P23378 (GCSP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Glycine dehydrogenase [decarboxylating], mitochondrial
EC=1.4.4.2

Alternative name(s):
Glycine cleavage system P protein
Glycine decarboxylase

Gene names

Name:	GLDC
Synonyms:	GCSP

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1020 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	The glycine cleavage system catalyzes the degradation of glycine. The P protein 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.
Catalytic activity	Glycine + H-protein-lipoyllysine = H-protein-S-aminomethyldihydrolipoyllysine + CO2.
Cofactor	Pyridoxal phosphate.
Subunit structure	Homodimer. The glycine cleavage system is composed of four proteins: P, T, L and H.
Subcellular location	Mitochondrion.
Involvement in disease	Defects in GLDC are a cause of non-ketotic hyperglycinemia (NKH) [MIM:605899]; also known as glycine encephalopathy (GCE). NKH is an autosomal recessive disease characterized by accumulation of a large amount of glycine in body fluid and by severe neurological symptoms. Ref.1 Ref.9 Ref.10 Ref.11
Sequence similarities	Belongs to the GcvP family.

Ontologies

Keywords
Cellular component	Mitochondrion
Disease	Disease mutation
Domain	Transit peptide
Ligand	Pyridoxal phosphate
Molecular function	Oxidoreductase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	glycine catabolic process Traceable author statement. Source: ProtInc
Cellular component	mitochondrion Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	electron carrier activity Traceable author statement. Source: UniProtKB glycine dehydrogenase (decarboxylating) activity Traceable author statement. Source: ProtInc lyase activity Inferred from electronic annotation. Source: InterPro pyridoxal phosphate binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 35	35	Mitochondrion Potential
	Chain	36 – 1020	985	Glycine dehydrogenase [decarboxylating], mitochondrial		PRO_0000010740
Amino acid modifications
	Modified residue	38	1	Phosphoserine Ref.7
	Modified residue	39	1	Phosphoserine Ref.7
	Modified residue	754	1	N6-(pyridoxal phosphate)lysine By similarity
Natural variations
	Natural variant	283	1	A → P in NKH. Ref.11		VAR_016849
	Natural variant	329	1	P → T in one non-ketotic hyperglycinemia patient. Ref.11		VAR_016850
	Natural variant	515	1	R → S in NKH. Ref.10		VAR_016851
	Natural variant	564	1	S → I in NKH; common mutation in Finland. Ref.9		VAR_004979
	Natural variant	756	1	Missing in NKH.		VAR_009939
Experimental info
	Sequence conflict	396	1	A → R in AAA36463. Ref.2
	Sequence conflict	396	1	A → R in BAA14286. Ref.2
	Sequence conflict	441	1	Q → H in AAA36478. Ref.1
	Sequence conflict	441	1	Q → H in AAA36463. Ref.2
	Sequence conflict	441	1	Q → H in BAA14286. Ref.2
	Sequence conflict	608	1	Y → H in AAA36478. Ref.1
	Sequence conflict	976	1	V → M in AAA36463. Ref.2
	Sequence conflict	976	1	V → M in BAA14286. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P23378 [UniParc]. Last modified May 5, 2009. Version 2. Checksum: 8FAEA7D56BEB17B2	FASTA	1,020	112,730
	10 20 30 40 50 60 MQSCARAWGL RLGRGVGGGR RLAGGSGPCW APRSRDSSSG GGDSAAAGAS RLLERLLPRH 70 80 90 100 110 120 DDFARRHIGP GDKDQREMLQ TLGLASIDEL IEKTVPANIR LKRPLKMEDP VCENEILATL 130 140 150 160 170 180 HAISSKNQIW RSYIGMGYYN CSVPQTILRN LLENSGWITQ YTPYQPEVSQ GRLESLLNYQ 190 200 210 220 230 240 TMVCDITGLD MANASLLDEG TAAAEALQLC YRHNKRRKFL VDPRCHPQTI AVVQTRAKYT 250 260 270 280 290 300 GVLTELKLPC EMDFSGKDVS GVLFQYPDTE GKVEDFTELV ERAHQSGSLA CCATDLLALC 310 320 330 340 350 360 ILRPPGEFGV DIALGSSQRF GVPLGYGGPH AAFFAVRESL VRMMPGRMVG VTRDATGKEV 370 380 390 400 410 420 YRLALQTREQ HIRRDKATSN ICTAQALLAN MAAMFAIYHG SHGLEHIARR VHNATLILSE 430 440 450 460 470 480 GLKRAGHQLQ HDLFFDTLKI QCGCSVKEVL GRAAQRQINF RLFEDGTLGI SLDETVNEKD 490 500 510 520 530 540 LDDLLWIFGC ESSAELVAES MGEECRGIPG SVFKRTSPFL THQVFNSYHS ETNIVRYMKK 550 560 570 580 590 600 LENKDISLVH SMIPLGSCTM KLNSSSELAP ITWKEFANIH PFVPLDQAQG YQQLFRELEK 610 620 630 640 650 660 DLCELTGYDQ VCFQPNSGAQ GEYAGLATIR AYLNQKGEGH RTVCLIPKSA HGTNPASAHM 670 680 690 700 710 720 AGMKIQPVEV DKYGNIDAVH LKAMVDKHKE NLAAIMITYP STNGVFEENI SDVCDLIHQH 730 740 750 760 770 780 GGQVYLDGAN MNAQVGICRP GDFGSDVSHL NLHKTFCIPH GGGGPGMGPI GVKKHLAPFL 790 800 810 820 830 840 PNHPVISLKR NEDACPVGTV SAAPWGSSSI LPISWAYIKM MGGKGLKQAT ETAILNANYM 850 860 870 880 890 900 AKRLETHYRI LFRGARGYVG HEFILDTRPF KKSANIEAVD VAKRLQDYGF HAPTMSWPVA 910 920 930 940 950 960 GTLMVEPTES EDKAELDRFC DAMISIRQEI ADIEEGRIDP RVNPLKMSPH SLTCVTSSHW 970 980 990 1000 1010 1020 DRPYSREVAA FPLPFVKPEN KFWPTIARID DIYGDQHLVC TCPPMEVYES PFSEQKRASS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structural and expression analyses of normal and mutant mRNA encoding glycine decarboxylase: three-base deletion in mRNA causes nonketotic hyperglycinemia." Kure S., Narisawa K., Tada K. Biochem. Biophys. Res. Commun. 174:1176-1182(1991) [PubMed: 1996985] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT NKH PHE-756 DEL.
[2]	"The glycine cleavage system. Molecular cloning of the chicken and human glycine decarboxylase cDNAs and some characteristics involved in the deduced protein structures." Kume A., Koyata H., Sakakibara T., Ishiguro Y., Kure S., Hiraga K. J. Biol. Chem. 266:3323-3329(1991) [PubMed: 1993704] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[7]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed: 18088087] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-38 AND SER-39, MASS SPECTROMETRY. Tissue: Platelet.
[8]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]	"Identification of a common mutation in Finnish patients with nonketotic hyperglycinemia." Kure S., Takayanagi M., Narisawa K., Tada K., Leisti J. J. Clin. Invest. 90:160-164(1992) [PubMed: 1634607] [Abstract] Cited for: VARIANT NKH ILE-564.
[10]	"Recurrent mutations in P- and T-proteins of the glycine cleavage complex and a novel T-protein mutation (N145I): a strategy for the molecular investigation of patients with nonketotic hyperglycinemia (NKH)." Toone J.R., Applegarth D.A., Coulter-Mackie M.B., James E.R. Mol. Genet. Metab. 72:322-325(2001) [PubMed: 11286506] [Abstract] Cited for: VARIANT NKH SER-515.
[11]	"Nonketotic hyperglycinemia (glycine encephalopathy): laboratory diagnosis." Applegarth D.A., Toone J.R. Mol. Genet. Metab. 74:139-146(2001) [PubMed: 11592811] [Abstract] Cited for: VARIANT NKH PRO-283, VARIANT THR-329.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	M63635 mRNA. Translation: AAA36478.1. M64590 mRNA. Translation: AAA36463.1. D90239 mRNA. Translation: BAA14286.1. AK314156 mRNA. Translation: BAG36841.1. AL353718, AL162411 Genomic DNA. Translation: CAQ07607.1. AL162411, AL353718 Genomic DNA. Translation: CAQ10367.1. CH471071 Genomic DNA. Translation: EAW58740.1. BC111993 mRNA. Translation: AAI11994.1. BC111995 mRNA. Translation: AAI11996.1.
IPI	IPI00843789.
PIR	JN0124.
RefSeq	NP_000161.2. NM_000170.2.
UniGene	Hs.584238.
3D structure databases
ProteinModelPortal	P23378.
SMR	P23378. Positions 66-489.
ModBase	Search...
Protein-protein interaction databases
IntAct	P23378. 4 interactions.
STRING	P23378.
PTM databases
PhosphoSite	P23378.
Polymorphism databases
DMDM	229462870.
Proteomic databases
PRIDE	P23378.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000321612; ENSP00000370737; ENSG00000178445.
GeneID	2731.
KEGG	hsa:2731.
Organism-specific databases
CTD	2731.
GeneCards	GC09M006522.
H-InvDB	HIX0034882.
HGNC	HGNC:4313. GLDC.
HPA	HPA002318.
MIM	238300. gene. 605899. phenotype.
neXtProt	NX_P23378.
Orphanet	407. Isolated nonketotic hyperglycinemia.
PharmGKB	PA28716.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG12334.
HOGENOM	HBG286723.
HOVERGEN	HBG005820.
OMA	AKRLIDC.
OrthoDB	EOG4J117D.
PhylomeDB	P23378.
Gene expression databases
ArrayExpress	P23378.
Bgee	P23378.
CleanEx	HS_GLDC.
Genevestigator	P23378.
GermOnline	ENSG00000178445. Homo sapiens.
Family and domain databases
InterPro	IPR001597. ArAA_b-elim_lyase/Thr_aldolase. IPR020580. GDC-P_N. IPR020581. GDC_P. IPR003437. GDC_P_homo. IPR015424. PyrdxlP-dep_Trfase_major_dom. IPR015421. PyrdxlP-dep_Trfase_major_sub1. [Graphical view]
Gene3D	G3DSA:3.40.640.10. PyrdxlP-dep_Trfase_major_sub1. 2 hits.
KO	K00281.
PANTHER	PTHR11773. GDC-P. 1 hit.
Pfam	PF01212. Beta_elim_lyase. 1 hit. PF02347. GDC-P. 1 hit. [Graphical view]
SUPFAM	SSF53383. PyrdxlP-dep_Trfase_major. 2 hits.
TIGRFAMs	TIGR00461. GcvP. 1 hit.
ProtoNet	Search...
Other
DrugBank	DB00145. Glycine. DB00114. Pyridoxal Phosphate.
SOURCE	Search...

Entry information

Entry name

GCSP_HUMAN

Accession

Primary (citable) accession number: P23378
Secondary accession number(s): Q2M2F8

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1991
Last sequence update:	May 5, 2009
Last modified:	January 25, 2012
This is version 111 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.