SIF2_DROME
ID SIF2_DROME Reviewed; 2061 AA.
AC P91620; Q8MT93; Q9VRN8;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2005, sequence version 2.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Protein still life, isoforms C/SIF type 2;
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] (ISOFORM SIF TYPE 2), FUNCTION, SUBCELLULAR
RP LOCATION, AND 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 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 [6]
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=C;
CC IsoId=P91620-2; Sequence=Displayed;
CC Name=SIF type 2; Synonyms=A;
CC IsoId=P91620-1; Sequence=VSP_015664;
CC Name=SIF type 1; Synonyms=B;
CC IsoId=P91621-1; Sequence=External;
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; D86546; BAA13108.1; -; mRNA.
DR EMBL; AE014296; AAF50756.3; -; Genomic_DNA.
DR EMBL; AE014296; AAS65075.1; -; Genomic_DNA.
DR EMBL; AY118305; AAM48334.1; -; mRNA.
DR PIR; T13704; T13704.
DR RefSeq; NP_524647.2; NM_079908.3. [P91620-1]
DR RefSeq; NP_996000.1; NM_206278.2. [P91620-2]
DR AlphaFoldDB; P91620; -.
DR SMR; P91620; -.
DR BioGRID; 68698; 6.
DR IntAct; P91620; 5.
DR PRIDE; P91620; -.
DR DNASU; 43892; -.
DR EnsemblMetazoa; FBtr0112709; FBpp0111621; FBgn0085447. [P91620-1]
DR EnsemblMetazoa; FBtr0112710; FBpp0111622; FBgn0085447. [P91620-2]
DR GeneID; 43892; -.
DR CTD; 43892; -.
DR FlyBase; FBgn0085447; sif.
DR VEuPathDB; VectorBase:FBgn0085447; -.
DR GeneTree; ENSGT00940000174094; -.
DR HOGENOM; CLU_000494_0_0_1; -.
DR SignaLink; P91620; -.
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; P91620; baseline.
DR Genevisible; P91620; 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: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 CDD; cd00160; RhoGEF; 1.
DR Gene3D; 1.20.900.10; -; 1.
DR Gene3D; 2.30.29.30; -; 2.
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 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 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.
PE 2: Evidence at transcript level;
KW Alternative splicing; Developmental protein;
KW Guanine-nucleotide releasing factor; Reference proteome; Repeat; Synapse.
FT CHAIN 1..2061
FT /note="Protein still life, isoforms C/SIF type 2"
FT /id="PRO_0000080975"
FT REPEAT 62..86
FT /note="1"
FT REPEAT 94..118
FT /note="2"
FT REPEAT 154..178
FT /note="3"
FT REPEAT 225..249
FT /note="4"
FT DOMAIN 822..935
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 1101..1168
FT /note="RBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00262"
FT DOMAIN 1184..1273
FT /note="PDZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 1425..1619
FT /note="DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT REGION 1..56
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 62..249
FT /note="4 X 25 AA approximate repeats"
FT REGION 181..241
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 259..399
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 453..474
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 536..600
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1068..1099
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1391..1414
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1792..1821
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1833..2028
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2040..2061
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..35
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 289..306
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 328..353
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 572..586
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1077..1092
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1902..1931
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1940..1980
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1981..2024
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1385..1393
FT /note="Missing (in isoform SIF type 2)"
FT /evidence="ECO:0000303|PubMed:8999801"
FT /id="VSP_015664"
FT CONFLICT 323
FT /note="T -> N (in Ref. 1; BAA13108)"
FT /evidence="ECO:0000305"
FT CONFLICT 453
FT /note="M -> I (in Ref. 1; BAA13108)"
FT /evidence="ECO:0000305"
FT CONFLICT 1354..1361
FT /note="Missing (in Ref. 1; BAA13108)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2061 AA; 229931 MW; 5A1621A34E5149DD CRC64;
MEQKCIRRKG SVRLTEPTGH AHVRIEQRPQ LPPRRQKSAE EVATMPKSAL RQPPEQLEWF
DRRAQQRHSA RSAEGGQVRE ETMEWLKLQK TASPIQPVRT SSGPSEITVL KDELPDWLLD
HLPRKKERER DRLPSDADKA VGSAYAKALA DLLKKPLSRQ GSGPCEFSLL KTDIVEWLTK
MQSSSGTDRG KSRRSHHRRN GSGGDAQPRS NSQEDAQDQS KTSHRKRHSL GHSGAVSEEE
QQQLTADWIA YPLHKLQSLG KQPPPAQPPE RMSIPSGYAV PSALSHTPLC QRREERSRER
RLRHSASEVV GSGGAGAAST SNTAHLERLY AKPHKERYQY VPKTKESSGR KERSRRHQTQ
RSATVSDMSA QRSGGHKRKS SSAERAPRSP SPGPCTDPDC PLLPICTDPH CRYQECQARQ
CITSSVSSVN LARHQQLAQV QLHAVPAHLV GAMGSDVPTT PSTTATPPPP TGGGTMGVGA
TGAGAGATSE RRLVICHDCR SCAPLLSCRN RKCLNAAKCN SLPRCAADFN RLRTQLSQPP
TTLDDIEPAP LDDLEMQPLP SPPHPHPHHH YRSNSQPNTL QRGDSASSAG MGAGVGGAGH
GGLGGPGSGL AWLEPTTTLV QPLPAYVHHS NGKLMKSASA ASLNSRRRRH KTVHFGENLL
REVCQNRKLI KTEAQVPSGS APMKANIQML YNFVEGVLSA WVDDDEDQVR SGAESEPEHG
VVPMQPIHRC NRLRYQCIRR VVEEAADLQG TLKLGNSRYR HRHWRSTAKQ CNEMFLRKIS
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
KTAEQVTGFC RSPQETRKSS PTGSVTSSVS TTALTPSRQL TDAEKLRKVV MELVDTERTY
VKHLNNLLEH YLEPMKRETF LSNAEINALF GNIHEIVTFQ RQFLQNLEES LDLEPDFNKF
EHCGQFRNVL FAIGSAFLYY VNHFKLYSSF CASHSKAQKV LHPNEGNHAL QEFLAARNPK
QQHSSTLESY LIKPIQRILK YPLLLQQMRN LTDTRADEHV HLCEALKGME KVAEHINEMQ
RIHEEYGAIF DHLFRQHQKS CKQPIDLSPG DLLYYGGVEW LNISDFLGKI KKGLELHAMC
FVFKSAVVFL CKERLRQKKK LMGVSSKNAT NEVEIIRYQV LIPVTEVQVR ASSAKDMDSH
FLWELIHLRS QLQRRSEKVY VLSNSTADFR NAFLKTIRQI IRESVRNMSI PMKNFGGSSG
SVSGHSSQGM GSMGYPGNSQ TLERPKQQIT IVHGSHTLGK PKKKSGSQRH SAGNIDYDNL
SGSQEADDLP PSVGVVHYAS GHTHGQQMQP AGFRGRSKTV GDVTEITCSS PEPHQQQQQQ
QQQQQQLMQQ GHAHAHPHPH PHPREPPPPP IRQPHLHHHS SDIERIDPGT KSEGEEDSQQ
GTIRPKATLG RTPNHLTLST TSTLSVGSTG SQARLIQSSH PPASYQPVLM KDLGSPVWKP
RDMINLGTDP QSTTRKDDVK N
