Q6UB35 · C1TM_HUMAN
- ProteinMonofunctional C1-tetrahydrofolate synthase, mitochondrial
- GeneMTHFD1L
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids978 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
May provide the missing metabolic reaction required to link the mitochondria and the cytoplasm in the mammalian model of one-carbon folate metabolism complementing thus the enzymatic activities of MTHFD2.
Miscellaneous
May participate in the progression of colorectal cancer by conferring growth advantage. Could be a new molecular target for cancer therapy.
Catalytic activity
- (6S)-5,6,7,8-tetrahydrofolate + ATP + formate = (6R)-10-formyltetrahydrofolate + ADP + phosphateThis reaction proceeds in the forward direction.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
500 μM | THF monoglutamate | |||||
16 μM | THF triglutamate | |||||
3.6 μM | THF pentaglutamate |
Pathway
One-carbon metabolism; tetrahydrofolate interconversion.
Features
Showing features for binding site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Cellular Component | membrane | |
Cellular Component | mitochondrial matrix | |
Cellular Component | mitochondrion | |
Molecular Function | ATP binding | |
Molecular Function | formate-tetrahydrofolate ligase activity | |
Molecular Function | methylenetetrahydrofolate dehydrogenase (NADP+) activity | |
Molecular Function | protein homodimerization activity | |
Biological Process | 10-formyltetrahydrofolate biosynthetic process | |
Biological Process | embryonic neurocranium morphogenesis | |
Biological Process | embryonic viscerocranium morphogenesis | |
Biological Process | folic acid-containing compound metabolic process | |
Biological Process | formate metabolic process | |
Biological Process | neural tube closure | |
Biological Process | tetrahydrofolate interconversion |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameMonofunctional C1-tetrahydrofolate synthase, mitochondrial
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ6UB35
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_044346 | 444 | in a colorectal cancer sample; somatic mutation | |||
Sequence: L → R |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 1,202 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for transit peptide, chain, modified residue (large scale data), modified residue.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Transit peptide | 1-31 | UniProt | Mitochondrion | ||||
Sequence: MGTRLPLVLRQLRRPPQPPGPPRRLRVPCRA | |||||||
Chain | PRO_0000343177 | 32-978 | UniProt | Monofunctional C1-tetrahydrofolate synthase, mitochondrial | |||
Sequence: SSGGGGGGGGGREGLLGQRRPQDGQARSSCSPGGRTPAARDSIVREVIQNSKEVLSLLQEKNPAFKPVLAIIQAGDDNLMQEINQNLAEEAGLNITHICLPPDSSEAEIIDEILKINEDTRVHGLALQISENLFSNKVLNALKPEKDVDGVTDINLGKLVRGDAHECFVSPVAKAVIELLEKSGVNLDGKKILVVGAHGSLEAALQCLFQRKGSMTMSIQWKTRQLQSKLHEADIVVLGSPKPEEIPLTWIQPGTTVLNCSHDFLSGKVGCGSPRIHFGGLIEEDDVILLAAALRIQNMVSSGRRWLREQQHRRWRLHCLKLQPLSPVPSDIEISRGQTPKAVDVLAKEIGLLADEIEIYGKSKAKVRLSVLERLKDQADGKYVLVAGITPTPLGEGKSTVTIGLVQALTAHLNVNSFACLRQPSQGPTFGVKGGAAGGGYAQVIPMEEFNLHLTGDIHAITAANNLLAAAIDTRILHENTQTDKALYNRLVPLVNGVREFSEIQLARLKKLGINKTDPSTLTEEEVSKFARLDIDPSTITWQRVLDTNDRFLRKITIGQGNTEKGHYRQAQFDIAVASEIMAVLALTDSLADMKARLGRMVVASDKSGQPVTADDLGVTGALTVLMKDAIKPNLMQTLEGTPVFVHAGPFANIAHGNSSVLADKIALKLVGEEGFVVTEAGFGADIGMEKFFNIKCRASGLVPNVVVLVATVRALKMHGGGPSVTAGVPLKKEYTEENIQLVADGCCNLQKQIQITQLFGVPVVVALNVFKTDTRAEIDLVCELAKRAGAFDAVPCYHWSVGGKGSVDLARAVREAASKRSRFQFLYDVQVPIVDKIRTIAQAVYGAKDIELSPEAQAKIDRYTQQGFGNLPICMAKTHLSLSHQPDKKGVPRDFILPISDVRASIGAGFIYPLVGTMSTMPGLPTRPCFYDIDLDTETEQVKGLF | |||||||
Modified residue (large scale data) | 62 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 189 | UniProt | N6-acetyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 189 | UniProt | N6-succinyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 357 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 357 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 391 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 596 | UniProt | N6-succinyllysine | ||||
Sequence: K |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Detected in most tissues, highest expression found in placenta, thymus and brain. Low expression is found in liver and skeletal muscle. Up-regulated in colon adenocarcinoma.
Gene expression databases
Organism-specific databases
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-71 | Disordered | ||||
Sequence: MGTRLPLVLRQLRRPPQPPGPPRRLRVPCRASSGGGGGGGGGREGLLGQRRPQDGQARSSCSPGGRTPAAR | ||||||
Region | 31-348 | Methylenetetrahydrofolate dehydrogenase and cyclohydrolase | ||||
Sequence: ASSGGGGGGGGGREGLLGQRRPQDGQARSSCSPGGRTPAARDSIVREVIQNSKEVLSLLQEKNPAFKPVLAIIQAGDDNLMQEINQNLAEEAGLNITHICLPPDSSEAEIIDEILKINEDTRVHGLALQISENLFSNKVLNALKPEKDVDGVTDINLGKLVRGDAHECFVSPVAKAVIELLEKSGVNLDGKKILVVGAHGSLEAALQCLFQRKGSMTMSIQWKTRQLQSKLHEADIVVLGSPKPEEIPLTWIQPGTTVLNCSHDFLSGKVGCGSPRIHFGGLIEEDDVILLAAALRIQNMVSSGRRWLREQQHRRWRL | ||||||
Region | 349-978 | Formyltetrahydrofolate synthetase | ||||
Sequence: HCLKLQPLSPVPSDIEISRGQTPKAVDVLAKEIGLLADEIEIYGKSKAKVRLSVLERLKDQADGKYVLVAGITPTPLGEGKSTVTIGLVQALTAHLNVNSFACLRQPSQGPTFGVKGGAAGGGYAQVIPMEEFNLHLTGDIHAITAANNLLAAAIDTRILHENTQTDKALYNRLVPLVNGVREFSEIQLARLKKLGINKTDPSTLTEEEVSKFARLDIDPSTITWQRVLDTNDRFLRKITIGQGNTEKGHYRQAQFDIAVASEIMAVLALTDSLADMKARLGRMVVASDKSGQPVTADDLGVTGALTVLMKDAIKPNLMQTLEGTPVFVHAGPFANIAHGNSSVLADKIALKLVGEEGFVVTEAGFGADIGMEKFFNIKCRASGLVPNVVVLVATVRALKMHGGGPSVTAGVPLKKEYTEENIQLVADGCCNLQKQIQITQLFGVPVVVALNVFKTDTRAEIDLVCELAKRAGAFDAVPCYHWSVGGKGSVDLARAVREAASKRSRFQFLYDVQVPIVDKIRTIAQAVYGAKDIELSPEAQAKIDRYTQQGFGNLPICMAKTHLSLSHQPDKKGVPRDFILPISDVRASIGAGFIYPLVGTMSTMPGLPTRPCFYDIDLDTETEQVKGLF |
Domain
This monofunctional enzyme consists of two major domains: an N-terminal inactive methylene-THF dehydrogenase and cyclohydrolase domain and an active larger formyl-THF synthetase C-terminal domain.
Sequence similarities
In the N-terminal section; belongs to the tetrahydrofolate dehydrogenase/cyclohydrolase family.
In the C-terminal section; belongs to the formate--tetrahydrofolate ligase family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
This entry describes 2 isoforms produced by Alternative splicing.
Q6UB35-1
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.
- Name1
- Length978
- Mass (Da)105,790
- Last updated2004-07-05 v1
- Checksum7D655CD8D2503378
Q6UB35-2
- Name2
Computationally mapped potential isoform sequences
There are 8 potential isoforms mapped to this entry
Sequence caution
Features
Showing features for sequence conflict, alternative sequence.
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AY374130 EMBL· GenBank· DDBJ | AAQ82696.1 EMBL· GenBank· DDBJ | mRNA | ||
AY374131 EMBL· GenBank· DDBJ | AAQ82697.1 EMBL· GenBank· DDBJ | mRNA | ||
AB127387 EMBL· GenBank· DDBJ | BAD93193.1 EMBL· GenBank· DDBJ | mRNA | ||
CH471051 EMBL· GenBank· DDBJ | EAW47762.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AL035086 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL133260 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL049694 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL117452 EMBL· GenBank· DDBJ | CAB55934.1 EMBL· GenBank· DDBJ | mRNA | ||
BC008629 EMBL· GenBank· DDBJ | AAH08629.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
BC017477 EMBL· GenBank· DDBJ | AAH17477.2 EMBL· GenBank· DDBJ | mRNA | ||
BC110319 EMBL· GenBank· DDBJ | AAI10320.1 EMBL· GenBank· DDBJ | mRNA | ||
AK024798 EMBL· GenBank· DDBJ | BAB15009.1 EMBL· GenBank· DDBJ | mRNA | Different initiation |