The protein encoded by this gene functions in a step-wise process of protein degradation through the N-end rule pathway. This protein acts as a tertiary destabilizing enzyme that deamidates N-terminal L-Asn residues on proteins to produce N-terminal L-Asp. L-Asp substrates are subsequently conjugated to L-Arg, which is recognized by specific E3 ubiquitin ligases and targeted to... See more...

Aliases for NTAN1 Gene

Aliases for NTAN1 Gene

  • N-Terminal Asparagine Amidase 2 3 5
  • Protein N-Terminal Asparagine Amidohydrolase 3 4
  • Protein NH2-Terminal Asparagine Deamidase 3 4
  • Protein N-Terminal Asparagine Amidase 3 4
  • Protein N-Terminal Asn Amidase 3 4
  • Protein NTN-Amidase 3 4
  • PNAA 3 4
  • PNAD 3 4
  • Protein NH2-Terminal Asparagine Amidohydrolase 4
  • EC 3.5.1.121 4

External Ids for NTAN1 Gene

Previous GeneCards Identifiers for NTAN1 Gene

  • GC16M015098
  • GC16M015039
  • GC16M015131
  • GC16M014776

Summaries for NTAN1 Gene

Entrez Gene Summary for NTAN1 Gene

  • The protein encoded by this gene functions in a step-wise process of protein degradation through the N-end rule pathway. This protein acts as a tertiary destabilizing enzyme that deamidates N-terminal L-Asn residues on proteins to produce N-terminal L-Asp. L-Asp substrates are subsequently conjugated to L-Arg, which is recognized by specific E3 ubiquitin ligases and targeted to the proteasome. Pseudogenes of this gene are located on the long arms of chromosomes 8, 10 and 12. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Jul 2012]

GeneCards Summary for NTAN1 Gene

NTAN1 (N-Terminal Asparagine Amidase) is a Protein Coding gene. Diseases associated with NTAN1 include Diabetes Mellitus, Insulin-Dependent, 21 and Secondary Progressive Multiple Sclerosis. Gene Ontology (GO) annotations related to this gene include protein-N-terminal asparagine amidohydrolase activity.

UniProtKB/Swiss-Prot Summary for NTAN1 Gene

  • N-terminal asparagine deamidase that mediates deamidation of N-terminal asparagine residues to aspartate. Required for the ubiquitin-dependent turnover of intracellular proteins that initiate with Met-Asn. These proteins are acetylated on the retained initiator methionine and can subsequently be modified by the removal of N-acetyl methionine by acylaminoacid hydrolase (AAH). Conversion of the resulting N-terminal asparagine to aspartate by NTAN1/PNAD renders the protein susceptible to arginylation, polyubiquitination and degradation as specified by the N-end rule. This enzyme does not act on substrates with internal or C-terminal asparagines and does not act on glutamine residues in any position, nor on acetylated N-terminal peptidyl Asn.

Additional gene information for NTAN1 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for NTAN1 Gene

Genomics for NTAN1 Gene

GeneHancer (GH) Regulatory Elements for NTAN1 Gene

Promoters and enhancers for NTAN1 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH16J015054 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 505.3 +0.7 678 2.8 RXRA ZBTB40 ZNF217 EP300 CTCF SIN3A TCF12 NRF1 POLR2G SP1 NTAN1 lnc-RRN3-1 NPIPA5 RRN3 NPIPA2 lnc-RRN3-2 PDXDC1
GH16J015057 Enhancer 0.8 Ensembl ENCODE 500.7 -1.8 -1830 1.2 CUX1 RBM22 MXD4 SMAD4 RXRA RARA THAP11 NR2F6 NR2F1 GATA3 NTAN1 lnc-RRN3-1 RRN3 PDXDC1 NPIPP1 RF00017-1982
GH16J014485 Enhancer 1.2 ENCODE dbSUPER 9.9 +568.8 568837 2.8 EP300 FOXK2 TCF12 POLR2G NCOR1 JUND FOS ZNF10 ZNF263 ZBTB11 LOC105371094 PARN BFAR RRN3 LOC100505915 PDXDC1 ENSG00000183458 MIR193B NTAN1 ERCC4
GH16J015122 Enhancer 0.2 Ensembl 4.7 -66.9 -66922 0.4 NPIPP1 NTAN1 ENSG00000270580 piR-53957-004 PKD1P6 PDXDC1
GH16J015052 Enhancer 0.9 ENCODE 0.7 +3.3 3270 1 EP300 FOXK2 ZBTB40 POLR2G USF1 NCOR1 TCF7 FOXA1 ZBTB25 TOE1 RRN3 NTAN1 lnc-RRN3-1 lnc-RRN3-2 PDXDC1
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around NTAN1 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for NTAN1

Top Transcription factor binding sites by QIAGEN in the NTAN1 gene promoter:
  • ITF-2
  • Nkx6-1
  • Pax-2
  • Pax-2a
  • Pax-2b
  • RREB-1
  • STAT5A
  • Tal-1beta
  • TBP
  • TFIID

Genomic Locations for NTAN1 Gene

Genomic Locations for NTAN1 Gene
chr16:15,037,853-15,056,079
(GRCh38/hg38)
Size:
18,227 bases
Orientation:
Minus strand
chr16:15,131,710-15,149,921
(GRCh37/hg19)
Size:
18,212 bases
Orientation:
Minus strand

Genomic View for NTAN1 Gene

Genes around NTAN1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NTAN1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NTAN1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NTAN1 Gene

Proteins for NTAN1 Gene

  • Protein details for NTAN1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q96AB6-NTAN1_HUMAN
    Recommended name:
    Protein N-terminal asparagine amidohydrolase
    Protein Accession:
    Q96AB6
    Secondary Accessions:
    • Q7Z4Z0

    Protein attributes for NTAN1 Gene

    Size:
    310 amino acids
    Molecular mass:
    34677 Da
    Quaternary structure:
    • Monomer.

neXtProt entry for NTAN1 Gene

Post-translational modifications for NTAN1 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for NTAN1 Gene

Domains & Families for NTAN1 Gene

Gene Families for NTAN1 Gene

Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for NTAN1 Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for NTAN1 Gene

GenScript: Design optimal peptide antigens:
  • Protein NH2-terminal asparagine deamidase (NTAN1_HUMAN)
genes like me logo Genes that share domains with NTAN1: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for NTAN1 Gene

Function for NTAN1 Gene

Molecular function for NTAN1 Gene

UniProtKB/Swiss-Prot Function:
N-terminal asparagine deamidase that mediates deamidation of N-terminal asparagine residues to aspartate. Required for the ubiquitin-dependent turnover of intracellular proteins that initiate with Met-Asn. These proteins are acetylated on the retained initiator methionine and can subsequently be modified by the removal of N-acetyl methionine by acylaminoacid hydrolase (AAH). Conversion of the resulting N-terminal asparagine to aspartate by NTAN1/PNAD renders the protein susceptible to arginylation, polyubiquitination and degradation as specified by the N-end rule. This enzyme does not act on substrates with internal or C-terminal asparagines and does not act on glutamine residues in any position, nor on acetylated N-terminal peptidyl Asn.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=H(+) + H2O + N-terminal L-asparaginyl-[protein] = N-terminal L-aspartyl-[protein] + NH4(+); Xref=Rhea:RHEA:50676, Rhea:RHEA-COMP:12669, Rhea:RHEA-COMP:12776, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28938, ChEBI:CHEBI:50348, ChEBI:CHEBI:64720; EC=3.5.1.121; Evidence=. ;.
UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by micromolar concentrations of copper and zinc ions.
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
pH dependence: Optimum pH is 6.0-7.5. {ECO:0000269 PubMed:21375249};

Enzyme Numbers (IUBMB) for NTAN1 Gene

Phenotypes From GWAS Catalog for NTAN1 Gene

Gene Ontology (GO) - Molecular Function for NTAN1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0008418 protein-N-terminal asparagine amidohydrolase activity IDA,IEA 21375249
GO:0016787 hydrolase activity IEA --
genes like me logo Genes that share ontologies with NTAN1: view
genes like me logo Genes that share phenotypes with NTAN1: view

Animal Models for NTAN1 Gene

MGI Knock Outs for NTAN1:

Animal Model Products

CRISPR Products

miRNA for NTAN1 Gene

miRTarBase miRNAs that target NTAN1

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NTAN1

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for NTAN1 Gene

Localization for NTAN1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NTAN1 Gene

Cytoplasm.

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 NTAN1 gene
Compartment Confidence
nucleus 4
cytosol 3
plasma membrane 2
extracellular 2
cytoskeleton 2
golgi apparatus 2
mitochondrion 1
endoplasmic reticulum 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Golgi apparatus (2)
  • Nucleoplasm (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for NTAN1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IBA 21873635
GO:0005737 cytoplasm IEA --
genes like me logo Genes that share ontologies with NTAN1: view

Pathways & Interactions for NTAN1 Gene

PathCards logo

SuperPathways for NTAN1 Gene

No Data Available

Interacting Proteins for NTAN1 Gene

;

Gene Ontology (GO) - Biological Process for NTAN1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006511 ubiquitin-dependent protein catabolic process IDA,IBA 21375249
GO:0007613 memory IEA --
GO:0008344 adult locomotory behavior IEA --
genes like me logo Genes that share ontologies with NTAN1: view

No data available for Pathways by source and SIGNOR curated interactions for NTAN1 Gene

Drugs & Compounds for NTAN1 Gene

(1) Additional Compounds for NTAN1 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with NTAN1: view

Transcripts for NTAN1 Gene

mRNA/cDNA for NTAN1 Gene

3 REFSEQ mRNAs :
6 NCBI additional mRNA sequence :
12 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 NTAN1

Alternative Splicing Database (ASD) splice patterns (SP) for NTAN1 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4a · 4b · 4c ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10a · 10b
SP1: -
SP2: - -
SP3:

Relevant External Links for NTAN1 Gene

GeneLoc Exon Structure for
NTAN1

Expression for NTAN1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for NTAN1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for NTAN1 Gene

This gene is overexpressed in Ovary (8.1) and Peripheral blood mononuclear cells (6.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for NTAN1 Gene



Protein tissue co-expression partners for NTAN1 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for NTAN1

SOURCE GeneReport for Unigene cluster for NTAN1 Gene:

Hs.592045

Evidence on tissue expression from TISSUES for NTAN1 Gene

  • Skin(4.4)
  • Lymph node(2.9)
  • Blood(2)
  • Heart(2)
genes like me logo Genes that share expression patterns with NTAN1: view

No data available for mRNA differential expression in normal tissues , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for NTAN1 Gene

Orthologs for NTAN1 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for NTAN1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia NTAN1 31 30
  • 99.14 (n)
OneToOne
cow
(Bos Taurus)
Mammalia NTAN1 31 30
  • 91.94 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Ntan1 17 31 30
  • 89.25 (n)
rat
(Rattus norvegicus)
Mammalia Ntan1 30
  • 89.1 (n)
dog
(Canis familiaris)
Mammalia NTAN1 31
  • 86 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia NTAN1 31
  • 77 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia -- 31
  • 69 (a)
OneToMany
-- 31
  • 67 (a)
OneToMany
chicken
(Gallus gallus)
Aves NTAN1 31 30
  • 71.23 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia NTAN1 31
  • 63 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia ntan1 30
  • 64.5 (n)
Str.2432 30
zebrafish
(Danio rerio)
Actinopterygii ntan1 31 30
  • 53.49 (n)
OneToOne
zgc77869 30
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.5805 30
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP010963 30
  • 49.18 (n)
fruit fly
(Drosophila melanogaster)
Insecta SP2637 31 30
  • 47.21 (n)
OneToOne
thale cress
(Arabidopsis thaliana)
eudicotyledons AT2G44420 30
  • 45.98 (n)
sea squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 35 (a)
OneToOne
Species where no ortholog for NTAN1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • 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 (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • 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)
  • worm (Caenorhabditis elegans)

Evolution for NTAN1 Gene

ENSEMBL:
Gene Tree for NTAN1 (if available)
TreeFam:
Gene Tree for NTAN1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for NTAN1: view image

Paralogs for NTAN1 Gene

(1) SIMAP similar genes for NTAN1 Gene using alignment to 6 proteins:

  • NTAN1_HUMAN
  • H3BMX8_HUMAN
  • H3BNJ5_HUMAN
  • H3BPN7_HUMAN
  • H3BR97_HUMAN
  • H3BU50_HUMAN

Pseudogenes.org Pseudogenes for NTAN1 Gene

genes like me logo Genes that share paralogs with NTAN1: view

No data available for Paralogs for NTAN1 Gene

Variants for NTAN1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for NTAN1 Gene

SNP ID Clinical significance and condition Chr 16 pos Variation AA Info Type
rs1135999 - p.Ser287Pro
rs1136001 - p.His283Asn

Additional dbSNP identifiers (rs#s) for NTAN1 Gene

Structural Variations from Database of Genomic Variants (DGV) for NTAN1 Gene

Variant ID Type Subtype PubMed ID
dgv2755n100 CNV gain 25217958
dgv2765n100 CNV gain 25217958
dgv2770n100 CNV loss 25217958
dgv344n27 CNV loss 19166990
dgv4919n54 CNV loss 21841781
dgv4922n54 CNV loss 21841781
esv2758632 CNV gain+loss 17122850
esv2762254 CNV gain+loss 21179565
esv3570354 CNV gain 25503493
esv3638020 CNV loss 21293372
esv3638021 CNV gain 21293372
esv3638022 CNV loss 21293372
esv3638023 CNV gain 21293372
esv3892796 CNV loss 25118596
esv3892797 CNV gain 25118596
nsv1036298 CNV gain 25217958
nsv1038955 CNV loss 25217958
nsv1042130 CNV gain 25217958
nsv1050325 CNV loss 25217958
nsv1053467 CNV loss 25217958
nsv457426 CNV gain 19166990
nsv509598 CNV insertion 20534489
nsv511045 OTHER complex 20534489
nsv571527 CNV gain+loss 21841781
nsv7277 OTHER inversion 18451855

Variation tolerance for NTAN1 Gene

Residual Variation Intolerance Score: 57.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 14.42; 96.39% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for NTAN1 Gene

Human Gene Mutation Database (HGMD)
NTAN1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
NTAN1

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NTAN1 Gene

Disorders for NTAN1 Gene

MalaCards: The human disease database

(2) MalaCards diseases for NTAN1 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
diabetes mellitus, insulin-dependent, 21
  • iddm21
secondary progressive multiple sclerosis
  • secondary-progressive ms
- elite association - COSMIC cancer census association via MalaCards
Search NTAN1 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for NTAN1

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with NTAN1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for NTAN1 Gene

Publications for NTAN1 Gene

  1. Genome-wide association study identifies novel loci associated with circulating phospho- and sphingolipid concentrations. (PMID: 22359512) Demirkan A … EUROSPAN consortium (PLoS genetics 2012) 3 41 54
  2. Genome-wide association study identifies multiple loci influencing human serum metabolite levels. (PMID: 22286219) Kettunen J … Ripatti S (Nature genetics 2012) 3 41 54
  3. Copy number variations of chromosome 16p13.1 region associated with schizophrenia. (PMID: 19786961) Ingason A … St Clair DM (Molecular psychiatry 2011) 3 41 54
  4. Expression and biochemical characterization of the human enzyme N-terminal asparagine amidohydrolase. (PMID: 21375249) Cantor JR … Georgiou G (Biochemistry 2011) 3 4 54
  5. A genome-wide association study in 19 633 Japanese subjects identified LHX3-QSOX2 and IGF1 as adult height loci. (PMID: 20189936) Okada Y … Kamatani N (Human molecular genetics 2010) 3 41 54

Products for NTAN1 Gene

Sources for NTAN1 Gene