FICD_DROME
ID FICD_DROME Reviewed; 492 AA.
AC Q8SWV6; Q9VMD8;
DT 01-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Protein adenylyltransferase Fic;
DE Short=dFic {ECO:0000303|PubMed:25395623};
DE EC=2.7.7.n1 {ECO:0000269|PubMed:25395623, ECO:0000269|PubMed:29089387};
DE AltName: Full=De-AMPylase Fic {ECO:0000305};
DE EC=3.1.4.- {ECO:0000269|PubMed:29089387};
GN Name=Fic {ECO:0000303|PubMed:25395623, ECO:0000312|FlyBase:FBgn0263278};
GN ORFNames=CG9523;
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 [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 [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo;
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]
RP FUNCTION, ACTIVE SITE, AND MUTAGENESIS OF HIS-375.
RX PubMed=19503829; DOI=10.1371/journal.pone.0005818;
RA Kinch L.N., Yarbrough M.L., Orth K., Grishin N.V.;
RT "Fido, a novel AMPylation domain common to fic, doc, and AvrB.";
RL PLoS ONE 4:E5818-E5818(2009).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, INDUCTION, AND MUTAGENESIS OF GLU-247 AND
RP HIS-375.
RX PubMed=25395623; DOI=10.1074/jbc.m114.612515;
RA Ham H., Woolery A.R., Tracy C., Stenesen D., Kraemer H., Orth K.;
RT "Unfolded protein response-regulated Drosophila Fic (dFic) protein
RT reversibly AMPylates BiP chaperone during endoplasmic reticulum
RT homeostasis.";
RL J. Biol. Chem. 289:36059-36069(2014).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, DISRUPTION PHENOTYPE, AND
RP MUTAGENESIS OF GLU-247; ILE-271 AND HIS-375.
RX PubMed=29089387; DOI=10.1074/jbc.m117.799296;
RA Casey A.K., Moehlman A.T., Zhang J., Servage K.A., Kraemer H., Orth K.;
RT "Fic-mediated deAMPylation is not dependent on homodimerization and rescues
RT toxic AMPylation in flies.";
RL J. Biol. Chem. 292:21193-21204(2017).
CC -!- FUNCTION: Protein that can both mediate the addition of adenosine 5'-
CC monophosphate (AMP) to specific residues of target proteins
CC (AMPylation), and the removal of the same modification from target
CC proteins (de-AMPylation), depending on the context (PubMed:29089387).
CC The side chain of Glu-247 determines which of the two opposing
CC activities (AMPylase or de-AMPylase) will take place (By similarity).
CC Acts as a key regulator of the unfolded protein response (UPR) by
CC mediating AMPylation or de-AMPylation of Hsc70-3/BiP (PubMed:25395623,
CC PubMed:29089387). In unstressed cells, acts as an adenylyltransferase
CC by mediating AMPylation of Hsc70-3/BiP at 'Thr-518', thereby
CC inactivating it (PubMed:29089387). In response to endoplasmic reticulum
CC stress, acts as a phosphodiesterase by mediating removal of ATP (de-
CC AMPylation) from Hsc70-3/BiP at 'Thr-518', leading to restore HSPA5/BiP
CC activity (PubMed:29089387). {ECO:0000250|UniProtKB:A0A061I403,
CC ECO:0000269|PubMed:19503829, ECO:0000269|PubMed:25395623,
CC ECO:0000269|PubMed:29089387}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = diphosphate + O-(5'-adenylyl)-L-
CC tyrosyl-[protein]; Xref=Rhea:RHEA:54288, Rhea:RHEA-COMP:10136,
CC Rhea:RHEA-COMP:13846, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:46858, ChEBI:CHEBI:83624; EC=2.7.7.n1;
CC Evidence={ECO:0000250|UniProtKB:Q9BVA6};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = 3-O-(5'-adenylyl)-L-threonyl-
CC [protein] + diphosphate; Xref=Rhea:RHEA:54292, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:13847, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:138113; EC=2.7.7.n1;
CC Evidence={ECO:0000269|PubMed:25395623, ECO:0000269|PubMed:29089387};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-O-(5'-adenylyl)-L-threonyl-[protein] + H2O = AMP + H(+) + L-
CC threonyl-[protein]; Xref=Rhea:RHEA:55932, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:13847, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30013, ChEBI:CHEBI:138113, ChEBI:CHEBI:456215;
CC Evidence={ECO:0000269|PubMed:29089387};
CC -!- ACTIVITY REGULATION: The side chain of Glu-247 determines which of the
CC two opposing activities (AMPylase or de-AMPylase) will take place. In
CC response to endoplasmic reticulum stress, mediates de-AMPylase activity
CC (By similarity). Adenylyltransferase activity is inhibited by the
CC inhibitory helix present at the N-terminus: Glu-247 binds ATP and
CC competes with ATP-binding at Arg-386, thereby preventing
CC adenylyltransferase activity (By similarity). In unstressed cells,
CC disengagement of Glu-247 promotes adenylyltransferase activity (By
CC similarity). Activation dissociates ATP-binding from Glu-247, allowing
CC ordered binding of the entire ATP moiety with the alpha-phosphate in an
CC orientation that is productive for accepting an incoming target
CC hydroxyl side chain (By similarity). {ECO:0000250|UniProtKB:A0A061I403,
CC ECO:0000250|UniProtKB:Q9BVA6}.
CC -!- SUBUNIT: Homodimer; homodimerization may regulate adenylyltransferase
CC and phosphodiesterase activities. {ECO:0000269|PubMed:29089387}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass membrane
CC protein {ECO:0000305}.
CC -!- INDUCTION: Up-regulated in response to endoplasmic reticulum stress.
CC {ECO:0000269|PubMed:25395623}.
CC -!- DOMAIN: The fido domain mediates the adenylyltransferase activity.
CC {ECO:0000250|UniProtKB:Q9BVA6}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype. Flies are viable.
CC {ECO:0000269|PubMed:29089387}.
CC -!- SIMILARITY: Belongs to the fic family. {ECO:0000305}.
CC -!- CAUTION: Was initially thought to mediate AMPylation of Hsc70-3/BiP at
CC 'Thr-366' (PubMed:25395623). However, it was later shown that it
CC catalyzes AMPylation of Hsc70-3/BiP at 'Thr-518'.
CC {ECO:0000269|PubMed:25395623, ECO:0000269|PubMed:29089387}.
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DR EMBL; AE014134; AAF52381.2; -; Genomic_DNA.
DR EMBL; AY095059; AAM11387.1; -; mRNA.
DR RefSeq; NP_609026.1; NM_135182.2.
DR AlphaFoldDB; Q8SWV6; -.
DR SMR; Q8SWV6; -.
DR BioGRID; 60054; 4.
DR IntAct; Q8SWV6; 4.
DR STRING; 7227.FBpp0078887; -.
DR PaxDb; Q8SWV6; -.
DR PRIDE; Q8SWV6; -.
DR DNASU; 33897; -.
DR EnsemblMetazoa; FBtr0079257; FBpp0078887; FBgn0263278.
DR GeneID; 33897; -.
DR KEGG; dme:Dmel_CG9523; -.
DR UCSC; CG9523-RA; d. melanogaster.
DR CTD; 33897; -.
DR FlyBase; FBgn0263278; Fic.
DR VEuPathDB; VectorBase:FBgn0263278; -.
DR eggNOG; KOG3824; Eukaryota.
DR GeneTree; ENSGT00390000008873; -.
DR HOGENOM; CLU_040460_0_0_1; -.
DR InParanoid; Q8SWV6; -.
DR OMA; CTEMTLD; -.
DR OrthoDB; 1057856at2759; -.
DR PhylomeDB; Q8SWV6; -.
DR BioGRID-ORCS; 33897; 0 hits in 1 CRISPR screen.
DR ChiTaRS; Btk29A; fly.
DR GenomeRNAi; 33897; -.
DR PRO; PR:Q8SWV6; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0263278; Expressed in spermathecum and 24 other tissues.
DR Genevisible; Q8SWV6; DM.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:FlyBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0051087; F:chaperone binding; IDA:UniProtKB.
DR GO; GO:0030544; F:Hsp70 protein binding; IPI:UniProtKB.
DR GO; GO:0044603; F:protein adenylylhydrolase activity; IDA:UniProtKB.
DR GO; GO:0070733; F:protein adenylyltransferase activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0050908; P:detection of light stimulus involved in visual perception; IMP:FlyBase.
DR GO; GO:0051608; P:histamine transport; IMP:FlyBase.
DR GO; GO:0018117; P:protein adenylylation; IDA:UniProtKB.
DR GO; GO:0044602; P:protein deadenylylation; IDA:UniProtKB.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IDA:UniProtKB.
DR GO; GO:0007632; P:visual behavior; IMP:FlyBase.
DR Gene3D; 1.10.3290.10; -; 1.
DR Gene3D; 1.25.40.10; -; 1.
DR InterPro; IPR003812; Fido.
DR InterPro; IPR036597; Fido-like_dom_sf.
DR InterPro; IPR040198; Fido_containing.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR PANTHER; PTHR13504; PTHR13504; 1.
DR Pfam; PF02661; Fic; 1.
DR SUPFAM; SSF140931; SSF140931; 1.
DR SUPFAM; SSF48452; SSF48452; 1.
DR PROSITE; PS51459; FIDO; 1.
DR PROSITE; PS50293; TPR_REGION; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Hydrolase; Membrane; Nucleotide-binding;
KW Nucleotidyltransferase; Reference proteome; Repeat; TPR repeat;
KW Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..492
FT /note="Protein adenylyltransferase Fic"
FT /id="PRO_0000381785"
FT TRANSMEM 33..55
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REPEAT 118..151
FT /note="TPR 1"
FT REPEAT 152..186
FT /note="TPR 2"
FT DOMAIN 297..432
FT /note="Fido"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00791"
FT REGION 1..26
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 243..248
FT /note="Inhibitory (S/T)XXXE(G/N) motif"
FT COMPBIAS 1..22
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 375
FT /evidence="ECO:0000269|PubMed:19503829"
FT BINDING 247
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT BINDING 328..331
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT BINDING 379..386
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT BINDING 411..412
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT BINDING 419
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT SITE 247
FT /note="Important for autoinhibition of adenylyltransferase
FT activity"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT MUTAGEN 247
FT /note="E->G: Promotes adenylyltransferase activity.
FT Overexpression is lethal in a Fic null background."
FT /evidence="ECO:0000269|PubMed:25395623,
FT ECO:0000269|PubMed:29089387"
FT MUTAGEN 271
FT /note="I->D: Disrupts homodimerization, leading to
FT increased adenylyltransferase activity and reduced
FT phosphodiesterase activity."
FT /evidence="ECO:0000269|PubMed:29089387"
FT MUTAGEN 375
FT /note="H->A: Abolishes adenylyltransferase and
FT phosphodiesterase activities."
FT /evidence="ECO:0000269|PubMed:19503829,
FT ECO:0000269|PubMed:29089387"
SQ SEQUENCE 492 AA; 55725 MW; 452412D2865FED3A CRC64;
MGTEAEQPSP PAQQQDQENP PLCKAQNPKP ARLYRFVLIF VAGSLAAWTF HALSSTNLVW
KLRQLHHLPT AHYLQTRDEF ALYSVEELNA FKEFYDKSVS DSVGASYTEA EQTNIKEALG
ALRMAQDLYL AGKDDKAARL FEHALALAPR HPEVLLRYGE FLEHNQRNIV LADQYYFQAL
TISPSNSEAL ANRQRTADVV QSLDERRLES LDSKRDALSA IHESNGALRR AKKEAYFQHI
YHSVGIEGNT MTLAQTRSIL ETRMAVDGKS IDEHNEILGM DLAMKYINAS LVQKIDITIK
DILELHRRVL GHVDPIEGGE FRRNQVYVGG HIPPGPGDLA LLMQRFERWL NSEHSSTLHP
VNYAALAHYK LVHIHPFVDG NGRTSRLLMN TLLMRAGYPP VIIPKQQRSK YYHFLKLANE
GDIRPFVRFI ADCTEKTLDL YLWATSDLPQ QIPMLIQTES EAGERLAQMQ SPNVAQRSSI
LEFYESGSGD LP
