UniProtKB - Q9CZN7 (GLYM_MOUSE)
Serine hydroxymethyltransferase, mitochondrial
Shmt2
Functioni
Catalyzes the cleavage of serine to glycine accompanied with the production of 5,10-methylenetetrahydrofolate, an essential intermediate for purine biosynthesis (By similarity).
Serine provides the major source of folate one-carbon in cells by catalyzing the transfer of one carbon from serine to tetrahydrofolate (By similarity).
Contributes to the de novo mitochondrial thymidylate biosynthesis pathway via its role in glycine and tetrahydrofolate metabolism: thymidylate biosynthesis is required to prevent uracil accumulation in mtDNA (By similarity).
Also required for mitochondrial translation by producing 5,10-methylenetetrahydrofolate; 5,10-methylenetetrahydrofolate providing methyl donors to produce the taurinomethyluridine base at the wobble position of some mitochondrial tRNAs (PubMed:29452640).
Associates with mitochondrial DNA (By similarity).
In addition to its role in mitochondria, also plays a role in the deubiquitination of target proteins as component of the BRISC complex: required for IFNAR1 deubiquitination by the BRISC complex (By similarity).
By similarity1 PublicationMiscellaneous
Catalytic activityi
- (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + glycine + H2O = (6S)-5,6,7,8-tetrahydrofolate + L-serineBy similarityEC:2.1.2.1By similarityThis reaction proceeds in the backwardBy similarity direction.
Cofactori
Activity regulationi
: tetrahydrofolate interconversion Pathwayi
This protein is involved in the pathway tetrahydrofolate interconversion, which is part of One-carbon metabolism.By similarityView all proteins of this organism that are known to be involved in the pathway tetrahydrofolate interconversion and in One-carbon metabolism.
GO - Molecular functioni
- amino acid binding Source: MGI
- chromatin binding Source: MGI
- glycine hydroxymethyltransferase activity Source: MGI
- identical protein binding Source: MGI
- L-allo-threonine aldolase activity Source: MGI
- mRNA 5'-UTR binding Source: GO_Central
- protein homodimerization activity Source: GO_Central
- pyridoxal phosphate binding Source: MGI
- serine binding Source: GO_Central
- translation repressor activity, mRNA regulatory element binding Source: GO_Central
- zinc ion binding Source: GO_Central
GO - Biological processi
- folic acid metabolic process Source: GO_Central
- glycine biosynthetic process Source: MGI
- glycine biosynthetic process from serine Source: MGI
- glycine metabolic process Source: UniProtKB
- L-serine biosynthetic process Source: MGI
- L-serine catabolic process Source: GO_Central
- L-serine metabolic process Source: UniProtKB
- one-carbon metabolic process Source: UniProtKB
- positive regulation of cell population proliferation Source: MGI
- protein homotetramerization Source: UniProtKB
- protein K63-linked deubiquitination Source: MGI
- protein tetramerization Source: MGI
- purine nucleobase biosynthetic process Source: GO_Central
- regulation of aerobic respiration Source: UniProtKB
- regulation of mitochondrial translation Source: UniProtKB
- regulation of oxidative phosphorylation Source: UniProtKB
- response to type I interferon Source: MGI
- tetrahydrofolate interconversion Source: MGI
- tetrahydrofolate metabolic process Source: MGI
Keywordsi
Molecular function | Transferase |
Biological process | One-carbon metabolism |
Ligand | Pyridoxal phosphate |
Enzyme and pathway databases
Reactomei | R-MMU-196757, Metabolism of folate and pterines R-MMU-9013408, RHOG GTPase cycle |
UniPathwayi | UPA00193 |
Names & Taxonomyi
Protein namesi | Recommended name: Serine hydroxymethyltransferase, mitochondrialCurated (EC:2.1.2.1By similarity)Short name: SHMTCurated Alternative name(s): Glycine hydroxymethyltransferaseCurated Serine methylaseCurated |
Gene namesi | Name:Shmt2Imported |
Organismi | Mus musculus (Mouse)Imported |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1277989, Shmt2 |
VEuPathDBi | HostDB:ENSMUSG00000025403 |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm By similarity
Mitochondrion
- Mitochondrion By similarity
- mitochondrion nucleoid By similarity
- Mitochondrion inner membrane By similarity
Nucleus
- Nucleus By similarity
Note: Mainly localizes in the mitochondrion. Also found in the cytoplasm and nucleus as part of the BRISC complex.By similarity
Cytoskeleton
- microtubule cytoskeleton Source: MGI
Cytosol
- cytosol Source: GO_Central
Mitochondrion
- mitochondrial inner membrane Source: MGI
- mitochondrial intermembrane space Source: MGI
- mitochondrial matrix Source: MGI
- mitochondrial nucleoid Source: MGI
- mitochondrion Source: MGI
Nucleus
- BRISC complex Source: MGI
- nucleus Source: MGI
Other locations
- cytoplasm Source: MGI
Keywords - Cellular componenti
Cytoplasm, Membrane, Mitochondrion, Mitochondrion inner membrane, Mitochondrion nucleoid, NucleusPathology & Biotechi
Disruption phenotypei
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transit peptidei | 1 – 29 | MitochondrionBy similarityAdd BLAST | 29 | |
ChainiPRO_0000443804 | 30 – 504 | Serine hydroxymethyltransferase, mitochondrialAdd BLAST | 475 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 103 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 181 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 196 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 280 | N6-(pyridoxal phosphate)lysine; alternateBy similarity | 1 | |
Modified residuei | 280 | N6-succinyllysine; alternateBy similarity | 1 | |
Modified residuei | 464 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 469 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 470 | PhosphoserineBy similarity | 1 | |
Modified residuei | 474 | N6-acetyllysineCombined sources | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
jPOSTi | Q9CZN7 |
MaxQBi | Q9CZN7 |
PaxDbi | Q9CZN7 |
PRIDEi | Q9CZN7 |
ProteomicsDBi | 338698 [Q9CZN7-1] 342776 |
PTM databases
iPTMneti | Q9CZN7 |
PhosphoSitePlusi | Q9CZN7 |
SwissPalmi | Q9CZN7 |
Expressioni
Developmental stagei
Gene expression databases
Bgeei | ENSMUSG00000025403, Expressed in proximal tubule and 301 other tissues |
Genevisiblei | Q3TFD0, MM |
Interactioni
Subunit structurei
Homotetramer; in the presence of bound pyridoxal 5'-phosphate. Homodimer; in the absence of bound pyridoxal 5'-phosphate. Pyridoxal 5'-phosphate binding mediates an important conformation change that is required for tetramerization.
Interacts with ABRAXAS2; the interaction is direct.
Identified in a complex with ABRAXAS2 and the other subunits of the BRISC complex, at least composed of the ABRAXAS2, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1.
Identified in a complex with ABRAXAS2 and IFNAR1.
Interacts with KIRREL3.
By similarityGO - Molecular functioni
- identical protein binding Source: MGI
- protein homodimerization activity Source: GO_Central
Protein-protein interaction databases
IntActi | Q9CZN7, 2 interactors |
STRINGi | 10090.ENSMUSP00000026470 |
Miscellaneous databases
RNActi | Q9CZN7, protein |
Family & Domainsi
Sequence similaritiesi
Keywords - Domaini
Transit peptidePhylogenomic databases
eggNOGi | KOG2467, Eukaryota |
GeneTreei | ENSGT00390000002762 |
HOGENOMi | CLU_022477_0_1_1 |
InParanoidi | Q9CZN7 |
OMAi | MFREYAL |
OrthoDBi | 372408at2759 |
PhylomeDBi | Q9CZN7 |
TreeFami | TF314667 |
Family and domain databases
CDDi | cd00378, SHMT, 1 hit |
Gene3Di | 3.40.640.10, 1 hit 3.90.1150.10, 1 hit |
HAMAPi | MF_00051, SHMT, 1 hit |
InterProi | View protein in InterPro IPR015424, PyrdxlP-dep_Trfase IPR015421, PyrdxlP-dep_Trfase_major IPR015422, PyrdxlP-dep_Trfase_small IPR001085, Ser_HO-MeTrfase IPR019798, Ser_HO-MeTrfase_PLP_BS IPR039429, SHMT-like_dom |
PANTHERi | PTHR11680, PTHR11680, 1 hit |
Pfami | View protein in Pfam PF00464, SHMT, 1 hit |
PIRSFi | PIRSF000412, SHMT, 1 hit |
SUPFAMi | SSF53383, SSF53383, 1 hit |
PROSITEi | View protein in PROSITE PS00096, SHMT, 1 hit |
s (2)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MVSFSLLRTT RPLQRCGQLV CMAARAQHSK VAQTQAGEAA GGWTGQESLS
60 70 80 90 100
DSDPEMWELL QREKDRQCRG LELIASENFC SRAALEALGS CLNNKYSEGY
110 120 130 140 150
PGKRYYGGAE VVDEIELLCQ RRALEAFDLD PAQWGVNVQP YSGSPANLAA
160 170 180 190 200
YTALLQPHDR IMGLDLPDGG HLTHGYMSDV KRISATSIFF ESMPYKLNPQ
210 220 230 240 250
TGLIDYDQLA LTARLFRPRL IIAGTSAYAR LIDYARMREV CDEVRAHLLA
260 270 280 290 300
DMAHISGLVA AKVIPSPFKY ADVVTTTTHK TLRGARSGLI FYRKGVRTVD
310 320 330 340 350
PKTGKEIPYT FEDRINFAVF PSLQGGPHNH AIAAVAVALK QACTPMFREY
360 370 380 390 400
SLQVLRNAQA MADALLKRGY SLVSGGTDTH LVLVDLRPKG LDGARAERVL
410 420 430 440 450
ELVSITANKN TCPGDRSAIT PGGLRLGAPA LTSRQFREDD FRRVVDFIDE
460 470 480 490 500
GVNIGLEVKR KTAKLQDFKS FLLKDPETSQ RLANLRQQVE QFARGFPMPG
FDER
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 40 | A → T in AAH04825 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 40 | A → T in AAH51396 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 238 | R → K in AAH04825 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 238 | R → K in AAH51396 (PubMed:15489334).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_059519 | 12 – 14 | Missing in isoform 2. | 3 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK012355 mRNA Translation: BAB28184.1 AK037339 mRNA Translation: BAC29790.1 AK051207 mRNA Translation: BAC34556.1 AK162421 mRNA Translation: BAE36907.1 AK169192 mRNA Translation: BAE40968.1 AC167719 Genomic DNA No translation available. BC004825 mRNA Translation: AAH04825.1 BC051396 mRNA Translation: AAH51396.1 |
CCDSi | CCDS24244.1 [Q9CZN7-1] CCDS88105.1 [Q9CZN7-2] |
RefSeqi | NP_001239245.1, NM_001252316.1 [Q9CZN7-2] NP_082506.1, NM_028230.4 [Q9CZN7-1] |
Genome annotation databases
Ensembli | ENSMUST00000026470; ENSMUSP00000026470; ENSMUSG00000025403 [Q9CZN7-1] ENSMUST00000219239; ENSMUSP00000151616; ENSMUSG00000025403 [Q9CZN7-2] |
GeneIDi | 108037 |
KEGGi | mmu:108037 |
UCSCi | uc007hju.2, mouse [Q9CZN7-1] uc007hjv.2, mouse |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK012355 mRNA Translation: BAB28184.1 AK037339 mRNA Translation: BAC29790.1 AK051207 mRNA Translation: BAC34556.1 AK162421 mRNA Translation: BAE36907.1 AK169192 mRNA Translation: BAE40968.1 AC167719 Genomic DNA No translation available. BC004825 mRNA Translation: AAH04825.1 BC051396 mRNA Translation: AAH51396.1 |
CCDSi | CCDS24244.1 [Q9CZN7-1] CCDS88105.1 [Q9CZN7-2] |
RefSeqi | NP_001239245.1, NM_001252316.1 [Q9CZN7-2] NP_082506.1, NM_028230.4 [Q9CZN7-1] |
3D structure databases
SMRi | Q9CZN7 |
ModBasei | Search... |
Protein-protein interaction databases
IntActi | Q9CZN7, 2 interactors |
STRINGi | 10090.ENSMUSP00000026470 |
PTM databases
iPTMneti | Q9CZN7 |
PhosphoSitePlusi | Q9CZN7 |
SwissPalmi | Q9CZN7 |
Proteomic databases
jPOSTi | Q9CZN7 |
MaxQBi | Q9CZN7 |
PaxDbi | Q9CZN7 |
PRIDEi | Q9CZN7 |
ProteomicsDBi | 338698 [Q9CZN7-1] 342776 |
Protocols and materials databases
Antibodypediai | 16145, 236 antibodies from 30 providers |
DNASUi | 108037 |
Genome annotation databases
Ensembli | ENSMUST00000026470; ENSMUSP00000026470; ENSMUSG00000025403 [Q9CZN7-1] ENSMUST00000219239; ENSMUSP00000151616; ENSMUSG00000025403 [Q9CZN7-2] |
GeneIDi | 108037 |
KEGGi | mmu:108037 |
UCSCi | uc007hju.2, mouse [Q9CZN7-1] uc007hjv.2, mouse |
Organism-specific databases
CTDi | 6472 |
MGIi | MGI:1277989, Shmt2 |
VEuPathDBi | HostDB:ENSMUSG00000025403 |
Phylogenomic databases
eggNOGi | KOG2467, Eukaryota |
GeneTreei | ENSGT00390000002762 |
HOGENOMi | CLU_022477_0_1_1 |
InParanoidi | Q9CZN7 |
OMAi | MFREYAL |
OrthoDBi | 372408at2759 |
PhylomeDBi | Q9CZN7 |
TreeFami | TF314667 |
Enzyme and pathway databases
UniPathwayi | UPA00193 |
Reactomei | R-MMU-196757, Metabolism of folate and pterines R-MMU-9013408, RHOG GTPase cycle |
Miscellaneous databases
BioGRID-ORCSi | 108037, 10 hits in 64 CRISPR screens |
ChiTaRSi | Shmt2, mouse |
PROi | PR:Q9CZN7 |
RNActi | Q9CZN7, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000025403, Expressed in proximal tubule and 301 other tissues |
Genevisiblei | Q3TFD0, MM |
Family and domain databases
CDDi | cd00378, SHMT, 1 hit |
Gene3Di | 3.40.640.10, 1 hit 3.90.1150.10, 1 hit |
HAMAPi | MF_00051, SHMT, 1 hit |
InterProi | View protein in InterPro IPR015424, PyrdxlP-dep_Trfase IPR015421, PyrdxlP-dep_Trfase_major IPR015422, PyrdxlP-dep_Trfase_small IPR001085, Ser_HO-MeTrfase IPR019798, Ser_HO-MeTrfase_PLP_BS IPR039429, SHMT-like_dom |
PANTHERi | PTHR11680, PTHR11680, 1 hit |
Pfami | View protein in Pfam PF00464, SHMT, 1 hit |
PIRSFi | PIRSF000412, SHMT, 1 hit |
SUPFAMi | SSF53383, SSF53383, 1 hit |
PROSITEi | View protein in PROSITE PS00096, SHMT, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | GLYM_MOUSE | |
Accessioni | Q9CZN7Primary (citable) accession number: Q9CZN7 Secondary accession number(s): Q3TFD0, Q99K87 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | March 28, 2018 |
Last sequence update: | June 1, 2001 | |
Last modified: | February 23, 2022 | |
This is version 159 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families