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Q04609 (FOLH1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 160. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Glutamate carboxypeptidase 2

EC=3.4.17.21
Alternative name(s):
Cell growth-inhibiting gene 27 protein
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
Short name=PSM
Short name=PSMA
Pteroylpoly-gamma-glutamate carboxypeptidase
Gene names
Name:FOLH1
Synonyms:FOLH, NAALAD1, PSM, PSMA
ORF Names:GIG27
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length750 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Has both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Has a preference for tri-alpha-glutamate peptides. 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. Isoform PSM-4and isoform PSM-5would appear to be physiologically irrelevant. Involved in prostate tumor progression.

Also exhibits a dipeptidyl-peptidase IV type activity. In vitro, cleaves Gly-Pro-AMC.

Catalytic activity

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

Cofactor

Binds 2 zinc ions per subunit. Required for NAALADase activity. Ref.27

Enzyme regulation

The NAALADase activity is inhibited by beta-NAAG, quisqualic acid, 2-(phosphonomethyl) pentanedioic acid (PMPA) and EDTA. Activated by cobalt. Ref.29

Subunit structure

Homodimer. Ref.27

Subcellular location

Cell membrane; Single-pass type II membrane protein Ref.17.

Isoform PSMA': Cytoplasm Ref.17.

Tissue specificity

Highly expressed in prostate epithelium. Detected in urinary bladder, kidney, testis, ovary, fallopian tube, breast, adrenal gland, liver, esophagus, stomach, small intestine, colon and brain (at protein level). Detected in the small intestine, brain, kidney, liver, spleen, colon, trachea, spinal cord and the capillary endothelium of a variety of tumors. Expressed specifically in jejunum brush border membranes. In the brain, highly expressed in the ventral striatum and brain stem. Also expressed in fetal liver and kidney. Isoform PSMA' is the most abundant form in normal prostate. Isoform PSMA-1 is the most abundant form in primary prostate tumors. Isoform PSMA-2is also found in normal prostate as well as in brain and liver. Isoform PSMA-9 is specifically expressed in prostate cancer. Ref.15 Ref.24 Ref.25 Ref.26

Induction

In the prostate, up-regulated in response to androgen deprivation. Ref.29

Domain

The NAALADase activity is found in the central region, the dipeptidyl peptidase IV type activity in the C-terminal. Ref.20

Post-translational modification

The first two amino acids at the N-terminus of isoform PSMA' appear to be cleaved by limited proteolysis.

The N-terminus is blocked.

Polymorphism

Genetic variation in FOLH1 may be associated with low folate levels and consequent hyperhomocysteinemia. This condition can result in increased risk of cardiovascular disease, neural tube defects, and cognitive deficits.

Miscellaneous

PSMA is used as a diagnostic and prognostic indicator of prostate cancer, and as a possible marker for various neurological disorders such as schizophrenia, Alzheimer disease and Huntington disease.

Sequence similarities

Belongs to the peptidase M28 family. M28B subfamily.

Biophysicochemical properties

pH dependence:

Stable at pH greater than 6.5.

Sequence caution

The sequence AAF31167.1 differs from that shown. Reason: Erroneous gene model prediction.

Alternative products

This entry describes 8 isoforms produced by alternative splicing. [Align] [Select]
Isoform PSMA-1 (identifier: Q04609-1)

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.
Note: No experimental confirmation available.
Isoform PSMA-3 (identifier: Q04609-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-585: Missing.
     657-750: NPIVLRMMND...AAAETLSEVA → MSSMLQAATT...KWTLPRPGEK
Note: No experimental confirmation available. Incomplete sequence.
Isoform PSMA-4 (identifier: Q04609-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-159: Missing.
     214-243: VKNAQLAGAKGVILYSDPADYFAPGVKSYP → NMLIGVELQRLLVFQVFLFIQLDTMMHRSS
     244-750: Missing.
Note: No experimental confirmation available. Incomplete sequence.
Isoform PSMA' (identifier: Q04609-6)

The sequence of this isoform differs from the canonical sequence as follows:
     1-57: Missing.
Isoform PSMA-7 (identifier: Q04609-7)

The sequence of this isoform differs from the canonical sequence as follows:
     1-39: MWNLLHETDSAVATARRPRWLCAGALVLAGGFFLLGFLF → MTAGSSYPLFLAAYACTGCLAERL
Isoform PSMA-8 (identifier: Q04609-8)

The sequence of this isoform differs from the canonical sequence as follows:
     657-688: NPIVLRMMNDQLMFLERAFIDPLGLPDRPFYR → K
Isoform PSMA-9 (identifier: Q04609-9)

Also known as: PSM-E;

The sequence of this isoform differs from the canonical sequence as follows:
     1-39: MWNLLHETDSAVATARRPRWLCAGALVLAGGFFLLGFLF → MTAGSSYPLFLAAYACTGCLAERL
     657-688: NPIVLRMMNDQLMFLERAFIDPLGLPDRPFYR → K
Isoform 10 (identifier: Q04609-10)

The sequence of this isoform differs from the canonical sequence as follows:
     1-308: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 750750Glutamate carboxypeptidase 2
PRO_0000174117

Regions

Topological domain1 – 1919Cytoplasmic Probable
Transmembrane20 – 4324Helical; Signal-anchor for type II membrane protein; Probable
Topological domain44 – 750707Extracellular Probable
Region274 – 587314NAALADase
Region534 – 5363Substrate binding
Region699 – 7002Substrate binding
Compositional bias146 – 1494Poly-Pro

Sites

Active site4241For NAALADase activity
Active site6281Charge relay system Potential
Active site6661Charge relay system Potential
Active site6891Charge relay system Potential
Metal binding2691Calcium
Metal binding2721Calcium; via carbonyl oxygen
Metal binding3771Zinc 1
Metal binding3871Zinc 1
Metal binding3871Zinc 2
Metal binding4251Zinc 2
Metal binding4331Calcium
Metal binding4361Calcium
Metal binding4531Zinc 1
Metal binding5531Zinc 2
Binding site2101Substrate
Binding site2571Substrate
Binding site5191Substrate
Binding site5521Substrate

Amino acid modifications

Glycosylation511N-linked (GlcNAc...) Ref.23
Glycosylation761N-linked (GlcNAc...) Ref.22 Ref.23 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32
Glycosylation1211N-linked (GlcNAc...) Ref.23 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32
Glycosylation1401N-linked (GlcNAc...) Ref.23 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32
Glycosylation1531N-linked (GlcNAc...) Ref.23
Glycosylation1951N-linked (GlcNAc...) Ref.23 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32
Glycosylation3361N-linked (GlcNAc...) Ref.22 Ref.23
Glycosylation4591N-linked (GlcNAc...) Ref.22 Ref.23 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32
Glycosylation4761N-linked (GlcNAc...) Ref.22 Ref.23 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32
Glycosylation6381N-linked (GlcNAc...) Ref.22 Ref.23 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32

Natural variations

Alternative sequence1 – 585585Missing in isoform PSMA-3.
VSP_040242
Alternative sequence1 – 308308Missing in isoform 10.
VSP_044287
Alternative sequence1 – 159159Missing in isoform PSMA-4.
VSP_040241
Alternative sequence1 – 5757Missing in isoform PSMA'.
VSP_005336
Alternative sequence1 – 3939MWNLL…LGFLF → MTAGSSYPLFLAAYACTGCL AERL in isoform PSMA-7 and isoform PSMA-9.
VSP_038058
Alternative sequence214 – 24330VKNAQ…VKSYP → NMLIGVELQRLLVFQVFLFI QLDTMMHRSS in isoform PSMA-4.
VSP_040243
Alternative sequence244 – 750507Missing in isoform PSMA-4.
VSP_040244
Alternative sequence657 – 75094NPIVL…LSEVA → MSSMLQAATTSMQGSHSQEF MMLCLILKAKWTLPRPGEK in isoform PSMA-3.
VSP_040245
Alternative sequence657 – 68832NPIVL…RPFYR → K in isoform PSMA-8 and isoform PSMA-9.
VSP_038059
Natural variant231A → T in a colorectal cancer sample; somatic mutation. Ref.33
VAR_036398
Natural variant751Y → H. Ref.3
Corresponds to variant rs202676 [ dbSNP | Ensembl ].
VAR_024592
Natural variant4751H → Y Can be associated with lower folate and higher homocysteine levels. Ref.6
Corresponds to variant rs61886492 [ dbSNP | Ensembl ].
VAR_012736
Natural variant6271V → L.
Corresponds to variant rs2988342 [ dbSNP | Ensembl ].
VAR_028882

Experimental info

Mutagenesis511N → A: Loss of glycosylation. Reduces enzyme activity. Ref.23
Mutagenesis761N → A: Loss of glycosylation. Reduces enzyme activity. Ref.23
Mutagenesis1211N → A: Loss of glycosylation. Severely reduced enzyme activity. Ref.23
Mutagenesis1401N → A: Loss of glycosylation. Severely reduced enzyme activity. Ref.23
Mutagenesis1531N → A: Loss of glycosylation. Severely reduced enzyme activity. Ref.23
Mutagenesis1951N → A: Loss of glycosylation. Severely reduced enzyme activity. Ref.23
Mutagenesis3361N → A: Loss of glycosylation. Reduces enzyme activity. Ref.23
Mutagenesis3771H → A, G or Q: Complete loss of activity.
Mutagenesis3791D → E or N: Complete loss of activity.
Mutagenesis3871D → E or L: Complete loss of activity.
Mutagenesis3871D → N: No effect on enzyme activity.
Mutagenesis3881P → A: No effect on enzyme activity.
Mutagenesis4241E → A: Complete loss of activity. Ref.32
Mutagenesis4241E → D: Reduces enzyme activity. Ref.32
Mutagenesis4241E → Q: Reduces enzyme activity. Ref.32
Mutagenesis4251E → Q or D: Complete loss of activity.
Mutagenesis4531D → N or L: Complete loss of activity.
Mutagenesis4531D → Q: Reduces enzyme activity.
Mutagenesis4541S → A: Reduces enzyme activity.
Mutagenesis4591N → A: Loss of glycosylation. Reduces enzyme activity. Ref.23
Mutagenesis4761N → A: Loss of glycosylation. Reduces enzyme activity. Ref.23
Mutagenesis6381N → A: Loss of glycosylation. Abolishes enzyme activity. Ref.23
Mutagenesis6401T → A: Abolishes enzyme activity. Ref.23
Sequence conflict1941I → V in AAZ66619. Ref.9
Sequence conflict3541R → K AA sequence Ref.1
Sequence conflict3981I → N in ABO93402. Ref.8

Secondary structure

.................................................................................................................... 750
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform PSMA-1 [UniParc].

Last modified June 1, 1994. Version 1.
Checksum: AD8C0A7DBF47901A

FASTA75084,331
        10         20         30         40         50         60 
MWNLLHETDS AVATARRPRW LCAGALVLAG GFFLLGFLFG WFIKSSNEAT NITPKHNMKA 

        70         80         90        100        110        120 
FLDELKAENI KKFLYNFTQI PHLAGTEQNF QLAKQIQSQW KEFGLDSVEL AHYDVLLSYP 

       130        140        150        160        170        180 
NKTHPNYISI INEDGNEIFN TSLFEPPPPG YENVSDIVPP FSAFSPQGMP EGDLVYVNYA 

       190        200        210        220        230        240 
RTEDFFKLER DMKINCSGKI VIARYGKVFR GNKVKNAQLA GAKGVILYSD PADYFAPGVK 

       250        260        270        280        290        300 
SYPDGWNLPG GGVQRGNILN LNGAGDPLTP GYPANEYAYR RGIAEAVGLP SIPVHPIGYY 

       310        320        330        340        350        360 
DAQKLLEKMG GSAPPDSSWR GSLKVPYNVG PGFTGNFSTQ KVKMHIHSTN EVTRIYNVIG 

       370        380        390        400        410        420 
TLRGAVEPDR YVILGGHRDS WVFGGIDPQS GAAVVHEIVR SFGTLKKEGW RPRRTILFAS 

       430        440        450        460        470        480 
WDAEEFGLLG STEWAEENSR LLQERGVAYI NADSSIEGNY TLRVDCTPLM YSLVHNLTKE 

       490        500        510        520        530        540 
LKSPDEGFEG KSLYESWTKK SPSPEFSGMP RISKLGSGND FEVFFQRLGI ASGRARYTKN 

       550        560        570        580        590        600 
WETNKFSGYP LYHSVYETYE LVEKFYDPMF KYHLTVAQVR GGMVFELANS IVLPFDCRDY 

       610        620        630        640        650        660 
AVVLRKYADK IYSISMKHPQ EMKTYSVSFD SLFSAVKNFT EIASKFSERL QDFDKSNPIV 

       670        680        690        700        710        720 
LRMMNDQLMF LERAFIDPLG LPDRPFYRHV IYAPSSHNKY AGESFPGIYD ALFDIESKVD 

       730        740        750 
PSKAWGEVKR QIYVAAFTVQ AAAETLSEVA 

« Hide

Isoform PSMA-3 [UniParc].

Checksum: E35692A0D83A0E53
Show »

FASTA11012,603
Isoform PSMA-4 [UniParc].

Checksum: 80FC286A66993939
Show »

FASTA849,754
Isoform PSMA' [UniParc].

Checksum: 5F3F6D31A9FECAEC
Show »

FASTA69378,000
Isoform PSMA-7 [UniParc].

Checksum: B8D9D69F67C3ABF2
Show »

FASTA73582,519
Isoform PSMA-8 [UniParc].

Checksum: AF79A10CA2BF9DF4
Show »

FASTA71980,597
Isoform PSMA-9 (PSM-E) [UniParc].

Checksum: 800DE87726E1328C
Show »

FASTA70478,785
Isoform 10 [UniParc].

Checksum: 444527FF83B757C6
Show »

FASTA44250,090

References

« Hide 'large scale' references
[1]"Molecular cloning of a complementary DNA encoding a prostate-specific membrane antigen."
Israeli R.S., Powell C.T., Fair W.R., Heston W.D.W.
Cancer Res. 53:227-230(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PSMA-1), PARTIAL PROTEIN SEQUENCE.
Tissue: Prostatic carcinoma.
[2]"Alternatively spliced variants of prostate-specific membrane antigen RNA: ratio of expression as a potential measurement of progression."
Su S.L., Huang I.-P., Fair W.R., Powell C.T., Heston W.D.W.
Cancer Res. 55:1441-1443(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PSMA').
Tissue: Prostate.
[3]"Mapping, genomic organization and promoter analysis of the human prostate-specific membrane antigen gene."
O'Keefe D.S., Su S.L., Bacich D.J., Horiguchi Y., Luo Y., Powell C.T., Zandvliet D., Russell P.J., Molloy P.L., Nowak N.J., Shows T.B., Mullins C., Vonder Haar R.A., Fair W.R., Heston W.D.W.
Biochim. Biophys. Acta 1443:113-127(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM PSMA-1), VARIANT HIS-75.
[4]"Molecular characterization of human brain N-acetylated alpha-linked acidic dipeptidase (NAALADase)."
Luthi-Carter R., Barczak A.K., Speno H., Coyle J.T.
J. Pharmacol. Exp. Ther. 286:1020-1025(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PSMA-1).
Tissue: Brain.
[5]"Isolation and expression of novel human glutamate carboxypeptidases with N-acetylated alpha-linked acidic dipeptidase and dipeptidyl peptidase IV activity."
Pangalos M.N., Neefs J.-M., Somers M., Verhasselt P., Bekkers M., van der Helm L., Fraiponts E., Ashton D., Gordon R.D.
J. Biol. Chem. 274:8470-8483(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PSMA-1), CHARACTERIZATION.
Tissue: Prostate.
[6]"Glutamate carboxypeptidase II: a polymorphism associated with lower levels of serum folate and hyperhomocysteinemia."
Devlin A.M., Ling E.-H., Peerson J.M., Fernando S., Clarke R., Smith A.D., Halsted C.H.
Hum. Mol. Genet. 9:2837-2844(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PSMA-1), VARIANT TYR-475.
Tissue: Jejunum and Small intestine.
[7]"Cloning and sequencing of Chinese prostate-specific membrane antigen."
Ye C.Z., Zhang F.L., Zhang Y.K., Chen C.Q.
Mian Yi Xue Za Zhi 17:328-330(2001)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PSMA-1).
Tissue: Prostatic carcinoma.
[8]"High expression of PSM-E correlated with tumor grade in prostate cancer: a new alternatively spliced variant of prostate-specific membrane antigen."
Cao K.Y., Mao X.P., Wang D.H., Xu L., Yuan G.Q., Dai S.Q., Zheng B.J., Qiu S.P.
Prostate 67:1791-1800(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PSMA-9).
[9]"Identification of three novel splice variants of prostate-specific membrane antigen."
Peace D.J., Zhang Y., Holt G., Ferrer K.T., Heller M., Sosman J.A., Xue B.H.
Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[10]"Identification of a cell growth-inhibiting gene."
Kim J.W., Kim H.K., Shin S.M.
Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PSMA-8).
[11]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS PSMA-1; PSMA-7 AND 10).
Tissue: Amygdala, Corpus callosum and Hippocampus.
[12]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[13]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[14]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM PSMA-8).
Tissue: Lung.
[15]"Molecular cloning of a peptidase against N-acetylaspartylglutamate from a rat hippocampal cDNA library."
Bzdega T., Turi T., Wroblewska B., She D., Chung H.S., Kim H., Neale J.H.
J. Neurochem. 69:2270-2277(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PSMA-3), TISSUE SPECIFICITY.
Tissue: Prostate.
[16]"Alternative splicing of the prostate-specific membrane antigen."
Lupold S.E., Criley S.C., Coffey D.S.
Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases
Cited for: PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PSMA-4).
[17]"Identification, purification, and subcellular localization of prostate-specific membrane antigen PSM' protein in the LNCaP prostatic carcinoma cell line."
Grauer L.S., Lawler K.D., Marignac J.L., Kumar A., Goel A.S., Wolfert R.L.
Cancer Res. 58:4787-4789(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 60-74, SUBCELLULAR LOCATION.
Tissue: Prostatic carcinoma.
[18]"Molecular cloning of alternatively spliced variants of the peptidase against N-acetylaspartylglutamate (NAAG) from human and rat nervous systems."
Bzdega T., She D., Turi T., Wroblewska B., Neale J.H.
Abstr. - Soc. Neurosci. 24:579-579(1998)
Cited for: ALTERNATIVE SPLICING.
[19]"Hydrolysis of the neuropeptide N-acetylaspartylglutamate (NAAG) by cloned human glutamate carboxypeptidase II."
Luthi-Carter R., Barczak A.K., Speno H.D., Coyle J.T.
Brain Res. 795:341-348(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION.
[20]"Structure of membrane glutamate carboxypeptidase."
Rawlings N.D., Barrett A.J.
Biochim. Biophys. Acta 1339:247-252(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: DOMAIN STRUCTURE.
[21]"Site-directed mutagenesis of predicted active site residues in glutamate carboxypeptidase II."
Speno H.S., Luthi-Carter R., Macias W.L., Valentine S.L., Joshi A.R.T., Coyle J.T.
Mol. Pharmacol. 55:179-185(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS.
[22]"Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry."
Zhang H., Li X.-J., Martin D.B., Aebersold R.
Nat. Biotechnol. 21:660-666(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-76; ASN-336; ASN-459; ASN-476 AND ASN-638.
[23]"Identification of the N-glycosylation sites on glutamate carboxypeptidase II necessary for proteolytic activity."
Barinka C., Sacha P., Sklenar J., Man P., Bezouska K., Slusher B.S., Konvalinka J.
Protein Sci. 13:1627-1635(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-51; ASN-76; ASN-121; ASN-140; ASN-153; ASN-195; ASN-336; ASN-459; ASN-476 AND ASN-638, MUTAGENESIS OF ASN-51; ASN-76; ASN-121; ASN-140; ASN-153; ASN-195; ASN-336; ASN-459; ASN-476; ASN-638 AND THR-640.
[24]"Comparative analysis of prostate-specific membrane antigen (PSMA) versus a prostate-specific membrane antigen-like gene."
O'Keefe D.S., Bacich D.J., Heston W.D.W.
Prostate 58:200-210(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
Tissue: Liver.
[25]"Expression of prostate-specific membrane antigen in normal and malignant human tissues."
Kinoshita Y., Kuratsukuri K., Landas S., Imaida K., Rovito P.M. Jr., Wang C.Y., Haas G.P.
World J. Surg. 30:628-636(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[26]"Expression of glutamate carboxypeptidase II in human brain."
Sacha P., Zamecnik J., Barinka C., Hlouchova K., Vicha A., Mlcochova P., Hilgert I., Eckschlager T., Konvalinka J.
Neuroscience 144:1361-1372(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[27]"Structure of glutamate carboxypeptidase II, a drug target in neuronal damage and prostate cancer."
Mesters J.R., Barinka C., Li W., Tsukamoto T., Majer P., Slusher B.S., Konvalinka J., Hilgenfeld R.
EMBO J. 25:1375-1384(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 44-750 IN COMPLEXES WITH GLUTAMATE; INHIBITORS; CALCIUM AND ZINC IONS, COFACTOR, SUBUNIT, GLYCOSYLATION AT ASN-76; ASN-121; ASN-140; ASN-195; ASN-459; ASN-476 AND ASN-638.
[28]"Human glutamate carboxypeptidase II inhibition: structures of GCPII in complex with two potent inhibitors, quisqualate and 2-PMPA."
Mesters J.R., Henning K., Hilgenfeld R.
Acta Crystallogr. D 63:508-513(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.19 ANGSTROMS) OF 44-750 IN COMPLEXES WITH THE INHIBITORS QUISQUALATE AND 2-PMPA; CALCIUM AND ZINC IONS, GLYCOSYLATION AT ASN-76; ASN-121; ASN-140; ASN-195; ASN-459; ASN-476 AND ASN-638.
[29]"Structural insight into the pharmacophore pocket of human glutamate carboxypeptidase II."
Barinka C., Rovenska M., Mlcochova P., Hlouchova K., Plechanovova A., Majer P., Tsukamoto T., Slusher B.S., Konvalinka J., Lubkowski J.
J. Med. Chem. 50:3267-3273(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.62 ANGSTROMS) OF 44-750 IN COMPLEXES WITH SUBSTRATE ANALOGS; CALCIUM AND ZINC IONS, ENZYME REGULATION, GLYCOSYLATION AT ASN-76; ASN-121; ASN-140 ASN-195; ASN-459; ASN-476 AND ASN-638.
[30]"Interactions between human glutamate carboxypeptidase II and urea-based inhibitors: structural characterization."
Barinka C., Byun Y., Dusich C.L., Banerjee S.R., Chen Y., Castanares M., Kozikowski A.P., Mease R.C., Pomper M.G., Lubkowski J.
J. Med. Chem. 51:7737-7743(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.54 ANGSTROMS) OF 44-750 IN COMPLEXES WITH UREA-BASED INHIBITORS; CALCIUM AND ZINC IONS, GLYCOSYLATION AT ASN-76; ASN-121; ASN-140; ASN-195; ASN-459; ASN-476 AND ASN-638.
[31]"Structural basis of interactions between human glutamate carboxypeptidase II and its substrate analogs."
Barinka C., Hlouchova K., Rovenska M., Majer P., Dauter M., Hin N., Ko Y.-S., Tsukamoto T., Slusher B.S., Konvalinka J., Lubkowski J.
J. Mol. Biol. 376:1438-1450(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 44-750 IN COMPLEXES WITH SUBSTRATE ANALOGS; CALCIUM AND ZINC IONS, GLYCOSYLATION AT ASN-76; ASN-121; ASN-140; ASN-195; ASN-459; ASN-476 AND ASN-638.
[32]"Reaction mechanism of glutamate carboxypeptidase II revealed by mutagenesis, X-ray crystallography, and computational methods."
Klusak V., Barinka C., Plechanovova A., Mlcochova P., Konvalinka J., Rulisek L., Lubkowski J.
Biochemistry 48:4126-4138(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 44-750 IN COMPLEX WITH SUBSTRATE; CALCIUM AND ZINC IONS, GLYCOSYLATION AT ASN-76; ASN-121; ASN-140; ASN-195; ASN-459; ASN-476 AND ASN-638, MUTAGENESIS OF GLU-424.
[33]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] THR-23.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M99487 mRNA. Translation: AAA60209.1.
S76978 mRNA. Translation: AAB33750.2.
AF007544 Genomic DNA. Translation: AAC83972.1.
AF176574 mRNA. Translation: AAD51121.1.
EF488811 mRNA. Translation: ABO93402.2.
AY101595 mRNA. Translation: AAM34479.1.
AF107214 Genomic DNA. Translation: AAF31167.1. Sequence problems.
DQ088979 mRNA. Translation: AAZ66619.1.
AK312366 mRNA. Translation: BAG35284.1.
AK295368 mRNA. Translation: BAH12048.1.
AK295470 mRNA. Translation: BAH12079.1.
AC110742 Genomic DNA. No translation available.
AC118273 Genomic DNA. No translation available.
CH471064 Genomic DNA. Translation: EAW67858.1.
CH471064 Genomic DNA. Translation: EAW67861.1.
CH471064 Genomic DNA. Translation: EAW67857.1.
CH471064 Genomic DNA. Translation: EAW67859.1.
BC025672 mRNA. Translation: AAH25672.1.
AF254358 mRNA. Translation: AAF71358.1.
AF254357 mRNA. Translation: AAF71357.1.
CCDSCCDS31493.1. [Q04609-8]
CCDS53626.1. [Q04609-10]
CCDS53627.1. [Q04609-9]
CCDS53628.1. [Q04609-7]
CCDS7946.1. [Q04609-1]
PIRA56881.
RefSeqNP_001014986.1. NM_001014986.1. [Q04609-8]
NP_001180400.1. NM_001193471.1. [Q04609-7]
NP_001180401.1. NM_001193472.1. [Q04609-9]
NP_001180402.1. NM_001193473.1. [Q04609-10]
NP_004467.1. NM_004476.1. [Q04609-1]
UniGeneHs.654487.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1Z8LX-ray3.50A/B/C/D56-750[»]
2C6CX-ray2.00A44-750[»]
2C6GX-ray2.20A44-750[»]
2C6PX-ray2.39A44-750[»]
2CIJX-ray2.40A44-750[»]
2JBJX-ray2.19A44-750[»]
2JBKX-ray2.99A44-750[»]
2OOTX-ray1.64A44-750[»]
2OR4X-ray1.62A44-750[»]
2PVVX-ray2.11A44-750[»]
2PVWX-ray1.71A44-750[»]
2XEFX-ray1.59A44-750[»]
2XEGX-ray1.59A44-750[»]
2XEIX-ray1.69A44-750[»]
2XEJX-ray1.78A44-750[»]
3BHXX-ray1.60A44-750[»]
3BI0X-ray1.67A44-750[»]
3BI1X-ray1.50A44-750[»]
3BXMX-ray1.71A44-750[»]
3D7DX-ray1.69A44-750[»]
3D7FX-ray1.54A44-750[»]
3D7GX-ray1.75A44-750[»]
3D7HX-ray1.55A44-750[»]
3IWWX-ray2.30A44-750[»]
3RBUX-ray1.60A44-750[»]
3SJEX-ray1.70A44-750[»]
3SJFX-ray1.65A44-750[»]
3SJGX-ray1.65A44-750[»]
3SJXX-ray1.66A44-750[»]
4JYWX-ray1.73A44-750[»]
4JZ0X-ray1.83A44-750[»]
4OC0X-ray1.85A44-750[»]
4OC1X-ray1.75A44-750[»]
4OC2X-ray1.65A44-750[»]
4OC3X-ray1.79A44-750[»]
4OC4X-ray1.66A44-750[»]
4OC5X-ray1.70A44-750[»]
ProteinModelPortalQ04609.
SMRQ04609. Positions 55-750.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108630. 4 interactions.
IntActQ04609. 4 interactions.
MINTMINT-3025010.

Chemistry

BindingDBQ04609.
ChEMBLCHEMBL1892.
DrugBankDB00089. Capromab.
DB00142. L-Glutamic Acid.
GuidetoPHARMACOLOGY1606.

Protein family/group databases

MEROPSM28.010.

PTM databases

PhosphoSiteQ04609.

Polymorphism databases

DMDM548615.

Proteomic databases

MaxQBQ04609.
PaxDbQ04609.
PRIDEQ04609.

Protocols and materials databases

DNASU2346.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000256999; ENSP00000256999; ENSG00000086205. [Q04609-1]
ENST00000340334; ENSP00000344131; ENSG00000086205. [Q04609-7]
ENST00000343844; ENSP00000344086; ENSG00000086205. [Q04609-10]
ENST00000356696; ENSP00000349129; ENSG00000086205. [Q04609-8]
ENST00000533034; ENSP00000431463; ENSG00000086205. [Q04609-9]
GeneID2346.
KEGGhsa:2346.
UCSCuc001ngx.3. human. [Q04609-3]
uc001ngy.3. human. [Q04609-1]
uc001ngz.3. human. [Q04609-8]
uc009yly.3. human. [Q04609-7]
uc009ylz.3. human. [Q04609-9]

Organism-specific databases

CTD2346.
GeneCardsGC11M049168.
H-InvDBHIX0129475.
HGNCHGNC:3788. FOLH1.
HPACAB001451.
HPA010593.
MIM600934. gene.
neXtProtNX_Q04609.
PharmGKBPA28205.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG74799.
HOVERGENHBG051639.
KOK14592.
OMAMWNPLHE.
OrthoDBEOG7QK0BC.
PhylomeDBQ04609.
TreeFamTF312981.

Gene expression databases

ArrayExpressQ04609.
BgeeQ04609.
CleanExHS_FOLH1.
GenevestigatorQ04609.

Family and domain databases

Gene3D1.20.930.40. 1 hit.
InterProIPR007484. Peptidase_M28.
IPR003137. Protease-assoc_domain.
IPR007365. TFR-like_dimer_dom.
[Graphical view]
PfamPF02225. PA. 1 hit.
PF04389. Peptidase_M28. 1 hit.
PF04253. TFR_dimer. 1 hit.
[Graphical view]
SUPFAMSSF47672. SSF47672. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceQ04609.
GeneWikiGlutamate_carboxypeptidase_II.
GenomeRNAi2346.
NextBio9513.
PROQ04609.
SOURCESearch...

Entry information

Entry nameFOLH1_HUMAN
AccessionPrimary (citable) accession number: Q04609
Secondary accession number(s): A4UU12 expand/collapse secondary AC list , A9CB79, B7Z312, B7Z343, D3DQS5, E9PDX8, O43748, Q16305, Q541A4, Q8TAY3, Q9NP15, Q9NYE2, Q9P1P8
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: July 9, 2014
This is version 160 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM