UBA7_HUMAN
ID UBA7_HUMAN Reviewed; 1012 AA.
AC P41226; Q9BRB2;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 2.
DT 03-AUG-2022, entry version 200.
DE RecName: Full=Ubiquitin-like modifier-activating enzyme 7;
DE Short=Ubiquitin-activating enzyme 7;
DE AltName: Full=D8;
DE AltName: Full=Ubiquitin-activating enzyme E1 homolog;
GN Name=UBA7 {ECO:0000303|PubMed:28397838, ECO:0000312|HGNC:HGNC:12471};
GN Synonyms=UBE1L, UBE2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=B-cell;
RX PubMed=8327486; DOI=10.1073/pnas.90.13.6071;
RA Kok K., Hofstra R., Pilz A., van den Berg A., Terpstra P., Buys C.H.C.M.,
RA Carritt B.;
RT "A gene in the chromosomal region 3p21 with greatly reduced expression in
RT lung cancer is similar to the gene for ubiquitin-activating enzyme.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:6071-6075(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7734949;
RA Kok K., Van den Berg A., Veldhuis P.M., Franke M., Terpstra P.,
RA Buys C.H.C.M.;
RT "The genomic structure of the human UBE1L gene.";
RL Gene Expr. 4:163-175(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
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 [6]
RP PROTEIN SEQUENCE OF 1-17.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R.,
RA Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass spectrometric
RT identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [7]
RP PROTEIN SEQUENCE OF 973-987, INTERACTION WITH G1P2, AND PATHWAY.
RX PubMed=11157743; DOI=10.1093/emboj/20.3.362;
RA Yuan W., Krug R.M.;
RT "Influenza B virus NS1 protein inhibits conjugation of the interferon
RT (IFN)-induced ubiquitin-like ISG15 protein.";
RL EMBO J. 20:362-371(2001).
RN [8]
RP FUNCTION.
RX PubMed=16254333; DOI=10.1128/jvi.79.22.13974-13983.2005;
RA Lenschow D.J., Giannakopoulos N.V., Gunn L.J., Johnston C., O'Guin A.K.,
RA Schmidt R.E., Levine B., Virgin H.W. IV;
RT "Identification of interferon-stimulated gene 15 as an antiviral molecule
RT during Sindbis virus infection in vivo.";
RL J. Virol. 79:13974-13983(2005).
RN [9]
RP FUNCTION.
RX PubMed=20133869; DOI=10.1073/pnas.0909144107;
RA Zhao C., Hsiang T.Y., Kuo R.L., Krug R.M.;
RT "ISG15 conjugation system targets the viral NS1 protein in influenza A
RT virus-infected cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:2253-2258(2010).
RN [10]
RP ISGYLATION.
RX PubMed=22693631; DOI=10.1371/journal.pone.0038294;
RA Bade V.N., Nickels J., Keusekotten K., Praefcke G.J.;
RT "Covalent protein modification with ISG15 via a conserved cysteine in the
RT hinge region.";
RL PLoS ONE 7:E38294-E38294(2012).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-266, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [12]
RP VARIANT 397-GLU--LEU-1012 DEL.
RX PubMed=28397838; DOI=10.1038/mp.2017.60;
RA Harripaul R., Vasli N., Mikhailov A., Rafiq M.A., Mittal K.,
RA Windpassinger C., Sheikh T.I., Noor A., Mahmood H., Downey S., Johnson M.,
RA Vleuten K., Bell L., Ilyas M., Khan F.S., Khan V., Moradi M., Ayaz M.,
RA Naeem F., Heidari A., Ahmed I., Ghadami S., Agha Z., Zeinali S., Qamar R.,
RA Mozhdehipanah H., John P., Mir A., Ansar M., French L., Ayub M.,
RA Vincent J.B.;
RT "Mapping autosomal recessive intellectual disability: combined microarray
RT and exome sequencing identifies 26 novel candidate genes in 192
RT consanguineous families.";
RL Mol. Psychiatry 23:973-984(2018).
CC -!- FUNCTION: Activates ubiquitin by first adenylating with ATP its C-
CC terminal glycine residue and thereafter linking this residue to the
CC side chain of a cysteine residue in E1, yielding a ubiquitin-E1
CC thioester and free AMP. Catalyzes the ISGylation of influenza A virus
CC NS1 protein. {ECO:0000269|PubMed:16254333,
CC ECO:0000269|PubMed:20133869}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:11157743}.
CC -!- SUBUNIT: Monomer (By similarity). Binds and is involved in the
CC conjugation of G1P2/ISG15. {ECO:0000250}.
CC -!- INTERACTION:
CC P41226; P05161: ISG15; NbExp=10; IntAct=EBI-751921, EBI-746466;
CC P41226; Q13148: TARDBP; NbExp=3; IntAct=EBI-751921, EBI-372899;
CC -!- TISSUE SPECIFICITY: Expressed in a variety of normal and tumor cell
CC types, but is reduced in lung cancer cell lines.
CC -!- PTM: ISGylated. {ECO:0000269|PubMed:22693631}.
CC -!- MISCELLANEOUS: There are two active sites within the E1 molecule,
CC allowing it to accommodate two ubiquitin moieties at a time, with a new
CC ubiquitin forming an adenylate intermediate as the previous one is
CC transferred to the thiol site.
CC -!- SIMILARITY: Belongs to the ubiquitin-activating E1 family.
CC {ECO:0000305}.
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DR EMBL; L13852; AAA75388.1; -; mRNA.
DR EMBL; AF294032; AAG49557.1; -; Genomic_DNA.
DR EMBL; BT007026; AAP35672.1; -; mRNA.
DR EMBL; CH471055; EAW65023.1; -; Genomic_DNA.
DR EMBL; BC006378; AAH06378.1; -; mRNA.
DR CCDS; CCDS2805.1; -.
DR RefSeq; NP_003326.2; NM_003335.2.
DR AlphaFoldDB; P41226; -.
DR SMR; P41226; -.
DR BioGRID; 113166; 12.
DR DIP; DIP-60526N; -.
DR IntAct; P41226; 6.
DR MINT; P41226; -.
DR STRING; 9606.ENSP00000333266; -.
DR BindingDB; P41226; -.
DR ChEMBL; CHEMBL2321623; -.
DR iPTMnet; P41226; -.
DR PhosphoSitePlus; P41226; -.
DR BioMuta; UBA7; -.
DR DMDM; 215273977; -.
DR EPD; P41226; -.
DR jPOST; P41226; -.
DR MassIVE; P41226; -.
DR MaxQB; P41226; -.
DR PaxDb; P41226; -.
DR PeptideAtlas; P41226; -.
DR PRIDE; P41226; -.
DR ProteomicsDB; 55434; -.
DR Antibodypedia; 4219; 345 antibodies from 36 providers.
DR DNASU; 7318; -.
DR Ensembl; ENST00000333486.4; ENSP00000333266.3; ENSG00000182179.13.
DR GeneID; 7318; -.
DR KEGG; hsa:7318; -.
DR MANE-Select; ENST00000333486.4; ENSP00000333266.3; NM_003335.3; NP_003326.2.
DR UCSC; uc003cxr.4; human.
DR CTD; 7318; -.
DR DisGeNET; 7318; -.
DR GeneCards; UBA7; -.
DR HGNC; HGNC:12471; UBA7.
DR HPA; ENSG00000182179; Low tissue specificity.
DR MIM; 191325; gene.
DR neXtProt; NX_P41226; -.
DR OpenTargets; ENSG00000182179; -.
DR PharmGKB; PA162407761; -.
DR VEuPathDB; HostDB:ENSG00000182179; -.
DR eggNOG; KOG2012; Eukaryota.
DR GeneTree; ENSGT00940000161447; -.
DR HOGENOM; CLU_002556_0_0_1; -.
DR InParanoid; P41226; -.
DR OMA; TGGIPMC; -.
DR OrthoDB; 91748at2759; -.
DR PhylomeDB; P41226; -.
DR TreeFam; TF300586; -.
DR PathwayCommons; P41226; -.
DR Reactome; R-HSA-1169408; ISG15 antiviral mechanism.
DR Reactome; R-HSA-168928; DDX58/IFIH1-mediated induction of interferon-alpha/beta.
DR Reactome; R-HSA-5656169; Termination of translesion DNA synthesis.
DR Reactome; R-HSA-936440; Negative regulators of DDX58/IFIH1 signaling.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; P41226; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 7318; 10 hits in 1085 CRISPR screens.
DR ChiTaRS; UBA7; human.
DR GeneWiki; UBE1L; -.
DR GenomeRNAi; 7318; -.
DR Pharos; P41226; Tbio.
DR PRO; PR:P41226; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P41226; protein.
DR Bgee; ENSG00000182179; Expressed in granulocyte and 96 other tissues.
DR Genevisible; P41226; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019782; F:ISG15 activating enzyme activity; IDA:HGNC-UCL.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; EXP:Reactome.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IBA:GO_Central.
DR GO; GO:0032020; P:ISG15-protein conjugation; IDA:HGNC-UCL.
DR GO; GO:0019941; P:modification-dependent protein catabolic process; IEA:Ensembl.
DR GO; GO:0032446; P:protein modification by small protein conjugation; IBA:GO_Central.
DR GO; GO:0036211; P:protein modification process; IDA:HGNC-UCL.
DR Gene3D; 1.10.10.2660; -; 1.
DR Gene3D; 2.40.30.180; -; 1.
DR Gene3D; 3.10.290.60; -; 1.
DR Gene3D; 3.50.50.80; -; 1.
DR InterPro; IPR032420; E1_4HB.
DR InterPro; IPR032418; E1_FCCH.
DR InterPro; IPR042302; E1_FCCH_sf.
DR InterPro; IPR045886; ThiF/MoeB/HesA.
DR InterPro; IPR000594; ThiF_NAD_FAD-bd.
DR InterPro; IPR018965; Ub-activating_enz_E1_C.
DR InterPro; IPR042449; Ub-E1_IAD_1.
DR InterPro; IPR038252; UBA_E1_C_sf.
DR InterPro; IPR019572; UBA_E1_SCCH.
DR InterPro; IPR042063; Ubi_acti_E1_SCCH.
DR InterPro; IPR035985; Ubiquitin-activating_enz.
DR InterPro; IPR018075; UBQ-activ_enz_E1.
DR InterPro; IPR033127; UBQ-activ_enz_E1_Cys_AS.
DR InterPro; IPR000011; UBQ/SUMO-activ_enz_E1-like.
DR PANTHER; PTHR10953; PTHR10953; 1.
DR Pfam; PF16191; E1_4HB; 1.
DR Pfam; PF16190; E1_FCCH; 1.
DR Pfam; PF09358; E1_UFD; 1.
DR Pfam; PF00899; ThiF; 2.
DR Pfam; PF10585; UBA_e1_thiolCys; 1.
DR PRINTS; PR01849; UBIQUITINACT.
DR SMART; SM00985; UBA_e1_C; 1.
DR SUPFAM; SSF69572; SSF69572; 2.
DR TIGRFAMs; TIGR01408; Ube1; 1.
DR PROSITE; PS00865; UBIQUITIN_ACTIVAT_2; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Direct protein sequencing; Ligase; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Repeat; Ubl conjugation;
KW Ubl conjugation pathway.
FT CHAIN 1..1012
FT /note="Ubiquitin-like modifier-activating enzyme 7"
FT /id="PRO_0000194937"
FT REPEAT 23..159
FT /note="1-1"
FT REPEAT 423..575
FT /note="1-2"
FT REGION 23..575
FT /note="2 approximate repeats"
FT ACT_SITE 599
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10132"
FT BINDING 442..471
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT MOD_RES 266
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VARIANT 397..1012
FT /note="Missing (found in a small consanguineous family with
FT learning disability; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:28397838"
FT /id="VAR_080759"
FT VARIANT 712
FT /note="P -> S (in dbSNP:rs11928913)"
FT /id="VAR_052434"
FT VARIANT 817
FT /note="H -> R (in dbSNP:rs2230149)"
FT /id="VAR_047793"
FT CONFLICT 355..378
FT /note="GVLSPMVAMLGAVAAQEVLKAISR -> RCLEPMVACWVSSCPGSAEGNLQ
FT (in Ref. 1; AAA75388 and 2; AAG49557)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1012 AA; 111694 MW; A01E1106D81778EB CRC64;
MDALDASKLL DEELYSRQLY VLGSPAMQRI QGARVLVSGL QGLGAEVAKN LVLMGVGSLT
LHDPHPTCWS DLAAQFLLSE QDLERSRAEA SQELLAQLNR AVQVVVHTGD ITEDLLLDFQ
VVVLTAAKLE EQLKVGTLCH KHGVCFLAAD TRGLVGQLFC DFGEDFTVQD PTEAEPLTAA
IQHISQGSPG ILTLRKGANT HYFRDGDLVT FSGIEGMVEL NDCDPRSIHV REDGSLEIGD
TTTFSRYLRG GAITEVKRPK TVRHKSLDTA LLQPHVVAQS SQEVHHAHCL HQAFCALHKF
QHLHGRPPQP WDPVDAETVV GLARDLEPLK RTEEEPLEEP LDEALVRTVA LSSAGVLSPM
VAMLGAVAAQ EVLKAISRKF MPLDQWLYFD ALDCLPEDGE LLPSPEDCAL RGSRYDGQIA
VFGAGFQEKL RRQHYLLVGA GAIGCELLKV FALVGLGAGN SGGLTVVDMD HIERSNLSRQ
FLFRSQDVGR PKAEVAAAAA RGLNPDLQVI PLTYPLDPTT EHIYGDNFFS RVDGVAAALD
SFQARRYVAA RCTHYLKPLL EAGTSGTWGS ATVFMPHVTE AYRAPASAAA SEDAPYPVCT
VRYFPSTAEH TLQWARHEFE ELFRLSAETI NHHQQAHTSL ADMDEPQTLT LLKPVLGVLR
VRPQNWQDCV AWALGHWKLC FHYGIKQLLR HFPPNKVLED GTPFWSGPKQ CPQPLEFDTN
QDTHLLYVLA AANLYAQMHG LPGSQDWTAL RELLKLLPQP DPQQMAPIFA SNLELASASA
EFGPEQQKEL NKALEVWSVG PPLKPLMFEK DDDSNFHVDF VVAAASLRCQ NYGIPPVNRA
QSKRIVGQII PAIATTTAAV AGLLGLELYK VVSGPRPRSA FRHSYLHLAE NYLIRYMPFA
PAIQTFHHLK WTSWDRLKVP AGQPERTLES LLAHLQEQHG LRVRILLHGS ALLYAAGWSP
EKQAQHLPLR VTELVQQLTG QAPAPGQRVL VLELSCEGDD EDTAFPPLHY EL
