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Q9Y3Q0

- NALD2_HUMAN

UniProt

Q9Y3Q0 - NALD2_HUMAN

Protein

N-acetylated-alpha-linked acidic dipeptidase 2

Gene

NAALAD2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 119 (01 Oct 2014)
      Sequence version 1 (01 Nov 1999)
      Previous versions | rss
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    Functioni

    Has N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Also exhibits a dipeptidyl-peptidase IV type activity. Inactivate the peptide neurotransmitter N-acetylaspartylglutamate.1 Publication

    Catalytic activityi

    Release of an unsubstituted, C-terminal glutamyl residue, typically from Ac-Asp-Glu or folylpoly-gamma-glutamates.

    Cofactori

    Binds 2 zinc ions per subunit. Required for NAALADase activity.

    Enzyme regulationi

    Inhibited by quisqualate.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi367 – 3671Zinc 1; catalytic
    Metal bindingi377 – 3771Zinc 1; catalytic
    Metal bindingi377 – 3771Zinc 2
    Active sitei414 – 4141Nucleophile; for NAALADase activityBy similarity
    Metal bindingi415 – 4151Zinc 2
    Metal bindingi443 – 4431Zinc 1; catalytic
    Metal bindingi543 – 5431Zinc 2
    Active sitei618 – 6181Charge relay systemSequence Analysis
    Active sitei656 – 6561Charge relay systemSequence Analysis
    Active sitei679 – 6791Charge relay systemSequence Analysis

    GO - Molecular functioni

    1. carboxypeptidase activity Source: UniProtKB
    2. dipeptidase activity Source: UniProtKB
    3. dipeptidyl-peptidase activity Source: UniProtKB
    4. metal ion binding Source: UniProtKB-KW
    5. metallopeptidase activity Source: UniProtKB-KW
    6. N-formylglutamate deformylase activity Source: Ensembl
    7. serine-type peptidase activity Source: UniProtKB

    GO - Biological processi

    1. neurotransmitter catabolic process Source: Ensembl
    2. proteolysis Source: UniProtKB

    Keywords - Molecular functioni

    Carboxypeptidase, Dipeptidase, Hydrolase, Metalloprotease, Protease

    Keywords - Ligandi

    Metal-binding, Zinc

    Protein family/group databases

    MEROPSiM28.012.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    N-acetylated-alpha-linked acidic dipeptidase 2 (EC:3.4.17.21)
    Alternative name(s):
    Glutamate carboxypeptidase III
    Short name:
    GCPIII
    N-acetylated-alpha-linked acidic dipeptidase II
    Short name:
    NAALADase II
    Gene namesi
    Name:NAALAD2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 11

    Organism-specific databases

    HGNCiHGNC:14526. NAALAD2.

    Subcellular locationi

    GO - Cellular componenti

    1. integral component of membrane Source: UniProtKB

    Keywords - Cellular componenti

    Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA31430.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 740740N-acetylated-alpha-linked acidic dipeptidase 2PRO_0000174121Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi111 – 1111N-linked (GlcNAc...)1 Publication
    Glycosylationi143 – 1431N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi185 – 1851N-linked (GlcNAc...)1 Publication
    Glycosylationi314 – 3141N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi449 – 4491N-linked (GlcNAc...)1 Publication
    Glycosylationi603 – 6031N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi628 – 6281N-linked (GlcNAc...)1 Publication

    Keywords - PTMi

    Glycoprotein

    Proteomic databases

    MaxQBiQ9Y3Q0.
    PaxDbiQ9Y3Q0.
    PRIDEiQ9Y3Q0.

    PTM databases

    PhosphoSiteiQ9Y3Q0.

    Expressioni

    Tissue specificityi

    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.

    Gene expression databases

    ArrayExpressiQ9Y3Q0.
    BgeeiQ9Y3Q0.
    CleanExiHS_NAALAD2.
    GenevestigatoriQ9Y3Q0.

    Organism-specific databases

    HPAiHPA060820.

    Interactioni

    Subunit structurei

    Homodimer.1 Publication

    Protein-protein interaction databases

    IntActiQ9Y3Q0. 1 interaction.
    MINTiMINT-2823431.

    Structurei

    Secondary structure

    1
    740
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi47 – 548
    Helixi57 – 6711
    Beta strandi68 – 703
    Helixi77 – 9317
    Beta strandi96 – 10914
    Beta strandi117 – 1215
    Beta strandi127 – 1304
    Beta strandi164 – 1663
    Helixi172 – 1809
    Beta strandi190 – 1945
    Helixi200 – 20910
    Beta strandi213 – 2186
    Helixi221 – 2244
    Turni232 – 2343
    Beta strandi235 – 2373
    Helixi273 – 2753
    Beta strandi284 – 2874
    Helixi289 – 2979
    Helixi307 – 3093
    Beta strandi312 – 3154
    Beta strandi320 – 3234
    Beta strandi331 – 3366
    Beta strandi339 – 35214
    Beta strandi355 – 36713
    Beta strandi371 – 3733
    Turni375 – 3784
    Helixi379 – 39719
    Beta strandi403 – 41210
    Helixi414 – 4163
    Helixi419 – 43517
    Beta strandi436 – 4416
    Beta strandi445 – 4473
    Beta strandi449 – 4568
    Helixi458 – 4603
    Helixi461 – 4688
    Helixi483 – 4908
    Beta strandi491 – 4933
    Beta strandi496 – 5005
    Beta strandi507 – 5093
    Helixi512 – 5165
    Beta strandi522 – 5287
    Turni531 – 5333
    Beta strandi536 – 5383
    Turni540 – 5434
    Helixi549 – 5557
    Helixi561 – 57919
    Helixi587 – 60519
    Helixi606 – 6083
    Helixi609 – 6157
    Helixi620 – 64021
    Helixi648 – 66417
    Beta strandi679 – 6857
    Beta strandi688 – 6958
    Helixi696 – 7027
    Helixi705 – 7073
    Helixi711 – 73626

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3FECX-ray1.49A36-740[»]
    3FEDX-ray1.29A36-740[»]
    3FEEX-ray1.56A36-740[»]
    3FF3X-ray1.37A36-740[»]
    ProteinModelPortaliQ9Y3Q0.
    SMRiQ9Y3Q0. Positions 46-739.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9Y3Q0.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 77CytoplasmicSequence Analysis
    Topological domaini32 – 740709ExtracellularSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei8 – 3124Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni264 – 577314NAALADaseAdd
    BLAST

    Domaini

    The NAALADase activity is found in the central region, the dipeptidyl peptidase IV type activity in the C-terminal.

    Sequence similaritiesi

    Belongs to the peptidase M28 family. M28B subfamily.Curated

    Keywords - Domaini

    Signal-anchor, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG2234.
    HOGENOMiHOG000211921.
    HOVERGENiHBG051639.
    InParanoidiQ9Y3Q0.
    KOiK01301.
    OMAiYDAIFDI.
    OrthoDBiEOG7QK0BC.
    PhylomeDBiQ9Y3Q0.
    TreeFamiTF312981.

    Family and domain databases

    Gene3Di1.20.930.40. 1 hit.
    InterProiIPR007484. Peptidase_M28.
    IPR003137. Protease-assoc_domain.
    IPR007365. TFR-like_dimer_dom.
    [Graphical view]
    PfamiPF02225. PA. 1 hit.
    PF04389. Peptidase_M28. 1 hit.
    PF04253. TFR_dimer. 1 hit.
    [Graphical view]
    SUPFAMiSSF47672. SSF47672. 1 hit.

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q9Y3Q0-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MAESRGRLYL WMCLAAALAS FLMGFMVGWF IKPLKETTTS VRYHQSIRWK    50
    LVSEMKAENI KSFLRSFTKL PHLAGTEQNF LLAKKIQTQW KKFGLDSAKL 100
    VHYDVLLSYP NETNANYISI VDEHETEIFK TSYLEPPPDG YENVTNIVPP 150
    YNAFSAQGMP EGDLVYVNYA RTEDFFKLER EMGINCTGKI VIARYGKIFR 200
    GNKVKNAMLA GAIGIILYSD PADYFAPEVQ PYPKGWNLPG TAAQRGNVLN 250
    LNGAGDPLTP GYPAKEYTFR LDVEEGVGIP RIPVHPIGYN DAEILLRYLG 300
    GIAPPDKSWK GALNVSYSIG PGFTGSDSFR KVRMHVYNIN KITRIYNVVG 350
    TIRGSVEPDR YVILGGHRDS WVFGAIDPTS GVAVLQEIAR SFGKLMSKGW 400
    RPRRTIIFAS WDAEEFGLLG STEWAEENVK ILQERSIAYI NSDSSIEGNY 450
    TLRVDCTPLL YQLVYKLTKE IPSPDDGFES KSLYESWLEK DPSPENKNLP 500
    RINKLGSGSD FEAYFQRLGI ASGRARYTKN KKTDKYSSYP VYHTIYETFE 550
    LVEKFYDPTF KKQLSVAQLR GALVYELVDS KIIPFNIQDY AEALKNYAAS 600
    IYNLSKKHDQ QLTDHGVSFD SLFSAVKNFS EAASDFHKRL IQVDLNNPIA 650
    VRMMNDQLML LERAFIDPLG LPGKLFYRHI IFAPSSHNKY AGESFPGIYD 700
    AIFDIENKAN SRLAWKEVKK HISIAAFTIQ AAAGTLKEVL 740
    Length:740
    Mass (Da):83,592
    Last modified:November 1, 1999 - v1
    Checksum:i040624D691ECF879
    GO
    Isoform 2 (identifier: Q9Y3Q0-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         266-305: EYTFRLDVEE...LRYLGGIAPP → GTSYLLQVAT...KPTLVWPGKK
         306-740: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:305
    Mass (Da):34,354
    Checksum:i31A9AA507C70BB5F
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti101 – 1011V → I.1 Publication
    Corresponds to variant rs11018879 [ dbSNP | Ensembl ].
    VAR_034120
    Natural varianti446 – 4461I → V.
    Corresponds to variant rs10830430 [ dbSNP | Ensembl ].
    VAR_034121

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei266 – 30540EYTFR…GIAPP → GTSYLLQVATTNMLENHFLE SMMLSLILKIKPTLVWPGKK in isoform 2. 1 PublicationVSP_054147Add
    BLAST
    Alternative sequencei306 – 740435Missing in isoform 2. 1 PublicationVSP_054148Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AJ012370 mRNA. Translation: CAB39967.1.
    AK075390 mRNA. Translation: BAG52126.1.
    AP000648 Genomic DNA. No translation available.
    CH471065 Genomic DNA. Translation: EAW66865.1.
    BC096316 mRNA. Translation: AAH96316.1.
    BC096317 mRNA. Translation: AAH96317.1.
    BC096318 mRNA. Translation: AAH96318.1.
    BC099646 mRNA. Translation: AAH99646.1.
    CCDSiCCDS8288.1. [Q9Y3Q0-1]
    RefSeqiNP_005458.1. NM_005467.3. [Q9Y3Q0-1]
    UniGeneiHs.503560.

    Genome annotation databases

    EnsembliENST00000375944; ENSP00000365111; ENSG00000077616. [Q9Y3Q0-2]
    ENST00000534061; ENSP00000432481; ENSG00000077616. [Q9Y3Q0-1]
    GeneIDi10003.
    KEGGihsa:10003.
    UCSCiuc001pdf.4. human. [Q9Y3Q0-1]

    Polymorphism databases

    DMDMi20139300.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AJ012370 mRNA. Translation: CAB39967.1 .
    AK075390 mRNA. Translation: BAG52126.1 .
    AP000648 Genomic DNA. No translation available.
    CH471065 Genomic DNA. Translation: EAW66865.1 .
    BC096316 mRNA. Translation: AAH96316.1 .
    BC096317 mRNA. Translation: AAH96317.1 .
    BC096318 mRNA. Translation: AAH96318.1 .
    BC099646 mRNA. Translation: AAH99646.1 .
    CCDSi CCDS8288.1. [Q9Y3Q0-1 ]
    RefSeqi NP_005458.1. NM_005467.3. [Q9Y3Q0-1 ]
    UniGenei Hs.503560.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    3FEC X-ray 1.49 A 36-740 [» ]
    3FED X-ray 1.29 A 36-740 [» ]
    3FEE X-ray 1.56 A 36-740 [» ]
    3FF3 X-ray 1.37 A 36-740 [» ]
    ProteinModelPortali Q9Y3Q0.
    SMRi Q9Y3Q0. Positions 46-739.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi Q9Y3Q0. 1 interaction.
    MINTi MINT-2823431.

    Chemistry

    BindingDBi Q9Y3Q0.
    ChEMBLi CHEMBL2609.

    Protein family/group databases

    MEROPSi M28.012.

    PTM databases

    PhosphoSitei Q9Y3Q0.

    Polymorphism databases

    DMDMi 20139300.

    Proteomic databases

    MaxQBi Q9Y3Q0.
    PaxDbi Q9Y3Q0.
    PRIDEi Q9Y3Q0.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000375944 ; ENSP00000365111 ; ENSG00000077616 . [Q9Y3Q0-2 ]
    ENST00000534061 ; ENSP00000432481 ; ENSG00000077616 . [Q9Y3Q0-1 ]
    GeneIDi 10003.
    KEGGi hsa:10003.
    UCSCi uc001pdf.4. human. [Q9Y3Q0-1 ]

    Organism-specific databases

    CTDi 10003.
    GeneCardsi GC11P089867.
    HGNCi HGNC:14526. NAALAD2.
    HPAi HPA060820.
    MIMi 611636. gene.
    neXtProti NX_Q9Y3Q0.
    PharmGKBi PA31430.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG2234.
    HOGENOMi HOG000211921.
    HOVERGENi HBG051639.
    InParanoidi Q9Y3Q0.
    KOi K01301.
    OMAi YDAIFDI.
    OrthoDBi EOG7QK0BC.
    PhylomeDBi Q9Y3Q0.
    TreeFami TF312981.

    Miscellaneous databases

    EvolutionaryTracei Q9Y3Q0.
    GenomeRNAii 10003.
    NextBioi 37781.
    PROi Q9Y3Q0.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9Y3Q0.
    Bgeei Q9Y3Q0.
    CleanExi HS_NAALAD2.
    Genevestigatori Q9Y3Q0.

    Family and domain databases

    Gene3Di 1.20.930.40. 1 hit.
    InterProi IPR007484. Peptidase_M28.
    IPR003137. Protease-assoc_domain.
    IPR007365. TFR-like_dimer_dom.
    [Graphical view ]
    Pfami PF02225. PA. 1 hit.
    PF04389. Peptidase_M28. 1 hit.
    PF04253. TFR_dimer. 1 hit.
    [Graphical view ]
    SUPFAMi SSF47672. SSF47672. 1 hit.
    ProtoNeti Search...

    Publicationsi

    1. "Isolation and expression of novel human glutamate carboxypeptidases with N-acetylated alpha-linked acidic dipeptidase and dipeptidyl peptidase IV activity."
      Pangalos M.N., Neefs J.-M., Somers M., Verhasselt P., Bekkers M., van der Helm L., Fraiponts E., Ashton D., Gordon R.D.
      J. Biol. Chem. 274:8470-8483(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION.
      Tissue: Lung carcinoma.
    2. "Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries."
      Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J., Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S., Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.
      , Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S., Isogai T.
      DNA Res. 12:117-126(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT ILE-101.
    6. "Structural insight into the evolutionary and pharmacologic homology of glutamate carboxypeptidases II and III."
      Hlouchova K., Barinka C., Konvalinka J., Lubkowski J.
      FEBS J. 276:4448-4462(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.29 ANGSTROMS) OF 36-740 ALONE AND IN COMPLEX WITH GLUTAMATE AND INHIBITORS, SUBUNIT, ZINC-BINDING SITES, GLYCOSYLATION AT ASN-111; ASN-185; ASN-449 AND ASN-628.

    Entry informationi

    Entry nameiNALD2_HUMAN
    AccessioniPrimary (citable) accession number: Q9Y3Q0
    Secondary accession number(s): B3KQR4, Q4KKV4, Q4VAM9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 11, 2002
    Last sequence update: November 1, 1999
    Last modified: October 1, 2014
    This is version 119 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Multifunctional enzyme, Reference proteome

    Documents

    1. Human chromosome 11
      Human chromosome 11: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. Peptidase families
      Classification of peptidase families and list of entries
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3