Reviewed, UniProtKB/Swiss-Prot P48728 (GCST_HUMAN)

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	403 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.
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	Defects in AMT 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.3 Ref.4 Ref.5 Ref.6 Ref.7
Sequence similarities	Belongs to the gcvT family.

Ontologies

Keywords
Cellular component	Mitochondrion
Disease	Disease mutation
Domain	Transit peptide
Molecular function	Aminotransferase Transferase
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	glycine catabolic process Ref.4 Traceable author statement. Source: ProtInc
Cellular component	mitochondrion Ref.2 Traceable author statement. Source: ProtInc
Molecular function	aminomethyltransferase activity Inferred from electronic annotation. Source: EC transaminase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 28

28

Mitochondrion By similarity

Chain

29 – 403

375

Aminomethyltransferase, mitochondrial

PRO_0000010755

Natural variations

Natural variant

42

1

H → R in NKH. Ref.4

VAR_007951

Natural variant

47

1

G → R in NKH. Ref.3

VAR_007952

Natural variant

145

1

N → I in NKH. Ref.7

VAR_016847

Natural variant

211

1

E → K in NKH. Ref.6

VAR_016848

Natural variant

269

1

G → D in NKH. Ref.3

VAR_007953

Natural variant

276

1

D → H in NKH. Ref.5

VAR_007954

Natural variant

320

1

R → H in NKH. Ref.3 Ref.6 Ref.7

VAR_007955

Experimental info

Sequence conflict

95

1

V → C in BAA03512. Ref.2

Secondary structure

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403

Helix Strand Turn

Details...

Helix

39 – 44

6

Beta strand

48 – 52

5

Beta strand

55 – 60

6

Helix

65 – 74

10

Beta strand

75 – 80

6

Beta strand

84 – 91

8

Helix

94 – 101

8

Beta strand

102 – 104

3

Beta strand

113 – 120

8

Beta strand

126 – 134

9

Beta strand

138 – 144

7

Helix

146 – 148

3

Helix

149 – 165

17

Beta strand

171 – 174

4

Beta strand

178 – 184

7

Helix

187 – 192

6

Helix

199 – 201

3

Beta strand

206 – 212

7

Beta strand

215 – 222

8

Beta strand

225 – 235

11

Helix

237 – 248

12

Beta strand

253 – 255

3

Helix

258 – 267

10

Turn

273 – 275

3

Turn

283 – 287

5

Helix

289 – 291

3

Helix

294 – 299

6

Helix

305 – 312

8

Beta strand

319 – 328

10

Beta strand

335 – 337

3

Beta strand

343 – 353

11

Turn

354 – 357

4

Beta strand

358 – 365

8

Helix

367 – 369

3

Beta strand

375 – 380

6

Beta strand

383 – 390

8

Sequences

	Sequence		Length	Mass (Da)
	P48728-1 [UniParc]. Last modified February 1, 1996. Version 1. Checksum: 218DC9EEADFA9102	FASTA	403	43,946
	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

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: 7916605] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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: 8188235] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"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: 8005589] [Abstract] Cited for: VARIANTS NKH ARG-47; ASP-269 AND HIS-320.
[4]	"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: 9600239] [Abstract] Cited for: VARIANT NKH ARG-42.
[5]	"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: 9621520] [Abstract] Cited for: VARIANT NKH HIS-276.
[6]	"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: 10873393] [Abstract] Cited for: VARIANTS NKH LYS-211 AND HIS-320.
[7]	"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: VARIANTS NKH ILE-145 AND HIS-320.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBLGenBankDDBJ

D13811 mRNA. Translation: BAA02967.1.
D14686 Genomic DNA. Translation: BAA03512.1.

IPI

IPI00299300.

PIR

I54192.

RefSeq

NP_000472.2.

UniGene

Hs.102

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1WSR	X-ray	2.00	A/B	29-403	[»]
1WSV	X-ray	2.60	A/B	29-403	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

P48728.

Proteomic databases

PRIDE

P48728.

Genome annotation databases

Ensembl

ENST00000273588; ENSP00000273588; ENSG00000145020; Homo sapiens. [Genome view]

GeneID

275.

KEGG

hsa:275.

NMPDR

fig|9606.3.peg.22532.

UCSC

uc003cww.1. human.

Organism-specific databases

CTD

275.

GeneCards

GC03M049429.

H-InvDB

HIX0003299.

HGNC

HGNC:473. AMT.

HPA

HPA005566.

MIM

238310. gene.
605899. phenotype.

Orphanet

407. Hyperglycinemia, isolated nonketotic.

PharmGKB

PA24780.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

HBG299834.

HOVERGEN

P48728.

InParanoid

P48728.

OMA

MPVQYPL.

Enzyme and pathway databases

BRENDA

2.1.2.10. 247.

Gene expression databases

ArrayExpress

P48728.

Bgee

P48728.

CleanEx

HS_AMT.

Genevestigator

P48728.

GermOnline

ENSG00000145020. Homo sapiens.

Family and domain databases

InterPro

IPR013977. GCV_T_C.
IPR006222. GCV_T_N.
IPR006223. GcvT.
[Graphical view]

Pfam

PF01571. GCV_T. 1 hit.
PF08669. GCV_T_C. 1 hit.
[Graphical view]

PIRSF

PIRSF006487. GcvT. 1 hit.

ProtoNet

Search...

Other Resources

DrugBank

DB00157. NADH.
DB00116. Tetrahydrofolic acid.

NextBio

1109.

SOURCE

Search...

Entry information

Entry name

GCST_HUMAN

Accession

Primary (citable) accession number: P48728

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	February 1, 1996
Last modified:	December 15, 2009
This is version 93 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.