Reviewed, UniProtKB/Swiss-Prot Q9H903 (MTD2L_HUMAN)

Names and origin

Protein names

Recommended name:
    Probable bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2
Alternative name(s):
    NADP-dependent methylenetetrahydrofolate dehydrogenase 2-like protein
Including the following 2 domains:
    1- Recommended name:
            NAD-dependent methylenetetrahydrofolate dehydrogenase
              EC=1.5.1.15
    2- Recommended name:
            Methenyltetrahydrofolate cyclohydrolase
              EC=3.5.4.9

Gene names

Name:

MTHFD2L

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	289 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level.

General annotation (Comments)

Catalytic activity	5,10-methylenetetrahydrofolate + NAD+ = 5,10-methenyltetrahydrofolate + NADH. 5,10-methenyltetrahydrofolate + H2O = 10-formyltetrahydrofolate.
Cofactor	Magnesium By similarity.
Pathway	One-carbon metabolism; tetrahydrofolate interconversion.
Sequence similarities	Belongs to the tetrahydrofolate dehydrogenase/cyclohydrolase family.
Sequence caution	The sequence BAB14441.1 differs from that shown. Reason: Miscellaneous discrepancy. Contaminating sequence. Sequence of unknown origin in the N-terminal part.

Ontologies

Keywords
Biological process	Amino-acid biosynthesis Histidine biosynthesis Methionine biosynthesis One-carbon metabolism Purine biosynthesis
Coding sequence diversity	Alternative splicing
Ligand	Magnesium NAD
Molecular function	Hydrolase Oxidoreductase
Technical term	Complete proteome Multifunctional enzyme
Gene Ontology (GO)
Biological process	folic acid and derivative biosynthetic process Inferred from electronic annotation. Source: InterPro histidine biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW methionine biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW one-carbon metabolic process Inferred from electronic annotation. Source: UniProtKB-KW oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW purine nucleotide biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW methenyltetrahydrofolate cyclohydrolase activity Inferred from electronic annotation. Source: EC methylenetetrahydrofolate dehydrogenase (NAD+) activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q9H903-1)

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: Q9H903-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-219: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: Q9H903-3)

The sequence of this isoform differs from the canonical sequence as follows:
     211-223: GIPKLITSDMVKE → ERFHHFAQDLSNS
     224-289: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 289	289	Probable bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2		PRO_0000337097
Natural variations
	Alternative sequence	1 – 219	219	Missing in isoform 2.		VSP_033880
	Alternative sequence	211 – 223	13	GIPKL…DMVKE → ERFHHFAQDLSNS in isoform 3.		VSP_033881
	Alternative sequence	224 – 289	66	Missing in isoform 3.		VSP_033882

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 20, 2008. Version 2. Checksum: 7AF37065528EA88A	FASTA	289	31,285
	10 20 30 40 50 60 MAKHIQKEIQ RGVESWVSLG NRRPHLSIIL VGDNPASHTY VRNKIRAASA VGICSELILK 70 80 90 100 110 120 PKDVSQEELL DVTDQLNMDP RVSGILVQLP LPDHVDERTI CNGIAPEKDV DGFHIINIGR 130 140 150 160 170 180 LCLDQHSLIP ATASAVWEII KRTGIQTFGK NVVVAGRSKN VGMPIAMLLH TDGEHERPGG 190 200 210 220 230 240 DATVTIAHRY TPKEQLKIHT QLADIIIVAA GIPKLITSDM VKEGAAVIDV GINYVHDPVT 250 260 270 280 GKTKLVGDVD FEAVKKKAGF ITPVPGGVGP MTVAMLLKNT LLAAKKIIY
	Isoform 2. Checksum: 2F10655C298DA41F	FASTA	70	7,340
	10 20 30 40 50 60 MVKEGAAVID VGINYVHDPV TGKTKLVGDV DFEAVKKKAG FITPVPGGVG PMTVAMLLKN 70 TLLAAKKIIY
	Isoform 3. Checksum: 0AE4A0AD8E097705	FASTA	223	24,608
	10 20 30 40 50 60 MAKHIQKEIQ RGVESWVSLG NRRPHLSIIL VGDNPASHTY VRNKIRAASA VGICSELILK 70 80 90 100 110 120 PKDVSQEELL DVTDQLNMDP RVSGILVQLP LPDHVDERTI CNGIAPEKDV DGFHIINIGR 130 140 150 160 170 180 LCLDQHSLIP ATASAVWEII KRTGIQTFGK NVVVAGRSKN VGMPIAMLLH TDGEHERPGG 190 200 210 220 DATVTIAHRY TPKEQLKIHT QLADIIIVAA ERFHHFAQDL SNS

References

[1]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3). Tissue: Lung and Testis.
[4]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 94-236 (ISOFORM 1). Tissue: Teratocarcinoma.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AC093677 Genomic DNA. No translation available. AC097470 Genomic DNA. No translation available. CH471057 Genomic DNA. Translation: EAX05705.1. BC032771 mRNA. Translation: AAH32771.1. Different initiation. BC065771 mRNA. Translation: AAH65771.1. AK023167 mRNA. Translation: BAB14441.1. Sequence problems.
IPI	IPI00017391. IPI00746020. IPI00873515.
RefSeq	NP_001138450.1.
UniGene	Hs.479954
3D structure databases
HSSP	HSSP built from PDB template 1A4I based on UniProtKB P11586.
SMR	Q9H903. Positions 2-287.
ModBase	Search...
Protein-protein interaction databases
STRING	Q9H903.
Proteomic databases
PRIDE	Q9H903.
Genome annotation databases
Ensembl	ENST00000325278; ENSP00000321984; ENSG00000163738; Homo sapiens. [Genome view] ENST00000395759; ENSP00000379108; ENSG00000163738; Homo sapiens. [Genome view]
GeneID	441024.
KEGG	hsa:441024.
UCSC	uc003hhp.1. human.
Organism-specific databases
CTD	441024.
GeneCards	GC04P075207.
HGNC	HGNC:31865. MTHFD2L.
PharmGKB	PA134943916.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	HBG328751.
HOVERGEN	Q9H903.
InParanoid	Q9H903.
OrthoDB	EOG92JRBB.
Gene expression databases
ArrayExpress	Q9H903.
Bgee	Q9H903.
CleanEx	HS_MTHFD2L.
Genevestigator	Q9H903.
Family and domain databases
InterPro	IPR016040. NAD(P)-bd_dom. IPR000672. THF_DH/CycHdrlase. IPR020630. THF_DH/CycHdrlase_cat_dom. IPR020867. THF_DH/CycHdrlase_CS. IPR020631. THF_DH/CycHdrlase_NAD-bd_dom. [Graphical view]
Gene3D	G3DSA:3.40.50.720. NAD(P)-bd. 1 hit.
Pfam	PF00763. THF_DHG_CYH. 1 hit. PF02882. THF_DHG_CYH_C. 1 hit. [Graphical view]
PRINTS	PR00085. THFDHDRGNASE.
PROSITE	PS00766. THF_DHG_CYH_1. False negative. PS00767. THF_DHG_CYH_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	109687.

Entry information

Entry name

MTD2L_HUMAN

Accession

Primary (citable) accession number: Q9H903
Secondary accession number(s): Q6P079, Q8N560

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 20, 2008
Last sequence update:	May 20, 2008
Last modified:	January 19, 2010
This is version 55 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.