FICD_CRIGR
ID FICD_CRIGR Reviewed; 455 AA.
AC A0A061I403; G3HVJ3;
DT 28-FEB-2018, integrated into UniProtKB/Swiss-Prot.
DT 03-SEP-2014, sequence version 1.
DT 03-AUG-2022, entry version 27.
DE RecName: Full=Protein adenylyltransferase FICD {ECO:0000305};
DE EC=2.7.7.n1 {ECO:0000269|PubMed:26673894, ECO:0000269|PubMed:27918543, ECO:0000269|PubMed:29064368};
DE AltName: Full=AMPylator FICD {ECO:0000305};
DE AltName: Full=De-AMPylase FICD {ECO:0000305};
DE EC=3.1.4.- {ECO:0000269|PubMed:27918543};
DE AltName: Full=FIC domain-containing protein {ECO:0000303|PubMed:26673894};
DE AltName: Full=Huntingtin-interacting protein E {ECO:0000250|UniProtKB:Q9BVA6};
GN Name=FICD {ECO:0000303|PubMed:26673894};
GN Synonyms=HYPE {ECO:0000250|UniProtKB:Q9BVA6};
GN ORFNames=H671_4g11989 {ECO:0000312|EMBL:ERE76236.1},
GN I79_014982 {ECO:0000312|EMBL:EGW11974.1};
OS Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Cricetulus.
OX NCBI_TaxID=10029;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=21804562; DOI=10.1038/nbt.1932;
RA Xu X., Nagarajan H., Lewis N.E., Pan S., Cai Z., Liu X., Chen W., Xie M.,
RA Wang W., Hammond S., Andersen M.R., Neff N., Passarelli B., Koh W.,
RA Fan H.C., Wang J., Gui Y., Lee K.H., Betenbaugh M.J., Quake S.R.,
RA Famili I., Palsson B.O., Wang J.;
RT "The genomic sequence of the Chinese hamster ovary (CHO)-K1 cell line.";
RL Nat. Biotechnol. 29:735-741(2011).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=23929341; DOI=10.1038/nbt.2645;
RA Brinkrolf K., Rupp O., Laux H., Kollin F., Ernst W., Linke B., Kofler R.,
RA Romand S., Hesse F., Budach W.E., Galosy S., Muller D., Noll T.,
RA Wienberg J., Jostock T., Leonard M., Grillari J., Tauch A., Goesmann A.,
RA Helk B., Mott J.E., Puhler A., Borth N.;
RT "Chinese hamster genome sequenced from sorted chromosomes.";
RL Nat. Biotechnol. 31:694-695(2013).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF GLU-231.
RX PubMed=26673894; DOI=10.7554/elife.12621;
RA Preissler S., Rato C., Chen R., Antrobus R., Ding S., Fearnley I.M.,
RA Ron D.;
RT "AMPylation matches BiP activity to client protein load in the endoplasmic
RT reticulum.";
RL Elife 4:E12621-E12621(2015).
RN [4]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=29064368; DOI=10.7554/elife.29428;
RA Preissler S., Rohland L., Yan Y., Chen R., Read R.J., Ron D.;
RT "AMPylation targets the rate-limiting step of BiP's ATPase cycle for its
RT functional inactivation.";
RL Elife 6:0-0(2017).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, AND MUTAGENESIS OF GLU-231 AND
RP HIS-360.
RX PubMed=27918543; DOI=10.1038/nsmb.3337;
RA Preissler S., Rato C., Perera L., Saudek V., Ron D.;
RT "FICD acts bifunctionally to AMPylate and de-AMPylate the endoplasmic
RT reticulum chaperone BiP.";
RL Nat. Struct. Mol. Biol. 24:23-29(2017).
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 (PubMed:27918543).
CC The side chain of Glu-231 determines which of the two opposing
CC activities (AMPylase or de-AMPylase) will take place (PubMed:27918543).
CC Acts as a key regulator of the ERN1/IRE1-mediated unfolded protein
CC response (UPR) by mediating AMPylation or de-AMPylation of HSPA5/BiP
CC (PubMed:27918543). In unstressed cells, acts as an adenylyltransferase
CC by mediating AMPylation of HSPA5/BiP at 'Thr-518', thereby inactivating
CC it (PubMed:26673894, PubMed:29064368, PubMed:27918543). In response to
CC endoplasmic reticulum stress, acts as a phosphodiesterase by mediating
CC removal of ATP (de-AMPylation) from HSPA5/BiP at 'Thr-518', leading to
CC restore HSPA5/BiP activity (PubMed:27918543). Although it is able to
CC AMPylate RhoA, Rac and Cdc42 Rho GTPases in vitro, Rho GTPases do not
CC constitute physiological substrates (By similarity).
CC {ECO:0000250|UniProtKB:Q9BVA6, ECO:0000269|PubMed:26673894,
CC ECO:0000269|PubMed:27918543, ECO:0000269|PubMed:29064368}.
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:0000269|PubMed:27918543};
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:0000269|PubMed:26673894, ECO:0000269|PubMed:27918543,
CC ECO:0000269|PubMed:29064368};
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-231 determines which of the
CC two opposing activities (AMPylase or de-AMPylase) will take place
CC (PubMed:27918543). In response to endoplasmic reticulum stress,
CC mediates de-AMPylase activity (PubMed:27918543). Adenylyltransferase
CC activity is inhibited by the inhibitory helix present at the N-
CC terminus: Glu-231 binds ATP and competes with ATP-binding at Arg-371,
CC thereby preventing adenylyltransferase activity (By similarity). In
CC unstressed cells, disengagement of Glu-231 promotes adenylyltransferase
CC activity (PubMed:27918543). Activation dissociates ATP-binding from
CC Glu-231, allowing ordered binding of the entire ATP moiety with the
CC alpha-phosphate in an orientation that is productive for accepting an
CC incoming target hydroxyl side chain (By similarity).
CC {ECO:0000250|UniProtKB:Q9BVA6, ECO:0000269|PubMed:27918543}.
CC -!- SUBUNIT: Homodimer. Interacts with HD. {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 -!- PTM: Auto-AMPylated in vitro. {ECO:0000250|UniProtKB:Q9BVA6}.
CC -!- SIMILARITY: Belongs to the fic family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EGW11974.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; KE674650; ERE76236.1; -; Genomic_DNA.
DR EMBL; JH000777; EGW11974.1; ALT_SEQ; Genomic_DNA.
DR AlphaFoldDB; A0A061I403; -.
DR SMR; A0A061I403; -.
DR STRING; 10029.XP_007607202.1; -.
DR eggNOG; KOG3824; Eukaryota.
DR Proteomes; UP000001075; Unassembled WGS sequence.
DR Proteomes; UP000030759; Unassembled WGS sequence.
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; IDA:UniProtKB.
DR GO; GO:0030544; F:Hsp70 protein binding; IPI:UniProtKB.
DR GO; GO:0044603; F:protein adenylylhydrolase activity; IDA:UniProtKB.
DR GO; GO:0070733; F:protein adenylyltransferase activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0018117; P:protein adenylylation; IDA:UniProtKB.
DR GO; GO:0044602; P:protein deadenylylation; IDA:UniProtKB.
DR GO; GO:1903894; P:regulation of IRE1-mediated unfolded protein response; IDA: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 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; 1.
DR PROSITE; PS50293; TPR_REGION; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Endoplasmic reticulum; Glycoprotein; Hydrolase; Magnesium;
KW Manganese; Membrane; Nucleotide-binding; Nucleotidyltransferase;
KW Phosphoprotein; Reference proteome; Repeat; Signal-anchor; TPR repeat;
KW Transferase; Transmembrane; Transmembrane helix; Unfolded protein response.
FT CHAIN 1..455
FT /note="Protein adenylyltransferase FICD"
FT /id="PRO_0000443449"
FT TOPO_DOM 1..20
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT TRANSMEM 21..41
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 42..455
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT REPEAT 103..136
FT /note="TPR 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00339"
FT REPEAT 137..170
FT /note="TPR 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00339"
FT DOMAIN 282..417
FT /note="Fido"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00791"
FT MOTIF 227..232
FT /note="Inhibitory (S/T)XXXE(G/N) motif"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT ACT_SITE 360
FT /evidence="ECO:0000269|PubMed:27918543"
FT BINDING 231
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT BINDING 313..316
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT BINDING 364..371
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT BINDING 396..397
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT BINDING 404
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT SITE 231
FT /note="Important for autoinhibition of adenylyltransferase
FT activity"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT MOD_RES 76
FT /note="O-AMP-serine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT MOD_RES 77
FT /note="O-AMP-threonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT MOD_RES 180
FT /note="O-AMP-threonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT CARBOHYD 272
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 231
FT /note="E->G: Impaired phosphodiesterase activity. Promotes
FT adenylyltransferase activity."
FT /evidence="ECO:0000269|PubMed:26673894,
FT ECO:0000269|PubMed:27918543"
FT MUTAGEN 360
FT /note="H->A: Abolishes adenylyltransferase and
FT phosphodiesterase activities."
FT /evidence="ECO:0000269|PubMed:27918543"
SQ SEQUENCE 455 AA; 51477 MW; 076346720C9EA6EE CRC64;
MPMASVIAVA EPKWISVWGR FLWLTLLSMA LGSLLALLLP LGAVEEQCLA VLRSFHLLRS
KLDRTQHVVT KCTSPSTELS VTSGDVGLLT VKTKTSPAGK LEAKAALNQA LEMKRQGKRE
KAHKLFLHAL KMDPGFVDAL NEFGIFSEEE KDIIQADYLY TRALTISPFH EKALVNRDRT
LPLVEEIDQR YFSIIDSKVK KVMSIPKGSS ALRRVMEETY YHHIYHTVAI EGNTLTLSEI
RHILETRYAV PGKSLEEQNE VIGMHAAMKY INTTLVSRIG SVTIDDMLEI HRRVLGYVDP
VEAGRFRRTQ VLVGHHIPPH PRDVEKQMQE FTQWLNSEDA MNLHPVEFAA LAHYKLVYIH
PFIDGNGRTS RLLMNLILMQ AGYPPITILK EQRSEYYHVL EVANEGDVRP FIRFIAKCTE
VTLDTLLLAT TEYSVALPEA QPNHSGLKET LPVRP
