ID   SINAL_DROME             Reviewed;         351 AA.
AC   Q8T3Y0; Q9VVB1;
DT   26-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT   26-APR-2004, sequence version 2.
DT   27-MAR-2024, entry version 158.
DE   RecName: Full=Probable E3 ubiquitin-protein ligase sinah;
DE            EC=2.3.2.27;
DE   AltName: Full=RING-type E3 ubiquitin transferase sinah {ECO:0000305};
DE   AltName: Full=Sina homolog;
GN   Name=sinah; ORFNames=CG13030;
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   FUNCTION, INTERACTION WITH EBI, DEVELOPMENTAL STAGE, AND DISRUPTION
RP   PHENOTYPE.
RX   PubMed=17561381; DOI=10.1016/j.mod.2007.04.007;
RA   Cooper S.E.;
RT   "In vivo function of a novel Siah protein in Drosophila.";
RL   Mech. Dev. 124:584-591(2007).
RN   [5]
RP   FUNCTION, AND INTERACTION WITH PHYL.
RX   PubMed=17962185; DOI=10.1074/jbc.m707765200;
RA   Cooper S.E., Murawsky C.M., Lowe N., Travers A.A.;
RT   "Two modes of degradation of the tramtrack transcription factors by Siah
RT   homologues.";
RL   J. Biol. Chem. 283:1076-1083(2008).
CC   -!- FUNCTION: E3 ubiquitin-protein ligase that mediates ubiquitination and
CC       subsequent proteasomal degradation of target proteins. The adapter phyl
CC       is required to direct the degradation of the two isoforms of the
CC       transcriptional repressor Tramtrack (Ttk). E3 ubiquitin ligases accept
CC       ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a
CC       thioester and then directly transfers the ubiquitin to targeted
CC       substrates. It probably triggers the ubiquitin-mediated degradation of
CC       different substrates. A phyl-independent mechanism of degradation
CC       exists for isoform beta of ttk that involves motifs in the C-terminus
CC       of ttk. {ECO:0000269|PubMed:17561381, ECO:0000269|PubMed:17962185}.
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;
CC   -!- PATHWAY: Protein modification; protein ubiquitination.
CC   -!- SUBUNIT: Interacts with ebi and phyl. {ECO:0000269|PubMed:17561381,
CC       ECO:0000269|PubMed:17962185}.
CC   -!- INTERACTION:
CC       Q8T3Y0; Q9W3H5: Dmel\CG2147; NbExp=3; IntAct=EBI-152023, EBI-136503;
CC       Q8T3Y0; A1Z6P3: Eb1; NbExp=4; IntAct=EBI-152023, EBI-15117051;
CC       Q8T3Y0; P17789: ttk; NbExp=4; IntAct=EBI-152023, EBI-6173284;
CC   -!- DEVELOPMENTAL STAGE: Expressed in pupae and in adults, with a higher
CC       expression in males than females. {ECO:0000269|PubMed:17561381}.
CC   -!- DOMAIN: The RING-type zinc finger domain is essential for ubiquitin
CC       ligase activity. {ECO:0000250}.
CC   -!- DOMAIN: The SBD domain (substrate-binding domain) mediates the
CC       homodimerization and the interaction with substrate proteins. It is
CC       related to the TRAF family. {ECO:0000250}.
CC   -!- DISRUPTION PHENOTYPE: Flies are viable. In combination with a mutation
CC       in ebi, flies show an extra dorsal central bristle phenotype. Flies
CC       that lack both sina and sinah show visible eye and bristle phenotypes,
CC       which can be explained by an inability to degrade the neuronal
CC       repressor, Tramtrack. {ECO:0000269|PubMed:17561381}.
CC   -!- SIMILARITY: Belongs to the SINA (Seven in absentia) family.
CC       {ECO:0000305}.
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DR   EMBL; AE014296; AAF49402.3; -; Genomic_DNA.
DR   EMBL; AY089445; AAL90183.1; -; mRNA.
DR   RefSeq; NP_648927.1; NM_140670.2.
DR   AlphaFoldDB; Q8T3Y0; -.
DR   SMR; Q8T3Y0; -.
DR   BioGRID; 65184; 77.
DR   DIP; DIP-17367N; -.
DR   IntAct; Q8T3Y0; 44.
DR   STRING; 7227.FBpp0290897; -.
DR   PaxDb; 7227-FBpp0290897; -.
DR   DNASU; 39885; -.
DR   EnsemblMetazoa; FBtr0301683; FBpp0290897; FBgn0259794.
DR   GeneID; 39885; -.
DR   KEGG; dme:Dmel_CG13030; -.
DR   UCSC; CG13030-RB; d. melanogaster.
DR   AGR; FB:FBgn0259794; -.
DR   CTD; 39885; -.
DR   FlyBase; FBgn0259794; sinah.
DR   VEuPathDB; VectorBase:FBgn0259794; -.
DR   eggNOG; KOG3002; Eukaryota.
DR   HOGENOM; CLU_028215_0_0_1; -.
DR   InParanoid; Q8T3Y0; -.
DR   OMA; YIMPPIM; -.
DR   OrthoDB; 3686344at2759; -.
DR   PhylomeDB; Q8T3Y0; -.
DR   Reactome; R-DME-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR   UniPathway; UPA00143; -.
DR   BioGRID-ORCS; 39885; 0 hits in 1 CRISPR screen.
DR   GenomeRNAi; 39885; -.
DR   PRO; PR:Q8T3Y0; -.
DR   Proteomes; UP000000803; Chromosome 3L.
DR   Bgee; FBgn0259794; Expressed in testis and 10 other cell types or tissues.
DR   ExpressionAtlas; Q8T3Y0; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0031624; F:ubiquitin conjugating enzyme binding; IBA:GO_Central.
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:0010498; P:proteasomal protein catabolic process; IDA:FlyBase.
DR   GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR   GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR   GO; GO:0045676; P:regulation of R7 cell differentiation; ISS:UniProtKB.
DR   GO; GO:0007423; P:sensory organ development; ISS:UniProtKB.
DR   CDD; cd03829; Sina; 1.
DR   Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 2.
DR   InterPro; IPR018121; 7-in-absentia-prot_TRAF-dom.
DR   InterPro; IPR004162; SINA-like_animal.
DR   InterPro; IPR049548; Sina-like_RING.
DR   InterPro; IPR008974; TRAF-like.
DR   InterPro; IPR001841; Znf_RING.
DR   InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR   InterPro; IPR013010; Znf_SIAH.
DR   PANTHER; PTHR45877; E3 UBIQUITIN-PROTEIN LIGASE SIAH2; 1.
DR   PANTHER; PTHR45877:SF2; E3 UBIQUITIN-PROTEIN LIGASE SINA-RELATED; 1.
DR   Pfam; PF21362; Sina_RING; 1.
DR   Pfam; PF03145; Sina_TRAF; 1.
DR   Pfam; PF21361; Sina_ZnF; 1.
DR   SUPFAM; SSF57850; RING/U-box; 1.
DR   SUPFAM; SSF49599; TRAF domain-like; 1.
DR   PROSITE; PS50089; ZF_RING_2; 1.
DR   PROSITE; PS51081; ZF_SIAH; 1.
DR   Genevisible; Q8T3Y0; DM.
PE   1: Evidence at protein level;
KW   Metal-binding; Reference proteome; Transferase; Ubl conjugation pathway;
KW   Zinc; Zinc-finger.
FT   CHAIN           1..351
FT                   /note="Probable E3 ubiquitin-protein ligase sinah"
FT                   /id="PRO_0000056178"
FT   ZN_FING         106..141
FT                   /note="RING-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT   ZN_FING         158..218
FT                   /note="SIAH-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00455"
FT   REGION          1..38
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          155..346
FT                   /note="SBD"
FT   COMPBIAS        1..33
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         163
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         170
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         182
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         186
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         193
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         200
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         212
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         217
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   CONFLICT        351
FT                   /note="N -> Y (in Ref. 3; AAL90183)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   351 AA;  39645 MW;  415764CBBD433331 CRC64;
     MSVRNSRPQL SWPERVSPQR TIDTPTASGE MLTRRQSAPA LVVPPEETTH VVVVKRQSPD
     AAAAGELVPS RRKDSVAVQS GIVATGPLDT TRSGARDDFL MALLECPVCF GYIMPPIMQC
     PRGHLICSTC RSKLTICPVC RVFMTNIRSL AMEKVASKLI FPCKHSHFGC RARLSYAEKT
     KHEEDCECRP YFCPYPDDKC SWQGPLRDVY QHLMSSHENV ITMEGNDIIF LATNVNLEGA
     LDWTMVQSCH GRHFLLSLEK INLGEDCQQY FTACRMIGSM KDAAEFVYNI SLEAYNRTLR
     WQSKPRSIRE NFSSFTNADF LVLNKHTVEL FSEDGNLALN VVIRKVEERT N
//