fol1

Functionⁱ

Catalyzes three sequential steps of tetrahydrofolate biosynthesis.1 Publication

Catalytic activityⁱ

7,8-dihydroneopterin = 6-hydroxymethyl-7,8-dihydropterin + glycolaldehyde.3 Publications

ATP + 6-hydroxymethyl-7,8-dihydropterin = AMP + 6-hydroxymethyl-7,8-dihydropterin diphosphate.3 Publications

6-hydroxymethyl-7,8-dihydropterin diphosphate + 4-aminobenzoate = diphosphate + dihydropteroate.3 Publications

Cofactorⁱ

Mg²⁺By similarity

Kineticsⁱ

K_M=
2.3 µM for 7,8-dihydroneopterin
2 Publications
Manual assertion based on experiment inⁱ
- Ref.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: PROTEIN SEQUENCE OF 281-293, BIOPHYSICOCHEMICAL PROPERTIES, CATALYTIC ACTIVITY.
- Ref.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.
K_M=
3.6 µM for 6-hydroxymethyl-7,8-dihydropterin
2 Publications
Manual assertion based on experiment inⁱ
- Ref.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: PROTEIN SEQUENCE OF 281-293, BIOPHYSICOCHEMICAL PROPERTIES, CATALYTIC ACTIVITY.
- Ref.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.

V_max=
36 nmol/min/mg enzyme for 7,8-dihydroneopterin
2 Publications
Manual assertion based on experiment inⁱ
- Ref.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: PROTEIN SEQUENCE OF 281-293, BIOPHYSICOCHEMICAL PROPERTIES, CATALYTIC ACTIVITY.
- Ref.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.

pH dependenceⁱ

Optimum pH is 8.2 Publications

Pathwayⁱ: tetrahydrofolate biosynthesis

This protein is involved in step 3 and 4 of the subpathway that synthesizes 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine diphosphate from 7,8-dihydroneopterin triphosphate.
Proteins known to be involved in the 4 steps of the subpathway in this organism are:

no protein annotated in this organism
no protein annotated in this organism
Folic acid synthesis protein fol1 (fol1)
Folic acid synthesis protein fol1 (fol1)

This subpathway is part of the pathway tetrahydrofolate biosynthesis, which is itself part of Cofactor biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine diphosphate from 7,8-dihydroneopterin triphosphate, the pathway tetrahydrofolate biosynthesis and in Cofactor biosynthesis.

Pathwayⁱ: tetrahydrofolate biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes 7,8-dihydrofolate from 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine diphosphate and 4-aminobenzoate.
Proteins known to be involved in the 2 steps of the subpathway in this organism are:

Folic acid synthesis protein fol1 (fol1)
no protein annotated in this organism

This subpathway is part of the pathway tetrahydrofolate biosynthesis, which is itself part of Cofactor biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes 7,8-dihydrofolate from 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine diphosphate and 4-aminobenzoate, the pathway tetrahydrofolate biosynthesis and in Cofactor biosynthesis.

Sites

Feature key	Position(s)	DescriptionActions	Length
Metal bindingⁱ	478	MagnesiumBy similarity	1
Binding siteⁱ	517	6-hydroxymethyl-7,8-dihydropterin diphosphateBy similarity	1
Binding siteⁱ	552	6-hydroxymethyl-7,8-dihydropterin diphosphateBy similarity	1
Binding siteⁱ	571	6-hydroxymethyl-7,8-dihydropterin diphosphateBy similarity	1
Binding siteⁱ	643	6-hydroxymethyl-7,8-dihydropterin diphosphateBy similarity	1
Binding siteⁱ	683	6-hydroxymethyl-7,8-dihydropterin diphosphateBy similarity	1

GO - Molecular functionⁱ

2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase activity Source: UniProtKB-EC
ATP binding Source: UniProtKB-KW
dihydroneopterin aldolase activity Source: UniProtKB-EC
dihydropteroate synthase activity Source: UniProtKB-EC
kinase activity Source: UniProtKB-KW
metal ion binding Source: UniProtKB-KW

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

folic acid biosynthetic process Source: UniProtKB-KW
tetrahydrofolate biosynthetic process Source: UniProtKB-UniPathway

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Kinase, Lyase, Multifunctional enzyme, Transferase
Biological process	Folate biosynthesis
Ligand	ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

SABIO-RKⁱ	P29251
UniPathwayⁱ	UPA00077;UER00154 UPA00077;UER00155 UPA00077;UER00156

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Folic acid synthesis protein fol1 Including the following 3 domains: Dihydroneopterin aldolase1 Publication (EC:4.1.2.252 Publications) Short name: DHNA1 Publication Alternative name(s): 7,8-dihydroneopterin aldolase FasA1 Publication FasB1 Publication 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase1 Publication (EC:2.7.6.32 Publications) Short name: HPPK Alternative name(s): 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase 7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase Short name: PPPK1 Publication Dihydropterin pyrophosphokinase1 Publication FasC1 Publication Dihydropteroate synthase1 Publication (EC:2.5.1.151 Publication) Short name: DHPS1 Publication Alternative name(s): Dihydropteroate pyrophosphorylase FasD1 Publication
Gene namesⁱ	Name:fol1 Synonyms:fas1 Publication
Organismⁱ	Pneumocystis carinii
Taxonomic identifierⁱ	4754 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Fungi › Dikarya › Ascomycota › Taphrinomycotina › Pneumocystidomycetes › Pneumocystidales › Pneumocystidaceae › Pneumocystis

Pathology & Biotechⁱ

Mutagenesis

Feature key	Position(s)	DescriptionActions	Length
Mutagenesisⁱ	39	D → E: Abolishes DHNA activity. 1 Publication	1
Mutagenesisⁱ	53	G → A: Reduces DHNA activity 11-fold. 1 Publication	1
Mutagenesisⁱ	63	Q → N: Reduces DHNA activity 16-fold. 1 Publication	1
Mutagenesisⁱ	161	D → E: No effect. 1 Publication	1
Mutagenesisⁱ	175	G → A: Abolishes DHNA activity. 1 Publication	1
Mutagenesisⁱ	185	Q → N: Reduces DHNA activity 24-fold. 1 Publication	1

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000168242	1 – 740	Folic acid synthesis protein fol1Add BLAST		740

Structureⁱ

3D structure databases

ProteinModelPortalⁱ	P29251
SMRⁱ	P29251
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	471 – 730	Pterin-bindingPROSITE-ProRule annotationAdd BLAST		260

Region

Feature key	Position(s)	DescriptionActions	Length
Regionⁱ	39 – 160	DHNA 1Add BLAST	122
Regionⁱ	161 – 280	DHNA 2Add BLAST	120
Regionⁱ	291 – 449	HPPKAdd BLAST	159
Regionⁱ	473 – 740	DHPSAdd BLAST	268
Regionⁱ	718 – 720	6-hydroxymethyl-7,8-dihydropterin diphosphate bindingBy similarity	3

Sequence similaritiesⁱ

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

In the central section; belongs to the HPPK family.Curated

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

Family and domain databases

Conserved Domains Database More...CDDⁱ	cd00534 DHNA_DHNTPE, 2 hits cd00739 DHPS, 1 hit cd00483 HPPK, 1 hit
Gene3Dⁱ	3.20.20.20, 1 hit 3.30.70.560, 1 hit
InterProⁱ	View protein in InterPro IPR006390 DHP_synth IPR011005 Dihydropteroate_synth-like IPR006157 FolB_dom IPR016261 Folic_acid_synth IPR000550 Hppk IPR035907 Hppk_sf IPR000489 Pterin-binding_dom
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF02152 FolB, 2 hits PF01288 HPPK, 1 hit PF00809 Pterin_bind, 1 hit
PIRSFⁱ	PIRSF000741 Folic_acid_synth, 1 hit
SMARTⁱ	View protein in SMART SM00905 FolB, 2 hits
SUPFAMⁱ	SSF51717 SSF51717, 1 hit SSF55083 SSF55083, 1 hit
TIGRFAMsⁱ	TIGR01496 DHPS, 1 hit TIGR00526 folB_dom, 2 hits TIGR01498 folK, 1 hit
PROSITEⁱ	View protein in PROSITE PS00792 DHPS_1, 1 hit PS00793 DHPS_2, 1 hit PS00794 HPPK, 1 hit PS50972 PTERIN_BINDING, 1 hit

Sequenceⁱ

Sequence statusⁱ: Complete.

P29251-1 [UniParc]FASTA Add to basket

« Hide

        10         20         30         40         50
MIFKSLKIFP FYQIYGFRFL KGMIFKKKIH LSKLNKNHDL IHIHSLTLKS 
        60         70         80         90        100
IVGKNSWAQR LLQPVVLTLS MGINASLSGN MDDLSYSIDY ATVYKEVFKL 
       110        120        130        140        150
VENSKFENLL DLSDKISKVV LGDKCKGNWV KVIAETPKGH LLAETGLQII 
       160        170        180        190        200
RRKDGIREID DQFFIKNLSL YTIIGINPEE RVNKQNIIID LILFKSSINL 
       210        220        230        240        250
ECKDDFIINT YNIEKLLKEI VKHVEESTFK TIEALALSIA RISCISHNIE 
       260        270        280        290        300
KIIVKVKKSC ALAFAESAGV EIVRSRSCFS SNNYIKSENS IDNEAVYISL 
       310        320        330        340        350
GSNLGNRIKF ILDAIEKMSI KGIKVLKTSM LYESKPMYFK DQPAFYNAVC 
       360        370        380        390        400
KVQTSLHPEQ LLFELQLIEK ELGRVKVIDK GPRCIDLDIV FYGRKIINSE 
       410        420        430        440        450
SLIIPHPRVL ERSFVLKPLL DISGDLVHPV TGLSIASYFE KIVDHDIKPV 
       460        470        480        490        500
LPFLYKNKSI DFSFRSYKAP TYIMAILNLT PDSFFDGGIH SYDSVLIDVE 
       510        520        530        540        550
KFINAGATII DIGGQSTRPG SYIIPLEEEI FRVIPAIKYL QKTYPDILIS 
       560        570        580        590        600
IDTFRSEVAE QAVKAGASLV NDISGGRYDP KMFNTVARLK VPICIMHMRG 
       610        620        630        640        650
NFLNMDNLTD YGTDIIEQIT IELEKLLNSA EKSGIPRWNI ILDPGLGFSK 
       660        670        680        690        700
TLHQNIELLR RFNELKSKNC FNGLPWLLGP SRKRFTGFIT GDNMPKDRIW 
       710        720        730        740
GTVAAVVASI SGGCDIIRVH DVYEMYKISK MSDAIWKEIY

Length:740

Mass (Da):83,962

Last modified:December 1, 1992 - v1

Checksum:ⁱ328F6EB91B4499EB

GO

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	M86602 Genomic DNA Translation: AAA33790.1
PIRⁱ	S28666

Protein	Similar proteins		Species	Score	Length	Source
P29251	Folic acid synthesis protein fol1		PNEC8		718	UniRef100_P29251

Protein	Similar proteins		Species	Score	Length	Source
P29251	Folic acid synthesis protein fol1		PNEC8		718	UniRef90_P29251
Folic acid synthesis protein fol1		PNEMU		742
Dihydropteroate synthase (Fragment)		Pneumocystis murina		82
Dihydropteroate synthase (Fragment)		Pneumocystis murina		285

Protein	Similar proteins		Species	Score	Length	Source
P29251	Folic acid synthesis protein fol1		PNEC8		718	UniRef50_P29251
Folic acid synthesis protein fol1		PNEMU		742
Dihydropteroate synthase (Fragment)		Pneumocystis murina		82
Folic acid synthesis protein fol1		Pneumocystis carinii f. sp. macacae		741
Folic acid synthesis protein fol1		PNEJ8		742
+4

Cross-referencesⁱ

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	M86602 Genomic DNA Translation: AAA33790.1
PIRⁱ	S28666

3D structure databases

ProteinModelPortalⁱ	P29251
SMRⁱ	P29251
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

Enzyme and pathway databases

UniPathwayⁱ	UPA00077;UER00154 UPA00077;UER00155 UPA00077;UER00156
SABIO-RKⁱ	P29251

Family and domain databases

CDDⁱ	cd00534 DHNA_DHNTPE, 2 hits cd00739 DHPS, 1 hit cd00483 HPPK, 1 hit
Gene3Dⁱ	3.20.20.20, 1 hit 3.30.70.560, 1 hit
InterProⁱ	View protein in InterPro IPR006390 DHP_synth IPR011005 Dihydropteroate_synth-like IPR006157 FolB_dom IPR016261 Folic_acid_synth IPR000550 Hppk IPR035907 Hppk_sf IPR000489 Pterin-binding_dom
Pfamⁱ	View protein in Pfam PF02152 FolB, 2 hits PF01288 HPPK, 1 hit PF00809 Pterin_bind, 1 hit
PIRSFⁱ	PIRSF000741 Folic_acid_synth, 1 hit
SMARTⁱ	View protein in SMART SM00905 FolB, 2 hits
SUPFAMⁱ	SSF51717 SSF51717, 1 hit SSF55083 SSF55083, 1 hit
TIGRFAMsⁱ	TIGR01496 DHPS, 1 hit TIGR00526 folB_dom, 2 hits TIGR01498 folK, 1 hit
PROSITEⁱ	View protein in PROSITE PS00792 DHPS_1, 1 hit PS00793 DHPS_2, 1 hit PS00794 HPPK, 1 hit PS50972 PTERIN_BINDING, 1 hit
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	FOL1_PNECA
Accessionⁱ	P29251Primary (citable) accession number: P29251
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	December 1, 1992
	Last sequence update:	December 1, 1992
	Last modified:	May 23, 2018
	This is version 95 of the entry and version 1 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Fungal Protein Annotation Program

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UniProtKB - P29251 (FOL1_PNECA)

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Folic acid synthesis protein fol1

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<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

<p>This subsection of the ‘Function’ section describes biophysical and chemical properties, such as maximal absorption, kinetic parameters, pH dependence, redox potentials and temperature dependence.<p><a href='/help/biophysicochemical_properties' target='_top'>More...</a></p>Kineticsi

pH dependencei

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section describes the metabolic pathway(s) associated with a protein.<p><a href='/help/pathway' target='_top'>More...</a></p>Pathwayi: tetrahydrofolate biosynthesis

Pathwayi: tetrahydrofolate biosynthesis

Sites

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Region

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Family and domain databases

Sequence databases

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

3D structure databases

Protocols and materials databases

Enzyme and pathway databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

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Keywords - Technical termi

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Functionⁱ

Kineticsⁱ

pH dependenceⁱ

Pathwayⁱ: tetrahydrofolate biosynthesis

Pathwayⁱ: tetrahydrofolate biosynthesis

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ