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Protein Page:
FH (human)
p Phosphorylation
ac Acetylation
me Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
ub Ubiquitylation
sm Sumoylation
ne Neddylation
gl O-GlcNAc
ga O-GalNAc
pa Palmitoylation
ad Adenylation
sn S-Nitrosylation
ca Caspase cleavage
sc Succinylation

Overview
FH a metabolic enzyme that participates in the tricarboxylic acid cycle that catalyzes the conversion of (S)-malate into fumarate + H2O. There are two 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. Fumarate accumulates in the cell when FH is inactivated. Fumarate inhibits the dioxygenases that hydroxylate the transcription factor HIF and leads to its degradation by VHL. Since HIF turns on oncogenic pathways, FH has apparent tumor suppressor activity. Defects in FH are the cause of hereditary leiomyomatosis and renal cell cancer (HLRCC), a highly metastatic form of RCC. Defects in FH are the cause of fumarase deficiency (FD) also known as fumaricaciduria. FD is characterized by progressive encephalopathy, developmental delay, hypotonia, cerebral atrophy and lactic and pyruvic acidemia. Cells derived from a patient with HLRCC exhibit compromised oxidative phosphorylation, dependence on anaerobic glycolysis, rapid glycolytic flux, and overexpression of lactate dehydrogenase A (LDHA) and GLUT1. Two human isoforms are produced by alternative initiation. The longer isoform is mitochondrial, while the shorter form, missing residues 1-43, is cytoplasmic. Note: This description may include information from UniProtKB.
Protein type: EC 4.2.1.2; Mitochondrial; Lyase; Carbohydrate Metabolism - citrate (TCA) cycle
Chromosomal Location of Human Ortholog: 1q42.1
Cellular Component: tricarboxylic acid cycle enzyme complex; mitochondrion; mitochondrial matrix; cytoplasm
Molecular Function: fumarate hydratase activity
Biological Process: cellular metabolic process; fumarate metabolic process; homeostasis of number of cells within a tissue; tricarboxylic acid cycle
Disease: Fumarase Deficiency
Reference #:  P07954 (UniProtKB)
Alt. Names/Synonyms: FH; Fumarase; fumarate hydratase; Fumarate hydratase, mitochondrial; FUMH; HLRCC; LRCC; MCL; MCUL1
Gene Symbols: FH
Molecular weight: 54,637 Da
Basal Isoelectric point: 8.85  Predict pI for various phosphorylation states
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
Select Structure to View Below

FH

Protein Structure Not Found.


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Modification Sites and Domains Show Modification Legend
Click here to view phosphorylation modifications only

Modification Sites in Parent Protein, Orthologs, and Isoforms Show Modification Legend
 

Show Multiple Sequence Alignment


 LTP 

LTP: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.


 HTP 

HTP: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.


       human

► Hide Isoforms
 
0 1 S46-p PNAARMAsQNSFRIE
0 4 Y54-p QNSFRIEyDTFGELk
0 5 K61-ac yDTFGELkVPNDkyy
0 1 K61 yDTFGELKVPNDkyy
0 2 K61 yDTFGELKVPNDkyy
0 13 K66-ac ELkVPNDkyyGAQTV
0 1 K66 ELkVPNDKyyGAQTV
0 2 K66-sc ELkVPNDkyyGAQTV
0 2 Y67-p LkVPNDkyyGAQTVR
0 2 Y68-p kVPNDkyyGAQTVRS
0 31 K80-ac VRSTMNFkIGGVTER
0 1 K80 VRSTMNFKIGGVTER
0 2 K80-sc VRSTMNFkIGGVTER
0 2 T85 NFkIGGVTERMPtPV
0 7 T90-p GVTERMPtPVIkAFG
0 7 K94-ac RMPtPVIkAFGILKR
0 5 K94-ub RMPtPVIkAFGILKR
0 1 K94-sc RMPtPVIkAFGILKR
0 1 K100 IkAFGILKRAAAEVN
0 1 K100 IkAFGILKRAAAEVN
0 6 K115-ac QDYGLDPkIANAIMk
0 1 K115 QDYGLDPKIANAIMk
0 2 K115 QDYGLDPKIANAIMk
0 1 N118 GLDPkIANAIMkAAD
0 3 K122-ac kIANAIMkAADEVAE
0 1 K122 kIANAIMKAADEVAE
0 2 K122-sc kIANAIMkAADEVAE
0 3 K131 ADEVAEGKLNDHFPL
0 1 S171-p MLGGELGskIPVHPN
0 3 K172-ac LGGELGskIPVHPND
0 2 I173 GGELGskIPVHPNDH
0 1 K183 HPNDHVNKSQSSNDT
0 1 E205 AAAIEVHEVLLPGLQ
0 1 K213 VLLPGLQKLHDALDA
0 1 K221-sc LHDALDAkSKEFAQI
0 7 K223 DALDAkSKEFAQIIK
0 1 K223 DALDAkSKEFAQIIK
0 2 K223 DALDAkSKEFAQIIK
0 8 K256-ac SGYVQQVkYAMTRIK
0 1 K263 kYAMTRIKAAMPRIY
0 9 K292-ac TRIGFAEkVAAKVAA
0 1 K292 TRIGFAEKVAAKVAA
0 2 K292-sc TRIGFAEkVAAKVAA
0 1 T301-p AAKVAALtGLPFVTA
0 1 S351-p FLGSGPRsGLGELIL
0 5 S366-p PENEPGSsIMPGKVN
0 1 K447 ANTERINKLMNESLM
0 51 Y465-p ALNPHIGyDkAAkIA
0 2 K467-ac NPHIGyDkAAkIAkT
0 3 K470-ac IGyDkAAkIAkTAHk
0 3 K473-ac DkAAkIAkTAHkNGS
0 4 K477-ac kIAkTAHkNGSTLKE
0 67 Y491-p ETAIELGyLtAEQFD
0 2 T493-p AIELGyLtAEQFDEW
0 2 K502 EQFDEWVKPKDMLGP
0 1 K504 FDEWVKPKDMLGPK_
  FH iso2  
S3 _____MASQNSFRIE
Y11 QNSFRIEYDTFGELK
K18 YDTFGELKVPNDKYY
K18 YDTFGELKVPNDKYY
K18 YDTFGELKVPNDKYY
K23 ELKVPNDKYYGAQTV
K23 ELKVPNDKYYGAQTV
K23 ELKVPNDKYYGAQTV
Y24 LKVPNDKYYGAQTVR
Y25 KVPNDKYYGAQTVRS
K37 VRSTMNFKIGGVTER
K37 VRSTMNFKIGGVTER
K37 VRSTMNFKIGGVTER
T42 NFKIGGVTERMPTPV
T47 GVTERMPTPVIKAFG
K51 RMPTPVIKAFGILKR
K51 RMPTPVIKAFGILKR
K51 RMPTPVIKAFGILKR
K57 IKAFGILKRAAAEVN
K57 IKAFGILKRAAAEVN
K72 QDYGLDPKIANAIMK
K72 QDYGLDPKIANAIMK
K72 QDYGLDPKIANAIMK
N75 GLDPKIANAIMKAAD
K79 KIANAIMKAADEVAE
K79 KIANAIMKAADEVAE
K79 KIANAIMKAADEVAE
K88 ADEVAEGKLNDHFPL
S128 MLGGELGSKIPVHPN
K129 LGGELGSKIPVHPND
I130 GGELGSKIPVHPNDH
K140 HPNDHVNKSQSSNDT
E162 AAAIEVHEVLLPGLQ
K170 VLLPGLQKLHDALDA
K178 LHDALDAKSKEFAQI
K180 DALDAKSKEFAQIIK
K180 DALDAKSKEFAQIIK
K180 DALDAKSKEFAQIIK
K213 SGYVQQVKYAMTRIK
K220 KYAMTRIKAAMPRIY
K249 TRIGFAEKVAAKVAA
K249 TRIGFAEKVAAKVAA
K249 TRIGFAEKVAAKVAA
T258 AAKVAALTGLPFVTA
S308 FLGSGPRSGLGELIL
S323 PENEPGSSIMPGKVN
K404 ANTERINKLMNESLM
Y422 ALNPHIGYDKAAKIA
K424 NPHIGYDKAAKIAKT
K427 IGYDKAAKIAKTAHK
K430 DKAAKIAKTAHKNGS
K434 KIAKTAHKNGSTLKE
Y448 ETAIELGYLTAEQFD
T450 AIELGYLTAEQFDEW
K459 EQFDEWVKPKDMLGP
K461 FDEWVKPKDMLGPK_
  mouse

 
S43 PNVARMASQNSFRVE
F51 QNSFRVEFDTFGELk
K58-ac FDTFGELkVPTDkYY
K58-ub FDTFGELkVPTDkYY
K58-sc FDTFGELkVPTDkYY
K63-ac ELkVPTDkYYGAQTV
K63-ub ELkVPTDkYYGAQTV
K63-sc ELkVPTDkYYGAQTV
Y64 LkVPTDkYYGAQTVR
Y65 kVPTDkYYGAQTVRS
K77-ac VRSTMNFkIGGAtER
K77-ub VRSTMNFkIGGAtER
K77-sc VRSTMNFkIGGAtER
T82-p NFkIGGAtERMPIPV
I87 GAtERMPIPVIQAFG
Q91 RMPIPVIQAFGILkR
Q91 RMPIPVIQAFGILkR
Q91 RMPIPVIQAFGILkR
K97 IQAFGILKRAAAEVN
K97-ub IQAFGILkRAAAEVN
K112-ac QEYGLDPkIAsAIMk
K112-ub QEYGLDPkIAsAIMk
K112-sc QEYGLDPkIAsAIMk
S115-p GLDPkIAsAIMkAAD
K119-ac kIAsAIMkAADEVAE
K119-ub kIAsAIMkAADEVAE
K119-sc kIAsAIMkAADEVAE
K128-ac ADEVAEGkLNDHFPL
S168 MLGGELGSkkPVHPN
K169-ac LGGELGSkkPVHPND
K170-ac GGELGSkkPVHPNDH
K180-sc HPNDHVNkSQSSNDT
K202-ac AAAVEVHkVLLPGLQ
K210-ac VLLPGLQkLHDALSA
K218 LHDALSAKSkEFAQV
K220-ac DALSAKSkEFAQVIK
K220-ub DALSAKSkEFAQVIK
K220-sc DALSAKSkEFAQVIK
Q253 SGYVQQVQYAMVRIk
K260-ac QYAMVRIkAAMPRIY
K289-ac TRIGFAEkVAAKVAA
K289-ub TRIGFAEkVAAKVAA
K289-sc TRIGFAEkVAAKVAA
T298 AAKVAALTGLPFVTA
S348 FLGSGPRSGLGELIL
S363-p PENEPGSsIMPGKVN
K444 ANTERINKLMNESLM
Y462-p ALNPHIGyDkAAkIA
K464-ac NPHIGyDkAAkIAkT
K467-ac IGyDkAAkIAkTAHk
K470-ac DkAAkIAkTAHkNGS
K474-ac kIAkTAHkNGSTLKE
Y488-p ETAIELGyLtAEQFD
T490-p AIELGyLtAEQFDEW
K499-ac EQFDEWVkPkDMLGP
K501-ac FDEWVkPkDMLGPK_
  rat

 
S43 PNVVRMASQNSFRIE
Y51 QNSFRIEYDTFGELk
K58-ac YDTFGELkVPTDkYY
K58 YDTFGELKVPTDkYY
K58 YDTFGELKVPTDkYY
K63-ac ELkVPTDkYYGAQTV
K63 ELkVPTDKYYGAQTV
K63 ELkVPTDKYYGAQTV
Y64 LkVPTDkYYGAQTVR
Y65 kVPTDkYYGAQTVRS
K77-ac VRSTMNFkIGGATER
K77 VRSTMNFKIGGATER
K77 VRSTMNFKIGGATER
T82 NFkIGGATERMPIPV
I87 GATERMPIPVIkAFG
K91-ac RMPIPVIkAFGILkR
K91 RMPIPVIKAFGILkR
K91 RMPIPVIKAFGILkR
K97-ac IkAFGILkRAAAEVN
K97 IkAFGILKRAAAEVN
K112-ac QEYGLDPkIASAIMk
K112 QEYGLDPKIASAIMk
K112 QEYGLDPKIASAIMk
S115 GLDPkIASAIMkAAD
K119-ac kIASAIMkAADEVAE
K119 kIASAIMKAADEVAE
K119 kIASAIMKAADEVAE
K128-ac ADEVAEGkLNDHFPL
S168 MLGGELGSkkPVHPN
K169-ac LGGELGSkkPVHPND
K170-ac GGELGSkkPVHPNDH
K180 HPNDHVNKSQSSNDT
Q202 AAALEVHQVLLPGLQ
K210 VLLPGLQKLHDALSA
K218 LHDALSAKSkEFAQV
K220-ac DALSAKSkEFAQVIK
K220 DALSAKSKEFAQVIK
K220 DALSAKSKEFAQVIK
Q253 SGYVQQVQYAMERIK
K260 QYAMERIKAAMPRIY
K289-ac TRIGFAEkVAAKVAA
K289 TRIGFAEKVAAKVAA
K289 TRIGFAEKVAAKVAA
T298 AAKVAALTGLPFVTA
S348 FLGSGPRSGLGELIL
S363 PENEPGSSIMPGKVN
K444-ac ANTERINkLMNESLM
Y462-p ALNPHIGyDKAAkIA
K464 NPHIGyDKAAkIAkT
K467-ac IGyDKAAkIAkTAHK
K470-ac DKAAkIAkTAHKNGS
K474 kIAkTAHKNGSTLKK
Y488 KTAIELGYLTAEQFD
T490 AIELGYLTAEQFDEW
K499 EQFDEWVKPKDMLGP
K501 FDEWVKPKDMLGPK_
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