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NAALAD2 N-acetylated alpha-linked acidic dipeptidase 2 [ Homo sapiens (human) ]

Gene ID: 10003, updated on 5-Mar-2024

Summary

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Official Symbol
NAALAD2provided by HGNC
Official Full Name
N-acetylated alpha-linked acidic dipeptidase 2provided by HGNC
Primary source
HGNC:HGNC:14526
See related
Ensembl:ENSG00000077616 MIM:611636; AllianceGenome:HGNC:14526
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
GCP3; GCPIII; GPCIII
Summary
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]
Expression
Broad expression in testis (RPKM 7.2), adrenal (RPKM 5.0) and 17 other tissues See more
Orthologs
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Genomic context

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Location:
11q14.3
Exon count:
21
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (90131699..90192894)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (90051780..90112974)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (89867831..89926062)

Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:89828635-89829290 Neighboring gene upstream binding transcription factor like 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:89837329-89837830 Neighboring gene small nucleolar RNA SNORD56 Neighboring gene H3K27ac hESC enhancer GRCh37_chr11:89867735-89868438 Neighboring gene MPRA-validated peak1387 silencer Neighboring gene cysteine and histidine rich domain containing 1 Neighboring gene uncharacterized LOC124902812 Neighboring gene NANOG hESC enhancer GRCh37_chr11:89961208-89961714

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Comparison of human glutamate carboxypeptidases II and III reveals their divergent substrate specificities. Navrátil M, et al. FEBS J, 2016 Jul. PMID 27208881
  2. Substrate specificity, inhibition and enzymological analysis of recombinant human glutamate carboxypeptidase II. Barinka C, et al. J Neurochem, 2002 Feb. PMID 11905994
  3. GCPII and its close homolog GCPIII: from a neuropeptidase to a cancer marker and beyond. Vorlova B, et al. Front Biosci (Landmark Ed), 2019 Mar 1. PMID 30844704
  4. Structural insight into the evolutionary and pharmacologic homology of glutamate carboxypeptidases II and III. Hlouchova K, et al. FEBS J, 2009 Aug. PMID 19678840
  5. Influence of a glutamate carboxypeptidase II (GCPII) polymorphism (1561C-->T) on plasma homocysteine, folate and vitamin B(12) levels and its relationship to cardiovascular disease risk. Lievers KJ, et al. Atherosclerosis, 2002 Oct. PMID 12204797

See all (22) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Novel susceptibility loci for steroid-associated osteonecrosis of the femoral head in systemic lupus erythematosus.
    Title: Novel susceptibility loci for steroid-associated osteonecrosis of the femoral head in systemic lupus erythematosus.
  2. Promoter Methylation of PRKCB, ADAMTS12, and NAALAD2 Is Specific to Prostate Cancer and Predicts Biochemical Disease Recurrence.
    Title: Promoter Methylation of PRKCB, ADAMTS12, and NAALAD2 Is Specific to Prostate Cancer and Predicts Biochemical Disease Recurrence.
  3. GCPII has been recognized as a neuropeptidase in the central nervous system, as a folate hydrolase participating in absorption of folates in the jejunum and, most importantly, as a prostate-specific membrane antigen that is highly expressed in prostate adenocarcinoma; GCPIII has not been associated with any specific physiolological functions [review]
    Title: GCPII and its close homolog GCPIII: from a neuropeptidase to a cancer marker and beyond.
  4. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
    Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
  5. four novel compounds, Ac-Glu-Met, Ac-Asp-Met and, surprisingly, Ac-Ala-Glu and Ac-Ala-Met were identified as substrates for GCPII
    Title: Substrate specificity, inhibition and enzymological analysis of recombinant human glutamate carboxypeptidase II.
  6. GCPII polymorphism may affect the predisposition to cardiovascular diseases.
    Title: Influence of a glutamate carboxypeptidase II (GCPII) polymorphism (1561C-->T) on plasma homocysteine, folate and vitamin B(12) levels and its relationship to cardiovascular disease risk.
Submit: New GeneRIF Correction

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

EBI GWAS Catalog

Description
Identification of nine novel loci associated with white blood cell subtypes in a Japanese population.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC26353, MGC116996

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables carboxypeptidase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables carboxypeptidase activity NAS
Non-traceable Author Statement
more info
 PubMed 
enables dipeptidase activity NAS
Non-traceable Author Statement
more info
 PubMed 
enables dipeptidyl-peptidase activity NAS
Non-traceable Author Statement
more info
 PubMed 
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables metallocarboxypeptidase activity IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables serine-type peptidase activity NAS
Non-traceable Author Statement
more info
 PubMed 
Process Evidence Code Pubs
involved_in proteolysis NAS
Non-traceable Author Statement
more info
 PubMed 
Component Evidence Code Pubs
located_in membrane NAS
Non-traceable Author Statement
more info
 PubMed 
located_in plasma membrane TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
N-acetylated-alpha-linked acidic dipeptidase 2
Names
N-acetylated alpha-linked acidic dipeptidase II
NAALADASE2
NAALADase II
glutamate carboxypeptidase III
NP_001287859.1
NP_005458.1
XP_016872532.1
XP_016872534.1
XP_016872535.1
XP_047282124.1
XP_054188397.1
XP_054188398.1
XP_054188399.1
XP_054188400.1
XP_054223318.1
XP_054223319.1
XP_054223320.1
XP_054223321.1

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)

  1. NM_001300930.2 → NP_001287859.1  N-acetylated-alpha-linked acidic dipeptidase 2 isoform 2

    See identical proteins and their annotated locations for NP_001287859.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1.
    Source sequence(s)
    AJ012370, AP000648, BC088727, BU618706, CN355388
    Consensus CDS
    CCDS73364.1
    UniProtKB/TrEMBL
    J3KNJ3
    Related
    ENSP00000320083.4, ENST00000321955.8
    Conserved Domains (3) summary
    cd08022
    Location:305 → 552
    M28_PSMA_like; M28 Zn-peptidase prostate-specific membrane antigen
    cd02121
    Location:110 → 296
    PA_GCPII_like; PA_GCPII_like: Protease-associated domain containing protein, glutamate carboxypeptidase II (GCPII)-like. This group contains various PA domain-containing proteins similar to GCPII including, GCPIII (NAALADase2) and NAALADase L. These proteins belong to ...
    pfam04253
    Location:589 → 704
    TFR_dimer; Transferrin receptor-like dimerization domain

  2. NM_005467.4 → NP_005458.1  N-acetylated-alpha-linked acidic dipeptidase 2 isoform 1

    See identical proteins and their annotated locations for NP_005458.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AJ012370, AK075390, AP000648, CN355388
    Consensus CDS
    CCDS8288.1
    UniProtKB/Swiss-Prot
    B3KQR4, Q4KKV4, Q4VAM9, Q9Y3Q0
    Related
    ENSP00000432481.1, ENST00000534061.6
    Conserved Domains (4) summary
    cd08022
    Location:338 → 585
    M28_PSMA_like; M28 Zn-peptidase prostate-specific membrane antigen
    cd02121
    Location:110 → 336
    PA_GCPII_like; PA_GCPII_like: Protease-associated domain containing protein, glutamate carboxypeptidase II (GCPII)-like. This group contains various PA domain-containing proteins similar to GCPII including, GCPIII (NAALADase2) and NAALADase L. These proteins belong to ...
    pfam04253
    Location:622 → 737
    TFR_dimer; Transferrin receptor-like dimerization domain
    cl14876
    Location:58 → 104
    Zinc_peptidase_like; Zinc peptidases M18, M20, M28, and M42

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000011.10 Reference GRCh38.p14 Primary Assembly

    Range
    90131699..90192894
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017017043.3 → XP_016872532.1  N-acetylated-alpha-linked acidic dipeptidase 2 isoform X1

    Conserved Domains (4) summary
    cd08022
    Location:373 → 620
    M28_PSMA_like; M28 Zn-peptidase prostate-specific membrane antigen
    cd02121
    Location:145 → 371
    PA_GCPII_like; PA_GCPII_like: Protease-associated domain containing protein, glutamate carboxypeptidase II (GCPII)-like. This group contains various PA domain-containing proteins similar to GCPII including, GCPIII (NAALADase2) and NAALADase L. These proteins belong to ...
    pfam04253
    Location:657 → 772
    TFR_dimer; Transferrin receptor-like dimerization domain
    cl14876
    Location:93 → 139
    Zinc_peptidase_like; Zinc peptidases M18, M20, M28, and M42

  2. XM_047426168.1 → XP_047282124.1  N-acetylated-alpha-linked acidic dipeptidase 2 isoform X2

  3. XM_017017046.3 → XP_016872535.1  N-acetylated-alpha-linked acidic dipeptidase 2 isoform X4

  4. XM_017017045.2 → XP_016872534.1  N-acetylated-alpha-linked acidic dipeptidase 2 isoform X3

    Conserved Domains (4) summary
    cd08022
    Location:284 → 531
    M28_PSMA_like; M28 Zn-peptidase prostate-specific membrane antigen
    cd02121
    Location:56 → 282
    PA_GCPII_like; PA_GCPII_like: Protease-associated domain containing protein, glutamate carboxypeptidase II (GCPII)-like. This group contains various PA domain-containing proteins similar to GCPII including, GCPIII (NAALADase2) and NAALADase L. These proteins belong to ...
    pfam04253
    Location:568 → 683
    TFR_dimer; Transferrin receptor-like dimerization domain
    cl14876
    Location:4 → 50
    Zinc_peptidase_like; Zinc peptidases M18, M20, M28, and M42

RNA

  1. XR_007062427.1 RNA Sequence

  2. XR_007062428.1 RNA Sequence

Reference GRCh38.p14 PATCHES

Genomic

  1. NW_019805497.1 Reference GRCh38.p14 PATCHES

    Range
    37822..99017
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054332422.1 → XP_054188397.1  N-acetylated-alpha-linked acidic dipeptidase 2 isoform X1

  2. XM_054332423.1 → XP_054188398.1  N-acetylated-alpha-linked acidic dipeptidase 2 isoform X2

  3. XM_054332425.1 → XP_054188400.1  N-acetylated-alpha-linked acidic dipeptidase 2 isoform X4

  4. XM_054332424.1 → XP_054188399.1  N-acetylated-alpha-linked acidic dipeptidase 2 isoform X3

RNA

  1. XR_008485770.1 RNA Sequence

  2. XR_008485771.1 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060935.1 Alternate T2T-CHM13v2.0

    Range
    90051780..90112974
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054367343.1 → XP_054223318.1  N-acetylated-alpha-linked acidic dipeptidase 2 isoform X1

  2. XM_054367344.1 → XP_054223319.1  N-acetylated-alpha-linked acidic dipeptidase 2 isoform X2

  3. XM_054367346.1 → XP_054223321.1  N-acetylated-alpha-linked acidic dipeptidase 2 isoform X4

  4. XM_054367345.1 → XP_054223320.1  N-acetylated-alpha-linked acidic dipeptidase 2 isoform X3

RNA

  1. XR_008488319.1 RNA Sequence

  2. XR_008488320.1 RNA Sequence

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9Y3Q0.1 GenPept UniProtKB/Swiss-Prot:Q9Y3Q0

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