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Protein

Adenosine monophosphate-protein transferase FICD

Gene

Ficd

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at transcript leveli

Functioni

Protein that can both mediate the addition of adenosine 5'-monophosphate (AMP) to specific residues of target proteins (AMPylation), and the removal of the same modification from target proteins (de-AMPylation), depending on the context (By similarity). The side chain of Glu-231 determines which of the two opposing activities (AMPylase or de-AMPylase) will take place (By similarity). Acts as a key regulator of the ERN1/IRE1-mediated unfolded protein response (UPR) by mediating AMPylation or de-AMPylation of HSPA5/BiP (By similarity). In unstressed cells, acts as an adenylyltransferase by mediating AMPylation of HSPA5/BiP at 'Thr-518', thereby inactivating it (By similarity). In response to endoplasmic reticulum stress, acts as a phosphodiesterase by mediating removal of ATP (de-AMPylation) from HSPA5/BiP at 'Thr-518', leading to restore HSPA5/BiP activity (By similarity). Although it is able to AMPylate RhoA, Rac and Cdc42 Rho GTPases in vitro, Rho GTPases do not constitute physiological substrates (By similarity).By similarity

Catalytic activityi

ATP + [protein]-L-tyrosine = diphosphate + [protein]-O4-(5'-adenylyl)-L-tyrosine.By similarity
[protein]-O4-(5'-adenylyl)-L-threonine + H2O = [protein]-L-threonine + AMP.By similarity
ATP + [protein]-L-threonine = diphosphate + [protein]-O4-(5'-adenylyl)-L-threonine.By similarity

Cofactori

Mg2+By similarity, Mn2+By similarityNote: Divalent metal cation. Prefers Mn2+ over Mg2+.By similarity

Enzyme regulationi

The side chain of Glu-234 determines which of the two opposing activities (AMPylase or de-AMPylase) will take place. In response to endoplasmic reticulum stress, mediates de-AMPylase activity (By similarity). Adenylyltransferase activity is inhibited by the inhibitory helix present at the N-terminus: Glu-234 binds ATP and competes with ATP-binding at Arg-374, thereby preventing adenylyltransferase activity (By similarity). In unstressed cells, disengagement of Glu-234 promotes adenylyltransferase activity (By similarity). Activation dissociates ATP-binding from Glu-234, allowing ordered binding of the entire ATP moiety with the alpha-phosphate in an orientation that is productive for accepting an incoming target hydroxyl side chain (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei234ATP; via amide nitrogenBy similarity1
Sitei234Important for autoinhibition of adenylyltransferase activityBy similarity1
Active sitei363By similarity1
Binding sitei407ATPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi316 – 319ATPBy similarity4
Nucleotide bindingi367 – 374ATPBy similarity8
Nucleotide bindingi399 – 400ATPBy similarity2

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Nucleotidyltransferase, Transferase
Biological processUnfolded protein response
LigandATP-binding, Magnesium, Manganese, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Adenosine monophosphate-protein transferase FICDCurated (EC:2.7.7.n1By similarity)
Alternative name(s):
AMPylator FICDBy similarity
De-AMPylase FICDBy similarity (EC:3.1.4.-By similarity)
FIC domain-containing proteinBy similarity
Gene namesi
Name:FicdImported
Synonyms:D5Ertd40eImported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:1098550 Ficd

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 23CytoplasmicBy similarityAdd BLAST23
Transmembranei24 – 44Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini45 – 458LumenalBy similarityAdd BLAST414

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003173021 – 458Adenosine monophosphate-protein transferase FICDAdd BLAST458

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei80O-AMP-threonine; by autocatalysisBy similarity1
Modified residuei183O-AMP-threonine; by autocatalysisBy similarity1
Glycosylationi275N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

Auto-AMPylated in vitro.By similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ8BIX9
PRIDEiQ8BIX9

PTM databases

iPTMnetiQ8BIX9
PhosphoSitePlusiQ8BIX9

Expressioni

Gene expression databases

BgeeiENSMUSG00000053334
CleanExiMM_FICD
GenevisibleiQ8BIX9 MM

Interactioni

Subunit structurei

Homodimer. Interacts with HD.By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000071719

Structurei

3D structure databases

ProteinModelPortaliQ8BIX9
SMRiQ8BIX9
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati106 – 139TPR 1Add BLAST34
Repeati140 – 173TPR 2Add BLAST34
Domaini285 – 420FidoPROSITE-ProRule annotationAdd BLAST136

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi230 – 235Inhibitory (S/T)XXXE(G/N) motifBy similarity6

Domaini

The fido domain mediates the adenylyltransferase activity.By similarity

Sequence similaritiesi

Belongs to the fic family.Curated

Keywords - Domaini

Repeat, Signal-anchor, TPR repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3824 Eukaryota
COG3177 LUCA
GeneTreeiENSGT00390000008873
HOGENOMiHOG000008059
HOVERGENiHBG095654
InParanoidiQ8BIX9
OMAiNYAALAH
OrthoDBiEOG091G0GN7
PhylomeDBiQ8BIX9
TreeFamiTF314692

Family and domain databases

Gene3Di1.10.3290.10, 1 hit
1.25.40.10, 1 hit
InterProiView protein in InterPro
IPR003812 Fido
IPR036597 Fido-like_dom_sf
IPR013026 TPR-contain_dom
IPR011990 TPR-like_helical_dom_sf
PfamiView protein in Pfam
PF02661 Fic, 1 hit
SUPFAMiSSF140931 SSF140931, 1 hit
SSF48452 SSF48452, 1 hit
PROSITEiView protein in PROSITE
PS51459 FIDO, 1 hit
PS50293 TPR_REGION, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8BIX9-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MILMPMASVV AVAEPKWVSV WGRFLWMALL SMALGSLLAL LLPLGVVEEH
60 70 80 90 100
CLAVLRGFHL LRSKLDRAQP VVPKCTSLCT ELSVSSRDAG LLTVKTTASP
110 120 130 140 150
AGKLEAKAAL NQALEMKRQG KRGKAHKLFL HALKMDPGFV DALNEFGIFS
160 170 180 190 200
EEDKDIIQAD YLYTRALTIS PFHEKALVNR DRTLPLVEEI DQRYFSVIDS
210 220 230 240 250
KVKKVMSIPK GSSALRRVME ETYYHHIYHT VAIEGNTLTL SEIRHILETR
260 270 280 290 300
YAVPGKSLEE QNEVIGMHAA MKYINTTLVS RIGSVTMDDM LEIHRRVLGY
310 320 330 340 350
VDPVEAGRFR RTQVLVGHHI PPHPRDVEKQ MQEFTQWLNS EDAMNLHPVE
360 370 380 390 400
FAALAHYKLV YIHPFIDGNG RTSRLLMNLI LMQAGYPPIT IRKEQRSEYY
410 420 430 440 450
HVLEVANEGD VRPFIRFIAK CTEVTLDTLL LATTEYSVAL PEAQPNHSGF

KETLPVRP
Length:458
Mass (Da):51,754
Last modified:March 1, 2003 - v1
Checksum:i7183EF0F989ACE4E
GO
Isoform 2 (identifier: Q8BIX9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-115: Missing.

Show »
Length:343
Mass (Da):39,463
Checksum:i62144BEB26AAE227
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti70P → L in BAC31924 (PubMed:16141072).Curated1
Sequence conflicti283G → R in AAI39822 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0309341 – 115Missing in isoform 2. 2 PublicationsAdd BLAST115

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK044446 mRNA Translation: BAC31924.1
AK054325 mRNA Translation: BAC35731.1
AK087477 mRNA Translation: BAC39889.1
BC139821 mRNA Translation: AAI39822.1
CCDSiCCDS51620.1 [Q8BIX9-1]
RefSeqiNP_001010825.2, NM_001010825.3 [Q8BIX9-1]
XP_006530348.1, XM_006530285.3 [Q8BIX9-1]
UniGeneiMm.21926

Genome annotation databases

EnsembliENSMUST00000065698; ENSMUSP00000071719; ENSMUSG00000053334 [Q8BIX9-1]
GeneIDi231630
KEGGimmu:231630
UCSCiuc008yyl.2 mouse [Q8BIX9-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiFICD_MOUSE
AccessioniPrimary (citable) accession number: Q8BIX9
Secondary accession number(s): A4QPF9, Q8BIC9, Q8BJ12
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 5, 2008
Last sequence update: March 1, 2003
Last modified: May 23, 2018
This is version 113 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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