Q3SY69 (AL1L2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Mitochondrial 10-formyltetrahydrofolate dehydrogenase
Short name=Mitochondrial 10-FTHFDH
Short name=mtFDH
EC=1.5.1.6

Alternative name(s):
Aldehyde dehydrogenase family 1 member L2

Gene names

Name:

ALDH1L2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	923 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Catalytic activity	10-formyltetrahydrofolate + NADP+ + H2O = tetrahydrofolate + CO2 + NADPH.
Subcellular location	Mitochondrion Ref.5.
Tissue specificity	Highly expressed in pancreas, heart, brain and skeletal muscle. 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.
Sequence caution	The sequence AAI03936.1 differs from that shown. Reason: Erroneous translation. Wrong choice of CDS.

Ontologies

Keywords
Biological process	One-carbon metabolism
Cellular component	Mitochondrion
Coding sequence diversity	Alternative splicing
Domain	Transit peptide
Ligand	NADP Phosphopantetheine
Molecular function	Oxidoreductase
PTM	Acetylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	10-formyltetrahydrofolate catabolic process Inferred from electronic annotation. Source: InterPro biosynthetic process Inferred from electronic annotation. Source: InterPro methylation Inferred from electronic annotation. Source: GOC one-carbon metabolic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	mitochondrion Inferred from direct assay. Source: HPA
Molecular_function	formyltetrahydrofolate dehydrogenase activity Inferred from electronic annotation. Source: UniProtKB-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...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q3SY69-1)

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: Q3SY69-2)

The sequence of this isoform differs from the canonical sequence as follows:
     199-203: VEAVQ → KLSNS
     204-923: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: Q3SY69-3)

The sequence of this isoform differs from the canonical sequence as follows:
     512-516: RLADL → SMRMN
     517-923: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 923	923	Mitochondrial 10-formyltetrahydrofolate dehydrogenase		PRO_0000316001
	Transit peptide	1 – 19	19	Mitochondrion; not cleaved
Regions
	Domain	344 – 413	70	Acyl carrier
	Region	23 – 225	203	GART
	Region	438 – 923	486	Aldehyde dehydrogenase
Sites
	Active site	128	1	Proton donor By similarity
	Active site	694	1	By similarity
	Active site	728	1	By similarity
	Site	164	1	Essential for catalytic activity By similarity
Amino acid modifications
	Modified residue	375	1	O-(pantetheine 4'-phosphoryl)serine By similarity
	Modified residue	903	1	N6-acetyllysine Ref.4
Natural variations
	Alternative sequence	199 – 203	5	VEAVQ → KLSNS in isoform 2.		VSP_030752
	Alternative sequence	204 – 923	720	Missing in isoform 2.		VSP_030753
	Alternative sequence	512 – 516	5	RLADL → SMRMN in isoform 3.		VSP_030754
	Alternative sequence	517 – 923	407	Missing in isoform 3.		VSP_030755
Experimental info
	Sequence conflict	712	1	A → T in AAI03935. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 15, 2008. Version 2. Checksum: C5DD74506F08AAFE	FASTA	923	101,746
	10 20 30 40 50 60 MLRRGSQALR RFSTGRVYFK NKLKLALIGQ SLFGQEVYSH LRKEGHRVVG VFTVPDKDGK 70 80 90 100 110 120 ADPLALAAEK DGTPVFKLPK WRVKGKTIKE VAEAYRSVGA ELNVLPFCTQ FIPMDIIDSP 130 140 150 160 170 180 KHGSIIYHPS ILPRHRGASA INWTLIMGDK KAGFSVFWAD DGLDTGPILL QRSCDVEPND 190 200 210 220 230 240 TVDALYNRFL FPEGIKAMVE AVQLIADGKA PRIPQPEEGA TYEGIQKKEN AEISWDQSAE 250 260 270 280 290 300 VLHNWIRGHD KVPGAWTEIN GQMVTFYGST LLNSSVPPGE PLEIKGAKKP GLVTKNGLVL 310 320 330 340 350 360 FGNDGKALTV RNLQFEDGKM IPASQYFSTG ETSVVELTAE EVKVAETIKV IWAGILSNVP 370 380 390 400 410 420 IIEDSTDFFK SGASSMDVAR LVEEIRQKCG GLQLQNEDVY MATKFEGFIQ KVVRKLRGED 430 440 450 460 470 480 QEVELVVDYI SKEVNEIMVK MPYQCFINGQ FTDADDGKTY DTINPTDGST ICKVSYASLA 490 500 510 520 530 540 DVDKAVAAAK DAFENGEWGR MNARERGRLM YRLADLLEEN QEELATIEAL DSGAVYTLAL 550 560 570 580 590 600 KTHIGMSVQT FRYFAGWCDK IQGSTIPINQ ARPNRNLTFT KKEPLGVCAI IIPWNYPLMM 610 620 630 640 650 660 LAWKSAACLA AGNTLVLKPA QVTPLTALKF AELSVKAGFP KGVINIIPGS GGIAGQRLSE 670 680 690 700 710 720 HPDIRKLGFT GSTPIGKQIM KSCAVSNLKK VSLELGGKSP LIIFNDCELD KAVRMGMGAV 730 740 750 760 770 780 FFNKGENCIA AGRLFVEESI HDEFVTRVVE EIKKMKIGDP LDRSTDHGPQ NHKAHLEKLL 790 800 810 820 830 840 QYCETGVKEG ATLVYGGRQV QRPGFFMEPT VFTDVEDYMY LAKEESFGPI MVISKFQNGD 850 860 870 880 890 900 IDGVLQRANS TEYGLASGVF TRDINKAMYV SEKLEAGTVF INTYNKTDVA APFGGVKQSG 910 920 FGKDLGEEAL NEYLKTKTVT LEY
	Isoform 2 [UniParc]. Checksum: 4D3484F504153102	FASTA	203	22,643
	10 20 30 40 50 60 MLRRGSQALR RFSTGRVYFK NKLKLALIGQ SLFGQEVYSH LRKEGHRVVG VFTVPDKDGK 70 80 90 100 110 120 ADPLALAAEK DGTPVFKLPK WRVKGKTIKE VAEAYRSVGA ELNVLPFCTQ FIPMDIIDSP 130 140 150 160 170 180 KHGSIIYHPS ILPRHRGASA INWTLIMGDK KAGFSVFWAD DGLDTGPILL QRSCDVEPND 190 200 TVDALYNRFL FPEGIKAMKL SNS
	Isoform 3 [UniParc]. Checksum: 8C14B32D61FEFFF4	FASTA	516	57,244
	10 20 30 40 50 60 MLRRGSQALR RFSTGRVYFK NKLKLALIGQ SLFGQEVYSH LRKEGHRVVG VFTVPDKDGK 70 80 90 100 110 120 ADPLALAAEK DGTPVFKLPK WRVKGKTIKE VAEAYRSVGA ELNVLPFCTQ FIPMDIIDSP 130 140 150 160 170 180 KHGSIIYHPS ILPRHRGASA INWTLIMGDK KAGFSVFWAD DGLDTGPILL QRSCDVEPND 190 200 210 220 230 240 TVDALYNRFL FPEGIKAMVE AVQLIADGKA PRIPQPEEGA TYEGIQKKEN AEISWDQSAE 250 260 270 280 290 300 VLHNWIRGHD KVPGAWTEIN GQMVTFYGST LLNSSVPPGE PLEIKGAKKP GLVTKNGLVL 310 320 330 340 350 360 FGNDGKALTV RNLQFEDGKM IPASQYFSTG ETSVVELTAE EVKVAETIKV IWAGILSNVP 370 380 390 400 410 420 IIEDSTDFFK SGASSMDVAR LVEEIRQKCG GLQLQNEDVY MATKFEGFIQ KVVRKLRGED 430 440 450 460 470 480 QEVELVVDYI SKEVNEIMVK MPYQCFINGQ FTDADDGKTY DTINPTDGST ICKVSYASLA 490 500 510 DVDKAVAAAK DAFENGEWGR MNARERGRLM YSMRMN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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] (ISOFORMS 1 AND 2).
[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. , 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] OF 1-752 (ISOFORM 1). Tissue: Chondrocyte.
[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] OF 221-511 (ISOFORM 3), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 762-923 (ISOFORM 1). Tissue: Cervix and Uterus.
[4]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-903, MASS SPECTROMETRY.
[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: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	BC103934 mRNA. Translation: AAI03935.1. BC103935 mRNA. Translation: AAI03936.1. Sequence problems. AK095827 mRNA. Translation: BAC04634.1. CR627287 mRNA. Translation: CAH10368.1. Different termination. CR749561 mRNA. Translation: CAH18358.1.
IPI	IPI00298308. IPI00878398. IPI00878818.
RefSeq	NP_001029345.2. NM_001034173.3.
UniGene	Hs.42572.
3D structure databases
ProteinModelPortal	Q3SY69.
SMR	Q3SY69. Positions 23-422, 426-923.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q3SY69. 1 interaction.
MINT	MINT-8051641.
STRING	9606.ENSP00000258494.
PTM databases
PhosphoSite	Q3SY69.
Polymorphism databases
DMDM	166198355.
Proteomic databases
PaxDb	Q3SY69.
PRIDE	Q3SY69.
Protocols and materials databases
DNASU	160428.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000258494; ENSP00000258494; ENSG00000136010. ENST00000424857; ENSP00000389608; ENSG00000136010. ENST00000552270; ENSP00000447538; ENSG00000136010.
GeneID	160428.
KEGG	hsa:160428.
UCSC	uc001tlc.3. human.
Organism-specific databases
CTD	160428.
GeneCards	GC12M105417.
H-InvDB	HIX0017226.
HGNC	HGNC:26777. ALDH1L2.
HPA	HPA039481.
MIM	613584. gene.
neXtProt	NX_Q3SY69.
PharmGKB	PA134928545.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1012.
HOGENOM	HOG000006902.
HOVERGEN	HBG051668.
InParanoid	Q3SY69.
KO	K00289.
OMA	THIGMSV.
OrthoDB	EOG7MSMN7.
Gene expression databases
Bgee	Q3SY69.
CleanEx	HS_ALDH1L2.
Genevestigator	Q3SY69.
Family and domain databases
Gene3D	1.10.1200.10. 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.
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. IPR006162. PPantetheine_attach_site. [Graphical view]
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	SSF50486. SSF50486. 1 hit. SSF53328. SSF53328. 1 hit. SSF53720. SSF53720. 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. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GeneWiki	ALDH1L2.
GenomeRNAi	160428.
NextBio	87968.
PRO	Q3SY69.
SOURCE	Search...

Entry information

Entry name

AL1L2_HUMAN

Accession

Primary (citable) accession number: Q3SY69
Secondary accession number(s): Q3SY68 , Q68D62, Q6AI55, Q8N922

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 15, 2008
Last sequence update:	January 15, 2008
Last modified:	November 13, 2013
This is version 85 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.