FICD_DROWI
ID FICD_DROWI Reviewed; 498 AA.
AC B4MUQ2;
DT 01-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT 23-SEP-2008, sequence version 1.
DT 03-AUG-2022, entry version 73.
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=GK14760;
OS Drosophila willistoni (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7260;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tucson 14030-0811.24;
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-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-394, 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; CH963857; EDW76247.1; -; Genomic_DNA.
DR RefSeq; XP_002065261.1; XM_002065225.2.
DR AlphaFoldDB; B4MUQ2; -.
DR SMR; B4MUQ2; -.
DR STRING; 7260.FBpp0243903; -.
DR EnsemblMetazoa; FBtr0245411; FBpp0243903; FBgn0216765.
DR GeneID; 6642575; -.
DR KEGG; dwi:6642575; -.
DR eggNOG; KOG3824; Eukaryota.
DR HOGENOM; CLU_040460_0_0_1; -.
DR InParanoid; B4MUQ2; -.
DR OMA; CTEMTLD; -.
DR OrthoDB; 1057856at2759; -.
DR PhylomeDB; B4MUQ2; -.
DR Proteomes; UP000007798; 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 InterPro; IPR019734; TPR_repeat.
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; PS50005; TPR; 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..498
FT /note="Protein adenylyltransferase Fic"
FT /id="PRO_0000381792"
FT TRANSMEM 43..63
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 305..440
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 383
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 336..339
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT BINDING 387..394
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT BINDING 419..420
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT BINDING 427
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 498 AA; 56666 MW; E918B0F9A114EB46 CRC64;
MPWEFLKKCD RQKAEVRGEK EEQEPVPGNP HFQVQFHVTS CRFAFLAFLA GSFLAFSLHA
LISSNLFWRL RQLHHLPTAH YLQTRDEFAV YSVDELNAFK EFYDKSTADS VGATYTEAEE
TNIKEALSSL RLAQDMYMAG KDDKAARLFE HALALAPRHP EVLLRYGEFL EHNQRNIVLA
DQYYFQALTI NPSHSEALAN RQRTADVVQT LDERRLASLD AKRAALSAIH EANSALRRAK
KEAYFQHIYH SVGIEGNTMT LAQTRSILET RMAVDGKSID EHNEILGMDL AMKYINASLV
QKLEITIKDI LELHRRVLGH VDPIEGGEFR RNQVYVGGHV PPGPGDLAVL MQRFEDWLNS
EYSSSLHPVN YAALAHYKLV HIHPFIDGNG RTSRLLMNTL LMRAGYPPVI IPKQQRSKYY
HFLKLANEGD IRPFVRFIAD CTEKTLDLYL WATSDLPQQI PMLIQTETEA GEQLVKLQSP
QMASIPESFY ESGSGALP
