FICD_XENTR
ID FICD_XENTR Reviewed; 446 AA.
AC B4F6I5;
DT 01-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT 23-SEP-2008, sequence version 1.
DT 03-AUG-2022, entry version 70.
DE RecName: Full=Protein adenylyltransferase FICD {ECO:0000305};
DE EC=2.7.7.n1 {ECO:0000250|UniProtKB:Q9BVA6};
DE AltName: Full=AMPylator FICD {ECO:0000250|UniProtKB:Q9BVA6};
DE AltName: Full=De-AMPylase FICD {ECO:0000250|UniProtKB:A0A061I403};
DE EC=3.1.4.- {ECO:0000250|UniProtKB:A0A061I403};
DE AltName: Full=FIC domain-containing protein {ECO:0000250|UniProtKB:Q9BVA6};
GN Name=ficd {ECO:0000250|UniProtKB:Q9BVA6};
OS Xenopus tropicalis (Western clawed frog) (Silurana tropicalis).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Silurana.
OX NCBI_TaxID=8364;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (JUL-2008) 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-222 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 ERN1/IRE1-mediated unfolded protein response (UPR)
CC by mediating AMPylation or de-AMPylation of HSPA5/BiP (By similarity).
CC In unstressed cells, acts as an adenylyltransferase by mediating
CC AMPylation of HSPA5/BiP at 'Thr-518', thereby inactivating it (By
CC similarity). In response to endoplasmic reticulum stress, acts as a
CC phosphodiesterase by mediating removal of ATP (de-AMPylation) from
CC HSPA5/BiP at 'Thr-518', leading to restore HSPA5/BiP activity (By
CC similarity). {ECO:0000250|UniProtKB:A0A061I403,
CC ECO:0000250|UniProtKB:Q9BVA6}.
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=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:A0A061I403};
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:Q9BVA6};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q9BVA6};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q9BVA6};
CC Note=Divalent metal cation. Prefers Mn(2+) over Mg(2+).
CC {ECO:0000250|UniProtKB:Q9BVA6};
CC -!- ACTIVITY REGULATION: The side chain of Glu-222 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-222 binds ATP and
CC competes with ATP-binding at Arg-362, thereby preventing
CC adenylyltransferase activity (By similarity). In unstressed cells,
CC disengagement of Glu-222 promotes adenylyltransferase activity (By
CC similarity). Activation dissociates ATP-binding from Glu-222, 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:Q9BVA6}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q9BVA6}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:Q9BVA6}.
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; BC167892; AAI67892.1; -; mRNA.
DR RefSeq; NP_001135492.1; NM_001142020.1.
DR RefSeq; XP_012812800.1; XM_012957346.2.
DR RefSeq; XP_012812805.1; XM_012957351.2.
DR RefSeq; XP_017946808.1; XM_018091319.1.
DR AlphaFoldDB; B4F6I5; -.
DR SMR; B4F6I5; -.
DR STRING; 8364.ENSXETP00000016191; -.
DR PaxDb; B4F6I5; -.
DR GeneID; 100216031; -.
DR KEGG; xtr:100216031; -.
DR CTD; 11153; -.
DR Xenbase; XB-GENE-992753; ficd.
DR eggNOG; KOG3824; Eukaryota.
DR HOGENOM; CLU_040460_0_0_1; -.
DR InParanoid; B4F6I5; -.
DR OrthoDB; 1057856at2759; -.
DR Proteomes; UP000008143; Chromosome 1.
DR Proteomes; UP000790000; Unplaced.
DR Bgee; ENSXETG00000017652; Expressed in egg cell and 15 other tissues.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0051087; F:chaperone binding; ISS:UniProtKB.
DR GO; GO:0044603; F:protein adenylylhydrolase activity; ISS:UniProtKB.
DR GO; GO:0070733; F:protein adenylyltransferase activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0018117; P:protein adenylylation; ISS:UniProtKB.
DR GO; GO:0044602; P:protein deadenylylation; ISS:UniProtKB.
DR GO; GO:1903894; P:regulation of IRE1-mediated unfolded protein response; ISS:UniProtKB.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; ISS:UniProtKB.
DR GO; GO:0006986; P:response to unfolded protein; IEA:UniProtKB-KW.
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 SMART; SM00028; TPR; 2.
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 2: Evidence at transcript level;
KW ATP-binding; Endoplasmic reticulum; Glycoprotein; Hydrolase; Magnesium;
KW Manganese; Membrane; Nucleotide-binding; Nucleotidyltransferase;
KW Reference proteome; Repeat; Signal-anchor; TPR repeat; Transferase;
KW Transmembrane; Transmembrane helix; Unfolded protein response.
FT CHAIN 1..446
FT /note="Protein adenylyltransferase FICD"
FT /id="PRO_0000381776"
FT TOPO_DOM 1..18
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT TRANSMEM 19..39
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 40..446
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT REPEAT 94..127
FT /note="TPR 1"
FT REPEAT 128..161
FT /note="TPR 2"
FT DOMAIN 273..408
FT /note="Fido"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00791"
FT MOTIF 218..223
FT /note="Inhibitory (S/T)XXXE(G/N) motif"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT ACT_SITE 351
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT BINDING 222
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT BINDING 304..307
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT BINDING 355..362
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT BINDING 387..388
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT BINDING 395
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT SITE 222
FT /note="Important for autoinhibition of adenylyltransferase
FT activity"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT CARBOHYD 263
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 446 AA; 50498 MW; 3F5FC144A948DD99 CRC64;
MAVTECEWAS LGSRIGLRAA LVLLSGSLLV VLFPLSGLEH QYRTALNILL QCNLWGGDDR
HTFTGQTRGL AVASTAIELL VLKQKPTSDV KFEAKAALNQ ALEMKRQGKK EKAHKLLHHA
LKMDPDHVDA LNELGILLEE EKDIIQADYL YSKALTISPH NEKALINRDR TLPLVEEIDQ
RYFSLIDSKV KKLMSIPKGN PALRRVMEES YYHHIYHTVA IEGNTLSLSE IRHIIETRYA
VPGKSLEEQN EVIGMHAAMK YVNATLVSRI GSVTIDNILE IHRRILGYVD PVEAGRFRRN
QVFVGHHIPP HPRDVEKLMQ EFVQWLNSEE AMSLHPVEFA ALAHYKLVYI HPFVDGNGRT
SRLLMNLILM QAGYPPITVR KEQRSEYYHV LEIANEGDVR PFIRFIAKCT ESTLDLLLIA
TAEHPVGLPE PNHGFSECKQ TITIKT
