Human Gene TPP1 (ENST00000299427.12_9) from GENCODE V47lift37
  Description: tripeptidyl peptidase 1 (from RefSeq NM_000391.4)
Gencode Transcript: ENST00000299427.12_9
Gencode Gene: ENSG00000166340.18_19
Transcript (Including UTRs)
   Position: hg19 chr11:6,633,999-6,640,653 Size: 6,655 Total Exon Count: 13 Strand: -
Coding Region
   Position: hg19 chr11:6,635,777-6,640,631 Size: 4,855 Coding Exon Count: 13 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesGeneReviewsModel Information
Methods
Data last updated at UCSC: 2024-08-22 23:36:26

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr11:6,633,999-6,640,653)mRNA (may differ from genome)Protein (563 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
HGNCMalacardsMGIOMIMPubMedReactome
UniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: TPP1_HUMAN
DESCRIPTION: RecName: Full=Tripeptidyl-peptidase 1; Short=TPP-1; EC=3.4.14.9; AltName: Full=Cell growth-inhibiting gene 1 protein; AltName: Full=Lysosomal pepstatin-insensitive protease; Short=LPIC; AltName: Full=Tripeptidyl aminopeptidase; AltName: Full=Tripeptidyl-peptidase I; Short=TPP-I; Flags: Precursor;
FUNCTION: Lysosomal serine protease with tripeptidyl-peptidase I activity. May act as a non-specific lysosomal peptidase which generates tripeptides from the breakdown products produced by lysosomal proteinases. Requires substrates with an unsubstituted N-terminus (By similarity).
CATALYTIC ACTIVITY: Release of an N-terminal tripeptide from a polypeptide, but also has endopeptidase activity.
COFACTOR: Binds 1 calcium ion per subunit.
SUBUNIT: Monomer.
SUBCELLULAR LOCATION: Lysosome. Melanosome. Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV.
TISSUE SPECIFICITY: Detected in all tissues examined with highest levels in heart and placenta and relatively similar levels in other tissues.
PTM: Activated by autocatalytic proteolytical processing upon acidification. N-glycosylation is required for processing and activity.
DISEASE: Defects in TPP1 are the cause of neuronal ceroid lipofuscinosis type 2 (CLN2) [MIM:204500]. A form of neuronal ceroid lipofuscinosis. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material, and clinically by seizures, dementia, visual loss, and/or cerebral atrophy. The lipopigment pattern seen most often in CLN2 consists of curvilinear profiles.
SIMILARITY: Belongs to the peptidase S53 family.
SEQUENCE CAUTION: Sequence=AAM08412.1; Type=Miscellaneous discrepancy; Note=Incorrectly indicated as originating from bovine; Sequence=AAQ88866.1; Type=Frameshift; Positions=551;
WEB RESOURCE: Name=NCL CLN2; Note=Neural Ceroid Lipofuscinoses mutation db; URL="http://www.ucl.ac.uk/ncl/cln2.shtml";
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/TPP1";
WEB RESOURCE: Name=Mendelian genes trieptidyl peptidase I (TPP1); Note=Leiden Open Variation Database (LOVD); URL="http://www.lovd.nl/TPP1";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: TPP1
Diseases sorted by gene-association score: ceroid lipofuscinosis, neuronal, 2* (1714), spinocerebellar ataxia, autosomal recessive 7* (1697), neuronal ceroid lipofuscinosis* (451), neuronal ceroid-lipofuscinoses* (58), ceroid lipofuscinosis, neuronal, 3 (16), spinocerebellar ataxia 7 (13), lysosomal storage disease (11), adult neuronal ceroid lipofuscinosis (7), ceroid lipofuscinosis, neuronal, 1 (7), lipid storage disease (5)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 97.18 RPKM in Adrenal Gland
Total median expression: 1758.26 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -2.1022-0.095 Picture PostScript Text
3' UTR -349.601778-0.197 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR015366 - Peptidase_S53_propep
IPR000209 - Peptidase_S8/S53
IPR009020 - Prot_inh_propept

Pfam Domains:
PF00082 - Subtilase family
PF09286 - Pro-kumamolisin, activation domain

SCOP Domains:
52743 - Subtilisin-like
54897 - Protease propeptides/inhibitors

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1R60 - Model 3EDY - X-ray MuPIT 3EE6 - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on O14773
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGDEnsembl   
      
      

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004175 endopeptidase activity
GO:0004252 serine-type endopeptidase activity
GO:0005515 protein binding
GO:0008233 peptidase activity
GO:0008236 serine-type peptidase activity
GO:0008240 tripeptidyl-peptidase activity
GO:0016787 hydrolase activity
GO:0042277 peptide binding
GO:0046872 metal ion binding

Biological Process:
GO:0006508 proteolysis
GO:0006629 lipid metabolic process
GO:0007040 lysosome organization
GO:0007399 nervous system development
GO:0007417 central nervous system development
GO:0030163 protein catabolic process
GO:0030855 epithelial cell differentiation
GO:0036498 IRE1-mediated unfolded protein response
GO:0043171 peptide catabolic process
GO:0045453 bone resorption
GO:0050885 neuromuscular process controlling balance

Cellular Component:
GO:0005764 lysosome
GO:0042470 melanosome
GO:0043202 lysosomal lumen
GO:0070062 extracellular exosome


-  Descriptions from all associated GenBank mRNAs
  AF017456 - Homo sapiens lysosomal pepstatin insensitive protease (CLN2) mRNA, complete cds.
AY268890 - Homo sapiens growth-inhibiting protein 1 mRNA, complete cds.
LF207832 - JP 2014500723-A/15335: Polycomb-Associated Non-Coding RNAs.
LF369396 - JP 2014500723-A/176899: Polycomb-Associated Non-Coding RNAs.
JD251015 - Sequence 232039 from Patent EP1572962.
JD109704 - Sequence 90728 from Patent EP1572962.
JD040317 - Sequence 21341 from Patent EP1572962.
JD423027 - Sequence 404051 from Patent EP1572962.
JD355104 - Sequence 336128 from Patent EP1572962.
JD538841 - Sequence 519865 from Patent EP1572962.
JD250734 - Sequence 231758 from Patent EP1572962.
JD512350 - Sequence 493374 from Patent EP1572962.
JD301778 - Sequence 282802 from Patent EP1572962.
JD362608 - Sequence 343632 from Patent EP1572962.
LF369397 - JP 2014500723-A/176900: Polycomb-Associated Non-Coding RNAs.
JD048777 - Sequence 29801 from Patent EP1572962.
BC014863 - Homo sapiens tripeptidyl peptidase I, mRNA (cDNA clone MGC:21297 IMAGE:4385872), complete cds.
AK222538 - Homo sapiens mRNA for tripeptidyl-peptidase I precursor variant, clone: adSH01606.
AY358502 - Homo sapiens clone DNA39520 CLN2 (UNQ267) mRNA, complete cds.
JD298230 - Sequence 279254 from Patent EP1572962.
LF369398 - JP 2014500723-A/176901: Polycomb-Associated Non-Coding RNAs.
JD248945 - Sequence 229969 from Patent EP1572962.
JD419107 - Sequence 400131 from Patent EP1572962.
JD248869 - Sequence 229893 from Patent EP1572962.
JD297489 - Sequence 278513 from Patent EP1572962.
JD565328 - Sequence 546352 from Patent EP1572962.
AK293518 - Homo sapiens cDNA FLJ59472 complete cds, highly similar to Tripeptidyl-peptidase 1 precursor (EC3.4.14.9).
JD326205 - Sequence 307229 from Patent EP1572962.
JD314835 - Sequence 295859 from Patent EP1572962.
JD252928 - Sequence 233952 from Patent EP1572962.
JD291965 - Sequence 272989 from Patent EP1572962.
AK300998 - Homo sapiens cDNA FLJ59997 complete cds, highly similar to Tripeptidyl-peptidase 1 precursor (EC 3.4.14.9).
JD221123 - Sequence 202147 from Patent EP1572962.
AK222499 - Homo sapiens mRNA for tripeptidyl-peptidase I precursor variant, clone: adSE00635.
JD417004 - Sequence 398028 from Patent EP1572962.
AK303323 - Homo sapiens cDNA FLJ58558 complete cds, highly similar to Tripeptidyl-peptidase 1 precursor (EC 3.4.14.9).
AK299703 - Homo sapiens cDNA FLJ57277 complete cds, highly similar to Tripeptidyl-peptidase 1 precursor (EC 3.4.14.9).
LF369399 - JP 2014500723-A/176902: Polycomb-Associated Non-Coding RNAs.
JD354585 - Sequence 335609 from Patent EP1572962.
AK295801 - Homo sapiens cDNA FLJ56402 complete cds, highly similar to Tripeptidyl-peptidase 1 precursor (EC 3.4.14.9).
JD529530 - Sequence 510554 from Patent EP1572962.
JD157507 - Sequence 138531 from Patent EP1572962.
AK312388 - Homo sapiens cDNA, FLJ92718, highly similar to Homo sapiens tripeptidyl peptidase I (TPP1), mRNA.
KJ896618 - Synthetic construct Homo sapiens clone ccsbBroadEn_06012 TPP1 gene, encodes complete protein.
KR709436 - Synthetic construct Homo sapiens clone CCSBHm_00002166 TPP1 (TPP1) mRNA, encodes complete protein.
KR709437 - Synthetic construct Homo sapiens clone CCSBHm_00002173 TPP1 (TPP1) mRNA, encodes complete protein.
KR709438 - Synthetic construct Homo sapiens clone CCSBHm_00002204 TPP1 (TPP1) mRNA, encodes complete protein.
DQ891682 - Synthetic construct clone IMAGE:100004312; FLH179244.01X; RZPDo839E05130D tripeptidyl peptidase I (TPP1) gene, encodes complete protein.
DQ894867 - Synthetic construct Homo sapiens clone IMAGE:100009327; FLH179240.01L; RZPDo839E05129D tripeptidyl peptidase I (TPP1) gene, encodes complete protein.
LF369400 - JP 2014500723-A/176903: Polycomb-Associated Non-Coding RNAs.
CU677099 - Synthetic construct Homo sapiens gateway clone IMAGE:100020400 5' read TPP1 mRNA.
LF369401 - JP 2014500723-A/176904: Polycomb-Associated Non-Coding RNAs.
AK293741 - Homo sapiens cDNA FLJ60442 complete cds, highly similar to Tripeptidyl-peptidase 1 precursor (EC 3.4.14.9).
LF369402 - JP 2014500723-A/176905: Polycomb-Associated Non-Coding RNAs.
LF369404 - JP 2014500723-A/176907: Polycomb-Associated Non-Coding RNAs.
JD314021 - Sequence 295045 from Patent EP1572962.
MA604973 - JP 2018138019-A/176899: Polycomb-Associated Non-Coding RNAs.
MA604974 - JP 2018138019-A/176900: Polycomb-Associated Non-Coding RNAs.
MA604975 - JP 2018138019-A/176901: Polycomb-Associated Non-Coding RNAs.
MA604976 - JP 2018138019-A/176902: Polycomb-Associated Non-Coding RNAs.
MA604977 - JP 2018138019-A/176903: Polycomb-Associated Non-Coding RNAs.
MA604978 - JP 2018138019-A/176904: Polycomb-Associated Non-Coding RNAs.
MA604979 - JP 2018138019-A/176905: Polycomb-Associated Non-Coding RNAs.
MA604981 - JP 2018138019-A/176907: Polycomb-Associated Non-Coding RNAs.
MA443409 - JP 2018138019-A/15335: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein O14773 (Reactome details) participates in the following event(s):

R-HSA-381038 XBP1(S) activates chaperone genes
R-HSA-381070 IRE1alpha activates chaperones
R-HSA-381119 Unfolded Protein Response (UPR)
R-HSA-392499 Metabolism of proteins

-  Other Names for This Gene
  Alternate Gene Symbols: CLN2, ENST00000299427.1, ENST00000299427.10, ENST00000299427.11, ENST00000299427.2, ENST00000299427.3, ENST00000299427.4, ENST00000299427.5, ENST00000299427.6, ENST00000299427.7, ENST00000299427.8, ENST00000299427.9, GIG1, NM_000391, O14773, Q53HT1, Q5JAK6, Q6UX56, Q71JP6, Q96C37, TPP1_HUMAN, uc317mjq.1, uc317mjq.2, UNQ267/PRO304
UCSC ID: ENST00000299427.12_9
RefSeq Accession: NM_000391.4
Protein: O14773 (aka TPP1_HUMAN)

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene TPP1:
dystonia-ov (Hereditary Dystonia Overview)

-  Gene Model Information
  Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.