FICD_DROPE
ID FICD_DROPE Reviewed; 508 AA.
AC B4GJC1;
DT 01-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT 23-SEP-2008, sequence version 1.
DT 03-AUG-2022, entry version 67.
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=GL25530;
OS Drosophila persimilis (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7234;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=MSH-3 / Tucson 14011-0111.49;
RX PubMed=17994087; DOI=10.1038/nature06341;
RG Drosophila 12 genomes consortium;
RT "Evolution of genes and genomes on the Drosophila phylogeny.";
RL Nature 450:203-218(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-261 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-261 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-261 binds ATP and
CC competes with ATP-binding at Arg-400, thereby preventing
CC adenylyltransferase activity (By similarity). In unstressed cells,
CC disengagement of Glu-261 promotes adenylyltransferase activity (By
CC similarity). Activation dissociates ATP-binding from Glu-261, 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; CH479184; EDW37435.1; -; Genomic_DNA.
DR RefSeq; XP_002019239.1; XM_002019203.1.
DR AlphaFoldDB; B4GJC1; -.
DR SMR; B4GJC1; -.
DR STRING; 7234.FBpp0189637; -.
DR EnsemblMetazoa; FBtr0191145; FBpp0189637; FBgn0163114.
DR GeneID; 6593652; -.
DR KEGG; dpe:6593652; -.
DR eggNOG; KOG3824; Eukaryota.
DR HOGENOM; CLU_040460_0_0_1; -.
DR OMA; CTEMTLD; -.
DR PhylomeDB; B4GJC1; -.
DR Proteomes; UP000008744; Unassembled WGS sequence.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:EnsemblMetazoa.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0051087; F:chaperone binding; IEA:EnsemblMetazoa.
DR GO; GO:0030544; F:Hsp70 protein binding; IEA:EnsemblMetazoa.
DR GO; GO:0044603; F:protein adenylylhydrolase activity; IEA:EnsemblMetazoa.
DR GO; GO:0070733; F:protein adenylyltransferase activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IEA:EnsemblMetazoa.
DR GO; GO:0050908; P:detection of light stimulus involved in visual perception; IEA:EnsemblMetazoa.
DR GO; GO:0051608; P:histamine transport; IEA:EnsemblMetazoa.
DR GO; GO:0018117; P:protein adenylylation; ISS:UniProtKB.
DR GO; GO:0044602; P:protein deadenylylation; IEA:EnsemblMetazoa.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IEA:EnsemblMetazoa.
DR GO; GO:0007632; P:visual behavior; IEA:EnsemblMetazoa.
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..508
FT /note="Protein adenylyltransferase Fic"
FT /id="PRO_0000381787"
FT TRANSMEM 48..70
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REPEAT 132..165
FT /note="TPR 1"
FT REPEAT 166..200
FT /note="TPR 2"
FT DOMAIN 311..446
FT /note="Fido"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00791"
FT MOTIF 257..262
FT /note="Inhibitory (S/T)XXXE(G/N) motif"
FT ACT_SITE 389
FT /evidence="ECO:0000250|UniProtKB:A0A061I403"
FT BINDING 261
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT BINDING 342..345
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT BINDING 393..400
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT BINDING 425..426
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT BINDING 433
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT SITE 261
FT /note="Important for autoinhibition of adenylyltransferase
FT activity"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
SQ SEQUENCE 508 AA; 57776 MW; 95E147D1C96A3533 CRC64;
MAMTILHASE KVNAEAEATT CPPTEKVKEE QQQQEQLQHS KTSKRVQFYR FALFFIAGSF
AAFSFHALTS SSSWRLRQLH HLPNAHYLQT REEFAVYSVE ELNAFKEFYD KSISDSVGAS
YSEAEQTNIK EALGALRLAQ DMHLSGKDDK ASRLFEHALA LAPKHPEVLL RYGEFLEHNQ
RNIVLADQYY FQALTLCPSN SEALANRQRT AEVVQTLDER RLQSLDSKRD ALSAIHESSS
ALRRAKKEAY FQHIYHSVGI EGNTMTLAQT RSILETRMAV DGKSIDEHNE ILGMDLAMKY
INASLVQKLE ITIKDILELH RRVLGHVDPI EGGEFRRNQV YVGGHVPPGP GDLALLMQRF
ERWLNSEHSS SLHPVNYAAY AHYKLVHIHP FIDGNGRTSR LLMNTLLMRA GYPPVIIPKQ
QRSKYYHFLK LANEGDIRPF VRFIADCTEK TLDLYLWATS DLPQQIPMLI QTESEAGEQL
AQMRSPHISA QSASIPEFYE FSGSGFQP
