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Entry version 221 (03 Jul 2019)
Sequence version 3 (01 Oct 1996)
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Protein

Fumarate hydratase, mitochondrial

Gene

FH

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Catalyzes the reversible stereospecific interconversion of fumarate to L-malate.1 Publication
Isoform Mitochondrial: 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
Isoform Cytoplasmic: Catalyzes the dehydration of L-malate to fumarate (By similarity). 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 (By similarity). Also plays a role in DNA repair by promoting non-homologous end-joining (NHEJ) (PubMed:20231875, PubMed:26237645). 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) (PubMed:26237645).By similarity2 Publications

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

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the ‘Function’ section describes biophysical and chemical properties, such as maximal absorption, kinetic parameters, pH dependence, redox potentials and temperature dependence.<p><a href='/help/biophysicochemical_properties' target='_top'>More...</a></p>Kineticsi

Kcat is 280 sec(-1) with L-malate (at pH 8.5) (PubMed:30761759). Kcat is 170 sec(-1) with fumarate (at pH 8.5) (PubMed:30761759).1 Publication
  1. KM=1.4 mM for L-malate (at pH 8.5)1 Publication
  2. KM=0.2 mM for fumarate (at pH 8.5)1 Publication

    pH dependencei

    Optimum pH is 7.5-8.0.1 Publication

    <p>This subsection of the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section describes the metabolic pathway(s) associated with a protein.<p><a href='/help/pathway' target='_top'>More...</a></p>Pathwayi: tricarboxylic acid cycle

    This protein is involved in step 1 of the subpathway that synthesizes (S)-malate from fumarate.By similarity
    Proteins known to be involved in this subpathway in this organism are:
    1. Fumarate hydratase, mitochondrial (FH)
    This subpathway is part of the pathway tricarboxylic acid cycle, which is itself part of Carbohydrate metabolism.
    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 keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei234SubstrateBy similarity1
    <p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei235Proton donor/acceptorBy similarity1
    Active sitei365By similarity1
    Binding sitei366SubstrateBy similarity1
    <p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections (‘Function’, ‘PTM / Processing’, ‘Pathology and Biotech’) according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei378Important for catalytic activityBy similarity1

    <p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

    GO - Biological processi

    <p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

    Molecular functionLyase
    Biological processDNA damage, DNA repair, Tricarboxylic acid cycle

    Enzyme and pathway databases

    BioCyc Collection of Pathway/Genome Databases

    More...
    BioCyci
    MetaCyc:ENSG00000091483-MONOMER

    BRENDA Comprehensive Enzyme Information System

    More...
    BRENDAi
    4.2.1.2 2681

    Reactome - a knowledgebase of biological pathways and processes

    More...
    Reactomei
    R-HSA-71403 Citric acid cycle (TCA cycle)

    UniPathway: a resource for the exploration and annotation of metabolic pathways

    More...
    UniPathwayi
    UPA00223;UER01007

    <p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

    <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
    Recommended name:
    Fumarate hydratase, mitochondrial2 Publications (EC:4.2.1.21 Publication)
    Short name:
    Fumarase3 Publications
    Short name:
    HsFH1 Publication
    <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
    Name:FH1 PublicationImported
    <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
    <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
    <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
    • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 1

    Organism-specific databases

    Human Gene Nomenclature Database

    More...
    HGNCi
    HGNC:3700 FH

    Online Mendelian Inheritance in Man (OMIM)

    More...
    MIMi
    136850 gene

    neXtProt; the human protein knowledge platform

    More...
    neXtProti
    NX_P07954

    <p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Chromosome, Cytoplasm, Mitochondrion, Nucleus

    <p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

    <p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

    Fumarase deficiency (FMRD)2 Publications
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionA severe autosomal recessive metabolic disorder characterized by early-onset hypotonia, profound psychomotor retardation, and brain abnormalities, such as agenesis of the corpus callosum, gyral defects, and ventriculomegaly. Many patients show neonatal distress, metabolic acidosis, and/or encephalopathy.
    Related information in OMIM
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_002445230K → R in FMRD and HLRCC. 2 PublicationsCorresponds to variant dbSNP:rs752232718EnsemblClinVar.1
    Natural variantiVAR_002446308A → T in FMRD. 2 PublicationsCorresponds to variant dbSNP:rs121913118Ensembl.1
    Natural variantiVAR_002447312F → C in FMRD. 1 Publication1
    Natural variantiVAR_002448425D → V in FMRD. 1 Publication1
    Hereditary leiomyomatosis and renal cell cancer (HLRCC)3 Publications
    The disease is caused by mutations affecting the gene represented in this entry. Isoform Cytoplasmic: HLRCC is probably caused by an accumulation of fumarate (PubMed:30718813). Accumulation of fumarate coupled with protonation promotes the formation of non-enzymatic post-translational modification cysteine S-succination (S-succinylcysteine) on proteins, such as SMARCC1 (PubMed:30718813).1 Publication
    Disease descriptionA disorder characterized by predisposition to cutaneous and uterine leiomyomas, and papillary type 2 renal cancer which occurs in about 20% of patients.
    Related information in OMIM
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_013497107N → T in HLRCC. 1 PublicationCorresponds to variant dbSNP:rs121913121EnsemblClinVar.1
    Natural variantiVAR_013498117A → P in HLRCC. 1 PublicationCorresponds to variant dbSNP:rs886039363EnsemblClinVar.1
    Natural variantiVAR_013499180H → R in HLRCC. 1 PublicationCorresponds to variant dbSNP:rs863224015EnsemblClinVar.1
    Natural variantiVAR_013500185Q → R in HLRCC. 1 PublicationCorresponds to variant dbSNP:rs779707997EnsemblClinVar.1
    Natural variantiVAR_002445230K → R in FMRD and HLRCC. 2 PublicationsCorresponds to variant dbSNP:rs752232718EnsemblClinVar.1
    Natural variantiVAR_013501233R → H in HLRCC; catalytically inactive mutant; abolished ability to promote DNA repair. 2 PublicationsCorresponds to variant dbSNP:rs121913123EnsemblClinVar.1
    Natural variantiVAR_013502282G → V in HLRCC. 1 PublicationCorresponds to variant dbSNP:rs935002190Ensembl.1
    Natural variantiVAR_013503328M → R in HLRCC. 1 Publication1
    Natural variantiVAR_081606362E → Q in HLRCC. 1 Publication1

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi46S → A: Does not affect phosphorylation by PRKDC. 1 Publication1
    Mutagenesisi147T → A: Does not affect phosphorylation by PRKDC. 1 Publication1
    Mutagenesisi187S → A: Does not affect phosphorylation by PRKDC. 1 Publication1
    Mutagenesisi236T → A: Abolished interaction with H2AFZ and localization to chromatin in response to DNA damage. 1 Publication1
    Mutagenesisi236T → D: Phosphomimetic mutant; promotes interaction with H2AFZ, leading to increased localization to chromatin in response to DNA damage. 1 Publication1

    Keywords - Diseasei

    Disease mutation, Tumor suppressor

    Organism-specific databases

    DisGeNET

    More...
    DisGeNETi
    2271

    GeneReviews a resource of expert-authored, peer-reviewed disease descriptions.

    More...
    GeneReviewsi
    FH

    MalaCards human disease database

    More...
    MalaCardsi
    FH
    MIMi150800 phenotype
    606812 phenotype

    Open Targets

    More...
    OpenTargetsi
    ENSG00000091483

    Orphanet; a database dedicated to information on rare diseases and orphan drugs

    More...
    Orphaneti
    24 Fumaric aciduria
    523 Hereditary leiomyomatosis and renal cell cancer
    29072 Hereditary pheochromocytoma-paraganglioma

    The Pharmacogenetics and Pharmacogenomics Knowledge Base

    More...
    PharmGKBi
    PA28139

    Polymorphism and mutation databases

    BioMuta curated single-nucleotide variation and disease association database

    More...
    BioMutai
    FH

    Domain mapping of disease mutations (DMDM)

    More...
    DMDMi
    1730117

    <p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the ‘PTM / Processing’ section describes the extent of a transit peptide.<p><a href='/help/transit' target='_top'>More...</a></p>Transit peptidei1 – 44MitochondrionBy similarityAdd BLAST44
    <p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_000001031945 – 510Fumarate hydratase, mitochondrialAdd BLAST466
    Isoform Cytoplasmic1 Publication (identifier: P07954-2)
    <p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section indicates that the initiator methionine is cleaved from the mature protein.<p><a href='/help/init_met' target='_top'>More...</a></p>Initiator methionineiRemoved1 Publication

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei61N6-acetyllysine; alternateBy similarity1
    Modified residuei61N6-succinyllysine; alternateBy similarity1
    Modified residuei66N6-acetyllysine; alternateCombined sources1
    Modified residuei66N6-succinyllysine; alternateBy similarity1
    Modified residuei80N6-acetyllysine; alternateCombined sources1
    Modified residuei80N6-succinyllysine; alternateBy similarity1
    Modified residuei85PhosphothreonineBy similarity1
    Modified residuei90PhosphothreonineCombined sources1
    Modified residuei94N6-acetyllysineCombined sources1
    Modified residuei115N6-acetyllysine; alternateBy similarity1
    Modified residuei115N6-succinyllysine; alternateBy similarity1
    Modified residuei122N6-acetyllysine; alternateBy similarity1
    Modified residuei122N6-succinyllysine; alternateBy similarity1
    Modified residuei213N6-acetyllysineBy similarity1
    Modified residuei223N6-acetyllysine; alternateBy similarity1
    Modified residuei223N6-succinyllysine; alternateBy similarity1
    Modified residuei236Phosphothreonine; by PRKDC1 Publication1
    Modified residuei256N6-acetyllysineCombined sources1
    Modified residuei292N6-acetyllysine; alternateCombined sources1
    Modified residuei292N6-succinyllysine; alternateBy similarity1
    Modified residuei366PhosphoserineCombined sources1
    Modified residuei467N6-succinyllysineBy similarity1
    Modified residuei473N6-succinyllysineBy similarity1
    Modified residuei502N6-acetyllysineBy similarity1

    <p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

    Isoform Cytoplasmic: Phosphorylation at Thr-236 by PRKDC in response to DNA damage promotes translocation to the nucleus and recruitment to DNA double-strand breaks (DSBs).1 Publication

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    Encyclopedia of Proteome Dynamics

    More...
    EPDi
    P07954

    jPOST - Japan Proteome Standard Repository/Database

    More...
    jPOSTi
    P07954

    MaxQB - The MaxQuant DataBase

    More...
    MaxQBi
    P07954

    PaxDb, a database of protein abundance averages across all three domains of life

    More...
    PaxDbi
    P07954

    PeptideAtlas

    More...
    PeptideAtlasi
    P07954

    PRoteomics IDEntifications database

    More...
    PRIDEi
    P07954

    ProteomicsDB human proteome resource

    More...
    ProteomicsDBi
    52052
    52053 [P07954-2]

    Consortium for Top Down Proteomics

    More...
    TopDownProteomicsi
    P07954-2 [P07954-2]

    2D gel databases

    REPRODUCTION-2DPAGE

    More...
    REPRODUCTION-2DPAGEi
    IPI00296053

    Two-dimensional polyacrylamide gel electrophoresis database from the Geneva University Hospital

    More...
    SWISS-2DPAGEi
    P07954

    University College Dublin 2-DE Proteome Database

    More...
    UCD-2DPAGEi
    P07954

    PTM databases

    iPTMnet integrated resource for PTMs in systems biology context

    More...
    iPTMneti
    P07954

    Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

    More...
    PhosphoSitePlusi
    P07954

    SwissPalm database of S-palmitoylation events

    More...
    SwissPalmi
    P07954

    <p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

    <p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

    Expressed in red blood cells; underexpressed in red blood cells (cytoplasm) of patients with hereditary non-spherocytic hemolytic anemia of unknown etiology.1 Publication

    Gene expression databases

    Bgee dataBase for Gene Expression Evolution

    More...
    Bgeei
    ENSG00000091483 Expressed in 236 organ(s), highest expression level in heart

    ExpressionAtlas, Differential and Baseline Expression

    More...
    ExpressionAtlasi
    P07954 baseline and differential

    Genevisible search portal to normalized and curated expression data from Genevestigator

    More...
    Genevisiblei
    P07954 HS

    Organism-specific databases

    Human Protein Atlas

    More...
    HPAi
    CAB017785
    HPA025770
    HPA025948
    HPA027341

    <p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

    <p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

    Homotetramer (PubMed:21445611, PubMed:30761759).

    Interacts with H2AFZ (PubMed:26237645).

    3 Publications

    <p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

    GO - Molecular functioni

    Protein-protein interaction databases

    The Biological General Repository for Interaction Datasets (BioGrid)

    More...
    BioGridi
    108562, 103 interactors

    Database of interacting proteins

    More...
    DIPi
    DIP-46920N

    Protein interaction database and analysis system

    More...
    IntActi
    P07954, 28 interactors

    STRING: functional protein association networks

    More...
    STRINGi
    9606.ENSP00000355518

    <p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

    Secondary structure

    1510
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    SWISS-MODEL Repository - a database of annotated 3D protein structure models

    More...
    SMRi
    P07954

    Database of comparative protein structure models

    More...
    ModBasei
    Search...

    Miscellaneous databases

    Relative evolutionary importance of amino acids within a protein sequence

    More...
    EvolutionaryTracei
    P07954

    <p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the ‘Family and Domains’ section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni145 – 147Substrate bindingBy similarity3
    Regioni176 – 179Substrate binding (B site)By similarity4
    Regioni186 – 188Substrate bindingBy similarity3
    Regioni371 – 373Substrate bindingBy similarity3

    <p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

    Keywords - Domaini

    Transit peptide

    Phylogenomic databases

    evolutionary genealogy of genes: Non-supervised Orthologous Groups

    More...
    eggNOGi
    KOG1317 Eukaryota
    COG0114 LUCA

    Ensembl GeneTree

    More...
    GeneTreei
    ENSGT00950000183122

    The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

    More...
    HOGENOMi
    HOG000061736

    InParanoid: Eukaryotic Ortholog Groups

    More...
    InParanoidi
    P07954

    KEGG Orthology (KO)

    More...
    KOi
    K01679

    Identification of Orthologs from Complete Genome Data

    More...
    OMAi
    FELNVYN

    Database of Orthologous Groups

    More...
    OrthoDBi
    241249at2759

    Database for complete collections of gene phylogenies

    More...
    PhylomeDBi
    P07954

    TreeFam database of animal gene trees

    More...
    TreeFami
    TF300441

    Family and domain databases

    Conserved Domains Database

    More...
    CDDi
    cd01362 Fumarase_classII, 1 hit

    Gene3D Structural and Functional Annotation of Protein Families

    More...
    Gene3Di
    1.10.275.10, 1 hit

    HAMAP database of protein families

    More...
    HAMAPi
    MF_00743 FumaraseC, 1 hit

    Integrated resource of protein families, domains and functional sites

    More...
    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

    The PANTHER Classification System

    More...
    PANTHERi
    PTHR11444 PTHR11444, 1 hit

    Pfam protein domain database

    More...
    Pfami
    View protein in Pfam
    PF10415 FumaraseC_C, 1 hit
    PF00206 Lyase_1, 1 hit

    Protein Motif fingerprint database; a protein domain database

    More...
    PRINTSi
    PR00149 FUMRATELYASE

    Superfamily database of structural and functional annotation

    More...
    SUPFAMi
    SSF48557 SSF48557, 1 hit

    TIGRFAMs; a protein family database

    More...
    TIGRFAMsi
    TIGR00979 fumC_II, 1 hit

    PROSITE; a protein domain and family database

    More...
    PROSITEi
    View protein in PROSITE
    PS00163 FUMARATE_LYASES, 1 hit

    <p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (2)i

    <p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

    <p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative initiation. AlignAdd to basket
    Isoform Mitochondrial1 Publication (identifier: P07954-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide
            10         20         30         40         50
    MYRALRLLAR SRPLVRAPAA ALASAPGLGG AAVPSFWPPN AARMASQNSF
    60 70 80 90 100
    RIEYDTFGEL KVPNDKYYGA QTVRSTMNFK IGGVTERMPT PVIKAFGILK
    110 120 130 140 150
    RAAAEVNQDY GLDPKIANAI MKAADEVAEG KLNDHFPLVV WQTGSGTQTN
    160 170 180 190 200
    MNVNEVISNR AIEMLGGELG SKIPVHPNDH VNKSQSSNDT FPTAMHIAAA
    210 220 230 240 250
    IEVHEVLLPG LQKLHDALDA KSKEFAQIIK IGRTHTQDAV PLTLGQEFSG
    260 270 280 290 300
    YVQQVKYAMT RIKAAMPRIY ELAAGGTAVG TGLNTRIGFA EKVAAKVAAL
    310 320 330 340 350
    TGLPFVTAPN KFEALAAHDA LVELSGAMNT TACSLMKIAN DIRFLGSGPR
    360 370 380 390 400
    SGLGELILPE NEPGSSIMPG KVNPTQCEAM TMVAAQVMGN HVAVTVGGSN
    410 420 430 440 450
    GHFELNVFKP MMIKNVLHSA RLLGDASVSF TENCVVGIQA NTERINKLMN
    460 470 480 490 500
    ESLMLVTALN PHIGYDKAAK IAKTAHKNGS TLKETAIELG YLTAEQFDEW
    510
    VKPKDMLGPK
    Length:510
    Mass (Da):54,637
    Last modified:October 1, 1996 - v3
    <p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i86F91F95DC046F64
    GO
    Isoform Cytoplasmic1 Publication (identifier: P07954-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-43: Missing.

    Show »
    Length:467
    Mass (Da):50,213
    Checksum:i5E1AC7903B062540
    GO

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_013497107N → T in HLRCC. 1 PublicationCorresponds to variant dbSNP:rs121913121EnsemblClinVar.1
    Natural variantiVAR_013498117A → P in HLRCC. 1 PublicationCorresponds to variant dbSNP:rs886039363EnsemblClinVar.1
    Natural variantiVAR_013499180H → R in HLRCC. 1 PublicationCorresponds to variant dbSNP:rs863224015EnsemblClinVar.1
    Natural variantiVAR_013500185Q → R in HLRCC. 1 PublicationCorresponds to variant dbSNP:rs779707997EnsemblClinVar.1
    Natural variantiVAR_002445230K → R in FMRD and HLRCC. 2 PublicationsCorresponds to variant dbSNP:rs752232718EnsemblClinVar.1
    Natural variantiVAR_013501233R → H in HLRCC; catalytically inactive mutant; abolished ability to promote DNA repair. 2 PublicationsCorresponds to variant dbSNP:rs121913123EnsemblClinVar.1
    Natural variantiVAR_013502282G → V in HLRCC. 1 PublicationCorresponds to variant dbSNP:rs935002190Ensembl.1
    Natural variantiVAR_002446308A → T in FMRD. 2 PublicationsCorresponds to variant dbSNP:rs121913118Ensembl.1
    Natural variantiVAR_002447312F → C in FMRD. 1 Publication1
    Natural variantiVAR_013503328M → R in HLRCC. 1 Publication1
    Natural variantiVAR_081606362E → Q in HLRCC. 1 Publication1
    Natural variantiVAR_002448425D → V in FMRD. 1 Publication1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_0189651 – 43Missing in isoform Cytoplasmic. 1 PublicationAdd BLAST43

    Sequence databases

    Select the link destinations:

    EMBL nucleotide sequence database

    More...
    EMBLi

    GenBank nucleotide sequence database

    More...
    GenBanki

    DNA Data Bank of Japan; a nucleotide sequence database

    More...
    DDBJi
    Links Updated
    U59309 mRNA Translation: AAB66354.1
    U48857 mRNA Translation: AAD00071.1
    BT009839 mRNA Translation: AAP88841.1
    AK312415 mRNA Translation: BAG35325.1
    CH471098 Genomic DNA Translation: EAW70092.1
    BC003108 mRNA Translation: AAH03108.1
    BC017444 mRNA Translation: AAH17444.1
    M15502 mRNA Translation: AAA52483.1

    The Consensus CDS (CCDS) project

    More...
    CCDSi
    CCDS1617.1 [P07954-1]

    Protein sequence database of the Protein Information Resource

    More...
    PIRi
    S06213 UFHUM

    NCBI Reference Sequences

    More...
    RefSeqi
    NP_000134.2, NM_000143.3 [P07954-1]

    Genome annotation databases

    Ensembl eukaryotic genome annotation project

    More...
    Ensembli
    ENST00000366560; ENSP00000355518; ENSG00000091483 [P07954-1]

    Database of genes from NCBI RefSeq genomes

    More...
    GeneIDi
    2271

    KEGG: Kyoto Encyclopedia of Genes and Genomes

    More...
    KEGGi
    hsa:2271

    UCSC genome browser

    More...
    UCSCi
    uc001hyx.4 human [P07954-1]

    Keywords - Coding sequence diversityi

    Alternative initiation

    <p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

    <p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

    <p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

    TCA Cycle Gene Mutation Database
    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U59309 mRNA Translation: AAB66354.1
    U48857 mRNA Translation: AAD00071.1
    BT009839 mRNA Translation: AAP88841.1
    AK312415 mRNA Translation: BAG35325.1
    CH471098 Genomic DNA Translation: EAW70092.1
    BC003108 mRNA Translation: AAH03108.1
    BC017444 mRNA Translation: AAH17444.1
    M15502 mRNA Translation: AAA52483.1
    CCDSiCCDS1617.1 [P07954-1]
    PIRiS06213 UFHUM
    RefSeqiNP_000134.2, NM_000143.3 [P07954-1]

    3D structure databases

    Select the link destinations:

    Protein Data Bank Europe

    More...
    PDBei

    Protein Data Bank RCSB

    More...
    RCSB PDBi

    Protein Data Bank Japan

    More...
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    3E04X-ray1.95A/B/C/D44-510[»]
    5D6BX-ray2.10A49-510[»]
    5UPPX-ray1.80A/B45-510[»]
    SMRiP07954
    ModBaseiSearch...

    Protein-protein interaction databases

    BioGridi108562, 103 interactors
    DIPiDIP-46920N
    IntActiP07954, 28 interactors
    STRINGi9606.ENSP00000355518

    PTM databases

    iPTMnetiP07954
    PhosphoSitePlusiP07954
    SwissPalmiP07954

    Polymorphism and mutation databases

    BioMutaiFH
    DMDMi1730117

    2D gel databases

    REPRODUCTION-2DPAGEiIPI00296053
    SWISS-2DPAGEiP07954
    UCD-2DPAGEiP07954

    Proteomic databases

    EPDiP07954
    jPOSTiP07954
    MaxQBiP07954
    PaxDbiP07954
    PeptideAtlasiP07954
    PRIDEiP07954
    ProteomicsDBi52052
    52053 [P07954-2]
    TopDownProteomicsiP07954-2 [P07954-2]

    Protocols and materials databases

    The DNASU plasmid repository

    More...
    DNASUi
    2271
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000366560; ENSP00000355518; ENSG00000091483 [P07954-1]
    GeneIDi2271
    KEGGihsa:2271
    UCSCiuc001hyx.4 human [P07954-1]

    Organism-specific databases

    Comparative Toxicogenomics Database

    More...
    CTDi
    2271
    DisGeNETi2271

    GeneCards: human genes, protein and diseases

    More...
    GeneCardsi
    FH
    GeneReviewsiFH
    HGNCiHGNC:3700 FH
    HPAiCAB017785
    HPA025770
    HPA025948
    HPA027341
    MalaCardsiFH
    MIMi136850 gene
    150800 phenotype
    606812 phenotype
    neXtProtiNX_P07954
    OpenTargetsiENSG00000091483
    Orphaneti24 Fumaric aciduria
    523 Hereditary leiomyomatosis and renal cell cancer
    29072 Hereditary pheochromocytoma-paraganglioma
    PharmGKBiPA28139

    GenAtlas: human gene database

    More...
    GenAtlasi
    Search...

    Phylogenomic databases

    eggNOGiKOG1317 Eukaryota
    COG0114 LUCA
    GeneTreeiENSGT00950000183122
    HOGENOMiHOG000061736
    InParanoidiP07954
    KOiK01679
    OMAiFELNVYN
    OrthoDBi241249at2759
    PhylomeDBiP07954
    TreeFamiTF300441

    Enzyme and pathway databases

    UniPathwayiUPA00223;UER01007
    BioCyciMetaCyc:ENSG00000091483-MONOMER
    BRENDAi4.2.1.2 2681
    ReactomeiR-HSA-71403 Citric acid cycle (TCA cycle)

    Miscellaneous databases

    EvolutionaryTraceiP07954

    Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

    More...
    GenomeRNAii
    2271

    Protein Ontology

    More...
    PROi
    PR:P07954

    The Stanford Online Universal Resource for Clones and ESTs

    More...
    SOURCEi
    Search...

    Gene expression databases

    BgeeiENSG00000091483 Expressed in 236 organ(s), highest expression level in heart
    ExpressionAtlasiP07954 baseline and differential
    GenevisibleiP07954 HS

    Family and domain databases

    CDDicd01362 Fumarase_classII, 1 hit
    Gene3Di1.10.275.10, 1 hit
    HAMAPiMF_00743 FumaraseC, 1 hit
    InterProiView 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
    PANTHERiPTHR11444 PTHR11444, 1 hit
    PfamiView protein in Pfam
    PF10415 FumaraseC_C, 1 hit
    PF00206 Lyase_1, 1 hit
    PRINTSiPR00149 FUMRATELYASE
    SUPFAMiSSF48557 SSF48557, 1 hit
    TIGRFAMsiTIGR00979 fumC_II, 1 hit
    PROSITEiView protein in PROSITE
    PS00163 FUMARATE_LYASES, 1 hit

    ProtoNet; Automatic hierarchical classification of proteins

    More...
    ProtoNeti
    Search...

    MobiDB: a database of protein disorder and mobility annotations

    More...
    MobiDBi
    Search...

    <p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

    <p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiFUMH_HUMAN
    <p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P07954
    Secondary accession number(s): B1ANK7
    <p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1988
    Last sequence update: October 1, 1996
    Last modified: July 3, 2019
    This is version 221 of the entry and version 3 of the sequence. See complete history.
    <p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>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.

    <p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. SIMILARITY comments
      Index of protein domains and families
    4. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    5. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    6. Human chromosome 1
      Human chromosome 1: entries, gene names and cross-references to MIM
    7. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
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