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Q9UQQ1

- NALDL_HUMAN

UniProt

Q9UQQ1 - NALDL_HUMAN

Protein

N-acetylated-alpha-linked acidic dipeptidase-like protein

Gene

NAALADL1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 124 (01 Oct 2014)
      Sequence version 2 (30 Nov 2010)
      Previous versions | rss
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    Functioni

    NAALADase-like activity unknown. Has no NAAG hydrolyzing activity. Exhibits a dipeptidyl-peptidase IV type activity. In vitro, cleaves Gly-Pro-AMC By similarity.By similarity

    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.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi368 – 3681Zinc 1By similarity
    Metal bindingi378 – 3781Zinc 1By similarity
    Metal bindingi378 – 3781Zinc 2By similarity
    Active sitei416 – 4161Nucleophile; for NAALADase activityBy similarity
    Metal bindingi417 – 4171Zinc 2By similarity
    Metal bindingi445 – 4451Zinc 1By similarity
    Metal bindingi545 – 5451Zinc 2By similarity
    Active sitei617 – 6171Charge relay systemSequence Analysis
    Active sitei657 – 6571Charge relay systemSequence Analysis
    Active sitei680 – 6801Charge relay systemSequence Analysis

    GO - Molecular functioni

    1. carboxypeptidase activity Source: UniProtKB-KW
    2. dipeptidase activity Source: UniProtKB-KW
    3. metal ion binding Source: UniProtKB-KW
    4. metallopeptidase activity Source: UniProtKB-KW
    5. peptidase activity Source: UniProtKB

    Keywords - Molecular functioni

    Carboxypeptidase, Dipeptidase, Hydrolase, Metalloprotease, Protease

    Keywords - Ligandi

    Metal-binding, Zinc

    Protein family/group databases

    MEROPSiM28.011.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    N-acetylated-alpha-linked acidic dipeptidase-like protein (EC:3.4.17.21)
    Short name:
    NAALADase L
    Alternative name(s):
    100 kDa ileum brush border membrane protein
    Short name:
    I100
    Ileal dipeptidylpeptidase
    Gene namesi
    Name:NAALADL1
    Synonyms:NAALADASEL, NAALADL
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 11

    Organism-specific databases

    HGNCiHGNC:23536. NAALADL1.

    Subcellular locationi

    GO - Cellular componenti

    1. apical plasma membrane Source: UniProtKB-SubCell
    2. integral component of membrane Source: UniProtKB

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA134867982.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 740740N-acetylated-alpha-linked acidic dipeptidase-like proteinPRO_0000174123Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi136 – 1361N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi274 – 2741N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi299 – 2991N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi334 – 3341N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi345 – 3451N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi451 – 4511N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi492 – 4921N-linked (GlcNAc...)Sequence Analysis

    Keywords - PTMi

    Glycoprotein

    Proteomic databases

    PaxDbiQ9UQQ1.
    PRIDEiQ9UQQ1.

    PTM databases

    PhosphoSiteiQ9UQQ1.

    Expressioni

    Tissue specificityi

    Mainly expressed in the distal small intestine. Also expressed in the spleen and testis. Weak expression in the brain, locating mainly to the brain stem, amygdala, thalamus and ventral striatum. Isoform 2 and 3 isoform 3 are found in the small intestine and colon.

    Gene expression databases

    ArrayExpressiQ9UQQ1.
    BgeeiQ9UQQ1.
    CleanExiHS_NAALADL1.
    GenevestigatoriQ9UQQ1.

    Organism-specific databases

    HPAiHPA047123.

    Interactioni

    Protein-protein interaction databases

    STRINGi9606.ENSP00000351484.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9UQQ1.
    SMRiQ9UQQ1. Positions 48-737.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 66CytoplasmicSequence Analysis
    Topological domaini29 – 740712ExtracellularSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei7 – 2822Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni263 – 579317NAALADaseAdd
    BLAST

    Sequence similaritiesi

    Belongs to the peptidase M28 family. M28B subfamily.Curated

    Keywords - Domaini

    Signal-anchor, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG2234.
    HOGENOMiHOG000211921.
    HOVERGENiHBG051639.
    KOiK01301.
    OMAiFLGITSM.
    OrthoDBiEOG7QK0BC.
    PhylomeDBiQ9UQQ1.
    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 (8)i

    Sequence statusi: Complete.

    This entry describes 8 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q9UQQ1-1) [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

    MQWTKVLGLG LGAAALLGLG IILGHFAIPK KANSLAPQDL DLEILETVMG    50
    QLDAHRIREN LRELSREPHL ASSPRDEDLV QLLLQRWKDP ESGLDSAEAS 100
    TYEVLLSFPS QEQPNVVDIV GPTGGIIHSC HRTEENVTGE QGGPDVVQPY 150
    AAYAPSGTPQ GLLVYANRGA EEDFKELQTQ GIKLEGTIAL TRYGGVGRGA 200
    KAVNAAKHGV AGVLVYTDPA DINDGLSSPD ETFPNSWYLP PSGVERGSYY 250
    EYFGDPLTPY LPAVPSSFRV DLANVSGFPP IPTQPIGFQD ARDLLCNLNG 300
    TLAPATWQGA LGCHYRLGPG FRPDGDFPAD SQVNVSVYNR LELRNSSNVL 350
    GIIRGAVEPD RYVLYGNHRD SWVHGAVDPS SGTAVLLELS RVLGTLLKKG 400
    TWRPRRSIVF ASWGAEEFGL IGSTEFTEEF FNKLQERTVA YINVDISVFA 450
    NATLRVQGTP PVQSVVFSAT KEIRSPGPGD LSIYDNWIRY FNRSSPVYGL 500
    VPSLGSLGAG SDYAPFVHFL GISSMDIAYT YDRSKTSARI YPTYHTAFDT 550
    FDYVDKFLDP GFSSHQAVAR TAGSVILRLS DSFFLPLKVS DYSETLRSFL 600
    QAAQQDLGAL LEQHSISLGP LVTAVEKFEA EAAALGQRIS TLQKGSPDPL 650
    QVRMLNDQLM LLERTFLNPR AFPEERYYSH VLWAPRTGSV VTFPGLSNAC 700
    SRARDTASGS EAWAEVQRQL SIVVTALEGA AATLRPVADL 740
    Length:740
    Mass (Da):80,558
    Last modified:November 30, 2010 - v2
    Checksum:i018D59835F2C48AC
    GO
    Isoform 2 (identifier: Q9UQQ1-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         161-201: Missing.

    Show »
    Length:699
    Mass (Da):76,195
    Checksum:iBDF2C67F921ED4CA
    GO
    Isoform 3 (identifier: Q9UQQ1-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         296-330: Missing.

    Show »
    Length:705
    Mass (Da):76,887
    Checksum:iB043A0DBBDEBFB8D
    GO
    Isoform 4 (identifier: Q9UQQ1-4) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         359-359: P → PGEPSSCCLHPRPLLCSGCRCPHPALPLPPPSPAPPAHLSLSSGSLPLFLWP

    Show »
    Length:791
    Mass (Da):85,832
    Checksum:i8872DB91F3669FD7
    GO
    Isoform 5 (identifier: Q9UQQ1-5) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         502-522: PSLGSLGAGSDYAPFVHFLGI → PRLQQPSGCGPDSGECDSPAQ
         523-740: Missing.

    Show »
    Length:522
    Mass (Da):56,573
    Checksum:iD9C30160F01AC93B
    GO
    Isoform 6 (identifier: Q9UQQ1-6) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         502-543: PSLGSLGAGS...SKTSARIYPT → PRARLQPGSP...IRLWPGQRGV
         544-740: Missing.

    Show »
    Length:543
    Mass (Da):59,132
    Checksum:i3DEF010A089357C9
    GO
    Isoform 7 (identifier: Q9UQQ1-7) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         562-579: FSSHQAVARTAGSVILRL → FEEGDKGHPETRTGEAED
         580-740: Missing.

    Show »
    Length:579
    Mass (Da):63,077
    Checksum:i62FAEF2C2C593E0F
    GO
    Isoform 8 (identifier: Q9UQQ1-8) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         619-635: GPLVTAVEKFEAEAAAL → GMHSPDPEVWGALHPHD
         636-740: Missing.

    Show »
    Length:635
    Mass (Da):69,188
    Checksum:i1388AE658E962A2C
    GO

    Sequence cautioni

    The sequence AAB87645.1 differs from that shown. Reason: Frameshift at positions 686 and 693.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti420 – 4245LIGST → SPGLQ in AAB87645. (PubMed:9388249)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti2 – 21Q → H.
    Corresponds to variant rs35422506 [ dbSNP | Ensembl ].
    VAR_057155
    Natural varianti398 – 3981K → T.
    Corresponds to variant rs12223986 [ dbSNP | Ensembl ].
    VAR_057156
    Natural varianti611 – 6111L → V.
    Corresponds to variant rs36053340 [ dbSNP | Ensembl ].
    VAR_057157

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei161 – 20141Missing in isoform 2. 1 PublicationVSP_005343Add
    BLAST
    Alternative sequencei296 – 33035Missing in isoform 3. 1 PublicationVSP_005344Add
    BLAST
    Alternative sequencei359 – 3591P → PGEPSSCCLHPRPLLCSGCR CPHPALPLPPPSPAPPAHLS LSSGSLPLFLWP in isoform 4. 1 PublicationVSP_005345
    Alternative sequencei502 – 54342PSLGS…RIYPT → PRARLQPGSPPTTQPLTPLT MWTSFWTRASAAIRLWPGQR GV in isoform 6. 1 PublicationVSP_005348Add
    BLAST
    Alternative sequencei502 – 52221PSLGS…HFLGI → PRLQQPSGCGPDSGECDSPA Q in isoform 5. 1 PublicationVSP_005346Add
    BLAST
    Alternative sequencei523 – 740218Missing in isoform 5. 1 PublicationVSP_005347Add
    BLAST
    Alternative sequencei544 – 740197Missing in isoform 6. 1 PublicationVSP_005349Add
    BLAST
    Alternative sequencei562 – 57918FSSHQ…VILRL → FEEGDKGHPETRTGEAED in isoform 7. 1 PublicationVSP_005350Add
    BLAST
    Alternative sequencei580 – 740161Missing in isoform 7. 1 PublicationVSP_005351Add
    BLAST
    Alternative sequencei619 – 63517GPLVT…EAAAL → GMHSPDPEVWGALHPHD in isoform 8. 1 PublicationVSP_005352Add
    BLAST
    Alternative sequencei636 – 740105Missing in isoform 8. 1 PublicationVSP_005353Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AJ012371 mRNA. Translation: CAB39968.1.
    AP003068 Genomic DNA. No translation available.
    AF010141 mRNA. Translation: AAB87645.1. Frameshift.
    CCDSiCCDS31604.1. [Q9UQQ1-1]
    RefSeqiNP_005459.2. NM_005468.2. [Q9UQQ1-1]
    UniGeneiHs.13967.

    Genome annotation databases

    EnsembliENST00000340252; ENSP00000344244; ENSG00000168060. [Q9UQQ1-4]
    ENST00000355721; ENSP00000347955; ENSG00000168060. [Q9UQQ1-2]
    ENST00000358658; ENSP00000351484; ENSG00000168060. [Q9UQQ1-1]
    GeneIDi10004.
    KEGGihsa:10004.
    UCSCiuc001ocn.3. human. [Q9UQQ1-1]

    Polymorphism databases

    DMDMi313104139.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AJ012371 mRNA. Translation: CAB39968.1 .
    AP003068 Genomic DNA. No translation available.
    AF010141 mRNA. Translation: AAB87645.1 . Frameshift.
    CCDSi CCDS31604.1. [Q9UQQ1-1 ]
    RefSeqi NP_005459.2. NM_005468.2. [Q9UQQ1-1 ]
    UniGenei Hs.13967.

    3D structure databases

    ProteinModelPortali Q9UQQ1.
    SMRi Q9UQQ1. Positions 48-737.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 9606.ENSP00000351484.

    Protein family/group databases

    MEROPSi M28.011.

    PTM databases

    PhosphoSitei Q9UQQ1.

    Polymorphism databases

    DMDMi 313104139.

    Proteomic databases

    PaxDbi Q9UQQ1.
    PRIDEi Q9UQQ1.

    Protocols and materials databases

    DNASUi 10004.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000340252 ; ENSP00000344244 ; ENSG00000168060 . [Q9UQQ1-4 ]
    ENST00000355721 ; ENSP00000347955 ; ENSG00000168060 . [Q9UQQ1-2 ]
    ENST00000358658 ; ENSP00000351484 ; ENSG00000168060 . [Q9UQQ1-1 ]
    GeneIDi 10004.
    KEGGi hsa:10004.
    UCSCi uc001ocn.3. human. [Q9UQQ1-1 ]

    Organism-specific databases

    CTDi 10004.
    GeneCardsi GC11M064812.
    H-InvDB HIX0035851.
    HGNCi HGNC:23536. NAALADL1.
    HPAi HPA047123.
    MIMi 602640. gene.
    neXtProti NX_Q9UQQ1.
    PharmGKBi PA134867982.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG2234.
    HOGENOMi HOG000211921.
    HOVERGENi HBG051639.
    KOi K01301.
    OMAi FLGITSM.
    OrthoDBi EOG7QK0BC.
    PhylomeDBi Q9UQQ1.
    TreeFami TF312981.

    Miscellaneous databases

    GenomeRNAii 10004.
    NextBioi 37785.
    PROi Q9UQQ1.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9UQQ1.
    Bgeei Q9UQQ1.
    CleanExi HS_NAALADL1.
    Genevestigatori Q9UQQ1.

    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] (ISOFORMS 1; 2; 3; 4; 5; 6; 7 AND 8).
      Tissue: Small intestine.
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 419-740.
      Tissue: Ileum.

    Entry informationi

    Entry nameiNALDL_HUMAN
    AccessioniPrimary (citable) accession number: Q9UQQ1
    Secondary accession number(s): C9J8A1
    , C9J964, C9JL35, C9JSN0, O43176
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 11, 2002
    Last sequence update: November 30, 2010
    Last modified: October 1, 2014
    This is version 124 of the entry and version 2 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

    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. Peptidase families
      Classification of peptidase families and list of entries
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3