UBA5_MOUSE
ID UBA5_MOUSE Reviewed; 403 AA.
AC Q8VE47; Q3TG27; Q3U8X9; Q3U9E7; Q9CYD6;
DT 27-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 02-MAR-2010, sequence version 2.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Ubiquitin-like modifier-activating enzyme 5 {ECO:0000305};
DE Short=Ubiquitin-activating enzyme 5 {ECO:0000303|PubMed:20018847};
DE AltName: Full=UFM1-activating enzyme {ECO:0000305};
GN Name=Uba5 {ECO:0000303|PubMed:20018847, ECO:0000312|MGI:MGI:1913913};
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].
RC STRAIN=C57BL/6J; TISSUE=Bone marrow, and Heart;
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 GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000312|EMBL:AAH19764.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II {ECO:0000312|EMBL:AAH19764.1};
RC TISSUE=Mammary gland {ECO:0000312|EMBL:AAH19764.1};
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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-392, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=20018847; DOI=10.1074/jbc.m109.036814;
RA Tatsumi K., Sou Y.S., Tada N., Nakamura E., Iemura S., Natsume T.,
RA Kang S.H., Chung C.H., Kasahara M., Kominami E., Yamamoto M., Tanaka K.,
RA Komatsu M.;
RT "A novel type of E3 ligase for the Ufm1 conjugation system.";
RL J. Biol. Chem. 285:5417-5427(2010).
RN [6]
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF CYS-248.
RX PubMed=21304510; DOI=10.1038/ncomms1182;
RA Tatsumi K., Yamamoto-Mukai H., Shimizu R., Waguri S., Sou Y.S.,
RA Sakamoto A., Taya C., Shitara H., Hara T., Chung C.H., Tanaka K.,
RA Yamamoto M., Komatsu M.;
RT "The Ufm1-activating enzyme Uba5 is indispensable for erythroid
RT differentiation in mice.";
RL Nat. Commun. 2:181-181(2011).
CC -!- FUNCTION: E1-like enzyme which specifically catalyzes the first step in
CC ufmylation (PubMed:21304510). Activates UFM1 by first adenylating its
CC C-terminal glycine residue with ATP, and thereafter linking this
CC residue to the side chain of a cysteine residue in E1, yielding a UFM1-
CC E1 thioester and free AMP (By similarity). Activates UFM1 via a trans-
CC binding mechanism, in which UFM1 interacts with distinct sites in both
CC subunits of the UBA5 homodimer (By similarity). Trans-binding also
CC promotes stabilization of the UBA5 homodimer, and enhances ATP-binding
CC (By similarity). Transfer of UFM1 from UBA5 to the E2-like enzyme UFC1
CC also takes place using a trans mechanism (By similarity). Ufmylation is
CC involved in reticulophagy (also called ER-phagy) induced in response to
CC endoplasmic reticulum stress (By similarity). Ufmylation is essential
CC for erythroid differentiation of both megakaryocytes and erythrocytes
CC (PubMed:21304510). {ECO:0000250|UniProtKB:Q9GZZ9,
CC ECO:0000269|PubMed:21304510}.
CC -!- SUBUNIT: Homodimer; homodimerization is required for UFM1 activation
CC (By similarity). Interacts (via UIS motif) with UFM1; binds UFM1 via a
CC trans-binding mechanism in which UFM1 interacts with distinct sites in
CC both subunits of the UBA5 homodimer (PubMed:21304510). Interacts (via
CC UIS motif) with GABARAPL2 and, with lower affinity, with GABARAP and
CC GABARAPL1 (By similarity). Interacts (via C-terminus) with UFC1 (By
CC similarity). {ECO:0000250|UniProtKB:Q9GZZ9,
CC ECO:0000269|PubMed:21304510}.
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 -!- DISRUPTION PHENOTYPE: Death at embryonic day 12.5 (PubMed:20018847,
CC PubMed:21304510). Embryonic lethality is caused by severe anemia
CC associated with defective differentiation of both megakaryocytes and
CC erythrocytes from common myeloid progenitors (PubMed:21304510).
CC {ECO:0000269|PubMed:20018847, ECO:0000269|PubMed:21304510}.
CC -!- SIMILARITY: Belongs to the ubiquitin-activating E1 family. UBA5
CC subfamily. {ECO:0000305}.
CC -!- CAUTION: Was initially reported to mediate activation of SUMO2 in
CC addition to UFM1 (By similarity). However, it was later shown that it
CC is specific for UFM1 (PubMed:21304510). {ECO:0000250|UniProtKB:Q9GZZ9,
CC ECO:0000269|PubMed:21304510}.
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DR EMBL; AK017787; BAB30933.1; -; mRNA.
DR EMBL; AK151823; BAE30720.1; -; mRNA.
DR EMBL; AK152029; BAE30888.1; -; mRNA.
DR EMBL; AK168907; BAE40721.1; -; mRNA.
DR EMBL; CH466560; EDL21084.1; -; Genomic_DNA.
DR EMBL; BC019764; AAH19764.1; -; mRNA.
DR CCDS; CCDS23457.1; -.
DR RefSeq; NP_079968.2; NM_025692.3.
DR AlphaFoldDB; Q8VE47; -.
DR SMR; Q8VE47; -.
DR BioGRID; 211631; 33.
DR IntAct; Q8VE47; 1.
DR MINT; Q8VE47; -.
DR STRING; 10090.ENSMUSP00000035166; -.
DR iPTMnet; Q8VE47; -.
DR PhosphoSitePlus; Q8VE47; -.
DR SwissPalm; Q8VE47; -.
DR EPD; Q8VE47; -.
DR MaxQB; Q8VE47; -.
DR PaxDb; Q8VE47; -.
DR PeptideAtlas; Q8VE47; -.
DR PRIDE; Q8VE47; -.
DR ProteomicsDB; 298057; -.
DR Antibodypedia; 2258; 169 antibodies from 29 providers.
DR DNASU; 66663; -.
DR Ensembl; ENSMUST00000035166; ENSMUSP00000035166; ENSMUSG00000032557.
DR GeneID; 66663; -.
DR KEGG; mmu:66663; -.
DR UCSC; uc009rhf.2; mouse.
DR CTD; 79876; -.
DR MGI; MGI:1913913; Uba5.
DR VEuPathDB; HostDB:ENSMUSG00000032557; -.
DR eggNOG; KOG2336; Eukaryota.
DR GeneTree; ENSGT00940000156177; -.
DR InParanoid; Q8VE47; -.
DR OMA; FTPDQAG; -.
DR OrthoDB; 1092362at2759; -.
DR PhylomeDB; Q8VE47; -.
DR TreeFam; TF314168; -.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR BioGRID-ORCS; 66663; 23 hits in 75 CRISPR screens.
DR ChiTaRS; Uba5; mouse.
DR PRO; PR:Q8VE47; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q8VE47; protein.
DR Bgee; ENSMUSG00000032557; Expressed in lacrimal gland and 259 other tissues.
DR ExpressionAtlas; Q8VE47; baseline and differential.
DR Genevisible; Q8VE47; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
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; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0030218; P:erythrocyte differentiation; IMP:UniProtKB.
DR GO; GO:0030219; P:megakaryocyte differentiation; IMP:UniProtKB.
DR GO; GO:0050905; P:neuromuscular process; ISO:MGI.
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; IDA: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_0000194971"
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:0000305|PubMed:21304510"
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:0007744|PubMed:21183079"
FT MUTAGEN 248
FT /note="C->S: Abolished ability to catalyze the first step
FT in ufmylation."
FT /evidence="ECO:0000269|PubMed:21304510"
FT CONFLICT 10..11
FT /note="QR -> HG (in Ref. 1; BAB30933)"
FT /evidence="ECO:0000305"
FT CONFLICT 30
FT /note="D -> G (in Ref. 1; BAE30888)"
FT /evidence="ECO:0000305"
FT CONFLICT 153
FT /note="E -> G (in Ref. 1; BAB30933)"
FT /evidence="ECO:0000305"
FT CONFLICT 156
FT /note="E -> G (in Ref. 1; BAB30933)"
FT /evidence="ECO:0000305"
FT CONFLICT 156
FT /note="E -> K (in Ref. 1; BAE30720/BAE30888)"
FT /evidence="ECO:0000305"
FT CONFLICT 164
FT /note="N -> K (in Ref. 1; BAB30933)"
FT /evidence="ECO:0000305"
FT CONFLICT 224
FT /note="C -> L (in Ref. 1; BAB30933)"
FT /evidence="ECO:0000305"
FT CONFLICT 300
FT /note="Q -> H (in Ref. 3; AAH19764)"
FT /evidence="ECO:0000305"
FT CONFLICT 402
FT /note="N -> T (in Ref. 3; AAH19764)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 403 AA; 44790 MW; 6C022AF9E0B7C83B CRC64;
MADSVERLRQ RVEELEQELA RERTRRSGGD GHCGRTRIQE MSDEVLDSNP YSRLMALKRM
GIVSDYKKIR TYAVAIVGVG GVGSVTAEML TRCGIGKLLL FDYDKVELAN MNRLFFQPYQ
AGLSKVHAAE HTLRNINPDV LFEVHNYNIT TVEHFEHFMN RISNGGLEEG QPVDLVLSCV
DNFEARMAIN TACNELGQTW MESGVSENAV SGHIQLMIPG ESACFACAPP LVVASNIDEK
TLKREGVCAA SLPTTMGVVA GILVQNVLKF LLKFGTVSFY LGYNAMQDFF PTMFMKPNPQ
CDDKNCRKQQ EEYKKRAAAL PTQEAEPQEE AEVVHEDNEW GIELVSEVSE EELKNSSGPV
PTLPEGITVA YTVPKKTEDS ASEVTVEDSG ESLEDLMARM KNM
