P10768 (ESTD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
S-formylglutathione hydrolase
Short name=FGH
EC=3.1.2.12

Alternative name(s):
Esterase D
Methylumbelliferyl-acetate deacetylase
EC=3.1.1.56

Gene names

Name:

ESD

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	282 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Serine hydrolase involved in the detoxification of formaldehyde. Ref.10 Ref.11
Catalytic activity	S-formylglutathione + H2O = glutathione + formate. Ref.10 4-methylumbelliferyl acetate + H2O = 4-methylumbelliferone + acetate. Ref.10
Subunit structure	Homodimer.
Subcellular location	Cytoplasm. Cytoplasmic vesicle.
Polymorphism	There are two major electrophoretic isotypes. The sequence of the ESD*1 variant is shown.
Sequence similarities	Belongs to the esterase D family.
Sequence caution	The sequence CAI12225.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAI12226.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Cellular component	Cytoplasm Cytoplasmic vesicle
Coding sequence diversity	Polymorphism
Molecular function	Hydrolase Serine esterase
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Cellular component	Golgi apparatus Inferred from direct assay. Source: HPA cytoplasmic membrane-bounded vesicle Non-traceable author statement. Source: UniProtKB nucleus Inferred from direct assay. Source: HPA
Molecular function	S-formylglutathione hydrolase activity Inferred from electronic annotation. Source: EC carboxylesterase activity Non-traceable author statement Ref.2. Source: UniProtKB methylumbelliferyl-acetate deacetylase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 282

282

S-formylglutathione hydrolase

PRO_0000210339

Sites

Active site

149

1

Charge relay system Ref.14

Active site

226

1

Charge relay system Ref.14

Active site

260

1

Charge relay system Ref.14

Amino acid modifications

Modified residue

39

1

N6-acetyllysine Ref.12

Modified residue

200

1

N6-acetyllysine Ref.12

Modified residue

278

1

N6-acetyllysine Ref.12

Natural variations

Natural variant

190

1

G → E in allele ESD*2. Ref.15 Ref.16
Corresponds to variant rs9778 [ dbSNP | Ensembl ].

VAR_005202

Natural variant

257

1

G → D. Ref.4 Ref.6
Corresponds to variant rs15303 [ dbSNP | Ensembl ].

VAR_022275

Experimental info

Mutagenesis

54

1

L → A: 83% of wild-type activity. Ref.14

Mutagenesis

149

1

S → A: Loss of activity. Ref.14

Mutagenesis

149

1

S → T: 1.3% of wild-type activity. Ref.14

Mutagenesis

150

1

M → A: 62% increase in activity. Ref.14

Mutagenesis

226

1

D → A: 4.3% of wild-type activity. Ref.14

Mutagenesis

226

1

D → N: 9% of wild-type activity. Ref.14

Mutagenesis

260

1

H → A: 3% of wild-type activity. Ref.14

Mutagenesis

260

1

H → Q: 1.3% of wild-type activity. Ref.14

Secondary structure

1

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282

Helix Strand Turn

Details...

Beta strand

4 – 9

6

Beta strand

16 – 23

8

Turn

24 – 27

4

Beta strand

28 – 35

8

Helix

38 – 41

4

Beta strand

45 – 50

6

Helix

59 – 64

6

Helix

68 – 73

6

Beta strand

77 – 81

5

Helix

114 – 117

4

Helix

120 – 125

6

Helix

127 – 135

9

Beta strand

136 – 146

11

Helix

156 – 160

5

Beta strand

169 – 173

5

Helix

178 – 180

3

Turn

186 – 188

3

Helix

199 – 202

4

Helix

204 – 208

5

Beta strand

218 – 222

5

Helix

227 – 230

4

Helix

236 – 245

10

Beta strand

250 – 254

5

Helix

262 – 279

18

Sequences

	Sequence		Length	Mass (Da)
	P10768 [UniParc]. Last modified June 1, 1994. Version 2. Checksum: BFC20D5FA2BB0DCE	FASTA	282	31,463
	10 20 30 40 50 60 MALKQISSNK CFGGLQKVFE HDSVELNCKM KFAVYLPPKA ETGKCPALYW LSGLTCTEQN 70 80 90 100 110 120 FISKSGYHQS ASEHGLVVIA PDTSPRGCNI KGEDESWDFG TGAGFYVDAT EDPWKTNYRM 130 140 150 160 170 180 YSYVTEELPQ LINANFPVDP QRMSIFGHSM GGHGALICAL KNPGKYKSVS AFAPICNPVL 190 200 210 220 230 240 CPWGKKAFSG YLGTDQSKWK AYDATHLVKS YPGSQLDILI DQGKDDQFLL DGQLLPDNFI 250 260 270 280 AACTEKKIPV VFRLQEGYDH SYYFIATFIT DHIRHHAKYL NA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of the human esterase D gene, a genetic marker of retinoblastoma." Lee E.Y.-H.P., Lee W.-H. Proc. Natl. Acad. Sci. U.S.A. 83:6337-6341(1986) [PubMed: 3462698] [Abstract] Cited for: PRELIMINARY NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
[2]	"Human esterase D gene: complete cDNA sequence, genomic structure, and application in the genetic diagnosis of human retinoblastoma." Young L.-J.S., Lee E.Y.-H.P., To H., Bookstein R., Shew J.-Y., Donoso L.A., Sery T., Giblin M., Shields J.A., Lee W.-H. Hum. Genet. 79:137-141(1988) [PubMed: 3164702] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning." Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X., Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M. , Zhou J., Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L. Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000) [PubMed: 10931946] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Hypothalamus.
[4]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ASP-257.
[5]	"The DNA sequence and analysis of human chromosome 13." Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T. Nature 428:522-528(2004) [PubMed: 15057823] [Abstract] 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], VARIANT ASP-257. Tissue: Muscle.
[7]	Lubec G., Vishwanath V. Submitted (MAR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 65-86 AND 254-274, MASS SPECTROMETRY. Tissue: Brain and Cajal-Retzius cell.
[8]	"Cloning of the esterase D gene: a polymorphic gene probe closely linked to the retinoblastoma locus on chromosome 13." Squire J., Dryja T.P., Dunn J., Goddard A., Hofmann T., Musarella M., Willard H.F., Becker A.J., Gallie B.L., Phillips R.A. Proc. Natl. Acad. Sci. U.S.A. 83:6573-6577(1986) [PubMed: 3462714] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 150-186, PROTEIN SEQUENCE OF 150-175.
[9]	Tuchhida S., Ikemoto S., Kajii E. Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 168-200.
[10]	"Esterase D: a new human polymorphism." Hopkinson D.A., Mestriner M.A., Cortner J., Harris H. Ann. Hum. Genet. 37:119-137(1973) [PubMed: 4768551] [Abstract] Cited for: FUNCTION AS METHYLUMBELLIFERYL-ACETATE DEACETYLASE, CATALYTIC ACTIVITY.
[11]	"Identity of the polymorphisms for esterase D and S-formylglutathione hydrolase in red blood cells." Eiberg H., Mohr J. Hum. Genet. 74:174-175(1986) [PubMed: 3770744] [Abstract] Cited for: FUNCTION.
[12]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-39; LYS-200 AND LYS-278, MASS SPECTROMETRY.
[13]	"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].
[14]	"Crystal structure of human esterase D: a potential genetic marker of retinoblastoma." Wu D., Li Y., Song G., Zhang D., Shaw N., Liu Z.-J. FASEB J. 23:1441-1446(2009) [PubMed: 19126594] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS), MUTAGENESIS OF LEU-54; SER-149; MET-150; ASP-226 AND HIS-260, ACTIVE SITE.
[15]	"Molecular analysis of esterase D polymorphism." Tsuchida S., Fukui E., Ikemoto S. Hum. Genet. 93:255-258(1994) [PubMed: 7907313] [Abstract] Cited for: VARIANT GLU-190.
[16]	"Catalog of 680 variations among eight cytochrome p450 (CYP) genes, nine esterase genes, and two other genes in the Japanese population." Saito S., Iida A., Sekine A., Kawauchi S., Higuchi S., Ogawa C., Nakamura Y. J. Hum. Genet. 48:249-270(2003) [PubMed: 12721789] [Abstract] Cited for: VARIANT GLU-190.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M13450 mRNA. Translation: AAA52408.1. Sequence problems.
AF112219 mRNA. Translation: AAC99788.1.
BT007059 mRNA. Translation: AAP35708.1.
AL136958 Genomic DNA. Translation: CAI12225.1. Sequence problems.
AL136958 Genomic DNA. Translation: CAI12226.1. Sequence problems.
AL136958 Genomic DNA. Translation: CAI12228.1.
BC001169 mRNA. Translation: AAH01169.1.
AF052509 Genomic DNA. Translation: AAC06298.1.

IPI

IPI00411706.

PIR

A23543.

RefSeq

NP_001975.1. NM_001984.1.

UniGene

Hs.432491.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3FCX	X-ray	1.50	A/B	1-282	[»]

ProteinModelPortal

P10768.

SMR

P10768. Positions 3-281.

ModBase

Search...

Protein-protein interaction databases

IntAct

P10768. 2 interactions.

STRING

P10768.

Protein family/group databases

MEROPS

S09.990.

PTM databases

PhosphoSite

P10768.

Polymorphism databases

DMDM

544254.

2D gel databases

DOSAC-COBS-2DPAGE

P10768.

OGP

P10768.

REPRODUCTION-2DPAGE

IPI00411706.

UCD-2DPAGE

P10768.

Proteomic databases

PeptideAtlas

P10768.

PRIDE

P10768.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000378720; ENSP00000367992; ENSG00000139684.

GeneID

2098.

KEGG

hsa:2098.

UCSC

uc001vbn.1. human.

Organism-specific databases

CTD

2098.

GeneCards

GC13M047345.

H-InvDB

HIX0011302.

HGNC

HGNC:3465. ESD.

HPA

HPA039700.

MIM

133280. gene.

neXtProt

NX_P10768.

PharmGKB

PA27882.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG13560.

GeneTree

ENSGT00390000011864.

HOGENOM

HBG286713.

HOVERGEN

HBG001326.

InParanoid

P10768.

OMA

HLRFHAE.

OrthoDB

EOG4RFKT1.

PhylomeDB

P10768.

Gene expression databases

ArrayExpress

P10768.

Bgee

P10768.

CleanEx

HS_ESD.

Genevestigator

P10768.

GermOnline

ENSG00000139684. Homo sapiens.

Family and domain databases

InterPro

IPR000801. Esterase_put.
IPR014186. S-formylglutathione_hydrol.
[Graphical view]

KO

K01070.

PANTHER

PTHR10061. S-formylglutathione_hydrol. 1 hit.

Pfam

PF00756. Esterase. 1 hit.
[Graphical view]

TIGRFAMs

TIGR02821. FghA_ester_D. 1 hit.

ProtoNet

Search...

Other

DrugBank

DB00143. Glutathione.

NextBio

8487.

SOURCE

Search...

Entry information

Entry name

ESTD_HUMAN

Accession

Primary (citable) accession number: P10768
Secondary accession number(s): Q5TBU8 , Q5TBV0, Q5TBV2, Q9BVJ2

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	June 1, 1994
Last modified:	January 25, 2012
This is version 117 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.