Palmitoyl-protein thioesterase 1 precursor

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Reviewed, UniProtKB/Swiss-Prot P50897 (PPT1_HUMAN)

Last modified June 16, 2009. Version 95. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    Palmitoyl-protein thioesterase 1
      Short name=PPT-1
    EC=3.1.2.22
Alternative name(s):
    Palmitoyl-protein hydrolase 1

Gene names

Name:	PPT1
Synonyms:	PPT

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

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Protein attributes

Sequence length	306 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Removes thioester-linked fatty acyl groups such as palmitate from modified cysteine residues in proteins or peptides during lysosomal degradation. Prefers acyl chain lengths of 14 to 18 carbons.
Catalytic activity	Palmitoyl-protein + H₂O = palmitate + protein.
Subcellular location	Lysosome.
Involvement in disease	Defects in PPT1 are the cause of infantile neuronal ceroid lipofuscinosis 1 (CLN1) [MIM:256730]; also called infantile neuronal ceroid lipofuscinosis (INCL). The neuronal ceroid lipofuscinosis are a group of progressive neurodegenerative diseases characterized by the intracellular accumulation of autofluorescent lipopigment storage material in different patterns ultrastructurally. The lipopigment pattern seen most often in CLN1 is referred to as granular osmiophilic deposits (GROD). There is a core group of four major clinical forms, the infantile, the late-infantile, the juvenile, and the adult forms. The infantile forms are characterized by progressive visual impairment, seizure, motor disturbances, dementia and premature death (8-11 years of age). Ref.1 Ref.9 Ref.10 Defects in PPT1 are a cause of neuronal ceroid lipofuscinosis 4 (CLN4) [MIM:204300]; also known as adult type neuronal ceroid lipofuscinosis (NCL) or Kufs disease. Ref.11
Sequence similarities	Belongs to the palmitoyl-protein thioesterase family.

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Ontologies

Keywords
Biological process	Sensory transduction Vision
Cellular component	Lysosome
Coding sequence diversity	Polymorphism
Disease	Disease mutation Neuronal ceroid lipofuscinosis
Domain	Signal
Molecular function	Hydrolase
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	DNA fragmentation involved in apoptosis Inferred from direct assay. Source: UniProtKB brain development Ref.1 Inferred from mutant phenotype. Source: UniProtKB cofactor metabolic process Inferred from mutant phenotype. Source: UniProtKB cofactor transport Inferred from mutant phenotype. Source: UniProtKB lysosomal lumen acidification Inferred from mutant phenotype. Source: UniProtKB membrane raft organization Inferred from mutant phenotype. Source: UniProtKB negative regulation of cell growth Inferred from mutant phenotype. Source: UniProtKB negative regulation of neuron apoptosis Inferred from mutant phenotype. Source: UniProtKB neuron development Traceable author statement. Source: UniProtKB pinocytosis Inferred from mutant phenotype. Source: MGI positive regulation of pinocytosis Inferred from mutant phenotype. Source: UniProtKB positive regulation of receptor-mediated endocytosis Inferred from mutant phenotype. Source: UniProtKB protein catabolic process Non-traceable author statement. Source: UniProtKB protein depalmitoylation Inferred from direct assay. Source: UniProtKB protein transport Inferred from mutant phenotype. Source: UniProtKB receptor-mediated endocytosis Inferred from mutant phenotype. Source: MGI regulation of synapse structure and activity Non-traceable author statement. Source: UniProtKB response to stimulus Inferred from electronic annotation. Source: UniProtKB-KW sphingolipid catabolic process Traceable author statement. Source: UniProtKB visual perception Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	Golgi apparatus Ref.1 Inferred from direct assay. Source: UniProtKB axon Inferred from direct assay. Source: UniProtKB cytosol Inferred from sequence or structural similarity. Source: UniProtKB extracellular region Inferred from direct assay. Source: UniProtKB lysosome Inferred from direct assay. Source: UniProtKB membrane fraction Inferred from sequence or structural similarity. Source: UniProtKB membrane raft Inferred from direct assay. Source: UniProtKB nucleus Inferred from direct assay. Source: UniProtKB synaptic vesicle Inferred from direct assay. Source: UniProtKB
Molecular function	palmitoyl-(protein) hydrolase activity Ref.1 Inferred from direct assay. Source: UniProtKB palmitoyl-CoA hydrolase activity Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 27

By similarity

Chain

28 – 306

279

Palmitoyl-protein thioesterase 1

PRO_0000025550

Sites

Active site

115

By similarity

Active site

233

By similarity

Active site

289

By similarity

Amino acid modifications

Glycosylation

197

N-linked (GlcNAc...)

Glycosylation

212

N-linked (GlcNAc...)

Glycosylation

232

N-linked (GlcNAc...) Ref.6

Disulfide bond

45 ↔ 46

By similarity

Disulfide bond

96 ↔ 128

By similarity

Disulfide bond

152 ↔ 160

By similarity

Natural variations

Natural variant

H → Q in CLN1.

VAR_005548

Natural variant

G → E in CLN1.

VAR_005549

Natural variant

T → P in CLN1; juvenile onset. Ref.9

VAR_005550

Natural variant

D → G in CLN1; juvenile onset. Ref.9

VAR_005551

Natural variant

108

G → R in CLN4. Ref.11

VAR_018511

Natural variant

109

Y → D in CLN1.

VAR_005552

Natural variant

122

R → W in CLN1; seems to results in intracellular accumulation of the enzyme. Ref.1

VAR_005553

Natural variant

134

I → T: dbSNP rs1800205. Ref.10

VAR_005554

Natural variant

177

Q → E in CLN1.

VAR_005555

Natural variant

181

V → L in CLN1.

VAR_005556

Natural variant

181

V → M in CLN1.

VAR_005557

Natural variant

219

L → Q in CLN1; juvenile onset. Ref.9

VAR_005558

Natural variant

247

Y → H in CLN1.

VAR_005559

Natural variant

250

G → V in CLN1.

VAR_005560

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Sequences

Sequence

Length

Mass (Da)

Tools

P50897-1 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: 69F8083FD1C15E92
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FASTA

306

34,193

        10         20         30         40         50         60 
MASPGCLWLL AVALLPWTCA SRALQHLDPP APLPLVIWHG MGDSCCNPLS MGAIKKMVEK 

        70         80         90        100        110        120 
KIPGIYVLSL EIGKTLMEDV ENSFFLNVNS QVTTVCQALA KDPKLQQGYN AMGFSQGGQF 

       130        140        150        160        170        180 
LRAVAQRCPS PPMINLISVG GQHQGVFGLP RCPGESSHIC DFIRKTLNAG AYSKVVQERL 

       190        200        210        220        230        240 
VQAEYWHDPI KEDVYRNHSI FLADINQERG INESYKKNLM ALKKFVMVKF LNDSIVDPVD 

       250        260        270        280        290        300 
SEWFGFYRSG QAKETIPLQE TSLYTQDRLG LKEMDNAGQL VFLATEGDHL QLSEEWFYAH 


IIPFLG

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mutations in the palmitoyl protein thioesterase gene causing infantile neuronal ceroid lipofuscinosis." Vesa J., Hellsten E., Verkruyse L.A., Camp L.A., Rapola J., Santavuori P., Hofmann S.L., Peltonen L. Nature 376:584-587(1995) [PubMed: 7637805] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], VARIANT CLN1 TRP-122. Tissue: Brain.
[2]	"Didemnin binds to the protein palmitoyl thioesterase responsible for infantile neuronal ceroid lipofuscinosis." Crews C.M., Lane W.S., Schreiber S.L. Proc. Natl. Acad. Sci. U.S.A. 93:4316-4319(1996) [PubMed: 8633062] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"cDNA and genomic cloning of human palmitoyl-protein thioesterase (PPT), the enzyme defective in infantile neuronal ceroid lipofuscinosis." Schriner J.E., Yi W., Hofmann S.L. Genomics 34:317-322(1996) [PubMed: 8786130] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"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]. Tissue: Prostate.
[5]	"Lipid thioesters derived from acylated proteins accumulate in infantile neuronal ceroid lipofuscinosis: correction of the defect in lymphoblasts by recombinant palmitoyl-protein thioesterase." Lu J.-Y., Verkruyse L.A., Hofmann S.L. Proc. Natl. Acad. Sci. U.S.A. 93:10046-10050(1996) [PubMed: 8816748] [Abstract] Cited for: CHARACTERIZATION.
[6]	"Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry." Zhang H., Li X.-J., Martin D.B., Aebersold R. Nat. Biotechnol. 21:660-666(2003) [PubMed: 12754519] [Abstract] Cited for: GLYCOSYLATION AT ASN-232.
[7]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[8]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-197; ASN-212 AND ASN-232, MASS SPECTROMETRY. Tissue: Liver.
[9]	"Mutations in the palmitoyl-protein thioesterase gene (PPT; CLN1) causing juvenile neuronal ceroid lipofuscinosis with granular osmiophilic deposits." Mitchison H.M., Hofmann S.L., Becerra C.H.R., Munroe P.B., Lake B.D., Crow Y.J., Stephenson J.B.P., Williams R.E., Hofman I.L., Taschner P.E.M., Martin J.-J., Philippart M., Andermann E., Andermann F., Mole S.E., Gardiner R.M., O'Rawe A.M. Hum. Mol. Genet. 7:291-297(1998) [PubMed: 9425237] [Abstract] Cited for: VARIANTS CLN1 PRO-75; GLY-79 AND GLN-219.
[10]	"Molecular genetics of palmitoyl-protein thioesterase deficiency in the U.S." Das A.K., Becerra C.H.R., Yi W., Lu J.-Y., Siakotos A.N., Wisniewski K.E., Hofmann S.L. J. Clin. Invest. 102:361-370(1998) [PubMed: 9664077] [Abstract] Cited for: VARIANTS CLN1, VARIANT THR-134.
[11]	"Adult neuronal ceroid lipofuscinosis with palmitoyl-protein thioesterase deficiency: first adult-onset patients of a childhood disease." van Diggelen O.P., Thobois S., Tilikete C., Zabot M.-T., Keulemans J.L.M., van Bunderen P.A., Taschner P.E.M., Losekoot M., Voznyi Y.V. Ann. Neurol. 50:269-272(2001) [PubMed: 11506414] [Abstract] Cited for: VARIANT CLN4 ARG-108.
+	Additional computationally mapped references.

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Web resources

NCL CLN1

Neural Ceroid Lipofuscinoses mutation db

Mutations of the PPT1 gene

Retina International's Scientific Newsletter

GeneReviews

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Cross-references

Sequence databases

L42809 Genomic DNA. Translation: AAA85337.1.
U44772 mRNA. Translation: AAB06236.1.
AF022211

AF022210 Genomic DNA. Translation: AAB72224.1.
BC008426 mRNA. Translation: AAH08426.1.

IPI

IPI00002412.

PIR

I58097.

RefSeq

NP_000301.1.

UniGene

Hs.3873

3D structure databases

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3GRO	X-ray	2.53	A/B	22-306	[»]

SMR

P50897. Positions 28-305.

ModBase

Search...

PTM databases

PhosphoSite

P50897.

Proteomic databases

PRIDE

P50897.

Genome annotation databases

Ensembl

ENSG00000131238. Homo sapiens. [Contig view]

GeneID

5538.

KEGG

hsa:5538.

Organism-specific databases

GeneCards

GC01M040310.

H-InvDB

HIX0000468.

HGNC

HGNC:9325. PPT1.

MIM

204300. phenotype.
256730. phenotype.
600722. gene.

Orphanet

216. Ceroid lipofuscinosis, neuronal.
79263. Infantile neuronal ceroid lipofuscinosis.

PharmGKB

PA33688.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P50897.

OMA

P50897. IWHGMGD.

Enzyme and pathway databases

BRENDA

3.1.2.22. 247.

Gene expression databases

Bgee

P50897.

CleanEx

HS_PPT1.

GermOnline

ENSG00000131238. Homo sapiens.

Family and domain databases

InterPro

IPR002472. Palm_thioest.
[Graphical view]

Pfam

PF02089. Palm_thioest. 1 hit.
[Graphical view]

PRINTS

PR00414. PPTHIESTRASE.

ProtoNet

Search...

Other Resources

NextBio

21454.

SOURCE

Search...

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Entry information

Entry name

PPT1_HUMAN

Accession

Primary (citable) accession number: P50897

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	June 16, 2009
This is version 95 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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