SIF1_DROME
ID SIF1_DROME Reviewed; 2072 AA.
AC P91621; Q9VRN7;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2005, sequence version 2.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Protein still life, isoform SIF type 1;
GN Name=sif; ORFNames=CG34418;
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], FUNCTION, SUBCELLULAR LOCATION, AND
RP DEVELOPMENTAL STAGE.
RC TISSUE=Head;
RX PubMed=8999801; DOI=10.1126/science.275.5299.543;
RA Sone M.;
RT "Still life, a protein in synaptic terminals of Drosophila homologous to
RT GDP-GTP exchangers.";
RL Science 275:543-547(1997).
RN [2]
RP ERRATUM OF PUBMED:8999801.
RX PubMed=9072802;
RA Sone M., Hoshino M., Suzuki E., Kuroda S., Kaibuchi K., Nakagoshi H.,
RA Saigo K., Nabeshima Y., Hama C.;
RL Science 275:1405-1405(1997).
RN [3]
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 [4]
RP GENOME REANNOTATION, AND ALTERNATIVE SPLICING.
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 [5]
RP FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=30290152; DOI=10.1016/j.ajhg.2018.09.004;
RA Ansar M., Chung H.L., Taylor R.L., Nazir A., Imtiaz S., Sarwar M.T.,
RA Manousopoulou A., Makrythanasis P., Saeed S., Falconnet E., Guipponi M.,
RA Pournaras C.J., Ansari M.A., Ranza E., Santoni F.A., Ahmed J., Shah I.,
RA Gul K., Black G.C., Bellen H.J., Antonarakis S.E.;
RT "Bi-allelic loss-of-function variants in DNMBP cause infantile cataracts.";
RL Am. J. Hum. Genet. 103:568-578(2018).
CC -!- FUNCTION: Regulates synaptic differentiation through the organization
CC of actin cytoskeleton possibly by activating Rho-like GTPases. Is
CC likely a factor in the cascade of Rac1 or Cdc42 in the neurons
CC (PubMed:8999801). May play a role in maintaining proper septate
CC junction functions. Required for eye development and most likely
CC affects corneal lens-formation (PubMed:30290152).
CC {ECO:0000269|PubMed:30290152, ECO:0000269|PubMed:8999801}.
CC -!- SUBCELLULAR LOCATION: Synapse {ECO:0000269|PubMed:8999801}.
CC Note=Localizes to the submembranous region of synaptic terminals.
CC {ECO:0000269|PubMed:8999801}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=SIF type 1; Synonyms=B;
CC IsoId=P91621-1; Sequence=Displayed;
CC Name=C;
CC IsoId=P91620-2; Sequence=External;
CC Name=SIF type 2; Synonyms=A;
CC IsoId=P91620-1; Sequence=External;
CC -!- TISSUE SPECIFICITY: In the adult eye is expressed in the two primary
CC pigment cells in the subapical region of the eye. Also present in
CC photoreceptors. {ECO:0000269|PubMed:30290152}.
CC -!- DEVELOPMENTAL STAGE: At stage 14, expression occurs in each segment of
CC the central nervous system. At stage 17, expression becomes restricted
CC to the synaptic regions of the brain and ventral nerve cord, where
CC synapses undergo maturation (PubMed:8999801). At 45 hours after
CC puparium formation (apf) expression is enriched in the shaft of bristle
CC cells in the sub-apical region. Present in all photoreceptors
CC (PubMed:30290152). {ECO:0000269|PubMed:30290152,
CC ECO:0000269|PubMed:8999801}.
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DR EMBL; D86547; BAA13109.1; -; mRNA.
DR EMBL; AE014296; AAF50755.3; -; Genomic_DNA.
DR PIR; T13707; T13707.
DR RefSeq; NP_001097519.2; NM_001104049.4. [P91621-1]
DR RefSeq; NP_729084.1; NM_168126.4. [P91621-1]
DR AlphaFoldDB; P91621; -.
DR SMR; P91621; -.
DR BioGRID; 68698; 6.
DR IntAct; P91621; 3.
DR STRING; 7227.FBpp0111624; -.
DR PaxDb; P91621; -.
DR DNASU; 43892; -.
DR EnsemblMetazoa; FBtr0112708; FBpp0111620; FBgn0085447. [P91621-1]
DR EnsemblMetazoa; FBtr0330122; FBpp0303155; FBgn0085447. [P91621-1]
DR GeneID; 43892; -.
DR KEGG; dme:Dmel_CG34418; -.
DR CTD; 43892; -.
DR FlyBase; FBgn0085447; sif.
DR VEuPathDB; VectorBase:FBgn0085447; -.
DR eggNOG; KOG3519; Eukaryota.
DR GeneTree; ENSGT00940000174094; -.
DR InParanoid; P91621; -.
DR Reactome; R-DME-193648; NRAGE signals death through JNK.
DR Reactome; R-DME-3928662; EPHB-mediated forward signaling.
DR Reactome; R-DME-3928665; EPH-ephrin mediated repulsion of cells.
DR Reactome; R-DME-416482; G alpha (12/13) signalling events.
DR Reactome; R-DME-8980692; RHOA GTPase cycle.
DR Reactome; R-DME-9013148; CDC42 GTPase cycle.
DR Reactome; R-DME-9013149; RAC1 GTPase cycle.
DR SignaLink; P91621; -.
DR BioGRID-ORCS; 43892; 0 hits in 3 CRISPR screens.
DR ChiTaRS; sif; fly.
DR GenomeRNAi; 43892; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0085447; Expressed in brain and 10 other tissues.
DR ExpressionAtlas; P91621; baseline.
DR Genevisible; P91621; DM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0045202; C:synapse; IDA:FlyBase.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; ISS:FlyBase.
DR GO; GO:0030036; P:actin cytoskeleton organization; IDA:FlyBase.
DR GO; GO:0090630; P:activation of GTPase activity; IBA:GO_Central.
DR GO; GO:0001654; P:eye development; IMP:UniProtKB.
DR GO; GO:0050772; P:positive regulation of axonogenesis; IBA:GO_Central.
DR GO; GO:0051491; P:positive regulation of filopodium assembly; IMP:FlyBase.
DR GO; GO:0050770; P:regulation of axonogenesis; IMP:FlyBase.
DR GO; GO:0043087; P:regulation of GTPase activity; ISS:FlyBase.
DR GO; GO:0050803; P:regulation of synapse structure or activity; TAS:FlyBase.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IBA:GO_Central.
DR GO; GO:0007601; P:visual perception; IMP:UniProtKB.
DR CDD; cd00160; RhoGEF; 1.
DR Gene3D; 1.20.900.10; -; 1.
DR Gene3D; 2.30.29.30; -; 3.
DR Gene3D; 2.30.42.10; -; 1.
DR InterPro; IPR035899; DBL_dom_sf.
DR InterPro; IPR000219; DH-domain.
DR InterPro; IPR001331; GDS_CDC24_CS.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR036034; PDZ_sf.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR003116; RBD_dom.
DR InterPro; IPR043537; Tiam1/Tiam2/Sif.
DR InterPro; IPR040655; TIAM1_CC-Ex.
DR InterPro; IPR000697; WH1/EVH1_dom.
DR PANTHER; PTHR46001; PTHR46001; 1.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF02196; RBD; 1.
DR Pfam; PF00621; RhoGEF; 1.
DR Pfam; PF18385; Tiam_CC_Ex; 1.
DR SMART; SM00228; PDZ; 1.
DR SMART; SM00233; PH; 2.
DR SMART; SM00455; RBD; 1.
DR SMART; SM00325; RhoGEF; 1.
DR SMART; SM00461; WH1; 1.
DR SUPFAM; SSF48065; SSF48065; 1.
DR SUPFAM; SSF50156; SSF50156; 1.
DR PROSITE; PS00741; DH_1; 1.
DR PROSITE; PS50010; DH_2; 1.
DR PROSITE; PS50106; PDZ; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS50898; RBD; 1.
DR PROSITE; PS50229; WH1; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Developmental protein;
KW Guanine-nucleotide releasing factor; Lipoprotein; Myristate;
KW Reference proteome; Repeat; Synapse.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000255"
FT CHAIN 2..2072
FT /note="Protein still life, isoform SIF type 1"
FT /id="PRO_0000080974"
FT DOMAIN 29..147
FT /note="WH1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00410"
FT DOMAIN 840..958
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 1121..1188
FT /note="RBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00262"
FT DOMAIN 1204..1293
FT /note="PDZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 1436..1630
FT /note="DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT REGION 153..188
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 245..284
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 327..355
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 459..486
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 502..576
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 618..655
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 699..747
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1088..1119
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1403..1424
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1803..1832
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1844..2039
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2051..2072
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 330..351
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 459..477
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 508..553
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 561..575
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 631..655
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 699..722
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 730..747
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1097..1112
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1913..1942
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1951..1991
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1992..2035
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000255"
FT CONFLICT 320
FT /note="D -> V (in Ref. 1; BAA13109)"
FT /evidence="ECO:0000305"
FT CONFLICT 1374..1381
FT /note="Missing (in Ref. 1; BAA13109)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2072 AA; 231130 MW; 3CAFE543F72DD331 CRC64;
MGNKLSCSCA PLMRKAYRYE DSPWQSSRRR DGHLLSSFRL WAEVFHVSAS GAGTVKWQQV
SEDLVPVNIT CIQDSPECIF HITAYNSQVD KILDVRLVQP GTRIGQASEC FVYWKDPMTN
DTWGLNFTSP IDAKQFRECC SPSFKFSRKA SSSYSLKLDP PGKGKVKAKR KPLSTPASPS
RVRQEPQCTC MSAEQYARLR TDPRVRGSST LPRNVGSHRI TDVDGQQQVG SGKVVSAVSS
TSLYDNVASG GPGTNQGADT LPRQMKGGQQ DRQDVANSGV NTNTPGVIVT GVGNVGSDMC
GQNHVGSQVG NDDPAACQMD MDLSKSEGTQ AGGGLHQSVG TCTSSSKGTG TRNKDFGDDM
TRDAHSHDMH QHNVINNNTR RKTKSTEDMN VDTSTLKRML KPMPSTESPV TSPEMGRRRY
NYYNANAAQT LGHPPHMHQH GMAMGMGGGG GGGHHIMNNN TMGRASSQSS RFSGSRSSHE
IGRGYPPRNL YLELERERSC IEGSPPSDNV MFDNQCYATT PSSSNGNSDQ DQSYGQQQSS
GQHPQQQQGP PQRSSRHQHH HQQAPNVTPT PGSPTSRLLL EYEMHLRNTL AKGMDAESYS
LHTFEALLSQ SMENLANAKS STLPLPPHRP LSTIRDKERD RDRDGYYSDR NELIRERERE
RDRGYLSDHN SSFSNSRCAS CIGESARAQW FRHSDGWRSG SSTIGSGSGH GMMTQQIPGS
GHKRSPWDSL PSLRQDSSLN DSGYKSARAD SLEQRAEFIR QDSLRSEYLS DRESRYGIVQ
QASIESTDSR MCYLTSSEIS DDDRMSLTTA VSDEDDGESV MASPYKAKAT GTAASSFNCT
GAVRKAGFLS VKKWLLRKKH QIELARKRGW KGYWVCLKGT TLLFYPCDSR EGRSVEAAPK
HLIIVDGAIM QPIPEHPKRD YIFCLSTAFG DAYLFQAPCQ VELENWVNSI HSACAAAFAR
HRGKTGTLHL LQEEIFRLEK AIESDHKLKH MAELQQSVVT DQETRHQIQT QILQWEENLE
RLHCEQFRLR CYMASLQSGE LPNPKSLLTH VSRPTKNTLN KLGVFTVSSF HAFICARSPS
LLNNLLAGRG ATKRRPPMLS RSNSGSSRRS MQMNSRDEPE KTFKVAMPDN AYSTVYLRDA
MSVEEFLASA CARRNLNPME HFVRVKKRRD MEDHNYFVPH RNDLIENYLH NHEFVEVCMK
ILYQVELQRT TLEQMWGFSV EAELIENAER QDELCCYVSR VEDKSVAMHN GIIKGDEIMV
INGAIVSDLD MMYLESVLQE EQSLSMMMRS SRTEPPDLVG IMRVTDDMID SLVCPPPPTD
PPVMSEEMIT GLIVPAPGWN GTSKDLYSPE AESSPATSFV DPAAMAAQLA VGGVGGVVVG
GLGVAKPTSR TSSFEIENLL KTAEQETRKS SPTGSVTSSV STTALTPSRQ LTDAEKLRKV
VMELVDTERT YVKHLNNLLE HYLEPMKRET FLSNAEINAL FGNIHEIVTF QRQFLQNLEE
SLDLEPDFNK FEHCGQFRNV LFAIGSAFLY YVNHFKLYSS FCASHSKAQK VLHPNEGNHA
LQEFLAARNP KQQHSSTLES YLIKPIQRIL KYPLLLQQMR NLTDTRADEH VHLCEALKGM
EKVAEHINEM QRIHEEYGAI FDHLFRQHQK SCKQPIDLSP GDLLYYGGVE WLNISDFLGK
IKKGLELHAM CFVFKSAVVF LCKERLRQKK KLMGVSSKNA TNEVEIIRYQ VLIPVTEVQV
RASSAKDMDS HFLWELIHLR SQLQRRSEKV YVLSNSTADF RNAFLKTIRQ IIRESVRNMS
IPMKNFGGSS GSVSGHSSQG MGSMGYPGNS QTLERPKQQI TIVHGSHTLG KPKKKSGSQR
HSAGNIDYDN LSGSQEADDL PPSVGVVHYA SGHTHGQQMQ PAGFRGRSKT VGDVTEITCS
SPEPHQQQQQ QQQQQQQLMQ QGHAHAHPHP HPHPREPPPP PIRQPHLHHH SSDIERIDPG
TKSEGEEDSQ QGTIRPKATL GRTPNHLTLS TTSTLSVGST GSQARLIQSS HPPASYQPVL
MKDLGSPVWK PRDMINLGTD PQSTTRKDDV KN