FICD
entrez
11153
canonical
uniprot
Q9BVA6
canonical
ensembl
ENSG00000198855
resolver
ensp
ENSP00000446479
resolver
ensp
ENSP00000528306
resolver
ensp
ENSP00000528307
resolver
ensp
ENSP00000528308
resolver
ensp
ENSP00000528309
resolver
enst
ENST00000552695
resolver
enst
ENST00000858247
resolver
enst
ENST00000858248
resolver
enst
ENST00000858249
resolver
enst
ENST00000858250
resolver
genesymbol
FICD
resolver
genesymbol_syn
HIP13
resolver
genesymbol_syn
HYPE
resolver
hgnc
HGNC:18416
resolver
uniprot
O75406
resolver
uniprot_entry
FICD_HUMAN
resolver
uniprot_sec
O75406
resolver
activity_regulation
ACTIVITY REGULATION: 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 (PubMed:22266942, PubMed:25435325). 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 (PubMed:22266942, PubMed:25435325). {ECO:0000250|UniProtKB:A0A061I403, ECO:0000269|PubMed:22266942, ECO:0000269|PubMed:25435325}.
uniprot
proteins
amino_acid_sequence
MMLIPMASVMAVTEPKWVSVWSRFLWVTLLSMVLGSLLALLLPLGAVEEQCLAVLKGLYLLRSKPDRAQHAATKCTSPSTELSITSRGATLLVAKTKASPAGKLEARAALNQALEMKRQGKREKAQKLFMHALKMDPDFVDALTEFGIFSEEDKDIIQADYLYTRALTISPYHEKALVNRDRTLPLVEEIDQRYFSIIDSKVKKVMSIPKGNSALRRVMEETYYHHIYHTVAIEGNTLTLSEIRHILETRYAVPGKSLEEQNEVIGMHAAMKYINTTLVSRIGSVTISDVLEIHRRVLGYVDPVEAGRFRTTQVLVGHHIPPHPQDVEKQMQEFVQWLNSEEAMNLHPVEFAALAHYKLVYIHPFIDGNGRTSRLLMNLILMQAGYPPITIRKEQRSDYYHVLEAANEGDVRPFIRFIAKCTETTLDTLLFATTEYSVALPEAQPNHSGFKETLPVKP
uniprot
proteins
disease_involvement
DISEASE: Spastic paraplegia 92, autosomal recessive (SPG92) [MIM:620911]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG92 is an autosomal recessive form characterized by onset of lower limb spasticity and gait abnormalities in the first or second decade of life. Some patients have mild cognitive deficits. {ECO:0000269|PubMed:36136088}. Note=The disease may be caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.7.7.108
uniprot
proteins
ec_number
3.1.4.-
uniprot
proteins
function
FUNCTION: 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 (PubMed:36136088). Acts as a key regulator of the ERN1/IRE1-mediated unfolded protein response (UPR) by mediating AMPylation or de-AMPylation of HSPA5/BiP (PubMed:25601083, PubMed:36136088). 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 (PubMed:19362538, PubMed:25601083). {ECO:0000250|UniProtKB:A0A061I403, ECO:0000269|PubMed:22266942, ECO:0000269|PubMed:25435325, ECO:0000269|PubMed:25601083, ECO:0000269|PubMed:36136088, ECO:0000305|PubMed:19362538}.
uniprot
proteins
mass_dalton
51778
uniprot
proteins
mutagenesis
MUTAGEN 76..77; /note="TS->AA: Does not affect auto-AMPylation."; /evidence="ECO:0000269|PubMed:25601083"; MUTAGEN 79..80; /note="ST->AA: Decreased AMPylation."; /evidence="ECO:0000269|PubMed:25601083"; MUTAGEN 168; /note="T->A: Does not affect level of auto-AMPylation."; /evidence="ECO:0000269|PubMed:25435325"; MUTAGEN 170; /note="S->A: Does not affect level of auto-AMPylation."; /evidence="ECO:0000269|PubMed:25435325"; MUTAGEN 172; /note="Y->F: Does not affect level of auto-AMPylation."; /evidence="ECO:0000269|PubMed:25435325"; MUTAGEN 183; /note="T->A: Decreased AMPylation."; /evidence="ECO:0000269|PubMed:25601083"; MUTAGEN 234; /note="E->G: Promotes adenylyltransferase activity."; /evidence="ECO:0000269|PubMed:22266942, ECO:0000269|PubMed:25435325, ECO:0000269|PubMed:25601083"; MUTAGEN 258; /note="L->D: Abolishes homodimerization."; /evidence="ECO:0000269|PubMed:25435325"; MUTAGEN 275; /note="N->Q: Strongly decreased N-glycosylation. Abolished N-glycosylation; when associated with Q-446."; /evidence="ECO:0000269|PubMed:25601083"; MUTAGEN 363; /note="H->A: Abolishes adenylyltransferase activity."; /evidence="ECO:0000269|PubMed:19362538, ECO:0000269|PubMed:25601083"; MUTAGEN 446; /note="N->Q: Slightly decreased N-glycosylation. Abolished N-glycosylation; when associated with Q-275."; /evidence="ECO:0000269|PubMed:25601083
uniprot
proteins
post_translational_modification
PTM: Auto-AMPylated in vitro; it is unclear whether auto-AMPylation is relevant in vivo. {ECO:0000269|PubMed:25435325, ECO:0000269|PubMed:25601083}.; PTM: N-glycosylated; predominantly glycosylated at Asn-275. {ECO:0000269|PubMed:25601083}.
uniprot
proteins
protein_family
Fic family
uniprot
proteins
pubmed
12975309
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
19362538
uniprot
proteins
pubmed
22266942
uniprot
proteins
pubmed
25435325
uniprot
proteins
pubmed
25601083
uniprot
proteins
pubmed
36136088
uniprot
proteins
pubmed
9700202
uniprot
proteins
sequence_length
458
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000269|PubMed:25601083, ECO:0000269|PubMed:36136088}; Single-pass type II membrane protein {ECO:0000305|PubMed:25601083}.
uniprot
proteins
transmembrane_region
TRANSMEM 24..44; /note="Helical; Signal-anchor for type II membrane protein"; /evidence="ECO:0000255
uniprot
proteins