Q03714 · USA1_YEAST
- ProteinU1 SNP1-associating protein 1
- GeneUSA1
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids838 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Scaffold protein of the endoplasmic reticulum-associated degradation (ERAD) (also known as endoplasmic reticulum quality control, ERQC) pathway involved in ubiquitin-dependent degradation of misfolded endoplasmic reticulum proteins. Component of the HRD1 ubiquitin ligase complex, which is part of the ERAD-L and ERAD-M pathways responsible for the rapid degradation of soluble lumenal and membrane proteins with misfolded lumenal domains (ERAD-L), or ER-membrane proteins with misfolded transmembrane domains (ERAD-M). Has multiple functions in ERAD including recruitment of DER1 to the HRD1 ubiquitin ligase, and regulation of HRD1 activity. Involved in oligomerization of HRD1 and in HRD1 autoubiquitination and degradation.
Miscellaneous
Present with 1890 molecules/cell in log phase SD medium.
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | endoplasmic reticulum | |
Cellular Component | endoplasmic reticulum membrane | |
Cellular Component | Hrd1p ubiquitin ligase complex | |
Molecular Function | identical protein binding | |
Molecular Function | molecular adaptor activity | |
Biological Process | ERAD pathway | |
Biological Process | mRNA splicing, via spliceosome | |
Biological Process | positive regulation of protein autoubiquitination |
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameU1 SNP1-associating protein 1
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Saccharomycotina > Saccharomycetes > Saccharomycetales > Saccharomycetaceae > Saccharomyces
Accessions
- Primary accessionQ03714
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Endoplasmic reticulum membrane ; Multi-pass membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-536 | Cytoplasmic | ||||
Sequence: MSEYLAQTPCKFTIWSSEIDLIRTNLLVNAHPLSTVGRLLQYIHYQIYKQLRAIYQPEEQCTNSEIPHTPLNSINTYFLSYEGRELSATCLLKDITSSSHPDSNHFIRLQLEKRTSPSGSAFDLEYDMEGEFNSMNIQFEINTLSSQRIFNSMEPNLPIGTTLARLEKLALERIKDFEKSAGNLCGIKEDHSVSDLQGFIIKGKQTPMFLNYGSDSDYYKDLNLVDLIGIDFAPAHNSFFTFLFKMNHEQNSHIANDEERFVLEFISDATLSITQMNVKPDTTVKQVKDFICSVYTHSLNLRRNDIKLIYKGQLLHENNFAGNSSKISEYIKEPHEVKVHVQINQEYTESGPGFWNEVFNNPNIFQFMPPDTRSQSPVSFAPTQGRSPAAIRGEERGIPYVTESGNDIVPTDELYRKCIINGDEVVFIPVSELNPQSSYLSVIKGDYGEIKIPISSNDYRINGDNILLSPSAIEQLESALNFKIERPRDSTLLHPSGEHVRAADNTSSANDNNTVENDESAWNRRVVRPLRNSFPL | ||||||
Transmembrane | 537-559 | Helical | ||||
Sequence: LLVLIRTFYLIGYNSLVPFFIIL | ||||||
Topological domain | 560-563 | Extracellular | ||||
Sequence: EFGS | ||||||
Transmembrane | 564-583 | Helical | ||||
Sequence: FLPWKYIILLSLLFIFRTVW | ||||||
Topological domain | 584-838 | Cytoplasmic | ||||
Sequence: NTQEVWNLWRDYLHLNEIDEVKFSQIKEFINSNSLTLNFYKKCKDTQSAIDLLMIPNLHEQRLSVYSKYDIEYDTNTPDVGQLNLLFIKVLSGEIPKDALDELFKEFFELYETTRNMNTLYPQDSLNELLLMIWKESQKKDINTLPKYRRWFQTLCSQIAEHNVLDVVLRYIIPDPVNDRVITAVIKNFVLFWVTLLPYVKEKLDDIVAQRARDREQPAPSAQQQENEDEALIIPDEEEPTATGAQPHLYIPDED |
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Impaired degradation of proteins with misfolded lumenal domains such as CPY*, a mutant, misfolded form of carboxypeptidase Y which is a known ERAD-L substrate. Impaired degradation of proteins with misfolded intramembrane domains. Impaired trans-ubiquitination and degradation of the HRD1 ligase. Degradation of proteins with misfolded cytosolic domains is not affected. Interaction of substrate with HRD1 is reduced; in USA1 and YOS9 double mutants this interaction is completely abolished.
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 17 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000114926 | 1-838 | U1 SNP1-associating protein 1 | |||
Sequence: MSEYLAQTPCKFTIWSSEIDLIRTNLLVNAHPLSTVGRLLQYIHYQIYKQLRAIYQPEEQCTNSEIPHTPLNSINTYFLSYEGRELSATCLLKDITSSSHPDSNHFIRLQLEKRTSPSGSAFDLEYDMEGEFNSMNIQFEINTLSSQRIFNSMEPNLPIGTTLARLEKLALERIKDFEKSAGNLCGIKEDHSVSDLQGFIIKGKQTPMFLNYGSDSDYYKDLNLVDLIGIDFAPAHNSFFTFLFKMNHEQNSHIANDEERFVLEFISDATLSITQMNVKPDTTVKQVKDFICSVYTHSLNLRRNDIKLIYKGQLLHENNFAGNSSKISEYIKEPHEVKVHVQINQEYTESGPGFWNEVFNNPNIFQFMPPDTRSQSPVSFAPTQGRSPAAIRGEERGIPYVTESGNDIVPTDELYRKCIINGDEVVFIPVSELNPQSSYLSVIKGDYGEIKIPISSNDYRINGDNILLSPSAIEQLESALNFKIERPRDSTLLHPSGEHVRAADNTSSANDNNTVENDESAWNRRVVRPLRNSFPLLLVLIRTFYLIGYNSLVPFFIILEFGSFLPWKYIILLSLLFIFRTVWNTQEVWNLWRDYLHLNEIDEVKFSQIKEFINSNSLTLNFYKKCKDTQSAIDLLMIPNLHEQRLSVYSKYDIEYDTNTPDVGQLNLLFIKVLSGEIPKDALDELFKEFFELYETTRNMNTLYPQDSLNELLLMIWKESQKKDINTLPKYRRWFQTLCSQIAEHNVLDVVLRYIIPDPVNDRVITAVIKNFVLFWVTLLPYVKEKLDDIVAQRARDREQPAPSAQQQENEDEALIIPDEEEPTATGAQPHLYIPDED | ||||||
Modified residue | 374 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 376 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 379 | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
Component of the HRD1 ubiquitin ligase complex which contains the E3 ligase HRD1, its cofactors HRD3, USA1 and DER1, substrate recruiting factor YOS9 and CDC48-binding protein UBX2 (PubMed:16873066).
Within the complex, interacts directly with HRD1 (via N-terminus) and DER1 (via C-terminus) and indirectly with HRD3 (PubMed:19898607, PubMed:20005842, PubMed:21074049, PubMed:32327568).
In ERAD-L, HRD3 and YOS9 jointly bind misfolded glycoproteins in the endoplasmic reticulum (ER) lumen (PubMed:32327568).
Movement of ERAD-L substrates through the ER membrane is facilitated by HRD1 and DER1 which have lateral gates facing each other and which distort the membrane region between the lateral gates, making it much thinner than a normal phospholipid bilayer (PubMed:32327568).
Substrates insert into the membrane as a hairpin loop with one strand interacting with DER1 and the other with HRD1 (PubMed:32327568).
The HRD1 complex interacts with the heterotrimeric CDC48-NPL4-UFD1 ATPase complex which is recruited by UBX2 via its interaction with CDC48 and which moves ubiquitinated substrates to the cytosol for targeting to the proteasome (PubMed:16873066).
Within the complex, interacts directly with HRD1 (via N-terminus) and DER1 (via C-terminus) and indirectly with HRD3 (PubMed:19898607, PubMed:20005842, PubMed:21074049, PubMed:32327568).
In ERAD-L, HRD3 and YOS9 jointly bind misfolded glycoproteins in the endoplasmic reticulum (ER) lumen (PubMed:32327568).
Movement of ERAD-L substrates through the ER membrane is facilitated by HRD1 and DER1 which have lateral gates facing each other and which distort the membrane region between the lateral gates, making it much thinner than a normal phospholipid bilayer (PubMed:32327568).
Substrates insert into the membrane as a hairpin loop with one strand interacting with DER1 and the other with HRD1 (PubMed:32327568).
The HRD1 complex interacts with the heterotrimeric CDC48-NPL4-UFD1 ATPase complex which is recruited by UBX2 via its interaction with CDC48 and which moves ubiquitinated substrates to the cytosol for targeting to the proteasome (PubMed:16873066).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q03714 | DER1 P38307 | 3 | EBI-27760, EBI-5761 | |
BINARY | Q03714 | UBX2 Q04228 | 2 | EBI-27760, EBI-27730 | |
BINARY | Q03714 | USA1 Q03714 | 2 | EBI-27760, EBI-27760 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 31-240 | Required for ERAD-L function | ||||
Sequence: HPLSTVGRLLQYIHYQIYKQLRAIYQPEEQCTNSEIPHTPLNSINTYFLSYEGRELSATCLLKDITSSSHPDSNHFIRLQLEKRTSPSGSAFDLEYDMEGEFNSMNIQFEINTLSSQRIFNSMEPNLPIGTTLARLEKLALERIKDFEKSAGNLCGIKEDHSVSDLQGFIIKGKQTPMFLNYGSDSDYYKDLNLVDLIGIDFAPAHNSFF | ||||||
Domain | 259-318 | Ubiquitin-like | ||||
Sequence: ERFVLEFISDATLSITQMNVKPDTTVKQVKDFICSVYTHSLNLRRNDIKLIYKGQLLHEN | ||||||
Region | 319-418 | Important for HRD1 oligomer formation | ||||
Sequence: NFAGNSSKISEYIKEPHEVKVHVQINQEYTESGPGFWNEVFNNPNIFQFMPPDTRSQSPVSFAPTQGRSPAAIRGEERGIPYVTESGNDIVPTDELYRKC | ||||||
Region | 345-535 | Interaction with HRD1 | ||||
Sequence: QEYTESGPGFWNEVFNNPNIFQFMPPDTRSQSPVSFAPTQGRSPAAIRGEERGIPYVTESGNDIVPTDELYRKCIINGDEVVFIPVSELNPQSSYLSVIKGDYGEIKIPISSNDYRINGDNILLSPSAIEQLESALNFKIERPRDSTLLHPSGEHVRAADNTSSANDNNTVENDESAWNRRVVRPLRNSFP | ||||||
Region | 437-490 | Required for ERAD-L function and HRD1 oligomer formation | ||||
Sequence: SSYLSVIKGDYGEIKIPISSNDYRINGDNILLSPSAIEQLESALNFKIERPRDS | ||||||
Region | 584-838 | Interaction with DER1 | ||||
Sequence: NTQEVWNLWRDYLHLNEIDEVKFSQIKEFINSNSLTLNFYKKCKDTQSAIDLLMIPNLHEQRLSVYSKYDIEYDTNTPDVGQLNLLFIKVLSGEIPKDALDELFKEFFELYETTRNMNTLYPQDSLNELLLMIWKESQKKDINTLPKYRRWFQTLCSQIAEHNVLDVVLRYIIPDPVNDRVITAVIKNFVLFWVTLLPYVKEKLDDIVAQRARDREQPAPSAQQQENEDEALIIPDEEEPTATGAQPHLYIPDED | ||||||
Region | 795-838 | Disordered | ||||
Sequence: ARDREQPAPSAQQQENEDEALIIPDEEEPTATGAQPHLYIPDED |
Domain
The ubiquitin-like domain is required for HRD1 trans-ubiquitination and degradation. Reported to be involved in ERAD-M but not ERAD-L function (PubMed:20005842).
However, a contradictory report states that it is not required for either ERAD-L or ERAD-M function (PubMed:19940128).
Reported to be required for HRD1 oligomer formation (PubMed:19940128).
However, a contradictory report does not observe any defects in oligomerization following deletion of the domain (PubMed:21074049).
However, a contradictory report states that it is not required for either ERAD-L or ERAD-M function (PubMed:19940128).
Reported to be required for HRD1 oligomer formation (PubMed:19940128).
However, a contradictory report does not observe any defects in oligomerization following deletion of the domain (PubMed:21074049).
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length838
- Mass (Da)96,653
- Last updated1997-11-01 v1
- Checksum9B93ECA6C5421FD6
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
Z46659 EMBL· GenBank· DDBJ | CAA86626.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BK006946 EMBL· GenBank· DDBJ | DAA09869.1 EMBL· GenBank· DDBJ | Genomic DNA |