P41226 · UBA7_HUMAN
- ProteinUbiquitin-like modifier-activating enzyme 7
- GeneUBA7
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1012 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
E1-activating enzyme that catalyzes the covalent conjugation of the ubiquitin-like protein product of ISG15 to additional interferon stimulated proteins (ISGs) as well as other cellular proteins such as P53 in a process termed protein ISGylation (PubMed:27545325).
Plays an essential role in antiviral immunity together with ISG15 by restricting the replication of many viruses including rabies virus, influenza virus, sindbis virus, rotavirus or human cytomegalovirus (PubMed:16254333, PubMed:19073728, PubMed:29056542, PubMed:29743376, PubMed:37722521).
For example, ISG15 modification of influenza A protein NS1 disrupts the association of the NS1 with importin-alpha leading to NS1 nuclear import inhibition (PubMed:20133869).
ISGylation of human cytomegalovirs protein UL26 regulates its stability and inhibits its activities to suppress NF-kappa-B signaling (PubMed:27564865).
Plays an essential role in antiviral immunity together with ISG15 by restricting the replication of many viruses including rabies virus, influenza virus, sindbis virus, rotavirus or human cytomegalovirus (PubMed:16254333, PubMed:19073728, PubMed:29056542, PubMed:29743376, PubMed:37722521).
For example, ISG15 modification of influenza A protein NS1 disrupts the association of the NS1 with importin-alpha leading to NS1 nuclear import inhibition (PubMed:20133869).
ISGylation of human cytomegalovirs protein UL26 regulates its stability and inhibits its activities to suppress NF-kappa-B signaling (PubMed:27564865).
Miscellaneous
There are two active sites within the E1 molecule, allowing it to accommodate two ubiquitin moieties at a time, with a new ubiquitin forming an adenylate intermediate as the previous one is transferred to the thiol site.
Pathway
Protein modification; protein ubiquitination.
Features
Showing features for binding site, active site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | cytosol | |
Cellular Component | nucleoplasm | |
Molecular Function | ATP binding | |
Molecular Function | ISG15 activating enzyme activity | |
Molecular Function | ubiquitin-protein transferase activity | |
Biological Process | DNA damage response | |
Biological Process | innate immune response | |
Biological Process | ISG15-protein conjugation | |
Biological Process | modification-dependent protein catabolic process | |
Biological Process | protein modification process | |
Biological Process | protein ubiquitination |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameUbiquitin-like modifier-activating enzyme 7
- EC number
- Short namesUbiquitin-activating enzyme 7
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP41226
- Secondary accessions
Proteomes
Organism-specific databases
Disease & Variants
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_080759 | 397-1012 | found in a small consanguineous family with learning disability; uncertain significance | |||
Sequence: Missing | ||||||
Natural variant | VAR_052434 | 712 | in dbSNP:rs11928913 | |||
Sequence: P → S | ||||||
Natural variant | VAR_047793 | 817 | in dbSNP:rs2230149 | |||
Sequence: H → R |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 1,056 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data), modified residue.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000194937 | 1-1012 | UniProt | Ubiquitin-like modifier-activating enzyme 7 | |||
Sequence: MDALDASKLLDEELYSRQLYVLGSPAMQRIQGARVLVSGLQGLGAEVAKNLVLMGVGSLTLHDPHPTCWSDLAAQFLLSEQDLERSRAEASQELLAQLNRAVQVVVHTGDITEDLLLDFQVVVLTAAKLEEQLKVGTLCHKHGVCFLAADTRGLVGQLFCDFGEDFTVQDPTEAEPLTAAIQHISQGSPGILTLRKGANTHYFRDGDLVTFSGIEGMVELNDCDPRSIHVREDGSLEIGDTTTFSRYLRGGAITEVKRPKTVRHKSLDTALLQPHVVAQSSQEVHHAHCLHQAFCALHKFQHLHGRPPQPWDPVDAETVVGLARDLEPLKRTEEEPLEEPLDEALVRTVALSSAGVLSPMVAMLGAVAAQEVLKAISRKFMPLDQWLYFDALDCLPEDGELLPSPEDCALRGSRYDGQIAVFGAGFQEKLRRQHYLLVGAGAIGCELLKVFALVGLGAGNSGGLTVVDMDHIERSNLSRQFLFRSQDVGRPKAEVAAAAARGLNPDLQVIPLTYPLDPTTEHIYGDNFFSRVDGVAAALDSFQARRYVAARCTHYLKPLLEAGTSGTWGSATVFMPHVTEAYRAPASAAASEDAPYPVCTVRYFPSTAEHTLQWARHEFEELFRLSAETINHHQQAHTSLADMDEPQTLTLLKPVLGVLRVRPQNWQDCVAWALGHWKLCFHYGIKQLLRHFPPNKVLEDGTPFWSGPKQCPQPLEFDTNQDTHLLYVLAAANLYAQMHGLPGSQDWTALRELLKLLPQPDPQQMAPIFASNLELASASAEFGPEQQKELNKALEVWSVGPPLKPLMFEKDDDSNFHVDFVVAAASLRCQNYGIPPVNRAQSKRIVGQIIPAIATTTAAVAGLLGLELYKVVSGPRPRSAFRHSYLHLAENYLIRYMPFAPAIQTFHHLKWTSWDRLKVPAGQPERTLESLLAHLQEQHGLRVRILLHGSALLYAAGWSPEKQAQHLPLRVTELVQQLTGQAPAPGQRVLVLELSCEGDDEDTAFPPLHYEL | |||||||
Modified residue (large scale data) | 15 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 16 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 266 | UniProt | Phosphoserine | ||||
Sequence: S |
Post-translational modification
ISGylated.
Ubiquitinated by RNF170.
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
(Microbial infection) Interacts with human cytomegalovirus proteins NEC2/UL50 and UL26; these interactions inhibit ISGylation and cause proteasomal degradation of UBA7.
(Microbial infection) Interacts with rotavirus non-structural protein 5 (NSP5); this interaction promotes UBA7 proteasomal degradation.
Monomer (By similarity).
Binds and is involved in the conjugation of G1P2/ISG15
Binds and is involved in the conjugation of G1P2/ISG15
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P41226 | ISG15 P05161 | 12 | EBI-751921, EBI-746466 | |
BINARY | P41226 | TARDBP Q13148 | 3 | EBI-751921, EBI-372899 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for repeat, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Repeat | 23-159 | 1-1 | ||||
Sequence: GSPAMQRIQGARVLVSGLQGLGAEVAKNLVLMGVGSLTLHDPHPTCWSDLAAQFLLSEQDLERSRAEASQELLAQLNRAVQVVVHTGDITEDLLLDFQVVVLTAAKLEEQLKVGTLCHKHGVCFLAADTRGLVGQLF | ||||||
Region | 23-575 | 2 approximate repeats | ||||
Sequence: GSPAMQRIQGARVLVSGLQGLGAEVAKNLVLMGVGSLTLHDPHPTCWSDLAAQFLLSEQDLERSRAEASQELLAQLNRAVQVVVHTGDITEDLLLDFQVVVLTAAKLEEQLKVGTLCHKHGVCFLAADTRGLVGQLFCDFGEDFTVQDPTEAEPLTAAIQHISQGSPGILTLRKGANTHYFRDGDLVTFSGIEGMVELNDCDPRSIHVREDGSLEIGDTTTFSRYLRGGAITEVKRPKTVRHKSLDTALLQPHVVAQSSQEVHHAHCLHQAFCALHKFQHLHGRPPQPWDPVDAETVVGLARDLEPLKRTEEEPLEEPLDEALVRTVALSSAGVLSPMVAMLGAVAAQEVLKAISRKFMPLDQWLYFDALDCLPEDGELLPSPEDCALRGSRYDGQIAVFGAGFQEKLRRQHYLLVGAGAIGCELLKVFALVGLGAGNSGGLTVVDMDHIERSNLSRQFLFRSQDVGRPKAEVAAAAARGLNPDLQVIPLTYPLDPTTEHIYGDNFFSRVDGVAAALDSFQARRYVAARCTHYLKPLLEAGTSGTWGSATVFM | ||||||
Repeat | 423-575 | 1-2 | ||||
Sequence: GAGFQEKLRRQHYLLVGAGAIGCELLKVFALVGLGAGNSGGLTVVDMDHIERSNLSRQFLFRSQDVGRPKAEVAAAAARGLNPDLQVIPLTYPLDPTTEHIYGDNFFSRVDGVAAALDSFQARRYVAARCTHYLKPLLEAGTSGTWGSATVFM |
Sequence similarities
Belongs to the ubiquitin-activating E1 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length1,012
- Mass (Da)111,694
- Last updated2008-11-25 v2
- ChecksumA01E1106D81778EB
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 355-378 | in Ref. 1; AAA75388 and 2; AAG49557 | ||||
Sequence: GVLSPMVAMLGAVAAQEVLKAISR → RCLEPMVACWVSSCPGSAEGNLQ |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
L13852 EMBL· GenBank· DDBJ | AAA75388.1 EMBL· GenBank· DDBJ | mRNA | ||
AF294032 EMBL· GenBank· DDBJ | AAG49557.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BT007026 EMBL· GenBank· DDBJ | AAP35672.1 EMBL· GenBank· DDBJ | mRNA | ||
CH471055 EMBL· GenBank· DDBJ | EAW65023.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC006378 EMBL· GenBank· DDBJ | AAH06378.1 EMBL· GenBank· DDBJ | mRNA |