FICD_DROAN
ID FICD_DROAN Reviewed; 497 AA.
AC B3MK83;
DT 01-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT 02-SEP-2008, sequence version 1.
DT 03-AUG-2022, entry version 69.
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=GF14521;
OS Drosophila ananassae (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7217;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tucson 14024-0371.13;
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-252 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-252 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-252 binds ATP and
CC competes with ATP-binding at Arg-391, thereby preventing
CC adenylyltransferase activity (By similarity). In unstressed cells,
CC disengagement of Glu-252 promotes adenylyltransferase activity (By
CC similarity). Activation dissociates ATP-binding from Glu-252, 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; CH902620; EDV31501.1; -; Genomic_DNA.
DR RefSeq; XP_001962280.1; XM_001962244.2.
DR AlphaFoldDB; B3MK83; -.
DR SMR; B3MK83; -.
DR STRING; 7217.FBpp0117713; -.
DR EnsemblMetazoa; FBtr0119221; FBpp0117713; FBgn0091548.
DR GeneID; 6497344; -.
DR KEGG; dan:6497344; -.
DR eggNOG; KOG3824; Eukaryota.
DR HOGENOM; CLU_040460_0_0_1; -.
DR InParanoid; B3MK83; -.
DR OMA; CTEMTLD; -.
DR OrthoDB; 1057856at2759; -.
DR PhylomeDB; B3MK83; -.
DR Proteomes; UP000007801; 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..497
FT /note="Protein adenylyltransferase Fic"
FT /id="PRO_0000381782"
FT TRANSMEM 38..58
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REPEAT 123..156
FT /note="TPR 1"
FT REPEAT 157..191
FT /note="TPR 2"
FT DOMAIN 302..437
FT /note="Fido"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00791"
FT REGION 1..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 468..497
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 248..253
FT /note="Inhibitory (S/T)XXXE(G/N) motif"
FT COMPBIAS 468..482
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 380
FT /evidence="ECO:0000250|UniProtKB:A0A061I403"
FT BINDING 252
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT BINDING 333..336
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT BINDING 384..391
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT BINDING 416..417
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT BINDING 424
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT SITE 252
FT /note="Important for autoinhibition of adenylyltransferase
FT activity"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
SQ SEQUENCE 497 AA; 55739 MW; D50C9E91E0A00BE9 CRC64;
MGATDQALEA ESKTTEPPKT PPVPEQHDRP FLGRQANLCH LLVLLFSGGL AAITLHIFTS
SNVGWRLRQL HHLPTAHYLQ TRDEFAVYSV DELNAFKEFY DRSISDSVGS SYSEAEETNI
KEALGALRLA QDMYLAGKDD KAARLFQHSL ALAPRHPTVL LRYGEFLEHS QRNIVLADQY
YFQALSISPS NSEALANRQR TADVVQSLDE RRLESLDSKR DALSAIHESS AALRRAKKEA
YFQHIYHTVG IEGNTMTLAQ TRSILETRMA VDGKSIDEHN EILGMDLAMK YINASLVQKM
EITIKDILEL HRRVLGHVDP IEGGEFRRNQ VYVGGHVPPG PGDLALLMQR FERWLNSEHS
SSMHPVNYAA LAHYKLVHIH PFIDGNGRTS RLLMNTLLMR AGYPPVIIPK QQRSKYYHFL
KLANEGDIRP FVRFIADCTE KTLDLYLWAT SDLPHQIPML IQSTSEAGEG VPQLQSSQMG
GGASIPEFHE SGSGSLP
