UBA5_RAT
ID UBA5_RAT Reviewed; 403 AA.
AC Q5M7A4;
DT 27-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-2005, sequence version 1.
DT 03-AUG-2022, entry version 119.
DE RecName: Full=Ubiquitin-like modifier-activating enzyme 5 {ECO:0000305};
DE Short=Ubiquitin-activating enzyme 5 {ECO:0000250|UniProtKB:Q9GZZ9};
DE AltName: Full=UFM1-activating enzyme {ECO:0000305};
GN Name=Uba5 {ECO:0000312|RGD:1311702};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
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).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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 (By similarity). Ufmylation is essential for erythroid
CC differentiation of both megakaryocytes and erythrocytes (By
CC similarity). {ECO:0000250|UniProtKB:Q8VE47,
CC 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 UIS motif) with GABARAPL2 and,
CC with lower affinity, with GABARAP and GABARAPL1. Interacts (via C-
CC terminus) with UFC1. {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}. Note=Localizes mainly in the cytoplasm,
CC while it localizes to the nucleus in presence of SUMO2. Interaction
CC with GABARAPL2 promotes localization to the endoplasmic reticulum
CC membrane. {ECO:0000250|UniProtKB:Q9GZZ9}.
CC -!- DOMAIN: The UFM1-interacting sequence (UIS) motif mediates interaction
CC with both UFM1 and LC3/GABARAP proteins (GABARAP, GABARAPL1 and
CC GABARAPL2). {ECO:0000250|UniProtKB:Q9GZZ9}.
CC -!- SIMILARITY: Belongs to the ubiquitin-activating E1 family. UBA5
CC subfamily. {ECO:0000305}.
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DR EMBL; BC088757; AAH88757.1; -; mRNA.
DR RefSeq; NP_001009669.1; NM_001009669.1.
DR AlphaFoldDB; Q5M7A4; -.
DR SMR; Q5M7A4; -.
DR STRING; 10116.ENSRNOP00000015240; -.
DR iPTMnet; Q5M7A4; -.
DR PhosphoSitePlus; Q5M7A4; -.
DR jPOST; Q5M7A4; -.
DR PaxDb; Q5M7A4; -.
DR PRIDE; Q5M7A4; -.
DR Ensembl; ENSRNOT00000015240; ENSRNOP00000015240; ENSRNOG00000011027.
DR GeneID; 300968; -.
DR KEGG; rno:300968; -.
DR UCSC; RGD:1311702; rat.
DR CTD; 79876; -.
DR RGD; 1311702; Uba5.
DR eggNOG; KOG2336; Eukaryota.
DR GeneTree; ENSGT00940000156177; -.
DR HOGENOM; CLU_013325_0_1_1; -.
DR InParanoid; Q5M7A4; -.
DR OMA; FTPDQAG; -.
DR OrthoDB; 1092362at2759; -.
DR PhylomeDB; Q5M7A4; -.
DR TreeFam; TF314168; -.
DR Reactome; R-RNO-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR PRO; PR:Q5M7A4; -.
DR Proteomes; UP000002494; Chromosome 8.
DR Bgee; ENSRNOG00000011027; Expressed in pancreas and 20 other tissues.
DR Genevisible; Q5M7A4; RN.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
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:0030219; P:megakaryocyte differentiation; ISS:UniProtKB.
DR GO; GO:0050905; P:neuromuscular process; ISO:RGD.
DR GO; GO:1990592; P:protein K69-linked ufmylation; 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:0033146; P:regulation of intracellular estrogen receptor signaling pathway; 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.
PE 1: Evidence at protein level;
KW ATP-binding; Cytoplasm; Endoplasmic reticulum; Golgi apparatus; Membrane;
KW Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Ubl conjugation pathway; Zinc.
FT CHAIN 1..403
FT /note="Ubiquitin-like modifier-activating enzyme 5"
FT /id="PRO_0000194973"
FT REGION 306..337
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 333..345
FT /note="UFM1-interacting sequence (UIS)"
FT /evidence="ECO:0000250|UniProtKB:Q9GZZ9"
FT ACT_SITE 248
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000250|UniProtKB:Q9GZZ9"
FT BINDING 81
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9GZZ9"
FT BINDING 102
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9GZZ9"
FT BINDING 125
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9GZZ9"
FT BINDING 148
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9GZZ9"
FT BINDING 182
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9GZZ9"
FT BINDING 224
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9GZZ9"
FT BINDING 227
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9GZZ9"
FT BINDING 301
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9GZZ9"
FT BINDING 306
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9GZZ9"
FT MOD_RES 357
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9GZZ9"
FT MOD_RES 392
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VE47"
SQ SEQUENCE 403 AA; 44895 MW; A30C6DB46D8253B4 CRC64;
MAESVERLLQ RVEELEQELA RERSRRIAGD GHCGRTRIQK MSDEVVDSNP YSRLMALKRM
GVVSDYEKIR TYAVAIVGVG GVGSVTAEML TRCGIGKLLL FDYDKVELAN MNRLFFQPYQ
AGMSKVQAAE HTLRSINPDV LFEVHNYNIT TVEHFEHFMN RISNGGLEEG QPVDLVLSCV
DNFEARMAIN TACNELGQTW MESGVSENAV SGHIQLMVPG ESACFACAPP LVVASNIDEK
TLKREGVCAA SLPTTMGVVA GILVQNVLKF LLKFGTVSFY LGYNAMQDFF PTMFMKPNPQ
CDDKNCRKQQ EEYKKRAPAQ PTQETAPQEE EEVVHEDNEW GIELVSEVSE EELKNSSGPV
PTLPEGITVA YTVPKKREDS VSEVTVEDSG ESLEDLMARM KKM
