FICD_AEDAE
ID FICD_AEDAE Reviewed; 499 AA.
AC Q17A75;
DT 01-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT 25-JUL-2006, sequence version 1.
DT 03-AUG-2022, entry version 86.
DE RecName: Full=Protein adenylyltransferase Fic;
DE EC=2.7.7.n1 {ECO:0000250|UniProtKB:Q8SWV6};
DE AltName: Full=De-AMPylase Fic {ECO:0000305};
DE EC=3.1.4.- {ECO:0000250|UniProtKB:A0A061I403, ECO:0000250|UniProtKB:Q8SWV6};
GN ORFNames=AAEL005383;
OS Aedes aegypti (Yellowfever mosquito) (Culex aegypti).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Nematocera; Culicoidea; Culicidae;
OC Culicinae; Aedini; Aedes; Stegomyia.
OX NCBI_TaxID=7159;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=LVPib12;
RX PubMed=17510324; DOI=10.1126/science.1138878;
RA Nene V., Wortman J.R., Lawson D., Haas B.J., Kodira C.D., Tu Z.J.,
RA Loftus B.J., Xi Z., Megy K., Grabherr M., Ren Q., Zdobnov E.M., Lobo N.F.,
RA Campbell K.S., Brown S.E., Bonaldo M.F., Zhu J., Sinkins S.P.,
RA Hogenkamp D.G., Amedeo P., Arensburger P., Atkinson P.W., Bidwell S.L.,
RA Biedler J., Birney E., Bruggner R.V., Costas J., Coy M.R., Crabtree J.,
RA Crawford M., DeBruyn B., DeCaprio D., Eiglmeier K., Eisenstadt E.,
RA El-Dorry H., Gelbart W.M., Gomes S.L., Hammond M., Hannick L.I.,
RA Hogan J.R., Holmes M.H., Jaffe D., Johnston S.J., Kennedy R.C., Koo H.,
RA Kravitz S., Kriventseva E.V., Kulp D., Labutti K., Lee E., Li S.,
RA Lovin D.D., Mao C., Mauceli E., Menck C.F., Miller J.R., Montgomery P.,
RA Mori A., Nascimento A.L., Naveira H.F., Nusbaum C., O'Leary S.B., Orvis J.,
RA Pertea M., Quesneville H., Reidenbach K.R., Rogers Y.-H.C., Roth C.W.,
RA Schneider J.R., Schatz M., Shumway M., Stanke M., Stinson E.O.,
RA Tubio J.M.C., Vanzee J.P., Verjovski-Almeida S., Werner D., White O.R.,
RA Wyder S., Zeng Q., Zhao Q., Zhao Y., Hill C.A., Raikhel A.S., Soares M.B.,
RA Knudson D.L., Lee N.H., Galagan J., Salzberg S.L., Paulsen I.T.,
RA Dimopoulos G., Collins F.H., Bruce B., Fraser-Liggett C.M., Severson D.W.;
RT "Genome sequence of Aedes aegypti, a major arbovirus vector.";
RL Science 316:1718-1723(2007).
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 (By similarity). The
CC side chain of Glu-255 determines which of the two opposing activities
CC (AMPylase or de-AMPylase) will take place (By similarity). Acts as a
CC key regulator of the unfolded protein response (UPR) by mediating
CC AMPylation or de-AMPylation of Hsc70-3/BiP. In unstressed cells, acts
CC as an adenylyltransferase by mediating AMPylation of Hsc70-3/BiP at
CC 'Thr-518', thereby inactivating it. In response to endoplasmic
CC reticulum stress, acts as a phosphodiesterase by mediating removal of
CC ATP (de-AMPylation) from Hsc70-3/BiP at 'Thr-518', leading to restore
CC HSPA5/BiP activity (By similarity). {ECO:0000250|UniProtKB:A0A061I403,
CC ECO:0000250|UniProtKB:Q8SWV6}.
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:0000250|UniProtKB:Q8SWV6};
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:0000250|UniProtKB:Q8SWV6};
CC -!- ACTIVITY REGULATION: The side chain of Glu-255 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-255 binds ATP and
CC competes with ATP-binding at Arg-395, thereby preventing
CC adenylyltransferase activity (By similarity). In unstressed cells,
CC disengagement of Glu-255 promotes adenylyltransferase activity (By
CC similarity). Activation dissociates ATP-binding from Glu-255, 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. {ECO:0000250|UniProtKB:Q8SWV6}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:Q8SWV6}; Single-
CC pass membrane protein {ECO:0000250|UniProtKB:Q8SWV6}.
CC -!- DOMAIN: The fido domain mediates the adenylyltransferase activity.
CC {ECO:0000250|UniProtKB:Q9BVA6}.
CC -!- SIMILARITY: Belongs to the fic family. {ECO:0000305}.
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DR EMBL; CH477339; EAT43151.1; -; Genomic_DNA.
DR RefSeq; XP_001650824.1; XM_001650774.1.
DR AlphaFoldDB; Q17A75; -.
DR SMR; Q17A75; -.
DR STRING; 7159.AAEL005383-PA; -.
DR GeneID; 5566424; -.
DR KEGG; aag:5566424; -.
DR VEuPathDB; VectorBase:AAEL005383; -.
DR eggNOG; KOG3824; Eukaryota.
DR HOGENOM; CLU_040460_0_0_1; -.
DR InParanoid; Q17A75; -.
DR OMA; CTEMTLD; -.
DR OrthoDB; 1057856at2759; -.
DR PhylomeDB; Q17A75; -.
DR Proteomes; UP000008820; Chromosome 2.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR GO; GO:0070733; F:protein adenylyltransferase activity; ISS:UniProtKB.
DR GO; GO:0018117; P:protein adenylylation; ISS:UniProtKB.
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 3: Inferred from homology;
KW ATP-binding; Hydrolase; Membrane; Nucleotide-binding;
KW Nucleotidyltransferase; Reference proteome; Repeat; TPR repeat;
KW Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..499
FT /note="Protein adenylyltransferase Fic"
FT /id="PRO_0000381780"
FT TRANSMEM 38..58
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REPEAT 126..159
FT /note="TPR 1"
FT REPEAT 160..194
FT /note="TPR 2"
FT DOMAIN 306..441
FT /note="Fido"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00791"
FT MOTIF 251..256
FT /note="Inhibitory (S/T)XXXE(G/N) motif"
FT ACT_SITE 384
FT /evidence="ECO:0000250|UniProtKB:A0A061I403"
FT BINDING 255
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT BINDING 337..340
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT BINDING 388..395
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT BINDING 420..421
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT BINDING 428
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT SITE 255
FT /note="Important for autoinhibition of adenylyltransferase
FT activity"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
SQ SEQUENCE 499 AA; 56399 MW; 16C02A4427ED46C1 CRC64;
MCCVCGEQSP DLKNGLQKQS RSARRSASKK WRYQMNSFHY FVIFASGSLF SGLMFGLLNY
APKYVLLPTR SAPHHLPDGK FLQISDEARV MEPYFPAVRM AGRLGDGNNG SGKIRTEPHD
TNEQEALSSL KVAIEMKTMG KDDKAARLFQ HALALSPKHP EILTKYGEFL EHNQQDVVRA
DHYYYQALTV NPSHSEALAN RQRTAQIVEH LDQKRFERLD QKRDALSSVS DTNMALKRAE
KEAYIQHIYH SVGIEGNTMS LAQTRSILET RMAVDGKSID EHNEILGLDA AMKYINATLV
NKNDFITLKD ILEIHRRVLG HVDPIEGGEF RRSQVYVGGH VPPGPGDLSI LMNHFESWLN
SKQAFLFHPV KYAAMAHYKL VHIHPFSDGN GRTSRLLMNT LLMRAGYPPV IIQKQHRHKY
YDYLQVANEG DIRPFVRFIA DCTERTLDLY LWATSELSHP VPLLAQETMP DGVPLINSFE
KESTIEGSGA GEAIRIGTI
