FICD_CAEEL
ID FICD_CAEEL Reviewed; 508 AA.
AC Q23544;
DT 01-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 2.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Protein adenylyltransferase fic-1;
DE EC=2.7.7.n1 {ECO:0000269|PubMed:27138431};
DE AltName: Full=De-AMPylase fic-1 {ECO:0000305};
DE EC=3.1.4.- {ECO:0000250|UniProtKB:A0A061I403, ECO:0000250|UniProtKB:Q8SWV6};
GN Name=fic-1 {ECO:0000312|WormBase:ZK593.8}; ORFNames=ZK593.8;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0007744|PDB:5JJ6, ECO:0007744|PDB:5JJ7}
RP X-RAY CRYSTALLOGRAPHY (2.91 ANGSTROMS) OF 134-508, FUNCTION, CATALYTIC
RP ACTIVITY, SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL
RP STAGE, AUTO-AMPYLATION AT THR-352 AND THR-476, IDENTIFICATION BY MASS
RP SPECTROMETRY, AND MUTAGENESIS OF GLU-274; ILE-298 AND HIS-404.
RX PubMed=27138431; DOI=10.1371/journal.pgen.1006023;
RA Truttmann M.C., Cruz V.E., Guo X., Engert C., Schwartz T.U., Ploegh H.L.;
RT "The Caenorhabditis elegans protein FIC-1 is an AMPylase that covalently
RT modifies heat-shock 70 family proteins, translation elongation factors and
RT histones.";
RL PLoS Genet. 12:E1006023-E1006023(2016).
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-274 determines which of the two opposing activities
CC (AMPylase or de-AMPylase) will take place (By similarity).
CC Adenylyltransferase that mediates the addition of adenosine 5'-
CC monophosphate (AMP) to specific residues of target proteins
CC (PubMed:27138431). In vivo target proteins include the heat-shock 70
CC family proteins hsp-1 and hsp-3 and the translation elongation factors
CC eef-1A, eef-1G and eef-2 (PubMed:27138431). Can AMPylate core histone
CC H3 in vitro (PubMed:27138431). Can also act as a phosphodiesterase by
CC mediating removal of ATP (de-AMPylation) from target proteins (By
CC similarity). Decreases susceptibility to P.aeruginosa-mediated killing
CC and might therefore play a role in the innate immune response
CC (PubMed:27138431). {ECO:0000250|UniProtKB:A0A061I403,
CC ECO:0000250|UniProtKB:Q8SWV6, ECO:0000269|PubMed:27138431}.
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-274 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-274 binds ATP and
CC competes with ATP-binding at Arg-415, thereby preventing
CC adenylyltransferase activity (By similarity). In unstressed cells,
CC disengagement of Glu-274 promotes adenylyltransferase activity (By
CC similarity). Activation dissociates ATP-binding from Glu-274, 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: Forms homodimers; homodimerization might be required for
CC adenylyltransferase activity. {ECO:0000269|PubMed:27138431}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:27138431}; Single-pass membrane protein. Nucleus
CC membrane {ECO:0000269|PubMed:27138431}; Single-pass membrane protein.
CC Note=Predominantly localized to the endoplasmic reticulum and to the
CC nucleus. {ECO:0000269|PubMed:27138431}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed, with high expression in the
CC germline. {ECO:0000269|PubMed:27138431}.
CC -!- DEVELOPMENTAL STAGE: Expressed at all developmental stages, with high
CC expression during embryogenesis. {ECO:0000269|PubMed:27138431}.
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; Z69385; CAA93429.2; -; Genomic_DNA.
DR PIR; T27927; T27927.
DR RefSeq; NP_502036.1; NM_069635.4.
DR PDB; 5JJ6; X-ray; 2.91 A; A/B=134-508.
DR PDB; 5JJ7; X-ray; 3.75 A; A/B=134-508.
DR PDBsum; 5JJ6; -.
DR PDBsum; 5JJ7; -.
DR AlphaFoldDB; Q23544; -.
DR SMR; Q23544; -.
DR BioGRID; 43090; 6.
DR STRING; 6239.ZK593.8; -.
DR EPD; Q23544; -.
DR PaxDb; Q23544; -.
DR EnsemblMetazoa; ZK593.8.1; ZK593.8.1; WBGene00014004.
DR GeneID; 177990; -.
DR KEGG; cel:CELE_ZK593.8; -.
DR UCSC; ZK593.8; c. elegans.
DR CTD; 177990; -.
DR WormBase; ZK593.8; CE28722; WBGene00014004; fic-1.
DR eggNOG; KOG3824; Eukaryota.
DR GeneTree; ENSGT00390000008873; -.
DR HOGENOM; CLU_040460_0_1_1; -.
DR InParanoid; Q23544; -.
DR OMA; CTEMTLD; -.
DR OrthoDB; 1057856at2759; -.
DR PhylomeDB; Q23544; -.
DR PRO; PR:Q23544; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00014004; Expressed in germ line (C elegans) and 4 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:WormBase.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005635; C:nuclear envelope; IDA:WormBase.
DR GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell.
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; IDA:WormBase.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IMP:WormBase.
DR GO; GO:0018117; P:protein adenylylation; IDA:WormBase.
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 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Endoplasmic reticulum; Hydrolase; Membrane;
KW Nucleotide-binding; Nucleotidyltransferase; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; TPR repeat; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..508
FT /note="Protein adenylyltransferase fic-1"
FT /id="PRO_0000381779"
FT TRANSMEM 44..64
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REPEAT 147..180
FT /note="TPR 1"
FT REPEAT 181..214
FT /note="TPR 2"
FT DOMAIN 326..461
FT /note="Fido"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00791"
FT REGION 482..508
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 270..275
FT /note="Inhibitory (S/T)XXXE(G/N) motif"
FT COMPBIAS 491..508
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 404
FT /evidence="ECO:0000250|UniProtKB:A0A061I403"
FT BINDING 274
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT BINDING 357..360
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT BINDING 408..415
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT BINDING 440..441
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT BINDING 448
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT SITE 274
FT /note="Important for autoinhibition of adenylyltransferase
FT activity"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT MOD_RES 352
FT /note="O-AMP-threonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:27138431"
FT MOD_RES 476
FT /note="O-AMP-threonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:27138431"
FT MUTAGEN 274
FT /note="E->G: Enhanced adenylyltransferase activity.
FT Promiscuous use of ATP, GTP, CTP or UTP. In vitro
FT adenylyltransferase activity towards histones H2A, H2B,
FT H3.1, H3.2 and H3.3, but not H1 or H4. Increases resistance
FT to P.aeruginosa-mediated killing. Reduced
FT adenylyltransferase activity when associated with D-298."
FT /evidence="ECO:0000269|PubMed:27138431"
FT MUTAGEN 298
FT /note="I->D: Disrupts homodimer formation. Reduced
FT adenylyltransferase activity when associated with G-274."
FT /evidence="ECO:0000269|PubMed:27138431"
FT MUTAGEN 404
FT /note="H->A: Abolishes adenylyltransferase activity."
FT /evidence="ECO:0000269|PubMed:27138431"
FT HELIX 147..159
FT /evidence="ECO:0007829|PDB:5JJ6"
FT HELIX 164..176
FT /evidence="ECO:0007829|PDB:5JJ6"
FT HELIX 181..193
FT /evidence="ECO:0007829|PDB:5JJ6"
FT HELIX 197..210
FT /evidence="ECO:0007829|PDB:5JJ6"
FT HELIX 215..244
FT /evidence="ECO:0007829|PDB:5JJ6"
FT HELIX 252..272
FT /evidence="ECO:0007829|PDB:5JJ6"
FT TURN 273..275
FT /evidence="ECO:0007829|PDB:5JJ6"
FT HELIX 280..289
FT /evidence="ECO:0007829|PDB:5JJ6"
FT HELIX 298..316
FT /evidence="ECO:0007829|PDB:5JJ6"
FT TURN 317..319
FT /evidence="ECO:0007829|PDB:5JJ6"
FT STRAND 320..322
FT /evidence="ECO:0007829|PDB:5JJ6"
FT HELIX 328..339
FT /evidence="ECO:0007829|PDB:5JJ6"
FT TURN 340..342
FT /evidence="ECO:0007829|PDB:5JJ6"
FT TURN 344..348
FT /evidence="ECO:0007829|PDB:5JJ6"
FT HELIX 369..380
FT /evidence="ECO:0007829|PDB:5JJ6"
FT HELIX 382..385
FT /evidence="ECO:0007829|PDB:5JJ6"
FT HELIX 389..403
FT /evidence="ECO:0007829|PDB:5JJ6"
FT STRAND 406..408
FT /evidence="ECO:0007829|PDB:5JJ6"
FT HELIX 410..423
FT /evidence="ECO:0007829|PDB:5JJ6"
FT TURN 424..426
FT /evidence="ECO:0007829|PDB:5JJ6"
FT HELIX 434..436
FT /evidence="ECO:0007829|PDB:5JJ6"
FT HELIX 437..447
FT /evidence="ECO:0007829|PDB:5JJ6"
FT TURN 448..450
FT /evidence="ECO:0007829|PDB:5JJ6"
FT HELIX 453..476
FT /evidence="ECO:0007829|PDB:5JJ6"
SQ SEQUENCE 508 AA; 56979 MW; 0E6465335825836A CRC64;
MSVRRRTHSD DFSYLLEKTR RPSKLNVVQE DPKSAPPQGY SLTTVIIISV LVSLICQHFV
PYAVSTLHTV IKNSPKQKSS PPPSNRLNIG FISGNSPEKY APAVQKPTFL VDPIYDEKWK
GIQTAVPVMS TQTDEKREND PAKVKEAILA AKAAGRSRKD GNLERAMTIM EHAMALAPTN
PQILIEMGQI REMHNELVEA DQCYVKALAY DPGNSEALVL RARTTPLVSA IDRKMLRSVH
DLRDEFNHLQ HSTALRRMMR ETYFLYVYHT VAIEGNTLSL GQTRAILESG MVIPGKSIRE
HNEVIGMDAA LRFLNCSLLS KEHDEISIDD ILEMHRRVLG NADPVEAGRI RTTQVYVGRF
TPVSPEYVME QLKDIVDWLN DESTLTIDPI ERAAIAHYKL VLVHPFTDGN GRTARLLLNL
IMMRSGFPPV ILPVETRAEY YASLHVANLG DLRPFVRYVA KHSEASIQRY IGAMKTSSDN
ILNSGDSKLT PEESEVSEKI EAECRAGN
