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RIF1_DROME
ID   RIF1_DROME              Reviewed;        1416 AA.
AC   Q9XZ34; Q4V5E2;
DT   18-JUL-2018, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1999, sequence version 1.
DT   03-AUG-2022, entry version 155.
DE   RecName: Full=Telomere-associated protein RIF1 {ECO:0000305};
DE   AltName: Full=Rap1 interacting factor 1 {ECO:0000303|PubMed:22712556, ECO:0000312|FlyBase:FBgn0050085};
GN   Name=Rif1 {ECO:0000303|PubMed:22712556, ECO:0000312|FlyBase:FBgn0050085};
GN   ORFNames=CG30085 {ECO:0000312|FlyBase:FBgn0050085};
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:AAD34780.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Berkeley {ECO:0000312|EMBL:AAD34780.1};
RC   TISSUE=Embryo {ECO:0000312|EMBL:AAD34780.1};
RX   PubMed=10731138; DOI=10.1126/science.287.5461.2222;
RA   Rubin G.M., Hong L., Brokstein P., Evans-Holm M., Frise E., Stapleton M.,
RA   Harvey D.A.;
RT   "A Drosophila complementary DNA resource.";
RL   Science 287:2222-2224(2000).
RN   [4] {ECO:0000312|EMBL:AAY55130.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Berkeley {ECO:0000312|EMBL:AAY55130.1};
RC   TISSUE=Embryo {ECO:0000312|EMBL:AAY55130.1};
RA   Stapleton M., Carlson J., Chavez C., Frise E., George R., Pacleb J.,
RA   Park S., Wan K., Yu C., Celniker S.;
RL   Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5] {ECO:0000305}
RP   FUNCTION, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX   PubMed=22712556; DOI=10.1186/1471-2164-13-255;
RA   Sreesankar E., Senthilkumar R., Bharathi V., Mishra R.K., Mishra K.;
RT   "Functional diversification of yeast telomere associated protein, Rif1, in
RT   higher eukaryotes.";
RL   BMC Genomics 13:255-255(2012).
RN   [6] {ECO:0000305}
RP   FUNCTION, INTERACTION WITH PP1-87B, SUBCELLULAR LOCATION, TISSUE
RP   SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX   PubMed=26022086; DOI=10.1038/srep10679;
RA   Sreesankar E., Bharathi V., Mishra R.K., Mishra K.;
RT   "Drosophila Rif1 is an essential gene and controls late developmental
RT   events by direct interaction with PP1-87B.";
RL   Sci. Rep. 5:10679-10679(2015).
RN   [7]
RP   ERRATUM OF PUBMED:26022086.
RX   PubMed=26859551; DOI=10.1038/srep17126;
RA   Sreesankar E., Bharathi V., Mishra R.K., Mishra K.;
RT   "Corrigendum: Drosophila Rif1 is an essential gene and controls late
RT   developmental events by direct interaction with PP1-87B.";
RL   Sci. Rep. 6:17126-17126(2016).
RN   [8]
RP   FUNCTION, INTERACTION WITH SUUR, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP   DISRUPTION PHENOTYPE, AND MUTAGENESIS OF 1076-ILE-LEU-1077 AND
RP   1101-VAL--PHE-1103.
RX   PubMed=30277458; DOI=10.7554/elife.39140;
RA   Munden A., Rong Z., Sun A., Gangula R., Mallal S., Nordman J.T.;
RT   "Rif1 inhibits replication fork progression and controls DNA copy number in
RT   Drosophila.";
RL   Elife 7:0-0(2018).
RN   [9] {ECO:0000305}
RP   FUNCTION, INTERACTION WITH PP1-87B, SUBCELLULAR LOCATION, DEVELOPMENTAL
RP   STAGE, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF SER-946; 958-SER-SER-959;
RP   969-SER-SER-970; SER-1002; THR-1019; 1031-SER-THR-1032; SER-1035; THR-1043;
RP   1047-SER-THR-1048; SER-1067; SER-1071; SER-1075; SER-1093; SER-1102 AND
RP   THR-1140.
RX   PubMed=29746464; DOI=10.1371/journal.pbio.2005687;
RA   Seller C.A., O'Farrell P.H.;
RT   "Rif1 prolongs the embryonic S phase at the Drosophila mid-blastula
RT   transition.";
RL   PLoS Biol. 16:E2005687-E2005687(2018).
CC   -!- FUNCTION: Regulates the timing of initiation of DNA replication
CC       (PubMed:29746464, PubMed:30277458, PubMed:26022086). Functions in copy
CC       number control by promoting the underreplication of DNA, which is found
CC       in many late replicating euchromatic regions of salivary gland polytene
CC       chromosomes (PubMed:30277458). Promotes underreplication by localizing
CC       to active DNA replication forks in a partially SuUR-dependent manner,
CC       and inhibiting replication fork progression (PubMed:30277458). Might
CC       also work as an adapter to recruit Pp1-87B to multiple sites on the
CC       chromosome and may function with Pp1-87B to mediate underreplication
CC       (PubMed:26022086, PubMed:29746464, PubMed:30277458). Plays an essential
CC       role in embryonic development, in the transition from larvae to pupae
CC       and, probably, in proliferating tissues later on (PubMed:26022086,
CC       PubMed:29746464). In embryos, during mid-blastula transition, binds to
CC       and selectively delays the replication of large blocks of repetitive
CC       DNA satellite sequences during S phase in response to the activity of
CC       Cdk1; maternal Rif1 is specifically required for the normal extension
CC       of S phase 14 (PubMed:29746464). Unlike mammalian orthologs, does not
CC       appear to play a role in DNA damage repair (PubMed:22712556,
CC       PubMed:26022086). {ECO:0000269|PubMed:22712556,
CC       ECO:0000269|PubMed:26022086, ECO:0000269|PubMed:29746464,
CC       ECO:0000269|PubMed:30277458}.
CC   -!- SUBUNIT: Interacts with Pp1-87b (PubMed:26022086, PubMed:29746464).
CC       Interacts with SuUR (via SNF2-like region) (PubMed:30277458).
CC       {ECO:0000269|PubMed:26022086, ECO:0000269|PubMed:29746464,
CC       ECO:0000269|PubMed:30277458}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:22712556,
CC       ECO:0000269|PubMed:26022086, ECO:0000269|PubMed:29746464,
CC       ECO:0000269|PubMed:30277458}. Chromosome {ECO:0000269|PubMed:22712556,
CC       ECO:0000269|PubMed:26022086, ECO:0000269|PubMed:29746464,
CC       ECO:0000269|PubMed:30277458}. Chromosome, telomere
CC       {ECO:0000269|PubMed:26022086}. Note=Localizes to heterochromatin in all
CC       stages of amplifying follicle cells and accumulates at active DNA
CC       replication forks in the later stages of DNA amplification
CC       (PubMed:30277458). Associates with polytene chromosomes in salivary
CC       glands (PubMed:26022086). Associates with heterochromatin in a dynamic
CC       manner in different mitotic stages of the cell cycle (PubMed:22712556,
CC       PubMed:26022086, PubMed:29746464, PubMed:30277458). Absent at metaphase
CC       chromosomes but re-associates with the condensed chromosomes during
CC       late anaphase (PubMed:22712556, PubMed:26022086, PubMed:29746464).
CC       During mid-blastula transition in the S phase of embryos, dissociates
CC       from chromatin before the replication of the bound DNA satellite
CC       sequences (PubMed:29746464). {ECO:0000269|PubMed:22712556,
CC       ECO:0000269|PubMed:26022086, ECO:0000269|PubMed:29746464,
CC       ECO:0000269|PubMed:30277458}.
CC   -!- TISSUE SPECIFICITY: Expressed in nurse cells and follicle cells in the
CC       adult female (at protein level) (PubMed:26022086, PubMed:30277458).
CC       Detected in adult at extremely low levels (PubMed:26022086).
CC       {ECO:0000269|PubMed:26022086, ECO:0000269|PubMed:30277458}.
CC   -!- DEVELOPMENTAL STAGE: Expressed in embryos at high levels between 0-2
CC       hours; from 8 to 14 hours, the highest levels are in the brain then
CC       diminishes to negligible levels (at protein level) (PubMed:22712556,
CC       PubMed:26022086, PubMed:29746464). Expressed in larval imaginal disks
CC       and salivary glands (at protein level) (PubMed:26022086). Detected in
CC       larvae at lower levels in imaginal disks, the central nervous system
CC       and ovary and, at extremely low levels, in testis (PubMed:26022086).
CC       {ECO:0000269|PubMed:22712556, ECO:0000269|PubMed:26022086,
CC       ECO:0000269|PubMed:29746464}.
CC   -!- PTM: Phosphorylated, probably by Cdk1; phosphorylation regulates
CC       dissociation from heterochromatin. {ECO:0000269|PubMed:29746464}.
CC   -!- DISRUPTION PHENOTYPE: Embryos have a reduced hatch rate and develop
CC       into adults with reduced survival (PubMed:29746464). During mid-
CC       blastula transition in embryos, S phase 14 is significantly shorter
CC       (PubMed:29746464). In larval salivary glands, loss of DNA
CC       underreplication resulting in abnormally enlarged chromocenters
CC       (PubMed:30277458). RNAi-mediated knockdown results in lethality
CC       (PubMed:26022086). Escaper flies only live for a few days and are
CC       infertile (PubMed:26022086). Females show increased necrotic spots in
CC       the abdominal segments (PubMed:26022086). RNAi-mediated knockdown in
CC       the imaginal disks does not affect viability (PubMed:26022086).
CC       {ECO:0000269|PubMed:26022086, ECO:0000269|PubMed:29746464,
CC       ECO:0000269|PubMed:30277458}.
CC   -!- SIMILARITY: Belongs to the RIF1 family. Highly divergent.
CC       {ECO:0000305}.
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DR   EMBL; AE013599; AAM70965.1; -; Genomic_DNA.
DR   EMBL; AF132192; AAD34780.1; -; mRNA.
DR   EMBL; BT022714; AAY55130.1; -; mRNA.
DR   RefSeq; NP_725497.1; NM_166120.2.
DR   AlphaFoldDB; Q9XZ34; -.
DR   STRING; 7227.FBpp0086441; -.
DR   PaxDb; Q9XZ34; -.
DR   PRIDE; Q9XZ34; -.
DR   EnsemblMetazoa; FBtr0087306; FBpp0086441; FBgn0050085.
DR   GeneID; 246445; -.
DR   KEGG; dme:Dmel_CG30085; -.
DR   UCSC; CG30085-RA; d. melanogaster.
DR   CTD; 55183; -.
DR   FlyBase; FBgn0050085; Rif1.
DR   VEuPathDB; VectorBase:FBgn0050085; -.
DR   eggNOG; ENOG502QV6C; Eukaryota.
DR   GeneTree; ENSGT00390000012204; -.
DR   HOGENOM; CLU_005092_0_0_1; -.
DR   InParanoid; Q9XZ34; -.
DR   OMA; PCLVALW; -.
DR   OrthoDB; 70741at2759; -.
DR   PhylomeDB; Q9XZ34; -.
DR   BioGRID-ORCS; 246445; 0 hits in 1 CRISPR screen.
DR   GenomeRNAi; 246445; -.
DR   PRO; PR:Q9XZ34; -.
DR   Proteomes; UP000000803; Chromosome 2R.
DR   Bgee; FBgn0050085; Expressed in egg cell and 41 other tissues.
DR   GO; GO:0010369; C:chromocenter; IDA:FlyBase.
DR   GO; GO:0000781; C:chromosome, telomeric region; IDA:FlyBase.
DR   GO; GO:0000792; C:heterochromatin; IDA:UniProtKB.
DR   GO; GO:0043596; C:nuclear replication fork; IDA:FlyBase.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR   GO; GO:0001700; P:embryonic development via the syncytial blastoderm; IMP:UniProtKB.
DR   GO; GO:2000104; P:negative regulation of DNA-templated DNA replication; IMP:FlyBase.
DR   GO; GO:1901991; P:negative regulation of mitotic cell cycle phase transition; IMP:UniProtKB.
DR   GO; GO:0030174; P:regulation of DNA-templated DNA replication initiation; IMP:UniProtKB.
DR   GO; GO:0071807; P:replication fork arrest involved in DNA replication termination; IMP:UniProtKB.
DR   GO; GO:0000723; P:telomere maintenance; IBA:GO_Central.
DR   InterPro; IPR016024; ARM-type_fold.
DR   InterPro; IPR028566; Rif1.
DR   InterPro; IPR022031; Rif1_N.
DR   PANTHER; PTHR22928; PTHR22928; 1.
DR   Pfam; PF12231; Rif1_N; 1.
DR   SUPFAM; SSF48371; SSF48371; 1.
PE   1: Evidence at protein level;
KW   Cell cycle; Chromosome; Nucleus; Reference proteome; Telomere.
FT   CHAIN           1..1416
FT                   /note="Telomere-associated protein RIF1"
FT                   /id="PRO_0000444898"
FT   REGION          789..858
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          886..984
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1021..1054
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1166..1186
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        789..803
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        951..977
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1021..1053
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MUTAGEN         946
FT                   /note="S->A: Probable loss of Cdk1-mediated regulation
FT                   leads to lack of dissociation from chromatin and block of
FT                   replication resulting in anaphase chromosome bridging
FT                   during mid-blastula transition in embryos; in the eye
FT                   imaginal disk, results in complete lethality with pupae
FT                   developing into headless nearly adult flies; when
FT                   associated with 958-A-A-959; 969-A-A-970; A-1002; A-1019;
FT                   1031-A-A-1032; A-1035; A-1043; 1047-A-A-1048; A-1067; A-
FT                   1071; A-1075; A-1093; A-1102 and A-1140."
FT                   /evidence="ECO:0000269|PubMed:29746464"
FT   MUTAGEN         958..959
FT                   /note="SS->AA: Probable loss of Cdk1-mediated regulation
FT                   leads to lack of dissociation from chromatin and block of
FT                   replication resulting in anaphase chromosome bridging
FT                   during mid-blastula transition in embryos; in the eye
FT                   imaginal disk, results in complete lethality with pupae
FT                   developing into headless nearly adult flies; when
FT                   associated with A-946; 969-A-A-970; A-1002; A-1019; 1031-A-
FT                   A-1032; A-1035; A-1043; 1047-A-A-1048; A-1067; A-1071; A-
FT                   1075; A-1093; A-1102 and A-1140."
FT                   /evidence="ECO:0000269|PubMed:29746464"
FT   MUTAGEN         969..970
FT                   /note="SS->AA: Probable loss of Cdk1-mediated regulation
FT                   leads to lack of dissociation from chromatin and block of
FT                   replication resulting in anaphase chromosome bridging
FT                   during mid-blastula transition in embryos; in the eye
FT                   imaginal disk, results in complete lethality with pupae
FT                   developing into headless nearly adult flies; when
FT                   associated with A-946; 958-A-A-959; A-1002; A-1019; 1031-A-
FT                   A-1032; A-1035; A-1043; 1047-A-A-1048; A-1067; A-1071; A-
FT                   1075; A-1093; A-1102 and A-1140."
FT                   /evidence="ECO:0000269|PubMed:29746464"
FT   MUTAGEN         1002
FT                   /note="S->A: Probable loss of Cdk1-mediated regulation
FT                   leads to lack of dissociation from chromatin and block of
FT                   replication resulting in anaphase chromosome bridging
FT                   during mid-blastula transition in embryos; in the eye
FT                   imaginal disk, results in complete lethality with pupae
FT                   developing into headless nearly adult flies; when
FT                   associated with A-946; 958-A-A-959; 969-A-A-970; A-1019;
FT                   1031-A-A-1032; A-1035; A-1043; 1047-A-A-1048; A-1067; A-
FT                   1071; A-1075; A-1093; A-1102 and A-1140."
FT                   /evidence="ECO:0000269|PubMed:29746464"
FT   MUTAGEN         1019
FT                   /note="T->A: Probable loss of Cdk1-mediated regulation
FT                   leads to lack of dissociation from chromatin and block of
FT                   replication resulting in anaphase chromosome bridging
FT                   during mid-blastula transition in embryos; in the eye
FT                   imaginal disk, results in complete lethality with pupae
FT                   developing into headless nearly adult flies; when
FT                   associated with A-946; 958-A-A-959; 969-A-A-970; A-1002;
FT                   1031-A-A-1032; A-1035; A-1043; 1047-A-A-1048; A-1067; A-
FT                   1071; A-1075; A-1093; A-1102 and A-1140."
FT                   /evidence="ECO:0000269|PubMed:29746464"
FT   MUTAGEN         1031..1032
FT                   /note="ST->AA: Probable loss of Cdk1-mediated regulation
FT                   leads to lack of dissociation from chromatin and block of
FT                   replication resulting in anaphase chromosome bridging
FT                   during mid-blastula transition in embryos; in the eye
FT                   imaginal disk, results in complete lethality with pupae
FT                   developing into headless nearly adult flies; when
FT                   associated with A-946; 958-A-A-959; 969-A-A-970; A-1002; A-
FT                   1019; A-1035; A-1043; 1047-A-A-1048; A-1067; A-1071; A-
FT                   1075; A-1093; A-1102 and A-1140."
FT                   /evidence="ECO:0000269|PubMed:29746464"
FT   MUTAGEN         1035
FT                   /note="S->A: Probable loss of Cdk1-mediated regulation
FT                   leads to lack of dissociation from chromatin and block of
FT                   replication resulting in anaphase chromosome bridging
FT                   during mid-blastula transition in embryos; in the eye
FT                   imaginal disk, results in complete lethality with pupae
FT                   developing into headless nearly adult flies; when
FT                   associated with A-946; 958-A-A-959; 969-A-A-970; A-1002; A-
FT                   1019; 1031-A-A-1032; A-1043; 1047-A-A-1048; A-1067; A-1071;
FT                   A-1075; A-1093; A-1102 and A-1140."
FT                   /evidence="ECO:0000269|PubMed:29746464"
FT   MUTAGEN         1043
FT                   /note="T->A: Probable loss of Cdk1-mediated regulation
FT                   leads to lack of dissociation from chromatin and block of
FT                   replication resulting in anaphase chromosome bridging
FT                   during mid-blastula transition in embryos; in the eye
FT                   imaginal disk, results in complete lethality with pupae
FT                   developing into headless nearly adult flies; when
FT                   associated with A-946; 958-A-A-959; 969-A-A-970; A-1002; A-
FT                   1019; 1031-A-A-1032; A-1035; 1047-A-A-1048; A-1067; A-1071;
FT                   A-1075; A-1093; A-1102 and A-1140."
FT                   /evidence="ECO:0000269|PubMed:29746464"
FT   MUTAGEN         1047..1048
FT                   /note="ST->AA: Probable loss of Cdk1-mediated regulation
FT                   leads to lack of dissociation from chromatin and block of
FT                   replication resulting in anaphase chromosome bridging
FT                   during mid-blastula transition in embryos; in the eye
FT                   imaginal disk, results in complete lethality with pupae
FT                   developing into headless nearly adult flies; when
FT                   associated with A-946; 958-A-A-959; 969-A-A-970; A-1002; A-
FT                   1019; 1031-A-A-1032; A-1035; A-1043; A-1067; A-1071; A-
FT                   1075; A-1093; A-1102 and A-1140."
FT                   /evidence="ECO:0000269|PubMed:29746464"
FT   MUTAGEN         1067
FT                   /note="S->A: Probable loss of Cdk1-mediated regulation
FT                   leads to lack of dissociation from chromatin and block of
FT                   replication resulting in anaphase chromosome bridging
FT                   during mid-blastula transition in embryos; in the eye
FT                   imaginal disk, results in complete lethality with pupae
FT                   developing into headless nearly adult flies; when
FT                   associated with A-946; 958-A-A-959; 969-A-A-970; A-1002; A-
FT                   1019; 1031-A-A-1032; A-1035; A-1043; 1047-A-A-1048; A-1071;
FT                   A-1075; A-1093; A-1102 and A-1140."
FT                   /evidence="ECO:0000269|PubMed:29746464"
FT   MUTAGEN         1071
FT                   /note="S->A: Probable loss of Cdk1-mediated regulation
FT                   leads to lack of dissociation from chromatin and block of
FT                   replication resulting in anaphase chromosome bridging
FT                   during mid-blastula transition in embryos; in the eye
FT                   imaginal disk, results in complete lethality with pupae
FT                   developing into headless nearly adult flies; when
FT                   associated with A-946; 958-A-A-959; 969-A-A-970; A-1002; A-
FT                   1019; 1031-A-A-1032; A-1035; A-1043; 1047-A-A-1048; A-1067;
FT                   A-1075; A-1093; A-1102 and A-1140."
FT                   /evidence="ECO:0000269|PubMed:29746464"
FT   MUTAGEN         1075
FT                   /note="S->A: Probable loss of Cdk1-mediated regulation
FT                   leads to lack of dissociation from chromatin and block of
FT                   replication resulting in anaphase chromosome bridging
FT                   during mid-blastula transition in embryos; in the eye
FT                   imaginal disk, results in complete lethality with pupae
FT                   developing into headless nearly adult flies; when
FT                   associated with A-946; 958-A-A-959; 969-A-A-970; A-1002; A-
FT                   1019; 1031-A-A-1032; A-1035; A-1043; 1047-A-A-1048; A-1067;
FT                   A-1071; A-1093; A-1102 and A-1140."
FT                   /evidence="ECO:0000269|PubMed:29746464"
FT   MUTAGEN         1076..1077
FT                   /note="IL->AA: Significant loss of DNA underreplication in
FT                   larval salivary glands; when associated with 1101-A--A-
FT                   1103."
FT                   /evidence="ECO:0000269|PubMed:30277458"
FT   MUTAGEN         1093
FT                   /note="S->A: Probable loss of Cdk1-mediated regulation
FT                   leads to lack of dissociation from chromatin and block of
FT                   replication resulting in anaphase chromosome bridging
FT                   during mid-blastula transition in embryos; in the eye
FT                   imaginal disk, results in complete lethality with pupae
FT                   developing into headless nearly adult flies; when
FT                   associated with A-946; 958-A-A-959; 969-A-A-970; A-1002; A-
FT                   1019; 1031-A-A-1032; A-1035; A-1043; 1047-A-A-1048; A-1067;
FT                   A-1071; A-1075; A-1102 and A-1140."
FT                   /evidence="ECO:0000269|PubMed:29746464"
FT   MUTAGEN         1101..1103
FT                   /note="VSF->ASA: Significant loss of DNA underreplication
FT                   in larval salivary glands; when associated with 1076-A-A-
FT                   1077."
FT                   /evidence="ECO:0000269|PubMed:30277458"
FT   MUTAGEN         1102
FT                   /note="S->A: Probable loss of Cdk1-mediated regulation
FT                   leads to lack of dissociation from chromatin and block of
FT                   replication resulting in anaphase chromosome bridging
FT                   during mid-blastula transition in embryos; in the eye
FT                   imaginal disk, results in complete lethality with pupae
FT                   developing into headless nearly adult flies; when
FT                   associated with A-946; 958-A-A-959; 969-A-A-970; A-1002; A-
FT                   1019; 1031-A-A-1032; A-1035; A-1043; 1047-A-A-1048; A-1067;
FT                   A-1071; A-1075; A-1093 and A-1140."
FT                   /evidence="ECO:0000269|PubMed:29746464"
FT   MUTAGEN         1140
FT                   /note="T->A: Probable loss of Cdk1-mediated regulation
FT                   leads to lack of dissociation from chromatin and block of
FT                   replication resulting in anaphase chromosome bridging
FT                   during mid-blastula transition in embryos; in the eye
FT                   imaginal disk, results in complete lethality with pupae
FT                   developing into headless nearly adult flies; when
FT                   associated with A-946; 958-A-A-959; 969-A-A-970; A-1002; A-
FT                   1019; 1031-A-A-1032; A-1035; A-1043; 1047-A-A-1048; A-1067;
FT                   A-1071; A-1075; A-1093 and A-1102."
FT                   /evidence="ECO:0000269|PubMed:29746464"
FT   CONFLICT        474
FT                   /note="K -> E (in Ref. 4; AAY55130)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1049
FT                   /note="P -> R (in Ref. 4; AAY55130)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1156
FT                   /note="I -> T (in Ref. 4; AAY55130)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1416 AA;  156820 MW;  307E007CF4B6F83E CRC64;
     MDVDFGAQAG QSYRTVQLSA KEVLAAGRRQ HYCNMIDLLA SSCKSSGLIA TSFTDDELVE
     FWLGDILPLM FDADRKIQDC AVAALAEALV ALDVSVIHSA KCWPQIRSEF VDKYTIIIGE
     MRDAKNSNWH KIWTLLVQIM DEDLLRGCVY INKFLALVEL GFRNPDNGVR SEAFLCWRVL
     IKIFAAYDEL TSAKRLRLLL IPLRTSQSRS SHVSGIKLRV WWYLLSCLDH ELPKSFDSAV
     EHFLAFMLGG GPRNLATGLA HNYQTARELA LPCLVALWGV ESSEPLQRLM RELRLETLVQ
     PSPLMSVEVF QQHWKPLLAA AVSGLKLLTE NDATEAEQLL LQLLVRNLCL AMFRLAVAPF
     NVACCSEIEK ILQAEDNSGG RVVRALFNTI AADNLVMERV SGSDHLDVLE AYLKLVLKSK
     TEVPAAILQR SIACIFAVDR IEANNQNEFR MLGSFAELLM QANDEEDFEG FAFKLQVWRQ
     VSQALSNYLR NNALEYRVAH NASLLDTWLL WPLQTLAAFA GRRASNSFDA SFCDQWRQLV
     NAGQNAPGRK KFLTDLKATL TDLLKSKDEP LFAELFDAYV TSLIKFGLCK EAPLYKDVFG
     LLQTIFEQPS SQKTLEACLN TLRNLVVELR QNELMVVFDS LKPTLSSGIQ CWNKMKCEGG
     FLEEWKRGIQ EKFRKLPMKT MANQLKELFK ADDLFVIIPS VWSLNPEKLT DRQKERFAEK
     SDIPALYNDM SQSQDSASIK PWTPKKVVIA KSKQGELALT GKDDNGEVID ITASEESEKE
     PVRVDVVTPI RKKPGRKSQA QKELEAAARA ASLAEEPPKR QTRTRAAQKE TEQVAQPQPA
     FEPQLRSPKK LPPSPVVQST AAAVKQAKVA KPTPVVVIAQ SEDLFPEVAA EPEPQPEPVK
     KPDPVPETTQ LTPPDVPLEA VPSTQLPGSS GDPAASAGAV AAGEMSPKKS GTRIYNLSSP
     PDRKQTNNSS SPTLRPKPTG HLTGRGAQLI NMIRNKKLDA ASGSPYACMS TSRLVHQVTP
     ARAQDRAEQV STPTSELNEL TGTDHTSTPI QAPPSKDLLV FSKRLPSPSA SPSVSILKRK
     LRCESLDDVT LDSPALKRKR VSFHDPPVSV TKEYLRDAEE TRSSLKPKRC LLMDKVAQTT
     EMRQALRRRG RLDSIIEIER FASEQTARTA TTDKSLDKST GEAPEEDAFT SLKWNDTGNA
     HNISISEEPV KAMEVESELE TAGQDLAIMD PEAALDLAVA QLPLESVLQR YFDKSPLKSA
     GMLAKFLSAQ MTANEKLKTN VLETLSENHS KDFLDHAVRE NLSSVVCDRL NPTSVLEYVC
     AKSKISASCR NGLLAQVPEI LKSGPRSDSE RLAFVQQLMV QCSPGDDLLL DLIDLLMRTR
     RERNNSTSTH ISKGVVSAVG SPDNVAETAA DSSSNL
 
 
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