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Protein

Glycine dehydrogenase (decarboxylating), mitochondrial

Gene

GLDC

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

The glycine cleavage system catalyzes the degradation of glycine. The P protein (GLDC) binds the alpha-amino group of glycine through its pyridoxal phosphate cofactor; CO2 is released and the remaining methylamine moiety is then transferred to the lipoamide cofactor of the H protein (GCSH).3 Publications

Catalytic activityi

Glycine + [glycine-cleavage complex H protein]-N6-lipoyl-L-lysine = [glycine-cleavage complex H protein]-S-aminomethyl-N6-dihydrolipoyl-L-lysine + CO2.3 Publications

Cofactori

pyridoxal 5'-phosphateBy similarity

Enzyme regulationi

Stimulated by lipoic acid. Inhibited in presence of methylamine (By similarity).By similarity

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionOxidoreductase
LigandPyridoxal phosphate

Enzyme and pathway databases

BioCyciMetaCyc:HS00622-MONOMER
ReactomeiR-HSA-6783984 Glycine degradation
SABIO-RKiP23378

Names & Taxonomyi

Protein namesi
Recommended name:
Glycine dehydrogenase (decarboxylating), mitochondrial1 Publication (EC:1.4.4.23 Publications)
Alternative name(s):
Glycine cleavage system P protein
Glycine decarboxylase2 Publications
Glycine dehydrogenase (aminomethyl-transferring)
Gene namesi
Name:GLDCImported
Synonyms:GCSPImported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000178445.8
HGNCiHGNC:4313 GLDC
MIMi238300 gene
neXtProtiNX_P23378

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Non-ketotic hyperglycinemia (NKH)6 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAutosomal recessive disease characterized by accumulation of a large amount of glycine in body fluid and by severe neurological symptoms.
See also OMIM:605899
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_078776146T → K in NKH; loss of glycine catabolic process; loss of expression. 1 PublicationCorresponds to variant dbSNP:rs376578742Ensembl.1
Natural variantiVAR_078777173L → P in NKH; loss of glycine catabolic process; decreased abundance. 1 Publication1
Natural variantiVAR_078778267P → A in NKH; decreased glycine catabolic process; changed localization to the mitochondria; also expressed diffusely throughout the cytosol; decreased abundance. 1 Publication1
Natural variantiVAR_016849283A → P in NKH. 1 PublicationCorresponds to variant dbSNP:rs386833589Ensembl.1
Natural variantiVAR_078779362R → C in NKH; decreased glycine catabolic process; decreased abundance. 1 PublicationCorresponds to variant dbSNP:rs10975674Ensembl.1
Natural variantiVAR_078780373R → W in NKH; decreased glycine catabolic process; decreased abundance. 1 PublicationCorresponds to variant dbSNP:rs150171524Ensembl.1
Natural variantiVAR_078781376K → E in NKH; decreased glycine catabolic process; decreased abundance. 1 PublicationCorresponds to variant dbSNP:rs774093619Ensembl.1
Natural variantiVAR_078782461R → W in NKH; decreased glycine catabolic process; changed localization to the mitochondria; also expressed diffusely throughout the cytosol; decreased abundance. 1 PublicationCorresponds to variant dbSNP:rs761957837Ensembl.1
Natural variantiVAR_016851515R → S in NKH. 1 PublicationCorresponds to variant dbSNP:rs121964976Ensembl.1
Natural variantiVAR_078783548L → P in NKH; decreased GCS P-protein glycine exchange activity; no effect on abundance. 1 Publication1
Natural variantiVAR_004979564S → I in NKH; common mutation in Finland. 1 PublicationCorresponds to variant dbSNP:rs121964974Ensembl.1
Natural variantiVAR_078784580H → Y in NKH; loss of glycine catabolic process; loss of expression. 1 Publication1
Natural variantiVAR_078785581P → R in NKH; loss of glycine catabolic process; decreased abundance. 1 PublicationCorresponds to variant dbSNP:rs772871471Ensembl.1
Natural variantiVAR_078786624A → D in NKH; loss of GCS P-protein glycine exchange activity; no effect on abundance. 1 Publication1
Natural variantiVAR_009939756Missing in NKH. 1 Publication1
Natural variantiVAR_078787763G → D in NKH; loss of GCS P-protein glycine exchange activity; no effect on abundance. 1 Publication1
Natural variantiVAR_078788768G → E in NKH; loss of GCS P-protein glycine exchange activity; no effect on abundance. 1 Publication1
Natural variantiVAR_078789790R → W in NKH; decreased glycine catabolic process; decreased abundance. 1 PublicationCorresponds to variant dbSNP:rs386833556Ensembl.1
Natural variantiVAR_079313839Y → C in NKH. 1 Publication1
Natural variantiVAR_078790866D → H in NKH; decreased glycine catabolic process; decreased abundance. 1 Publication1
Natural variantiVAR_078791905V → G in NKH; decreased GCS P-protein glycine exchange activity; no effect on abundance. 1 PublicationCorresponds to variant dbSNP:rs188269735Ensembl.1
Natural variantiVAR_078792933I → T in NKH; decreased glycine catabolic process; decreased abundance. 1 PublicationCorresponds to variant dbSNP:rs758029533Ensembl.1
Natural variantiVAR_078793994G → R in NKH; loss of glycine catabolic process; loss of expression. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi2731
GeneReviewsiGLDC
MalaCardsiGLDC
MIMi605899 phenotype
OpenTargetsiENSG00000178445
Orphaneti289863 Atypical glycine encephalopathy
289860 Infantile glycine encephalopathy
289857 Neonatal glycine encephalopathy
PharmGKBiPA28716

Chemistry databases

DrugBankiDB00145 Glycine
DB00114 Pyridoxal Phosphate

Polymorphism and mutation databases

BioMutaiGLDC
DMDMi229462870

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 35MitochondrionSequence analysisAdd BLAST35
ChainiPRO_000001074036 – 1020Glycine dehydrogenase (decarboxylating), mitochondrialAdd BLAST985

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei447N6-acetyllysineBy similarity1
Modified residuei514N6-acetyllysineBy similarity1
Modified residuei648N6-acetyllysineBy similarity1
Modified residuei664N6-acetyllysineBy similarity1
Modified residuei754N6-(pyridoxal phosphate)lysineBy similarity1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiP23378
MaxQBiP23378
PaxDbiP23378
PeptideAtlasiP23378
PRIDEiP23378

PTM databases

iPTMnetiP23378
PhosphoSitePlusiP23378

Expressioni

Gene expression databases

BgeeiENSG00000178445
CleanExiHS_GLDC
ExpressionAtlasiP23378 baseline and differential
GenevisibleiP23378 HS

Organism-specific databases

HPAiHPA002318
HPA052887

Interactioni

Subunit structurei

Homodimer (By similarity). Interacts with GCSH (By similarity). The glycine cleavage system is composed of four proteins: P (GLDC), T (GCST), L (DLD) and H (GCSH).By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi108993, 21 interactors
IntActiP23378, 10 interactors
MINTiP23378
STRINGi9606.ENSP00000370737

Structurei

3D structure databases

ProteinModelPortaliP23378
SMRiP23378
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the GcvP family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG2040 Eukaryota
COG0403 LUCA
COG1003 LUCA
GeneTreeiENSGT00390000017970
HOGENOMiHOG000239369
HOVERGENiHBG005820
InParanoidiP23378
KOiK00281
OMAiQTMVCDL
OrthoDBiEOG091G019V
PhylomeDBiP23378
TreeFamiTF300678

Family and domain databases

CDDicd00613 GDC-P, 2 hits
Gene3Di3.40.640.10, 2 hits
3.90.1150.10, 1 hit
HAMAPiMF_00711 GcvP, 1 hit
InterProiView protein in InterPro
IPR001597 ArAA_b-elim_lyase/Thr_aldolase
IPR003437 GcvP
IPR020581 GDC_P
IPR015424 PyrdxlP-dep_Trfase
IPR015422 PyrdxlP-dep_Trfase_dom1
IPR015421 PyrdxlP-dep_Trfase_major
PANTHERiPTHR11773 PTHR11773, 1 hit
PfamiView protein in Pfam
PF01212 Beta_elim_lyase, 1 hit
PF02347 GDC-P, 1 hit
SUPFAMiSSF53383 SSF53383, 3 hits
TIGRFAMsiTIGR00461 gcvP, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P23378-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQSCARAWGL RLGRGVGGGR RLAGGSGPCW APRSRDSSSG GGDSAAAGAS
60 70 80 90 100
RLLERLLPRH DDFARRHIGP GDKDQREMLQ TLGLASIDEL IEKTVPANIR
110 120 130 140 150
LKRPLKMEDP VCENEILATL HAISSKNQIW RSYIGMGYYN CSVPQTILRN
160 170 180 190 200
LLENSGWITQ YTPYQPEVSQ GRLESLLNYQ TMVCDITGLD MANASLLDEG
210 220 230 240 250
TAAAEALQLC YRHNKRRKFL VDPRCHPQTI AVVQTRAKYT GVLTELKLPC
260 270 280 290 300
EMDFSGKDVS GVLFQYPDTE GKVEDFTELV ERAHQSGSLA CCATDLLALC
310 320 330 340 350
ILRPPGEFGV DIALGSSQRF GVPLGYGGPH AAFFAVRESL VRMMPGRMVG
360 370 380 390 400
VTRDATGKEV YRLALQTREQ HIRRDKATSN ICTAQALLAN MAAMFAIYHG
410 420 430 440 450
SHGLEHIARR VHNATLILSE GLKRAGHQLQ HDLFFDTLKI QCGCSVKEVL
460 470 480 490 500
GRAAQRQINF RLFEDGTLGI SLDETVNEKD LDDLLWIFGC ESSAELVAES
510 520 530 540 550
MGEECRGIPG SVFKRTSPFL THQVFNSYHS ETNIVRYMKK LENKDISLVH
560 570 580 590 600
SMIPLGSCTM KLNSSSELAP ITWKEFANIH PFVPLDQAQG YQQLFRELEK
610 620 630 640 650
DLCELTGYDQ VCFQPNSGAQ GEYAGLATIR AYLNQKGEGH RTVCLIPKSA
660 670 680 690 700
HGTNPASAHM AGMKIQPVEV DKYGNIDAVH LKAMVDKHKE NLAAIMITYP
710 720 730 740 750
STNGVFEENI SDVCDLIHQH GGQVYLDGAN MNAQVGICRP GDFGSDVSHL
760 770 780 790 800
NLHKTFCIPH GGGGPGMGPI GVKKHLAPFL PNHPVISLKR NEDACPVGTV
810 820 830 840 850
SAAPWGSSSI LPISWAYIKM MGGKGLKQAT ETAILNANYM AKRLETHYRI
860 870 880 890 900
LFRGARGYVG HEFILDTRPF KKSANIEAVD VAKRLQDYGF HAPTMSWPVA
910 920 930 940 950
GTLMVEPTES EDKAELDRFC DAMISIRQEI ADIEEGRIDP RVNPLKMSPH
960 970 980 990 1000
SLTCVTSSHW DRPYSREVAA FPLPFVKPEN KFWPTIARID DIYGDQHLVC
1010 1020
TCPPMEVYES PFSEQKRASS
Length:1,020
Mass (Da):112,730
Last modified:May 5, 2009 - v2
Checksum:i8FAEA7D56BEB17B2
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti396A → R in AAA36463 (PubMed:1993704).Curated1
Sequence conflicti396A → R in BAA14286 (PubMed:1993704).Curated1
Sequence conflicti441Q → H in AAA36478 (PubMed:1996985).Curated1
Sequence conflicti441Q → H in AAA36463 (PubMed:1993704).Curated1
Sequence conflicti441Q → H in BAA14286 (PubMed:1993704).Curated1
Sequence conflicti608Y → H in AAA36478 (PubMed:1996985).Curated1
Sequence conflicti976V → M in AAA36463 (PubMed:1993704).Curated1
Sequence conflicti976V → M in BAA14286 (PubMed:1993704).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_078776146T → K in NKH; loss of glycine catabolic process; loss of expression. 1 PublicationCorresponds to variant dbSNP:rs376578742Ensembl.1
Natural variantiVAR_078777173L → P in NKH; loss of glycine catabolic process; decreased abundance. 1 Publication1
Natural variantiVAR_078778267P → A in NKH; decreased glycine catabolic process; changed localization to the mitochondria; also expressed diffusely throughout the cytosol; decreased abundance. 1 Publication1
Natural variantiVAR_016849283A → P in NKH. 1 PublicationCorresponds to variant dbSNP:rs386833589Ensembl.1
Natural variantiVAR_016850329P → T in one non-ketotic hyperglycinemia patient. 1 PublicationCorresponds to variant dbSNP:rs386833593Ensembl.1
Natural variantiVAR_078779362R → C in NKH; decreased glycine catabolic process; decreased abundance. 1 PublicationCorresponds to variant dbSNP:rs10975674Ensembl.1
Natural variantiVAR_078780373R → W in NKH; decreased glycine catabolic process; decreased abundance. 1 PublicationCorresponds to variant dbSNP:rs150171524Ensembl.1
Natural variantiVAR_078781376K → E in NKH; decreased glycine catabolic process; decreased abundance. 1 PublicationCorresponds to variant dbSNP:rs774093619Ensembl.1
Natural variantiVAR_078782461R → W in NKH; decreased glycine catabolic process; changed localization to the mitochondria; also expressed diffusely throughout the cytosol; decreased abundance. 1 PublicationCorresponds to variant dbSNP:rs761957837Ensembl.1
Natural variantiVAR_016851515R → S in NKH. 1 PublicationCorresponds to variant dbSNP:rs121964976Ensembl.1
Natural variantiVAR_078783548L → P in NKH; decreased GCS P-protein glycine exchange activity; no effect on abundance. 1 Publication1
Natural variantiVAR_004979564S → I in NKH; common mutation in Finland. 1 PublicationCorresponds to variant dbSNP:rs121964974Ensembl.1
Natural variantiVAR_078784580H → Y in NKH; loss of glycine catabolic process; loss of expression. 1 Publication1
Natural variantiVAR_078785581P → R in NKH; loss of glycine catabolic process; decreased abundance. 1 PublicationCorresponds to variant dbSNP:rs772871471Ensembl.1
Natural variantiVAR_078786624A → D in NKH; loss of GCS P-protein glycine exchange activity; no effect on abundance. 1 Publication1
Natural variantiVAR_009939756Missing in NKH. 1 Publication1
Natural variantiVAR_078787763G → D in NKH; loss of GCS P-protein glycine exchange activity; no effect on abundance. 1 Publication1
Natural variantiVAR_078788768G → E in NKH; loss of GCS P-protein glycine exchange activity; no effect on abundance. 1 Publication1
Natural variantiVAR_078789790R → W in NKH; decreased glycine catabolic process; decreased abundance. 1 PublicationCorresponds to variant dbSNP:rs386833556Ensembl.1
Natural variantiVAR_079313839Y → C in NKH. 1 Publication1
Natural variantiVAR_078790866D → H in NKH; decreased glycine catabolic process; decreased abundance. 1 Publication1
Natural variantiVAR_078791905V → G in NKH; decreased GCS P-protein glycine exchange activity; no effect on abundance. 1 PublicationCorresponds to variant dbSNP:rs188269735Ensembl.1
Natural variantiVAR_078792933I → T in NKH; decreased glycine catabolic process; decreased abundance. 1 PublicationCorresponds to variant dbSNP:rs758029533Ensembl.1
Natural variantiVAR_078793994G → R in NKH; loss of glycine catabolic process; loss of expression. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M63635 mRNA Translation: AAA36478.1
M64590 mRNA Translation: AAA36463.1
D90239 mRNA Translation: BAA14286.1
AK314156 mRNA Translation: BAG36841.1
AL353718 Genomic DNA No translation available.
AL162411 Genomic DNA No translation available.
CH471071 Genomic DNA Translation: EAW58740.1
BC111993 mRNA Translation: AAI11994.1
BC111995 mRNA Translation: AAI11996.1
CCDSiCCDS34987.1
PIRiJN0124
RefSeqiNP_000161.2, NM_000170.2
UniGeneiHs.584238

Genome annotation databases

EnsembliENST00000321612; ENSP00000370737; ENSG00000178445
GeneIDi2731
KEGGihsa:2731
UCSCiuc003zkc.4 human

Similar proteinsi

Entry informationi

Entry nameiGCSP_HUMAN
AccessioniPrimary (citable) accession number: P23378
Secondary accession number(s): Q2M2F8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: May 5, 2009
Last modified: February 28, 2018
This is version 166 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health