NAE1 (NEDD8 activating enzyme E1 subunit 1)

Gene

• Entrez ID: 8883
• Gene name: NEDD8 activating enzyme E1 subunit 1
• Gene symbol: NAE1
• Synonyms (NCBI Gene): A-116A10.1, APPBP1, HPP1, NEDFIH, ula-1
• Chromosome: 16
• Chromosome location: 16q22.1
• Summary: The protein encoded by this gene binds to the beta-amyloid precursor protein. Beta-amyloid precursor protein is a cell surface protein with signal-transducing properties, and it is thought to play a role in the pathogenesis of Alzheimer`s disease. In addi

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT029193	hsa-miR-26b-5p	Microarray	19088304
MIRT030401	hsa-miR-24-3p	Microarray	19748357
MIRT2050119	hsa-miR-582-5p	CLIP-seq
MIRT2278992	hsa-miR-15a	CLIP-seq
MIRT2278993	hsa-miR-15b	CLIP-seq
MIRT2278994	hsa-miR-16	CLIP-seq
MIRT2278995	hsa-miR-18a	CLIP-seq
MIRT2278996	hsa-miR-18b	CLIP-seq
MIRT2278997	hsa-miR-195	CLIP-seq
MIRT2278998	hsa-miR-424	CLIP-seq
MIRT2278999	hsa-miR-4275	CLIP-seq
MIRT2279000	hsa-miR-4327	CLIP-seq
MIRT2279001	hsa-miR-4422	CLIP-seq
MIRT2279002	hsa-miR-4524	CLIP-seq
MIRT2279003	hsa-miR-4660	CLIP-seq
MIRT2279004	hsa-miR-4705	CLIP-seq
MIRT2279005	hsa-miR-4735-3p	CLIP-seq
MIRT2279006	hsa-miR-497	CLIP-seq
MIRT2279007	hsa-miR-503	CLIP-seq
MIRT2050119	hsa-miR-582-5p	CLIP-seq
MIRT2279008	hsa-miR-590-3p	CLIP-seq
MIRT2279009	hsa-miR-603	CLIP-seq
MIRT2279010	hsa-miR-636	CLIP-seq
MIRT2279011	hsa-miR-646	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005515	Function	Protein binding	IPI	8626687, 10722740, 12694406, 14557245, 15361859, 32296183, 32814053
GO:0005737	Component	Cytoplasm	TAS	8626687
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IEA
GO:0006915	Process	Apoptotic process	IEA
GO:0007165	Process	Signal transduction	TAS	8626687
GO:0008641	Function	Ubiquitin-like modifier activating enzyme activity	IEA
GO:0016020	Component	Membrane	IEA
GO:0019781	Function	NEDD8 activating enzyme activity	IDA	12740388
GO:0019781	Function	NEDD8 activating enzyme activity	IEA
GO:0031625	Function	Ubiquitin protein ligase binding	IPI	18627766
GO:0032991	Component	Protein-containing complex	IDA	12740388
GO:0033314	Process	Mitotic DNA replication checkpoint signaling	IDA	10722740
GO:0042981	Process	Regulation of apoptotic process	IDA	14557245
GO:0042981	Process	Regulation of apoptotic process	IMP	10722740
GO:0043523	Process	Regulation of neuron apoptotic process	IDA	10722740
GO:0045116	Process	Protein neddylation	IDA	10207026, 12740388
GO:0045116	Process	Protein neddylation	IEA
GO:0045116	Process	Protein neddylation	IMP	36608681
GO:0046982	Function	Protein heterodimerization activity	IPI	12740388
GO:0051402	Process	Neuron apoptotic process	IDA	14557245
GO:0098978	Component	Glutamatergic synapse	IEA
GO:0150052	Process	Regulation of postsynapse assembly	IEA

Other IDs

• MIM: 603385
• HGNC: 621
• e!Ensembl: ENSG00000159593

Protein

• UniProt ID: Q13564
• Protein name: NEDD8-activating enzyme E1 regulatory subunit (Amyloid beta precursor protein-binding protein 1, 59 kDa) (APP-BP1) (Amyloid protein-binding protein 1) (Proto-oncogene protein 1)
• Protein function: Regulatory subunit of the dimeric UBA3-NAE1 E1 enzyme. E1 activates NEDD8 by first adenylating its C-terminal glycine residue with ATP, thereafter linking this residue to the side chain of the catalytic cysteine, yielding a NEDD8-UBA3 thioester
• PDB: 1R4M, 1R4N, 1TT5, 1YOV, 2NVU, 3DBH, 3DBL, 3DBR, 3GZN
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00899	ThiF	13 → 533	ThiF family	Domain

• Tissue specificity: TISSUE SPECIFICITY: Ubiquitous in fetal tissues. Expressed throughout the adult brain. {ECO:0000269|PubMed:8626687}.
• Sequence:

  MAQLGKLLKEQKYDRQLRLWGDHGQEALESAHVCLINATATGTEILKNLVLPGIGSFTII
  DGNQVSGEDAGNNFFLQRSSIGKNRAEAAMEFLQELNSDVSGSFVEESPENLLDNDPSFF
  CRFTVVVATQLPESTSLRLADVLWNSQIPLLICRTYGLVGYMRIIIKEHPVIESHPDNAL
  EDLRLDKPFPELREHFQSYDLDHMEKKDHSHTPWIVIIAKYLAQWYSETNGRIPKTYKEK
  EDFRDLIRQGILKNENGAPEDEENFEEAIKNVNTALNTTQIPSSIEDIFNDDRCINITKQ
  TPSFWILARALKEFVAKEGQGNLPVRGTIPDMIADSGKYIKLQNVYREKAKKDAAAVGNH
  VAKLLQSIGQAPESISEKELKLLCSNSAFLRVVRCRSLAEEYGLDTINKDEIISSMDNPD
  NEIVLYLMLRAVDRFHKQQGRYPGVSNYQVEEDIGKLKSCLTGFLQEYGLSVMVKDDYVH
  EFCRYGAAEPHTIAAFLGGAAAQEVIKIITKQFVIFNNTYIYSGMSQTSATFQL

• Sequence length: 534

Pathways

KEGG:

Alzheimer disease

Reactome:

Neddylation

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)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Neurodevelopmental disorder with dysmorphic facies and ischiopubic hypoplasia	Pathogenic	rs1959664594, rs777573115, rs760101172	RCV003126108 RCV003126109 RCV003126203	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Malignant tumor of urinary bladder	Uncertain significance	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	29910671		★☆☆☆☆ Found in Text Mining only
ANOPHTHALMIA AND PULMONARY HYPOPLASIA	Syndromic microphthalmia	BEFREE	28535453		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	36632463	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Pancreatic Ductal	Pancreatic ductal carcinoma	Pubtator	28535453	Associate	★☆☆☆☆ Found in Text Mining only
Cardiomyopathies	Cardiomyopathy	Pubtator	36662623	Associate	★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	26206335	Associate	★☆☆☆☆ Found in Text Mining only
Congestive heart failure	Congestive Heart Failure	BEFREE	29632206		★☆☆☆☆ Found in Text Mining only
Down Syndrome	Down Syndrome	BEFREE	15192323, 17611268		★☆☆☆☆ Found in Text Mining only
Heart failure	Heart Failure	BEFREE	29632206		★☆☆☆☆ Found in Text Mining only
Heart Failure	Heart failure	Pubtator	36662623	Associate	★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Intellectual developmental disorder	Pubtator	36608681	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia	Leukemia	Pubtator	31349760	Associate	★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	29846044, 31002342, 31817100		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of pancreas	Pancreatic cancer	BEFREE	31404297		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	31404297		★☆☆☆☆ Found in Text Mining only
MERRF Syndrome	MERRF Syndrome	BEFREE	2124485		★☆☆☆☆ Found in Text Mining only
Neurodegenerative Diseases	Neurodegenerative disorder	Pubtator	36608681	Associate	★☆☆☆☆ Found in Text Mining only
Non-Small Cell Lung Carcinoma	Lung carcinoma	BEFREE	15201980		★☆☆☆☆ Found in Text Mining only
Pancreatic carcinoma	Pancreatic carcinoma	BEFREE	31404297		★☆☆☆☆ Found in Text Mining only
Squamous Cell Carcinoma of Head and Neck	Squamous cell carcinoma	Pubtator	30341788	Associate	★☆☆☆☆ Found in Text Mining only
Uveal melanoma	Uveal Melanoma	BEFREE	29233905		★☆☆☆☆ Found in Text Mining only
Vitiligo	Vitiligo	Pubtator	36890149	Associate	★☆☆☆☆ Found in Text Mining only