FOLH1_PIG
ID FOLH1_PIG Reviewed; 751 AA.
AC O77564;
DT 11-FEB-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=Glutamate carboxypeptidase 2;
DE EC=3.4.17.21;
DE AltName: Full=Folate hydrolase 1;
DE AltName: Full=Folylpoly-gamma-glutamate carboxypeptidase;
DE Short=FGCP;
DE AltName: Full=Glutamate carboxypeptidase II;
DE Short=GCPII;
DE AltName: Full=Membrane glutamate carboxypeptidase;
DE Short=mGCP;
DE AltName: Full=N-acetylated-alpha-linked acidic dipeptidase I;
DE Short=NAALADase I;
DE AltName: Full=Prostate-specific membrane antigen homolog;
DE AltName: Full=Pteroylpoly-gamma-glutamate carboxypeptidase;
GN Name=FOLH1; Synonyms=NAALAD1;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 200-210 AND 471-483.
RC TISSUE=Jejunal mucosa;
RX PubMed=9685395; DOI=10.1074/jbc.273.32.20417;
RA Halsted C.H., Ling E.-H., Luthi-Carter R., Villanueva J.A., Gardner J.M.,
RA Coyle J.T.;
RT "Folylpoly-gamma-glutamate carboxypeptidase from pig jejunum. Molecular
RT characterization and relation to glutamate carboxypeptidase II.";
RL J. Biol. Chem. 273:20417-20424(1998).
RN [2]
RP ERRATUM OF PUBMED:9685395.
RA Halsted C.H., Ling E.-H., Luthi-Carter R., Villanueva J.A., Gardner J.M.,
RA Coyle J.T.;
RL J. Biol. Chem. 275:30746-30746(2000).
RN [3]
RP CHARACTERIZATION.
RX PubMed=2867095; DOI=10.1016/s0021-9258(17)36185-9;
RA Chandler C.J., Wang T.T., Halsted C.H.;
RT "Pteroylpolyglutamate hydrolase from human jejunal brush borders.
RT Purification and characterization.";
RL J. Biol. Chem. 261:928-933(1986).
CC -!- FUNCTION: Has both folate hydrolase and N-acetylated-alpha-linked-
CC acidic dipeptidase (NAALADase) activity. Has a preference for tri-
CC alpha-glutamate peptides (By similarity). In the intestine, required
CC for the uptake of folate. In the brain, modulates excitatory
CC neurotransmission through the hydrolysis of the neuropeptide, N-
CC aceylaspartylglutamate (NAAG), thereby releasing glutamate.
CC {ECO:0000250}.
CC -!- FUNCTION: Also exhibits a dipeptidyl-peptidase IV type activity. In
CC vitro, cleaves Gly-Pro-AMC. {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Release of an unsubstituted, C-terminal glutamyl residue,
CC typically from Ac-Asp-Glu or folylpoly-gamma-glutamates.;
CC EC=3.4.17.21;
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Note=Binds 2 Zn(2+) ions per subunit. Required for NAALADase activity.;
CC -!- ACTIVITY REGULATION: The NAALADase activity is inhibited by quisqualic
CC acid, beta-NAAG and 2-(phosphonomethyl) pentanedioic acid (PMPA).
CC Ethanol ingestion decreases the folate hydrolase activity by 50%.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 6.0.;
CC -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q04609};
CC Single-pass type II membrane protein {ECO:0000250|UniProtKB:Q04609}.
CC -!- TISSUE SPECIFICITY: High expression in the duodenum and in the jejunum
CC brush-border membrane. Weak expression in kidney.
CC -!- DOMAIN: The NAALADase activity is found in the central region, the
CC dipeptidyl peptidase IV type activity in the C-terminal.
CC -!- SIMILARITY: Belongs to the peptidase M28 family. M28B subfamily.
CC {ECO:0000305}.
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DR EMBL; AF050502; AAC39269.1; -; mRNA.
DR RefSeq; NP_999549.1; NM_214384.1.
DR AlphaFoldDB; O77564; -.
DR SMR; O77564; -.
DR STRING; 9823.ENSSSCP00000027466; -.
DR MEROPS; M28.010; -.
DR PaxDb; O77564; -.
DR PeptideAtlas; O77564; -.
DR GeneID; 397677; -.
DR KEGG; ssc:397677; -.
DR CTD; 219595; -.
DR eggNOG; KOG2195; Eukaryota.
DR InParanoid; O77564; -.
DR OrthoDB; 804230at2759; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0004180; F:carboxypeptidase activity; IBA:GO_Central.
DR GO; GO:0016805; F:dipeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004181; F:metallocarboxypeptidase activity; IEA:UniProtKB-EC.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR Gene3D; 1.20.930.40; -; 1.
DR InterPro; IPR003137; PA_domain.
DR InterPro; IPR007484; Peptidase_M28.
DR InterPro; IPR039373; Peptidase_M28B.
DR InterPro; IPR007365; TFR-like_dimer_dom.
DR InterPro; IPR036757; TFR-like_dimer_dom_sf.
DR PANTHER; PTHR10404; PTHR10404; 1.
DR Pfam; PF02225; PA; 1.
DR Pfam; PF04389; Peptidase_M28; 1.
DR Pfam; PF04253; TFR_dimer; 1.
DR SUPFAM; SSF47672; SSF47672; 1.
PE 1: Evidence at protein level;
KW Calcium; Carboxypeptidase; Cell membrane; Dipeptidase;
KW Direct protein sequencing; Glycoprotein; Hydrolase; Membrane;
KW Metal-binding; Metalloprotease; Multifunctional enzyme; Phosphoprotein;
KW Protease; Reference proteome; Signal-anchor; Transmembrane;
KW Transmembrane helix; Zinc.
FT CHAIN 1..751
FT /note="Glutamate carboxypeptidase 2"
FT /id="PRO_0000174119"
FT TOPO_DOM 1..19
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 20..43
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 44..750
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT REGION 275..588
FT /note="NAALADase"
FT ACT_SITE 425
FT /note="Nucleophile; for NAALADase activity"
FT /evidence="ECO:0000250"
FT ACT_SITE 629
FT /note="Charge relay system"
FT /evidence="ECO:0000255"
FT ACT_SITE 667
FT /note="Charge relay system"
FT /evidence="ECO:0000255"
FT ACT_SITE 690
FT /note="Charge relay system"
FT /evidence="ECO:0000255"
FT BINDING 211
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Q0"
FT BINDING 258
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Q0"
FT BINDING 270
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q04609"
FT BINDING 273
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q04609"
FT BINDING 378
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Q0"
FT BINDING 388
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Q0"
FT BINDING 388
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q04609"
FT BINDING 425
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Q0"
FT BINDING 426
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q04609"
FT BINDING 434
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q04609"
FT BINDING 437
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q04609"
FT BINDING 454
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Q0"
FT BINDING 518..519
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Q0"
FT BINDING 520
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q04609"
FT BINDING 535..537
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q04609"
FT BINDING 553..554
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Q0"
FT BINDING 553
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q04609"
FT BINDING 554
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q04609"
FT BINDING 700..701
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Q0"
FT MOD_RES 10
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70627"
FT CARBOHYD 51
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:Q04609"
FT CARBOHYD 77
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:Q04609"
FT CARBOHYD 122
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:Q04609"
FT CARBOHYD 141
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:Q04609"
FT CARBOHYD 154
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:Q04609"
FT CARBOHYD 196
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:Q04609"
FT CARBOHYD 337
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:Q04609"
FT CARBOHYD 460
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:Q04609"
FT CARBOHYD 477
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:Q04609"
FT CARBOHYD 614
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 639
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:Q04609"
FT CARBOHYD 646
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 751 AA; 84524 MW; AF77B35236328CCA CRC64;
MWNPLHETDS TSVAWRRPRW LCAGALVLAA GLFVLGFLFG WFIKSPNEAA NISPQHNVKK
AFLDELKAEN IKTFLYNFTR IPHLAGTEQN FQLAKQIQSQ WKEFGLDSVE LAHYDVLLSY
PNKTRPNYIS IIDEDGNEIF NTSLFEPPPP GYENVSDVVP PFSAFSPQGM PEGDLVYVNY
ARTEDFFKLE RDMKINCSGK ILIARYGKIF RGNKVKNAQL AGAKGIILYS DPADYFAPGV
QSYPDGWNLP GGGVQRGNIL NLNGAGDPLT PGYPANEYAY RLQIAEAVGL PRIPVHPIGY
SDAQKLLEKM GGSAPPDDSW KGSLHVPYNV GPGFTGNFST QKVKMHIHSD NKVKRIYNVI
GTLRGAVEPD RYVILGGHRD SWVFGGIDPQ SGAAVVHEIV RSFGKLKKEG WRPRRTVLFA
SWDAEEYGLF GSTEWAEENS RILQERGVAY INADSSIEGN YTLRVDCTPL MYSLVYNLTK
ELQSPDEGFE GKSLFESWNE KSPSPEFSGL PRISKLGSGN DFEVFFQRLG IASGRARYTK
DWVTNKFSSY PLYHSVYETY ELVEKFYDPT FKYHLAVAQV RGGIVFELAN SVVRPFDCRD
YAVVLRNYAD KLYNISMNHP QEMKAYSVSF DSLFSAVKNF TEIASNFSER VQDLDKNNPI
LLRIMNDQLM FLERAFIVPL GLPDRAFYRH VIYAPSSHNK YMGESFPGIY DALFDIENKV
DPSKAWGEVK RQISIAAFTV QAAAGTLREV A
