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Protein

Dihydrofolate reductase, mitochondrial

Gene

DHFRL1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Required to prevent uracil accumulation in mtDNA. Binds its own mRNA and that of DHFR.2 Publications

Catalytic activityi

5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH.PROSITE-ProRule annotation1 Publication

Kineticsi

  1. KM=209 µM for dihydrofolate1 Publication
  2. KM=20 µM for NADPH1 Publication

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei10 – 101NADP; via amide nitrogen and carbonyl oxygenBy similarity
Binding sitei71 – 711SubstrateBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi16 – 227NADPBy similarity
Nucleotide bindingi55 – 573NADPBy similarity
Nucleotide bindingi77 – 793NADPBy similarity
Nucleotide bindingi117 – 1248NADPBy similarity

GO - Molecular functioni

  1. dihydrofolate reductase activity Source: UniProtKB
  2. mRNA binding Source: UniProtKB
  3. NADP binding Source: InterPro

GO - Biological processi

  1. glycine biosynthetic process Source: InterPro
  2. nucleotide biosynthetic process Source: InterPro
  3. one-carbon metabolic process Source: UniProtKB-KW
  4. tetrahydrofolate biosynthetic process Source: UniProtKB-UniPathway
  5. tetrahydrofolate metabolic process Source: UniProtKB
  6. thymidine biosynthetic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

One-carbon metabolism

Keywords - Ligandi

NADP

Enzyme and pathway databases

ReactomeiREACT_11167. Metabolism of folate and pterines.
UniPathwayiUPA00077; UER00158.

Names & Taxonomyi

Protein namesi
Recommended name:
Dihydrofolate reductase, mitochondrial (EC:1.5.1.3)
Alternative name(s):
Dihydrofolate reductase-like protein 1
Gene namesi
Name:DHFRL1
Synonyms:DHFRP4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:27309. DHFRL1.

Subcellular locationi

GO - Cellular componenti

  1. mitochondrial inner membrane Source: UniProtKB
  2. mitochondrial matrix Source: UniProtKB
  3. mitochondrion Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Membrane, Mitochondrion, Mitochondrion inner membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA134889916.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 187187Dihydrofolate reductase, mitochondrialPRO_0000186368Add
BLAST

Proteomic databases

PaxDbiQ86XF0.
PRIDEiQ86XF0.

PTM databases

PhosphoSiteiQ86XF0.

Expressioni

Tissue specificityi

Expressed in numerous cell lines.1 Publication

Gene expression databases

BgeeiQ86XF0.
ExpressionAtlasiQ86XF0. baseline and differential.
GenevestigatoriQ86XF0.

Organism-specific databases

HPAiHPA051465.

Interactioni

Protein-protein interaction databases

BioGridi128354. 12 interactions.
IntActiQ86XF0. 1 interaction.
STRINGi9606.ENSP00000319170.

Structurei

3D structure databases

ProteinModelPortaliQ86XF0.
SMRiQ86XF0. Positions 5-186.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini4 – 185182DHFRPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni31 – 366Substrate bindingBy similarity

Sequence similaritiesi

Belongs to the dihydrofolate reductase family.Curated
Contains 1 DHFR (dihydrofolate reductase) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0262.
GeneTreeiENSGT00390000010283.
HOGENOMiHOG000040235.
HOVERGENiHBG000773.
InParanoidiQ86XF0.
KOiK00287.
OMAiDNDLPWH.
OrthoDBiEOG7V1FS3.
PhylomeDBiQ86XF0.
TreeFamiTF317636.

Family and domain databases

Gene3Di3.40.430.10. 1 hit.
InterProiIPR012259. DHFR.
IPR024072. DHFR-like_dom.
IPR001796. DHFR_dom.
[Graphical view]
PfamiPF00186. DHFR_1. 1 hit.
[Graphical view]
PRINTSiPR00070. DHFR.
SUPFAMiSSF53597. SSF53597. 1 hit.
PROSITEiPS51330. DHFR_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q86XF0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MFLLLNCIVA VSQNMGIGKN GDLPRPPLRN EFRYFQRMTT TSSVEGKQNL
60 70 80 90 100
VIMGRKTWFS IPEKNRPLKD RINLVLSREL KEPPQGAHFL ARSLDDALKL
110 120 130 140 150
TERPELANKV DMIWIVGGSS VYKEAMNHLG HLKLFVTRIM QDFESDTFFS
160 170 180
EIDLEKYKLL PEYPGVLSDV QEGKHIKYKF EVCEKDD
Length:187
Mass (Da):21,620
Last modified:June 1, 2003 - v1
Checksum:iBA6548FB0F576FF7
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti166 – 1661V → I.1 Publication
Corresponds to variant rs17855824 [ dbSNP | Ensembl ].
VAR_061135

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL832912 mRNA. Translation: CAH10617.1.
CH471052 Genomic DNA. Translation: EAW79895.1.
CH471052 Genomic DNA. Translation: EAW79896.1.
BC045541 mRNA. Translation: AAH45541.1.
BC063379 mRNA. Translation: AAH63379.1.
CCDSiCCDS2926.1.
RefSeqiNP_001182572.1. NM_001195643.1.
NP_789785.1. NM_176815.4.
UniGeneiHs.718516.

Genome annotation databases

EnsembliENST00000314636; ENSP00000319170; ENSG00000178700.
ENST00000394221; ENSP00000377768; ENSG00000178700.
ENST00000461173; ENSP00000418415; ENSG00000178700.
ENST00000619045; ENSP00000480823; ENSG00000178700.
GeneIDi200895.
KEGGihsa:200895.
UCSCiuc003dri.3. human.

Polymorphism databases

DMDMi74727819.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL832912 mRNA. Translation: CAH10617.1.
CH471052 Genomic DNA. Translation: EAW79895.1.
CH471052 Genomic DNA. Translation: EAW79896.1.
BC045541 mRNA. Translation: AAH45541.1.
BC063379 mRNA. Translation: AAH63379.1.
CCDSiCCDS2926.1.
RefSeqiNP_001182572.1. NM_001195643.1.
NP_789785.1. NM_176815.4.
UniGeneiHs.718516.

3D structure databases

ProteinModelPortaliQ86XF0.
SMRiQ86XF0. Positions 5-186.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi128354. 12 interactions.
IntActiQ86XF0. 1 interaction.
STRINGi9606.ENSP00000319170.

PTM databases

PhosphoSiteiQ86XF0.

Polymorphism databases

DMDMi74727819.

Proteomic databases

PaxDbiQ86XF0.
PRIDEiQ86XF0.

Protocols and materials databases

DNASUi200895.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000314636; ENSP00000319170; ENSG00000178700.
ENST00000394221; ENSP00000377768; ENSG00000178700.
ENST00000461173; ENSP00000418415; ENSG00000178700.
ENST00000619045; ENSP00000480823; ENSG00000178700.
GeneIDi200895.
KEGGihsa:200895.
UCSCiuc003dri.3. human.

Organism-specific databases

CTDi200895.
GeneCardsiGC03M093766.
HGNCiHGNC:27309. DHFRL1.
HPAiHPA051465.
neXtProtiNX_Q86XF0.
PharmGKBiPA134889916.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0262.
GeneTreeiENSGT00390000010283.
HOGENOMiHOG000040235.
HOVERGENiHBG000773.
InParanoidiQ86XF0.
KOiK00287.
OMAiDNDLPWH.
OrthoDBiEOG7V1FS3.
PhylomeDBiQ86XF0.
TreeFamiTF317636.

Enzyme and pathway databases

UniPathwayiUPA00077; UER00158.
ReactomeiREACT_11167. Metabolism of folate and pterines.

Miscellaneous databases

ChiTaRSiDHFRL1. human.
GenomeRNAii200895.
NextBioi90000.
PROiQ86XF0.

Gene expression databases

BgeeiQ86XF0.
ExpressionAtlasiQ86XF0. baseline and differential.
GenevestigatoriQ86XF0.

Family and domain databases

Gene3Di3.40.430.10. 1 hit.
InterProiIPR012259. DHFR.
IPR024072. DHFR-like_dom.
IPR001796. DHFR_dom.
[Graphical view]
PfamiPF00186. DHFR_1. 1 hit.
[Graphical view]
PRINTSiPR00070. DHFR.
SUPFAMiSSF53597. SSF53597. 1 hit.
PROSITEiPS51330. DHFR_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Melanoma.
  2. 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(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ILE-166.
    Tissue: Brain and Muscle.
  4. "Identification of a de novo thymidylate biosynthesis pathway in mammalian mitochondria."
    Anderson D.D., Quintero C.M., Stover P.J.
    Proc. Natl. Acad. Sci. U.S.A. 108:15163-15168(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.
  5. "The former annotated human pseudogene dihydrofolate reductase-like 1 (DHFRL1) is expressed and functional."
    McEntee G., Minguzzi S., O'Brien K., Ben Larbi N., Loscher C., O'Fagain C., Parle-McDermott A.
    Proc. Natl. Acad. Sci. U.S.A. 108:15157-15162(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, RNA-BINDING, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.

Entry informationi

Entry nameiDYRL1_HUMAN
AccessioniPrimary (citable) accession number: Q86XF0
Secondary accession number(s): D3DN30, Q6P4I9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 20, 2005
Last sequence update: June 1, 2003
Last modified: January 7, 2015
This is version 96 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.