Q9H903 (MTD2L_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Probable bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2

Alternative name(s):
NADP-dependent methylenetetrahydrofolate dehydrogenase 2-like protein
Short name=MTHFD2-like

Including the following 2 domains:

1. NAD-dependent methylenetetrahydrofolate dehydrogenase
   EC=1.5.1.15
2. Methenyltetrahydrofolate cyclohydrolase
   EC=3.5.4.9

Gene names

Name:

MTHFD2L

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	347 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.
Subcellular location	Mitochondrion inner membrane; Peripheral membrane protein; Matrix side By similarity.
Tissue specificity	Isoforms 1, 4 and 5 are expressed in brain and placenta. Ref.6
Sequence similarities	Belongs to the tetrahydrofolate dehydrogenase/cyclohydrolase family.
Sequence caution	The sequence AAH32771.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence BAB14441.1 differs from that shown. Reason: 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
Cellular component	Membrane Mitochondrion Mitochondrion inner membrane
Coding sequence diversity	Alternative splicing
Ligand	Magnesium NAD
Molecular function	Hydrolase Oxidoreductase
Technical term	Complete proteome Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological process	folic acid-containing compound 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 purine nucleotide biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	mitochondrial inner membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	methenyltetrahydrofolate cyclohydrolase activity Inferred from electronic annotation. Source: EC methylenetetrahydrofolate dehydrogenase (NAD+) activity Inferred from electronic annotation. Source: EC methylenetetrahydrofolate dehydrogenase (NADP+) activity Inferred from electronic annotation. Source: InterPro nucleotide binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 4 (identifier: Q9H903-4)

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 1 (identifier: Q9H903-1)

The sequence of this isoform differs from the canonical sequence as follows:
     1-58: Missing.

Isoform 2 (identifier: Q9H903-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-277: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: Q9H903-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-58: Missing.
     269-281: GIPKLITSDMVKE → ERFHHFAQDLSNS
     282-347: Missing.

Note: No experimental confirmation available.

Isoform 5 (identifier: Q9H903-5)

The sequence of this isoform differs from the canonical sequence as follows:
     269-310: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 347	347	Probable bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2		PRO_0000337097
Natural variations
	Alternative sequence	1 – 277	277	Missing in isoform 2.		VSP_041877
	Alternative sequence	1 – 58	58	Missing in isoform 1 and isoform 3.		VSP_041878
	Alternative sequence	269 – 310	42	Missing in isoform 5.		VSP_041879
	Alternative sequence	269 – 281	13	GIPKL…DMVKE → ERFHHFAQDLSNS in isoform 3.		VSP_041880
	Alternative sequence	282 – 347	66	Missing in isoform 3.		VSP_041881

Sequences

	Sequence		Length	Mass (Da)
	Isoform 4 [UniParc]. Last modified October 19, 2011. Version 3. Checksum: 2A2C787BF7C89C2E	FASTA	347	37,315
	10 20 30 40 50 60 MTVPVRGFSL LRGRLGRAPA LGRSTAPSVR APGEPGSAFR GFRSSGVRHE AIIISGTEMA 70 80 90 100 110 120 KHIQKEIQRG VESWVSLGNR RPHLSIILVG DNPASHTYVR NKIRAASAVG ICSELILKPK 130 140 150 160 170 180 DVSQEELLDV TDQLNMDPRV SGILVQLPLP DHVDERTICN GIAPEKDVDG FHIINIGRLC 190 200 210 220 230 240 LDQHSLIPAT ASAVWEIIKR TGIQTFGKNV VVAGRSKNVG MPIAMLLHTD GEHERPGGDA 250 260 270 280 290 300 TVTIAHRYTP KEQLKIHTQL ADIIIVAAGI PKLITSDMVK EGAAVIDVGI NYVHDPVTGK 310 320 330 340 TKLVGDVDFE AVKKKAGFIT PVPGGVGPMT VAMLLKNTLL AAKKIIY
	Isoform 1 [UniParc]. 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 [UniParc]. Checksum: 2F10655C298DA41F	FASTA	70	7,340
	10 20 30 40 50 60 MVKEGAAVID VGINYVHDPV TGKTKLVGDV DFEAVKKKAG FITPVPGGVG PMTVAMLLKN 70 TLLAAKKIIY
	Isoform 3 [UniParc]. 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
	Isoform 5 [UniParc]. Checksum: 2C88E9615943EE91	FASTA	305	32,891
	10 20 30 40 50 60 MTVPVRGFSL LRGRLGRAPA LGRSTAPSVR APGEPGSAFR GFRSSGVRHE AIIISGTEMA 70 80 90 100 110 120 KHIQKEIQRG VESWVSLGNR RPHLSIILVG DNPASHTYVR NKIRAASAVG ICSELILKPK 130 140 150 160 170 180 DVSQEELLDV TDQLNMDPRV SGILVQLPLP DHVDERTICN GIAPEKDVDG FHIINIGRLC 190 200 210 220 230 240 LDQHSLIPAT ASAVWEIIKR TGIQTFGKNV VVAGRSKNVG MPIAMLLHTD GEHERPGGDA 250 260 270 280 290 300 TVTIAHRYTP KEQLKIHTQL ADIIIVAAAV KKKAGFITPV PGGVGPMTVA MLLKNTLLAA KKIIY

References

	« Hide 'large scale' referencesShow 'large scale' 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]	"Regulation of human tetrahydrofolate dehydrogenase/cyclohydrolase." Liou J.R. Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 13-180 (ISOFORM 4).
[5]	"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 152-347 (ISOFORM 1). Tissue: Teratocarcinoma.
[6]	"Mammalian MTHFD2L encodes a mitochondrial methylenetetrahydrofolate dehydrogenase isozyme expressed in adult tissues." Bolusani S., Young B.A., Cole N.A., Tibbetts A.S., Momb J., Bryant J.D., Solmonson A., Appling D.R. J. Biol. Chem. 286:5166-5174(2011) [PubMed: 21163947] [Abstract] Cited for: ALTERNATIVE SPLICING (ISOFORMS 1; 4 AND 5), TISSUE SPECIFICITY.
+	Additional computationally mapped references.

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. AX794779 mRNA. No translation available. 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. NM_001144978.1.
UniGene	Hs.721011. Hs.729421.
3D structure databases
HSSP	HSSP built from PDB template 1A4I based on UniProtKB P11586.
ProteinModelPortal	Q9H903.
ModBase	Search...
Protein-protein interaction databases
STRING	Q9H903.
Polymorphism databases
DMDM	189029220.
Proteomic databases
PRIDE	Q9H903.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000325278; ENSP00000321984; ENSG00000163738. ENST00000395759; ENSP00000379108; ENSG00000163738.
GeneID	441024.
KEGG	hsa:441024.
UCSC	uc003hhp.1. human.
Organism-specific databases
CTD	441024.
GeneCards	GC04P074979.
HGNC	HGNC:31865. MTHFD2L.
HPA	HPA035434.
MIM	614047. gene.
neXtProt	NX_Q9H903.
PharmGKB	PA134943916.
GenAtlas	Search...
Phylogenomic databases
GeneTree	ENSGT00600000084403.
HOGENOM	HBG328751.
HOVERGEN	HBG006411.
InParanoid	Q9H903.
PhylomeDB	Q9H903.
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.
KO	K13403.
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
NextBio	109687.
SOURCE	Search...

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:	October 19, 2011
Last modified:	January 25, 2012
This is version 72 of the entry and version 3 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.