Serine racemase

Serine racemase is an enzyme which generates D-serine from L-serine. D-serine acts as a neuronal signaling molecule by activating NMDA receptors in the brain. In humans, the serine racemase protein is encoded by the SRR gene.[5]

SRR
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3L6B, 3L6R
Identifiers
Aliases	SRR, ILV1, ISO1, serine racemase
External IDs	OMIM: 606477 MGI: 1351636 HomoloGene: 22775 GeneCards: SRR
Gene location (Human) Chr. Chromosome 17 (human)[1] Band 17p13.3 Start 2,303,383 bp[1] End 2,325,260 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11|11 B5 Start 74,906,359 bp[2] End 74,925,948 bp[2]
Gene ontology Molecular function • threonine racemase activity • nucleotide binding • calcium ion binding • PDZ domain binding • protein homodimerization activity • L-serine ammonia-lyase activity • isomerase activity • glycine binding • metal ion binding • catalytic activity • lyase activity • pyridoxal phosphate binding • ATP binding • magnesium ion binding • D-serine ammonia-lyase activity • serine racemase activity Cellular component • cytoplasm • cell membrane • apical part of cell • neuronal cell body • cytosol Biological process • response to organic cyclic compound • serine family amino acid metabolic process • L-serine metabolic process • cellular amino acid metabolic process • D-serine metabolic process • aging • pyruvate biosynthetic process • response to morphine • response to lipopolysaccharide • D-serine biosynthetic process • metabolism • protein homotetramerization • response to drug • brain development • L-serine biosynthetic process Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	63826	27364
Ensembl	ENSG00000167720	ENSMUSG00000001323
UniProt	Q9GZT4	Q9QZX7
RefSeq (mRNA)	NM_001304803 NM_021947	NM_001163311 NM_013761 NM_001362742 NM_001362743 NM_001362744
RefSeq (protein)	NP_001291732 NP_068766	NP_001156783 NP_038789 NP_001349671 NP_001349672 NP_001349673
Location (UCSC)	Chr 17: 2.3 – 2.33 Mb	Chr 11: 74.91 – 74.93 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Mammalian serine racemase is a pyridoxal 5'-phosphate dependent enzyme that catalyzes both the racemization of L-serine to D-serine and also the elimination of water from L-serine, generating pyruvate and ammonia.[6] The enzyme is physiologically stimulated by divalent cations (e.g., magnesium) and is allosterically activated by the magnesium/ATP complex.

References

1. GRCh38: Ensembl release 89: ENSG00000167720 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000001323 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. De Miranda J, Santoro A, Engelender S, Wolosker H (Oct 2000). "Human serine racemase: moleular cloning, genomic organization and functional analysis". Gene. 256 (1–2): 183–8. doi:10.1016/S0378-1119(00)00356-5. PMID 11054547.
6. De Miranda J, Panizzutti R, Foltyn VN, Wolosker H (Oct 2002). "Cofactors of serine racemase that physiologically stimulate the synthesis of the N-methyl-D-aspartate (NMDA) receptor coagonist D-serine". Proceedings of the National Academy of Sciences of the United States of America. 99 (22): 14542–7. doi:10.1073/pnas.222421299. PMC 137919. PMID 12393813.

Further reading

• Morita Y, Ujike H, Tanaka Y, Otani K, Kishimoto M, Morio A, Kotaka T, Okahisa Y, Matsushita M, Morikawa A, Hamase K, Zaitsu K, Kuroda S (May 2007). "A genetic variant of the serine racemase gene is associated with schizophrenia". Biological Psychiatry. 61 (10): 1200–3. doi:10.1016/j.biopsych.2006.07.025. PMID 17067558. S2CID 8142062.
• Steffek AE, Haroutunian V, Meador-Woodruff JH (Jul 2006). "Serine racemase protein expression in cortex and hippocampus in schizophrenia". NeuroReport. 17 (11): 1181–5. doi:10.1097/01.wnr.0000230512.01339.72. PMID 16837850. S2CID 35663584.
• Fujii K, Maeda K, Hikida T, Mustafa AK, Balkissoon R, Xia J, Yamada T, Ozeki Y, Kawahara R, Okawa M, Huganir RL, Ujike H, Snyder SH, Sawa A (Feb 2006). "Serine racemase binds to PICK1: potential relevance to schizophrenia". Molecular Psychiatry. 11 (2): 150–7. doi:10.1038/sj.mp.4001776. PMID 16314870.
• Dumin E, Bendikov I, Foltyn VN, Misumi Y, Ikehara Y, Kartvelishvily E, Wolosker H (Jul 2006). "Modulation of D-serine levels via ubiquitin-dependent proteasomal degradation of serine racemase". The Journal of Biological Chemistry. 281 (29): 20291–302. doi:10.1074/jbc.M601971200. PMID 16714286.
• Strísovský K, Jirásková J, Barinka C, Majer P, Rojas C, Slusher BS, Konvalinka J (Jan 2003). "Mouse brain serine racemase catalyzes specific elimination of L-serine to pyruvate". FEBS Letters. 535 (1–3): 44–8. doi:10.1016/s0014-5793(02)03855-3. PMID 12560076. S2CID 43772379.
• Hoffman HE, Jirásková J, Ingr M, Zvelebil M, Konvalinka J (Jan 2009). "Recombinant human serine racemase: enzymologic characterization and comparison with its mouse ortholog". Protein Expression and Purification. 63 (1): 62–7. doi:10.1016/j.pep.2008.09.003. PMID 18812225.
• Sarras H, Semeralul MO, Fadel MP, Feldcamp LA, Labrie V, Wong AH (Jul 2010). "Elevated PICK1 mRNA in schizophrenia increased SRR mRNA in suicide". Schizophrenia Research. 120 (1–3): 236–7. doi:10.1016/j.schres.2010.03.002. PMID 20385472. S2CID 21820692.
• Yamada K, Ohnishi T, Hashimoto K, Ohba H, Iwayama-Shigeno Y, Toyoshima M, Okuno A, Takao H, Toyota T, Minabe Y, Nakamura K, Shimizu E, Itokawa M, Mori N, Iyo M, Yoshikawa T (Jun 2005). "Identification of multiple serine racemase (SRR) mRNA isoforms and genetic analyses of SRR and DAO in schizophrenia and D-serine levels". Biological Psychiatry. 57 (12): 1493–503. doi:10.1016/j.biopsych.2005.03.018. PMID 15953485. S2CID 22811942.
• Xia M, Liu Y, Figueroa DJ, Chiu CS, Wei N, Lawlor AM, Lu P, Sur C, Koblan KS, Connolly TM (Jun 2004). "Characterization and localization of a human serine racemase". Brain Research. Molecular Brain Research. 125 (1–2): 96–104. doi:10.1016/j.molbrainres.2004.03.007. PMID 15193426.

External links

• Serine+racemase at the US National Library of Medicine Medical Subject Headings (MeSH)
• Overview of all the structural information available in the PDB for UniProt: Q9GZT4 (Serine racemase) at the PDBe-KB.