Reviewed, UniProtKB/Swiss-Prot P50897 (PPT1_HUMAN)

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

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.

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 + H(2)O = 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). 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.
Sequence similarities	Belongs to the palmitoyl-protein thioesterase family.

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	Glycoprotein
Gene Ontology (GO)
Biological process	DNA fragmentation during 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 positive regulation of pinocytosis Inferred from mutant phenotype. Source: UniProtKB positive regulation of receptor-mediated endocytosis Inferred from mutant phenotype. Source: UniProtKB protein depalmitoylation Inferred from direct assay. Source: UniProtKB protein transport Inferred from mutant phenotype. Source: UniProtKB regulation of synapse structure and activity Non-traceable author statement. Source: UniProtKB 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 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...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 27	27	By similarity
	Chain	28 – 306	279	Palmitoyl-protein thioesterase 1		PRO_0000025550
Sites
	Active site	115	1	By similarity
	Active site	233	1	By similarity
	Active site	289	1	By similarity
Amino acid modifications
	Glycosylation	197	1	N-linked (GlcNAc...) Potential
	Glycosylation	212	1	N-linked (GlcNAc...) Potential
	Glycosylation	232	1	N-linked (GlcNAc...)
	Disulfide bond	45 ↔ 46		By similarity
	Disulfide bond	96 ↔ 128		By similarity
	Disulfide bond	152 ↔ 160		By similarity
Natural variations
	Natural variant	39	1	H → Q in CLN1.		VAR_005548
	Natural variant	42	1	G → E in CLN1.		VAR_005549
	Natural variant	75	1	T → P in CLN1; juvenile onset.		VAR_005550
	Natural variant	79	1	D → G in CLN1; juvenile onset.		VAR_005551
	Natural variant	108	1	G → R in CLN4.		VAR_018511
	Natural variant	109	1	Y → D in CLN1.		VAR_005552
	Natural variant	122	1	R → W in CLN1; seems to results in intracellular accumulation of the enzyme.		VAR_005553
	Natural variant	134	1	I → T: dbSNP rs1800205.		VAR_005554
	Natural variant	177	1	Q → E in CLN1.		VAR_005555
	Natural variant	181	1	V → L in CLN1.		VAR_005556
	Natural variant	181	1	V → M in CLN1.		VAR_005557
	Natural variant	219	1	L → Q in CLN1; juvenile onset.		VAR_005558
	Natural variant	247	1	Y → H in CLN1.		VAR_005559
	Natural variant	250	1	G → V in CLN1.		VAR_005560

Sequences

	Sequence		Length	Mass (Da)
	P50897-1 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 69F8083FD1C15E92	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

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]	"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.
[8]	"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.
[9]	"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.

Web resources

NCL CLN1

Neural Ceroid Lipofuscinoses mutation db

Mutations of the PPT1 gene

Retina International's Scientific Newsletter

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	L42809 Genomic DNA. Translation: AAA85337.1. U44772 mRNA. Translation: AAB06236.1. AF022211 , AF022203, AF022204, AF022205, AF022206, AF022207, AF022208, AF022209, AF022210 Genomic DNA. Translation: AAB72224.1. BC008426 mRNA. Translation: AAH08426.1.
PIR	I58097.
RefSeq	NP_000301.1.
UniGene	Hs.3873
3D structure databases
HSSP	HSSP built from PDB template 1EI9 based on UniProtKB P45478.
SMR	P50897. Positions 28-305.
ModBase	Search...
Genome annotation databases
Ensembl	ENSG00000131238. Homo sapiens. [Contig view]
GeneID	5538.
KEGG	hsa:5538.
Organism-specific databases
H-InvDB	HIX0000468.
HGNC	HGNC:9325. PPT1.
MIM	204300. phenotype. 256730. phenotype. 600722. gene.
Orphanet	216. Ceroid lipofuscinosis, neuronal.
PharmGKB	PA33688.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOVERGEN	P50897.
Gene expression databases
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...

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:	November 25, 2008
This is version 87 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)