Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei210 – 2101SubstrateCombined sources6 Publications
Binding sitei257 – 2571SubstrateCombined sources6 Publications
Metal bindingi269 – 2691CalciumCombined sources6 Publications
Metal bindingi272 – 2721Calcium; via carbonyl oxygenCombined sources6 Publications
Metal bindingi377 – 3771Zinc 1; via tele nitrogen; catalyticCombined sources6 Publications
Metal bindingi387 – 3871Zinc 1; catalyticCombined sources6 Publications
Metal bindingi387 – 3871Zinc 2Combined sources6 Publications
Active sitei424 – 4241Nucleophile; for NAALADase activity
Binding sitei424 – 4241SubstrateBy similarity
Metal bindingi425 – 4251Zinc 2Combined sources6 Publications
Metal bindingi433 – 4331CalciumCombined sources6 Publications
Metal bindingi436 – 4361CalciumCombined sources6 Publications
Metal bindingi453 – 4531Zinc 1; catalyticCombined sources6 Publications
Binding sitei519 – 5191SubstrateCombined sources6 Publications
Binding sitei552 – 5521SubstrateCombined sources6 Publications
Metal bindingi553 – 5531Zinc 2; via tele nitrogenCombined sources6 Publications
Active sitei628 – 6281Charge relay systemSequence analysis
Active sitei666 – 6661Charge relay systemSequence analysis
Active sitei689 – 6891Charge relay systemSequence analysis

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

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)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 1919CytoplasmicCuratedAdd
BLAST
Transmembranei20 – 4324Helical; Signal-anchor for type II membrane proteinCuratedAdd
BLAST
Topological domaini44 – 750707ExtracellularCuratedAdd
BLAST

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)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi51 – 511N → A: Loss of glycosylation. Reduces enzyme activity. 1 Publication
Mutagenesisi76 – 761N → A: Loss of glycosylation. Reduces enzyme activity. 1 Publication
Mutagenesisi121 – 1211N → A: Loss of glycosylation. Severely reduced enzyme activity. 1 Publication
Mutagenesisi140 – 1401N → A: Loss of glycosylation. Severely reduced enzyme activity. 1 Publication
Mutagenesisi153 – 1531N → A: Loss of glycosylation. Severely reduced enzyme activity. 1 Publication
Mutagenesisi195 – 1951N → A: Loss of glycosylation. Severely reduced enzyme activity. 1 Publication
Mutagenesisi336 – 3361N → A: Loss of glycosylation. Reduces enzyme activity. 1 Publication
Mutagenesisi377 – 3771H → A, G or Q: Complete loss of activity. 1 Publication
Mutagenesisi379 – 3791D → E or N: Complete loss of activity. 1 Publication
Mutagenesisi387 – 3871D → E or L: Complete loss of activity. 1 Publication
Mutagenesisi387 – 3871D → N: No effect on enzyme activity. 1 Publication
Mutagenesisi388 – 3881P → A: No effect on enzyme activity. 1 Publication
Mutagenesisi424 – 4241E → A: Complete loss of activity. 1 Publication
Mutagenesisi424 – 4241E → D: Reduces enzyme activity. 1 Publication
Mutagenesisi424 – 4241E → Q: Reduces enzyme activity. 1 Publication
Mutagenesisi425 – 4251E → Q or D: Complete loss of activity. 1 Publication
Mutagenesisi453 – 4531D → N or L: Complete loss of activity. 1 Publication
Mutagenesisi453 – 4531D → Q: Reduces enzyme activity. 1 Publication
Mutagenesisi454 – 4541S → A: Reduces enzyme activity. 1 Publication
Mutagenesisi459 – 4591N → A: Loss of glycosylation. Reduces enzyme activity. 1 Publication
Mutagenesisi476 – 4761N → A: Loss of glycosylation. Reduces enzyme activity. 1 Publication
Mutagenesisi638 – 6381N → A: Loss of glycosylation. Abolishes enzyme activity. 1 Publication
Mutagenesisi640 – 6401T → A: Abolishes enzyme activity. 1 Publication

Organism-specific databases

PharmGKBiPA28205.

Chemistry

ChEMBLiCHEMBL1892.
DrugBankiDB00089. Capromab.
GuidetoPHARMACOLOGYi1606.

Polymorphism and mutation databases

BioMutaiFOLH1.
DMDMi548615.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 750750Glutamate carboxypeptidase 2PRO_0000174117Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei10 – 101PhosphoserineBy similarity
Glycosylationi51 – 511N-linked (GlcNAc...)1 Publication
Glycosylationi76 – 761N-linked (GlcNAc...)Combined sources8 Publications
Glycosylationi121 – 1211N-linked (GlcNAc...)Combined sources7 Publications
Glycosylationi140 – 1401N-linked (GlcNAc...)Combined sources7 Publications
Glycosylationi153 – 1531N-linked (GlcNAc...)Combined sources1 Publication
Glycosylationi195 – 1951N-linked (GlcNAc...)Combined sources7 Publications
Glycosylationi336 – 3361N-linked (GlcNAc...)2 Publications
Glycosylationi459 – 4591N-linked (GlcNAc...)Combined sources8 Publications
Glycosylationi476 – 4761N-linked (GlcNAc...)Combined sources8 Publications
Glycosylationi638 – 6381N-linked (GlcNAc...)Combined sources8 Publications

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.
PhosphoSiteiQ04609.

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 interactions.
IntActiQ04609. 4 interactions.
MINTiMINT-3025010.
STRINGi9606.ENSP00000256999.

Chemistry

BindingDBiQ04609.

Structurei

Secondary structure

1
750
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi58 – 647Combined sources
Helixi67 – 7711Combined sources
Beta strandi78 – 803Combined sources
Helixi87 – 10317Combined sources
Beta strandi106 – 11914Combined sources
Beta strandi122 – 1243Combined sources
Beta strandi127 – 1315Combined sources
Beta strandi137 – 1404Combined sources
Turni149 – 1513Combined sources
Helixi154 – 1563Combined sources
Beta strandi174 – 1763Combined sources
Helixi182 – 1909Combined sources
Beta strandi200 – 2045Combined sources
Helixi210 – 21910Combined sources
Beta strandi223 – 2286Combined sources
Helixi231 – 2344Combined sources
Beta strandi244 – 2474Combined sources
Beta strandi269 – 2724Combined sources
Helixi283 – 2853Combined sources
Beta strandi294 – 2974Combined sources
Helixi299 – 3068Combined sources
Helixi317 – 3193Combined sources
Beta strandi322 – 3254Combined sources
Beta strandi330 – 3334Combined sources
Helixi335 – 3373Combined sources
Beta strandi341 – 3466Combined sources
Beta strandi349 – 36214Combined sources
Beta strandi365 – 37713Combined sources
Beta strandi381 – 3833Combined sources
Turni385 – 3884Combined sources
Helixi389 – 40719Combined sources
Beta strandi413 – 42311Combined sources
Helixi424 – 4263Combined sources
Helixi429 – 44517Combined sources
Beta strandi446 – 4516Combined sources
Beta strandi455 – 4573Combined sources
Beta strandi459 – 4668Combined sources
Helixi468 – 4703Combined sources
Helixi471 – 4799Combined sources
Beta strandi480 – 4823Combined sources
Turni486 – 4905Combined sources
Helixi493 – 5008Combined sources
Beta strandi504 – 5063Combined sources
Beta strandi507 – 5104Combined sources
Beta strandi517 – 5193Combined sources
Helixi521 – 5266Combined sources
Beta strandi531 – 5388Combined sources
Beta strandi541 – 5433Combined sources
Turni545 – 5473Combined sources
Turni550 – 5534Combined sources
Helixi559 – 5657Combined sources
Helixi571 – 58919Combined sources
Helixi597 – 61519Combined sources
Helixi619 – 6246Combined sources
Helixi630 – 65223Combined sources
Helixi658 – 67316Combined sources
Beta strandi684 – 6863Combined sources
Beta strandi689 – 6957Combined sources
Beta strandi698 – 7058Combined sources
Helixi706 – 7127Combined sources
Helixi715 – 7173Combined sources
Helixi721 – 74424Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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. Positions 55-750.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ04609.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni274 – 587314NAALADaseAdd
BLAST
Regioni517 – 5182Substrate bindingBy similarity
Regioni534 – 5363Substrate bindingCombined sources2 Publications
Regioni552 – 5532Substrate bindingBy similarity
Regioni699 – 7002Substrate bindingCombined sources5 Publications

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi146 – 1494Poly-ProSequence analysis

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti194 – 1941I → V in AAZ66619 (Ref. 9) Curated
Sequence conflicti354 – 3541R → K AA sequence (PubMed:8417812).Curated
Sequence conflicti398 – 3981I → N in ABO93402 (PubMed:17929272).Curated

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti23 – 231A → T in a colorectal cancer sample; somatic mutation. 1 Publication
VAR_036398
Natural varianti75 – 751Y → H.1 Publication
Corresponds to variant rs202676 [ dbSNP | Ensembl ].
VAR_024592
Natural varianti475 – 4751H → Y Can be associated with lower folate and higher homocysteine levels. 1 Publication
Corresponds to variant rs61886492 [ dbSNP | Ensembl ].
VAR_012736
Natural varianti627 – 6271V → L.
Corresponds to variant rs2988342 [ dbSNP | Ensembl ].
VAR_028882

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 585585Missing in isoform PSMA-3. CuratedVSP_040242Add
BLAST
Alternative sequencei1 – 308308Missing in isoform 10. 1 PublicationVSP_044287Add
BLAST
Alternative sequencei1 – 159159Missing in isoform PSMA-4. CuratedVSP_040241Add
BLAST
Alternative sequencei1 – 5757Missing in isoform PSMA'. 1 PublicationVSP_005336Add
BLAST
Alternative sequencei1 – 3939MWNLL…LGFLF → MTAGSSYPLFLAAYACTGCL AERL in isoform PSMA-7 and isoform PSMA-9. 2 PublicationsVSP_038058Add
BLAST
Alternative sequencei214 – 24330VKNAQ…VKSYP → NMLIGVELQRLLVFQVFLFI QLDTMMHRSS in isoform PSMA-4. CuratedVSP_040243Add
BLAST
Alternative sequencei244 – 750507Missing in isoform PSMA-4. CuratedVSP_040244Add
BLAST
Alternative sequencei657 – 75094NPIVL…LSEVA → MSSMLQAATTSMQGSHSQEF MMLCLILKAKWTLPRPGEK in isoform PSMA-3. CuratedVSP_040245Add
BLAST
Alternative sequencei657 – 68832NPIVL…RPFYR → K in isoform PSMA-8 and isoform PSMA-9. 3 PublicationsVSP_038059Add
BLAST

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]
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]
UniGeneiHs.645352.
Hs.654487.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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. Positions 55-750.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

Chemistry

BindingDBiQ04609.
ChEMBLiCHEMBL1892.
DrugBankiDB00089. Capromab.
GuidetoPHARMACOLOGYi1606.

Protein family/group databases

MEROPSiM28.010.

PTM databases

iPTMnetiQ04609.
PhosphoSiteiQ04609.

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

Phylogenomic databases

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

Enzyme and pathway databases

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: September 7, 2016
This is version 180 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.