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O35409 (FOLH1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 111. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
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to top of pageNames·Attributes·General annotation·Ontologies·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):
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 names
Name:Folh1
Synonyms:Mopsm, Naalad1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length752 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript 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 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.

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

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.

Enzyme regulation

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

Subunit structure

Homodimer By similarity.

Subcellular location

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

Tissue specificity

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

Domain

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

Sequence similarities

Belongs to the peptidase M28 family. M28B subfamily.

Caution

There are amino acid differences between the sequence shown in fig.1 (Ref.1) and the sequence deposited in the database (AF026380). The sequence from fig.1 shows only 3 conflicts between Ref.1 and Ref.2. These are at AA positions 141, 240 and 287.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 752752Glutamate carboxypeptidase 2
PRO_0000174118

Regions

Topological domain1 – 2222Cytoplasmic Potential
Transmembrane23 – 4422Helical; Signal-anchor for type II membrane protein; Potential
Topological domain45 – 752708Extracellular Potential
Region276 – 589314NAALADase
Region536 – 5383Substrate binding By similarity
Region701 – 7022Substrate binding By similarity

Sites

Active site4261Nucleophile; for NAALADase activity By similarity
Active site6301Charge relay system Potential
Active site6681Charge relay system Potential
Active site6911Charge relay system Potential
Metal binding2711Calcium By similarity
Metal binding2741Calcium; via carbonyl oxygen By similarity
Metal binding3791Zinc 1 By similarity
Metal binding3891Zinc 1 By similarity
Metal binding3891Zinc 2 By similarity
Metal binding4271Zinc 2 By similarity
Metal binding4351Calcium By similarity
Metal binding4381Calcium By similarity
Metal binding4551Zinc 1 By similarity
Metal binding5551Zinc 2 By similarity
Binding site2121Substrate By similarity
Binding site2591Substrate By similarity
Binding site5211Substrate By similarity
Binding site5541Substrate By similarity

Amino acid modifications

Glycosylation781N-linked (GlcNAc...) Potential
Glycosylation1231N-linked (GlcNAc...) Potential
Glycosylation1551N-linked (GlcNAc...) Potential
Glycosylation3381N-linked (GlcNAc...) Potential
Glycosylation4611N-linked (GlcNAc...) Potential
Glycosylation4781N-linked (GlcNAc...) Potential
Glycosylation6151N-linked (GlcNAc...) Potential
Glycosylation6401N-linked (GlcNAc...) Potential
Glycosylation7221N-linked (GlcNAc...) Potential

Experimental info

Sequence conflict1411F → S in BAB22457. Ref.2
Sequence conflict1781Y → F in AAB81971. Ref.1
Sequence conflict2191A → V in AAB81971. Ref.1
Sequence conflict2401A → G in AAB81971. Ref.1
Sequence conflict2871N → E in AAB81971. Ref.1
Sequence conflict5831G → R in AAB81971. Ref.1
Sequence conflict6251K → E in AAB81971. Ref.1
Sequence conflict7281N → S in AAB81971. Ref.1
Sequence conflict7491R → M in AAB81971. Ref.1

Sequences

Sequence LengthMass (Da)Tools
O35409 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: F96041949214E8F3

FASTA75284,574
        10         20         30         40         50         60 
MWNALQDRDS AEVLGHRQRW LRVGTLVLAL TGTFLIGFLF GWFIKPSNEA TGNVSHSGMK 

        70         80         90        100        110        120 
KEFLHELKAE NIKKFLYNFT RTPHLAGTQN NFELAKQIHD QWKEFGLDLV ELSHYDVLLS 

       130        140        150        160        170        180 
YPNKTHPNYI SIINEDGNEI FKTSLSEQPP PGYENISDVV PPYSAFSPQG TPEGDLVYVN 

       190        200        210        220        230        240 
YARTEDFFKL EREMKISCSG KIVIARYGKV FRGNMVKNAQ LAGAKGMILY SDPADYFVPA 

       250        260        270        280        290        300 
VKSYPDGWNL PGGGVQRGNV LNLNGAGDPL TPGYPANEHA YRHELTNAVG LPSIPVHPIG 

       310        320        330        340        350        360 
YDDAQKLLEH MGGPAPPDSS WKGGLKVPYN VGPGFAGNFS TQKVKMHIHS YTKVTRIYNV 

       370        380        390        400        410        420 
IGTLKGALEP DRYVILGGHR DAWVFGGIDP QSGAAVVHEI VRSFGTLKKK GRRPRRTILF 

       430        440        450        460        470        480 
ASWDAEEFGL LGSTEWAEEH SRLLQERGVA YINADSSIEG NYTLRVDCTP LMYSLVYNLT 

       490        500        510        520        530        540 
KELQSPDEGF EGKSLYDSWK EKSPSPEFIG MPRISKLGSG NDFEVFFQRL GIASGRARYT 

       550        560        570        580        590        600 
KNWKTNKVSS YPLYHSVYET YELVVKFYDP TFKYHLTVAQ VRGAMVFELA NSIVLPFDCQ 

       610        620        630        640        650        660 
SYAVALKKYA DTIYNISMKH PQEMKAYMIS FDSLFSAVNN FTDVASKFNQ RLQELDKSNP 

       670        680        690        700        710        720 
ILLRIMNDQL MYLERAFIDP LGLPGRPFYR HIIYAPSSHN KYAGESFPGI YDALFDISSK 

       730        740        750 
VNASKAWNEV KRQISIATFT VQAAAETLRE VA

« Hide

References

« Hide 'large scale' references
[1]"Cloning, expression, genomic localization, and enzymatic activities of the mouse homolog of prostate-specific membrane antigen/NAALADase/ folate hydrolase."
Bacich D.J., Pinto J.T., Tong W.P., Heston W.D.W.
Mamm. Genome 12:117-123(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: NIH Swiss.
Tissue: Brain.
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J.
Tissue: Kidney.
[3]"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].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		AF026380 mRNA. Translation: AAB81971.1.
AK002920 mRNA. Translation: BAB22457.1.
BC119605 mRNA. Translation: AAI19606.1.
IPIIPI00130630.
RefSeqNP_001153178.1. NM_001159706.1.
NP_058050.3. NM_016770.3.
UniGeneMm.269137.

3D structure databases

ProteinModelPortalO35409.
SMRO35409. Positions 61-752.
ModBaseSearch...

Protein family/group databases

MEROPSM28.010.

PTM databases

PhosphoSiteO35409.

Proteomic databases

PaxDbO35409.
PRIDEO35409.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000001824; ENSMUSP00000001824; ENSMUSG00000001773.
GeneID53320.
KEGGmmu:53320.

Organism-specific databases

CTD2346.
MGIMGI:1858193. Folh1.

Phylogenomic databases

eggNOGNOG74799.
GeneTreeENSGT00550000074421.
HOGENOMHOG000211921.
HOVERGENHBG051639.
InParanoidQ0VDM5.
KOK14592.
OMANEYAYRR.
OrthoDBEOG48GW2N.

Gene expression databases

ArrayExpressO35409.
BgeeO35409.
CleanExMM_FOLH1.
GenevestigatorO35409.
GermOnlineENSMUSG00000001773. Mus musculus.

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. Transferrin_rcpt-like_dimerise. 1 hit.
ProtoNetSearch...

Other

NextBio310121.
SOURCESearch...

Entry information

Entry nameFOLH1_MOUSE
AccessionPrimary (citable) accession number: O35409
Secondary accession number(s): Q0VDM5, Q9DCC2
Entry history
Integrated into UniProtKB/Swiss-Prot: February 11, 2002
Last sequence update: July 27, 2011
Last modified: April 3, 2013
This is version 111 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

Peptidase families

Classification of peptidase families and list of entries

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents