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

    Gene ID: 10003, updated on 10-Dec-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
    mouse all
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    Genomic context

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    See NAALAD2 in Genome Data Viewer
    Location:
    11q14.3
    Exon count:
    21
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (90131699..90192894)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (90051780..90112974)
    RS_2024_09 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. Substrate specificity, inhibition and enzymological analysis of recombinant human glutamate carboxypeptidase II. Barinka C, et al. J Neurochem, 2002 Feb. PMID 11905994
    2. Comparison of human glutamate carboxypeptidases II and III reveals their divergent substrate specificities. Navrátil M, et al. FEBS J, 2016 Jul. PMID 27208881
    3. 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
    4. 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
    5. Structural insight into the evolutionary and pharmacologic homology of glutamate carboxypeptidases II and III. Hlouchova K, et al. FEBS J, 2009 Aug. PMID 19678840

    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)

    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_2024_08

    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

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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