FUMH_RHIOR
ID FUMH_RHIOR Reviewed; 494 AA.
AC P55250;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 100.
DE RecName: Full=Fumarate hydratase, mitochondrial {ECO:0000250|UniProtKB:P08417};
DE Short=Fumarase {ECO:0000303|PubMed:7557464};
DE EC=4.2.1.2 {ECO:0000250|UniProtKB:P08417};
DE Flags: Precursor;
GN Name=FUMR {ECO:0000303|PubMed:7557464};
OS Rhizopus oryzae (Mucormycosis agent) (Rhizopus arrhizus var. delemar).
OC Eukaryota; Fungi; Fungi incertae sedis; Mucoromycota; Mucoromycotina;
OC Mucoromycetes; Mucorales; Mucorineae; Rhizopodaceae; Rhizopus.
OX NCBI_TaxID=64495;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 10260 / CBS 329.47 / DSM 905 / NRRL 1526;
RX PubMed=7557464; DOI=10.1016/0378-1119(95)00367-f;
RA Friedberg D., Peleg Y., Monsonego A., Maissi S., Battat E., Rokem J.S.,
RA Goldberg I.;
RT "The fumR gene encoding fumarase in the filamentous fungus Rhizopus oryzae:
RT cloning, structure and expression.";
RL Gene 163:139-144(1995).
CC -!- FUNCTION: Catalyzes the reversible stereospecific interconversion of
CC fumarate to L-malate. In mitochondrion, catalyzes the hydration of
CC fumarate to L-malate in the tricarboxylic acid (TCA) cycle to
CC facilitate a transition step in the production of energy in the form of
CC NADH. In cytoplasm and nucleus, involved in DNA repair in response to
CC DNA damage: following DNA double-strand breaks (DSBs), translocates
CC from the cytosol to the nucleus and promotes DNA repair by catalyzing
CC the dehydration of L-malate to fumarate.
CC {ECO:0000250|UniProtKB:P08417}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-malate = fumarate + H2O; Xref=Rhea:RHEA:12460,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15589, ChEBI:CHEBI:29806; EC=4.2.1.2;
CC Evidence={ECO:0000250|UniProtKB:P08417};
CC -!- PATHWAY: Carbohydrate metabolism; tricarboxylic acid cycle; (S)-malate
CC from fumarate: step 1/1. {ECO:0000250|UniProtKB:P08417}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:P08417}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000250|UniProtKB:P08417}. Cytoplasm
CC {ECO:0000250|UniProtKB:P08417}. Nucleus {ECO:0000250|UniProtKB:P08417}.
CC Note=Translocates from the cytosol to the nucleus in response to DNA
CC damage. {ECO:0000250|UniProtKB:P08417}.
CC -!- MISCELLANEOUS: There are 2 substrate-binding sites: the catalytic A
CC site, and the non-catalytic B site that may play a role in the transfer
CC of substrate or product between the active site and the solvent.
CC Alternatively, the B site may bind allosteric effectors (By
CC similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the class-II fumarase/aspartase family. Fumarase
CC subfamily. {ECO:0000305}.
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DR EMBL; X78576; CAA55314.1; -; Genomic_DNA.
DR AlphaFoldDB; P55250; -.
DR SMR; P55250; -.
DR PRIDE; P55250; -.
DR BRENDA; 4.2.1.2; 5365.
DR UniPathway; UPA00223; UER01007.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0045239; C:tricarboxylic acid cycle enzyme complex; IEA:InterPro.
DR GO; GO:0004333; F:fumarate hydratase activity; ISS:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0006302; P:double-strand break repair; ISS:UniProtKB.
DR GO; GO:0006106; P:fumarate metabolic process; ISS:UniProtKB.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IEA:UniProtKB-UniPathway.
DR CDD; cd01362; Fumarase_classII; 1.
DR Gene3D; 1.10.275.10; -; 1.
DR HAMAP; MF_00743; FumaraseC; 1.
DR InterPro; IPR005677; Fum_hydII.
DR InterPro; IPR024083; Fumarase/histidase_N.
DR InterPro; IPR018951; Fumarase_C_C.
DR InterPro; IPR020557; Fumarate_lyase_CS.
DR InterPro; IPR000362; Fumarate_lyase_fam.
DR InterPro; IPR022761; Fumarate_lyase_N.
DR InterPro; IPR008948; L-Aspartase-like.
DR PANTHER; PTHR11444; PTHR11444; 1.
DR Pfam; PF10415; FumaraseC_C; 1.
DR Pfam; PF00206; Lyase_1; 1.
DR PRINTS; PR00149; FUMRATELYASE.
DR SUPFAM; SSF48557; SSF48557; 1.
DR TIGRFAMs; TIGR00979; fumC_II; 1.
DR PROSITE; PS00163; FUMARATE_LYASES; 1.
PE 3: Inferred from homology;
KW Cytoplasm; DNA damage; DNA repair; Lyase; Mitochondrion; Nucleus;
KW Transit peptide; Tricarboxylic acid cycle.
FT TRANSIT 1..15
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 16..494
FT /note="Fumarate hydratase, mitochondrial"
FT /id="PRO_0000010331"
FT ACT_SITE 218
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:P05042"
FT ACT_SITE 348
FT /evidence="ECO:0000250|UniProtKB:P9WN93"
FT BINDING 128..130
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P05042"
FT BINDING 159..162
FT /ligand="substrate"
FT /note="in site B"
FT /evidence="ECO:0000250|UniProtKB:P05042"
FT BINDING 169..171
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P05042"
FT BINDING 217
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P9WN93"
FT BINDING 349
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P9WN93"
FT BINDING 354..356
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P9WN93"
FT SITE 361
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000250|UniProtKB:P05042"
SQ SEQUENCE 494 AA; 53157 MW; 8FDB9D323A9146EE CRC64;
MLRASATRFL SQAKNMNNSP RLFSSASAAL QKFRAERDTF GDLQVPADRY WGAQTQRSLQ
NFDIGGPTER MPEPLIRAFG VLKKAAATVN MTYGLDPKVG EAIQKAADEV IDGSLIDHFP
LVVWQTGSGT QTKMNVNEVI SNRAIELLGG ELGSKAPVHP NDHVNMSQSS NDTFPTAMHV
AAVVEIHGRL IPALTTLRDA LQAKSAEFEH IIKIGRTHLQ DATPLTLGQE FSGYTQQLTY
GIARVQGTLE RLYNLAQGGT AVGTGLNTRK GFDAKVAEAI ASITGLPFKT APNKFEALAA
HDALVEAHGA LNTVACSLMK IANDIRYLGS GPRCGLGELS LPENEPGSSI MPGKVNPTQC
EAMTMVCAQV MGNNTAISVA GSNGQFELNV FKPVMIKNLI QSIRLISDAS ISFTKNCVVG
IEANEKKISS IMNESLMLVT ALNPHIGYDK AAKCAKKAHK EGTTLKEAAL SLGYLTSEEF
DQWVRPEDMI SAKD
