SINAL_DROME
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 03-AUG-2022, entry version 151.
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; Q8T3Y0; -.
DR DNASU; 39885; -.
DR EnsemblMetazoa; FBtr0301683; FBpp0290897; FBgn0259794.
DR GeneID; 39885; -.
DR KEGG; dme:Dmel_CG13030; -.
DR UCSC; CG13030-RB; d. melanogaster.
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; 780610at2759; -.
DR PhylomeDB; Q8T3Y0; -.
DR Reactome; R-DME-373752; Netrin-1 signaling.
DR Reactome; R-DME-5689880; Ub-specific processing proteases.
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 tissues.
DR ExpressionAtlas; Q8T3Y0; baseline and differential.
DR Genevisible; Q8T3Y0; DM.
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:0045676; P:regulation of R7 cell differentiation; ISS:UniProtKB.
DR GO; GO:0007423; P:sensory organ development; ISS:UniProtKB.
DR Gene3D; 2.60.210.10; -; 1.
DR Gene3D; 3.30.40.10; -; 2.
DR InterPro; IPR018121; 7-in-absentia-prot_TRAF-dom.
DR InterPro; IPR004162; SINA-like_animal.
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; PTHR45877; 1.
DR Pfam; PF03145; Sina; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
DR PROSITE; PS51081; ZF_SIAH; 1.
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
