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Information on EC 2.6.1.52 - phosphoserine transaminase and Organism(s) Homo sapiens
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2.6.1.52 phosphoserine transaminaseIUBMB Comments
A pyridoxal 5'-phosphate protein. This enzyme catalyses the second step in the phosphorylated pathway of serine biosynthesis [1,3] and the third step in pyridoxal 5'-phosphate biosynthesis in the bacterium Escherichia coli . Pyridoxal 5'-phosphate is the cofactor for both activities and therefore seems to be involved in its own biosynthesis . Non-phosphorylated forms of serine and threonine are not substrates . The archaeal enzyme has a relaxed specificity and can act on L-cysteate and L-alanine as alternative substrates to O-phospho-L-serine .
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The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
Synonyms
psat, phosphoserine aminotransferase, phosphoserine aminotransferase 1, ehpsat, 3-phosphoserine aminotransferase, psat2, l-phosphoserine aminotransferase, psat beta, bmpsat, psat alpha, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
3-phosphoserine aminotransferase
-
-
-
-
hydroxypyruvic phosphate-glutamic transaminase
-
-
-
-
L-phosphoserine aminotransferase
-
-
-
-
phosphohydroxypyruvate transaminase
-
-
-
-
phosphohydroxypyruvic-glutamic transaminase
-
-
-
-
phosphoserine aminotransferase
PSAT
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-
-
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PSAT1
phosphoserine aminotransferase
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-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
amino group transfer
-
-
-
-
PATHWAY SOURCE
PATHWAYS
KEGG
-
-, -, -
SYSTEMATIC NAME
IUBMB Comments
O-phospho-L-serine:2-oxoglutarate aminotransferase
A pyridoxal 5'-phosphate protein. This enzyme catalyses the second step in the phosphorylated pathway of serine biosynthesis [1,3] and the third step in pyridoxal 5'-phosphate biosynthesis in the bacterium Escherichia coli [3]. Pyridoxal 5'-phosphate is the cofactor for both activities and therefore seems to be involved in its own biosynthesis [4]. Non-phosphorylated forms of serine and threonine are not substrates [4]. The archaeal enzyme has a relaxed specificity and can act on L-cysteate and L-alanine as alternative substrates to O-phospho-L-serine [7].
CAS REGISTRY NUMBER
COMMENTARY
9030-90-4
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
3-phosphonooxypyruvate + L-glutamate
O-phospho-L-serine + 2-oxoglutarate
-
-
-
?
O-phospho-L-serine + 2-oxoglutarate
3-phosphooxypyruvate + L-glutamate
-
-
-
r
L-glutamate + 3-phosphohydroxypyruvate
O-phospho-L-serine + 2-oxoglutarate
-
-
-
r
L-glutamate + 3-phosphohydroxypyruvate
O-phospho-L-serine + 2-oxoglutarate
phosphorylated pathway for serine biosynthesis
-
-
r
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
L-glutamate + 3-phosphohydroxypyruvate
O-phospho-L-serine + 2-oxoglutarate
phosphorylated pathway for serine biosynthesis
-
-
r
O-phospho-L-serine + 2-oxoglutarate
3-phosphooxypyruvate + L-glutamate
-
-
-
r
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Aminooxyacetate
AOA, the transaminase inhibitor represses cell growth in a TAZ/YAP-dependent manner
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
immunohistochemical detection, in breast carcinoma PSAT1 expression is significantly associated with poor grade tumors and local relapse
transcriptional regulators TAZ/YAP activity positively correlates with transaminase expression in breast cancer patients
additional information
very weak mRNA expression in thymus,prostate, testis and colon
additional information
-
very weak mRNA expression in thymus,prostate, testis and colon
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
transcriptional regulators TAZ and YAP (TAZ/YAP) promote glutamine dependence in breast cancer cells and activate the expression of glutamine-utilizing transaminases to support cell growth. TAZ and YAP induce glutamic-oxaloacetic transaminase (GOT1, EC 2.6.1.64) and phosphoserine aminotransferase (PSAT1) expression. Transcriptional regulators TAZ/YAP activity positively correlates with transaminase expression in breast cancer patients, while transaminase inhibitor aminooxyacetate (AOA) represses cell growth in a TAZ/YAP-dependent manner. Thus, transamination is a potential vulnerable metabolic requirement for TAZ/YAP-driven breast cancer
physiological function
physiological function
-
hepatic PSAT1 expression and liver serine levels are reduced in genetically engineered leptin receptor-deficient (db/db) mice and high-fat diet (HFD)-induced diabetic mice. Overexpression of PSAT1 by adenovirus expressing PSAT1 improves insulin signaling and insulin sensitivity in vitro and in vivo under normal conditions. Opposite effects are observed when PSAT1 is knocked down by small hairpin RNA specific for PSAT1. Overexpression of PSAT1 also significantly ameliorates insulin resistance in diabetic mice. PSAT1 inhibits the expression of hepatic tribbles homolog TRB3 in vitro and in vivo. Serine mediates PSAT1 regulation of TRB3 expression and insulin signaling in vitro
physiological function
analysis of association of PSAT1 protein levels upon tamoxifen treatment and enzyme role in tamoxifen resistance, PSAT1 protein and mRNA levels are significantly associated to poor outcome to tamoxifen treatment. Cytokine and JAK-STAT signaling are associated with PSAT1 expression. Clinical significance of PSAT1 in the gene expression cohort and pathway analysis
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). SERC_HUMAN
370
0
40423
Swiss-Prot
other Location (Reliability: 3)
A0A024R222_HUMAN
370
0
40423
TrEMBL
other Location (Reliability: 3)
B4DHQ3_HUMAN
415
0
45355
TrEMBL
Mitochondrion (Reliability: 3)
A0A024R280_HUMAN
324
0
35189
TrEMBL
other Location (Reliability: 3)
B4DHX7_HUMAN
194
0
21315
TrEMBL
other Location (Reliability: 3)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
native enzyme from rat brain by ultracentrifugation at 220000 x g, followed by ammonium sulfate fractionation, hydropbobic interaction chromatography, anion exchange chromatography, and hydroxyapatite chromatography
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
2 forms results from alternative splicing, PSATalpha and PSATbeta, cDNA cloned and expressed in Escherichia coli and in human cell lines, leukaemia Jurkat, colon adenocarcinoma COLO 320DM, heptacellular carcinoma HepG2 and weakly in leukaemia MOLT-3, complementation of Saccharomyces cerevisiae SER-1 deletion mutation
gene PSAT1, quantitative reverse transcriptase PCR enzyme expression analysis
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
GOT1 expression level is reduced in TAZ/YAP siRNA knockout cells. The inhibition of transamination preferentially suppresses those breast cancer cells that express high levels of TAZ/YAP (e.g. MDA-MB-231 and HCC38 cells ), not TAZ/YAP-low-level expressing cell lines (e.g. BT474 and HMT-3522 S1)
transcriptional regulators TAZ and YAP (TAZ/YAP) promote glutamine dependence in breast cancer cells and activate the expression of glutamine-utilizing transaminases to support cell growth. TAZ/YAP induce glutamic-oxaloacetic transaminase (GOT1) and phosphoserine aminotransferase (PSAT1) expression. TAZ and YAP are required for glutamine-utilizing transaminase expression in breast cancer cells
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
diagnostics
phosphoserine aminotransferase 1 is associated to poor outcome on tamoxifen therapy in recurrent breast cancer
medicine
medicine
useful for creating a new concept or target for the diagnosis and therapy of human serine metabolism-related disorders and cancer
medicine
-
promoter hypermethylation and mRNA expression of PSAT1 are indicators of response to tamoxifen-based endocrine therapy in steroid hormone receptorpositive patients with recurrent breast cancer
medicine
-
hepatic PSAT1 expression and liver serine levels are reduced in genetically engineered leptin receptor-deficient (db/db) mice and high-fat diet (HFD)-induced diabetic mice. Overexpression of PSAT1 by adenovirus expressing PSAT1 improves insulin signaling and insulin sensitivity in vitro and in vivo under normal conditions. Opposite effects are observed when PSAT1 is knocked down by small hairpin RNA specific for PSAT1. Overexpression of PSAT1 also significantly ameliorates insulin resistance in diabetic mice. PSAT1 inhibits the expression of hepatic tribbles homolog TRB3 in vitro and in vivo. Serine mediates PSAT1 regulation of TRB3 expression and insulin signaling in vitro
medicine
-
isoform PSAT1 expression is elevated in esophageal squamous cell carcinoma tissues compared to normal esophageal tissues. Increased PSAT1 expression is significantly associated with stage of disease, lymph node metastasis, distant metastasis and poor prognosis. In vitro, PSAT1 overexpression promotes esophageal squamous cell carcinoma cell proliferation and matrigel invasion. In vivo, injection of mice with esophageal squamous cell carcinoma cells overexpressing PSAT1 enhances tumor formation. PSAT1 upregulatesthe expression and/or activity of GSK3beta/Snail
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Baek, J.Y.; Jun do, Y.; Taub, D.; Kim, Y.H.
Characterization of human phosphoserine aminotransferase involved in the phosphorylated pathway of L-serine biosynthesis
Biochem. J.
373
191-200
2003
Homo sapiens (Q9Y617), Homo sapiens
Martens, J.W.; Nimmrich, I.; Koenig, T.; Look, M.P.; Harbeck, N.; Model, F.; Kluth, A.; Bolt-de Vries, J.; Sieuwerts, A.M.; Portengen, H.; Meijer-Van Gelder, M.E.; Piepenbrock, C.; Olek, A.; Hoefler, H.; Kiechle, M.; Klijn, J.G.; Schmitt, M.; Maier, S.; Foekens, J.A.
Association of DNA methylation of phosphoserine aminotransferase with response to endocrine therapy in patients with recurrent breast cancer
Cancer Res.
65
4101-4107
2005
Homo sapiens
Vie, N.; Copois, V.; Bascoul-Mollevi, C.; Denis, V.; Bec, N.; Robert, B.; Fraslon, C.; Conseiller, E.; Molina, F.; Larroque, C.; Martineau, P.; Del Rio, M.; Gongora, C.
Overexpression of phosphoserine aminotransferase PSAT1 stimulates cell growth and increases chemoresistance of colon cancer cells
Mol. Cancer
7
14
2008
Homo sapiens (Q9Y617), Homo sapiens
Donini, S.; Ferrari, M.; Fedeli, C.; Faini, M.; Lamberto, I.; Marletta, A.S.; Mellini, L.; Panini, M.; Percudani, R.; Pollegioni, L.; Caldinelli, L.; Petrucco, S.; Peracchi, A.
Recombinant production of eight human cytosolic aminotransferases and assessment of their potential involvement in glyoxylate metabolism
Biochem. J.
422
265-272
2009
Homo sapiens (Q9Y617)
Liu, B.; Jia, Y.; Cao, Y.; Wu, S.; Jiang, H.; Sun, X.; Ma, J.; Yin, X.; Mao, A.; Shang, M.
Overexpression of phosphoserine aminotransferase 1 (PSAT1) predicts poor prognosis and associates with tumor progression in human esophageal squamous cell carcinoma
Cell. Physiol. Biochem.
39
395-406
2016
Homo sapiens
Yu, J.; Xiao, F.; Guo, Y.; Deng, J.; Liu, B.; Zhang, Q.; Li, K.; Wang, C.; Chen, S.; Guo, F.
Hepatic phosphoserine aminotransferase 1 regulates insulin sensitivity in mice via Tribbles Homolog 3
Diabetes
64
1591-1602
2015
Homo sapiens
Yang, C.; Stampouloglou, E.; Kingston, N.; Zhang, L.; Monti, S.; Varelas, X.
Glutamine-utilizing transaminases are a metabolic vulnerability of TAZ/YAP-activated cancer cells
EMBO Rep.
19
e43577
2018
Homo sapiens (Q9Y617), Homo sapiens
De Marchi, T.; Timmermans, M.A.; Sieuwerts, A.M.; Smid, M.; Look, M.P.; Grebenchtchikov, N.; Sweep, F.C.G.J.; Smits, J.G.; Magdolen, V.; van Deurzen, C.H.M.; Foekens, J.A.; Umar, A.; Martens, J.W.
Phosphoserine aminotransferase 1 is associated to poor outcome on tamoxifen therapy in recurrent breast cancer
Sci. Rep.
7
2099
2017
Homo sapiens (Q9Y617), Homo sapiens
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