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O75891 (AL1L1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 143. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·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
Gene names
Name:ALDH1L1
Synonyms:FTHFD
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

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

General annotation (Comments)

Catalytic activity

10-formyltetrahydrofolate + NADP+ + H2O = tetrahydrofolate + CO2 + NADPH.

Subcellular location

Cytoplasm.

Tissue specificity

Highly expressed in liver, pancreas and kidney. Ref.5

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.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O75891-1)

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.
Isoform 2 (identifier: O75891-2)

The sequence of this isoform differs from the canonical sequence as follows:
     118-218: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: O75891-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MAGPSNPPATM

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 902902Cytosolic 10-formyltetrahydrofolate dehydrogenase
PRO_0000199419

Regions

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

Sites

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

Amino acid modifications

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

Natural variations

Alternative sequence11M → MAGPSNPPATM in isoform 3.
VSP_047260
Alternative sequence118 – 218101Missing in isoform 2.
VSP_045569
Natural variant2541L → P.
Corresponds to variant rs3796191 [ dbSNP | Ensembl ].
VAR_052290
Natural variant3301V → F.
Corresponds to variant rs2886059 [ dbSNP | Ensembl ].
VAR_052291
Natural variant4291E → A.
Corresponds to variant rs9282691 [ dbSNP | Ensembl ].
VAR_052292
Natural variant4361A → T.
Corresponds to variant rs9282692 [ dbSNP | Ensembl ].
VAR_052293
Natural variant4361A → V.
Corresponds to variant rs9282693 [ dbSNP | Ensembl ].
VAR_052294
Natural variant4481S → N.
Corresponds to variant rs9282697 [ dbSNP | Ensembl ].
VAR_052295
Natural variant4811S → G.
Corresponds to variant rs2276724 [ dbSNP | Ensembl ].
VAR_052296
Natural variant5111A → V in a colorectal cancer sample; somatic mutation. Ref.8
VAR_036101
Natural variant7931D → G.
Corresponds to variant rs1127717 [ dbSNP | Ensembl ].
VAR_052297
Natural variant8031E → K.
Corresponds to variant rs9282689 [ dbSNP | Ensembl ].
VAR_052298
Natural variant8121I → V.
Corresponds to variant rs4646750 [ dbSNP | Ensembl ].
VAR_052299

Experimental info

Sequence conflict631G → A in AAC35000. Ref.1
Sequence conflict851F → S in AAC35000. Ref.1
Sequence conflict1761M → V in AAC35000. Ref.1
Sequence conflict1951E → K in AAC35000. Ref.1
Sequence conflict4701D → G in AAC35000. Ref.1
Sequence conflict4721F → L in BAG57647. Ref.2
Sequence conflict6771K → E in AAC35000. Ref.1
Sequence conflict6801L → F in AAC35000. Ref.1
Sequence conflict7021N → S in AAC35000. Ref.1

Secondary structure

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

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 15, 2005. Version 2.
Checksum: D92CB2930617F7CF

FASTA90298,829
        10         20         30         40         50         60 
MKIAVIGQSL FGQEVYCHLR KEGHEVVGVF TVPDKDGKAD PLGLEAEKDG VPVFKYSRWR 

        70         80         90        100        110        120 
AKGQALPDVV AKYQALGAEL NVLPFCSQFI PMEIISAPRH GSIIYHPSLL PRHRGASAIN 

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

       190        200        210        220        230        240 
RLIAEGKAPR LPQPEEGATY EGIQKKETAK INWDQPAEAI HNWIRGNDKV PGAWTEACEQ 

       250        260        270        280        290        300 
KLTFFNSTLN TSGLVPEGDA LPIPGAHRPG VVTKAGLILF GNDDKMLLVK NIQLEDGKMI 

       310        320        330        340        350        360 
LASNFFKGAA SSVLELTEAE LVTAEAVRSV WQRILPKVLE VEDSTDFFKS GAASVDVVRL 

       370        380        390        400        410        420 
VEEVKELCDG LELENEDVYM ASTFGDFIQL LVRKLRGDDE EGECSIDYVE MAVNKRTVRM 

       430        440        450        460        470        480 
PHQLFIGGEF VDAEGAKTSE TINPTDGSVI CQVSLAQVTD VDKAVAAAKD AFENGRWGKI 

       490        500        510        520        530        540 
SARDRGRLMY RLADLMEQHQ EELATIEALD AGAVYTLALK THVGMSIQTF RYFAGWCDKI 

       550        560        570        580        590        600 
QGSTIPINQA RPNRNLTLTR KEPVGVCGII IPWNYPLMML SWKTAACLAA GNTVVIKPAQ 

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

       670        680        690        700        710        720 
SCAISNVKKV SLELGGKSPL IIFADCDLNK AVQMGMSSVF FNKGENCIAA GRLFVEDSIH 

       730        740        750        760        770        780 
DEFVRRVVEE VRKMKVGNPL DRDTDHGPQN HHAHLVKLME YCQHGVKEGA TLVCGGNQVP 

       790        800        810        820        830        840 
RPGFFFEPTV FTDVEDHMFI AKEESFGPVM IISRFADGDL DAVLSRANAT EFGLASGVFT 

       850        860        870        880        890        900 
RDINKALYVS DKLQAGTVFV NTYNKTDVAA PFGGFKQSGF GKDLGEAALN EYLRVKTVTF 


EY 

« Hide

Isoform 2 [UniParc].

Checksum: 2749168F3D76D548
Show »

FASTA80187,602
Isoform 3 [UniParc].

Checksum: 4703ADF87C0467D9
Show »

FASTA91299,753

References

« Hide 'large scale' references
[1]Hong M.H., Lee Y., Kim J.W., Kang B.S., Choe I.S.
Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Amygdala.
[3]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Tissue: Colon carcinoma.
[4]"The DNA sequence, annotation and analysis of human chromosome 3."
Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. expand/collapse author list , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"ALDH1L2 is the mitochondrial homolog of 10-formyltetrahydrofolate dehydrogenase."
Krupenko N.I., Dubard M.E., Strickland K.C., Moxley K.M., Oleinik N.V., Krupenko S.A.
J. Biol. Chem. 285:23056-23063(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[6]"Solution structure of RSGI RUH-033, a PP-binding domain of 10-FTHFDH from human cDNA."
RIKEN structural genomics initiative (RSGI)
Submitted (NOV-2005) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 303-405.
[7]"Structures of the hydrolase domain of human 10-formyltetrahydrofolate dehydrogenase and its complex with a substrate analogue."
Kursula P., Schuler H., Flodin S., Nilsson-Ehle P., Ogg D.J., Savitsky P., Nordlund P., Stenmark P.
Acta Crystallogr. D 62:1294-1299(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 1-307 IN COMPLEX WITH 6-FORMYLTETRAHYDROPTERIN, ACTIVE SITE.
[8]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] VAL-511.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF052732 mRNA. Translation: AAC35000.1.
AK294392 mRNA. Translation: BAG57647.1.
CR749807 mRNA. Translation: CAH18667.1.
AC079848 Genomic DNA. No translation available.
CCDSCCDS3034.1. [O75891-1]
CCDS58850.1. [O75891-2]
CCDS58851.1. [O75891-3]
RefSeqNP_001257293.1. NM_001270364.1. [O75891-3]
NP_001257294.1. NM_001270365.1. [O75891-2]
NP_036322.2. NM_012190.3. [O75891-1]
XP_006713544.1. XM_006713481.1. [O75891-1]
UniGeneHs.434435.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2BW0X-ray1.70A1-307[»]
2CFIX-ray1.85A1-307[»]
2CQ8NMR-A305-401[»]
ProteinModelPortalO75891.
SMRO75891. Positions 1-401, 406-902.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000377083.

Chemistry

DrugBankDB00116. Tetrahydrofolic acid.

PTM databases

PhosphoSiteO75891.

Proteomic databases

MaxQBO75891.
PaxDbO75891.
PRIDEO75891.

Protocols and materials databases

DNASU10840.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000273450; ENSP00000273450; ENSG00000144908. [O75891-3]
ENST00000393434; ENSP00000377083; ENSG00000144908. [O75891-1]
ENST00000452905; ENSP00000395881; ENSG00000144908. [O75891-2]
ENST00000472186; ENSP00000420293; ENSG00000144908. [O75891-1]
GeneID10840.
KEGGhsa:10840.
UCSCuc003eim.2. human. [O75891-1]

Organism-specific databases

CTD10840.
GeneCardsGC03M125822.
HGNCHGNC:3978. ALDH1L1.
HPAHPA036900.
MIM600249. gene.
neXtProtNX_O75891.
PharmGKBPA28393.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1012.
HOVERGENHBG051668.
InParanoidO75891.
KOK00289.
OMAMASTFGD.
OrthoDBEOG7MSMN7.
PhylomeDBO75891.
TreeFamTF354242.

Enzyme and pathway databases

BioCycMetaCyc:HS07217-MONOMER.

Gene expression databases

ArrayExpressO75891.
BgeeO75891.
CleanExHS_ALDH1L1.
GenevestigatorO75891.

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

EvolutionaryTraceO75891.
GeneWikiALDH1L1.
GenomeRNAi10840.
NextBio41156.
PROO75891.
SOURCESearch...

Entry information

Entry nameAL1L1_HUMAN
AccessionPrimary (citable) accession number: O75891
Secondary accession number(s): B4DG36, E9PBX3, Q68CS1
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: February 15, 2005
Last modified: July 9, 2014
This is version 143 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM