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 addition, the encoded protein can form a heterodimer with UBE1C and bind and activate NEDD8, a ubiquitin-like protein. This prote... See more...

Aliases for NAE1 Gene

Aliases for NAE1 Gene

  • NEDD8 Activating Enzyme E1 Subunit 1 2 3 5
  • APP-BP1 2 3 4
  • Amyloid Beta Precursor Protein-Binding Protein 1, 59 KDa 3 4
  • Amyloid Beta Precursor Protein Binding Protein 1, 59kDa 2 3
  • NEDD8-Activating Enzyme E1 Regulatory Subunit 3 4
  • Amyloid Protein-Binding Protein 1 3 4
  • Proto-Oncogene Protein 1 3 4
  • APPBP1 3 4
  • Ula-1 2 3
  • Amyloid Beta Precursor Protein-Binding Protein 1, 59kD 3
  • NEDD8-Activating Enzyme E1 Subunit 3
  • Protooncogene Protein 1 3
  • A-116A10.1 3
  • HPP1 3
  • NAE1 5

External Ids for NAE1 Gene

Previous HGNC Symbols for NAE1 Gene

  • APPBP1

Previous GeneCards Identifiers for NAE1 Gene

  • GC16M065395
  • GC16M066836
  • GC16M052710

Summaries for NAE1 Gene

Entrez Gene Summary for NAE1 Gene

  • 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 addition, the encoded protein can form a heterodimer with UBE1C and bind and activate NEDD8, a ubiquitin-like protein. This protein is required for cell cycle progression through the S/M checkpoint. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

GeneCards Summary for NAE1 Gene

NAE1 (NEDD8 Activating Enzyme E1 Subunit 1) is a Protein Coding gene. Diseases associated with NAE1 include Alzheimer Disease. Among its related pathways are Parkinson disease and Alzheimers Disease. Gene Ontology (GO) annotations related to this gene include protein heterodimerization activity and NEDD8 activating enzyme activity. An important paralog of this gene is UBA1.

UniProtKB/Swiss-Prot Summary for NAE1 Gene

  • 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 and free AMP. E1 finally transfers NEDD8 to the catalytic cysteine of UBE2M. Necessary for cell cycle progression through the S-M checkpoint. Overexpression of NAE1 causes apoptosis through deregulation of NEDD8 conjugation.

Gene Wiki entry for NAE1 Gene

Additional gene information for NAE1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for NAE1 Gene

Genomics for NAE1 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for NAE1 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around NAE1 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for NAE1

Top Transcription factor binding sites by QIAGEN in the NAE1 gene promoter:
  • E47
  • Ik-2
  • NF-1
  • p53
  • Pax-5
  • SRF
  • SRF (504 AA)
  • Tal-1

Genomic Locations for NAE1 Gene

Genomic Locations for NAE1 Gene
chr16:66,802,875-66,873,256
(GRCh38/hg38)
Size:
70,382 bases
Orientation:
Minus strand
chr16:66,836,778-66,907,159
(GRCh37/hg19)
Size:
70,382 bases
Orientation:
Minus strand

Genomic View for NAE1 Gene

Genes around NAE1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NAE1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NAE1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NAE1 Gene

Proteins for NAE1 Gene

  • Protein details for NAE1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q13564-ULA1_HUMAN
    Recommended name:
    NEDD8-activating enzyme E1 regulatory subunit
    Protein Accession:
    Q13564
    Secondary Accessions:
    • A6NCK0
    • A6NFN4
    • A8MU28
    • B2R700
    • B3KUP9

    Protein attributes for NAE1 Gene

    Size:
    534 amino acids
    Molecular mass:
    60246 Da
    Quaternary structure:
    • Heterodimer of UBA3 and NAE1. The complex binds NEDD8 and UBE2M. Binds APP and TP53BP2.
    Miscellaneous:
    • NAE1 and UBA3 correspond to the N-terminal and the C-terminal part of yeast UBA3. In yeast the two subunits form a single polypeptide chain.

    Three dimensional structures from OCA and Proteopedia for NAE1 Gene

    Alternative splice isoforms for NAE1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for NAE1 Gene

Post-translational modifications for NAE1 Gene

  • Ubiquitinated by TRIP12, leading to its degradation by the proteasome.
  • Ubiquitination at Lys12, Lys167, Lys187, Lys299, Lys317, Lys341, Lys363, Lys378, and Lys381
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for NAE1 Gene

Domains & Families for NAE1 Gene

Gene Families for NAE1 Gene

HGNC:
Human Protein Atlas (HPA):
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for NAE1 Gene

InterPro:
Blocks:
  • UBA/THIF-type NAD/FAD binding fold
ProtoNet:

Suggested Antigen Peptide Sequences for NAE1 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ55878, highly similar to NEDD8-activating enzyme E1 regulatory subunit (A6NFN4_HUMAN)
  • Proto-oncogene protein 1 (ULA1_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q13564

UniProtKB/Swiss-Prot:

ULA1_HUMAN :
  • Belongs to the ubiquitin-activating E1 family. ULA1 subfamily.
Family:
  • Belongs to the ubiquitin-activating E1 family. ULA1 subfamily.
genes like me logo Genes that share domains with NAE1: view

Function for NAE1 Gene

Molecular function for NAE1 Gene

UniProtKB/Swiss-Prot 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 and free AMP. E1 finally transfers NEDD8 to the catalytic cysteine of UBE2M. Necessary for cell cycle progression through the S-M checkpoint. Overexpression of NAE1 causes apoptosis through deregulation of NEDD8 conjugation.
UniProtKB/Swiss-Prot EnzymeRegulation:
Binding of TP53BP2 to the regulatory subunit NAE1 decreases neddylation activity.

Phenotypes From GWAS Catalog for NAE1 Gene

Gene Ontology (GO) - Molecular Function for NAE1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 8626687
GO:0008641 ubiquitin-like modifier activating enzyme activity IEA --
GO:0019781 contributes_to NEDD8 activating enzyme activity IDA 12740388
GO:0031625 ubiquitin protein ligase binding IPI 18627766
GO:0046982 protein heterodimerization activity IPI 12740388
genes like me logo Genes that share ontologies with NAE1: view
genes like me logo Genes that share phenotypes with NAE1: view

Animal Models for NAE1 Gene

MGI Knock Outs for NAE1:
  • Nae1 Nae1<tm1b(EUCOMM)Wtsi>

Animal Model Products

CRISPR Products

miRNA for NAE1 Gene

miRTarBase miRNAs that target NAE1

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NAE1

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for NAE1 Gene

Localization for NAE1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NAE1 Gene

Cell membrane. Note=Colocalizes with APP in lipid rafts.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for NAE1 gene
Compartment Confidence
nucleus 4
cytosol 4
plasma membrane 3
cytoskeleton 3
extracellular 1
mitochondrion 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Centrosome (2)
  • Microtubules (2)
  • Nucleoplasm (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for NAE1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm TAS,IBA 21873635
GO:0005829 cytosol TAS --
GO:0005886 plasma membrane IEA --
GO:0016020 membrane IEA --
GO:0032991 protein-containing complex IDA 12740388
genes like me logo Genes that share ontologies with NAE1: view

Pathways & Interactions for NAE1 Gene

PathCards logo

SuperPathways for NAE1 Gene

SuperPathway Contained pathways
1 Parkinson disease
2 Alzheimers Disease
genes like me logo Genes that share pathways with NAE1: view

Pathways by source for NAE1 Gene

1 BioSystems pathway for NAE1 Gene
1 KEGG pathway for NAE1 Gene

UniProtKB/Swiss-Prot Q13564-ULA1_HUMAN

  • Pathway: Protein modification; protein neddylation.

SIGNOR curated interactions for NAE1 Gene

Is activated by:

Gene Ontology (GO) - Biological Process for NAE1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006915 apoptotic process IEA --
GO:0007049 cell cycle IEA --
GO:0007165 signal transduction TAS 8626687
GO:0032446 protein modification by small protein conjugation IBA 21873635
GO:0033314 mitotic DNA replication checkpoint IDA 10722740
genes like me logo Genes that share ontologies with NAE1: view

Drugs & Compounds for NAE1 Gene

(3) Drugs for NAE1 Gene - From: DrugBank and ApexBio

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
ATP Investigational Nutra Agonist, Activator, Partial agonist, Antagonist, Full agonist, Gating inhibitor, Pore Blocker, Potentiation, Target 0
MLN4924 Pharma NAE inhibitor 0
MLN4924 HCl salt Pharma NAE inhibitor 0

(2) ApexBio Compounds for NAE1 Gene

Compound Action Cas Number
MLN4924 NAE inhibitor 905579-51-3
MLN4924 HCl salt NAE inhibitor 1160295-21-5
genes like me logo Genes that share compounds with NAE1: view

Drug Products

Transcripts for NAE1 Gene

mRNA/cDNA for NAE1 Gene

4 REFSEQ mRNAs :
12 NCBI additional mRNA sequence :
22 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NAE1

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for NAE1 Gene

ExUns: 1a · 1b ^ 2a · 2b ^ 3a · 3b ^ 4a · 4b ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11a · 11b ^ 12 ^ 13a · 13b ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19 ^ 20
SP1: - - - -
SP2: - - - - -
SP3: - -
SP4:
SP5: -

Relevant External Links for NAE1 Gene

GeneLoc Exon Structure for
NAE1

Expression for NAE1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for NAE1 Gene

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for NAE1 Gene



Protein tissue co-expression partners for NAE1 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for NAE1

SOURCE GeneReport for Unigene cluster for NAE1 Gene:

Hs.460978

mRNA Expression by UniProt/SwissProt for NAE1 Gene:

Q13564-ULA1_HUMAN
Tissue specificity: Ubiquitous in fetal tissues. Expressed throughout the adult brain.

Evidence on tissue expression from TISSUES for NAE1 Gene

  • Nervous system(4.9)
  • Muscle(4.4)
  • Skin(3)
  • Intestine(2.8)
  • Spleen(2.6)
  • Kidney(2.6)
  • Adrenal gland(2.6)
  • Gall bladder(2.3)
  • Pancreas(2.3)
  • Stomach(2.3)
  • Thyroid gland(2.3)
  • Heart(2.3)
  • Liver(2.2)
  • Bone marrow(2.1)
  • Blood(2.1)
  • Eye(2)
genes like me logo Genes that share expression patterns with NAE1: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , Protein differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for NAE1 Gene

Orthologs for NAE1 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for NAE1 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia NAE1 30 31
  • 99.75 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia NAE1 30 31
  • 95.76 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia NAE1 30 31
  • 94.94 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Nae1 30 17 31
  • 92.51 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Nae1 30
  • 92.32 (n)
Oppossum
(Monodelphis domestica)
Mammalia NAE1 31
  • 91 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia NAE1 31
  • 83 (a)
OneToOne
Chicken
(Gallus gallus)
Aves NAE1 30 31
  • 79.28 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia NAE1 31
  • 74 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia nae1 30
  • 74.32 (n)
Str.15276 30
African clawed frog
(Xenopus laevis)
Amphibia Xl.32585 30
Zebrafish
(Danio rerio)
Actinopterygii nae1 30 31
  • 67.36 (n)
OneToOne
zgc66148 30
Rainbow Trout
(Oncorhynchus mykiss)
Actinopterygii Omy.11046 30
Fruit Fly
(Drosophila melanogaster)
Insecta APP-BP1 30 31
  • 52.18 (n)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP005544 30
  • 48.76 (n)
Worm
(Caenorhabditis elegans)
Secernentea ula-1 31
  • 36 (a)
OneToOne
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes ULA1 31 33
  • 29 (a)
OneToOne
Thale Cress
(Arabidopsis thaliana)
eudicotyledons AXL 30
  • 50.52 (n)
Rice
(Oryza sativa)
Liliopsida Os03g0820100 30
  • 53.88 (n)
Os.17427 30
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 47 (a)
OneToOne
Species where no ortholog for NAE1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for NAE1 Gene

ENSEMBL:
Gene Tree for NAE1 (if available)
TreeFam:
Gene Tree for NAE1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for NAE1: view image

Paralogs for NAE1 Gene

Paralogs for NAE1 Gene

(29) SIMAP similar genes for NAE1 Gene using alignment to 14 proteins:

  • ULA1_HUMAN
  • A6NCK0_HUMAN
  • A8MU28_HUMAN
  • H3BMN8_HUMAN
  • H3BMR3_HUMAN
  • H3BQ16_HUMAN
  • H3BQW6_HUMAN
  • H3BS69_HUMAN
  • H3BSS8_HUMAN
  • J3KRK3_HUMAN
  • J3KTE3_HUMAN
  • J3QLH4_HUMAN
  • J3QRA5_HUMAN
  • L8E934_HUMAN

Pseudogenes.org Pseudogenes for NAE1 Gene

genes like me logo Genes that share paralogs with NAE1: view

Variants for NAE1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for NAE1 Gene

SNP ID Clinical significance and condition Chr 16 pos Variation AA Info Type
rs363212 - p.Ser101Phe

Additional dbSNP identifiers (rs#s) for NAE1 Gene

Structural Variations from Database of Genomic Variants (DGV) for NAE1 Gene

Variant ID Type Subtype PubMed ID
nsv510690 CNV deletion 20534489
nsv819809 CNV loss 19587683

Variation tolerance for NAE1 Gene

Residual Variation Intolerance Score: 15.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.16; 51.66% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for NAE1 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
NAE1

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NAE1 Gene

Disorders for NAE1 Gene

MalaCards: The human disease database

(1) MalaCards diseases for NAE1 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
alzheimer disease
  • ad
- elite association - COSMIC cancer census association via MalaCards
Search NAE1 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for NAE1

genes like me logo Genes that share disorders with NAE1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for NAE1 Gene

Publications for NAE1 Gene

  1. APP-BP1 mediates APP-induced apoptosis and DNA synthesis and is increased in Alzheimer's disease brain. (PMID: 14557245) Chen Y … Neve RL (The Journal of cell biology 2003) 3 4 23
  2. Conservation in the mechanism of Nedd8 activation by the human AppBp1-Uba3 heterodimer. (PMID: 12740388) Bohnsack RN … Haas AL (The Journal of biological chemistry 2003) 2 3 4
  3. APP-BP1, a novel protein that binds to the carboxyl-terminal region of the amyloid precursor protein. (PMID: 8626687) Chow N … Neve RL (The Journal of biological chemistry 1996) 2 3 4
  4. TRIP12 functions as an E3 ubiquitin ligase of APP-BP1. (PMID: 18627766) Park Y … Yoon JB (Biochemical and biophysical research communications 2008) 3 4
  5. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T … Sugano S (Nature genetics 2004) 3 4

Products for NAE1 Gene

  • Signalway ELISA kits for NAE1
  • Signalway Proteins for NAE1

Sources for NAE1 Gene