This gene is a member of the N-acetylated alpha-linked acidic dipeptidase (NAALADase) gene family. The representative member of this family is the gene encoding human prostate-specific membrane antigen (PSM), which is a marker of prostatic carcinomas and is the first to be shown to possess NAALADase activity. NAALADase cleaves N-acetyl-L-aspartate-L-glutamate (NAAG), which is a... See more...

Aliases for NAALAD2 Gene

Aliases for NAALAD2 Gene

  • N-Acetylated Alpha-Linked Acidic Dipeptidase 2 2 3 5
  • Glutamate Carboxypeptidase III 2 3 4
  • GCPIII 2 3 4
  • N-Acetylated-Alpha-Linked Acidic Dipeptidase 2 3 4
  • NAALADase II 3 4
  • EC 3.4.17.21 4 51
  • NAALADASE2 2 3
  • N-Acetylated Alpha-Linked Acidic Dipeptidase II 3
  • N-Acetylated-Alpha-Linked Acidic Dipeptidase II 4
  • NAADALASE2 3
  • NAALAD2 5
  • GPCIII 3

External Ids for NAALAD2 Gene

Previous GeneCards Identifiers for NAALAD2 Gene

  • GC11P092197
  • GC11P091374
  • GC11P090052
  • GC11P089555
  • GC11P089556
  • GC11P089508
  • GC11P089867
  • GC11P085952

Summaries for NAALAD2 Gene

Entrez Gene Summary for NAALAD2 Gene

  • This gene is a member of the N-acetylated alpha-linked acidic dipeptidase (NAALADase) gene family. The representative member of this family is the gene encoding human prostate-specific membrane antigen (PSM), which is a marker of prostatic carcinomas and is the first to be shown to possess NAALADase activity. NAALADase cleaves N-acetyl-L-aspartate-L-glutamate (NAAG), which is a neuropeptide expressed both in the central nervous systems and in the periphery and is thought to function as a neurotransmitter. The product of this gene is a type II integral membrane protein. Transient transfection of this gene confers both NAALADase and dipetidyl peptidase IV activities to mammalian cells. This gene is highly expressed in ovary and testis as well as within discrete brain areas. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

GeneCards Summary for NAALAD2 Gene

NAALAD2 (N-Acetylated Alpha-Linked Acidic Dipeptidase 2) is a Protein Coding gene. Among its related pathways are Viral mRNA Translation and Metabolism. Gene Ontology (GO) annotations related to this gene include peptidase activity and serine-type peptidase activity. An important paralog of this gene is FOLH1.

UniProtKB/Swiss-Prot Summary for NAALAD2 Gene

  • Has N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Also exhibits a dipeptidyl-peptidase IV type activity. Inactivates the peptide neurotransmitter N-acetylaspartylglutamate.

Additional gene information for NAALAD2 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for NAALAD2 Gene

Genomics for NAALAD2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for NAALAD2 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
GH11J090133 Promoter/Enhancer 1.8 EPDnew Ensembl ENCODE CraniofacialAtlas 625.8 +3.6 3627 2.9 TEAD4 PRDM10 ZIC2 RBFOX2 POLR2A RXRB PATZ1 GABPA KMT2B ZBTB20 NAALAD2 TRIM49C piR-39098-040 CHORDC1
GH11J090132 Enhancer 0.2 Ensembl 600.7 +0.6 586 0.2 NAALAD2 piR-39098-040 CHORDC1
GH11J090220 Promoter/Enhancer 1.9 EPDnew Ensembl ENCODE CraniofacialAtlas 5.7 +90.8 90786 4.6 HNRNPL GATAD2A PRDM10 ZNF629 RFX1 ZNF692 POLR2A BACH1 LARP7 GABPA CHORDC1 ENSG00000280367 lnc-TRIM49D1-2 lnc-NAALAD2-3 NAALAD2 TRIM49C lnc-CHORDC1-1
GH11J090204 Enhancer 0.7 Ensembl ENCODE 5.9 +73.9 73856 1.3 CTCF ZNF629 REST RAD21 TRIM22 SMC3 CEBPG ZNF213 ZNF654 ZNF143 NAALAD2 lnc-CHORDC1-1 CHORDC1 lnc-TRIM49D1-2
GH11J090139 Enhancer 0.2 Ensembl 25.5 +7.9 7886 0.4 NAALAD2 CHORDC1 piR-39098-040
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around NAALAD2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for NAALAD2

Top Transcription factor binding sites by QIAGEN in the NAALAD2 gene promoter:
  • CUTL1
  • FOXD1
  • FOXD3
  • Meis-1
  • Meis-1a
  • Meis-1b
  • NCX
  • Pax-2
  • Pax-2a
  • Pax-2b

Genomic Locations for NAALAD2 Gene

Genomic Locations for NAALAD2 Gene
chr11:90,131,515-90,193,577
(GRCh38/hg38)
Size:
62,063 bases
Orientation:
Plus strand
chr11:89,864,683-89,926,062
(GRCh37/hg19)
Size:
61,380 bases
Orientation:
Plus strand

Genomic View for NAALAD2 Gene

Genes around NAALAD2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NAALAD2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NAALAD2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NAALAD2 Gene

Proteins for NAALAD2 Gene

  • Protein details for NAALAD2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9Y3Q0-NALD2_HUMAN
    Recommended name:
    N-acetylated-alpha-linked acidic dipeptidase 2
    Protein Accession:
    Q9Y3Q0
    Secondary Accessions:
    • B3KQR4
    • Q4KKV4
    • Q4VAM9

    Protein attributes for NAALAD2 Gene

    Size:
    740 amino acids
    Molecular mass:
    83592 Da
    Cofactor:
    Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
    Quaternary structure:
    • Homodimer.

    Three dimensional structures from OCA and Proteopedia for NAALAD2 Gene

    Alternative splice isoforms for NAALAD2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for NAALAD2 Gene

Selected DME Specific Peptides for NAALAD2 Gene

Q9Y3Q0:
  • FYDPTFK
  • EPDRYVILGGHRD
  • IEGNYTLRVDCTPL
  • ILYSDPADYF
  • NDQLMLLER
  • LERAFIDPLGLP
  • SFDSLFSAV

Post-translational modifications for NAALAD2 Gene

  • Glycosylation at Asn111, Asn143, Asn185, Asn314, Asn449, Asn603, and Asn628
  • Modification sites at PhosphoSitePlus

Domains & Families for NAALAD2 Gene

Gene Families for NAALAD2 Gene

IUPHAR :
Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins
  • Predicted membrane proteins

Protein Domains for NAALAD2 Gene

InterPro:
Blocks:
  • Protease-associated PA
  • Transferrin receptor-like dimerisation domain
  • Peptidase family M28
ProtoNet:

Suggested Antigen Peptide Sequences for NAALAD2 Gene

GenScript: Design optimal peptide antigens:
  • N-acetylated-alpha-linked acidic dipeptidase II (NALD2_HUMAN)
  • NAALAD2 protein (Q4G181_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9Y3Q0

UniProtKB/Swiss-Prot:

NALD2_HUMAN :
  • The NAALADase activity is found in the central region, the dipeptidyl peptidase IV type activity in the C-terminal.
  • Belongs to the peptidase M28 family. M28B subfamily.
Domain:
  • The NAALADase activity is found in the central region, the dipeptidyl peptidase IV type activity in the C-terminal.
Family:
  • Belongs to the peptidase M28 family. M28B subfamily.
genes like me logo Genes that share domains with NAALAD2: view

Function for NAALAD2 Gene

Molecular function for NAALAD2 Gene

UniProtKB/Swiss-Prot Function:
Has N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Also exhibits a dipeptidyl-peptidase IV type activity. Inactivates the peptide neurotransmitter N-acetylaspartylglutamate.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=Release of an unsubstituted, C-terminal glutamyl residue, typically from Ac-Asp-Glu or folylpoly-gamma-glutamates.; EC=3.4.17.21;.
UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by quisqualate.

Enzyme Numbers (IUBMB) for NAALAD2 Gene

Phenotypes From GWAS Catalog for NAALAD2 Gene

Gene Ontology (GO) - Molecular Function for NAALAD2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003824 catalytic activity IEA --
GO:0004180 carboxypeptidase activity IBA,NAS 10085079
GO:0008233 peptidase activity IEA --
GO:0008236 serine-type peptidase activity NAS 10085079
GO:0008237 metallopeptidase activity IEA --
genes like me logo Genes that share ontologies with NAALAD2: view
genes like me logo Genes that share phenotypes with NAALAD2: view

Animal Model Products

  • Taconic Biosciences Mouse Models for NAALAD2

CRISPR Products

miRNA for NAALAD2 Gene

miRTarBase miRNAs that target NAALAD2

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NAALAD2

No data available for Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for NAALAD2 Gene

Localization for NAALAD2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NAALAD2 Gene

Cell membrane. Single-pass type II membrane protein.

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 NAALAD2 gene
Compartment Confidence
plasma membrane 4
nucleus 3
mitochondrion 2
extracellular 1
peroxisome 1
endoplasmic reticulum 1
cytosol 1
cytoskeleton 0
golgi apparatus 0

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for NAALAD2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane TAS --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane NAS 10085079
genes like me logo Genes that share ontologies with NAALAD2: view

Pathways & Interactions for NAALAD2 Gene

genes like me logo Genes that share pathways with NAALAD2: view

Pathways by source for NAALAD2 Gene

Gene Ontology (GO) - Biological Process for NAALAD2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006508 proteolysis NAS 10085079
GO:0008152 metabolic process IEA --
GO:0008652 cellular amino acid biosynthetic process TAS --
GO:0042135 neurotransmitter catabolic process IEA --
genes like me logo Genes that share ontologies with NAALAD2: view

No data available for SIGNOR curated interactions for NAALAD2 Gene

Drugs & Compounds for NAALAD2 Gene

No Compound Related Data Available

Transcripts for NAALAD2 Gene

mRNA/cDNA for NAALAD2 Gene

2 REFSEQ mRNAs :
13 NCBI additional mRNA sequence :
10 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 NAALAD2

Alternative Splicing Database (ASD) splice patterns (SP) for NAALAD2 Gene

ExUns: 1a · 1b · 1c · 1d ^ 2 ^ 3 ^ 4 ^ 5a · 5b ^ 6 ^ 7 ^ 8a · 8b ^ 9 ^ 10a · 10b ^ 11 ^ 12a · 12b ^ 13a · 13b ^ 14 ^ 15 ^ 16a · 16b · 16c ^
SP1: - - - - - - - -
SP2: - -
SP3: -
SP4: - - - - - - - - - - - - - - - -
SP5:
SP6: -
SP7:

ExUns: 17 ^ 18 ^ 19 ^ 20 ^ 21
SP1:
SP2:
SP3:
SP4: - - - -
SP5:
SP6:
SP7:

Relevant External Links for NAALAD2 Gene

GeneLoc Exon Structure for
NAALAD2

Expression for NAALAD2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for NAALAD2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for NAALAD2 Gene

This gene is overexpressed in Pituitary (x6.1).

Protein differential expression in normal tissues from HIPED for NAALAD2 Gene

This gene is overexpressed in Fetal ovary (16.1), Ovary (14.3), Testis (11.1), Prostate (6.9), and Stomach (6.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for NAALAD2 Gene



Protein tissue co-expression partners for NAALAD2 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for NAALAD2

SOURCE GeneReport for Unigene cluster for NAALAD2 Gene:

Hs.503560

mRNA Expression by UniProt/SwissProt for NAALAD2 Gene:

Q9Y3Q0-NALD2_HUMAN
Tissue specificity: Highest expression in the testis. Also found in ovary and spleen. Weak expression in prostate, heart and placenta. In brain, expressed in striatum, parietal cortex and ventral striatum with lower levels in hippocampus, brain stem, putamen and superior colliculus.

Evidence on tissue expression from TISSUES for NAALAD2 Gene

  • Heart(5)
  • Nervous system(2)
genes like me logo Genes that share expression patterns with NAALAD2: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for NAALAD2 Gene

Orthologs for NAALAD2 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for NAALAD2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia NAALAD2 30 31
  • 99.59 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia NAALAD2 30 31
  • 89.82 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia NAALAD2 30 31
  • 87.84 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Naalad2 30
  • 85.72 (n)
Mouse
(Mus musculus)
Mammalia Naalad2 30 17 31
  • 84.82 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia NAALAD2 31
  • 79 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia NAALAD2 31
  • 78 (a)
OneToOne
Chicken
(Gallus gallus)
Aves NAALAD2 30 31
  • 73.07 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia NAALAD2 31
  • 72 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia naalad2 30
  • 70.11 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.15462 30
Zebrafish
(Danio rerio)
Actinopterygii naalad2 31
  • 66 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea R57.1 30
  • 49.93 (n)
gcp-2.1 31
  • 33 (a)
ManyToMany
C35C5.2 32
  • 32 (a)
gcp-2.2 31
  • 30 (a)
ManyToMany
gcp-2.3 31
  • 28 (a)
ManyToMany
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes VPS70 31 33
  • 21 (a)
OneToMany
Thale Cress
(Arabidopsis thaliana)
eudicotyledons AT5G19740 30
  • 49.71 (n)
Rice
(Oryza sativa)
Liliopsida Os01g0740500 30
  • 46.62 (n)
Os.18145 30
Barley
(Hordeum vulgare)
Liliopsida Hv.3035 30
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 44 (a)
ManyToMany
Bread mold
(Neurospora crassa)
Ascomycetes NCU06285 30
  • 43.3 (n)
Fission Yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes SPBC354.09c 30
  • 42.61 (n)
Species where no ortholog for NAALAD2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fruit Fly (Drosophila melanogaster)
  • 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)
  • Rainbow Trout (Oncorhynchus mykiss)
  • 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 NAALAD2 Gene

ENSEMBL:
Gene Tree for NAALAD2 (if available)
TreeFam:
Gene Tree for NAALAD2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for NAALAD2: view image

Paralogs for NAALAD2 Gene

Paralogs for NAALAD2 Gene

(4) SIMAP similar genes for NAALAD2 Gene using alignment to 9 proteins:

  • NALD2_HUMAN
  • E9PII2_HUMAN
  • E9PJ53_HUMAN
  • E9PJV2_HUMAN
  • E9PKX5_HUMAN
  • J3KNJ3_HUMAN
  • L8EAF7_HUMAN
  • Q4G181_HUMAN
  • Q4KKV4_HUMAN
genes like me logo Genes that share paralogs with NAALAD2: view

Variants for NAALAD2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for NAALAD2 Gene

SNP ID Clinical significance and condition Chr 11 pos Variation AA Info Type
rs10830430 - p.Ile446Val
rs11018879 - p.Val101Ile

Additional dbSNP identifiers (rs#s) for NAALAD2 Gene

Structural Variations from Database of Genomic Variants (DGV) for NAALAD2 Gene

Variant ID Type Subtype PubMed ID
dgv687n106 CNV deletion 24896259
esv1511526 CNV insertion 17803354
esv2759849 CNV gain+loss 17122850
esv3307873 CNV mobile element insertion 20981092
esv3331098 CNV insertion 20981092
esv3548126 CNV deletion 23714750
esv3579841 CNV loss 25503493
esv3579993 CNV gain 25503493
esv3627188 CNV loss 21293372
esv3892056 CNV gain+loss 25118596
nsv1035213 CNV gain 25217958
nsv1036092 CNV loss 25217958
nsv1048042 CNV loss 25217958
nsv1048624 CNV loss 25217958
nsv1054560 CNV loss 25217958
nsv1111059 CNV tandem duplication 24896259
nsv1116681 CNV tandem duplication 24896259
nsv1119422 CNV insertion 24896259
nsv1138061 CNV deletion 24896259
nsv468787 CNV loss 19166990
nsv555830 CNV loss 21841781
nsv555831 CNV loss 21841781
nsv555832 CNV gain 21841781
nsv555833 CNV loss 21841781

Variation tolerance for NAALAD2 Gene

Residual Variation Intolerance Score: 72.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 8.45; 85.71% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for NAALAD2 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
NAALAD2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NAALAD2 Gene

Disorders for NAALAD2 Gene

Additional Disease Information for NAALAD2

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform

No disorders were found for NAALAD2 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for NAALAD2 Gene

Publications for NAALAD2 Gene

  1. Isolation and expression of novel human glutamate carboxypeptidases with N-acetylated alpha-linked acidic dipeptidase and dipeptidyl peptidase IV activity. (PMID: 10085079) Pangalos MN … Gordon RD (The Journal of biological chemistry 1999) 2 3 4 23
  2. Identification of nine novel loci associated with white blood cell subtypes in a Japanese population. (PMID: 21738478) Okada Y … Kamatani N (PLoS genetics 2011) 3 41
  3. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 41
  4. Structural insight into the evolutionary and pharmacologic homology of glutamate carboxypeptidases II and III. (PMID: 19678840) Hlouchova K … Lubkowski J (The FEBS journal 2009) 3 4
  5. Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries. (PMID: 16303743) Otsuki T … Isogai T (DNA research : an international journal for rapid publication of reports on genes and genomes 2005) 3 4

Products for NAALAD2 Gene

Sources for NAALAD2 Gene