ID GLYM_RABIT Reviewed; 504 AA.
AC P14519; P79219;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 27-MAR-2024, entry version 139.
DE RecName: Full=Serine hydroxymethyltransferase, mitochondrial;
DE Short=SHMT;
DE EC=2.1.2.1 {ECO:0000250|UniProtKB:P34897};
DE AltName: Full=Glycine hydroxymethyltransferase;
DE AltName: Full=Serine methylase;
DE Flags: Precursor;
GN Name=SHMT2;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=New Zealand white; TISSUE=Liver;
RA Whitehouse S.K., Sanders P.G., Snell K.;
RL Submitted (FEB-1997) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP PROTEIN SEQUENCE OF 30-504.
RC TISSUE=Liver;
RX PubMed=2656682; DOI=10.1016/s0021-9258(18)81821-x;
RA Martini F., Maras B., Tanci P., Angelaccio S., Pascarella S., Barra D.,
RA Bossa F., Schirch V.;
RT "The primary structure of rabbit liver mitochondrial serine
RT hydroxymethyltransferase.";
RL J. Biol. Chem. 264:8509-8519(1989).
CC -!- FUNCTION: Catalyzes the cleavage of serine to glycine accompanied with
CC the production of 5,10-methylenetetrahydrofolate, an essential
CC intermediate for purine biosynthesis. Serine provides the major source
CC of folate one-carbon in cells by catalyzing the transfer of one carbon
CC from serine to tetrahydrofolate. Contributes to the de novo
CC mitochondrial thymidylate biosynthesis pathway via its role in glycine
CC and tetrahydrofolate metabolism: thymidylate biosynthesis is required
CC to prevent uracil accumulation in mtDNA. Also required for
CC mitochondrial translation by producing 5,10-methylenetetrahydrofolate;
CC 5,10-methylenetetrahydrofolate providing methyl donors to produce the
CC taurinomethyluridine base at the wobble position of some mitochondrial
CC tRNAs. Associates with mitochondrial DNA. In addition to its role in
CC mitochondria, also plays a role in the deubiquitination of target
CC proteins as component of the BRISC complex: required for IFNAR1
CC deubiquitination by the BRISC complex. {ECO:0000250|UniProtKB:P34897}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + glycine + H2O =
CC (6S)-5,6,7,8-tetrahydrofolate + L-serine; Xref=Rhea:RHEA:15481,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15636, ChEBI:CHEBI:33384,
CC ChEBI:CHEBI:57305, ChEBI:CHEBI:57453; EC=2.1.2.1;
CC Evidence={ECO:0000250|UniProtKB:P34897};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:15483;
CC Evidence={ECO:0000250|UniProtKB:P34897};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000250|UniProtKB:P34897};
CC -!- ACTIVITY REGULATION: Hydroxymethyltransferase is inhibited by
CC succinylation at Lys-280. {ECO:0000250|UniProtKB:P34897}.
CC -!- PATHWAY: One-carbon metabolism; tetrahydrofolate interconversion.
CC {ECO:0000250|UniProtKB:P34897}.
CC -!- SUBUNIT: Homotetramer; in the presence of bound pyridoxal 5'-phosphate.
CC Homodimer; in the absence of bound pyridoxal 5'-phosphate. Pyridoxal
CC 5'-phosphate binding mediates an important conformation change that is
CC required for tetramerization. Interacts with ABRAXAS2; the interaction
CC is direct. Identified in a complex with ABRAXAS2 and the other subunits
CC of the BRISC complex, at least composed of the ABRAXAS2, BRCC3/BRCC36,
CC BABAM2 and BABAM1/NBA1. Identified in a complex with ABRAXAS2 and
CC IFNAR1. Interacts with KIRREL3. {ECO:0000250|UniProtKB:P34897}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:P34897}.
CC Mitochondrion matrix, mitochondrion nucleoid
CC {ECO:0000250|UniProtKB:P34897}. Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:P34897}. Cytoplasm
CC {ECO:0000250|UniProtKB:P34897}. Nucleus {ECO:0000250|UniProtKB:P34897}.
CC Note=Mainly localizes in the mitochondrion. Also found in the cytoplasm
CC and nucleus as part of the BRISC complex.
CC {ECO:0000250|UniProtKB:P34897}.
CC -!- PTM: Succinylation at Lys-280 inhibits the hydroxymethyltransferase
CC activity. Desuccinylation by SIRT5 restores the activity, leading to
CC promote cell proliferation. {ECO:0000250|UniProtKB:P34897}.
CC -!- MISCELLANEOUS: In eukaryotes there are two forms of the enzymes: a
CC cytosolic one and a mitochondrial one. {ECO:0000250|UniProtKB:P34897}.
CC -!- SIMILARITY: Belongs to the SHMT family. {ECO:0000305}.
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DR EMBL; X91902; CAA62998.1; -; mRNA.
DR RefSeq; NP_001075874.1; NM_001082405.1.
DR AlphaFoldDB; P14519; -.
DR SMR; P14519; -.
DR STRING; 9986.ENSOCUP00000019769; -.
DR PaxDb; 9986-ENSOCUP00000019769; -.
DR GeneID; 100009293; -.
DR KEGG; ocu:100009293; -.
DR CTD; 6472; -.
DR eggNOG; KOG2467; Eukaryota.
DR InParanoid; P14519; -.
DR OrthoDB; 5358603at2759; -.
DR UniPathway; UPA00193; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0070552; C:BRISC complex; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
DR GO; GO:0005759; C:mitochondrial matrix; ISS:UniProtKB.
DR GO; GO:0042645; C:mitochondrial nucleoid; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0004372; F:glycine hydroxymethyltransferase activity; ISS:UniProtKB.
DR GO; GO:0030170; F:pyridoxal phosphate binding; ISS:UniProtKB.
DR GO; GO:0019264; P:glycine biosynthetic process from serine; IEA:InterPro.
DR GO; GO:0006544; P:glycine metabolic process; ISS:UniProtKB.
DR GO; GO:0006563; P:L-serine metabolic process; ISS:UniProtKB.
DR GO; GO:0006730; P:one-carbon metabolic process; ISS:UniProtKB.
DR GO; GO:0051289; P:protein homotetramerization; ISS:UniProtKB.
DR GO; GO:0070536; P:protein K63-linked deubiquitination; ISS:UniProtKB.
DR GO; GO:0051262; P:protein tetramerization; ISS:UniProtKB.
DR GO; GO:1903715; P:regulation of aerobic respiration; ISS:UniProtKB.
DR GO; GO:0070129; P:regulation of mitochondrial translation; ISS:UniProtKB.
DR GO; GO:0002082; P:regulation of oxidative phosphorylation; ISS:UniProtKB.
DR GO; GO:0034340; P:response to type I interferon; ISS:UniProtKB.
DR GO; GO:0035999; P:tetrahydrofolate interconversion; IEA:UniProtKB-UniPathway.
DR GO; GO:0046653; P:tetrahydrofolate metabolic process; ISS:UniProtKB.
DR CDD; cd00378; SHMT; 1.
DR Gene3D; 3.90.1150.10; Aspartate Aminotransferase, domain 1; 1.
DR Gene3D; 3.40.640.10; Type I PLP-dependent aspartate aminotransferase-like (Major domain); 1.
DR HAMAP; MF_00051; SHMT; 1.
DR InterPro; IPR015424; PyrdxlP-dep_Trfase.
DR InterPro; IPR015421; PyrdxlP-dep_Trfase_major.
DR InterPro; IPR015422; PyrdxlP-dep_Trfase_small.
DR InterPro; IPR001085; Ser_HO-MeTrfase.
DR InterPro; IPR019798; Ser_HO-MeTrfase_PLP_BS.
DR InterPro; IPR039429; SHMT-like_dom.
DR PANTHER; PTHR11680; SERINE HYDROXYMETHYLTRANSFERASE; 1.
DR PANTHER; PTHR11680:SF65; SERINE HYDROXYMETHYLTRANSFERASE, MITOCHONDRIAL; 1.
DR Pfam; PF00464; SHMT; 1.
DR PIRSF; PIRSF000412; SHMT; 1.
DR SUPFAM; SSF53383; PLP-dependent transferases; 1.
DR PROSITE; PS00096; SHMT; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasm; Direct protein sequencing; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Mitochondrion nucleoid; Nucleus;
KW One-carbon metabolism; Phosphoprotein; Pyridoxal phosphate;
KW Reference proteome; Transferase; Transit peptide.
FT TRANSIT 1..29
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:2656682"
FT CHAIN 30..504
FT /note="Serine hydroxymethyltransferase, mitochondrial"
FT /id="PRO_0000032563"
FT REGION 28..49
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 103
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P34897"
FT MOD_RES 181
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P34897"
FT MOD_RES 196
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P34897"
FT MOD_RES 280
FT /note="N6-(pyridoxal phosphate)lysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P34897"
FT MOD_RES 280
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P34897"
FT MOD_RES 356
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P34897"
FT MOD_RES 464
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P34897"
FT MOD_RES 469
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P34897"
FT MOD_RES 470
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P34897"
FT MOD_RES 474
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P34897"
FT CONFLICT 81
FT /note="I -> S (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 481
FT /note="H -> R (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 504 AA; 55902 MW; BE598B9CC0A1B13F CRC64;
MLPFSLLWAV RPLQRCGPLV RTAVRAQHGK AAQTQTGEAS RGWTGQESLS DTDPEMWELL
QREKDRQCRG LELIASENFC IRAALEALGS CLNNKYSEGY PGKRYYGGAE VVDEIELLCQ
RRALEAFDLD PAQWGVNVQP YSGSPANLAA YTALLQPHDR IMGLDLPDGG HLTHGYMSDV
KRVSATSIFF ESMPYKLNPQ TGLIDYEQLA LTARLFRPRL IIAGTSAYAR LIDYARMREV
CDEVKAHLLA DMAHISGLVA AKVIPSPFKH ADVVTTTTHK TLRGARSGLI FYRKGVRTVD
PKTGQEIPYT FEDRINFAVF PSLQGGPHNH AIAAVAVALK QACTPMFREY SLQVLKNARA
MADALLERGY SLVSGGTDNH LVLVDLRPKG LDGARAERVL ELVSITANKN TCPGDRSAIT
PGGLRLGAPA LTSRQFREDD FRRVVDFIDE GVNIGLEVKR KTAKLQDFKS FLLKDPETSQ
HLADLRRRVQ QFARAFPMPG FPEH
//
