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INT1_DROME
ID   INT1_DROME              Reviewed;        2053 AA.
AC   Q9W1C5; Q8IGA9;
DT   02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2002, sequence version 2.
DT   03-AUG-2022, entry version 138.
DE   RecName: Full=Integrator complex subunit 1 {ECO:0000303|PubMed:21078872};
GN   Name=IntS1 {ECO:0000312|FlyBase:FBgn0034964};
GN   ORFNames=CG3173 {ECO:0000312|FlyBase:FBgn0034964};
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 {ECO:0000312|Proteomes:UP000000803};
RN   [1] {ECO:0000312|Proteomes:UP000000803}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
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] {ECO:0000312|Proteomes:UP000000803}
RP   GENOME REANNOTATION.
RC   STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
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] {ECO:0000312|EMBL:AAN71641.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Berkeley {ECO:0000312|EMBL:AAN71641.1};
RC   TISSUE=Embryo {ECO:0000312|EMBL:AAN71641.1};
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] {ECO:0000305}
RP   FUNCTION.
RX   PubMed=21078872; DOI=10.1128/mcb.00943-10;
RA   Ezzeddine N., Chen J., Waltenspiel B., Burch B., Albrecht T., Zhuo M.,
RA   Warren W.D., Marzluff W.F., Wagner E.J.;
RT   "A subset of Drosophila integrator proteins is essential for efficient U7
RT   snRNA and spliceosomal snRNA 3'-end formation.";
RL   Mol. Cell. Biol. 31:328-341(2011).
RN   [5] {ECO:0000305}
RP   FUNCTION, SUBUNIT, AND INTERACTION WITH CDK8 AND CYCC.
RX   PubMed=23097424; DOI=10.1261/rna.035725.112;
RA   Chen J., Ezzeddine N., Waltenspiel B., Albrecht T.R., Warren W.D.,
RA   Marzluff W.F., Wagner E.J.;
RT   "An RNAi screen identifies additional members of the Drosophila Integrator
RT   complex and a requirement for cyclin C/Cdk8 in snRNA 3'-end formation.";
RL   RNA 18:2148-2156(2012).
RN   [6] {ECO:0000305}
RP   FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH INTS12 AND INTS9.
RX   PubMed=23288851; DOI=10.1074/jbc.m112.425892;
RA   Chen J., Waltenspiel B., Warren W.D., Wagner E.J.;
RT   "Functional analysis of the integrator subunit 12 identifies a microdomain
RT   that mediates activation of the Drosophila integrator complex.";
RL   J. Biol. Chem. 288:4867-4877(2013).
CC   -!- FUNCTION: Component of the Integrator complex, a complex involved in
CC       the transcription of small nuclear RNAs (snRNA) and their 3'-box-
CC       dependent processing (PubMed:21078872, PubMed:23097424). Involved in
CC       the 3'-end processing of the U7 snRNA, and also the spliceosomal snRNAs
CC       U1, U2, U4 and U5 (PubMed:21078872, PubMed:23097424, PubMed:23288851).
CC       Required for the normal expression of the Integrator complex component
CC       IntS12 (PubMed:23288851). May mediate recruitment of cytoplasmic dynein
CC       to the nuclear envelope, probably as component of the INT complex (By
CC       similarity). {ECO:0000250|UniProtKB:Q8N201,
CC       ECO:0000269|PubMed:21078872, ECO:0000269|PubMed:23097424,
CC       ECO:0000269|PubMed:23288851}.
CC   -!- SUBUNIT: Belongs to the multiprotein complex Integrator, at least
CC       composed of IntS1, IntS2, IntS3, IntS4, omd/IntS5, IntS6, defl/IntS7,
CC       IntS8, IntS9, IntS10, IntS11, IntS12, asun/IntS13 and IntS14
CC       (PubMed:23097424). Within the complex, interacts with IntS12 and IntS9
CC       (PubMed:23288851). Interaction with IntS12 is likely to be important
CC       for promoting 3'-end processing of snRNAs (PubMed:23288851). Interacts
CC       with Mediator complex members Cdk8 and CycC (PubMed:23097424).
CC       {ECO:0000269|PubMed:23097424, ECO:0000269|PubMed:23288851}.
CC   -!- SUBCELLULAR LOCATION: Nucleus membrane {ECO:0000269|PubMed:23288851};
CC       Single-pass membrane protein {ECO:0000255}.
CC   -!- SIMILARITY: Belongs to the Integrator subunit 1 family. {ECO:0000305}.
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DR   EMBL; AE013599; AAF47145.2; -; Genomic_DNA.
DR   EMBL; BT001870; AAN71641.1; -; mRNA.
DR   RefSeq; NP_611875.1; NM_138031.3.
DR   AlphaFoldDB; Q9W1C5; -.
DR   IntAct; Q9W1C5; 12.
DR   STRING; 7227.FBpp0072077; -.
DR   PaxDb; Q9W1C5; -.
DR   PRIDE; Q9W1C5; -.
DR   EnsemblMetazoa; FBtr0072168; FBpp0072077; FBgn0034964.
DR   GeneID; 37840; -.
DR   KEGG; dme:Dmel_CG3173; -.
DR   UCSC; CG3173-RA; d. melanogaster.
DR   CTD; 26173; -.
DR   FlyBase; FBgn0034964; IntS1.
DR   VEuPathDB; VectorBase:FBgn0034964; -.
DR   eggNOG; KOG4596; Eukaryota.
DR   GeneTree; ENSGT00390000015743; -.
DR   HOGENOM; CLU_001690_0_0_1; -.
DR   InParanoid; Q9W1C5; -.
DR   OMA; NWDTIER; -.
DR   OrthoDB; 357673at2759; -.
DR   PhylomeDB; Q9W1C5; -.
DR   Reactome; R-DME-6807505; RNA polymerase II transcribes snRNA genes.
DR   SignaLink; Q9W1C5; -.
DR   BioGRID-ORCS; 37840; 0 hits in 1 CRISPR screen.
DR   GenomeRNAi; 37840; -.
DR   PRO; PR:Q9W1C5; -.
DR   Proteomes; UP000000803; Chromosome 2R.
DR   Bgee; FBgn0034964; Expressed in adult Malpighian tubule (Drosophila) and 26 other tissues.
DR   Genevisible; Q9W1C5; DM.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0032039; C:integrator complex; ISS:FlyBase.
DR   GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0045666; P:positive regulation of neuron differentiation; IMP:FlyBase.
DR   GO; GO:0034472; P:snRNA 3'-end processing; IDA:FlyBase.
DR   GO; GO:0016180; P:snRNA processing; ISS:FlyBase.
DR   GO; GO:0034474; P:U2 snRNA 3'-end processing; IBA:GO_Central.
DR   InterPro; IPR016024; ARM-type_fold.
DR   InterPro; IPR022145; DUF3677.
DR   InterPro; IPR038902; INTS1.
DR   PANTHER; PTHR21224; PTHR21224; 1.
DR   Pfam; PF12432; DUF3677; 1.
DR   SUPFAM; SSF48371; SSF48371; 1.
PE   1: Evidence at protein level;
KW   Membrane; Nucleus; Reference proteome; Transmembrane; Transmembrane helix.
FT   CHAIN           1..2053
FT                   /note="Integrator complex subunit 1"
FT                   /id="PRO_0000437668"
FT   TRANSMEM        708..728
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   REGION          36..58
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          249..285
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        265..280
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CONFLICT        150
FT                   /note="S -> T (in Ref. 3; AAN71641)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1539
FT                   /note="D -> E (in Ref. 3; AAN71641)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   2053 AA;  235099 MW;  832B92FAE75EB3F3 CRC64;
     MDRGKGSGSN RSQKKVPLGG ELFALGKSVR DDSKSKILPI KGMSSSDRKR EASTALASSS
     KRFRGNLKDA GAPDMSSGSS QCETWEQFAV DCDLDTVVET IYAALEQNDS ETVGRLVCGV
     IKQTTTSSSR SKVDNIALLA LIYVAKVQPS IFCTDIVACA LLSFLRREAN VKMRYNTNLH
     ILFANLLTRG FMEISQWPEV LLRIYIDDAV NERYWADNEL CAPLVKNICA AFKTRTPHIS
     LLRWDVSSSL PSGQAHRDSM TVDDDSGDNS TQSLDASPLN TESEPIPDAM CTTKSRFSDA
     VVQKHVSDAI RDQLNKRQQQ DNYTRNFLKF LCTTSGIAEV RCLSISRLEL WIHNGKLVKF
     AQQLLSYICF NIKGRNTQDN EVLLVLVKMR LKTKPLINHY MSCLKEMIFL QPEILSTVMK
     LVVQNELSNT RNPNNMGMLA TMFQTSADQS AATLAEIYQE FLLQRDDCLR TLRVFLRELV
     RMLRFDVNLV KFCKTFLSER EDLTPQIEMF EFKERIFNSM VDIVCLCMFL SATPQAREAS
     LSLKTNRDTK NNHALLKLYN QMSQIQLDTV SWMYETVPTL FKIPAAEYHQ ALHKLLLLDS
     PEQYSRCDQW PSEPERGAIL RIISETPIHE ETLLRIILIG ITKDIPFSIA NTFDVLLLVI
     KRVSGMKATN IPAVQANKFD IIDFLFSMSE YHHPENIRLP AEYEPPKLAI IAFYWKAWLI
     LLMISAHNPS SFGAFCWDHY PTMKMMMEIC ITNQFNNSSA TKDELQIITM ERDHILQFET
     YLAAQTSPHA VITEETAILI TQLMLMDPMG TPRKVPSMVL DQLKFLNQTY KLGHLFCRCR
     KPDLLLDIIQ RQGTTQSMPW LSDLVQNSEG DFSHLPVQCL CEFLLFNAHI INEENSRDAE
     LVNFLRNLIF DGNLSHQIVC ELLDYIFRRL SSTVKQSRVA ALSGLKIIFR HSGDFENEWL
     LKSLQQIPHF YEVKPFIIPQ LRAACQVENC PELIMAYIQF ITAHTLNDPV NEMLDHVIDM
     AQLIVERSTM FQHIIISQED YDYVPDENRI QTLKCLFVMF NNYIIKLREY HEPYEWTEYP
     DLLMVQFDDG VQLPLHINII HAFIILLTYS NSNMPESIPI LDYWFPPGRP APVAFLPSMP
     QEQVQLLPDW LKLKMIRSSV DRLIEAALND LTPDQIVLFV QNFGTPVNSM SKLLAMLDTA
     VLEQFDLVKN AILNKAYLAQ LIEIQQARGA KNGHYTVQAL DLHSHSQTVP DLPKISVVIQ
     EAVEIDDYDS SDSDDRPTNF LATKEVAQTI LTQPDQLTES RSDCRSLIQK LLDMLASPNS
     NRADVVNAIT EVLAVGCSVT MSRHACTFLR TFFSCMLHSD KYHILENALQ KNLSMFKHTF
     ADSSLLQKSE LYHESLVFML RNSREIYAQQ FKANTALVAR KRIVRAIVQS FDQTKDSKTV
     AKSKSDQLFH NGLFIDWLSE MDPEIVSTQL MKERFLFSKS CSEFRFYLLS LINHQTNWDT
     IERIAEYLFK NFHEDYDYAT VLNYFEALTT NPKLWKGRDK YMSKNVRPDA FFMLRTSELE
     PFSHFILHEG LSEVKLDSKN YDFKLCSRMN LLFKLTEKRR DLMVKVMEHV EKSSVSDYLK
     LQVLQQMYIM YPRIKFLKPG KTGEQAYKLQ NLKGCQADKV SNNLITCLGS LVGKKDFETL
     STDTELLLRK LAASHPLLFL RQLGVLSSIM QGRAQLSMKA LREEHHFHRF VQILRTLELL
     QPTIFEEAYK NEIQNTLSCY FNFFKHHSNV KEACQMLNKF VQMLQAYINY NPSSALLFIE
     QYVGILKELA AKYTSLGKLQ VLVQAVALLQ HKSHSATELD DEEVKYEYDL DEHFDVKPSA
     SKPVVTEDPI EVNPQTPIDP SSSRGPLSVL TLGSYSRSNY TDISPHFLDL VKIIKQSNTE
     DVVLGPMQEL ECLTSKRFVF INELFERLLN LIFSPSAQIR SIAFIILIRH LKHNPGNSDI
     NLCTLNAYIQ CLRDENSSVA ATAIDNLPEM SVLLQEHAID ILTVAFSLGL KSCLNTGHQI
     RKVLQTLVIQ HGY
 
 
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