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Protein

N-acetylated-alpha-linked acidic dipeptidase 2

Gene

NAALAD2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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

Zn2+1 PublicationNote: Binds 2 Zn2+ ions per subunit. Required for NAALADase activity.1 Publication

Enzyme regulationi

Inhibited by quisqualate.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei200SubstrateCombined sources1 Publication1
Binding sitei247SubstrateCombined sources1 Publication1
Metal bindingi259CalciumCombined sources1 Publication1
Metal bindingi262Calcium; via carbonyl oxygenCombined sources1 Publication1
Metal bindingi367Zinc 1; via tele nitrogen; catalyticCombined sources1 Publication1
Metal bindingi377Zinc 1; catalyticCombined sources1 Publication1
Metal bindingi377Zinc 2Combined sources1 Publication1
Active sitei414Nucleophile; for NAALADase activityBy similarity1
Binding sitei414SubstrateCombined sources1 Publication1
Metal bindingi415Zinc 2Combined sources1 Publication1
Metal bindingi423CalciumCombined sources1 Publication1
Metal bindingi426CalciumCombined sources1 Publication1
Metal bindingi443Zinc 1; catalyticCombined sources1 Publication1
Binding sitei542SubstrateBy similarity1
Metal bindingi543Zinc 2; via tele nitrogenCombined sources1 Publication1
Active sitei618Charge relay systemSequence analysis1
Active sitei656Charge relay systemSequence analysis1
Active sitei679Charge relay systemSequence analysis1

GO - Molecular functioni

  • carboxypeptidase activity Source: UniProtKB
  • dipeptidase activity Source: UniProtKB
  • dipeptidyl-peptidase activity Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • metallopeptidase activity Source: UniProtKB-KW
  • N-formylglutamate deformylase activity Source: Ensembl
  • serine-type peptidase activity Source: UniProtKB

GO - Biological processi

  • cellular amino acid biosynthetic process Source: Reactome
  • neurotransmitter catabolic process Source: Ensembl
  • proteolysis Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Carboxypeptidase, Dipeptidase, Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Calcium, Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:HS01253-MONOMER.
ReactomeiR-HSA-70614. Amino acid synthesis and interconversion (transamination).

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
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:14526. NAALAD2.

Subcellular locationi

  • Cell membrane By similarity; Single-pass type II membrane protein By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 7CytoplasmicSequence analysis7
Transmembranei8 – 31Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST24
Topological domaini32 – 740ExtracellularSequence analysisAdd BLAST709

GO - Cellular componenti

  • integral component of membrane Source: UniProtKB
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi10003.
OpenTargetsiENSG00000077616.
PharmGKBiPA31430.

Chemistry databases

ChEMBLiCHEMBL2609.

Polymorphism and mutation databases

BioMutaiNAALAD2.
DMDMi20139300.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001741211 – 740N-acetylated-alpha-linked acidic dipeptidase 2Add BLAST740

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi111N-linked (GlcNAc...)Combined sources1 Publication1
Glycosylationi143N-linked (GlcNAc...)By similarity1
Glycosylationi185N-linked (GlcNAc...)Combined sources1 Publication1
Glycosylationi314N-linked (GlcNAc...)Sequence analysis1
Glycosylationi449N-linked (GlcNAc...)Combined sources1 Publication1
Glycosylationi603N-linked (GlcNAc...)Sequence analysis1
Glycosylationi628N-linked (GlcNAc...)Combined sources1 Publication1

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiQ9Y3Q0.
PaxDbiQ9Y3Q0.
PeptideAtlasiQ9Y3Q0.
PRIDEiQ9Y3Q0.

PTM databases

iPTMnetiQ9Y3Q0.
PhosphoSitePlusiQ9Y3Q0.

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

BgeeiENSG00000077616.
CleanExiHS_NAALAD2.
ExpressionAtlasiQ9Y3Q0. baseline and differential.
GenevisibleiQ9Y3Q0. HS.

Organism-specific databases

HPAiHPA060820.
HPA065419.

Interactioni

Subunit structurei

Homodimer.1 Publication

Protein-protein interaction databases

BioGridi115321. 4 interactors.
IntActiQ9Y3Q0. 1 interactor.
MINTiMINT-2823431.
STRINGi9606.ENSP00000432481.

Chemistry databases

BindingDBiQ9Y3Q0.

Structurei

Secondary structure

1740
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi47 – 54Combined sources8
Helixi57 – 67Combined sources11
Beta strandi68 – 70Combined sources3
Helixi77 – 93Combined sources17
Beta strandi96 – 109Combined sources14
Beta strandi117 – 121Combined sources5
Beta strandi127 – 130Combined sources4
Beta strandi164 – 166Combined sources3
Helixi172 – 180Combined sources9
Beta strandi190 – 194Combined sources5
Helixi200 – 209Combined sources10
Beta strandi213 – 218Combined sources6
Helixi221 – 224Combined sources4
Turni232 – 234Combined sources3
Beta strandi235 – 237Combined sources3
Helixi273 – 275Combined sources3
Beta strandi284 – 287Combined sources4
Helixi289 – 297Combined sources9
Helixi307 – 309Combined sources3
Beta strandi312 – 315Combined sources4
Beta strandi320 – 323Combined sources4
Beta strandi331 – 336Combined sources6
Beta strandi339 – 352Combined sources14
Beta strandi355 – 367Combined sources13
Beta strandi371 – 373Combined sources3
Turni375 – 378Combined sources4
Helixi379 – 397Combined sources19
Beta strandi403 – 412Combined sources10
Helixi414 – 416Combined sources3
Helixi419 – 435Combined sources17
Beta strandi436 – 441Combined sources6
Beta strandi445 – 447Combined sources3
Beta strandi449 – 456Combined sources8
Helixi458 – 460Combined sources3
Helixi461 – 468Combined sources8
Helixi483 – 490Combined sources8
Beta strandi491 – 493Combined sources3
Beta strandi496 – 500Combined sources5
Beta strandi507 – 509Combined sources3
Helixi512 – 516Combined sources5
Beta strandi522 – 528Combined sources7
Turni531 – 533Combined sources3
Beta strandi536 – 538Combined sources3
Turni540 – 543Combined sources4
Helixi549 – 555Combined sources7
Helixi561 – 579Combined sources19
Helixi587 – 605Combined sources19
Helixi606 – 608Combined sources3
Helixi609 – 615Combined sources7
Helixi620 – 640Combined sources21
Helixi648 – 664Combined sources17
Beta strandi679 – 685Combined sources7
Beta strandi688 – 695Combined sources8
Helixi696 – 702Combined sources7
Helixi705 – 707Combined sources3
Helixi711 – 736Combined sources26

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3FECX-ray1.49A36-740[»]
3FEDX-ray1.29A36-740[»]
3FEEX-ray1.56A36-740[»]
3FF3X-ray1.37A36-740[»]
ProteinModelPortaliQ9Y3Q0.
SMRiQ9Y3Q0.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9Y3Q0.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni264 – 577NAALADaseAdd BLAST314
Regioni507 – 508Substrate bindingCombined sources1 Publication2
Regioni524 – 526Substrate bindingBy similarity3
Regioni542 – 543Substrate bindingCombined sources1 Publication2
Regioni689 – 690Substrate bindingCombined sources1 Publication2

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

eggNOGiKOG2195. Eukaryota.
COG2234. LUCA.
GeneTreeiENSGT00550000074421.
HOGENOMiHOG000134689.
HOVERGENiHBG051639.
InParanoidiQ9Y3Q0.
KOiK01301.
OMAiHINCTGK.
OrthoDBiEOG091G02ZM.
PhylomeDBiQ9Y3Q0.
TreeFamiTF312981.

Family and domain databases

Gene3Di1.20.930.40. 1 hit.
InterProiIPR003137. PA_domain.
IPR007484. Peptidase_M28.
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. AlignAdd to basket

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)DescriptionActionsGraphical viewLength
Natural variantiVAR_034120101V → I.1 PublicationCorresponds to variant rs11018879dbSNPEnsembl.1
Natural variantiVAR_034121446I → V.Corresponds to variant rs10830430dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_054147266 – 305EYTFR…GIAPP → GTSYLLQVATTNMLENHFLE SMMLSLILKIKPTLVWPGKK in isoform 2. 1 PublicationAdd BLAST40
Alternative sequenceiVSP_054148306 – 740Missing in isoform 2. 1 PublicationAdd BLAST435

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_001287859.1. NM_001300930.1.
NP_005458.1. NM_005467.3. [Q9Y3Q0-1]
UniGeneiHs.112482.
Hs.503560.

Genome annotation databases

EnsembliENST00000375944; ENSP00000365111; ENSG00000077616. [Q9Y3Q0-2]
ENST00000534061; ENSP00000432481; ENSG00000077616. [Q9Y3Q0-1]
GeneIDi10003.
KEGGihsa:10003.
UCSCiuc001pdf.5. human. [Q9Y3Q0-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_001287859.1. NM_001300930.1.
NP_005458.1. NM_005467.3. [Q9Y3Q0-1]
UniGeneiHs.112482.
Hs.503560.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3FECX-ray1.49A36-740[»]
3FEDX-ray1.29A36-740[»]
3FEEX-ray1.56A36-740[»]
3FF3X-ray1.37A36-740[»]
ProteinModelPortaliQ9Y3Q0.
SMRiQ9Y3Q0.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115321. 4 interactors.
IntActiQ9Y3Q0. 1 interactor.
MINTiMINT-2823431.
STRINGi9606.ENSP00000432481.

Chemistry databases

BindingDBiQ9Y3Q0.
ChEMBLiCHEMBL2609.

Protein family/group databases

MEROPSiM28.012.

PTM databases

iPTMnetiQ9Y3Q0.
PhosphoSitePlusiQ9Y3Q0.

Polymorphism and mutation databases

BioMutaiNAALAD2.
DMDMi20139300.

Proteomic databases

EPDiQ9Y3Q0.
PaxDbiQ9Y3Q0.
PeptideAtlasiQ9Y3Q0.
PRIDEiQ9Y3Q0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000375944; ENSP00000365111; ENSG00000077616. [Q9Y3Q0-2]
ENST00000534061; ENSP00000432481; ENSG00000077616. [Q9Y3Q0-1]
GeneIDi10003.
KEGGihsa:10003.
UCSCiuc001pdf.5. human. [Q9Y3Q0-1]

Organism-specific databases

CTDi10003.
DisGeNETi10003.
GeneCardsiNAALAD2.
HGNCiHGNC:14526. NAALAD2.
HPAiHPA060820.
HPA065419.
MIMi611636. gene.
neXtProtiNX_Q9Y3Q0.
OpenTargetsiENSG00000077616.
PharmGKBiPA31430.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2195. Eukaryota.
COG2234. LUCA.
GeneTreeiENSGT00550000074421.
HOGENOMiHOG000134689.
HOVERGENiHBG051639.
InParanoidiQ9Y3Q0.
KOiK01301.
OMAiHINCTGK.
OrthoDBiEOG091G02ZM.
PhylomeDBiQ9Y3Q0.
TreeFamiTF312981.

Enzyme and pathway databases

BioCyciZFISH:HS01253-MONOMER.
ReactomeiR-HSA-70614. Amino acid synthesis and interconversion (transamination).

Miscellaneous databases

EvolutionaryTraceiQ9Y3Q0.
GenomeRNAii10003.
PROiQ9Y3Q0.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000077616.
CleanExiHS_NAALAD2.
ExpressionAtlasiQ9Y3Q0. baseline and differential.
GenevisibleiQ9Y3Q0. HS.

Family and domain databases

Gene3Di1.20.930.40. 1 hit.
InterProiIPR003137. PA_domain.
IPR007484. Peptidase_M28.
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.
ProtoNetiSearch...

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: November 2, 2016
This is version 137 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.