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Protein

Lysosomal thioesterase PPT2

Gene

PPT2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Removes thioester-linked fatty acyl groups from various substrates including S-palmitoyl-CoA. Has the highest S-thioesterase activity for the acyl groups palmitic and myristic acid followed by other short- and long-chain acyl substrates. However, because of structural constraints, is unable to remove palmitate from peptides or proteins.3 Publications

Caution

Was originally referred as a palmitoyl-protein thioesterase (palmitoyl-protein hydrolase).1 Publication

Kineticsi

  1. KM=67 µM for S-palmitoyl-CoA1 Publication
  2. KM=37 µM for S-palmitoyl-N-acetylcysteamine1 Publication
  3. KM=117 µM for 4-methylumbelliferyl-6-S-palmitoyl-beta-D-glucopyranoside1 Publication
  1. Vmax=1.7 µmol/min/mg enzyme toward S-palmitoyl-CoA1 Publication
  2. Vmax=3.3 µmol/min/mg enzyme toward S-palmitoyl-N-acetylcysteamine1 Publication
  3. Vmax=0.43 µmol/min/mg enzyme toward 4-methylumbelliferyl-6-S-palmitoyl-beta-D-glucopyranoside1 Publication

pH dependencei

Optimum pH is 7.0.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei111Nucleophile1
Active sitei2281
Active sitei2831

GO - Molecular functioni

  • palmitoyl-(protein) hydrolase activity Source: InterPro
  • palmitoyl hydrolase activity Source: UniProtKB
  • thiolester hydrolase activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionHydrolase

Enzyme and pathway databases

ReactomeiR-HSA-75105 Fatty acyl-CoA biosynthesis

Protein family/group databases

ESTHERihuman-PPT2 Palmitoyl-protein_thioesterase

Names & Taxonomyi

Protein namesi
Recommended name:
Lysosomal thioesterase PPT2 (EC:3.1.2.-)
Short name:
PPT-2
Alternative name(s):
S-thioesterase G14
Gene namesi
Name:PPT2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000221988.12
HGNCiHGNC:9326 PPT2
MIMi603298 gene
neXtProtiNX_Q9UMR5

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Lysosome

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi111S → A: Abolishes enzymatic activity. 1 Publication1
Mutagenesisi228D → A: Abolishes enzymatic activity. 1 Publication1
Mutagenesisi283H → A: Abolishes enzymatic activity. 1 Publication1
Mutagenesisi287H → A: No effect on enzymatic activity. 1 Publication1

Organism-specific databases

DisGeNETi9374
OpenTargetsiENSG00000221988
ENSG00000258388
PharmGKBiPA33689

Chemistry databases

ChEMBLiCHEMBL2189137

Polymorphism and mutation databases

BioMutaiPPT2
DMDMi296453016

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 27Sequence analysisAdd BLAST27
ChainiPRO_000002555428 – 302Lysosomal thioesterase PPT2Add BLAST275

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi60N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi109 ↔ 1171 Publication
Disulfide bondi165 ↔ 1761 Publication
Glycosylationi190N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi206N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi245N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi276 ↔ 2961 Publication
Glycosylationi289N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ9UMR5
PeptideAtlasiQ9UMR5
PRIDEiQ9UMR5
ProteomicsDBi85198
85199 [Q9UMR5-2]

PTM databases

iPTMnetiQ9UMR5

Expressioni

Tissue specificityi

Broadly expressed, with highest levels in skeletal muscle.1 Publication

Gene expression databases

BgeeiENSG00000221988
ExpressionAtlasiQ9UMR5 baseline and differential
GenevisibleiQ9UMR5 HS

Interactioni

Protein-protein interaction databases

BioGridi114775, 37 interactors
STRINGi9606.ENSP00000354608

Structurei

Secondary structure

1302
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi39 – 42Combined sources4
Helixi49 – 52Combined sources4
Helixi53 – 62Combined sources10
Beta strandi68 – 70Combined sources3
Helixi77 – 80Combined sources4
Helixi83 – 100Combined sources18
Beta strandi105 – 110Combined sources6
Helixi112 – 123Combined sources12
Beta strandi129 – 136Combined sources8
Helixi147 – 152Combined sources6
Helixi158 – 165Combined sources8
Helixi170 – 172Combined sources3
Helixi175 – 178Combined sources4
Helixi185 – 191Combined sources7
Helixi195 – 198Combined sources4
Helixi207 – 214Combined sources8
Beta strandi218 – 224Combined sources7
Beta strandi229 – 233Combined sources5
Helixi234 – 238Combined sources5
Helixi251 – 253Combined sources3
Helixi255 – 258Combined sources4
Turni259 – 262Combined sources4
Helixi264 – 269Combined sources6
Beta strandi273 – 277Combined sources5
Turni283 – 287Combined sources5
Helixi290 – 296Combined sources7
Helixi298 – 300Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1PJAX-ray2.70A1-302[»]
ProteinModelPortaliQ9UMR5
SMRiQ9UMR5
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9UMR5

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG2541 Eukaryota
COG1075 LUCA
GeneTreeiENSGT00530000063368
HOVERGENiHBG019159
InParanoidiQ9UMR5
KOiK01074
OMAiISHTAWH
OrthoDBiEOG09370EJN
PhylomeDBiQ9UMR5
TreeFamiTF323926

Family and domain databases

Gene3Di3.40.50.1820, 1 hit
InterProiView protein in InterPro
IPR029058 AB_hydrolase
IPR002472 Palm_thioest
IPR030295 PPT2
PANTHERiPTHR11247:SF27 PTHR11247:SF27, 1 hit
PfamiView protein in Pfam
PF02089 Palm_thioest, 1 hit
PRINTSiPR00414 PPTHIESTRASE
SUPFAMiSSF53474 SSF53474, 1 hit

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9UMR5-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MLGLCGQRLP AAWVLLLLPF LPLLLLAAPA PHRASYKPVI VVHGLFDSSY
60 70 80 90 100
SFRHLLEYIN ETHPGTVVTV LDLFDGRESL RPLWEQVQGF REAVVPIMAK
110 120 130 140 150
APQGVHLICY SQGGLVCRAL LSVMDDHNVD SFISLSSPQM GQYGDTDYLK
160 170 180 190 200
WLFPTSMRSN LYRICYSPWG QEFSICNYWH DPHHDDLYLN ASSFLALING
210 220 230 240 250
ERDHPNATVW RKNFLRVGHL VLIGGPDDGV ITPWQSSFFG FYDANETVLE
260 270 280 290 300
MEEQLVYLRD SFGLKTLLAR GAIVRCPMAG ISHTAWHSNR TLYETCIEPW

LS
Length:302
Mass (Da):34,225
Last modified:May 18, 2010 - v4
Checksum:iE242D677970B4BEA
GO
Isoform 2 (identifier: Q9UMR5-2) [UniParc]FASTAAdd to basket
Also known as: I

The sequence of this isoform differs from the canonical sequence as follows:
     256-300: VYLRDSFGLK...TLYETCIEPW → PARPTHQSEL...ESWGPGLSCA

Note: Catalytically inactive due to lack of His-283. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »
Length:301
Mass (Da):34,055
Checksum:i37EC25978B3FE96E
GO
Isoform 3 (identifier: Q9UMR5-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MKSCGSM

Note: No experimental confirmation available.
Show »
Length:308
Mass (Da):34,819
Checksum:iE83460052465B3A4
GO

Sequence cautioni

The sequence CAG38577 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti189L → P in CAG38577 (Ref. 4) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0271075C → W10 PublicationsCorresponds to variant dbSNP:rs3134604Ensembl.1
Natural variantiVAR_02710834A → E3 PublicationsCorresponds to variant dbSNP:rs3096696Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0540271M → MKSCGSM in isoform 3. 1 Publication1
Alternative sequenceiVSP_005188256 – 300VYLRD…CIEPW → PARPTHQSELLLLRLVCLKP PRRKKPACRVQRQSESWGPG LSCA in isoform 2. 2 PublicationsAdd BLAST45

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF020543 mRNA Translation: AAB80730.1
AF020544 mRNA Translation: AAB80731.1
Y17958 mRNA Translation: CAB46981.1
AL110128 mRNA Translation: CAB53659.1
CR533546 mRNA Translation: CAG38577.1 Different initiation.
AK292729 mRNA Translation: BAF85418.1
U89336 Genomic DNA Translation: AAB47495.1
AL662828 Genomic DNA Translation: CAI17424.1
AL662828 Genomic DNA Translation: CAI17426.2
AL662828 Genomic DNA Translation: CAM24823.1
AL662828 Genomic DNA Translation: CAM24825.1
AL662884 Genomic DNA Translation: CAI18342.1
AL662884 Genomic DNA Translation: CAI18344.1
AL662884 Genomic DNA Translation: CAI41763.1
AL845464 Genomic DNA Translation: CAI41797.1
AL845464 Genomic DNA Translation: CAI41798.1
AL845464 Genomic DNA Translation: CAI41799.1
AL845464 Genomic DNA Translation: CAM25714.1
BX284686 Genomic DNA Translation: CAM26213.1
BX284686 Genomic DNA Translation: CAM26215.1
BX284686 Genomic DNA Translation: CAM26216.1
BX284686 Genomic DNA Translation: CAM26218.1
BX927239 Genomic DNA Translation: CAQ06588.1
BX927239 Genomic DNA Translation: CAQ06590.1
CR753803 Genomic DNA Translation: CAQ09561.1
CR933878 Genomic DNA Translation: CAQ09617.1
CR933878 Genomic DNA Translation: CAQ09619.1
CR812478 Genomic DNA Translation: CAQ10692.1
CR812478 Genomic DNA Translation: CAQ10694.1
CH471081 Genomic DNA Translation: EAX03597.1
CH471081 Genomic DNA Translation: EAX03591.1
BC001355 mRNA Translation: AAH01355.1
CCDSiCCDS4740.1 [Q9UMR5-3]
CCDS4742.1 [Q9UMR5-1]
RefSeqiNP_001191032.1, NM_001204103.1 [Q9UMR5-1]
NP_005146.4, NM_005155.6 [Q9UMR5-1]
NP_619731.2, NM_138717.2 [Q9UMR5-3]
UniGeneiHs.332138
Hs.731888

Genome annotation databases

EnsembliENST00000324816; ENSP00000320528; ENSG00000221988 [Q9UMR5-1]
ENST00000361568; ENSP00000354608; ENSG00000221988 [Q9UMR5-3]
ENST00000375137; ENSP00000364279; ENSG00000221988 [Q9UMR5-1]
ENST00000375143; ENSP00000364285; ENSG00000221988 [Q9UMR5-1]
ENST00000383301; ENSP00000372789; ENSG00000206329
ENST00000395523; ENSP00000378894; ENSG00000221988 [Q9UMR5-1]
ENST00000412651; ENSP00000416505; ENSG00000236649
ENST00000414356; ENSP00000398462; ENSG00000168452
ENST00000415972; ENSP00000408333; ENSG00000228116
ENST00000423347; ENSP00000406219; ENSG00000231618
ENST00000433748; ENSP00000410001; ENSG00000206256
ENST00000476214; ENSP00000432308; ENSG00000168452
ENST00000480383; ENSP00000432502; ENSG00000236649
ENST00000483565; ENSP00000431928; ENSG00000231618
ENST00000488579; ENSP00000434992; ENSG00000236649
ENST00000490624; ENSP00000433323; ENSG00000168452
ENST00000493809; ENSP00000436963; ENSG00000227600
ENST00000496937; ENSP00000432964; ENSG00000231618
ENST00000527704; ENSP00000433061; ENSG00000227600
GeneIDi9374
KEGGihsa:9374
UCSCiuc003nzw.4 human [Q9UMR5-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiPPT2_HUMAN
AccessioniPrimary (citable) accession number: Q9UMR5
Secondary accession number(s): A2ABC9
, A2ABD1, A2ARM7, A2BFH7, A2BFH9, A2BFI2, A8K9L4, B0S868, G8JLE1, O14799, Q0P6K0, Q5JP13, Q5JP14, Q5JQF0, Q5SSX4, Q5SSX5, Q5SSX6, Q5STJ4, Q5STJ5, Q5STJ6, Q6FI80, Q99945
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 5, 2002
Last sequence update: May 18, 2010
Last modified: June 20, 2018
This is version 154 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

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