Tripeptidyl peptidase I

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Tripeptidyl peptidase I
3EE6.png
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols TPP1 ; CLN2; LPIC; SCAR7; TPP-1
External IDs OMIM607998 MGI1336194 HomoloGene335 GeneCards: TPP1 Gene
EC number 3.4.14.9
RNA expression pattern
PBB GE TPP1 200743 s at tn.png
PBB GE TPP1 200742 s at tn.png
PBB GE TPP1 214196 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 1200 12751
Ensembl ENSG00000166340 ENSMUSG00000030894
UniProt O14773 O89023
RefSeq (mRNA) NM_000391 NM_009906
RefSeq (protein) NP_000382 NP_034036
Location (UCSC) Chr 11:
6.63 – 6.64 Mb
Chr 7:
105.74 – 105.75 Mb
PubMed search [1] [2]

Tripeptidyl-peptidase 1, also known as Lysosomal pepstatin-insensitive protease, is an enzyme that in humans is encoded by the TPP1 gene.[1][2]

Gene[edit]

The human gene TPP1 encodes a member of the sedolisin family of serine proteases. The human gene has 13 Exons and locates at the chromosome band 11p15.[2]

Structure[edit]

The human tripeptidyl-peptidase 1 is 61kDa in size and composed of 563 amino acids. An isoform of 34.5kDa and 320 amino acids is generated by alternative splicing and a peptide fragment of 1-243 amino acid is missing.[3]

Function[edit]

The protease functions in the lysosome to cleave N-terminal tripeptides from substrates and has weaker endopeptidase activity. It is synthesized as a catalytically inactive enzyme which is activated and autoproteolyzed upon acidification. Interestingly, TPP1 has been found to regulate the length of telomeres. Telomeres are the ends of linear eukaryotic chromosomes and consist of multiple repeats of a short DNA sequence.The mammalian chromosome end is capped by a protein complex known as shelterin that is composed of six proteins: TRF1, TRF2, RAP1, TIN2, POT1 and TPP1.[4]

Clinical significance[edit]

The neuronal ceroid lipofuscinoses (NCLs) are a group of inherited neurodegenerative disorders with pathological phenotypes that auto fluorescent lipopigments present in neurons and other cell types. Over the past two decades, accumulating evidences indicates that NCLs are caused by mutations in eight different genes, including genes encoding several soluble proteins (cathepsin D, PPT1, and TPP1).[5] Mutations of gene TPP1 result in late-infantile neuronal ceroid lipofuscinosis which is associated with the failure to degrade specific neuropeptides and a subunit of ATP synthase in the lysosome.[6]

References[edit]

  1. ^ Liu CG, Sleat DE, Donnelly RJ, Lobel P (Jun 1998). "Structural organization and sequence of CLN2, the defective gene in classical late infantile neuronal ceroid lipofuscinosis". Genomics 50 (2): 206–12. doi:10.1006/geno.1998.5328. PMID 9653647. 
  2. ^ a b "Entrez Gene: TPP1 tripeptidyl peptidase I". 
  3. ^ "Uniprot: O14773 - TPP1_HUMAN". 
  4. ^ Nandakumar J, Cech TR (Feb 2013). "Finding the end: recruitment of telomerase to telomeres". Nature Reviews. Molecular Cell Biology 14 (2): 69–82. doi:10.1038/nrm3505. PMID 23299958. 
  5. ^ Getty AL, Pearce DA (Feb 2011). "Interactions of the proteins of neuronal ceroid lipofuscinosis: clues to function". Cellular and Molecular Life Sciences 68 (3): 453–74. doi:10.1007/s00018-010-0468-6. PMID 20680390. 
  6. ^ Gardiner RM (2000). "The molecular genetic basis of the neuronal ceroid lipofuscinoses". Neurological Sciences 21 (3 Suppl): S15–9. PMID 11073223. 

Further reading[edit]

External links[edit]