Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Entry version 236 (29 Sep 2021)
Sequence version 3 (01 Oct 1996)
Previous versions | rss
Add a publicationFeedback
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 (PubMed:30761759).

Experiments in other 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 (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 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

Pathway Commons web resource for biological pathway data

More...
PathwayCommonsi
P07954

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

Eukaryotic Pathogen, Vector and Host Database Resources

More...
VEuPathDBi
HostDB:ENSG00000091483

<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

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 variants 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 PublicationCorresponds to variant dbSNP:rs1553341046EnsemblClinVar.1
Natural variantiVAR_002448425D → V in FMRD. 1 Publication1
Hereditary leiomyomatosis and renal cell cancer (HLRCC)3 Publications
The disease is caused by variants 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-(2-succinyl)cysteine) 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 PublicationCorresponds to variant dbSNP:rs121913119EnsemblClinVar.1

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 H2AZ1 and localization to chromatin in response to DNA damage. 1 Publication1
Mutagenesisi236T → D: Phosphomimetic mutant; promotes interaction with H2AZ1, leading to increased localization to chromatin in response to DNA damage. 1 Publication1

Keywords - Diseasei

Disease variant, 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

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...
Pharosi
P07954, Tbio

Genetic variation 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 or proteolytic cleavage.<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

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

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...
MassIVEi
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: a multi-organism proteome resource

More...
ProteomicsDBi
52052 [P07954-1]
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

GlyGen: Computational and Informatics Resources for Glycoscience

More...
GlyGeni
P07954, 1 site, 1 O-linked glycan (1 site)

iPTMnet integrated resource for PTMs in systems biology context

More...
iPTMneti
P07954

MetOSite database of methionine sulfoxide sites

More...
MetOSitei
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 heart and 248 other tissues

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
ENSG00000091483, Tissue enhanced (liver)

<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 H2AZ1 (PubMed:26237645).

3 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section">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="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Hide details

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...
BioGRIDi
108562, 165 interactors

Database of interacting proteins

More...
DIPi
DIP-46920N

Protein interaction database and analysis system

More...
IntActi
P07954, 35 interactors

Molecular INTeraction database

More...
MINTi
P07954

STRING: functional protein association networks

More...
STRINGi
9606.ENSP00000355518

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...
RNActi
P07954, protein

<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...

Protein Data Bank in Europe - Knowledge Base

More...
PDBe-KBi
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

Ensembl GeneTree

More...
GeneTreei
ENSGT00950000183122

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...
HOGENOMi
CLU_021594_4_1_1

InParanoid: Eukaryotic Ortholog Groups

More...
InParanoidi
P07954

Identification of Orthologs from Complete Genome Data

More...
OMAi
HDSMGEV

Database of Orthologous Groups

More...
OrthoDBi
507784at2759

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

This entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

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

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A804HI24A0A804HI24_HUMAN
Fumarate hydratase, mitochondrial
FH
480Annotation score:

Annotation score:1 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>
A0A804HKE6A0A804HKE6_HUMAN
Fumarate hydratase, mitochondrial
FH
192Annotation score:

Annotation score:1 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>
A0A804HL52A0A804HL52_HUMAN
Fumarate hydratase, mitochondrial
FH
61Annotation score:

Annotation score:1 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>

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 PublicationCorresponds to variant dbSNP:rs1553341046EnsemblClinVar.1
Natural variantiVAR_013503328M → R in HLRCC. 1 Publication1
Natural variantiVAR_081606362E → Q in HLRCC. 1 PublicationCorresponds to variant dbSNP:rs121913119EnsemblClinVar.1
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[»]
6EBTX-ray2.30A/B45-510[»]
6V8FX-ray2.30A/B45-510[»]
6VBEX-ray1.90A/B45-510[»]
SMRiP07954
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGRIDi108562, 165 interactors
DIPiDIP-46920N
IntActiP07954, 35 interactors
MINTiP07954
STRINGi9606.ENSP00000355518

PTM databases

GlyGeniP07954, 1 site, 1 O-linked glycan (1 site)
iPTMnetiP07954
MetOSiteiP07954
PhosphoSitePlusiP07954
SwissPalmiP07954

Genetic variation databases

BioMutaiFH
DMDMi1730117

2D gel databases

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

Proteomic databases

EPDiP07954
jPOSTiP07954
MassIVEiP07954
MaxQBiP07954
PaxDbiP07954
PeptideAtlasiP07954
PRIDEiP07954
ProteomicsDBi52052 [P07954-1]
52053 [P07954-2]
TopDownProteomicsiP07954-2 [P07954-2]

Protocols and materials databases

Antibodypedia a portal for validated antibodies

More...
Antibodypediai
34701, 658 antibodies

The DNASU plasmid repository

More...
DNASUi
2271

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
HPAiENSG00000091483, Tissue enhanced (liver)
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
VEuPathDBiHostDB:ENSG00000091483

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG1317, Eukaryota
GeneTreeiENSGT00950000183122
HOGENOMiCLU_021594_4_1_1
InParanoidiP07954
OMAiHDSMGEV
OrthoDBi507784at2759
PhylomeDBiP07954
TreeFamiTF300441

Enzyme and pathway databases

UniPathwayiUPA00223;UER01007
BioCyciMetaCyc:ENSG00000091483-MONOMER
BRENDAi4.2.1.2, 2681
PathwayCommonsiP07954
ReactomeiR-HSA-71403, Citric acid cycle (TCA cycle)

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...
BioGRID-ORCSi
2271, 123 hits in 1021 CRISPR screens
EvolutionaryTraceiP07954

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

More...
GenomeRNAii
2271
PharosiP07954, Tbio

Protein Ontology

More...
PROi
PR:P07954
RNActiP07954, protein

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000091483, Expressed in heart and 248 other tissues
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

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: September 29, 2021
This is version 236 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, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with genetic variants
    List of human entries with genetic variants
  3. Human variants curated from literature reports
    Index of human variants curated from literature reports
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again