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P28037 (AL1L1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 134. 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:
Cytosolic 10-formyltetrahydrofolate dehydrogenase

Short name=10-FTHFDH
Short name=FDH
EC=1.5.1.6
Alternative name(s):
Aldehyde dehydrogenase family 1 member L1
FBP-CI
Gene names
Name:Aldh1l1
Synonyms:Fthfd
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length902 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Catalytic activity

10-formyltetrahydrofolate + NADP+ + H2O = tetrahydrofolate + CO2 + NADPH. Ref.7 Ref.8

Subunit structure

Homotetramer. Ref.5 Ref.9

Subcellular location

Cytoplasm Ref.4.

Sequence similarities

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

In the C-terminal section; belongs to the aldehyde dehydrogenase family. ALDH1L subfamily.

Contains 1 acyl carrier domain.

Caution

The phosphoserine observed at Ser-354 in Ref.6 undoubtedly results from the secondary neutral loss of pantetheine from the phosphodiester linked cofactor.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 902902Cytosolic 10-formyltetrahydrofolate dehydrogenase
PRO_0000199422

Regions

Domain323 – 39270Acyl carrier
Nucleotide binding571 – 5733NADP
Nucleotide binding597 – 6004NADP
Nucleotide binding630 – 6356NADP
Nucleotide binding650 – 6512NADP
Nucleotide binding804 – 8063NADP
Region1 – 203203GART
Region88 – 903Substrate binding By similarity
Region417 – 902486Aldehyde dehydrogenase

Sites

Active site1061Proton donor By similarity
Active site6731Proton acceptor Probable
Active site7071Proton donor Probable
Binding site1421Substrate By similarity
Binding site7571NADP
Site1421Essential for catalytic activity

Amino acid modifications

Modified residue381N6-succinyllysine By similarity
Modified residue3541O-(pantetheine 4'-phosphoryl)serine; alternate Probable
Modified residue3541Phosphoserine; alternate Ref.6
Modified residue7671N6-succinyllysine By similarity

Experimental info

Mutagenesis1421D → A, N, E or Q: Loss of hydrolase activity. Ref.3
Mutagenesis6731E → A: Loss of aldehyde dehydrogenase activity. Ref.8
Mutagenesis7071C → A: Loss of dehydrogenase activity. No effect on hydrolase activity and NADP binding. Ref.5
Sequence conflict51 – 522VP → RA in AAA70429. Ref.1
Sequence conflict283 – 2842DD → EH in AAA70429. Ref.1
Sequence conflict3861G → E in AAA70429. Ref.1
Sequence conflict4111K → R in AAA70429. Ref.1
Sequence conflict5111A → R in AAA70429. Ref.1

Secondary structure

................................................................................................................................................. 902
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P28037 [UniParc].

Last modified March 21, 2012. Version 3.
Checksum: 562A8CBD73D6474A

FASTA90298,874
        10         20         30         40         50         60 
MKIAVIGQSL FGQEVYCQLR KEGHEVVGVF TIPDKDGKAD PLGLEAEKDG VPVFKFPRWR 

        70         80         90        100        110        120 
ARGQALPEVV AKYQALGAEL NVLPFCSQFI PMEVINAPRH GSIIYHPSLL PRHRGASAIN 

       130        140        150        160        170        180 
WTLIHGDKKG GFTIFWADDG LDTGDLLLQK ECEVLPDDTV STLYNRFLFP EGIKGMVQAV 

       190        200        210        220        230        240 
RLIAEGTAPR CPQSEEGATY EGIQKKETAK INWDQPAEAI HNWIRGNDKV PGAWTEACGQ 

       250        260        270        280        290        300 
KLTFFNSTLN TSGLSTQGEA LPIPGAHRPG VVTKAGLILF GNDDRMLLVK NIQLEDGKMM 

       310        320        330        340        350        360 
PASQFFKGSA SSDLELTEAE LATAEAVRSS WMRILPNVPE VEDSTDFFKS GAASVDVVRL 

       370        380        390        400        410        420 
VEEVKELCDG LELENEDVYM ATTFRGFIQL LVRKLRGEDD ESECVINYVE KAVNKLTLQM 

       430        440        450        460        470        480 
PYQLFIGGEF VDAEGSKTYN TINPTDGSVI CQVSLAQVSD VDKAVAAAKE AFENGLWGKI 

       490        500        510        520        530        540 
NARDRGRLLY RLADVMEQHQ EELATIEALD AGAVYTLALK THVGMSIQTF RYFAGWCDKI 

       550        560        570        580        590        600 
QGATIPINQA RPNRNLTLTK KEPVGVCGIV IPWNYPLMML SWKTAACLAA GNTVVIKPAQ 

       610        620        630        640        650        660 
VTPLTALKFA ELTLKAGIPK GVVNILPGSG SLVGQRLSDH PDVRKIGFTG STEVGKHIMK 

       670        680        690        700        710        720 
SCALSNVKKV SLELGGKSPL IIFADCDLNK AVQMGMSSVF FNKGENCIAA GRLFVEESIH 

       730        740        750        760        770        780 
NQFVQKVVEE VEKMKIGNPL ERDTNHGPQN HEAHLRKLVE YCQRGVKEGA TLVCGGNQVP 

       790        800        810        820        830        840 
RPGFFFQPTV FTDVEDHMYI AKEESFGPIM IISRFADGDV DAVLSRANAT EFGLASGVFT 

       850        860        870        880        890        900 
RDINKALYVS DKLQAGTVFI NTYNKTDVAA PFGGFKQSGF GKDLGEAALN EYLRIKTVTF 


EY 

« Hide

References

« Hide 'large scale' references
[1]"Isolation and characterization of cDNA clones for rat liver 10-formyltetrahydrofolate dehydrogenase."
Cook R.J., Lloyd R.S., Wagner C.
J. Biol. Chem. 266:4965-4973(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
Strain: Sprague-Dawley.
Tissue: Liver.
[2]"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].
Tissue: Ovary.
[3]"Aspartate 142 is involved in both hydrolase and dehydrogenase catalytic centers of 10-formyltetrahydrofolate dehydrogenase."
Krupenko S.A., Wagner C.
J. Biol. Chem. 274:35777-35784(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF N-TERMINUS, MUTAGENESIS OF ASP-142.
[4]"Resolution of rat liver 10-formyltetrahydrofolate dehydrogenase/hydrolase activities."
Case G.L., Kaisaki P.J., Steele R.D.
J. Biol. Chem. 263:10204-10207(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[5]"Cysteine 707 is involved in the dehydrogenase activity site of rat 10-formyltetrahydrofolate dehydrogenase."
Krupenko S.A., Wagner C., Cook R.J.
J. Biol. Chem. 270:519-522(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF CYS-707, FUNCTION, SUBUNIT.
[6]"Phosphoproteomic analysis of rat liver by high capacity IMAC and LC-MS/MS."
Moser K., White F.M.
J. Proteome Res. 5:98-104(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-354, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]"The crystal structure of the hydrolase domain of 10-formyltetrahydrofolate dehydrogenase: mechanism of hydrolysis and its interplay with the dehydrogenase domain."
Chumanevich A.A., Krupenko S.A., Davies C.
J. Biol. Chem. 279:14355-14364(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1-309, CATALYTIC ACTIVITY.
[8]"Crystal structures of the carboxyl terminal domain of rat 10-formyltetrahydrofolate dehydrogenase: implications for the catalytic mechanism of aldehyde dehydrogenases."
Tsybovsky Y., Donato H., Krupenko N.I., Davies C., Krupenko S.A.
Biochemistry 46:2917-2929(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 397-902 IN COMPLEX WITH NADP, CATALYTIC ACTIVITY, MUTAGENESIS OF GLU-673, ACTIVE SITE.
[9]"Conserved catalytic residues of the ALDH1L1 aldehyde dehydrogenase domain control binding and discharging of the coenzyme."
Tsybovsky Y., Krupenko S.A.
J. Biol. Chem. 286:23357-23367(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.89 ANGSTROMS) OF 397-902 IN COMPLEX WITH NADP, ACTIVE SITE, SUBUNIT.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M59861 mRNA. Translation: AAA70429.1.
BC089101 mRNA. Translation: AAH89101.1.
PIRA60560. A23709.
RefSeqNP_071992.1. NM_022547.1.
UniGeneRn.2328.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1S3IX-ray2.30A1-310[»]
2O2PX-ray1.70A/B/C/D397-902[»]
2O2QX-ray2.00A/B/C/D397-902[»]
2O2RX-ray2.20A/B/C/D397-902[»]
3RHJX-ray1.89A/B/C/D397-902[»]
3RHLX-ray2.00A/B/C/D397-902[»]
3RHMX-ray2.38A/B/C/D397-902[»]
3RHOX-ray2.26A/B/C/D397-902[»]
3RHPX-ray2.50A/B/C/D397-902[»]
3RHQX-ray2.10A/B/C/D397-902[»]
3RHRX-ray2.30A/B/C/D397-902[»]
4GNZX-ray2.30A/B/C/D397-902[»]
4GO0X-ray3.38A/B/C/D397-902[»]
4GO2X-ray2.28A/B/C/D397-902[»]
ProteinModelPortalP28037.
SMRP28037. Positions 1-402, 405-902.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

MINTMINT-4565983.

PTM databases

PhosphoSiteP28037.

Proteomic databases

PRIDEP28037.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID64392.
KEGGrno:64392.

Organism-specific databases

CTD10840.
RGD621294. Aldh1l1.

Phylogenomic databases

HOVERGENHBG051668.
KOK00289.

Enzyme and pathway databases

BRENDA1.5.1.6. 5301.
SABIO-RKP28037.

Gene expression databases

GenevestigatorP28037.

Family and domain databases

Gene3D1.10.1200.10. 1 hit.
3.10.25.10. 1 hit.
3.40.309.10. 1 hit.
3.40.50.170. 1 hit.
3.40.605.10. 1 hit.
InterProIPR011407. 10_FTHF_DH.
IPR009081. Acyl_carrier_prot-like.
IPR016161. Ald_DH/histidinol_DH.
IPR016163. Ald_DH_C.
IPR016160. Ald_DH_CS_CYS.
IPR029510. Ald_DH_CS_GLU.
IPR016162. Ald_DH_N.
IPR015590. Aldehyde_DH_dom.
IPR005793. Formyl_trans_C.
IPR002376. Formyl_transf_N.
IPR011034. Formyl_transferase_C-like.
IPR001555. GART_AS.
[Graphical view]
PfamPF00171. Aldedh. 1 hit.
PF02911. Formyl_trans_C. 1 hit.
PF00551. Formyl_trans_N. 1 hit.
PF00550. PP-binding. 1 hit.
[Graphical view]
PIRSFPIRSF036489. 10-FTHFDH. 1 hit.
SUPFAMSSF47336. SSF47336. 1 hit.
SSF50486. SSF50486. 1 hit.
SSF53328. SSF53328. 1 hit.
SSF53720. SSF53720. 1 hit.
PROSITEPS50075. ACP_DOMAIN. 1 hit.
PS00070. ALDEHYDE_DEHYDR_CYS. 1 hit.
PS00687. ALDEHYDE_DEHYDR_GLU. 1 hit.
PS00373. GART. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP28037.
NextBio613150.

Entry information

Entry nameAL1L1_RAT
AccessionPrimary (citable) accession number: P28037
Secondary accession number(s): Q5HZB2
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: March 21, 2012
Last modified: July 9, 2014
This is version 134 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references