NAE1 NEDD8 activating enzyme E1 subunit 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: NAE1provided by HGNC
Official Full Name: NEDD8 activating enzyme E1 subunit 1provided by HGNC
Primary source: HGNC:HGNC:621
See related: Ensembl:ENSG00000159593 MIM:603385; AllianceGenome:HGNC:621
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: HPP1; ula-1; APPBP1; NEDFIH; A-116A10.1
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 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]
Expression: Ubiquitous expression in testis (RPKM 28.1), thyroid (RPKM 17.4) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 16q22.1

Exon count:: 21

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	16	NC_000016.10 (66802878..66830976, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	16	NC_060940.1 (72597172..72625270, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	16	NC_000016.9 (66836781..66864879, complement)

Chromosome 16 - NC_000016.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

NAE1 expression was readily detectable in Uveal Melanoma. Inhibition of the neddylation pathway by MLN4924 repressed the cancer stem-like cells properties in Uveal Melanoma
Title: Neddylation Blockade Diminishes Hepatic Metastasis by Dampening Cancer Stem-Like Cells and Angiogenesis in Uveal Melanoma.
it was demonstrated that high expression of neddylation components, neural precursor cell expressed, developmentally downregulated 8 (NEDD8) and NEDD8activating enzyme 1 (NAE1), were associated with poor survival of patients with hepatocellular carcinoma (HCC)
Title: Inhibition of neddylation modification by MLN4924 sensitizes hepatocellular carcinoma cells to sorafenib.
Here we report that high expression of neddylation components, NEDD8 and NAE1, are associated with poor survival of Pancreatic ductal adenocarcinoma patients. Blockage of neddylation by MLN4924 significantly sensitizes pancreatic cancer cells to gemcitabine, reduced clonogenic survival, decreased invasion capacity, increased apoptosis and senescence
Title: Inhibition of Neddylation Modification Sensitizes Pancreatic Cancer Cells to Gemcitabine.
E1 (NAE1 and UBA3) and E2 (UBC12) enzymes, as well as global NEDD8 conjugation, were upregulated in over 2/3 of human intrahepatic cholangiocarcinoma
Title: Neddylation pathway is up-regulated in human intrahepatic cholangiocarcinoma and serves as a potential therapeutic target.
analysis of a metal-based inhibitor of NEDD8-activating enzyme
Title: A metal-based inhibitor of NEDD8-activating enzyme.
our results suggest that APP-BP1 modulates neuronal differentiation by altering gene expression profiles in fetal neural stem cells
Title: Amyloid precursor protein binding protein-1 knockdown reduces neuronal differentiation in fetal neural stem cells.
APP-BP1 plays an important role in the cell cycle progression of fetal neural stem cells
Title: Amyloid precursor protein binding protein-1 modulates cell cycle progression in fetal neural stem cells.
APP-BP1 displayed decreased expression levels in HPV-positive head and neck squamous cell carcinoma
Title: Biological and clinical relevance of transcriptionally active human papillomavirus (HPV) infection in oropharynx squamous cell carcinoma.
APP-BP1 is degraded by ubiquitin-dependent proteolysis.
Title: TRIP12 functions as an E3 ubiquitin ligase of APP-BP1.
Conservation in the mechanism of Nedd8 activation by the human AppBp1-Uba3 heterodimer.
Title: Conservation in the mechanism of Nedd8 activation by the human AppBp1-Uba3 heterodimer.

Submit: New GeneRIF Correction See all GeneRIFs (12)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Neurodevelopmental disorder with dysmorphic facies and ischiopubic hypoplasia MedGen: C5774298 OMIM: 620210 GeneReviews: Not available	not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Vpu	vpu	HIV-1 Vpu depends on NAE1-mediated neddylation (covalent addition of NEDD8 protein onto cullin backbone lysine residue rendering the cullin-RING E3 ubiquitin ligase complex catalytically active) to downregulate CD4	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH65010 (e-PCR)
- UniSTS:85575

Cda01h11 (e-PCR)
- UniSTS:76629

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
contributes_to NEDD8 activating enzyme activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein heterodimerization activity	IPI Inferred from Physical Interaction more info	PubMed
enables ubiquitin protein ligase binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in mitotic DNA replication checkpoint signaling	IDA Inferred from Direct Assay more info	PubMed
involved_in neuron apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in protein neddylation	IDA Inferred from Direct Assay more info	PubMed
involved_in protein neddylation	IEA Inferred from Electronic Annotation more info
involved_in protein neddylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of neuron apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of postsynapse assembly	IEA Inferred from Electronic Annotation more info
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in cytosol	TAS Traceable Author Statement more info
located_in glutamatergic synapse	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	IEA Inferred from Electronic Annotation more info
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: NEDD8-activating enzyme E1 regulatory subunit

Names: APP-BP1; NEDD8-activating enzyme E1 subunit; amyloid beta precursor protein binding protein 1, 59kDa; amyloid beta precursor protein-binding protein 1, 59 kDa; amyloid beta precursor protein-binding protein 1, 59kD; amyloid protein-binding protein 1; proto-oncogene protein 1; protooncogene protein 1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001018159.2 → NP_001018169.1 NEDD8-activating enzyme E1 regulatory subunit isoform b

See identical proteins and their annotated locations for NP_001018169.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) contains an alternate exon compared to variant 1. The resulting isoform (b) is shorter and has a distinct C-terminus compared to isoform a.

Source sequence(s)

BC000480, BM045535, BM785899

Consensus CDS

CCDS42171.1

UniProtKB/Swiss-Prot

Q13564

Related

ENSP00000368776.2, ENST00000379463.6

Conserved Domains (2) summary

COG0476
Location:12 → 187

ThiF; Molybdopterin or thiamine biosynthesis adenylyltransferase [Coenzyme transport and metabolism]

cd01493
Location:12 → 526

APPBP1_RUB; Ubiquitin activating enzyme (E1) subunit APPBP1. APPBP1 is part of the heterodimeric activating enzyme (E1), specific for the Rub family of ubiquitin-like proteins (Ubls). E1 enzymes are part of a conjugation cascade to attach Ub or Ubls, covalently to ...
NM_001018160.2 → NP_001018170.1 NEDD8-activating enzyme E1 regulatory subunit isoform c

See identical proteins and their annotated locations for NP_001018170.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an alternate exon compared to variant 1. The resulting isoform (c) is shorter at the N-terminus compared to isoform a.

Source sequence(s)

BC000480, BM785899

Consensus CDS

CCDS42172.1

UniProtKB/Swiss-Prot

Q13564

Related

ENSP00000377637.2, ENST00000394074.6

Conserved Domains (1) summary

cd01493
Location:1 → 443

APPBP1_RUB; Ubiquitin activating enzyme (E1) subunit APPBP1. APPBP1 is part of the heterodimeric activating enzyme (E1), specific for the Rub family of ubiquitin-like proteins (Ubls). E1 enzymes are part of a conjugation cascade to attach Ub or Ubls, covalently to ...
NM_001286500.2 → NP_001273429.1 NEDD8-activating enzyme E1 regulatory subunit isoform d

Status: REVIEWED

Description

Transcript Variant: This variant (4) uses an alternate in-frame splice junction at the 3' end of an exon compared to variant 1. The resulting isoform (d) has the same N- and C-termini but contains an additional 3 aa compared to variant 1.

Source sequence(s)

AK097680, U50939

Consensus CDS

CCDS67050.1

UniProtKB/Swiss-Prot

Q13564

Related

ENSP00000351990.4, ENST00000359087.8

Conserved Domains (2) summary

COG0476
Location:9 → 196

ThiF; Molybdopterin or thiamine biosynthesis adenylyltransferase [Coenzyme transport and metabolism]

cd01493
Location:11 → 535

APPBP1_RUB; Ubiquitin activating enzyme (E1) subunit APPBP1. APPBP1 is part of the heterodimeric activating enzyme (E1), specific for the Rub family of ubiquitin-like proteins (Ubls). E1 enzymes are part of a conjugation cascade to attach Ub or Ubls, covalently to ...
NM_003905.4 → NP_003896.1 NEDD8-activating enzyme E1 regulatory subunit isoform a

See identical proteins and their annotated locations for NP_003896.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the predominant isoform (a).

Source sequence(s)

BC000480, BM785899

Consensus CDS

CCDS10820.1

UniProtKB/Swiss-Prot

A6NCK0, A6NFN4, A8MU28, B2R700, B3KUP9, Q13564

Related

ENSP00000290810.3, ENST00000290810.8

Conserved Domains (1) summary

cd01493
Location:11 → 532

APPBP1_RUB; Ubiquitin activating enzyme (E1) subunit APPBP1. APPBP1 is part of the heterodimeric activating enzyme (E1), specific for the Rub family of ubiquitin-like proteins (Ubls). E1 enzymes are part of a conjugation cascade to attach Ub or Ubls, covalently to ...