UniProtKB - P97807 (FUMH_MOUSE)
Protein
Fumarate hydratase, mitochondrial
Gene
Fh
Organism
Mus musculus (Mouse)
Status
Functioni
Catalyzes the reversible stereospecific interconversion of fumarate to L-malate (PubMed:23643539). Experiments in different species have demonstrated that specific isoforms of this protein act in defined pathways and favor one direction over the other (Probable).Curated1 Publication
Catalyzes the hydration of fumarate to L-malate in the tricarboxylic acid (TCA) cycle to facilitate a transition step in the production of energy in the form of NADH.By similarity
Catalyzes the dehydration of L-malate to fumarate (PubMed:23643539). Fumarate metabolism in the cytosol plays a role during urea cycle and arginine metabolism; fumarate being a by-product of the urea cycle and amino-acid catabolism (PubMed:23643539). Also plays a role in DNA repair by promoting non-homologous end-joining (NHEJ) (By similarity). In response to DNA damage and phosphorylation by PRKDC, translocates to the nucleus and accumulates at DNA double-strand breaks (DSBs): acts by catalyzing formation of fumarate, an inhibitor of KDM2B histone demethylase activity, resulting in enhanced dimethylation of histone H3 'Lys-36' (H3K36me2) (By similarity).By similarity1 Publication
Miscellaneous
There are 2 substrate-binding sites: the catalytic A site, and the non-catalytic B site that may play a role in the transfer of substrate or product between the active site and the solvent. Alternatively, the B site may bind allosteric effectors.By similarity
Catalytic activityi
- EC:4.2.1.2By similarity EC:4.2.1.21 PublicationThis reaction proceeds in the backwardBy similarity direction.
: tricarboxylic acid cycle Pathwayi
This protein is involved in step 1 of the subpathway that synthesizes (S)-malate from fumarate.By similarityProteins known to be involved in this subpathway in this organism are:
- Fumarate hydratase, mitochondrial (Fh)
View all proteins of this organism that are known to be involved in the subpathway that synthesizes (S)-malate from fumarate, the pathway tricarboxylic acid cycle and in Carbohydrate metabolism.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 231 | SubstrateBy similarity | 1 | |
Active sitei | 232 | Proton donor/acceptorBy similarity | 1 | |
Active sitei | 362 | By similarity | 1 | |
Binding sitei | 363 | SubstrateBy similarity | 1 | |
Sitei | 375 | Important for catalytic activityBy similarity | 1 |
GO - Molecular functioni
- fumarate hydratase activity Source: UniProtKB
- histone binding Source: MGI
GO - Biological processi
- cellular response to DNA damage stimulus Source: UniProtKB
- DNA repair Source: UniProtKB-KW
- fumarate metabolic process Source: UniProtKB
- homeostasis of number of cells within a tissue Source: MGI
- malate metabolic process Source: UniProtKB
- negative regulation of histone H3-K36 methylation Source: UniProtKB
- positive regulation of cold-induced thermogenesis Source: YuBioLab
- positive regulation of double-strand break repair via nonhomologous end joining Source: UniProtKB
- regulation of arginine metabolic process Source: UniProtKB
- tricarboxylic acid cycle Source: MGI
- urea cycle Source: UniProtKB
Keywordsi
Molecular function | Lyase |
Biological process | DNA damage, DNA repair, Tricarboxylic acid cycle |
Enzyme and pathway databases
Reactomei | R-MMU-71403, Citric acid cycle (TCA cycle) |
UniPathwayi | UPA00223;UER01007 |
Names & Taxonomyi
Protein namesi | Recommended name: Fumarate hydratase, mitochondrial1 Publication (EC:4.2.1.21 Publication)Short name: Fumarase1 Publication Alternative name(s): EF-3 |
Gene namesi | Name:Fh1 PublicationImported Synonyms:Fh11 Publication |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:95530, Fh1 |
Subcellular locationi
Mitochondrion
- Mitochondrion By similarity
Cytosol
- cytosol By similarity
Nucleus
- Nucleus By similarity
Other locations
- Chromosome By similarity
Note: Translocates to the nucleus in response to DNA damage: localizes to DNA double-strand breaks (DSBs) following phosphorylation by PRKDC.By similarity
Cytosol
- cytosol Source: MGI
Mitochondrion
- mitochondrion Source: MGI
Nucleus
- nucleus Source: MGI
Other locations
- cytoplasm Source: MGI
- site of double-strand break Source: MGI
- tricarboxylic acid cycle enzyme complex Source: InterPro
Keywords - Cellular componenti
Chromosome, Cytoplasm, Mitochondrion, NucleusPathology & Biotechi
Disruption phenotypei
Embryonic lethality (PubMed:17418408). Conditional deletion in the kidney leads to the development of renal cysts, reminiscent of hereditary leiomyomatosis and renal cell cancer (HLRCC) phenotype in human (PubMed:17418408). Renal cysts are caused by accumulation of fumarate that promotes the formation of non-enzymatic post-translational modification cysteine S-succination (S-(2-succinyl)cysteine) on proteins, such as Keap1 (PubMed:22014577).2 Publications
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length | |
---|---|---|---|---|---|
Transit peptidei | 1 – 41 | MitochondrionBy similarityAdd BLAST | 41 | ||
ChainiPRO_0000010323 | 42 – 507 | Fumarate hydratase, mitochondrialAdd BLAST | 466 | ||
Isoform Cytoplasmic (identifier: P97807-2) | |||||
Initiator methioninei | RemovedBy similarity |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 58 | N6-acetyllysine; alternateCombined sources | 1 | |
Modified residuei | 58 | N6-succinyllysine; alternateCombined sources | 1 | |
Modified residuei | 63 | N6-acetyllysine; alternateCombined sources | 1 | |
Modified residuei | 63 | N6-succinyllysine; alternateCombined sources | 1 | |
Modified residuei | 77 | N6-acetyllysine; alternateCombined sources | 1 | |
Modified residuei | 77 | N6-succinyllysine; alternateCombined sources | 1 | |
Modified residuei | 82 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 112 | N6-acetyllysine; alternateCombined sources | 1 | |
Modified residuei | 112 | N6-succinyllysine; alternateCombined sources | 1 | |
Modified residuei | 119 | N6-acetyllysine; alternateCombined sources | 1 | |
Modified residuei | 119 | N6-succinyllysine; alternateCombined sources | 1 | |
Modified residuei | 210 | N6-acetyllysineCombined sources | 1 | |
Modified residuei | 220 | N6-acetyllysine; alternateCombined sources | 1 | |
Modified residuei | 220 | N6-succinyllysine; alternateCombined sources | 1 | |
Modified residuei | 233 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 289 | N6-acetyllysine; alternateCombined sources | 1 | |
Modified residuei | 289 | N6-succinyllysine; alternateCombined sources | 1 | |
Modified residuei | 363 | PhosphoserineCombined sources | 1 | |
Modified residuei | 464 | N6-succinyllysineCombined sources | 1 | |
Modified residuei | 470 | N6-succinyllysineCombined sources | 1 | |
Modified residuei | 499 | N6-acetyllysineCombined sources | 1 |
Post-translational modificationi
Phosphorylation at Thr-233 by PRKDC in response to DNA damage promotes translocation to the nucleus and recruitment to DNA double-strand breaks (DSBs).By similarity
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
CPTACi | non-CPTAC-3579 |
jPOSTi | P97807 |
MaxQBi | P97807 |
PaxDbi | P97807 |
PeptideAtlasi | P97807 |
PRIDEi | P97807 |
2D gel databases
REPRODUCTION-2DPAGEi | IPI00759940 P97807 |
PTM databases
iPTMneti | P97807 |
PhosphoSitePlusi | P97807 |
SwissPalmi | P97807 |
Expressioni
Gene expression databases
Bgeei | ENSMUSG00000026526, Expressed in brown adipose tissue and 319 other tissues |
Genevisiblei | P97807, MM |
Interactioni
Subunit structurei
Homotetramer.
Interacts with H2AZ1.
By similarityGO - Molecular functioni
- histone binding Source: MGI
Protein-protein interaction databases
BioGRIDi | 199665, 22 interactors |
IntActi | P97807, 6 interactors |
MINTi | P97807 |
STRINGi | 10090.ENSMUSP00000027810 |
Miscellaneous databases
RNActi | P97807, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 142 – 144 | Substrate bindingBy similarity | 3 | |
Regioni | 173 – 176 | Substrate binding (B site)By similarity | 4 | |
Regioni | 183 – 185 | Substrate bindingBy similarity | 3 | |
Regioni | 368 – 370 | Substrate bindingBy similarity | 3 |
Sequence similaritiesi
Keywords - Domaini
Transit peptidePhylogenomic databases
eggNOGi | KOG1317, Eukaryota |
GeneTreei | ENSGT00950000183122 |
HOGENOMi | CLU_021594_4_1_1 |
InParanoidi | P97807 |
OMAi | HDSMGEV |
OrthoDBi | 1022919at2759 |
TreeFami | TF300441 |
Family and domain databases
CDDi | cd01362, Fumarase_classII, 1 hit |
Gene3Di | 1.10.275.10, 1 hit |
HAMAPi | MF_00743, FumaraseC, 1 hit |
InterProi | View protein in InterPro IPR005677, Fum_hydII IPR024083, Fumarase/histidase_N IPR018951, Fumarase_C_C IPR020557, Fumarate_lyase_CS IPR000362, Fumarate_lyase_fam IPR022761, Fumarate_lyase_N IPR008948, L-Aspartase-like |
PANTHERi | PTHR11444, PTHR11444, 1 hit |
Pfami | View protein in Pfam PF10415, FumaraseC_C, 1 hit PF00206, Lyase_1, 1 hit |
PRINTSi | PR00149, FUMRATELYASE |
SUPFAMi | SSF48557, SSF48557, 1 hit |
TIGRFAMsi | TIGR00979, fumC_II, 1 hit |
PROSITEi | View protein in PROSITE PS00163, FUMARATE_LYASES, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative initiation. AlignAdd to basketThis entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All
Isoform Mitochondrial (identifier: P97807-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MYRALRLLAR SRRLLRVPSA GAAVSGEATT LPRCAPNVAR MASQNSFRVE
60 70 80 90 100
FDTFGELKVP TDKYYGAQTV RSTMNFKIGG ATERMPIPVI QAFGILKRAA
110 120 130 140 150
AEVNQEYGLD PKIASAIMKA ADEVAEGKLN DHFPLVVWQT GSGTQTNMNV
160 170 180 190 200
NEVISNRAIE MLGGELGSKK PVHPNDHVNK SQSSNDTFPT AMHIAAAVEV
210 220 230 240 250
HKVLLPGLQK LHDALSAKSK EFAQVIKIGR THTQDAVPLT LGQEFSGYVQ
260 270 280 290 300
QVQYAMVRIK AAMPRIYELA AGGTAVGTGL NTRIGFAEKV AAKVAALTGL
310 320 330 340 350
PFVTAPNKFE ALAAHDALVE LSGAMNTAAC SLMKIANDIR FLGSGPRSGL
360 370 380 390 400
GELILPENEP GSSIMPGKVN PTQCEAMTMV AAQVMGNHVA VTVGGSNGHF
410 420 430 440 450
ELNVFKPMMI KNVLHSARLL GDASVSFTDN CVVGIQANTE RINKLMNESL
460 470 480 490 500
MLVTALNPHI GYDKAAKIAK TAHKNGSTLK ETAIELGYLT AEQFDEWVKP
KDMLGPK
Isoform Cytoplasmic (identifier: P97807-2) [UniParc]FASTAAdd to basket
The sequence of this isoform differs from the canonical sequence as follows:
1-40: Missing.
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketH3BKG7 | H3BKG7_MOUSE | Fumarate hydratase 1 | Fh1 | 167 | Annotation score: | ||
H3BJV5 | H3BJV5_MOUSE | Fumarate hydratase 1 | Fh1 | 61 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 183 | S → N in AK002379 (PubMed:16141072).Curated | 1 | |
Sequence conflicti | 236 | A → T in AK002379 (PubMed:16141072).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_018967 | 1 – 40 | Missing in isoform Cytoplasmic. CuratedAdd BLAST | 40 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK002379 mRNA No translation available. AK147000 mRNA Translation: BAE27597.1 CH466555 Genomic DNA Translation: EDL13210.1 BC006048 mRNA Translation: AAH06048.1 U72679 mRNA Translation: AAB51039.1 |
CCDSi | CCDS15547.1 [P97807-1] |
RefSeqi | NP_034339.2, NM_010209.2 [P97807-1] |
Genome annotation databases
Ensembli | ENSMUST00000027810; ENSMUSP00000027810; ENSMUSG00000026526 [P97807-1] |
GeneIDi | 14194 |
KEGGi | mmu:14194 |
UCSCi | uc007dtn.2, mouse [P97807-1] |
Keywords - Coding sequence diversityi
Alternative initiationSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK002379 mRNA No translation available. AK147000 mRNA Translation: BAE27597.1 CH466555 Genomic DNA Translation: EDL13210.1 BC006048 mRNA Translation: AAH06048.1 U72679 mRNA Translation: AAB51039.1 |
CCDSi | CCDS15547.1 [P97807-1] |
RefSeqi | NP_034339.2, NM_010209.2 [P97807-1] |
3D structure databases
SMRi | P97807 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 199665, 22 interactors |
IntActi | P97807, 6 interactors |
MINTi | P97807 |
STRINGi | 10090.ENSMUSP00000027810 |
PTM databases
iPTMneti | P97807 |
PhosphoSitePlusi | P97807 |
SwissPalmi | P97807 |
2D gel databases
REPRODUCTION-2DPAGEi | IPI00759940 P97807 |
Proteomic databases
CPTACi | non-CPTAC-3579 |
jPOSTi | P97807 |
MaxQBi | P97807 |
PaxDbi | P97807 |
PeptideAtlasi | P97807 |
PRIDEi | P97807 |
Protocols and materials databases
Antibodypediai | 34701, 630 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000027810; ENSMUSP00000027810; ENSMUSG00000026526 [P97807-1] |
GeneIDi | 14194 |
KEGGi | mmu:14194 |
UCSCi | uc007dtn.2, mouse [P97807-1] |
Organism-specific databases
CTDi | 14194 |
MGIi | MGI:95530, Fh1 |
Phylogenomic databases
eggNOGi | KOG1317, Eukaryota |
GeneTreei | ENSGT00950000183122 |
HOGENOMi | CLU_021594_4_1_1 |
InParanoidi | P97807 |
OMAi | HDSMGEV |
OrthoDBi | 1022919at2759 |
TreeFami | TF300441 |
Enzyme and pathway databases
UniPathwayi | UPA00223;UER01007 |
Reactomei | R-MMU-71403, Citric acid cycle (TCA cycle) |
Miscellaneous databases
BioGRID-ORCSi | 14194, 8 hits in 19 CRISPR screens |
ChiTaRSi | Fh1, mouse |
PROi | PR:P97807 |
RNActi | P97807, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000026526, Expressed in brown adipose tissue and 319 other tissues |
Genevisiblei | P97807, MM |
Family and domain databases
CDDi | cd01362, Fumarase_classII, 1 hit |
Gene3Di | 1.10.275.10, 1 hit |
HAMAPi | MF_00743, FumaraseC, 1 hit |
InterProi | View protein in InterPro IPR005677, Fum_hydII IPR024083, Fumarase/histidase_N IPR018951, Fumarase_C_C IPR020557, Fumarate_lyase_CS IPR000362, Fumarate_lyase_fam IPR022761, Fumarate_lyase_N IPR008948, L-Aspartase-like |
PANTHERi | PTHR11444, PTHR11444, 1 hit |
Pfami | View protein in Pfam PF10415, FumaraseC_C, 1 hit PF00206, Lyase_1, 1 hit |
PRINTSi | PR00149, FUMRATELYASE |
SUPFAMi | SSF48557, SSF48557, 1 hit |
TIGRFAMsi | TIGR00979, fumC_II, 1 hit |
PROSITEi | View protein in PROSITE PS00163, FUMARATE_LYASES, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | FUMH_MOUSE | |
Accessioni | P97807Primary (citable) accession number: P97807 Secondary accession number(s): Q3UIA9, Q99JL0, Q9DCX0 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 15, 1998 |
Last sequence update: | July 27, 2011 | |
Last modified: | December 2, 2020 | |
This is version 186 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Direct protein sequencing, Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families