNDNGYDR PLSEISYESC EPNNYDMLSG SLAPGTTAAA SVGGGNLSKF HRSYSMGQGW
ASLAQHNHPP PHHPQQQHHQ QQQMNLQLQQ HQAPPVDGQP KVVYRRRNNS TSEGDGSLLI
CYPSEHLRRL VPQKLLASVS VMQTASGEGT GKDHATGTLG LDQSAGQNGG GNLLLTRPAM
AFITQKHELD RLRAAMRRSL RIAACRIYAL QALNWLLRSV TQGVCLHDLM WWFVSSLNPT
GGHQPVERGE EASEPALEHP VAYTQISGRF AHLITQSLHV FLQSVADLTL HLPLGSPLQR
VAIQCFGIRF RQADHQFLHS SHVFGNISKI LSKSDEQNDA MAVSTILKPD CDVEHNQVHS
VATGGSSGAG ARLLCYTDLA GMFEVTVSSR PAMAESLTDN STETFWESDE EDRNKCKIIE
LSLTKLNYAC RYLLVHIDNS RDIQNKVLNV VFYAGQSLGD TNIIKSADVD PKACSWISAK
ICDDSCTHFR LELHGPENTL RVRQIKLLGL PIGGAVGSDD SSDHKHQPHL RLSHASRIQQ
QICEAETLRV FRLITGQVFG KLISNVSSDL VPPDSAGIGP PSGGAASTSL LADSLDLREH
MVGILFSRSK LSHLQKQVIV HIVHAIRKEA QRAKEDWELA NLAHVLKQSP QQQTAPALAA
SASCESTPER SRAPDTYCFE MLSMVLALSG SVVGRSYLSQ QHGLLRDLLG LLHTGSDRVQ
RQVTALLRRI LPEITPESFA ELLGVQRLPP ADYSIAHQSA SDFDMSRLGL LDIFLAVIAK
SLQLQVKVKT TVASTGPSGS GGVSGSSSGN GGAVLKAGQQ EKTPAFVRLW SSLDLSVQQL
RSRPPTGEPG TTDPFQFDAL PPRKESKRNL NQRWFLNGVI STKQAESIIS LIRDLASGKL
SEKWSQITKA AIAESVLNLT RLEEIYRSPE HCTKTSTLWL ALASLCVLER DHVEKLSSGQ
WSKLCDTRPL CSNHDDGETA AIIQCETCGS LCGDCDRFLH LNRKTRSHKR TVCKEEEEAI
RVELHESCGR TKLFWLLALA DSKTLKAMVE FRDGSHTIIS GPQEAVGRCR FCGLTGNSGL
LEIGNVCADA QCQEYAANSC LKTKPCGHAC GGVTGERKCL PCLQHVCHTR ENELAEELRD
PKLTQDADDM CMICFVEALS CAPSIHLECG HVFHYHCCKA VLEKRWSGPR ITFGFSLCPI
CKADIQHPLL SDILEPINGL KQDVKRKALM RIKYEGVVKD TDSKNVNMTQ LAMDRYAYYV
CFKCQKAYYG GEARCDAEIG EKFDPEELVC GGCSDVARAQ MCPKHGTDFL EYKCRYCCSV
AVFFCFGTTH FCDTCHDDFQ RLTNIPKVKL PQCPAGPKAK QLLGDECPLH VMHPPTGEEF
ALGCGVCRNA QTF
