Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q9Y3Q0 (NALD2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 114. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:NAALAD2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length740 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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

Catalytic activity

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

Cofactor

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

Enzyme regulation

Inhibited by quisqualate.

Subunit structure

Homodimer. Ref.6

Subcellular location

Membrane; Single-pass type II membrane protein Potential.

Tissue specificity

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.

Domain

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

Sequence similarities

Belongs to the peptidase M28 family. M28B subfamily.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9Y3Q0-1)

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.
Isoform 2 (identifier: Q9Y3Q0-2)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 740740N-acetylated-alpha-linked acidic dipeptidase 2
PRO_0000174121

Regions

Topological domain1 – 77Cytoplasmic Potential
Transmembrane8 – 3124Helical; Signal-anchor for type II membrane protein; Potential
Topological domain32 – 740709Extracellular Potential
Region264 – 577314NAALADase

Sites

Active site4141Nucleophile; for NAALADase activity By similarity
Active site6181Charge relay system Potential
Active site6561Charge relay system Potential
Active site6791Charge relay system Potential
Metal binding3671Zinc 2; catalytic
Metal binding3771Zinc 1
Metal binding3771Zinc 2; catalytic
Metal binding4151Zinc 1
Metal binding4431Zinc 2; catalytic
Metal binding5431Zinc 1

Amino acid modifications

Glycosylation1111N-linked (GlcNAc...) Ref.6
Glycosylation1431N-linked (GlcNAc...) Potential
Glycosylation1851N-linked (GlcNAc...) Ref.6
Glycosylation3141N-linked (GlcNAc...) Potential
Glycosylation4491N-linked (GlcNAc...) Ref.6
Glycosylation6031N-linked (GlcNAc...) Potential
Glycosylation6281N-linked (GlcNAc...) Ref.6

Natural variations

Alternative sequence266 – 30540EYTFR…GIAPP → GTSYLLQVATTNMLENHFLE SMMLSLILKIKPTLVWPGKK in isoform 2.
VSP_054147
Alternative sequence306 – 740435Missing in isoform 2.
VSP_054148
Natural variant1011V → I. Ref.5
Corresponds to variant rs11018879 [ dbSNP | Ensembl ].
VAR_034120
Natural variant4461I → V.
Corresponds to variant rs10830430 [ dbSNP | Ensembl ].
VAR_034121

Secondary structure

........................................................................................................ 740
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1999. Version 1.
Checksum: 040624D691ECF879

FASTA74083,592
        10         20         30         40         50         60 
MAESRGRLYL WMCLAAALAS FLMGFMVGWF IKPLKETTTS VRYHQSIRWK LVSEMKAENI 

        70         80         90        100        110        120 
KSFLRSFTKL PHLAGTEQNF LLAKKIQTQW KKFGLDSAKL VHYDVLLSYP NETNANYISI 

       130        140        150        160        170        180 
VDEHETEIFK TSYLEPPPDG YENVTNIVPP YNAFSAQGMP EGDLVYVNYA RTEDFFKLER 

       190        200        210        220        230        240 
EMGINCTGKI VIARYGKIFR GNKVKNAMLA GAIGIILYSD PADYFAPEVQ PYPKGWNLPG 

       250        260        270        280        290        300 
TAAQRGNVLN LNGAGDPLTP GYPAKEYTFR LDVEEGVGIP RIPVHPIGYN DAEILLRYLG 

       310        320        330        340        350        360 
GIAPPDKSWK GALNVSYSIG PGFTGSDSFR KVRMHVYNIN KITRIYNVVG TIRGSVEPDR 

       370        380        390        400        410        420 
YVILGGHRDS WVFGAIDPTS GVAVLQEIAR SFGKLMSKGW RPRRTIIFAS WDAEEFGLLG 

       430        440        450        460        470        480 
STEWAEENVK ILQERSIAYI NSDSSIEGNY TLRVDCTPLL YQLVYKLTKE IPSPDDGFES 

       490        500        510        520        530        540 
KSLYESWLEK DPSPENKNLP RINKLGSGSD FEAYFQRLGI ASGRARYTKN KKTDKYSSYP 

       550        560        570        580        590        600 
VYHTIYETFE LVEKFYDPTF KKQLSVAQLR GALVYELVDS KIIPFNIQDY AEALKNYAAS 

       610        620        630        640        650        660 
IYNLSKKHDQ QLTDHGVSFD SLFSAVKNFS EAASDFHKRL IQVDLNNPIA VRMMNDQLML 

       670        680        690        700        710        720 
LERAFIDPLG LPGKLFYRHI IFAPSSHNKY AGESFPGIYD AIFDIENKAN SRLAWKEVKK 

       730        740 
HISIAAFTIQ AAAGTLKEVL 

« Hide

Isoform 2 [UniParc].

Checksum: 31A9AA507C70BB5F
Show »

FASTA30534,354

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_005458.1. NM_005467.3.
UniGeneHs.503560.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3FECX-ray1.49A36-740[»]
3FEDX-ray1.29A36-740[»]
3FEEX-ray1.56A36-740[»]
3FF3X-ray1.37A36-740[»]
ProteinModelPortalQ9Y3Q0.
SMRQ9Y3Q0. Positions 46-739.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ9Y3Q0. 1 interaction.
MINTMINT-2823431.

Chemistry

BindingDBQ9Y3Q0.
ChEMBLCHEMBL2609.

Protein family/group databases

MEROPSM28.012.

PTM databases

PhosphoSiteQ9Y3Q0.

Polymorphism databases

DMDM20139300.

Proteomic databases

PaxDbQ9Y3Q0.
PRIDEQ9Y3Q0.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000375944; ENSP00000365111; ENSG00000077616.
ENST00000534061; ENSP00000432481; ENSG00000077616.
GeneID10003.
KEGGhsa:10003.
UCSCuc001pdf.4. human.

Organism-specific databases

CTD10003.
GeneCardsGC11P089867.
HGNCHGNC:14526. NAALAD2.
HPAHPA060820.
MIM611636. gene.
neXtProtNX_Q9Y3Q0.
PharmGKBPA31430.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2234.
HOGENOMHOG000211921.
HOVERGENHBG051639.
InParanoidQ9Y3Q0.
KOK01301.
OMAYDAIFDI.
OrthoDBEOG7QK0BC.
PhylomeDBQ9Y3Q0.
TreeFamTF312981.

Gene expression databases

ArrayExpressQ9Y3Q0.
BgeeQ9Y3Q0.
CleanExHS_NAALAD2.
GenevestigatorQ9Y3Q0.

Family and domain databases

Gene3D1.20.930.40. 1 hit.
InterProIPR007484. Peptidase_M28.
IPR003137. Protease-assoc_domain.
IPR007365. TFR-like_dimer_dom.
[Graphical view]
PfamPF02225. PA. 1 hit.
PF04389. Peptidase_M28. 1 hit.
PF04253. TFR_dimer. 1 hit.
[Graphical view]
SUPFAMSSF47672. SSF47672. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceQ9Y3Q0.
GenomeRNAi10003.
NextBio37781.
PROQ9Y3Q0.
SOURCESearch...

Entry information

Entry nameNALD2_HUMAN
AccessionPrimary (citable) accession number: Q9Y3Q0
Secondary accession number(s): B3KQR4, Q4KKV4, Q4VAM9
Entry history
Integrated into UniProtKB/Swiss-Prot: February 11, 2002
Last sequence update: November 1, 1999
Last modified: April 16, 2014
This is version 114 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM