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P23378 (GCSP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 132. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Glycine dehydrogenase (decarboxylating), mitochondrial

EC=1.4.4.2
Alternative name(s):
Glycine cleavage system P protein
Glycine decarboxylase
Glycine dehydrogenase (aminomethyl-transferring)
Gene names
Name:GLDC
Synonyms:GCSP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1020 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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). HAMAP-Rule MF_00711

Catalytic activity

Glycine + [glycine-cleavage complex H protein]-N(6)-lipoyl-L-lysine = [glycine-cleavage complex H protein]-S-aminomethyl-N(6)-dihydrolipoyl-L-lysine + CO2. HAMAP-Rule MF_00711

Cofactor

Pyridoxal phosphate.

Enzyme regulation

Stimulated by lipoic acid. Inhibited in presence of methylamine By similarity. HAMAP-Rule MF_00711

Subunit structure

Interacts with GCSH By similarity. Homodimer. The glycine cleavage system is composed of four proteins: P (GLDC), T (GCST), L (DLD) and H (GCSH). HAMAP-Rule MF_00711

Subcellular location

Mitochondrion HAMAP-Rule MF_00711.

Involvement in disease

Non-ketotic hyperglycinemia (NKH) [MIM:605899]: Autosomal recessive disease characterized by accumulation of a large amount of glycine in body fluid and by severe neurological symptoms.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.9 Ref.10 Ref.11

Sequence similarities

Belongs to the GcvP family.

Ontologies

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 3535Mitochondrion Potential
Chain36 – 1020985Glycine dehydrogenase (decarboxylating), mitochondrial HAMAP-Rule MF_00711
PRO_0000010740

Amino acid modifications

Modified residue4471N6-acetyllysine By similarity
Modified residue5141N6-acetyllysine By similarity
Modified residue6481N6-acetyllysine By similarity
Modified residue6641N6-acetyllysine By similarity
Modified residue7541N6-(pyridoxal phosphate)lysine By similarity

Natural variations

Natural variant2831A → P in NKH. Ref.11
VAR_016849
Natural variant3291P → T in one non-ketotic hyperglycinemia patient. Ref.11
VAR_016850
Natural variant5151R → S in NKH. Ref.10
Corresponds to variant rs121964976 [ dbSNP | Ensembl ].
VAR_016851
Natural variant5641S → I in NKH; common mutation in Finland. Ref.9
VAR_004979
Natural variant7561Missing in NKH. Ref.1
VAR_009939

Experimental info

Sequence conflict3961A → R in AAA36463. Ref.2
Sequence conflict3961A → R in BAA14286. Ref.2
Sequence conflict4411Q → H in AAA36478. Ref.1
Sequence conflict4411Q → H in AAA36463. Ref.2
Sequence conflict4411Q → H in BAA14286. Ref.2
Sequence conflict6081Y → H in AAA36478. Ref.1
Sequence conflict9761V → M in AAA36463. Ref.2
Sequence conflict9761V → M in BAA14286. Ref.2

Sequences

Sequence LengthMass (Da)Tools
P23378 [UniParc].

Last modified May 5, 2009. Version 2.
Checksum: 8FAEA7D56BEB17B2

FASTA1,020112,730
        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 

« Hide

References

« Hide '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] [Europe PMC] [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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: VARIANT NKH PRO-283, VARIANT THR-329.
+Additional computationally mapped references.

Web resources

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.
PIRJN0124.
RefSeqNP_000161.2. NM_000170.2.
UniGeneHs.584238.

3D structure databases

ProteinModelPortalP23378.
SMRP23378. Positions 46-1005.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108993. 4 interactions.
IntActP23378. 6 interactions.
MINTMINT-7554996.
STRING9606.ENSP00000370737.

Chemistry

DrugBankDB00145. Glycine.
DB00114. Pyridoxal Phosphate.

PTM databases

PhosphoSiteP23378.

Polymorphism databases

DMDM229462870.

Proteomic databases

PaxDbP23378.
PRIDEP23378.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000321612; ENSP00000370737; ENSG00000178445.
GeneID2731.
KEGGhsa:2731.
UCSCuc003zkc.3. human.

Organism-specific databases

CTD2731.
GeneCardsGC09M006522.
H-InvDBHIX0034882.
HGNCHGNC:4313. GLDC.
HPAHPA002318.
MIM238300. gene.
605899. phenotype.
neXtProtNX_P23378.
Orphanet289863. Atypical glycine encephalopathy.
289860. Infantile glycine encephalopathy.
289857. Neonatal glycine encephalopathy.
PharmGKBPA28716.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1003.
HOGENOMHOG000239369.
HOVERGENHBG005820.
KOK00281.
OMAQTMVCDL.
OrthoDBEOG7FJGZQ.
PhylomeDBP23378.
TreeFamTF300678.

Enzyme and pathway databases

BioCycMetaCyc:HS00622-MONOMER.
SABIO-RKP23378.

Gene expression databases

BgeeP23378.
CleanExHS_GLDC.
GenevestigatorP23378.

Family and domain databases

Gene3D3.40.640.10. 2 hits.
HAMAPMF_00711. GcvP.
InterProIPR001597. ArAA_b-elim_lyase/Thr_aldolase.
IPR020580. GDC-P_N.
IPR020581. GDC_P.
IPR003437. GDC_P_homo.
IPR015424. PyrdxlP-dep_Trfase.
IPR015421. PyrdxlP-dep_Trfase_major_sub1.
[Graphical view]
PANTHERPTHR11773. PTHR11773. 1 hit.
PfamPF01212. Beta_elim_lyase. 1 hit.
PF02347. GDC-P. 1 hit.
[Graphical view]
SUPFAMSSF53383. SSF53383. 3 hits.
TIGRFAMsTIGR00461. gcvP. 1 hit.
ProtoNetSearch...

Other

GeneWikiGlycine_dehydrogenase_(decarboxylating).
GenomeRNAi2731.
NextBio10764.
PROP23378.
SOURCESearch...

Entry information

Entry nameGCSP_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 132 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM