UBA7 (ubiquitin like modifier activating enzyme 7)

Gene

• Entrez ID: 7318
• Gene name: Ubiquitin like modifier activating enzyme 7
• Gene symbol: UBA7
• Synonyms (NCBI Gene): D8, UBA1B, UBE1L, UBE2, UBE7
• Chromosome: 3
• Chromosome location: 3p21.31
• Summary: The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conju

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT732231	hsa-miR-455-5p	Luciferase reporter assay, qRT-PCR, Western blot	27235675
MIRT732231	hsa-miR-455-5p	Luciferase reporter assay, qRT-PCR, Western blot	27235675
MIRT1466655	hsa-miR-4265	CLIP-seq
MIRT1466656	hsa-miR-4296	CLIP-seq
MIRT1466657	hsa-miR-4318	CLIP-seq
MIRT1466658	hsa-miR-4322	CLIP-seq
MIRT1466659	hsa-miR-4417	CLIP-seq
MIRT1466660	hsa-miR-4461	CLIP-seq
MIRT1466661	hsa-miR-4658	CLIP-seq
MIRT1466662	hsa-miR-4693-5p	CLIP-seq
MIRT1466663	hsa-miR-4729	CLIP-seq
MIRT1466664	hsa-miR-4758-5p	CLIP-seq
MIRT1466665	hsa-miR-515-3p	CLIP-seq
MIRT1466666	hsa-miR-519e	CLIP-seq
MIRT1466667	hsa-miR-892a	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
PML	Repression	11891284

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0004842	Function	Ubiquitin-protein transferase activity	EXP	18583345, 19073728
GO:0005515	Function	Protein binding	IPI	16189514, 17597759, 25416956, 32296183, 32814053, 33961781
GO:0005524	Function	ATP binding	IEA
GO:0005634	Component	Nucleus	IEA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IDA	29743376
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	TAS
GO:0006974	Process	DNA damage response	IBA
GO:0008641	Function	Ubiquitin-like modifier activating enzyme activity	IEA
GO:0016567	Process	Protein ubiquitination	IEA
GO:0016874	Function	Ligase activity	IEA
GO:0019782	Function	ISG15 activating enzyme activity	IBA
GO:0019782	Function	ISG15 activating enzyme activity	IDA	16428300
GO:0019782	Function	ISG15 activating enzyme activity	IEA
GO:0019941	Process	Modification-dependent protein catabolic process	IEA
GO:0032020	Process	ISG15-protein conjugation	IBA
GO:0032020	Process	ISG15-protein conjugation	IDA	15131269, 16407192
GO:0032020	Process	ISG15-protein conjugation	IDA	16428300
GO:0032020	Process	ISG15-protein conjugation	IEA
GO:0032020	Process	ISG15-protein conjugation	IEA
GO:0045087	Process	Innate immune response	IBA
GO:0045087	Process	Innate immune response	IDA	28724761
GO:0045087	Process	Innate immune response	IDA	28724761

Other IDs

• MIM: 191325
• HGNC: 12471
• e!Ensembl: ENSG00000182179

Protein

• UniProt ID: P41226
• Protein name: Ubiquitin-like modifier-activating enzyme 7 (Ubiquitin-activating enzyme 7) (EC 6.2.1.-) (D8) (Ubiquitin-activating enzyme E1 homolog)
• Protein 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
• PDB: 8OIF, 8SE9, 8SEA, 8SEB, 8SV8, 8WWX
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00899	ThiF	15 → 410	ThiF family	Domain
  PF16190	E1_FCCH	187 → 258	Ubiquitin-activating enzyme E1 FCCH domain	Domain
  PF16191	E1_4HB	259 → 327	Ubiquitin-activating enzyme E1 four-helix bundle	Domain
  PF00899	ThiF	415 → 910	ThiF family	Domain
  PF10585	UBA_e1_thiolCys	605 → 843	Ubiquitin-activating enzyme active site	Domain
  PF09358	E1_UFD	914 → 1008	Ubiquitin fold domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed in a variety of normal and tumor cell types, but is reduced in lung cancer cell lines.
• Sequence:

  MDALDASKLLDEELYSRQLYVLGSPAMQRIQGARVLVSGLQGLGAEVAKNLVLMGVGSLT
  LHDPHPTCWSDLAAQFLLSEQDLERSRAEASQELLAQLNRAVQVVVHTGDITEDLLLDFQ
  VVVLTAAKLEEQLKVGTLCHKHGVCFLAADTRGLVGQLFCDFGEDFTVQDPTEAEPLTAA
  IQHISQGSPGILTLRKGANTHYFRDGDLVTFSGIEGMVELNDCDPRSIHVREDGSLEIGD
  TTTFSRYLRGGAITEVKRPKTVRHKSLDTALLQPHVVAQSSQEVHHAHCLHQAFCALHKF
  QHLHGRPPQPWDPVDAETVVGLARDLEPLKRTEEEPLEEPLDEALVRTVALSSAGVLSPM
  VAMLGAVAAQEVLKAISRKFMPLDQWLYFDALDCLPEDGELLPSPEDCALRGSRYDGQIA
  VFGAGFQEKLRRQHYLLVGAGAIGCELLKVFALVGLGAGNSGGLTVVDMDHIERSNLSRQ
  FLFRSQDVGRPKAEVAAAAARGLNPDLQVIPLTYPLDPTTEHIYGDNFFSRVDGVAAALD
  SFQARRYVAARCTHYLKPLLEAGTSGTWGSATVFMPHVTEAYRAPASAAASEDAPYPVCT
  VRYFPSTAEHTLQWARHEFEELFRLSAETINHHQQAHTSLADMDEPQTLTLLKPVLGVLR
  VRPQNWQDCVAWALGHWKLCFHYGIKQLLRHFPPNKVLEDGTPFWSGPKQCPQPLEFDTN
  QDTHLLYVLAAANLYAQMHGLPGSQDWTALRELLKLLPQPDPQQMAPIFASNLELASASA
  EFGPEQQKELNKALEVWSVGPPLKPLMFEKDDDSNFHVDFVVAAASLRCQNYGIPPVNRA
  QSKRIVGQIIPAIATTTAAVAGLLGLELYKVVSGPRPRSAFRHSYLHLAENYLIRYMPFA
  PAIQTFHHLKWTSWDRLKVPAGQPERTLESLLAHLQEQHGLRVRILLHGSALLYAAGWSP
  EKQAQHLPLRVTELVQQLTGQAPAPGQRVLVLELSCEGDDEDTAFPPLHYEL

• Sequence length: 1012

Pathways

KEGG:

Ubiquitin mediated proteolysis
Parkinson disease
Pathways of neurodegeneration - multiple diseases

Reactome:

ISG15 antiviral mechanism
DDX58/IFIH1-mediated induction of interferon-alpha/beta
Termination of translesion DNA synthesis
Negative regulators of DDX58/IFIH1 signaling
Antigen processing: Ubiquitination & Proteasome degradation

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ATTENTION DEFICIT HYPERACTIVITY DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISM SPECTRUM DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARCINOMA, SQUAMOUS CELL	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INFLAMMATORY BOWEL DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INSOMNIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Intellectual disability	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Lung cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MAJOR DEPRESSIVE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of urinary bladder	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MOOD DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SUBSTANCE ABUSE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
UBA7-related disorder	Uncertain significance; Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acute Promyelocytic Leukemia	Promyelocytic Leukemia	BEFREE	11891284, 14976209		★☆☆☆☆ Found in Text Mining only
Acute Promyelocytic Leukemia	Promyelocytic Leukemia	LHGDN	11891284		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	39684409	Associate	★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	19074853	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma of lung	Lung carcinoma	BEFREE	10709110, 15520223, 31428903		★☆☆☆☆ Found in Text Mining only
Carcinoma Renal Cell	Renal cell carcinoma	Pubtator	39871215	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus Type 2	Diabetes mellitus, type 2	Pubtator	26606528	Associate	★☆☆☆☆ Found in Text Mining only
Endometrial Neoplasms	Endometrial neoplasm	Pubtator	37803076	Associate	★☆☆☆☆ Found in Text Mining only
Head and Neck Neoplasms	Head and neck neoplasm	Pubtator	36010616	Associate	★☆☆☆☆ Found in Text Mining only
Inflammatory Bowel Diseases	Inflammatory bowel disease	Pubtator	25766683	Associate	★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	BEFREE	28397838		★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Lung Neoplasms	Lung Neoplasms	BEFREE	10709110		★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung neoplasms	Pubtator	19074853, 7734949	Associate	★☆☆☆☆ Found in Text Mining only
Major Depressive Disorder	Mental Depression	GWASCAT_DG	29942085		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant neoplasm of lung	Lung Cancer	BEFREE	10709110, 15520223		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	BEFREE	31563279, 31841638		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	14976209		★☆☆☆☆ Found in Text Mining only
Mesothelioma Malignant	Mesothelioma	Pubtator	19218339	Inhibit	★☆☆☆☆ Found in Text Mining only
Mood Disorders	Mood Disorder	GWASCAT_DG	29942085		★☆☆☆☆ Found in Text Mining only
Myelodysplastic Syndromes	Myelodysplastic syndrome	Pubtator	40158006	Associate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	10709110, 15520223		★☆☆☆☆ Found in Text Mining only
Neuroblastoma	Neuroblastoma	BEFREE	29056542		★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	Pubtator	23251400	Associate	★☆☆☆☆ Found in Text Mining only
Obesity Morbid	Obesity	Pubtator	23251400	Associate	★☆☆☆☆ Found in Text Mining only
Rett Syndrome	Rett syndrome	Pubtator	10745042	Associate	★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma	Carcinoma	CTD_human_DG	19014429		★☆☆☆☆ Found in Text Mining only
Squamous Cell Carcinoma of Head and Neck	Squamous cell carcinoma	Pubtator	35615976	Associate	★☆☆☆☆ Found in Text Mining only
VEXAS syndrome	Vexas syndrome	Pubtator	34611997	Associate	★☆☆☆☆ Found in Text Mining only