GCSH_HUMAN
ID GCSH_HUMAN Reviewed; 173 AA.
AC P23434; Q9H1E9;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2010, sequence version 2.
DT 03-AUG-2022, entry version 209.
DE RecName: Full=Glycine cleavage system H protein, mitochondrial {ECO:0000303|PubMed:1671321};
DE AltName: Full=Lipoic acid-containing protein;
DE Flags: Precursor;
GN Name=GCSH {ECO:0000312|HGNC:HGNC:4208};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, VARIANT LEU-21, LIPOYLATION AT
RP LYS-107, AND COFACTOR.
RX PubMed=1671321;
RA Koyata H., Hiraga K.;
RT "The glycine cleavage system: structure of a cDNA encoding human H-protein,
RT and partial characterization of its gene in patients with
RT hyperglycinemias.";
RL Am. J. Hum. Genet. 48:351-361(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT LEU-21.
RX PubMed=2025283; DOI=10.1016/s0006-291x(05)80242-6;
RA Fujiwara K., Okamura-Ikeda K., Hayasaka K., Motokawa Y.;
RT "The primary structure of human H-protein of the glycine cleavage system
RT deduced by cDNA cloning.";
RL Biochem. Biophys. Res. Commun. 176:711-716(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LEU-21 AND SER-73.
RG NIEHS SNPs program;
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LEU-21.
RC TISSUE=Placenta, and Skeletal muscle;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
CC -!- FUNCTION: The glycine cleavage system catalyzes the degradation of
CC glycine. The H protein (GCSH) shuttles the methylamine group of glycine
CC from the P protein (GLDC) to the T protein (GCST).
CC {ECO:0000269|PubMed:1671321}.
CC -!- COFACTOR:
CC Name=(R)-lipoate; Xref=ChEBI:CHEBI:83088;
CC Evidence={ECO:0000269|PubMed:1671321};
CC Note=Binds 1 lipoyl cofactor covalently. {ECO:0000269|PubMed:1671321};
CC -!- SUBUNIT: Interacts with GLDC (By similarity). The glycine cleavage
CC system is composed of four proteins: P (GLDC), T (GCST), L (DLD) and H
CC (GCSH). {ECO:0000250|UniProtKB:P11183}.
CC -!- INTERACTION:
CC P23434; Q9UHD4: CIDEB; NbExp=3; IntAct=EBI-715444, EBI-7062247;
CC P23434; P43364: MAGEA11; NbExp=3; IntAct=EBI-715444, EBI-739552;
CC P23434; P43360: MAGEA6; NbExp=3; IntAct=EBI-715444, EBI-1045155;
CC P23434; Q9P086: MED11; NbExp=3; IntAct=EBI-715444, EBI-394704;
CC P23434; Q9NYP9: MIS18A; NbExp=3; IntAct=EBI-715444, EBI-1104552;
CC P23434; Q13287: NMI; NbExp=4; IntAct=EBI-715444, EBI-372942;
CC P23434; Q6NTF9-3: RHBDD2; NbExp=3; IntAct=EBI-715444, EBI-17589229;
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:P20821}.
CC -!- DISEASE: Non-ketotic hyperglycinemia (NKH) [MIM:605899]: Autosomal
CC recessive disease characterized by accumulation of a large amount of
CC glycine in body fluid and by severe neurological symptoms. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the GcvH family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/gcsh/";
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DR EMBL; D00723; BAA00625.1; -; mRNA.
DR EMBL; M69175; AAA36011.1; -; mRNA.
DR EMBL; AY310735; AAP50260.1; -; Genomic_DNA.
DR EMBL; AC092718; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC000790; AAH00790.1; -; mRNA.
DR EMBL; BC020922; AAH20922.1; -; mRNA.
DR CCDS; CCDS10933.1; -.
DR PIR; A36662; GCHUH.
DR RefSeq; NP_004474.2; NM_004483.4.
DR AlphaFoldDB; P23434; -.
DR SMR; P23434; -.
DR BioGRID; 108923; 56.
DR IntAct; P23434; 12.
DR STRING; 9606.ENSP00000319531; -.
DR DrugBank; DB03187; 6-(Hydroxyethyldithio)-8-(Aminomethylthio)Octanoic Acid.
DR DrugBank; DB03760; Dihydrolipoic Acid.
DR DrugBank; DB00145; Glycine.
DR iPTMnet; P23434; -.
DR PhosphoSitePlus; P23434; -.
DR BioMuta; GCSH; -.
DR DMDM; 311033385; -.
DR EPD; P23434; -.
DR jPOST; P23434; -.
DR MassIVE; P23434; -.
DR MaxQB; P23434; -.
DR PaxDb; P23434; -.
DR PeptideAtlas; P23434; -.
DR PRIDE; P23434; -.
DR ProteomicsDB; 54093; -.
DR TopDownProteomics; P23434; -.
DR Antibodypedia; 30442; 226 antibodies from 29 providers.
DR DNASU; 2653; -.
DR Ensembl; ENST00000315467.9; ENSP00000319531.3; ENSG00000140905.11.
DR GeneID; 2653; -.
DR KEGG; hsa:2653; -.
DR MANE-Select; ENST00000315467.9; ENSP00000319531.3; NM_004483.5; NP_004474.2.
DR UCSC; uc002fgd.4; human.
DR CTD; 2653; -.
DR DisGeNET; 2653; -.
DR GeneCards; GCSH; -.
DR GeneReviews; GCSH; -.
DR HGNC; HGNC:4208; GCSH.
DR HPA; ENSG00000140905; Low tissue specificity.
DR MalaCards; GCSH; -.
DR MIM; 238330; gene.
DR MIM; 605899; phenotype.
DR neXtProt; NX_P23434; -.
DR OpenTargets; ENSG00000140905; -.
DR Orphanet; 289863; Atypical glycine encephalopathy.
DR Orphanet; 289860; Infantile glycine encephalopathy.
DR Orphanet; 289857; Neonatal glycine encephalopathy.
DR VEuPathDB; HostDB:ENSG00000140905; -.
DR eggNOG; KOG3373; Eukaryota.
DR GeneTree; ENSGT00390000011666; -.
DR HOGENOM; CLU_097408_1_1_1; -.
DR InParanoid; P23434; -.
DR OMA; YRDSHEW; -.
DR OrthoDB; 1348095at2759; -.
DR PhylomeDB; P23434; -.
DR TreeFam; TF300258; -.
DR BioCyc; MetaCyc:HS06771-MON; -.
DR BRENDA; 1.4.1.27; 2681.
DR BRENDA; 1.4.4.2; 2681.
DR PathwayCommons; P23434; -.
DR Reactome; R-HSA-389661; Glyoxylate metabolism and glycine degradation.
DR Reactome; R-HSA-6783984; Glycine degradation.
DR SABIO-RK; P23434; -.
DR SignaLink; P23434; -.
DR SIGNOR; P23434; -.
DR BioGRID-ORCS; 2653; 137 hits in 1072 CRISPR screens.
DR GeneWiki; GCSH; -.
DR GenomeRNAi; 2653; -.
DR Pharos; P23434; Tbio.
DR PRO; PR:P23434; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; P23434; protein.
DR Bgee; ENSG00000140905; Expressed in C1 segment of cervical spinal cord and 102 other tissues.
DR ExpressionAtlas; P23434; baseline and differential.
DR Genevisible; P23434; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005960; C:glycine cleavage complex; TAS:ProtInc.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0004047; F:aminomethyltransferase activity; TAS:ProtInc.
DR GO; GO:0006546; P:glycine catabolic process; TAS:ProtInc.
DR GO; GO:0019464; P:glycine decarboxylation via glycine cleavage system; IBA:GO_Central.
DR GO; GO:0009249; P:protein lipoylation; IDA:UniProtKB.
DR CDD; cd06848; GCS_H; 1.
DR HAMAP; MF_00272; GcvH; 1.
DR InterPro; IPR003016; 2-oxoA_DH_lipoyl-BS.
DR InterPro; IPR000089; Biotin_lipoyl.
DR InterPro; IPR002930; GCV_H.
DR InterPro; IPR033753; GCV_H/Fam206.
DR InterPro; IPR017453; GCV_H_sub.
DR InterPro; IPR011053; Single_hybrid_motif.
DR PANTHER; PTHR11715; PTHR11715; 1.
DR Pfam; PF01597; GCV_H; 1.
DR SUPFAM; SSF51230; SSF51230; 1.
DR TIGRFAMs; TIGR00527; gcvH; 1.
DR PROSITE; PS50968; BIOTINYL_LIPOYL; 1.
DR PROSITE; PS00189; LIPOYL; 1.
PE 1: Evidence at protein level;
KW Lipoyl; Mitochondrion; Reference proteome; Transit peptide.
FT TRANSIT 1..48
FT /note="Mitochondrion"
FT CHAIN 49..173
FT /note="Glycine cleavage system H protein, mitochondrial"
FT /id="PRO_0000010723"
FT DOMAIN 66..148
FT /note="Lipoyl-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01066"
FT MOD_RES 107
FT /note="N6-lipoyllysine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01066,
FT ECO:0000269|PubMed:1671321"
FT VARIANT 21
FT /note="S -> L (in dbSNP:rs8052579)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:1671321, ECO:0000269|PubMed:2025283,
FT ECO:0000269|Ref.3"
FT /id="VAR_018846"
FT VARIANT 73
FT /note="N -> S (in dbSNP:rs8177877)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_018847"
SQ SEQUENCE 173 AA; 18885 MW; 3CC5D09D59C1243D CRC64;
MALRVVRSVR ALLCTLRAVP SPAAPCPPRP WQLGVGAVRT LRTGPALLSV RKFTEKHEWV
TTENGIGTVG ISNFAQEALG DVVYCSLPEV GTKLNKQDEF GALESVKAAS ELYSPLSGEV
TEINEALAEN PGLVNKSCYE DGWLIKMTLS NPSELDELMS EEAYEKYIKS IEE
