GLYM_BOVIN
ID GLYM_BOVIN Reviewed; 504 AA.
AC Q3SZ20;
DT 13-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 114.
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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Thymus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
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; BC103242; AAI03243.1; -; mRNA.
DR RefSeq; NP_001029454.1; NM_001034282.1.
DR AlphaFoldDB; Q3SZ20; -.
DR SMR; Q3SZ20; -.
DR STRING; 9913.ENSBTAP00000038059; -.
DR PaxDb; Q3SZ20; -.
DR PeptideAtlas; Q3SZ20; -.
DR PRIDE; Q3SZ20; -.
DR Ensembl; ENSBTAT00000038244; ENSBTAP00000038059; ENSBTAG00000031500.
DR GeneID; 507197; -.
DR KEGG; bta:507197; -.
DR CTD; 6472; -.
DR VEuPathDB; HostDB:ENSBTAG00000031500; -.
DR VGNC; VGNC:34604; SHMT2.
DR eggNOG; KOG2467; Eukaryota.
DR GeneTree; ENSGT00390000002762; -.
DR HOGENOM; CLU_022477_0_1_1; -.
DR InParanoid; Q3SZ20; -.
DR OMA; RCQHSEV; -.
DR OrthoDB; 372408at2759; -.
DR TreeFam; TF314667; -.
DR Reactome; R-BTA-196757; Metabolism of folate and pterines.
DR Reactome; R-BTA-9013408; RHOG GTPase cycle.
DR UniPathway; UPA00193; -.
DR Proteomes; UP000009136; Chromosome 5.
DR Bgee; ENSBTAG00000031500; Expressed in placenta and 107 other tissues.
DR GO; GO:0070552; C:BRISC complex; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0015630; C:microtubule cytoskeleton; IEA:Ensembl.
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:0048027; F:mRNA 5'-UTR binding; IBA:GO_Central.
DR GO; GO:0000900; F:mRNA regulatory element binding translation repressor activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; IBA:GO_Central.
DR GO; GO:0030170; F:pyridoxal phosphate binding; ISS:UniProtKB.
DR GO; GO:0070905; F:serine binding; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IBA:GO_Central.
DR GO; GO:0046655; P:folic acid metabolic process; IBA:GO_Central.
DR GO; GO:0019264; P:glycine biosynthetic process from serine; IBA:GO_Central.
DR GO; GO:0006544; P:glycine metabolic process; ISS:UniProtKB.
DR GO; GO:0006565; P:L-serine catabolic process; IBA:GO_Central.
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:0009113; P:purine nucleobase biosynthetic process; IBA:GO_Central.
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; IBA:GO_Central.
DR GO; GO:0046653; P:tetrahydrofolate metabolic process; ISS:UniProtKB.
DR CDD; cd00378; SHMT; 1.
DR Gene3D; 3.40.640.10; -; 1.
DR Gene3D; 3.90.1150.10; -; 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; PTHR11680; 1.
DR Pfam; PF00464; SHMT; 1.
DR PIRSF; PIRSF000412; SHMT; 1.
DR SUPFAM; SSF53383; SSF53383; 1.
DR PROSITE; PS00096; SHMT; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Cytoplasm; 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:0000250|UniProtKB:P14519"
FT CHAIN 30..504
FT /note="Serine hydroxymethyltransferase, mitochondrial"
FT /id="PRO_0000239655"
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"
SQ SEQUENCE 504 AA; 55605 MW; ED59264587E8B3E6 CRC64;
MLSFSFIWAT RPLRRCGQLV GMAVRCQHSE AAQTQTGEAS KGWSGQESLS DSDPEMWELL
RREKDRQCRG LELIASENFC SRAALEALGS CLNNKYSEGY PGKRYYGGAE VVDEIELLCQ
RRALEAFDLD PAQWGVNVQP YSGSPANLAA YTALLQPHDR IMGLDLPDGG HLTHGYMSDV
KRISATSIFF ESMPYKLNPQ TGLIDYDQLA LTARLFKPRL IIAGTSAYAR LIDYARMREV
CDEVKAHLLA DMAHISGLVA AKVIPSPFKH ADIVTTTTHK TLRGARSGLI FYRKGVQAVD
PKTGREIPYT FEDRINFAVF PSLQGGPHNH AIAAVAVALK QACTPMFREY SLQILKNAQA
MANALLERGY SLVSGGTDNH LVLVDLRPKG LDGARAERVL ELVSITANKN TCPGDRSAIT
PGGLRLGAPA LTSRGFLEDD FRKVVGFIDE GVNIGLEVKS KTTKLQDFKS FLLKDPETSH
QLADLRQRVE QFARAFPMPG FDDH
