SINA_DROME
ID SINA_DROME Reviewed; 314 AA.
AC P21461; A4V214; Q9VVB0;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 2.
DT 03-AUG-2022, entry version 194.
DE RecName: Full=E3 ubiquitin-protein ligase sina;
DE EC=2.3.2.27;
DE AltName: Full=RING-type E3 ubiquitin transferase sina {ECO:0000305};
DE AltName: Full=Seven in absentia protein;
GN Name=sina; ORFNames=CG9949;
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 [MRNA].
RX PubMed=2146028; DOI=10.1016/0092-8674(90)90452-k;
RA Carthew R.W., Rubin G.M.;
RT "Seven in absentia, a gene required for specification of R7 cell fate in
RT the Drosophila eye.";
RL Cell 63:561-577(1990).
RN [2]
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 [3]
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]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Head;
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 IN TTK DEGRADATION, AND INTERACTION WITH PHYL AND EFF.
RX PubMed=9267026; DOI=10.1016/s0092-8674(00)80506-1;
RA Tang A.H., Neufeld T.P., Kwan E., Rubin G.M.;
RT "PHYL acts to down-regulate TTK88, a transcriptional repressor of neuronal
RT cell fates, by a SINA-dependent mechanism.";
RL Cell 90:459-467(1997).
RN [6]
RP FUNCTION IN TTK DEGRADATION, AND INTERACTION WITH PHYL.
RX PubMed=9267027; DOI=10.1016/s0092-8674(00)80507-3;
RA Li S., Li Y., Carthew R.W., Lai Z.-C.;
RT "Photoreceptor cell differentiation requires regulated proteolysis of the
RT transcriptional repressor Tramtrack.";
RL Cell 90:469-478(1997).
RN [7]
RP COMPONENT OF A COMPLEX WITH EBI AND PHYL.
RX PubMed=11032805; DOI=10.1093/emboj/19.20.5376;
RA Boulton S.J., Brook A., Staehling-Hampton K., Heitzler P., Dyson N.;
RT "A role for Ebi in neuronal cell cycle control.";
RL EMBO J. 19:5376-5386(2000).
RN [8]
RP FUNCTION.
RX PubMed=11526076; DOI=10.1242/dev.128.14.2699;
RA Pi H., Wu H.-J., Chien C.-T.;
RT "A dual function of phyllopod in Drosophila external sensory organ
RT development: cell fate specification of sensory organ precursor and its
RT progeny.";
RL Development 128:2699-2710(2001).
RN [9]
RP FUNCTION OF THE COMPLEX.
RX PubMed=12215542; DOI=10.1128/mcb.22.19.6854-6865.2002;
RA Li S., Xu C., Carthew R.W.;
RT "Phyllopod acts as an adaptor protein to link the sina ubiquitin ligase to
RT the substrate protein tramtrack.";
RL Mol. Cell. Biol. 22:6854-6865(2002).
RN [10]
RP FUNCTION.
RX PubMed=18160715; DOI=10.1128/mcb.01567-07;
RA Bajpe P.K., van der Knaap J.A., Demmers J.A., Bezstarosti K., Bassett A.,
RA van Beusekom H.M., Travers A.A., Verrijzer C.P.;
RT "Deubiquitylating enzyme UBP64 controls cell fate through stabilization of
RT the transcriptional repressor tramtrack.";
RL Mol. Cell. Biol. 28:1606-1615(2008).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that is required for
CC specification of R7 photoreceptor cell fate in the eye by mediating the
CC ubiquitination and subsequent proteasomal degradation of Tramtrack
CC (ttk) (PubMed:9267026, PubMed:9267027, PubMed:11526076,
CC PubMed:12215542, PubMed:18160715). 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 (PubMed:12215542). Acts via the formation of a complex with
CC ebi and phyl that ubiquitinates the transcription repressor ttk, a
CC general inhibitor of photoreceptor differentiation, in a subset of
CC photoreceptor cells in the eye, leading to the differentiation of cells
CC into neurons (PubMed:9267026, PubMed:9267027, PubMed:11526076,
CC PubMed:12215542). Also involved in external sensory organ development
CC (PubMed:11526076). {ECO:0000269|PubMed:11526076,
CC ECO:0000269|PubMed:12215542, ECO:0000269|PubMed:18160715,
CC ECO:0000269|PubMed:9267026, ECO:0000269|PubMed:9267027}.
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: Component of some E3 complex at least composed of sina, ebi
CC and phyl. Interacts with eff. {ECO:0000269|PubMed:9267026,
CC ECO:0000269|PubMed:9267027}.
CC -!- INTERACTION:
CC P21461; A1Z8K2: Dmel\CG13204; NbExp=4; IntAct=EBI-77019, EBI-170347;
CC P21461; Q9W3H5: Dmel\CG2147; NbExp=5; IntAct=EBI-77019, EBI-136503;
CC P21461; Q95RJ9: ebi; NbExp=3; IntAct=EBI-77019, EBI-421390;
CC P21461; Q27934: phyl; NbExp=11; IntAct=EBI-77019, EBI-77033;
CC P21461; P21461: sina; NbExp=2; IntAct=EBI-77019, EBI-77019;
CC P21461; P42282: ttk; NbExp=4; IntAct=EBI-77019, EBI-77008;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
CC -!- TISSUE SPECIFICITY: In many ommatidial precursor cells.
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 interaction with substrate proteins. It is related to the TRAF family.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the SINA (Seven in absentia) family.
CC {ECO:0000305}.
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DR EMBL; M38384; AAA28901.1; -; mRNA.
DR EMBL; AE014296; AAF49403.1; -; Genomic_DNA.
DR EMBL; AE014296; AAN11744.1; -; Genomic_DNA.
DR EMBL; AY060358; AAL25397.1; -; mRNA.
DR PIR; A36195; A36195.
DR RefSeq; NP_001287089.1; NM_001300160.1.
DR RefSeq; NP_476725.1; NM_057377.4.
DR RefSeq; NP_730206.1; NM_168689.2.
DR AlphaFoldDB; P21461; -.
DR SMR; P21461; -.
DR BioGRID; 65183; 64.
DR DIP; DIP-17392N; -.
DR IntAct; P21461; 89.
DR STRING; 7227.FBpp0075091; -.
DR PaxDb; P21461; -.
DR DNASU; 39884; -.
DR EnsemblMetazoa; FBtr0075332; FBpp0075091; FBgn0003410.
DR EnsemblMetazoa; FBtr0075333; FBpp0075092; FBgn0003410.
DR EnsemblMetazoa; FBtr0344230; FBpp0310636; FBgn0003410.
DR GeneID; 39884; -.
DR KEGG; dme:Dmel_CG9949; -.
DR CTD; 39884; -.
DR FlyBase; FBgn0003410; sina.
DR VEuPathDB; VectorBase:FBgn0003410; -.
DR eggNOG; KOG3002; Eukaryota.
DR HOGENOM; CLU_028215_0_0_1; -.
DR InParanoid; P21461; -.
DR OMA; ADHEDAC; -.
DR OrthoDB; 780610at2759; -.
DR PhylomeDB; P21461; -.
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 SignaLink; P21461; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 39884; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 39884; -.
DR PRO; PR:P21461; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0003410; Expressed in eye disc (Drosophila) and 28 other tissues.
DR ExpressionAtlas; P21461; baseline and differential.
DR Genevisible; P21461; DM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:FlyBase.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000151; C:ubiquitin ligase complex; IDA:FlyBase.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0031624; F:ubiquitin conjugating enzyme binding; IBA:GO_Central.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:FlyBase.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:FlyBase.
DR GO; GO:0008270; F:zinc ion binding; ISM:FlyBase.
DR GO; GO:0035883; P:enteroendocrine cell differentiation; IMP:FlyBase.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IDA:FlyBase.
DR GO; GO:0010498; P:proteasomal protein catabolic process; IDA:FlyBase.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IDA:FlyBase.
DR GO; GO:0016567; P:protein ubiquitination; IDA:FlyBase.
DR GO; GO:0007465; P:R7 cell fate commitment; IMP:FlyBase.
DR GO; GO:0045676; P:regulation of R7 cell differentiation; IMP:UniProtKB.
DR GO; GO:0007423; P:sensory organ development; IMP:FlyBase.
DR GO; GO:0045500; P:sevenless signaling pathway; IGI:FlyBase.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IPI:FlyBase.
DR GO; GO:0007601; P:visual perception; IEA:UniProtKB-KW.
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 Cytoplasm; Developmental protein; Metal-binding; Nucleus;
KW Reference proteome; Sensory transduction; Transferase;
KW Ubl conjugation pathway; Vision; Zinc; Zinc-finger.
FT CHAIN 1..314
FT /note="E3 ubiquitin-protein ligase sina"
FT /id="PRO_0000056175"
FT ZN_FING 73..108
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 125..185
FT /note="SIAH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00455"
FT REGION 1..55
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 122..314
FT /note="SBD"
FT COMPBIAS 22..55
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 130
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 137
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 149
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 153
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 160
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 167
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 179
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 184
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
SQ SEQUENCE 314 AA; 33707 MW; B58D7D5E8DA2F958 CRC64;
MSNKINPKRR EPTAAAAGAG ATGVATNTST STGSSSAGNT SSANTSSSSS SSLSSAGGGD
AGMSADLTSL FECPVCFDYV LPPILQCSSG HLVCVSCRSK LTCCPTCRGP LANIRNLAME
KVASNVKFPC KHSGYGCTAS LVYTEKTEHE ETCECRPYLC PCPGASCKWQ GPLDLVMQHL
MMSHKSITTL QGEDIVFLAT DINLPGAVDW VMMQSCFGHH FMLVLEKQEK YDGHQQFFAI
VQLIGSRKEA ENFVYRLELN GNRRRLTWEA MPRSIHEGVA SAIHNSDCLV FDTSIAQLFA
DNGNLGINVT ISLV
