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P48728 (GCST_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 137. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Aminomethyltransferase, mitochondrial

EC=2.1.2.10
Alternative name(s):
Glycine cleavage system T protein
Short name=GCVT
Gene names
Name:AMT
Synonyms:GCST
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length403 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.

Catalytic activity

[Protein]-S(8)-aminomethyldihydrolipoyllysine + tetrahydrofolate = [protein]-dihydrolipoyllysine + 5,10-methylenetetrahydrofolate + NH3.

Subunit structure

The glycine cleavage system is composed of four proteins: P, T, L and H.

Subcellular location

Mitochondrion.

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.8 Ref.9 Ref.10 Ref.11 Ref.12

Sequence similarities

Belongs to the GcvT family.

Ontologies

Keywords
   Cellular componentMitochondrion
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
   DomainTransit peptide
   Molecular functionAminotransferase
Transferase
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processglycine catabolic process

Traceable author statement Ref.9. Source: ProtInc

   Cellular_componentmitochondrion

Traceable author statement Ref.2. Source: ProtInc

   Molecular_functionaminomethyltransferase activity

Inferred from electronic annotation. Source: UniProtKB-EC

transaminase activity

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P48728-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P48728-2)

The sequence of this isoform differs from the canonical sequence as follows:
     30-85: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: P48728-3)

The sequence of this isoform differs from the canonical sequence as follows:
     113-156: Missing.
Note: No experimental confirmation available.
Isoform 4 (identifier: P48728-4)

The sequence of this isoform differs from the canonical sequence as follows:
     380-403: VRRKQQMAVVSKMPFVPTNYYTLK → LPSGPCF
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 2828Mitochondrion By similarity
Chain29 – 403375Aminomethyltransferase, mitochondrial
PRO_0000010755

Sites

Binding site2321Substrate
Binding site2611Substrate
Binding site3991Substrate

Natural variations

Alternative sequence30 – 8556Missing in isoform 2.
VSP_042557
Alternative sequence113 – 15644Missing in isoform 3.
VSP_043288
Alternative sequence380 – 40324VRRKQ…YYTLK → LPSGPCF in isoform 4.
VSP_045418
Natural variant421H → R in NKH. Ref.9
VAR_007951
Natural variant471G → R in NKH. Ref.8
VAR_007952
Natural variant1451N → I in NKH. Ref.12
VAR_016847
Natural variant2111E → K in NKH. Ref.11
Corresponds to variant rs116192290 [ dbSNP | Ensembl ].
VAR_016848
Natural variant2691G → D in NKH. Ref.8
VAR_007953
Natural variant2761D → H in NKH. Ref.10
VAR_007954
Natural variant3201R → H in NKH. Ref.8 Ref.11 Ref.12
VAR_007955

Experimental info

Sequence conflict951V → C in BAA03512. Ref.2

Secondary structure

.................................................................... 403
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 1, 1996. Version 1.
Checksum: 218DC9EEADFA9102

FASTA40343,946
        10         20         30         40         50         60 
MQRAVSVVAR LGFRLQAFPP ALCRPLSCAQ EVLRRTPLYD FHLAHGGKMV AFAGWSLPVQ 

        70         80         90        100        110        120 
YRDSHTDSHL HTRQHCSLFD VSHMLQTKIL GSDRVKLMES LVVGDIAELR PNQGTLSLFT 

       130        140        150        160        170        180 
NEAGGILDDL IVTNTSEGHL YVVSNAGCWE KDLALMQDKV RELQNQGRDV GLEVLDNALL 

       190        200        210        220        230        240 
ALQGPTAAQV LQAGVADDLR KLPFMTSAVM EVFGVSGCRV TRCGYTGEDG VEISVPVAGA 

       250        260        270        280        290        300 
VHLATAILKN PEVKLAGLAA RDSLRLEAGL CLYGNDIDEH TTPVEGSLSW TLGKRRRAAM 

       310        320        330        340        350        360 
DFPGAKVIVP QLKGRVQRRR VGLMCEGAPM RAHSPILNME GTKIGTVTSG CPSPSLKKNV 

       370        380        390        400 
AMGYVPCEYS RPGTMLLVEV RRKQQMAVVS KMPFVPTNYY TLK 

« Hide

Isoform 2 [UniParc].

Checksum: 4C99E4B0F9C76299
Show »

FASTA34737,434
Isoform 3 [UniParc].

Checksum: B1DA25DDC565ECB8
Show »

FASTA35939,267
Isoform 4 [UniParc].

Checksum: 3938EB3D01A8846B
Show »

FASTA38641,780

References

« Hide 'large scale' references
[1]"Isolation and sequence determination of cDNA encoding human T-protein of the glycine cleavage system."
Hayasaka K., Nanao K., Takada G., Okamura-Ikeda K., Motokawa Y.
Biochem. Biophys. Res. Commun. 192:766-771(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Structure and chromosomal localization of the aminomethyltransferase gene (AMT)."
Nanao K., Takada G., Takahashi E., Seki N., Komatsu Y., Okamura-Ikeda K., Motokawa Y., Hayasaka K.
Genomics 19:27-30(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[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] (ISOFORMS 1; 2 AND 3).
Tissue: Cerebellum, Heart and Thalamus.
[4]"The DNA sequence, annotation and analysis of human chromosome 3."
Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. expand/collapse author list , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
Nature 440:1194-1198(2006) [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 (JUL-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] OF 4-386 (ISOFORM 4).
Tissue: Colon.
[7]"Crystal structure of human T-protein of glycine cleavage system at 2.0 A resolution and its implication for understanding non-ketotic hyperglycinemia."
Okamura-Ikeda K., Hosaka H., Yoshimura M., Yamashita E., Toma S., Nakagawa A., Fujiwara K., Motokawa Y., Taniguchi H.
J. Mol. Biol. 351:1146-1159(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 29-403 ALONE AND IN COMPLEX WITH 5-METHYLTETRAHYDROFOLATE, SUBSTRATE-BINDING SITES.
[8]"Identification of the mutations in the T-protein gene causing typical and atypical nonketotic hyperglycinemia."
Nanao K., Okamura-Ikeda K., Motokawa Y., Danks D.M., Baumgartner E.R., Takada G., Hayasaka K.
Hum. Genet. 93:655-658(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NKH ARG-47; ASP-269 AND HIS-320.
[9]"A missense mutation (His42Arg) in the T-protein gene from a large Israeli-Arab kindred with nonketotic hyperglycinemia."
Kure S., Mandel H., Rolland M.-O., Sakata Y., Shinka T., Drugan A., Boneh A., Tada K., Matsubara Y., Narisawa K.
Hum. Genet. 102:430-434(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NKH ARG-42.
[10]"A one-base deletion (183delC) and a missense mutation (D276H) in the T-protein gene from a Japanese family with nonketotic hyperglycinemia."
Kure S., Shinka T., Sakata Y., Osamu N., Takayanagi M., Tada K., Matsubara Y., Narisawa K.
J. Hum. Genet. 43:135-137(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NKH HIS-276.
[11]"Biochemical and molecular investigations of patients with nonketotic hyperglycinemia."
Toone J.R., Applegarth D.A., Coulter-Mackie M.B., James E.R.
Mol. Genet. Metab. 70:116-121(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NKH LYS-211 AND HIS-320.
[12]"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: VARIANTS NKH ILE-145 AND HIS-320.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D13811 mRNA. Translation: BAA02967.1.
D14686 Genomic DNA. Translation: BAA03512.1.
AK290600 mRNA. Translation: BAF83289.1.
AK293481 mRNA. Translation: BAG56972.1.
AK296177 mRNA. Translation: BAG58912.1.
AC104452 Genomic DNA. No translation available.
CH471055 Genomic DNA. Translation: EAW64984.1.
BC007546 mRNA. Translation: AAH07546.2.
CCDSCCDS2797.1. [P48728-1]
CCDS54583.1. [P48728-2]
CCDS54584.1. [P48728-3]
CCDS54585.1. [P48728-4]
PIRI54192.
RefSeqNP_000472.2. NM_000481.3. [P48728-1]
NP_001158182.1. NM_001164710.1. [P48728-3]
NP_001158183.1. NM_001164711.1. [P48728-2]
NP_001158184.1. NM_001164712.1. [P48728-4]
UniGeneHs.102.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1WSRX-ray2.00A/B29-403[»]
1WSVX-ray2.60A/B29-403[»]
ProteinModelPortalP48728.
SMRP48728. Positions 32-402.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000273588.

Chemistry

DrugBankDB00157. NADH.
DB00116. Tetrahydrofolic acid.

PTM databases

PhosphoSiteP48728.

Polymorphism databases

DMDM1346122.

Proteomic databases

MaxQBP48728.
PaxDbP48728.
PRIDEP48728.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000273588; ENSP00000273588; ENSG00000145020. [P48728-1]
ENST00000395338; ENSP00000378747; ENSG00000145020. [P48728-4]
ENST00000458307; ENSP00000415619; ENSG00000145020. [P48728-3]
ENST00000538581; ENSP00000443200; ENSG00000145020. [P48728-2]
GeneID275.
KEGGhsa:275.
UCSCuc003cww.3. human. [P48728-1]
uc011bco.2. human. [P48728-3]
uc011bcq.2. human. [P48728-2]

Organism-specific databases

CTD275.
GeneCardsGC03M049429.
GeneReviewsAMT.
HGNCHGNC:473. AMT.
HPAHPA005566.
MIM238310. gene.
605899. phenotype.
neXtProtNX_P48728.
Orphanet289863. Atypical glycine encephalopathy.
289860. Infantile glycine encephalopathy.
289857. Neonatal glycine encephalopathy.
PharmGKBPA24780.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0404.
HOGENOMHOG000239380.
HOVERGENHBG005822.
InParanoidP48728.
KOK00605.
OMAFGPSFDG.
PhylomeDBP48728.
TreeFamTF313026.

Enzyme and pathway databases

BioCycMetaCyc:HS07223-MONOMER.
SABIO-RKP48728.

Gene expression databases

ArrayExpressP48728.
BgeeP48728.
CleanExHS_AMT.
GenevestigatorP48728.

Family and domain databases

Gene3D2.40.30.110. 1 hit.
3.30.1360.120. 2 hits.
InterProIPR006223. GCS_T.
IPR028896. GCST/DmdA.
IPR013977. GCV_T_C.
IPR006222. GCV_T_N.
IPR029043. GcvT/YgfZ_C.
IPR027266. TrmE/GcvT_dom1.
[Graphical view]
PANTHERPTHR13847:SF5. PTHR13847:SF5. 1 hit.
PfamPF01571. GCV_T. 1 hit.
PF08669. GCV_T_C. 1 hit.
[Graphical view]
PIRSFPIRSF006487. GcvT. 1 hit.
SUPFAMSSF101790. SSF101790. 1 hit.
TIGRFAMsTIGR00528. gcvT. 1 hit.
ProtoNetSearch...

Other

ChiTaRSAMT. human.
EvolutionaryTraceP48728.
GenomeRNAi275.
NextBio1109.
PROP48728.
SOURCESearch...

Entry information

Entry nameGCST_HUMAN
AccessionPrimary (citable) accession number: P48728
Secondary accession number(s): A8K3I5 expand/collapse secondary AC list , B4DE61, B4DJQ0, E9PBG1, Q96IG6
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: July 9, 2014
This is version 137 of the entry and version 1 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

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 3

Human chromosome 3: entries, gene names and cross-references to MIM