N-acetylated-alpha-linked acidic dipeptidase 2

Preferred order of sections

Names and origin

Protein names

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 names

Name:

NAALAD2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	740 AA.
Sequence status	Complete.
Protein existence	Evidence 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.5
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.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Signal-anchor Transmembrane Transmembrane helix
Ligand	Metal-binding Zinc
Molecular function	Carboxypeptidase Dipeptidase Hydrolase Metalloprotease Protease
PTM	Glycoprotein
Technical term	3D-structure Complete proteome Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological_process	neurotransmitter catabolic process Inferred from electronic annotation. Source: Compara proteolysis Non-traceable author statement Ref.1. Source: UniProtKB
Cellular_component	integral to membrane Non-traceable author statement Ref.1. Source: UniProtKB
Molecular_function	N-formylglutamate deformylase activity Inferred from electronic annotation. Source: Compara carboxypeptidase activity Non-traceable author statement Ref.1. Source: UniProtKB dipeptidase activity Non-traceable author statement Ref.1. Source: UniProtKB dipeptidyl-peptidase activity Non-traceable author statement Ref.1. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW metallopeptidase activity Inferred from electronic annotation. Source: UniProtKB-KW serine-type peptidase activity Non-traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 740

740

N-acetylated-alpha-linked acidic dipeptidase 2

PRO_0000174121

Regions

Topological domain

1 – 7

7

Cytoplasmic Potential

Transmembrane

8 – 31

24

Helical; Signal-anchor for type II membrane protein; Potential

Topological domain

32 – 740

709

Extracellular Potential

Region

264 – 577

314

NAALADase

Sites

Active site

414

1

Nucleophile; for NAALADase activity By similarity

Active site

618

1

Charge relay system Potential

Active site

656

1

Charge relay system Potential

Active site

679

1

Charge relay system Potential

Metal binding

367

1

Zinc 2; catalytic

Metal binding

377

1

Zinc 1

Metal binding

377

1

Zinc 2; catalytic

Metal binding

415

1

Zinc 1

Metal binding

443

1

Zinc 2; catalytic

Metal binding

543

1

Zinc 1

Amino acid modifications

Glycosylation

111

1

N-linked (GlcNAc...) Ref.5

Glycosylation

143

1

N-linked (GlcNAc...) Potential

Glycosylation

185

1

N-linked (GlcNAc...) Ref.5

Glycosylation

314

1

N-linked (GlcNAc...) Potential

Glycosylation

449

1

N-linked (GlcNAc...) Ref.5

Glycosylation

603

1

N-linked (GlcNAc...) Potential

Glycosylation

628

1

N-linked (GlcNAc...) Ref.5

Natural variations

Natural variant

101

1

V → I. Ref.4
Corresponds to variant rs11018879 [ dbSNP | Ensembl ].

VAR_034120

Natural variant

446

1

I → V.
Corresponds to variant rs10830430 [ dbSNP | Ensembl ].

VAR_034121

Secondary structure

1

.

740

Helix Strand Turn

Details...

Sequences

Sequence

Length

Mass (Da)

Tools

Q9Y3Q0 [UniParc].

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

FASTA

740

83,592

        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

References

	« Hide 'large scale' referencesShow '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], 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. Isogai T. DNA Res. 12:117-126(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	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. Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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], VARIANT ILE-101.
[5]	"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.
CH471065 Genomic DNA. Translation: EAW66865.1.
BC096316 mRNA. Translation: AAH96316.1.
BC096317 mRNA. Translation: AAH96317.1.
BC096318 mRNA. Translation: AAH96318.1.

IPI

IPI00023151.

RefSeq

NP_005458.1. NM_005467.3.

UniGene

Hs.503560.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]

ProteinModelPortal

Q9Y3Q0.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9Y3Q0. 1 interaction.

Protein family/group databases

MEROPS

M28.012.

PTM databases

PhosphoSite

Q9Y3Q0.

Polymorphism databases

DMDM

20139300.

Proteomic databases

PaxDb

Q9Y3Q0.

PRIDE

Q9Y3Q0.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000534061; ENSP00000432481; ENSG00000077616.

GeneID

10003.

KEGG

hsa:10003.

UCSC

uc001pdf.4. human.

Organism-specific databases

CTD

10003.

GeneCards

GC11P089867.

HGNC

HGNC:14526. NAALAD2.

MIM

611636. gene.

neXtProt

NX_Q9Y3Q0.

PharmGKB

PA31430.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG2234.

HOGENOM

HOG000211921.

HOVERGEN

HBG051639.

InParanoid

Q9Y3Q0.

KO

K01301.

OMA

MHVHNIN.

OrthoDB

EOG48GW2N.

PhylomeDB

Q9Y3Q0.

Gene expression databases

ArrayExpress

Q9Y3Q0.

Bgee

Q9Y3Q0.

CleanEx

HS_NAALAD2.

Genevestigator

Q9Y3Q0.

GermOnline

ENSG00000077616. Homo sapiens.

Family and domain databases

Gene3D

1.20.930.40. 1 hit.

InterPro

IPR007484. Peptidase_M28.
IPR003137. Protease-assoc_domain.
IPR007365. TFR-like_dimer_dom.
[Graphical view]

Pfam

PF02225. PA. 1 hit.
PF04389. Peptidase_M28. 1 hit.
PF04253. TFR_dimer. 1 hit.
[Graphical view]

SUPFAM

SSF47672. Transferrin_rcpt-like_dimerise. 1 hit.

ProtoNet

Search...

Other

BindingDB

Q9Y3Q0.

ChEMBL

CHEMBL2609.

EvolutionaryTrace

Q9Y3Q0.

GenomeRNAi

10003.

NextBio

37781.

SOURCE

Search...

Entry information

Entry name

NALD2_HUMAN

Accession

Primary (citable) accession number: Q9Y3Q0
Secondary accession number(s): B3KQR4, Q4VAM9

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 11, 2002
Last sequence update:	November 1, 1999
Last modified:	May 1, 2013
This is version 106 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.