ULA1_DROME
ID ULA1_DROME Reviewed; 524 AA.
AC Q9VTE9; B6IDX9; Q8IHE1;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Nedd8-activating enzyme E1 regulatory subunit;
DE AltName: Full=Beta-amyloid precursor binding protein 1;
DE Short=dAPP-BP1;
GN Name=APP-BP1; ORFNames=CG7828;
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].
RC STRAIN=Berkeley; TISSUE=Testis;
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].
RC STRAIN=Berkeley;
RA Carlson J.W., Booth B., Frise E., Park S., Wan K.H., Yu C., Celniker S.E.;
RL Submitted (NOV-2008) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION, INTERACTION WITH APPL, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=16628230; DOI=10.1038/sj.cdd.4401935;
RA Kim H.J., Kim S.H., Shim S.O., Park E., Kim C., Kim K., Tanouye M.A.,
RA Yim J.;
RT "Drosophila homolog of APP-BP1 (dAPP-BP1) interacts antagonistically with
RT APPL during Drosophila development.";
RL Cell Death Differ. 14:103-115(2007).
RN [6]
RP FUNCTION, AND INTERACTION WITH UBA3.
RX PubMed=21931660; DOI=10.1371/journal.pone.0024168;
RA Du J., Zhang J., Su Y., Liu M., Ospina J.K., Yang S., Zhu A.J.;
RT "In vivo RNAi screen reveals neddylation genes as novel regulators of
RT Hedgehog signaling.";
RL PLoS ONE 6:E24168-E24168(2011).
CC -!- FUNCTION: Regulatory subunit of the dimeric Uba3-APP-BP1 E1 enzyme. E1
CC activates Nedd8 by first adenylating its C-terminal glycine residue
CC with ATP, thereafter linking this residue to the side chain of the
CC catalytic cysteine, yielding a Nedd8-Uba3 thioester and free AMP. E1
CC finally transfers Nedd8 to the catalytic cysteine of UbcE2M. Required
CC for Cul1 and Cul3 neddylation. Appl and APP-BP1 interact
CC antagonistically during development. {ECO:0000269|PubMed:16628230,
CC ECO:0000269|PubMed:21931660}.
CC -!- PATHWAY: Protein modification; protein neddylation.
CC -!- SUBUNIT: Heterodimer of Uba3 and APP-BP1. The complex binds Nedd8 and
CC UbcE2M. Interacts with Appl (via the intracellular domain, ICD).
CC {ECO:0000269|PubMed:16628230, ECO:0000269|PubMed:21931660}.
CC -!- DEVELOPMENTAL STAGE: Expressed throughout development.
CC {ECO:0000269|PubMed:16628230}.
CC -!- DISRUPTION PHENOTYPE: Hinders tissue development, causes apoptosis in
CC imaginal disk cells, and blocks the Nedd8 conjugation pathway.
CC {ECO:0000269|PubMed:16628230}.
CC -!- SIMILARITY: Belongs to the ubiquitin-activating E1 family. ULA1
CC subfamily. {ECO:0000305}.
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DR EMBL; AE014296; AAF50102.1; -; Genomic_DNA.
DR EMBL; BT001291; AAN71047.1; -; mRNA.
DR EMBL; BT050569; ACJ23453.1; -; mRNA.
DR RefSeq; NP_001261699.1; NM_001274770.1.
DR RefSeq; NP_648435.1; NM_140178.4.
DR AlphaFoldDB; Q9VTE9; -.
DR SMR; Q9VTE9; -.
DR BioGRID; 64618; 5.
DR DIP; DIP-21214N; -.
DR IntAct; Q9VTE9; 5.
DR STRING; 7227.FBpp0075938; -.
DR PaxDb; Q9VTE9; -.
DR PRIDE; Q9VTE9; -.
DR DNASU; 39244; -.
DR EnsemblMetazoa; FBtr0076208; FBpp0075938; FBgn0261112.
DR EnsemblMetazoa; FBtr0331179; FBpp0303606; FBgn0261112.
DR GeneID; 39244; -.
DR KEGG; dme:Dmel_CG7828; -.
DR UCSC; CG7828-RA; d. melanogaster.
DR CTD; 39244; -.
DR FlyBase; FBgn0261112; APP-BP1.
DR VEuPathDB; VectorBase:FBgn0261112; -.
DR eggNOG; KOG2016; Eukaryota.
DR GeneTree; ENSGT00550000074901; -.
DR HOGENOM; CLU_019618_2_1_1; -.
DR InParanoid; Q9VTE9; -.
DR OMA; LHEICRY; -.
DR OrthoDB; 454386at2759; -.
DR PhylomeDB; Q9VTE9; -.
DR Reactome; R-DME-8951664; Neddylation.
DR SignaLink; Q9VTE9; -.
DR UniPathway; UPA00885; -.
DR BioGRID-ORCS; 39244; 1 hit in 3 CRISPR screens.
DR GenomeRNAi; 39244; -.
DR PRO; PR:Q9VTE9; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0261112; Expressed in testis and 25 other tissues.
DR ExpressionAtlas; Q9VTE9; baseline and differential.
DR Genevisible; Q9VTE9; DM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0032991; C:protein-containing complex; IPI:FlyBase.
DR GO; GO:0001540; F:amyloid-beta binding; IPI:UniProtKB.
DR GO; GO:0019781; F:NEDD8 activating enzyme activity; IEA:InterPro.
DR GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR GO; GO:0032446; P:protein modification by small protein conjugation; IBA:GO_Central.
DR GO; GO:0045116; P:protein neddylation; IDA:FlyBase.
DR InterPro; IPR030667; APP-BP1.
DR InterPro; IPR045886; ThiF/MoeB/HesA.
DR InterPro; IPR000594; ThiF_NAD_FAD-bd.
DR InterPro; IPR035985; Ubiquitin-activating_enz.
DR PANTHER; PTHR10953; PTHR10953; 1.
DR Pfam; PF00899; ThiF; 1.
DR PIRSF; PIRSF039099; APP-BP1; 1.
DR SUPFAM; SSF69572; SSF69572; 1.
PE 1: Evidence at protein level;
KW Reference proteome; Ubl conjugation pathway.
FT CHAIN 1..524
FT /note="Nedd8-activating enzyme E1 regulatory subunit"
FT /id="PRO_0000194958"
FT CONFLICT 306
FT /note="H -> N (in Ref. 3; AAN71047)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 524 AA; 58717 MW; 355078EBECDC6233 CRC64;
MSSPAPKSPE LSDKSKKYDR QIRLWGEHGQ TLLEAATVCL VNVTAVGCET AKGLVLPGIG
GFTVADGSTV KEEDLGNNFF LDSSYLGKSK ALACMQLLQE LNPDVNGDYV DESADFLLAN
RPNFFDSFDL VIASNLNEQT LLLLAERLWE LNVPLIYCRS LGMLGTIRLQ IREHCIVEAH
PDNRQFDLRL EHPFDALREH LDGTEVTSKV PWLLVLHKYL NVWQKQQADG TQTPRNYKEK
NQLKETIREE MKADEENYEE AIKAVNTAFG AGQVPKSLKA IFEDDACEQL NKKSNVFWIM
AKALKHFVIH ENEGHLPLPG VLPDMTANTD SYIALQHIYR QQALQDADQV YHKCQEYLKQ
LALPADSIDE RSVRLICKEA AGLAVIRGTR IAEEYEKSSR LLPLVEDNEL QGNLTAYNFA
LRAYERFLSE CGNIPGECIV EQDIGRLKSI AAKMLSDLGM HATISDDVLH EICRYGGAEL
HAVSAFIGGC AAQEVIKIIT KQYKPIDNTF IYNAITTESV TLKL
