FICD_CULQU
ID FICD_CULQU Reviewed; 500 AA.
AC B0W429;
DT 01-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT 08-APR-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=CPIJ001789;
OS Culex quinquefasciatus (Southern house mosquito) (Culex pungens).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Nematocera; Culicoidea; Culicidae;
OC Culicinae; Culicini; Culex; Culex.
OX NCBI_TaxID=7176;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=JHB;
RG The Broad Institute Genome Sequencing Platform;
RA Atkinson P.W., Hemingway J., Christensen B.M., Higgs S., Kodira C.D.,
RA Hannick L.I., Megy K., O'Leary S.B., Pearson M., Haas B.J., Mauceli E.,
RA Wortman J.R., Lee N.H., Guigo R., Stanke M., Alvarado L., Amedeo P.,
RA Antoine C.H., Arensburger P., Bidwell S.L., Crawford M., Camaro F.,
RA Devon K., Engels R., Hammond M., Howarth C., Koehrsen M., Lawson D.,
RA Montgomery P., Nene V., Nusbaum C., Puiu D., Romero-Severson J.,
RA Severson D.W., Shumway M., Sisk P., Stolte C., Zeng Q., Eisenstadt E.,
RA Fraser-Liggett C.M., Strausberg R., Galagan J., Birren B., Collins F.H.;
RT "Annotation of Culex pipiens quinquefasciatus.";
RL Submitted (MAR-2007) to the EMBL/GenBank/DDBJ databases.
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-251 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-251 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-251 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-251 promotes adenylyltransferase activity (By
CC similarity). Activation dissociates ATP-binding from Glu-251, 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; DS231834; EDS32622.1; -; Genomic_DNA.
DR RefSeq; XP_001843463.1; XM_001843411.1.
DR AlphaFoldDB; B0W429; -.
DR SMR; B0W429; -.
DR STRING; 7176.CPIJ001789-PA; -.
DR GeneID; 6032944; -.
DR KEGG; cqu:CpipJ_CPIJ001789; -.
DR VEuPathDB; VectorBase:CPIJ001789; -.
DR VEuPathDB; VectorBase:CQUJHB009259; -.
DR eggNOG; KOG3824; Eukaryota.
DR HOGENOM; CLU_040460_0_0_1; -.
DR InParanoid; B0W429; -.
DR OMA; CTEMTLD; -.
DR OrthoDB; 1057856at2759; -.
DR PhylomeDB; B0W429; -.
DR Proteomes; UP000002320; Partially assembled WGS sequence.
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..500
FT /note="Protein adenylyltransferase Fic"
FT /id="PRO_0000381781"
FT TRANSMEM 39..59
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REPEAT 122..155
FT /note="TPR 1"
FT REPEAT 156..190
FT /note="TPR 2"
FT DOMAIN 302..437
FT /note="Fido"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00791"
FT REGION 477..500
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 247..252
FT /note="Inhibitory (S/T)XXXE(G/N) motif"
FT ACT_SITE 380
FT /evidence="ECO:0000250|UniProtKB:A0A061I403"
FT BINDING 251
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 251
FT /note="Important for autoinhibition of adenylyltransferase
FT activity"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
SQ SEQUENCE 500 AA; 56031 MW; 0BEC135F0CB5B1CA CRC64;
MCSVCEGSAE GLVTRKRTHS GGGRSAGSKR KWHRRMGGLS FLIFFVIGSL FSGLMFALLS
YAPSYRSRVT PHYLPDGRFL QIADEARVLE PYLSAAVRLP DSLNGTPAGK QQQTARSNEQ
EALSSLKVAV EMKLMGKDDK ALRLFQHAMA LSPRHPEILT KYGEFLEHSQ QDIVTADHYY
YQALTVNPSH SEALANRQRT ASIVEHLDQK RFERLDKKRD ALSSVHALDA GLKRAEKEAY
IQHIYHSVGI EGNTMSLAQT RSILETKMAV DGKSIDEHNE ILGLDAAMKY INATLVNKND
FITLKDLLEI HRRVLGHVDP VEGGEFRRTQ VYVGGHIPPG PGDLSILMSR FEGWLNAEQS
FLMHPVRYAA MAHYKLVHIH PFSDGNGRTS RLLMNTLLMR AGYPPVIIQK QHRHKYYDYL
QVANEGDIRP FVRFIADCTE RTLDLYLWAT SELSHPVPLL AQEEMGGAIG EREHGFGREG
GSTVHEGSGT GDSIRIGTMW
