GLYC_RABIT
ID GLYC_RABIT Reviewed; 484 AA.
AC P07511;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Serine hydroxymethyltransferase, cytosolic;
DE Short=SHMT;
DE EC=2.1.2.1 {ECO:0000269|PubMed:1381582};
DE AltName: Full=Glycine hydroxymethyltransferase;
DE AltName: Full=Serine methylase;
GN Name=SHMT1;
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], FUNCTION, AND CATALYTIC ACTIVITY.
RC STRAIN=New Zealand white; TISSUE=Liver;
RX PubMed=1381582; DOI=10.1042/bj2860117;
RA Byrne P.C., Sanders P.G., Snell K.;
RT "Nucleotide sequence and expression of a cDNA encoding rabbit liver
RT cytosolic serine hydroxymethyltransferase.";
RL Biochem. J. 286:117-123(1992).
RN [2]
RP PROTEIN SEQUENCE OF 2-484, AND ACETYLATION AT ALA-2.
RC TISSUE=Liver;
RX PubMed=3553178; DOI=10.1016/s0021-9258(18)45600-1;
RA Martini F., Angelaccio S., Pascarella S., Barra D., Bossa F., Schirch V.;
RT "The primary structure of rabbit liver cytosolic serine
RT hydroxymethyltransferase.";
RL J. Biol. Chem. 262:5499-5509(1987).
RN [3]
RP PROTEIN SEQUENCE OF 2-15, DEAMIDATION AT ASN-6, AND ISOPEPTIDE BOND AT
RP ASN-6.
RX PubMed=2318867; DOI=10.1016/s0021-9258(19)34052-9;
RA Artigues A., Birkett A., Schirch V.;
RT "Evidence for the in vivo deamidation and isomerization of an asparaginyl
RT residue in cytosolic serine hydroxymethyltransferase.";
RL J. Biol. Chem. 265:4853-4858(1990).
RN [4]
RP PROTEIN SEQUENCE OF 194-205, AND ACTIVE SITE CYS-204.
RX PubMed=7358720; DOI=10.1016/s0021-9258(19)85839-8;
RA Schirch L., Slagel S., Barra D., Martini F., Bossa F.;
RT "Evidence for a sulfhydryl group at the active site of serine
RT transhydroxymethylase.";
RL J. Biol. Chem. 255:2986-2989(1980).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) IN COMPLEX WITH PYRIDOXAL PHOSPHATE,
RP COFACTOR, AND SUBUNIT.
RC STRAIN=New Zealand white; TISSUE=Liver;
RX PubMed=10387080; DOI=10.1021/bi9904151;
RA Scarsdale J.N., Kazanina G., Radaev S., Schirch V., Wright H.T.;
RT "Crystal structure of rabbit cytosolic serine hydroxymethyltransferase at
RT 2.8-A resolution: mechanistic implications.";
RL Biochemistry 38:8347-8358(1999).
CC -!- FUNCTION: Interconversion of serine and glycine.
CC {ECO:0000269|PubMed:1381582}.
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:0000269|PubMed:1381582};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000269|PubMed:10387080};
CC -!- PATHWAY: One-carbon metabolism; tetrahydrofolate interconversion.
CC {ECO:0000305}.
CC -!- SUBUNIT: Homotetramer (PubMed:10387080). Identified in complex with
CC ABRAXAS2 and the other subunits of the BRISC complex, at least composed
CC of ABRAXAS2, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1.
CC {ECO:0000250|UniProtKB:P34896, ECO:0000269|PubMed:10387080}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- PTM: Deamidation of asparagine produces alternatively aspartate or
CC isoaspartate, which in turn can be converted to aspartate through
CC carboxylmethylation/demethylation. {ECO:0000269|PubMed:2318867}.
CC -!- MISCELLANEOUS: In eukaryotes there are two forms of the enzymes: a
CC cytosolic one and a mitochondrial one. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the SHMT family. {ECO:0000305}.
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DR EMBL; Z11846; CAA77870.1; -; mRNA.
DR PIR; S24342; XYRBSC.
DR RefSeq; NP_001095187.1; NM_001101717.1.
DR PDB; 1CJ0; X-ray; 2.80 A; A/B=15-484.
DR PDB; 1LS3; X-ray; 2.70 A; A/B/C/D=2-484.
DR PDB; 1RV3; X-ray; 2.40 A; A/B=2-484.
DR PDB; 1RV4; X-ray; 2.95 A; A/B=2-484.
DR PDB; 1RVU; X-ray; 2.50 A; A/B=2-484.
DR PDB; 1RVY; X-ray; 2.90 A; A/B=2-484.
DR PDBsum; 1CJ0; -.
DR PDBsum; 1LS3; -.
DR PDBsum; 1RV3; -.
DR PDBsum; 1RV4; -.
DR PDBsum; 1RVU; -.
DR PDBsum; 1RVY; -.
DR AlphaFoldDB; P07511; -.
DR SMR; P07511; -.
DR STRING; 9986.ENSOCUP00000017814; -.
DR iPTMnet; P07511; -.
DR Ensembl; ENSOCUT00000030926; ENSOCUP00000017814; ENSOCUG00000021541.
DR GeneID; 100009405; -.
DR KEGG; ocu:100009405; -.
DR CTD; 6470; -.
DR eggNOG; KOG2467; Eukaryota.
DR GeneTree; ENSGT00390000002762; -.
DR HOGENOM; CLU_022477_0_1_1; -.
DR InParanoid; P07511; -.
DR OMA; SHPAGLI; -.
DR OrthoDB; 372408at2759; -.
DR TreeFam; TF314667; -.
DR BRENDA; 2.1.2.1; 1749.
DR SABIO-RK; P07511; -.
DR UniPathway; UPA00193; -.
DR EvolutionaryTrace; P07511; -.
DR Proteomes; UP000001811; Unplaced.
DR Bgee; ENSOCUG00000021541; Expressed in liver and 16 other tissues.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0004372; F:glycine hydroxymethyltransferase activity; ISS:UniProtKB.
DR GO; GO:0048027; F:mRNA 5'-UTR binding; IEA:Ensembl.
DR GO; GO:0000900; F:mRNA regulatory element binding translation repressor activity; IEA:Ensembl.
DR GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
DR GO; GO:0030170; F:pyridoxal phosphate binding; ISS:UniProtKB.
DR GO; GO:0070905; F:serine binding; IEA:Ensembl.
DR GO; GO:1904482; P:cellular response to tetrahydrofolate; IEA:Ensembl.
DR GO; GO:0046655; P:folic acid metabolic process; IEA:Ensembl.
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:0006565; P:L-serine catabolic process; IEA:Ensembl.
DR GO; GO:0006563; P:L-serine metabolic process; ISS:UniProtKB.
DR GO; GO:0051289; P:protein homotetramerization; ISS:UniProtKB.
DR GO; GO:0009113; P:purine nucleobase biosynthetic process; IEA:Ensembl.
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; 3.40.640.10; -; 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 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cytoplasm; Direct protein sequencing;
KW Isopeptide bond; One-carbon metabolism; Pyridoxal phosphate;
KW Reference proteome; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:2318867,
FT ECO:0000269|PubMed:3553178"
FT CHAIN 2..484
FT /note="Serine hydroxymethyltransferase, cytosolic"
FT /id="PRO_0000113506"
FT ACT_SITE 204
FT /note="Nucleophile"
FT /evidence="ECO:0000305|PubMed:7358720"
FT ACT_SITE 256
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|PubMed:3553178"
FT MOD_RES 6
FT /note="Deamidated asparagine; alternate"
FT /evidence="ECO:0000269|PubMed:2318867"
FT MOD_RES 257
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000269|PubMed:10387080"
FT CROSSLNK 6..7
FT /note="Isoaspartyl glycine isopeptide (Asn-Gly); alternate"
FT /evidence="ECO:0000269|PubMed:2318867"
FT HELIX 18..21
FT /evidence="ECO:0007829|PDB:1RV3"
FT STRAND 22..24
FT /evidence="ECO:0007829|PDB:1CJ0"
FT HELIX 26..29
FT /evidence="ECO:0007829|PDB:1RV3"
FT HELIX 31..45
FT /evidence="ECO:0007829|PDB:1RV3"
FT STRAND 46..49
FT /evidence="ECO:0007829|PDB:1RV3"
FT HELIX 59..65
FT /evidence="ECO:0007829|PDB:1RV3"
FT HELIX 68..70
FT /evidence="ECO:0007829|PDB:1RV3"
FT STRAND 80..84
FT /evidence="ECO:0007829|PDB:1RV3"
FT HELIX 87..103
FT /evidence="ECO:0007829|PDB:1RV3"
FT TURN 108..110
FT /evidence="ECO:0007829|PDB:1RV3"
FT STRAND 111..114
FT /evidence="ECO:0007829|PDB:1RV3"
FT HELIX 120..131
FT /evidence="ECO:0007829|PDB:1RV3"
FT STRAND 137..141
FT /evidence="ECO:0007829|PDB:1RV3"
FT HELIX 143..145
FT /evidence="ECO:0007829|PDB:1RV3"
FT HELIX 149..151
FT /evidence="ECO:0007829|PDB:1RV3"
FT HELIX 162..166
FT /evidence="ECO:0007829|PDB:1RV3"
FT STRAND 167..172
FT /evidence="ECO:0007829|PDB:1RV3"
FT TURN 176..178
FT /evidence="ECO:0007829|PDB:1RV3"
FT STRAND 179..181
FT /evidence="ECO:0007829|PDB:1LS3"
FT HELIX 183..193
FT /evidence="ECO:0007829|PDB:1RV3"
FT STRAND 196..200
FT /evidence="ECO:0007829|PDB:1RV3"
FT HELIX 211..220
FT /evidence="ECO:0007829|PDB:1RV3"
FT STRAND 224..228
FT /evidence="ECO:0007829|PDB:1RV3"
FT TURN 230..232
FT /evidence="ECO:0007829|PDB:1RV3"
FT HELIX 233..238
FT /evidence="ECO:0007829|PDB:1RV3"
FT HELIX 244..246
FT /evidence="ECO:0007829|PDB:1RV3"
FT STRAND 249..256
FT /evidence="ECO:0007829|PDB:1RV3"
FT HELIX 257..259
FT /evidence="ECO:0007829|PDB:1RV3"
FT STRAND 265..270
FT /evidence="ECO:0007829|PDB:1RV3"
FT HELIX 288..296
FT /evidence="ECO:0007829|PDB:1RV3"
FT TURN 297..300
FT /evidence="ECO:0007829|PDB:1RV3"
FT HELIX 306..319
FT /evidence="ECO:0007829|PDB:1RV3"
FT HELIX 322..344
FT /evidence="ECO:0007829|PDB:1RV3"
FT HELIX 350..352
FT /evidence="ECO:0007829|PDB:1RV3"
FT STRAND 355..362
FT /evidence="ECO:0007829|PDB:1RV3"
FT HELIX 363..366
FT /evidence="ECO:0007829|PDB:1RV3"
FT HELIX 370..379
FT /evidence="ECO:0007829|PDB:1RV3"
FT STRAND 385..387
FT /evidence="ECO:0007829|PDB:1RV3"
FT STRAND 393..397
FT /evidence="ECO:0007829|PDB:1LS3"
FT STRAND 400..404
FT /evidence="ECO:0007829|PDB:1RV3"
FT HELIX 406..410
FT /evidence="ECO:0007829|PDB:1RV3"
FT HELIX 415..437
FT /evidence="ECO:0007829|PDB:1RV3"
FT HELIX 445..453
FT /evidence="ECO:0007829|PDB:1RV3"
FT HELIX 456..473
FT /evidence="ECO:0007829|PDB:1RV3"
FT STRAND 480..482
FT /evidence="ECO:0007829|PDB:1RV3"
SQ SEQUENCE 484 AA; 52975 MW; C2742A5A8052C5BF CRC64;
MATAVNGAPR DAALWSSHEQ MLAQPLKDSD AEVYDIIKKE SNRQRVGLEL IASENFASRA
VLEALGSCLN NKYSEGYPGQ RYYGGTEHID ELETLCQKRA LQAYGLDPQC WGVNVQPYSG
SPANFAVYTA LVEPHGRIMG LDLPDGGHLT HGFMTDKKKI SATSIFFESM AYKVNPDTGY
IDYDRLEENA RLFHPKLIIA GTSCYSRNLD YGRLRKIADE NGAYLMADMA HISGLVVAGV
VPSPFEHCHV VTTTTHKTLR GCRAGMIFYR RGVRSVDPKT GKEILYNLES LINSAVFPGL
QGGPHNHAIA GVAVALKQAM TPEFKEYQRQ VVANCRALSA ALVELGYKIV TGGSDNHLIL
VDLRSKGTDG GRAEKVLEAC SIACNKNTCP GDKSALRPSG LRLGTPALTS RGLLEKDFQK
VAHFIHRGIE LTVQIQDDTG PRATLKEFKE KLAGDEKHQR AVRALRQEVE SFAALFPLPG
LPGF
