FICD_NEMVE
ID FICD_NEMVE Reviewed; 427 AA.
AC A7SVT1;
DT 01-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT 02-OCT-2007, sequence version 1.
DT 03-AUG-2022, entry version 79.
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=v1g194069;
OS Nematostella vectensis (Starlet sea anemone).
OC Eukaryota; Metazoa; Cnidaria; Anthozoa; Hexacorallia; Actiniaria;
OC Edwardsiidae; Nematostella.
OX NCBI_TaxID=45351;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CH2 X CH6;
RX PubMed=17615350; DOI=10.1126/science.1139158;
RA Putnam N.H., Srivastava M., Hellsten U., Dirks B., Chapman J., Salamov A.,
RA Terry A., Shapiro H., Lindquist E., Kapitonov V.V., Jurka J.,
RA Genikhovich G., Grigoriev I.V., Lucas S.M., Steele R.E., Finnerty J.R.,
RA Technau U., Martindale M.Q., Rokhsar D.S.;
RT "Sea anemone genome reveals ancestral eumetazoan gene repertoire and
RT genomic organization.";
RL Science 317:86-94(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-204 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,
CC thereby inactivating it. In response to endoplasmic reticulum stress,
CC acts as a phosphodiesterase by mediating removal of ATP (de-AMPylation)
CC from Hsc70-3/BiP, leading to restore HSPA5/BiP activity (By
CC 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-204 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-204 binds ATP and
CC competes with ATP-binding at Arg-344, thereby preventing
CC adenylyltransferase activity (By similarity). In unstressed cells,
CC disengagement of Glu-204 promotes adenylyltransferase activity (By
CC similarity). Activation dissociates ATP-binding from Glu-204, 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; DS469844; EDO32183.1; -; Genomic_DNA.
DR RefSeq; XP_001624283.1; XM_001624233.1.
DR AlphaFoldDB; A7SVT1; -.
DR SMR; A7SVT1; -.
DR STRING; 45351.EDO32183; -.
DR PRIDE; A7SVT1; -.
DR EnsemblMetazoa; EDO32183; EDO32183; NEMVEDRAFT_v1g194069.
DR GeneID; 5503191; -.
DR KEGG; nve:5503191; -.
DR eggNOG; KOG3824; Eukaryota.
DR HOGENOM; CLU_040460_0_1_1; -.
DR InParanoid; A7SVT1; -.
DR OMA; CTEMTLD; -.
DR OrthoDB; 1057856at2759; -.
DR PhylomeDB; A7SVT1; -.
DR Proteomes; UP000001593; Unassembled 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 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; 2.
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..427
FT /note="Protein adenylyltransferase Fic"
FT /id="PRO_0000381777"
FT TRANSMEM 17..37
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REPEAT 77..110
FT /note="TPR 1"
FT REPEAT 111..143
FT /note="TPR 2"
FT DOMAIN 255..390
FT /note="Fido"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00791"
FT MOTIF 200..205
FT /note="Inhibitory (S/T)XXXE(G/N) motif"
FT ACT_SITE 333
FT /evidence="ECO:0000250|UniProtKB:A0A061I403"
FT BINDING 204
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT BINDING 286..289
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT BINDING 337..344
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT BINDING 369..370
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT BINDING 377
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT SITE 204
FT /note="Important for autoinhibition of adenylyltransferase
FT activity"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
SQ SEQUENCE 427 AA; 48496 MW; 6C3627BA137B1164 CRC64;
MDSTQIKQGN LRYLIHLLLA SLAGLSIAII VTHAPVFWRL RSSKNTLDPP GFREGLNMLI
PEIHFDAEVQ DPLYGEALAA LKAASAMKHG GKHSKAVKLF QQAVSLAPHH PEILLQYGEF
LEQHDVVQAE HLYNRALTAN PLDSRALANR QRALPKVKQL DQEMLDKIDE KRDKLFSIPA
GSLPMKRAIK EAYFQHIYHS NAIEGNTMTL SMTRAIVETK MAVPGKSILE HNEVLGLDEA
LKYVNSTLIQ KSESITIDDI IEIHRRVLGH AHPLEAGRYR STQVFVSDHV PPAPEDLEKQ
MNAFNDWLLS KDPEILHPIE FAALSHYKLV YIHPFTDGNG RTARLLMNAI LMRAGFPPVI
IRFQDRHDYY EYLNQANHGD IRPFIRFVAR CTERTIDAYL ASTTIYPLGH ERTRELTDAH
DEKDPNR
