UniProtKB - Q9Y3Q0 (NALD2_HUMAN)
Protein
N-acetylated-alpha-linked acidic dipeptidase 2
Gene
NAALAD2
Organism
Homo sapiens (Human)
Status
Functioni
Has N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Also exhibits a dipeptidyl-peptidase IV type activity. Inactivates 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. EC:3.4.17.21
Cofactori
Zn2+1 PublicationNote: Binds 2 Zn2+ ions per subunit. Required for NAALADase activity.1 Publication
Activity regulationi
Inhibited by quisqualate.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 200 | SubstrateCombined sources1 Publication | 1 | |
Binding sitei | 247 | SubstrateCombined sources1 Publication | 1 | |
Metal bindingi | 259 | CalciumCombined sources1 Publication | 1 | |
Metal bindingi | 262 | Calcium; via carbonyl oxygenCombined sources1 Publication | 1 | |
Metal bindingi | 367 | Zinc 1; via tele nitrogen; catalyticCombined sources1 Publication | 1 | |
Metal bindingi | 377 | Zinc 1; catalyticCombined sources1 Publication | 1 | |
Metal bindingi | 377 | Zinc 2Combined sources1 Publication | 1 | |
Active sitei | 414 | Nucleophile; for NAALADase activityBy similarity | 1 | |
Binding sitei | 414 | SubstrateCombined sources1 Publication | 1 | |
Metal bindingi | 415 | Zinc 2Combined sources1 Publication | 1 | |
Metal bindingi | 423 | CalciumCombined sources1 Publication | 1 | |
Metal bindingi | 426 | CalciumCombined sources1 Publication | 1 | |
Metal bindingi | 443 | Zinc 1; catalyticCombined sources1 Publication | 1 | |
Binding sitei | 542 | SubstrateBy similarity | 1 | |
Metal bindingi | 543 | Zinc 2; via tele nitrogenCombined sources1 Publication | 1 | |
Active sitei | 618 | Charge relay systemSequence analysis | 1 | |
Active sitei | 656 | Charge relay systemSequence analysis | 1 | |
Active sitei | 679 | Charge relay systemSequence analysis | 1 |
GO - Molecular functioni
- carboxypeptidase activity Source: GO_Central
- dipeptidase activity Source: UniProtKB
- dipeptidyl-peptidase activity Source: UniProtKB
- metal ion binding Source: UniProtKB-KW
- metallocarboxypeptidase activity Source: UniProtKB-EC
- 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
Keywordsi
Molecular function | Carboxypeptidase, Dipeptidase, Hydrolase, Metalloprotease, Multifunctional enzyme, Protease |
Ligand | Calcium, Metal-binding, Zinc |
Enzyme and pathway databases
PathwayCommonsi | Q9Y3Q0 |
Reactomei | R-HSA-8963693, Aspartate and asparagine metabolism |
Protein family/group databases
MEROPSi | M28.012 |
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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000077616.10 |
HGNCi | HGNC:14526, NAALAD2 |
MIMi | 611636, gene |
neXtProti | NX_Q9Y3Q0 |
Subcellular locationi
Plasma membrane
- Cell membrane By similarity; Single-pass type II membrane protein By similarity
Plasma Membrane
- plasma membrane Source: Reactome
Other locations
- integral component of membrane Source: UniProtKB
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 7 | CytoplasmicSequence analysis | 7 | |
Transmembranei | 8 – 31 | Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST | 24 | |
Topological domaini | 32 – 740 | ExtracellularSequence analysisAdd BLAST | 709 |
Keywords - Cellular componenti
Cell membrane, MembranePathology & Biotechi
Organism-specific databases
DisGeNETi | 10003 |
OpenTargetsi | ENSG00000077616 |
PharmGKBi | PA31430 |
Miscellaneous databases
Pharosi | Q9Y3Q0, Tchem |
Chemistry databases
ChEMBLi | CHEMBL2609 |
Polymorphism and mutation databases
BioMutai | NAALAD2 |
DMDMi | 20139300 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000174121 | 1 – 740 | N-acetylated-alpha-linked acidic dipeptidase 2Add BLAST | 740 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 111 | N-linked (GlcNAc...) asparagineCombined sources1 Publication | 1 | |
Glycosylationi | 143 | N-linked (GlcNAc...) asparagineBy similarity | 1 | |
Glycosylationi | 185 | N-linked (GlcNAc...) asparagineCombined sources1 Publication | 1 | |
Glycosylationi | 314 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 449 | N-linked (GlcNAc...) asparagineCombined sources1 Publication | 1 | |
Glycosylationi | 603 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 628 | N-linked (GlcNAc...) asparagineCombined sources1 Publication | 1 |
Keywords - PTMi
GlycoproteinProteomic databases
EPDi | Q9Y3Q0 |
jPOSTi | Q9Y3Q0 |
MassIVEi | Q9Y3Q0 |
PaxDbi | Q9Y3Q0 |
PeptideAtlasi | Q9Y3Q0 |
PRIDEi | Q9Y3Q0 |
ProteomicsDBi | 62191 86058 [Q9Y3Q0-1] |
PTM databases
GlyGeni | Q9Y3Q0, 7 sites |
iPTMneti | Q9Y3Q0 |
PhosphoSitePlusi | Q9Y3Q0 |
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
Bgeei | ENSG00000077616, Expressed in pituitary gland and 185 other tissues |
ExpressionAtlasi | Q9Y3Q0, baseline and differential |
Genevisiblei | Q9Y3Q0, HS |
Organism-specific databases
HPAi | ENSG00000077616, Tissue enhanced (pituitary) |
Interactioni
Subunit structurei
Homodimer.
1 PublicationBinary interactionsi
Hide detailsQ9Y3Q0
With | #Exp. | IntAct |
---|---|---|
CIDEB [Q9UHD4] | 3 | EBI-2863682,EBI-7062247 |
RHBDD2 - isoform 3 [Q6NTF9-3] | 3 | EBI-2863682,EBI-17589229 |
SMIM1 [B2RUZ4] | 3 | EBI-2863682,EBI-12188413 |
Protein-protein interaction databases
BioGRIDi | 115321, 8 interactors |
IntActi | Q9Y3Q0, 8 interactors |
STRINGi | 9606.ENSP00000432481 |
Chemistry databases
BindingDBi | Q9Y3Q0 |
Miscellaneous databases
RNActi | Q9Y3Q0, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q9Y3Q0 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q9Y3Q0 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 264 – 577 | NAALADaseAdd BLAST | 314 | |
Regioni | 507 – 508 | Substrate bindingCombined sources1 Publication | 2 | |
Regioni | 524 – 526 | Substrate bindingBy similarity | 3 | |
Regioni | 542 – 543 | Substrate bindingCombined sources1 Publication | 2 | |
Regioni | 689 – 690 | Substrate bindingCombined sources1 Publication | 2 |
Domaini
The NAALADase activity is found in the central region, the dipeptidyl peptidase IV type activity in the C-terminal.
Sequence similaritiesi
Keywords - Domaini
Signal-anchor, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG2195, Eukaryota |
GeneTreei | ENSGT01010000222351 |
InParanoidi | Q9Y3Q0 |
OMAi | YVAFQDI |
OrthoDBi | 804230at2759 |
PhylomeDBi | Q9Y3Q0 |
TreeFami | TF312981 |
Family and domain databases
Gene3Di | 1.20.930.40, 1 hit |
InterProi | View protein in InterPro IPR003137, PA_domain IPR007484, Peptidase_M28 IPR039373, Peptidase_M28B IPR007365, TFR-like_dimer_dom IPR036757, TFR-like_dimer_dom_sf |
PANTHERi | PTHR10404, PTHR10404, 1 hit |
Pfami | View protein in Pfam PF02225, PA, 1 hit PF04389, Peptidase_M28, 1 hit PF04253, TFR_dimer, 1 hit |
SUPFAMi | SSF47672, SSF47672, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q9Y3Q0-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketJ3KNJ3 | J3KNJ3_HUMAN | N-acetylated-alpha-linked acidic di... | NAALAD2 | 707 | Annotation score: | ||
E9PKX5 | E9PKX5_HUMAN | N-acetylated-alpha-linked acidic di... | NAALAD2 | 372 | Annotation score: | ||
E9PII2 | E9PII2_HUMAN | N-acetylated-alpha-linked acidic di... | NAALAD2 | 88 | Annotation score: | ||
E9PJV2 | E9PJV2_HUMAN | N-acetylated-alpha-linked acidic di... | NAALAD2 | 283 | Annotation score: | ||
E9PJ53 | E9PJ53_HUMAN | N-acetylated-alpha-linked acidic di... | NAALAD2 | 107 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_034120 | 101 | V → I1 PublicationCorresponds to variant dbSNP:rs11018879Ensembl. | 1 | |
Natural variantiVAR_034121 | 446 | I → V. Corresponds to variant dbSNP:rs10830430Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_054147 | 266 – 305 | EYTFR…GIAPP → GTSYLLQVATTNMLENHFLE SMMLSLILKIKPTLVWPGKK in isoform 2. 1 PublicationAdd BLAST | 40 | |
Alternative sequenceiVSP_054148 | 306 – 740 | Missing in isoform 2. 1 PublicationAdd BLAST | 435 |
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 |
CCDSi | CCDS8288.1 [Q9Y3Q0-1] |
RefSeqi | NP_001287859.1, NM_001300930.1 NP_005458.1, NM_005467.3 [Q9Y3Q0-1] |
Genome annotation databases
Ensembli | ENST00000375944; ENSP00000365111; ENSG00000077616 [Q9Y3Q0-2] ENST00000534061; ENSP00000432481; ENSG00000077616 [Q9Y3Q0-1] ENST00000644696; ENSP00000494081; ENSG00000285516 [Q9Y3Q0-2] ENST00000647397; ENSP00000494766; ENSG00000285516 [Q9Y3Q0-1] |
GeneIDi | 10003 |
KEGGi | hsa:10003 |
UCSCi | uc001pdf.5, human [Q9Y3Q0-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
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 |
CCDSi | CCDS8288.1 [Q9Y3Q0-1] |
RefSeqi | NP_001287859.1, NM_001300930.1 NP_005458.1, NM_005467.3 [Q9Y3Q0-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB 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 | [»] | |
SMRi | Q9Y3Q0 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 115321, 8 interactors |
IntActi | Q9Y3Q0, 8 interactors |
STRINGi | 9606.ENSP00000432481 |
Chemistry databases
BindingDBi | Q9Y3Q0 |
ChEMBLi | CHEMBL2609 |
Protein family/group databases
MEROPSi | M28.012 |
PTM databases
GlyGeni | Q9Y3Q0, 7 sites |
iPTMneti | Q9Y3Q0 |
PhosphoSitePlusi | Q9Y3Q0 |
Polymorphism and mutation databases
BioMutai | NAALAD2 |
DMDMi | 20139300 |
Proteomic databases
EPDi | Q9Y3Q0 |
jPOSTi | Q9Y3Q0 |
MassIVEi | Q9Y3Q0 |
PaxDbi | Q9Y3Q0 |
PeptideAtlasi | Q9Y3Q0 |
PRIDEi | Q9Y3Q0 |
ProteomicsDBi | 62191 86058 [Q9Y3Q0-1] |
Protocols and materials databases
Antibodypediai | 67811, 49 antibodies |
Genome annotation databases
Ensembli | ENST00000375944; ENSP00000365111; ENSG00000077616 [Q9Y3Q0-2] ENST00000534061; ENSP00000432481; ENSG00000077616 [Q9Y3Q0-1] ENST00000644696; ENSP00000494081; ENSG00000285516 [Q9Y3Q0-2] ENST00000647397; ENSP00000494766; ENSG00000285516 [Q9Y3Q0-1] |
GeneIDi | 10003 |
KEGGi | hsa:10003 |
UCSCi | uc001pdf.5, human [Q9Y3Q0-1] |
Organism-specific databases
CTDi | 10003 |
DisGeNETi | 10003 |
EuPathDBi | HostDB:ENSG00000077616.10 |
GeneCardsi | NAALAD2 |
HGNCi | HGNC:14526, NAALAD2 |
HPAi | ENSG00000077616, Tissue enhanced (pituitary) |
MIMi | 611636, gene |
neXtProti | NX_Q9Y3Q0 |
OpenTargetsi | ENSG00000077616 |
PharmGKBi | PA31430 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2195, Eukaryota |
GeneTreei | ENSGT01010000222351 |
InParanoidi | Q9Y3Q0 |
OMAi | YVAFQDI |
OrthoDBi | 804230at2759 |
PhylomeDBi | Q9Y3Q0 |
TreeFami | TF312981 |
Enzyme and pathway databases
PathwayCommonsi | Q9Y3Q0 |
Reactomei | R-HSA-8963693, Aspartate and asparagine metabolism |
Miscellaneous databases
BioGRID-ORCSi | 10003, 6 hits in 841 CRISPR screens |
ChiTaRSi | NAALAD2, human |
EvolutionaryTracei | Q9Y3Q0 |
GenomeRNAii | 10003 |
Pharosi | Q9Y3Q0, Tchem |
PROi | PR:Q9Y3Q0 |
RNActi | Q9Y3Q0, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000077616, Expressed in pituitary gland and 185 other tissues |
ExpressionAtlasi | Q9Y3Q0, baseline and differential |
Genevisiblei | Q9Y3Q0, HS |
Family and domain databases
Gene3Di | 1.20.930.40, 1 hit |
InterProi | View protein in InterPro IPR003137, PA_domain IPR007484, Peptidase_M28 IPR039373, Peptidase_M28B IPR007365, TFR-like_dimer_dom IPR036757, TFR-like_dimer_dom_sf |
PANTHERi | PTHR10404, PTHR10404, 1 hit |
Pfami | View protein in Pfam PF02225, PA, 1 hit PF04389, Peptidase_M28, 1 hit PF04253, TFR_dimer, 1 hit |
SUPFAMi | SSF47672, SSF47672, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | NALD2_HUMAN | |
Accessioni | Q9Y3Q0Primary (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: | December 2, 2020 | |
This is version 163 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human chromosome 11
Human chromosome 11: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations - Peptidase families
Classification of peptidase families and list of entries