Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Glutamate carboxypeptidase 2

Gene

Folh1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Has both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Has a preference for tri-alpha-glutamate peptides (By similarity). In the intestine, required for the uptake of folate. In the brain, modulates excitatory neurotransmission through the hydrolysis of the neuropeptide, N-aceylaspartylglutamate (NAAG), thereby releasing glutamate.By similarity
Also exhibits a dipeptidyl-peptidase IV type activity. In vitro, cleaves Gly-Pro-AMC.By similarity

Catalytic activityi

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

Cofactori

Zn2+Note: Binds 2 Zn2+ ions per subunit. Required for NAALADase activity.

Enzyme regulationi

The NAALADase and folate hydrolase activities are inhibited by quisqualic acid.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei212SubstrateBy similarity1
Binding sitei259SubstrateBy similarity1
Metal bindingi271CalciumBy similarity1
Metal bindingi274Calcium; via carbonyl oxygenBy similarity1
Metal bindingi379Zinc 1; via tele nitrogen; catalyticBy similarity1
Metal bindingi389Zinc 1; catalyticBy similarity1
Metal bindingi389Zinc 2By similarity1
Active sitei426Nucleophile; for NAALADase activityBy similarity1
Binding sitei426SubstrateBy similarity1
Metal bindingi427Zinc 2By similarity1
Metal bindingi435CalciumBy similarity1
Metal bindingi438CalciumBy similarity1
Metal bindingi455Zinc 1; catalyticBy similarity1
Binding sitei521SubstrateBy similarity1
Binding sitei554SubstrateBy similarity1
Metal bindingi555Zinc 2; via tele nitrogenBy similarity1
Active sitei630Charge relay systemSequence analysis1
Active sitei668Charge relay systemSequence analysis1
Active sitei691Charge relay systemSequence analysis1

GO - Molecular functioni

  • Ac-Asp-Glu binding Source: Ensembl
  • carboxypeptidase activity Source: MGI
  • dipeptidase activity Source: MGI
  • metal ion binding Source: UniProtKB-KW
  • metallocarboxypeptidase activity Source: Ensembl
  • peptidase activity Source: MGI
  • tetrahydrofolyl-poly(glutamate) polymer binding Source: Ensembl

GO - Biological processi

  • C-terminal protein deglutamylation Source: Ensembl
  • folic acid-containing compound metabolic process Source: MGI
  • proteolysis Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Carboxypeptidase, Dipeptidase, Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Calcium, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-70614. Amino acid synthesis and interconversion (transamination).

Protein family/group databases

MEROPSiM28.010.

Names & Taxonomyi

Protein namesi
Recommended name:
Glutamate carboxypeptidase 2 (EC:3.4.17.21)
Alternative name(s):
Folate hydrolase 1
Folylpoly-gamma-glutamate carboxypeptidase
Short name:
FGCP
Glutamate carboxypeptidase II
Short name:
GCPII
Membrane glutamate carboxypeptidase
Short name:
mGCP
N-acetylated-alpha-linked acidic dipeptidase I
Short name:
NAALADase I
Prostate-specific membrane antigen homolog
Pteroylpoly-gamma-glutamate carboxypeptidase
Gene namesi
Name:Folh1
Synonyms:Mopsm, Naalad1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:1858193. Folh1.

Subcellular locationi

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

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 22CytoplasmicSequence analysisAdd BLAST22
Transmembranei23 – 44Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST22
Topological domaini45 – 752ExtracellularSequence analysisAdd BLAST708

GO - Cellular componenti

  • cell surface Source: Ensembl
  • extracellular exosome Source: Ensembl
  • integral component of membrane Source: MGI
  • integral component of plasma membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001741181 – 752Glutamate carboxypeptidase 2Add BLAST752

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei10PhosphoserineBy similarity1
Glycosylationi78N-linked (GlcNAc...)By similarity1
Glycosylationi123N-linked (GlcNAc...)By similarity1
Glycosylationi155N-linked (GlcNAc...)By similarity1
Glycosylationi338N-linked (GlcNAc...)By similarity1
Glycosylationi461N-linked (GlcNAc...)By similarity1
Glycosylationi478N-linked (GlcNAc...)By similarity1
Glycosylationi615N-linked (GlcNAc...)Sequence analysis1
Glycosylationi640N-linked (GlcNAc...)By similarity1
Glycosylationi722N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiO35409.
PaxDbiO35409.
PeptideAtlasiO35409.
PRIDEiO35409.

PTM databases

iPTMnetiO35409.
PhosphoSitePlusiO35409.

Expressioni

Tissue specificityi

Expressed predominantly in the hippocampal region of the brain and in kidney. Lower levels in the ovary, testis and mandibular gland.

Gene expression databases

BgeeiENSMUSG00000001773.
CleanExiMM_FOLH1.
ExpressionAtlasiO35409. baseline and differential.
GenevisibleiO35409. MM.

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

IntActiO35409. 1 interactor.
MINTiMINT-4996170.
STRINGi10090.ENSMUSP00000001824.

Structurei

3D structure databases

ProteinModelPortaliO35409.
SMRiO35409.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni276 – 589NAALADaseAdd BLAST314
Regioni519 – 520Substrate bindingBy similarity2
Regioni536 – 538Substrate bindingBy similarity3
Regioni554 – 555Substrate bindingBy similarity2
Regioni701 – 702Substrate bindingBy similarity2

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.
HOGENOMiHOG000211921.
HOVERGENiHBG051639.
InParanoidiO35409.
KOiK14592.
OMAiYPANEHA.
OrthoDBiEOG091G02ZM.
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.

Sequencei

Sequence statusi: Complete.

O35409-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MWNALQDRDS AEVLGHRQRW LRVGTLVLAL TGTFLIGFLF GWFIKPSNEA
60 70 80 90 100
TGNVSHSGMK KEFLHELKAE NIKKFLYNFT RTPHLAGTQN NFELAKQIHD
110 120 130 140 150
QWKEFGLDLV ELSHYDVLLS YPNKTHPNYI SIINEDGNEI FKTSLSEQPP
160 170 180 190 200
PGYENISDVV PPYSAFSPQG TPEGDLVYVN YARTEDFFKL EREMKISCSG
210 220 230 240 250
KIVIARYGKV FRGNMVKNAQ LAGAKGMILY SDPADYFVPA VKSYPDGWNL
260 270 280 290 300
PGGGVQRGNV LNLNGAGDPL TPGYPANEHA YRHELTNAVG LPSIPVHPIG
310 320 330 340 350
YDDAQKLLEH MGGPAPPDSS WKGGLKVPYN VGPGFAGNFS TQKVKMHIHS
360 370 380 390 400
YTKVTRIYNV IGTLKGALEP DRYVILGGHR DAWVFGGIDP QSGAAVVHEI
410 420 430 440 450
VRSFGTLKKK GRRPRRTILF ASWDAEEFGL LGSTEWAEEH SRLLQERGVA
460 470 480 490 500
YINADSSIEG NYTLRVDCTP LMYSLVYNLT KELQSPDEGF EGKSLYDSWK
510 520 530 540 550
EKSPSPEFIG MPRISKLGSG NDFEVFFQRL GIASGRARYT KNWKTNKVSS
560 570 580 590 600
YPLYHSVYET YELVVKFYDP TFKYHLTVAQ VRGAMVFELA NSIVLPFDCQ
610 620 630 640 650
SYAVALKKYA DTIYNISMKH PQEMKAYMIS FDSLFSAVNN FTDVASKFNQ
660 670 680 690 700
RLQELDKSNP ILLRIMNDQL MYLERAFIDP LGLPGRPFYR HIIYAPSSHN
710 720 730 740 750
KYAGESFPGI YDALFDISSK VNASKAWNEV KRQISIATFT VQAAAETLRE

VA
Length:752
Mass (Da):84,574
Last modified:July 27, 2011 - v2
Checksum:iF96041949214E8F3
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti141F → S in BAB22457 (PubMed:16141072).Curated1
Sequence conflicti178Y → F in AAB81971 (PubMed:11210180).Curated1
Sequence conflicti219A → V in AAB81971 (PubMed:11210180).Curated1
Sequence conflicti240A → G in AAB81971 (PubMed:11210180).Curated1
Sequence conflicti287N → E in AAB81971 (PubMed:11210180).Curated1
Sequence conflicti583G → R in AAB81971 (PubMed:11210180).Curated1
Sequence conflicti625K → E in AAB81971 (PubMed:11210180).Curated1
Sequence conflicti728N → S in AAB81971 (PubMed:11210180).Curated1
Sequence conflicti749R → M in AAB81971 (PubMed:11210180).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF026380 mRNA. Translation: AAB81971.1.
AK002920 mRNA. Translation: BAB22457.1.
BC119605 mRNA. Translation: AAI19606.1.
CCDSiCCDS21436.1.
RefSeqiNP_001153178.1. NM_001159706.1.
NP_058050.3. NM_016770.3.
UniGeneiMm.269137.

Genome annotation databases

EnsembliENSMUST00000001824; ENSMUSP00000001824; ENSMUSG00000001773.
GeneIDi53320.
KEGGimmu:53320.
UCSCiuc009ifh.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF026380 mRNA. Translation: AAB81971.1.
AK002920 mRNA. Translation: BAB22457.1.
BC119605 mRNA. Translation: AAI19606.1.
CCDSiCCDS21436.1.
RefSeqiNP_001153178.1. NM_001159706.1.
NP_058050.3. NM_016770.3.
UniGeneiMm.269137.

3D structure databases

ProteinModelPortaliO35409.
SMRiO35409.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiO35409. 1 interactor.
MINTiMINT-4996170.
STRINGi10090.ENSMUSP00000001824.

Protein family/group databases

MEROPSiM28.010.

PTM databases

iPTMnetiO35409.
PhosphoSitePlusiO35409.

Proteomic databases

MaxQBiO35409.
PaxDbiO35409.
PeptideAtlasiO35409.
PRIDEiO35409.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000001824; ENSMUSP00000001824; ENSMUSG00000001773.
GeneIDi53320.
KEGGimmu:53320.
UCSCiuc009ifh.2. mouse.

Organism-specific databases

CTDi2346.
MGIiMGI:1858193. Folh1.

Phylogenomic databases

eggNOGiKOG2195. Eukaryota.
COG2234. LUCA.
GeneTreeiENSGT00550000074421.
HOGENOMiHOG000211921.
HOVERGENiHBG051639.
InParanoidiO35409.
KOiK14592.
OMAiYPANEHA.
OrthoDBiEOG091G02ZM.
TreeFamiTF312981.

Enzyme and pathway databases

ReactomeiR-MMU-70614. Amino acid synthesis and interconversion (transamination).

Miscellaneous databases

PROiO35409.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000001773.
CleanExiMM_FOLH1.
ExpressionAtlasiO35409. baseline and differential.
GenevisibleiO35409. MM.

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 nameiFOLH1_MOUSE
AccessioniPrimary (citable) accession number: O35409
Secondary accession number(s): Q0VDM5, Q9DCC2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 11, 2002
Last sequence update: July 27, 2011
Last modified: November 2, 2016
This is version 140 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

There are amino acid differences between the sequence shown in fig.1 (PubMed:11210180) and the sequence deposited in the database (AF026380). The sequence from fig.1 shows only 3 conflicts between PubMed:11210180 and PubMed:16141072. These are at AA positions 141, 240 and 287.1 Publication

Keywords - Technical termi

Complete proteome, Multifunctional enzyme, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. 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.