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Protein

Glutamate carboxypeptidase 2

Gene

Folh1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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 activity is inhibited by beta-NAAG, quisqualic acid and 2-(phosphonomethyl)glutaric acid (PMG).

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

GO - Biological processi

  • positive regulation of apoptotic process Source: RGD
  • proteolysis Source: RGD

Keywordsi

Molecular functionCarboxypeptidase, Dipeptidase, Hydrolase, Metalloprotease, Multifunctional enzyme, Protease
LigandCalcium, Metal-binding, Zinc

Enzyme and pathway databases

BRENDAi3.4.17.21 5301

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:Naalad1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi

Organism-specific databases

RGDi70963 Folh1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 19CytoplasmicSequence analysisAdd BLAST19
Transmembranei20 – 44Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST25
Topological domaini45 – 752ExtracellularSequence analysisAdd BLAST708

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL5098

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001741201 – 752Glutamate carboxypeptidase 2Add BLAST752

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei10PhosphoserineCombined sources1
Glycosylationi48N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi78N-linked (GlcNAc...) asparagineBy similarity1
Glycosylationi123N-linked (GlcNAc...) asparagineBy similarity1
Glycosylationi155N-linked (GlcNAc...) asparagineBy similarity1
Glycosylationi197N-linked (GlcNAc...) asparagineBy similarity1
Glycosylationi338N-linked (GlcNAc...) asparagineBy similarity1
Glycosylationi461N-linked (GlcNAc...) asparagineBy similarity1
Glycosylationi478N-linked (GlcNAc...) asparagine; alternateBy similarity1
Glycosylationi478N-linked (HexNAc...) asparagine; alternateCombined sources1
Glycosylationi615N-linked (GlcNAc...) asparagine; alternateSequence analysis1
Glycosylationi615N-linked (HexNAc...) asparagine; alternateCombined sources1
Glycosylationi640N-linked (GlcNAc...) asparagineBy similarity1

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP70627
PRIDEiP70627

PTM databases

iPTMnetiP70627
PhosphoSitePlusiP70627
UniCarbKBiP70627

Expressioni

Tissue specificityi

Widely expressed throughout brain regions with highest levels in the hippocampus, dentate gyrus, priform cortex, choroid plexus of ventricles, pineal gland, anterior lobe of the pituitary gland and supraoptic nucleus. High levels also found in the cerebral cortex, substantia nigra, pontine nucleus and the granule cell layer of cerebellum. Highly expressed in astrocytes and non-myelinating Schwann cells. Also expressed in kidney, localizing to the proximal brush border of the renal tube.

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000018592

Chemistry databases

BindingDBiP70627

Structurei

3D structure databases

ProteinModelPortaliP70627
SMRiP70627
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
HOGENOMiHOG000211921
HOVERGENiHBG051639
InParanoidiP70627
KOiK14592
PhylomeDBiP70627

Family and domain databases

Gene3Di1.20.930.40, 1 hit
InterProiView protein in InterPro
IPR003137 PA_domain
IPR007484 Peptidase_M28
IPR007365 TFR-like_dimer_dom
IPR036757 TFR-like_dimer_dom_sf
PfamiView protein in Pfam
PF02225 PA, 1 hit
PF04389 Peptidase_M28, 1 hit
PF04253 TFR_dimer, 1 hit
SUPFAMiSSF47672 SSF47672, 1 hit

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Experimental confirmation may be lacking for some isoforms.
Isoform 1 (identifier: P70627-1) [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
MWNAQQDSDS AEALGRRQRW FCAGTLVLAF TGTFIIGFLF GWFIKPSNDS
60 70 80 90 100
TSSVSYPGMK KAFLQELKAE NIKKFLYNFT RTPHLAGTQH NFELAKQIHA
110 120 130 140 150
QWKEFGLDLV ELSDYDVLLS YPNKTHPNYI SIINEDGNEI FKTSLAELSP
160 170 180 190 200
PGYENISDVV PPYSAFSPQG TPEGDLVYVN YARTEDFFKL ERVMKINCSG
210 220 230 240 250
KIVIARYGQV FRGNKVKNAQ LAGAKGIILY SDPADYFVPG VKSYPDGWNL
260 270 280 290 300
PGGGVQRGNV LNLNGAGDPL TPGYPANEYA YRHEFTEAVG LPSIPVHPIG
310 320 330 340 350
YDDAQKLLEH MGGSAPPDSS WKGGLKVPYN VGPGFAGNFS KQKVKLHIHS
360 370 380 390 400
YNKVTRIYNV IGTLKGAVEP DRYVILGGHR DAWVFGGIDP QSGAAVVHEI
410 420 430 440 450
VRTFGTLKKK GWRPRRTILF ASWDAEEFGL LGSTEWAEEH SRLLQERGVA
460 470 480 490 500
YINADSSIEG NYTLRVDCTP LMHSLVYNLT KELPSPDEGF EGKSLYDSWK
510 520 530 540 550
EKSPSTEFIG MPRISKLGSG NDFEVFFQRL GIASGRARYT KNWKNNKVSS
560 570 580 590 600
YPLYHSVYET YELVEKFYDP TFKYHLTVAQ VRGAMVFELA NSIVLPFDCQ
610 620 630 640 650
SYAVALKKHA ETIYNISMNH PQEMKAYMIS FDSLFSAVNN FTDVASKFNQ
660 670 680 690 700
RLQDLDKSNP ILLRILNDQL MYLERAFIDP LGLPGRPFYR HIIYAPSSHN
710 720 730 740 750
KYAGESFPGI YDALFDINNK VDTSKAWREV KRQISIAAFT VQAAAETLRE

VD
Length:752
Mass (Da):84,540
Last modified:February 1, 1997 - v1
Checksum:i5C0915A3B9C71E41
GO
Isoform 2 (identifier: P70627-2)
Also known as: Short form
Sequence is not available
Note: Probably inactive.
Length:
Mass (Da):
Isoform 3 (identifier: P70627-3)
Also known as: Long form
Sequence is not available
Length:
Mass (Da):

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U75973 mRNA Translation: AAC53423.1
AF040256 mRNA Translation: AAC40067.1
AF513486 mRNA Translation: AAM47015.1
AF039707 mRNA Translation: AAB96759.1
RefSeqiNP_476533.1, NM_057185.2 [P70627-1]
UniGeneiRn.89278

Genome annotation databases

GeneIDi85309
KEGGirno:85309
UCSCiRGD:70963 rat [P70627-1]

Keywords - Coding sequence diversityi

Alternative splicing

Entry informationi

Entry nameiFOLH1_RAT
AccessioniPrimary (citable) accession number: P70627
Secondary accession number(s): Q547B6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 11, 2002
Last sequence update: February 1, 1997
Last modified: May 23, 2018
This is version 129 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Peptidase families
    Classification of peptidase families and list of entries
  2. SIMILARITY comments
    Index of protein domains and families

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