FICD_MOUSE
ID FICD_MOUSE Reviewed; 458 AA.
AC Q8BIX9; A4QPF9; Q8BIC9; Q8BJ12;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 131.
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:0000312|MGI:MGI:1098550};
GN Synonyms=D5Ertd40e {ECO:0000312|MGI:MGI:1098550};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Ovary, and Retina;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
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-231 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). Although it is able to AMPylate RhoA, Rac and Cdc42 Rho
CC GTPases in vitro, Rho GTPases do not constitute physiological
CC substrates (By 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-234 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-234 binds ATP and
CC competes with ATP-binding at Arg-374, thereby preventing
CC adenylyltransferase activity (By similarity). In unstressed cells,
CC disengagement of Glu-234 promotes adenylyltransferase activity (By
CC similarity). Activation dissociates ATP-binding from Glu-234, 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. 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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8BIX9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8BIX9-2; Sequence=VSP_030934;
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}.
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DR EMBL; AK044446; BAC31924.1; -; mRNA.
DR EMBL; AK054325; BAC35731.1; -; mRNA.
DR EMBL; AK087477; BAC39889.1; -; mRNA.
DR EMBL; BC139821; AAI39822.1; -; mRNA.
DR CCDS; CCDS51620.1; -. [Q8BIX9-1]
DR RefSeq; NP_001010825.2; NM_001010825.3. [Q8BIX9-1]
DR RefSeq; XP_006530348.1; XM_006530285.3. [Q8BIX9-1]
DR AlphaFoldDB; Q8BIX9; -.
DR SMR; Q8BIX9; -.
DR STRING; 10090.ENSMUSP00000071719; -.
DR GlyGen; Q8BIX9; 1 site.
DR iPTMnet; Q8BIX9; -.
DR PhosphoSitePlus; Q8BIX9; -.
DR EPD; Q8BIX9; -.
DR PaxDb; Q8BIX9; -.
DR PRIDE; Q8BIX9; -.
DR ProteomicsDB; 267474; -. [Q8BIX9-1]
DR ProteomicsDB; 267475; -. [Q8BIX9-2]
DR Antibodypedia; 18273; 297 antibodies from 25 providers.
DR Ensembl; ENSMUST00000065698; ENSMUSP00000071719; ENSMUSG00000053334. [Q8BIX9-1]
DR GeneID; 231630; -.
DR KEGG; mmu:231630; -.
DR UCSC; uc008yyl.2; mouse. [Q8BIX9-1]
DR CTD; 11153; -.
DR MGI; MGI:1098550; Ficd.
DR VEuPathDB; HostDB:ENSMUSG00000053334; -.
DR eggNOG; KOG3824; Eukaryota.
DR GeneTree; ENSGT00390000008873; -.
DR HOGENOM; CLU_040460_0_0_1; -.
DR InParanoid; Q8BIX9; -.
DR OMA; CTEMTLD; -.
DR OrthoDB; 1057856at2759; -.
DR PhylomeDB; Q8BIX9; -.
DR TreeFam; TF314692; -.
DR BioGRID-ORCS; 231630; 1 hit in 71 CRISPR screens.
DR PRO; PR:Q8BIX9; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q8BIX9; protein.
DR Bgee; ENSMUSG00000053334; Expressed in cleaving embryo and 188 other tissues.
DR Genevisible; Q8BIX9; MM.
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:0030544; F:Hsp70 protein binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
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 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 2: Evidence at transcript level;
KW Alternative splicing; ATP-binding; Endoplasmic reticulum; Glycoprotein;
KW Hydrolase; Magnesium; Manganese; Membrane; Nucleotide-binding;
KW Nucleotidyltransferase; Phosphoprotein; Reference proteome; Repeat;
KW Signal-anchor; TPR repeat; Transferase; Transmembrane; Transmembrane helix;
KW Unfolded protein response.
FT CHAIN 1..458
FT /note="Protein adenylyltransferase FICD"
FT /id="PRO_0000317302"
FT TOPO_DOM 1..23
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT TRANSMEM 24..44
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 45..458
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT REPEAT 106..139
FT /note="TPR 1"
FT REPEAT 140..173
FT /note="TPR 2"
FT DOMAIN 285..420
FT /note="Fido"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00791"
FT MOTIF 230..235
FT /note="Inhibitory (S/T)XXXE(G/N) motif"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT ACT_SITE 363
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT BINDING 234
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT BINDING 316..319
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT BINDING 367..374
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT BINDING 399..400
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT BINDING 407
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT SITE 234
FT /note="Important for autoinhibition of adenylyltransferase
FT activity"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT MOD_RES 80
FT /note="O-AMP-threonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT MOD_RES 183
FT /note="O-AMP-threonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q9BVA6"
FT CARBOHYD 275
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..115
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_030934"
FT CONFLICT 70
FT /note="P -> L (in Ref. 1; BAC31924)"
FT /evidence="ECO:0000305"
FT CONFLICT 283
FT /note="G -> R (in Ref. 2; AAI39822)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 458 AA; 51754 MW; 7183EF0F989ACE4E CRC64;
MILMPMASVV AVAEPKWVSV WGRFLWMALL SMALGSLLAL LLPLGVVEEH CLAVLRGFHL
LRSKLDRAQP VVPKCTSLCT ELSVSSRDAG LLTVKTTASP AGKLEAKAAL NQALEMKRQG
KRGKAHKLFL HALKMDPGFV DALNEFGIFS EEDKDIIQAD YLYTRALTIS PFHEKALVNR
DRTLPLVEEI DQRYFSVIDS KVKKVMSIPK GSSALRRVME ETYYHHIYHT VAIEGNTLTL
SEIRHILETR YAVPGKSLEE QNEVIGMHAA MKYINTTLVS RIGSVTMDDM LEIHRRVLGY
VDPVEAGRFR RTQVLVGHHI PPHPRDVEKQ MQEFTQWLNS EDAMNLHPVE FAALAHYKLV
YIHPFIDGNG RTSRLLMNLI LMQAGYPPIT IRKEQRSEYY HVLEVANEGD VRPFIRFIAK
CTEVTLDTLL LATTEYSVAL PEAQPNHSGF KETLPVRP
