UBA5_DANRE
ID UBA5_DANRE Reviewed; 398 AA.
AC X1WER2;
DT 18-JAN-2017, integrated into UniProtKB/Swiss-Prot.
DT 20-JAN-2016, sequence version 2.
DT 03-AUG-2022, entry version 44.
DE RecName: Full=Ubiquitin-like modifier-activating enzyme 5 {ECO:0000305};
DE Short=Ubiquitin-activating enzyme 5 {ECO:0000303|PubMed:27545681};
DE AltName: Full=UFM1-activating enzyme {ECO:0000305};
GN Name=uba5 {ECO:0000303|PubMed:27545681};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP DISRUPTION PHENOTYPE.
RX PubMed=27545681; DOI=10.1016/j.ajhg.2016.06.030;
RG FREX Consortium;
RA Colin E., Daniel J., Ziegler A., Wakim J., Scrivo A., Haack T.B.,
RA Khiati S., Denomme A.S., Amati-Bonneau P., Charif M., Procaccio V.,
RA Reynier P., Aleck K.A., Botto L.D., Herper C.L., Kaiser C.S., Nabbout R.,
RA N'Guyen S., Mora-Lorca J.A., Assmann B., Christ S., Meitinger T.,
RA Strom T.M., Prokisch H., Miranda-Vizuete A., Hoffmann G.F., Lenaers G.,
RA Bomont P., Liebau E., Bonneau D.;
RT "Biallelic variants in UBA5 reveal that disruption of the UFM1 cascade can
RT result in early-onset encephalopathy.";
RL Am. J. Hum. Genet. 99:695-703(2016).
CC -!- FUNCTION: E1-like enzyme which specifically catalyzes the first step in
CC ufmylation. Activates ufm1 by first adenylating its C-terminal glycine
CC residue with ATP, and thereafter linking this residue to the side chain
CC of a cysteine residue in E1, yielding a ufm1-E1 thioester and free AMP.
CC Activates ufm1 via a trans-binding mechanism, in which ufm1 interacts
CC with distinct sites in both subunits of the uba5 homodimer. Trans-
CC binding also promotes stabilization of the uba5 homodimer, and enhances
CC ATP-binding. Transfer of ufm1 from uba5 to the E2-like enzyme UFC1 also
CC takes place using a trans mechanism. Ufmylation is involved in
CC reticulophagy (also called ER-phagy) induced in response to endoplasmic
CC reticulum stress. {ECO:0000250|UniProtKB:Q9GZZ9}.
CC -!- SUBUNIT: Homodimer; homodimerization is required for ufm1 activation.
CC Interacts (via UIS motif) with ufm1; binds ufm1 via a trans-binding
CC mechanism in which ufm1 interacts with distinct sites in both subunits
CC of the uba5 homodimer. Interacts (via C-terminus) with ufc1.
CC {ECO:0000250|UniProtKB:Q9GZZ9}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9GZZ9}. Nucleus
CC {ECO:0000250|UniProtKB:Q9GZZ9}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q9GZZ9}. Golgi apparatus
CC {ECO:0000250|UniProtKB:Q9GZZ9}.
CC -!- DISRUPTION PHENOTYPE: Morpholino knockdown results in seizure-like
CC behavior and decreases locomotor function (PubMed:27545681).
CC {ECO:0000269|PubMed:27545681}.
CC -!- SIMILARITY: Belongs to the ubiquitin-activating E1 family. UBA5
CC subfamily. {ECO:0000305}.
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DR EMBL; CR381660; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; X1WER2; -.
DR SMR; X1WER2; -.
DR STRING; 7955.ENSDARP00000128713; -.
DR ZFIN; ZDB-GENE-031112-2; uba5.
DR eggNOG; KOG2336; Eukaryota.
DR HOGENOM; CLU_013325_0_1_1; -.
DR Reactome; R-DRE-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR PRO; PR:X1WER2; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0071566; F:UFM1 activating enzyme activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0030218; P:erythrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0040011; P:locomotion; IMP:UniProtKB.
DR GO; GO:0007626; P:locomotory behavior; IMP:ZFIN.
DR GO; GO:0030219; P:megakaryocyte differentiation; ISS:UniProtKB.
DR GO; GO:0032446; P:protein modification by small protein conjugation; IBA:GO_Central.
DR GO; GO:0071569; P:protein ufmylation; ISS:UniProtKB.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; ISS:UniProtKB.
DR GO; GO:0061709; P:reticulophagy; ISS:UniProtKB.
DR InterPro; IPR029752; D-isomer_DH_CS1.
DR InterPro; IPR045886; ThiF/MoeB/HesA.
DR InterPro; IPR000594; ThiF_NAD_FAD-bd.
DR InterPro; IPR035985; Ubiquitin-activating_enz.
DR PANTHER; PTHR10953; PTHR10953; 1.
DR Pfam; PF00899; ThiF; 1.
DR SUPFAM; SSF69572; SSF69572; 1.
DR PROSITE; PS00065; D_2_HYDROXYACID_DH_1; 1.
PE 3: Inferred from homology;
KW ATP-binding; Cytoplasm; Endoplasmic reticulum; Golgi apparatus; Membrane;
KW Metal-binding; Nucleotide-binding; Nucleus; Reference proteome;
KW Ubl conjugation pathway; Zinc.
FT CHAIN 1..398
FT /note="Ubiquitin-like modifier-activating enzyme 5"
FT /id="PRO_0000438781"
FT MOTIF 330..342
FT /note="UFM1-interacting sequence (UIS)"
FT /evidence="ECO:0000250|UniProtKB:Q9GZZ9"
FT ACT_SITE 246
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000250|UniProtKB:Q9GZZ9"
FT BINDING 79
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9GZZ9"
FT BINDING 100
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9GZZ9"
FT BINDING 123
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9GZZ9"
FT BINDING 146
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9GZZ9"
FT BINDING 180
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9GZZ9"
FT BINDING 222
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9GZZ9"
FT BINDING 225
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9GZZ9"
FT BINDING 299
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9GZZ9"
FT BINDING 304
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9GZZ9"
SQ SEQUENCE 398 AA; 44234 MW; CBDB4F027DB7C4CC CRC64;
MATVEELKLR IRELENELIK SKQKQSDAEH NIRPKIEQMS AEVVDSNPYS RLMALKRMGI
VQDYEKIRSF AVAVVGVGGV GSVTAEMLTR CGIGKLLLFD YDKVELANMN RLFFQPHQAG
LSKVEAAQHT LRNINPDVAF ETHNYNITTM DNFTHFMDRV SHGGLEEGKP VDLILSCVDN
FEARMAINTA CNELGQIWME SGVSENAVSG HIQLIIPGET ACFACAPPLV VAANIDEKTL
KRDGVCAASL PTTMGVVAGL LVQNVLKYLL GFGTVSYYLG YNAMQDFFPS MAMKANPQCD
DRHCRRQQDE YKKKEAERPK QEVVQEEEEV VHEDNEWGIE LVSEVTEAEL QDASGPIPDL
PEGITVAYTI PEKDGGSGET VEETEQSLEE LMAQMKKI
