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Protein

Fumarate hydratase, mitochondrial

Gene

FH

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

Functioni

Also acts as a tumor suppressor.

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).By similarity

Catalytic activityi

(S)-malate = fumarate + H2O.

Pathwayi: tricarboxylic acid cycle

This protein is involved in step 1 of the subpathway that synthesizes (S)-malate from fumarate.
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
Binding sitei147SubstrateBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionLyase
Biological processTricarboxylic acid cycle

Enzyme and pathway databases

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

Names & Taxonomyi

Protein namesi
Recommended name:
Fumarate hydratase, mitochondrial (EC:4.2.1.2)
Short name:
Fumarase
Gene namesi
Name:FH
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000091483.6
HGNCiHGNC:3700 FH
MIMi136850 gene
neXtProtiNX_P07954

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; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Mitochondrion

Pathology & Biotechi

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.
See also OMIM:606812
Feature keyPosition(s)DescriptionActionsGraphical viewLength
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)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by predisposition to cutaneous and uterine leiomyomas, and papillary type 2 renal cancer which occurs in about 20% of patients.
See also OMIM:150800
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_013501233R → H in HLRCC. 1 PublicationCorresponds 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

Keywords - Diseasei

Disease mutation, Tumor suppressor

Organism-specific databases

DisGeNETi2271
GeneReviewsiFH
MalaCardsiFH
MIMi150800 phenotype
606812 phenotype
OpenTargetsiENSG00000091483
Orphaneti24 Fumaric aciduria
523 Hereditary leiomyomatosis and renal cell cancer
29072 Hereditary pheochromocytoma-paraganglioma
PharmGKBiPA28139

Polymorphism and mutation databases

BioMutaiFH
DMDMi1730117

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 44MitochondrionBy similarityAdd BLAST44
ChainiPRO_000001031945 – 510Fumarate hydratase, mitochondrialAdd BLAST466
Isoform Cytoplasmic (identifier: P07954-2)
Initiator methionineiRemovedBy similarity

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
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 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
Isoform Cytoplasmic (identifier: P07954-2)
Modified residuei2N-acetylalanine By similarityBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP07954
MaxQBiP07954
PaxDbiP07954
PeptideAtlasiP07954
PRIDEiP07954
TopDownProteomicsiP07954-2 [P07954-2]

2D gel databases

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

PTM databases

iPTMnetiP07954
PhosphoSitePlusiP07954
SwissPalmiP07954

Expressioni

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

BgeeiENSG00000091483
CleanExiHS_FH
ExpressionAtlasiP07954 baseline and differential
GenevisibleiP07954 HS

Organism-specific databases

HPAiCAB017785
HPA025770
HPA025948
HPA027341

Interactioni

Subunit structurei

Homotetramer.1 Publication

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi108562, 84 interactors
DIPiDIP-46920N
IntActiP07954, 27 interactors
STRINGi9606.ENSP00000355518

Structurei

Secondary structure

1510
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi50 – 55Combined sources6
Beta strandi58 – 63Combined sources6
Helixi70 – 78Combined sources9
Helixi84 – 86Combined sources3
Helixi90 – 107Combined sources18
Helixi108 – 110Combined sources3
Helixi114 – 128Combined sources15
Helixi133 – 135Combined sources3
Beta strandi139 – 142Combined sources4
Helixi147 – 164Combined sources18
Helixi177 – 181Combined sources5
Turni182 – 184Combined sources3
Turni187 – 189Combined sources3
Helixi190 – 205Combined sources16
Helixi207 – 224Combined sources18
Turni225 – 227Combined sources3
Beta strandi229 – 234Combined sources6
Beta strandi237 – 243Combined sources7
Helixi244 – 264Combined sources21
Turni267 – 270Combined sources4
Turni277 – 279Combined sources3
Helixi289 – 301Combined sources13
Helixi311 – 316Combined sources6
Helixi319 – 345Combined sources27
Beta strandi349 – 352Combined sources4
Beta strandi366 – 368Combined sources3
Helixi375 – 399Combined sources25
Helixi409 – 433Combined sources25
Helixi435 – 437Combined sources3
Helixi442 – 451Combined sources10
Helixi454 – 459Combined sources6
Helixi460 – 463Combined sources4
Helixi465 – 478Combined sources14
Helixi482 – 488Combined sources7
Helixi494 – 500Combined sources7
Helixi503 – 505Combined sources3
Beta strandi506 – 508Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3E04X-ray1.95A/B/C/D44-510[»]
5D6BX-ray2.10A49-510[»]
5UPPX-ray1.80A/B45-510[»]
ProteinModelPortaliP07954
SMRiP07954
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP07954

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni176 – 179B siteBy similarity4
Regioni186 – 188Substrate bindingBy similarity3

Sequence similaritiesi

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG1317 Eukaryota
COG0114 LUCA
GeneTreeiENSGT00390000002779
HOGENOMiHOG000061736
HOVERGENiHBG002183
InParanoidiP07954
KOiK01679
OMAiVSFTDNC
OrthoDBiEOG091G05UL
PhylomeDBiP07954
TreeFamiTF300441

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

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative initiation. AlignAdd to basket

Isoform Mitochondrial (identifier: P07954-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« 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
Checksum:i86F91F95DC046F64
GO
Isoform Cytoplasmic (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. 1 PublicationCorresponds 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_002448425D → V in FMRD. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0189651 – 43Missing in isoform Cytoplasmic. CuratedAdd BLAST43

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]
UniGeneiHs.592490

Genome annotation databases

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

Keywords - Coding sequence diversityi

Alternative initiation

Similar proteinsi

Entry informationi

Entry nameiFUMH_HUMAN
AccessioniPrimary (citable) accession number: P07954
Secondary accession number(s): B1ANK7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: October 1, 1996
Last modified: May 23, 2018
This is version 210 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, 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 polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. 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

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