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P29251 (FOL1_PNECA) Reviewed, UniProtKB/Swiss-Prot

Last modified October 16, 2013. Version 83. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Folic acid synthesis protein fol1

Including the following 3 domains:

  1. Dihydroneopterin aldolase
    Short name=DHNA
    EC=4.1.2.25
    Alternative name(s):
    FASA
    FASB
  2. 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase
    EC=2.7.6.3
    Alternative name(s):
    6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase
    Short name=PPPK
    7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase
    Short name=HPPK
    FASC
  3. Dihydropteroate synthase
    Short name=DHPS
    EC=2.5.1.15
    Alternative name(s):
    Dihydropteroate pyrophosphorylase
    FASD
Gene names
Name:fol1
Synonyms:fas
OrganismPneumocystis carinii
Taxonomic identifier4754 [NCBI]
Taxonomic lineageEukaryotaFungiDikaryaAscomycotaTaphrinomycotinaPneumocystidomycetesPneumocystidaceaePneumocystis

Protein attributes

Sequence length740 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes three sequential steps of tetrahydrofolate biosynthesis. Ref.2

Catalytic activity

2-amino-4-hydroxy-6-(D-erythro-1,2,3-trihydroxypropyl)-7,8-dihydropteridine = 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine + glycolaldehyde. Ref.2 Ref.3 Ref.4

ATP + 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine = AMP + (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate. Ref.2 Ref.3 Ref.4

(2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate + 4-aminobenzoate = diphosphate + dihydropteroate. Ref.2 Ref.3 Ref.4

Cofactor

Binds 1 magnesium ion per subunit. Magnesium is required for activity, even if it interacts primarily with the substrate By similarity.

Pathway

Cofactor biosynthesis; tetrahydrofolate biosynthesis; 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine diphosphate from 7,8-dihydroneopterin triphosphate: step 3/4.

Cofactor biosynthesis; tetrahydrofolate biosynthesis; 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine diphosphate from 7,8-dihydroneopterin triphosphate: step 4/4.

Cofactor biosynthesis; tetrahydrofolate biosynthesis; 7,8-dihydrofolate from 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine diphosphate and 4-aminobenzoate: step 1/2.

Sequence similarities

In the N-terminal section; belongs to the DHNA family.

In the central section; belongs to the HPPK family.

In the C-terminal section; belongs to the DHPS family.

Contains 1 pterin-binding domain.

Biophysicochemical properties

Kinetic parameters:

KM=2.3 µM for 7,8-dihydroneopterin Ref.3 Ref.5

KM=3.6 µM for 6-hydroxymethyl-7,8-dihydropterin

Vmax=36 nmol/min/mg enzyme for 7,8-dihydroneopterin

pH dependence:

Optimum pH is 8.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 740740Folic acid synthesis protein fol1
PRO_0000168242

Regions

Domain471 – 730260Pterin-binding
Region39 – 160122DHNA 1
Region161 – 280120DHNA 2
Region291 – 449159HPPK
Region463 – 740278DHPS
Region517 – 5182Substrate binding By similarity

Sites

Metal binding4781Magnesium By similarity
Binding site4861Substrate By similarity
Binding site5521Substrate By similarity
Binding site5711Substrate By similarity
Binding site6431Substrate By similarity
Binding site6831Substrate By similarity
Binding site7181Substrate By similarity
Binding site7201Substrate By similarity

Experimental info

Mutagenesis391D → E: Abolishes DHNA activity. Ref.5
Mutagenesis531G → A: Reduces DHNA activity 11-fold. Ref.5
Mutagenesis631Q → N: Reduces DHNA activity 16-fold. Ref.5
Mutagenesis1611D → E: No effect. Ref.5
Mutagenesis1751G → A: Abolishes DHNA activity. Ref.5
Mutagenesis1851Q → N: Reduces DHNA activity 24-fold. Ref.5

Sequences

Sequence LengthMass (Da)Tools
P29251 [UniParc].

Last modified December 1, 1992. Version 1.
Checksum: 328F6EB91B4499EB

FASTA74083,962
        10         20         30         40         50         60 
MIFKSLKIFP FYQIYGFRFL KGMIFKKKIH LSKLNKNHDL IHIHSLTLKS IVGKNSWAQR 

        70         80         90        100        110        120 
LLQPVVLTLS MGINASLSGN MDDLSYSIDY ATVYKEVFKL VENSKFENLL DLSDKISKVV 

       130        140        150        160        170        180 
LGDKCKGNWV KVIAETPKGH LLAETGLQII RRKDGIREID DQFFIKNLSL YTIIGINPEE 

       190        200        210        220        230        240 
RVNKQNIIID LILFKSSINL ECKDDFIINT YNIEKLLKEI VKHVEESTFK TIEALALSIA 

       250        260        270        280        290        300 
RISCISHNIE KIIVKVKKSC ALAFAESAGV EIVRSRSCFS SNNYIKSENS IDNEAVYISL 

       310        320        330        340        350        360 
GSNLGNRIKF ILDAIEKMSI KGIKVLKTSM LYESKPMYFK DQPAFYNAVC KVQTSLHPEQ 

       370        380        390        400        410        420 
LLFELQLIEK ELGRVKVIDK GPRCIDLDIV FYGRKIINSE SLIIPHPRVL ERSFVLKPLL 

       430        440        450        460        470        480 
DISGDLVHPV TGLSIASYFE KIVDHDIKPV LPFLYKNKSI DFSFRSYKAP TYIMAILNLT 

       490        500        510        520        530        540 
PDSFFDGGIH SYDSVLIDVE KFINAGATII DIGGQSTRPG SYIIPLEEEI FRVIPAIKYL 

       550        560        570        580        590        600 
QKTYPDILIS IDTFRSEVAE QAVKAGASLV NDISGGRYDP KMFNTVARLK VPICIMHMRG 

       610        620        630        640        650        660 
NFLNMDNLTD YGTDIIEQIT IELEKLLNSA EKSGIPRWNI ILDPGLGFSK TLHQNIELLR 

       670        680        690        700        710        720 
RFNELKSKNC FNGLPWLLGP SRKRFTGFIT GDNMPKDRIW GTVAAVVASI SGGCDIIRVH 

       730        740 
DVYEMYKISK MSDAIWKEIY 

« Hide

References

[1]"The multifunctional folic acid synthesis fas gene of Pneumocystis carinii appears to encode dihydropteroate synthase and hydroxymethyldihydropterin pyrophosphokinase."
Volpes F., Dyer M., Scaife J.G., Darby G., Stammers D.K., Delves C.J.
Gene 112:213-218(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"The multifunctional folic acid synthesis fas gene of Pneumocystis carinii encodes dihydroneopterin aldolase, hydroxymethyldihydropterin pyrophosphokinase and dihydropteroate synthase."
Volpe F., Ballantine S.P., Delves C.J.
Eur. J. Biochem. 216:449-458(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY.
[3]"The hydroxymethyldihydropterin pyrophosphokinase domain of the multifunctional folic acid synthesis Fas protein of Pneumocystis carinii expressed as an independent enzyme in Escherichia coli: refolding and characterization of the recombinant enzyme."
Ballantine S.P., Volpe F., Delves C.J.
Protein Expr. Purif. 5:371-378(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: BIOPHYSICOCHEMICAL PROPERTIES, CATALYTIC ACTIVITY.
[4]"Two domains with amino-acid sequence similarity are required for dihydroneopterin aldolase function in the multifunctional folic acid synthesis Fas protein of Pneumocystis carinii."
Volpe F., Ballantine S.P., Delves C.J.
Gene 160:41-46(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY.
[5]"Single amino acid substitutions disrupt tetramer formation in the dihydroneopterin aldolase enzyme of Pneumocystis carinii."
Thomas M.C., Ballantine S.P., Bethell S.S., Bains S., Kellam P., Delves C.J.
Biochemistry 37:11629-11636(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF ASP-39; GLY-53; GLN-63; ASP-161; GLY-175 AND GLN-185.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M86602 Genomic DNA. Translation: AAA33790.1.
PIRS28666.

3D structure databases

ProteinModelPortalP29251.
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Enzyme and pathway databases

SABIO-RKP29251.
UniPathwayUPA00077; UER00154.
UPA00077; UER00155.
UPA00077; UER00156.

Family and domain databases

Gene3D3.20.20.20. 1 hit.
3.30.70.560. 1 hit.
InterProIPR006390. DHP_synth.
IPR011005. Dihydropteroate_synth-like.
IPR006157. FolB_dom.
IPR016261. Folic_acid_synth.
IPR000550. Hppk.
IPR000489. Pterin-binding.
[Graphical view]
PfamPF02152. FolB. 2 hits.
PF01288. HPPK. 1 hit.
PF00809. Pterin_bind. 1 hit.
[Graphical view]
PIRSFPIRSF000741. Folic_acid_synth. 1 hit.
SMARTSM00905. FolB. 2 hits.
[Graphical view]
SUPFAMSSF51717. SSF51717. 1 hit.
SSF55083. SSF55083. 1 hit.
TIGRFAMsTIGR01496. DHPS. 1 hit.
TIGR00526. folB_dom. 2 hits.
TIGR01498. folK. 1 hit.
PROSITEPS00792. DHPS_1. 1 hit.
PS00793. DHPS_2. 1 hit.
PS00794. HPPK. 1 hit.
PS50972. PTERIN_BINDING. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameFOL1_PNECA
AccessionPrimary (citable) accession number: P29251
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: December 1, 1992
Last modified: October 16, 2013
This is version 83 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways