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Protein

Glutamate carboxypeptidase 2

Gene

FOLH1

Organism
Homo sapiens (Human)
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. 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. Involved in prostate tumor progression.
Also exhibits a dipeptidyl-peptidase IV type activity. In vitro, cleaves Gly-Pro-AMC.

Catalytic activityi

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

Cofactori

Zn2+6 PublicationsNote: Binds 2 Zn2+ ions per subunit. Required for NAALADase activity.1 Publication

Enzyme regulationi

The NAALADase activity is inhibited by beta-NAAG, quisqualic acid, 2-(phosphonomethyl) pentanedioic acid (PMPA) and EDTA. Activated by cobalt.1 Publication

pH dependencei

Stable at pH greater than 6.5.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei210SubstrateCombined sources6 Publications1
Binding sitei257SubstrateCombined sources6 Publications1
Metal bindingi269CalciumCombined sources6 Publications1
Metal bindingi272Calcium; via carbonyl oxygenCombined sources6 Publications1
Metal bindingi377Zinc 1; via tele nitrogen; catalyticCombined sources6 Publications1
Metal bindingi387Zinc 1; catalyticCombined sources6 Publications1
Metal bindingi387Zinc 2Combined sources6 Publications1
Active sitei424Nucleophile; for NAALADase activity1
Binding sitei424SubstrateBy similarity1
Metal bindingi425Zinc 2Combined sources6 Publications1
Metal bindingi433CalciumCombined sources6 Publications1
Metal bindingi436CalciumCombined sources6 Publications1
Metal bindingi453Zinc 1; catalyticCombined sources6 Publications1
Binding sitei519SubstrateCombined sources6 Publications1
Binding sitei552SubstrateCombined sources6 Publications1
Metal bindingi553Zinc 2; via tele nitrogenCombined sources6 Publications1
Active sitei628Charge relay systemSequence analysis1
Active sitei666Charge relay systemSequence analysis1
Active sitei689Charge relay systemSequence analysis1

GO - Molecular functioni

  • Ac-Asp-Glu binding Source: BHF-UCL
  • dipeptidase activity Source: Reactome
  • metal ion binding Source: UniProtKB-KW
  • metallocarboxypeptidase activity Source: BHF-UCL
  • peptidase activity Source: UniProtKB
  • tetrahydrofolyl-poly(glutamate) polymer binding Source: BHF-UCL

GO - Biological processi

  • cellular amino acid biosynthetic process Source: Reactome
  • C-terminal protein deglutamylation Source: BHF-UCL
  • folic acid-containing compound metabolic process Source: Ensembl
  • proteolysis Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Carboxypeptidase, Dipeptidase, Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Calcium, Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:HS01525-MONOMER.
BRENDAi3.4.17.21. 2681.
ReactomeiR-HSA-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):
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 namesi
Name:FOLH1
Synonyms:FOLH, NAALAD1, PSM, PSMA
ORF Names:GIG27
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:3788. FOLH1.

Subcellular locationi

Isoform PSMA' :
  • Cytoplasm 1 Publication

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 19CytoplasmicCuratedAdd BLAST19
Transmembranei20 – 43Helical; Signal-anchor for type II membrane proteinCuratedAdd BLAST24
Topological domaini44 – 750ExtracellularCuratedAdd BLAST707

GO - Cellular componenti

  • cell surface Source: BHF-UCL
  • cytoplasm Source: UniProtKB-SubCell
  • extracellular exosome Source: UniProtKB
  • integral component of plasma membrane Source: ProtInc
  • membrane Source: UniProtKB
  • plasma membrane Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi51N → A: Loss of glycosylation. Reduces enzyme activity. 1 Publication1
Mutagenesisi76N → A: Loss of glycosylation. Reduces enzyme activity. 1 Publication1
Mutagenesisi121N → A: Loss of glycosylation. Severely reduced enzyme activity. 1 Publication1
Mutagenesisi140N → A: Loss of glycosylation. Severely reduced enzyme activity. 1 Publication1
Mutagenesisi153N → A: Loss of glycosylation. Severely reduced enzyme activity. 1 Publication1
Mutagenesisi195N → A: Loss of glycosylation. Severely reduced enzyme activity. 1 Publication1
Mutagenesisi336N → A: Loss of glycosylation. Reduces enzyme activity. 1 Publication1
Mutagenesisi377H → A, G or Q: Complete loss of activity. 1 Publication1
Mutagenesisi379D → E or N: Complete loss of activity. 1 Publication1
Mutagenesisi387D → E or L: Complete loss of activity. 1 Publication1
Mutagenesisi387D → N: No effect on enzyme activity. 1 Publication1
Mutagenesisi388P → A: No effect on enzyme activity. 1 Publication1
Mutagenesisi424E → A: Complete loss of activity. 1 Publication1
Mutagenesisi424E → D: Reduces enzyme activity. 1 Publication1
Mutagenesisi424E → Q: Reduces enzyme activity. 1 Publication1
Mutagenesisi425E → Q or D: Complete loss of activity. 1 Publication1
Mutagenesisi453D → N or L: Complete loss of activity. 1 Publication1
Mutagenesisi453D → Q: Reduces enzyme activity. 1 Publication1
Mutagenesisi454S → A: Reduces enzyme activity. 1 Publication1
Mutagenesisi459N → A: Loss of glycosylation. Reduces enzyme activity. 1 Publication1
Mutagenesisi476N → A: Loss of glycosylation. Reduces enzyme activity. 1 Publication1
Mutagenesisi638N → A: Loss of glycosylation. Abolishes enzyme activity. 1 Publication1
Mutagenesisi640T → A: Abolishes enzyme activity. 1 Publication1

Organism-specific databases

DisGeNETi2346.
OpenTargetsiENSG00000086205.
PharmGKBiPA28205.

Chemistry databases

ChEMBLiCHEMBL1892.
DrugBankiDB00089. Capromab.
GuidetoPHARMACOLOGYi1606.

Polymorphism and mutation databases

BioMutaiFOLH1.
DMDMi548615.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001741171 – 750Glutamate carboxypeptidase 2Add BLAST750

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei10PhosphoserineBy similarity1
Glycosylationi51N-linked (GlcNAc...)1 Publication1
Glycosylationi76N-linked (GlcNAc...)Combined sources8 Publications1
Glycosylationi121N-linked (GlcNAc...)Combined sources7 Publications1
Glycosylationi140N-linked (GlcNAc...)Combined sources7 Publications1
Glycosylationi153N-linked (GlcNAc...)Combined sources1 Publication1
Glycosylationi195N-linked (GlcNAc...)Combined sources7 Publications1
Glycosylationi336N-linked (GlcNAc...)2 Publications1
Glycosylationi459N-linked (GlcNAc...)Combined sources8 Publications1
Glycosylationi476N-linked (GlcNAc...)Combined sources8 Publications1
Glycosylationi638N-linked (GlcNAc...)Combined sources8 Publications1

Post-translational modificationi

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

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ04609.
PaxDbiQ04609.
PeptideAtlasiQ04609.
PRIDEiQ04609.

PTM databases

iPTMnetiQ04609.
PhosphoSitePlusiQ04609.

Expressioni

Tissue specificityi

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-3 is also found in normal prostate as well as in brain and liver. Isoform PSMA-9 is specifically expressed in prostate cancer.5 Publications

Inductioni

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

Gene expression databases

BgeeiENSG00000086205.
CleanExiHS_FOLH1.
ExpressionAtlasiQ04609. baseline and differential.
GenevisibleiQ04609. HS.

Organism-specific databases

HPAiCAB001451.
HPA010593.

Interactioni

Subunit structurei

Homodimer.2 Publications

Protein-protein interaction databases

BioGridi108630. 5 interactors.
IntActiQ04609. 4 interactors.
MINTiMINT-3025010.
STRINGi9606.ENSP00000256999.

Chemistry databases

BindingDBiQ04609.

Structurei

Secondary structure

1750
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi58 – 64Combined sources7
Helixi67 – 77Combined sources11
Beta strandi78 – 80Combined sources3
Helixi87 – 103Combined sources17
Beta strandi106 – 119Combined sources14
Beta strandi122 – 124Combined sources3
Beta strandi127 – 131Combined sources5
Beta strandi137 – 140Combined sources4
Turni149 – 151Combined sources3
Helixi154 – 156Combined sources3
Beta strandi174 – 176Combined sources3
Helixi182 – 190Combined sources9
Beta strandi200 – 204Combined sources5
Helixi210 – 219Combined sources10
Beta strandi223 – 228Combined sources6
Helixi231 – 234Combined sources4
Beta strandi244 – 247Combined sources4
Beta strandi269 – 272Combined sources4
Helixi283 – 285Combined sources3
Beta strandi294 – 297Combined sources4
Helixi299 – 306Combined sources8
Helixi317 – 319Combined sources3
Beta strandi322 – 325Combined sources4
Beta strandi330 – 333Combined sources4
Helixi335 – 337Combined sources3
Beta strandi341 – 346Combined sources6
Beta strandi349 – 362Combined sources14
Beta strandi365 – 377Combined sources13
Beta strandi381 – 383Combined sources3
Turni385 – 388Combined sources4
Helixi389 – 407Combined sources19
Beta strandi413 – 423Combined sources11
Helixi424 – 426Combined sources3
Helixi429 – 445Combined sources17
Beta strandi446 – 451Combined sources6
Beta strandi455 – 457Combined sources3
Beta strandi459 – 466Combined sources8
Helixi468 – 470Combined sources3
Helixi471 – 479Combined sources9
Beta strandi480 – 482Combined sources3
Turni486 – 490Combined sources5
Helixi493 – 500Combined sources8
Beta strandi504 – 506Combined sources3
Beta strandi507 – 510Combined sources4
Beta strandi517 – 519Combined sources3
Helixi521 – 526Combined sources6
Beta strandi531 – 538Combined sources8
Beta strandi541 – 543Combined sources3
Turni545 – 547Combined sources3
Turni550 – 553Combined sources4
Helixi559 – 565Combined sources7
Helixi571 – 589Combined sources19
Helixi597 – 615Combined sources19
Helixi619 – 624Combined sources6
Helixi630 – 652Combined sources23
Helixi658 – 673Combined sources16
Beta strandi684 – 686Combined sources3
Beta strandi689 – 695Combined sources7
Beta strandi698 – 705Combined sources8
Helixi706 – 712Combined sources7
Helixi715 – 717Combined sources3
Helixi721 – 744Combined sources24

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
4LQGX-ray1.77A44-750[»]
4MCPX-ray1.65A44-750[»]
4MCQX-ray2.00A44-750[»]
4MCRX-ray1.65A44-750[»]
4MCSX-ray1.83A44-750[»]
4NGMX-ray1.84A44-750[»]
4NGNX-ray1.64A44-750[»]
4NGPX-ray1.63A44-750[»]
4NGQX-ray2.08A44-750[»]
4NGRX-ray1.90A44-750[»]
4NGSX-ray1.68A44-750[»]
4NGTX-ray2.31A44-750[»]
4OC0X-ray1.85A44-750[»]
4OC1X-ray1.75A44-750[»]
4OC2X-ray1.65A44-750[»]
4OC3X-ray1.79A44-750[»]
4OC4X-ray1.66A44-750[»]
4OC5X-ray1.70A44-750[»]
4OMEX-ray1.79A44-750[»]
4P44X-ray1.75A44-750[»]
4P45X-ray1.87A44-750[»]
4P4BX-ray1.93A44-750[»]
4P4DX-ray1.65A44-750[»]
4P4EX-ray1.67A44-750[»]
4P4FX-ray1.86A44-750[»]
4P4IX-ray1.87A44-750[»]
4P4JX-ray1.66A44-750[»]
4W9YX-ray1.64A44-750[»]
4X3RX-ray1.86A44-750[»]
5D29X-ray1.80A56-750[»]
5ELYX-ray1.81A55-750[»]
5F09X-ray1.85A44-750[»]
ProteinModelPortaliQ04609.
SMRiQ04609.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ04609.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni274 – 587NAALADaseAdd BLAST314
Regioni517 – 518Substrate bindingBy similarity2
Regioni534 – 536Substrate bindingCombined sources2 Publications3
Regioni552 – 553Substrate bindingBy similarity2
Regioni699 – 700Substrate bindingCombined sources5 Publications2

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi146 – 149Poly-ProSequence analysis4

Domaini

The NAALADase activity is found in the central region, the dipeptidyl peptidase IV type activity in the C-terminal.1 Publication

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.
InParanoidiQ04609.
KOiK14592.
OMAiSANDKEQ.
OrthoDBiEOG091G02ZM.
PhylomeDBiQ04609.
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.

Sequences (8)i

Sequence statusi: Complete.

This entry describes 8 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform PSMA-1 (identifier: Q04609-1) [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
MWNLLHETDS AVATARRPRW LCAGALVLAG GFFLLGFLFG WFIKSSNEAT
60 70 80 90 100
NITPKHNMKA FLDELKAENI KKFLYNFTQI PHLAGTEQNF QLAKQIQSQW
110 120 130 140 150
KEFGLDSVEL AHYDVLLSYP NKTHPNYISI INEDGNEIFN TSLFEPPPPG
160 170 180 190 200
YENVSDIVPP FSAFSPQGMP EGDLVYVNYA RTEDFFKLER DMKINCSGKI
210 220 230 240 250
VIARYGKVFR GNKVKNAQLA GAKGVILYSD PADYFAPGVK SYPDGWNLPG
260 270 280 290 300
GGVQRGNILN LNGAGDPLTP GYPANEYAYR RGIAEAVGLP SIPVHPIGYY
310 320 330 340 350
DAQKLLEKMG GSAPPDSSWR GSLKVPYNVG PGFTGNFSTQ KVKMHIHSTN
360 370 380 390 400
EVTRIYNVIG TLRGAVEPDR YVILGGHRDS WVFGGIDPQS GAAVVHEIVR
410 420 430 440 450
SFGTLKKEGW RPRRTILFAS WDAEEFGLLG STEWAEENSR LLQERGVAYI
460 470 480 490 500
NADSSIEGNY TLRVDCTPLM YSLVHNLTKE LKSPDEGFEG KSLYESWTKK
510 520 530 540 550
SPSPEFSGMP RISKLGSGND FEVFFQRLGI ASGRARYTKN WETNKFSGYP
560 570 580 590 600
LYHSVYETYE LVEKFYDPMF KYHLTVAQVR GGMVFELANS IVLPFDCRDY
610 620 630 640 650
AVVLRKYADK IYSISMKHPQ EMKTYSVSFD SLFSAVKNFT EIASKFSERL
660 670 680 690 700
QDFDKSNPIV LRMMNDQLMF LERAFIDPLG LPDRPFYRHV IYAPSSHNKY
710 720 730 740 750
AGESFPGIYD ALFDIESKVD PSKAWGEVKR QIYVAAFTVQ AAAETLSEVA
Note: No experimental confirmation available.
Length:750
Mass (Da):84,331
Last modified:June 1, 1994 - v1
Checksum:iAD8C0A7DBF47901A
GO
Isoform PSMA-3 (identifier: Q04609-3) [UniParc]FASTAAdd to basket

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.
Show »
Length:110
Mass (Da):12,603
Checksum:iE35692A0D83A0E53
GO
Isoform PSMA-4 (identifier: Q04609-4) [UniParc]FASTAAdd to basket

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.
Show »
Length:84
Mass (Da):9,754
Checksum:i80FC286A66993939
GO
Isoform PSMA' (identifier: Q04609-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-57: Missing.

Show »
Length:693
Mass (Da):78,000
Checksum:i5F3F6D31A9FECAEC
GO
Isoform PSMA-7 (identifier: Q04609-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-39: MWNLLHETDSAVATARRPRWLCAGALVLAGGFFLLGFLF → MTAGSSYPLFLAAYACTGCLAERL

Show »
Length:735
Mass (Da):82,519
Checksum:iB8D9D69F67C3ABF2
GO
Isoform PSMA-8 (identifier: Q04609-8) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     657-688: NPIVLRMMNDQLMFLERAFIDPLGLPDRPFYR → K

Show »
Length:719
Mass (Da):80,597
Checksum:iAF79A10CA2BF9DF4
GO
Isoform PSMA-9 (identifier: Q04609-9) [UniParc]FASTAAdd to basket
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

Show »
Length:704
Mass (Da):78,785
Checksum:i800DE87726E1328C
GO
Isoform 10 (identifier: Q04609-10) [UniParc]FASTAAdd to basket

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

Show »
Length:442
Mass (Da):50,090
Checksum:i444527FF83B757C6
GO

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti194I → V in AAZ66619 (Ref. 9) Curated1
Sequence conflicti354R → K AA sequence (PubMed:8417812).Curated1
Sequence conflicti398I → N in ABO93402 (PubMed:17929272).Curated1

Polymorphismi

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.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03639823A → T in a colorectal cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_02459275Y → H.1 PublicationCorresponds to variant rs202676dbSNPEnsembl.1
Natural variantiVAR_012736475H → Y Can be associated with lower folate and higher homocysteine levels. 1 PublicationCorresponds to variant rs61886492dbSNPEnsembl.1
Natural variantiVAR_028882627V → L.Corresponds to variant rs2988342dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0402421 – 585Missing in isoform PSMA-3. CuratedAdd BLAST585
Alternative sequenceiVSP_0442871 – 308Missing in isoform 10. 1 PublicationAdd BLAST308
Alternative sequenceiVSP_0402411 – 159Missing in isoform PSMA-4. CuratedAdd BLAST159
Alternative sequenceiVSP_0053361 – 57Missing in isoform PSMA'. 1 PublicationAdd BLAST57
Alternative sequenceiVSP_0380581 – 39MWNLL…LGFLF → MTAGSSYPLFLAAYACTGCL AERL in isoform PSMA-7 and isoform PSMA-9. 2 PublicationsAdd BLAST39
Alternative sequenceiVSP_040243214 – 243VKNAQ…VKSYP → NMLIGVELQRLLVFQVFLFI QLDTMMHRSS in isoform PSMA-4. CuratedAdd BLAST30
Alternative sequenceiVSP_040244244 – 750Missing in isoform PSMA-4. CuratedAdd BLAST507
Alternative sequenceiVSP_040245657 – 750NPIVL…LSEVA → MSSMLQAATTSMQGSHSQEF MMLCLILKAKWTLPRPGEK in isoform PSMA-3. CuratedAdd BLAST94
Alternative sequenceiVSP_038059657 – 688NPIVL…RPFYR → K in isoform PSMA-8 and isoform PSMA-9. 3 PublicationsAdd BLAST32

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS31493.1. [Q04609-8]
CCDS53626.1. [Q04609-10]
CCDS53627.1. [Q04609-9]
CCDS53628.1. [Q04609-7]
CCDS7946.1. [Q04609-1]
PIRiA56881.
RefSeqiNP_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]
XP_016872923.1. XM_017017434.1. [Q04609-7]
XP_016872924.1. XM_017017435.1. [Q04609-9]
XP_016872925.1. XM_017017436.1. [Q04609-6]
XP_016872926.1. XM_017017437.1. [Q04609-6]
XP_016872931.1. XM_017017442.1. [Q04609-6]
XP_016872932.1. XM_017017443.1. [Q04609-6]
XP_016872933.1. XM_017017444.1. [Q04609-10]
XP_016872934.1. XM_017017445.1. [Q04609-10]
XP_016872935.1. XM_017017446.1. [Q04609-10]
XP_016872936.1. XM_017017447.1. [Q04609-10]
XP_016872937.1. XM_017017448.1. [Q04609-10]
UniGeneiHs.645352.
Hs.654487.

Genome annotation databases

EnsembliENST00000256999; ENSP00000256999; ENSG00000086205. [Q04609-1]
ENST00000340334; ENSP00000344131; ENSG00000086205. [Q04609-7]
ENST00000343844; ENSP00000344086; ENSG00000086205. [Q04609-10]
ENST00000356696; ENSP00000349129; ENSG00000086205. [Q04609-8]
ENST00000533034; ENSP00000431463; ENSG00000086205. [Q04609-9]
GeneIDi2346.
KEGGihsa:2346.
UCSCiuc001ngy.3. human. [Q04609-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS31493.1. [Q04609-8]
CCDS53626.1. [Q04609-10]
CCDS53627.1. [Q04609-9]
CCDS53628.1. [Q04609-7]
CCDS7946.1. [Q04609-1]
PIRiA56881.
RefSeqiNP_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]
XP_016872923.1. XM_017017434.1. [Q04609-7]
XP_016872924.1. XM_017017435.1. [Q04609-9]
XP_016872925.1. XM_017017436.1. [Q04609-6]
XP_016872926.1. XM_017017437.1. [Q04609-6]
XP_016872931.1. XM_017017442.1. [Q04609-6]
XP_016872932.1. XM_017017443.1. [Q04609-6]
XP_016872933.1. XM_017017444.1. [Q04609-10]
XP_016872934.1. XM_017017445.1. [Q04609-10]
XP_016872935.1. XM_017017446.1. [Q04609-10]
XP_016872936.1. XM_017017447.1. [Q04609-10]
XP_016872937.1. XM_017017448.1. [Q04609-10]
UniGeneiHs.645352.
Hs.654487.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
4LQGX-ray1.77A44-750[»]
4MCPX-ray1.65A44-750[»]
4MCQX-ray2.00A44-750[»]
4MCRX-ray1.65A44-750[»]
4MCSX-ray1.83A44-750[»]
4NGMX-ray1.84A44-750[»]
4NGNX-ray1.64A44-750[»]
4NGPX-ray1.63A44-750[»]
4NGQX-ray2.08A44-750[»]
4NGRX-ray1.90A44-750[»]
4NGSX-ray1.68A44-750[»]
4NGTX-ray2.31A44-750[»]
4OC0X-ray1.85A44-750[»]
4OC1X-ray1.75A44-750[»]
4OC2X-ray1.65A44-750[»]
4OC3X-ray1.79A44-750[»]
4OC4X-ray1.66A44-750[»]
4OC5X-ray1.70A44-750[»]
4OMEX-ray1.79A44-750[»]
4P44X-ray1.75A44-750[»]
4P45X-ray1.87A44-750[»]
4P4BX-ray1.93A44-750[»]
4P4DX-ray1.65A44-750[»]
4P4EX-ray1.67A44-750[»]
4P4FX-ray1.86A44-750[»]
4P4IX-ray1.87A44-750[»]
4P4JX-ray1.66A44-750[»]
4W9YX-ray1.64A44-750[»]
4X3RX-ray1.86A44-750[»]
5D29X-ray1.80A56-750[»]
5ELYX-ray1.81A55-750[»]
5F09X-ray1.85A44-750[»]
ProteinModelPortaliQ04609.
SMRiQ04609.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108630. 5 interactors.
IntActiQ04609. 4 interactors.
MINTiMINT-3025010.
STRINGi9606.ENSP00000256999.

Chemistry databases

BindingDBiQ04609.
ChEMBLiCHEMBL1892.
DrugBankiDB00089. Capromab.
GuidetoPHARMACOLOGYi1606.

Protein family/group databases

MEROPSiM28.010.

PTM databases

iPTMnetiQ04609.
PhosphoSitePlusiQ04609.

Polymorphism and mutation databases

BioMutaiFOLH1.
DMDMi548615.

Proteomic databases

MaxQBiQ04609.
PaxDbiQ04609.
PeptideAtlasiQ04609.
PRIDEiQ04609.

Protocols and materials databases

DNASUi2346.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000256999; ENSP00000256999; ENSG00000086205. [Q04609-1]
ENST00000340334; ENSP00000344131; ENSG00000086205. [Q04609-7]
ENST00000343844; ENSP00000344086; ENSG00000086205. [Q04609-10]
ENST00000356696; ENSP00000349129; ENSG00000086205. [Q04609-8]
ENST00000533034; ENSP00000431463; ENSG00000086205. [Q04609-9]
GeneIDi2346.
KEGGihsa:2346.
UCSCiuc001ngy.3. human. [Q04609-1]

Organism-specific databases

CTDi2346.
DisGeNETi2346.
GeneCardsiFOLH1.
H-InvDBHIX0129475.
HGNCiHGNC:3788. FOLH1.
HPAiCAB001451.
HPA010593.
MIMi600934. gene.
neXtProtiNX_Q04609.
OpenTargetsiENSG00000086205.
PharmGKBiPA28205.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2195. Eukaryota.
COG2234. LUCA.
GeneTreeiENSGT00550000074421.
HOGENOMiHOG000211921.
HOVERGENiHBG051639.
InParanoidiQ04609.
KOiK14592.
OMAiSANDKEQ.
OrthoDBiEOG091G02ZM.
PhylomeDBiQ04609.
TreeFamiTF312981.

Enzyme and pathway databases

BioCyciZFISH:HS01525-MONOMER.
BRENDAi3.4.17.21. 2681.
ReactomeiR-HSA-70614. Amino acid synthesis and interconversion (transamination).

Miscellaneous databases

EvolutionaryTraceiQ04609.
GeneWikiiGlutamate_carboxypeptidase_II.
GenomeRNAii2346.
PROiQ04609.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000086205.
CleanExiHS_FOLH1.
ExpressionAtlasiQ04609. baseline and differential.
GenevisibleiQ04609. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: Q04609
Secondary accession number(s): A4UU12
, A9CB79, B7Z312, B7Z343, D3DQS5, E9PDX8, O43748, Q16305, Q541A4, Q8TAY3, Q9NP15, Q9NYE2, Q9P1P8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: November 2, 2016
This is version 182 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

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.

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Multifunctional enzyme, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. 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.