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Q9Y3Q0

- NALD2_HUMAN

UniProt

Q9Y3Q0 - NALD2_HUMAN

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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

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
Complete GO annotation...

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
Complete GO annotation...

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

BgeeiQ9Y3Q0.
CleanExiHS_NAALAD2.
ExpressionAtlasiQ9Y3Q0. baseline and differential.
GenevestigatoriQ9Y3Q0.

Organism-specific databases

HPAiHPA060820.

Interactioni

Subunit structurei

Homodimer.1 Publication

Protein-protein interaction databases

BioGridi115321. 1 interaction.
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.
GeneTreeiENSGT00550000074421.
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

        10         20         30         40         50
MAESRGRLYL WMCLAAALAS FLMGFMVGWF IKPLKETTTS VRYHQSIRWK
60 70 80 90 100
LVSEMKAENI KSFLRSFTKL PHLAGTEQNF LLAKKIQTQW KKFGLDSAKL
110 120 130 140 150
VHYDVLLSYP NETNANYISI VDEHETEIFK TSYLEPPPDG YENVTNIVPP
160 170 180 190 200
YNAFSAQGMP EGDLVYVNYA RTEDFFKLER EMGINCTGKI VIARYGKIFR
210 220 230 240 250
GNKVKNAMLA GAIGIILYSD PADYFAPEVQ PYPKGWNLPG TAAQRGNVLN
260 270 280 290 300
LNGAGDPLTP GYPAKEYTFR LDVEEGVGIP RIPVHPIGYN DAEILLRYLG
310 320 330 340 350
GIAPPDKSWK GALNVSYSIG PGFTGSDSFR KVRMHVYNIN KITRIYNVVG
360 370 380 390 400
TIRGSVEPDR YVILGGHRDS WVFGAIDPTS GVAVLQEIAR SFGKLMSKGW
410 420 430 440 450
RPRRTIIFAS WDAEEFGLLG STEWAEENVK ILQERSIAYI NSDSSIEGNY
460 470 480 490 500
TLRVDCTPLL YQLVYKLTKE IPSPDDGFES KSLYESWLEK DPSPENKNLP
510 520 530 540 550
RINKLGSGSD FEAYFQRLGI ASGRARYTKN KKTDKYSSYP VYHTIYETFE
560 570 580 590 600
LVEKFYDPTF KKQLSVAQLR GALVYELVDS KIIPFNIQDY AEALKNYAAS
610 620 630 640 650
IYNLSKKHDQ QLTDHGVSFD SLFSAVKNFS EAASDFHKRL IQVDLNNPIA
660 670 680 690 700
VRMMNDQLML LERAFIDPLG LPGKLFYRHI IFAPSSHNKY AGESFPGIYD
710 720 730 740
AIFDIENKAN SRLAWKEVKK HISIAAFTIQ AAAGTLKEVL
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]
uc009yvy.3. human.

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

BioGridi 115321. 1 interaction.
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 ]
uc009yvy.3. human.

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.
GeneTreei ENSGT00550000074421.
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

Bgeei Q9Y3Q0.
CleanExi HS_NAALAD2.
ExpressionAtlasi Q9Y3Q0. baseline and differential.
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

« Hide 'large scale' publications
  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 29, 2014
This is version 120 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