O75891 (AL1L1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	902 AA.
Sequence status	Complete.
Protein existence	Evidence 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.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.
Sequence caution	The sequence CAH18667.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	One-carbon metabolism
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	NADP Phosphopantetheine
Molecular function	Oxidoreductase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	10-formyltetrahydrofolate catabolic process Traceable author statement. Source: ProtInc biosynthetic process Inferred from electronic annotation. Source: InterPro
Molecular function	acyl carrier activity Inferred from electronic annotation. Source: InterPro cofactor binding Inferred from electronic annotation. Source: InterPro formyltetrahydrofolate dehydrogenase activity Inferred from electronic annotation. Source: EC hydroxymethyl-, formyl- and related transferase activity Inferred from electronic annotation. Source: InterPro methyltransferase activity Inferred from electronic annotation. Source: InterPro oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 902

902

Cytosolic 10-formyltetrahydrofolate dehydrogenase

PRO_0000199419

Regions

Domain

323 – 392

70

Acyl carrier

Region

1 – 203

203

GART

Region

417 – 902

486

Aldehyde dehydrogenase

Sites

Active site

106

1

Proton donor By similarity

Active site

673

1

By similarity

Active site

707

1

By similarity

Site

142

1

Essential for catalytic activity By similarity

Amino acid modifications

Modified residue

354

1

O-(pantetheine 4'-phosphoryl)serine By similarity

Modified residue

613

1

Phosphothreonine Ref.3

Natural variations

Natural variant

254

1

L → P.
Corresponds to variant rs3796191 [ dbSNP | Ensembl ].

VAR_052290

Natural variant

330

1

V → F.
Corresponds to variant rs2886059 [ dbSNP | Ensembl ].

VAR_052291

Natural variant

429

1

E → A.
Corresponds to variant rs9282691 [ dbSNP | Ensembl ].

VAR_052292

Natural variant

436

1

A → T.
Corresponds to variant rs9282692 [ dbSNP | Ensembl ].

VAR_052293

Natural variant

436

1

A → V.
Corresponds to variant rs9282693 [ dbSNP | Ensembl ].

VAR_052294

Natural variant

448

1

S → N.
Corresponds to variant rs9282697 [ dbSNP | Ensembl ].

VAR_052295

Natural variant

481

1

S → G.
Corresponds to variant rs2276724 [ dbSNP | Ensembl ].

VAR_052296

Natural variant

511

1

A → V in a colorectal cancer sample; somatic mutation. Ref.7

VAR_036101

Natural variant

793

1

D → G.
Corresponds to variant rs1127717 [ dbSNP | Ensembl ].

VAR_052297

Natural variant

803

1

E → K.
Corresponds to variant rs9282689 [ dbSNP | Ensembl ].

VAR_052298

Natural variant

812

1

I → V.
Corresponds to variant rs4646750 [ dbSNP | Ensembl ].

VAR_052299

Experimental info

Sequence conflict

63

1

G → A in AAC35000. Ref.1

Sequence conflict

85

1

F → S in AAC35000. Ref.1

Sequence conflict

176

1

M → V in AAC35000. Ref.1

Sequence conflict

195

1

E → K in AAC35000. Ref.1

Sequence conflict

470

1

D → G in AAC35000. Ref.1

Sequence conflict

677

1

K → E in AAC35000. Ref.1

Sequence conflict

680

1

L → F in AAC35000. Ref.1

Sequence conflict

702

1

N → S in AAC35000. Ref.1

Secondary structure

1

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902

Helix Strand Turn

Details...

Beta strand

2 – 6

5

Helix

9 – 21

13

Beta strand

25 – 31

7

Helix

41 – 49

9

Beta strand

53 – 55

3

Helix

67 – 74

8

Beta strand

79 – 85

7

Helix

92 – 95

4

Beta strand

102 – 108

7

Turn

110 – 113

4

Beta strand

114 – 116

3

Helix

118 – 124

7

Beta strand

128 – 136

9

Beta strand

139 – 142

4

Beta strand

146 – 153

8

Helix

160 – 166

7

Turn

167 – 169

3

Helix

170 – 185

16

Helix

206 – 209

4

Helix

217 – 225

9

Turn

226 – 231

6

Beta strand

234 – 237

4

Beta strand

240 – 249

10

Beta strand

258 – 261

4

Beta strand

270 – 273

4

Beta strand

276 – 280

5

Beta strand

286 – 293

8

Beta strand

299 – 301

3

Helix

302 – 304

3

Helix

320 – 334

15

Helix

347 – 351

5

Helix

356 – 367

12

Helix

375 – 380

6

Helix

384 – 397

14

Sequences

	Sequence		Length	Mass (Da)
	O75891 [UniParc]. Last modified February 15, 2005. Version 2. Checksum: D92CB2930617F7CF	FASTA	902	98,829
	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

References

	« Hide 'large scale' referencesShow '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].
[2]	"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: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Colon carcinoma.
[3]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-613, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[4]	"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: 20498374] [Abstract] Cited for: TISSUE SPECIFICITY.
[5]	"Crystal structure of human 10-formyltetrahydrofolate dehydrogenase." Ogg D.J., Stenmark P., Arrowsmith C., Edwards A., Ehn M., Graslund S., Hammarstrom M., Hallberg M., Kotenyova T., Nilsson-Ehle P., Nordlund P., Persson C., Sagemark J., Schuler H., Sundstrom M., Thorsell A., Weigelt J. Submitted (JUL-2005) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 1-307.
[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]	"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. , 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: 16959974] [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.
CR749807 mRNA. Translation: CAH18667.1. Different initiation.

IPI

IPI00290553.

RefSeq

NP_036322.2. NM_012190.2.

UniGene

Hs.434435.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2BW0	X-ray	1.70	A	1-307	[»]
2CFI	X-ray	1.85	A	1-307	[»]
2CQ8	NMR	-	A	305-401	[»]

ProteinModelPortal

O75891.

SMR

O75891. Positions 1-401, 406-902.

ModBase

Search...

Protein-protein interaction databases

STRING

O75891.

PTM databases

PhosphoSite

O75891.

Proteomic databases

PRIDE

O75891.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000273450; ENSP00000273450; ENSG00000144908.
ENST00000393434; ENSP00000377083; ENSG00000144908.
ENST00000472186; ENSP00000420293; ENSG00000144908.

GeneID

10840.

KEGG

hsa:10840.

NMPDR

fig|9606.3.peg.23112.

UCSC

uc003eim.1. human.

Organism-specific databases

CTD

10840.

GeneCards

GC03M125822.

H-InvDB

HIX0003632.
HIX0017226.

HGNC

HGNC:3978. ALDH1L1.

HPA

HPA036900.

MIM

600249. gene.

neXtProt

NX_O75891.

PharmGKB

PA28393.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG12626.

HOVERGEN

HBG051668.

InParanoid

O75891.

OrthoDB

EOG45TCMG.

PhylomeDB

O75891.

Gene expression databases

ArrayExpress

O75891.

Bgee

O75891.

CleanEx

HS_ALDH1L1.

Genevestigator

O75891.

GermOnline

ENSG00000144908. Homo sapiens.

Family and domain databases

InterPro

IPR011407. 10_FTHF_DH.
IPR009081. Acyl_carrier_prot-like.
IPR016161. Ald_DH/histidinol_DH.
IPR016163. Ald_DH_C.
IPR016160. Ald_DH_CS.
IPR016162. Ald_DH_N.
IPR015590. Aldehyde_DH_dom.
IPR005793. Formyl_trans_C.
IPR002376. Formyl_transf_N.
IPR011034. Formyl_transferase_C-like.
IPR001555. GART_AS.
IPR006163. Phsphopanteth-bd.
[Graphical view]

Gene3D

G3DSA:1.10.1200.10. ACP_like. 1 hit.
G3DSA:3.40.309.10. Aldehyde_dehydrogenase_C. 1 hit.
G3DSA:3.40.605.10. Aldehyde_dehydrogenase_N. 1 hit.
G3DSA:3.10.25.10. Formyl_trans_C. 1 hit.
G3DSA:3.40.50.170. Formyl_transf_N. 1 hit.

KO

K00289.

Pfam

PF00171. Aldedh. 1 hit.
PF02911. Formyl_trans_C. 1 hit.
PF00551. Formyl_trans_N. 1 hit.
PF00550. PP-binding. 1 hit.
[Graphical view]

PIRSF

PIRSF036489. 10-FTHFDH. 1 hit.

SUPFAM

SSF47336. ACP_like. 1 hit.
SSF53720. Aldehyde_DH/Histidinol_DH. 1 hit.
SSF50486. FMT_C_like. 1 hit.
SSF53328. formyl_transf. 1 hit.

PROSITE

PS50075. ACP_DOMAIN. 1 hit.
PS00070. ALDEHYDE_DEHYDR_CYS. 1 hit.
PS00687. ALDEHYDE_DEHYDR_GLU. 1 hit.
PS00373. GART. 1 hit.
PS00012. PHOSPHOPANTETHEINE. False negative.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB00116. Tetrahydrofolic acid.

NextBio

41156.

SOURCE

Search...

Entry information

Entry name

AL1L1_HUMAN

Accession

Primary (citable) accession number: O75891
Secondary accession number(s): Q68CS1

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	February 15, 2005
Last modified:	January 25, 2012
This is version 116 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.