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O14773 (TPP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 154. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Tripeptidyl-peptidase 1

Short name=TPP-1
EC=3.4.14.9
Alternative name(s):
Cell growth-inhibiting gene 1 protein
Lysosomal pepstatin-insensitive protease
Short name=LPIC
Tripeptidyl aminopeptidase
Tripeptidyl-peptidase I
Short name=TPP-I
Gene names
Name:TPP1
Synonyms:CLN2
ORF Names:GIG1, UNQ267/PRO304
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length563 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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 structure

Monomer. Ref.16

Subcellular location

Lysosome. Melanosome. Note: Identified by mass spectrometry in melanosome fractions from stage I to stage IV. Ref.9 Ref.12

Tissue specificity

Detected in all tissues examined with highest levels in heart and placenta and relatively similar levels in other tissues.

Post-translational modification

Activated by autocatalytic proteolytical processing upon acidification. N-glycosylation is required for processing and activity.

Involvement in disease

Ceroid lipofuscinosis, neuronal, 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29

Spinocerebellar ataxia, autosomal recessive, 7 (SCAR7) [MIM:609270]: Spinocerebellar ataxia defines a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR7 patients show difficulty walking and writing, dysarthria, limb ataxia, and cerebellar atrophy.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.30

Sequence similarities

Contains 1 peptidase S53 domain.

Sequence caution

The sequence AAM08412.1 differs from that shown. Reason: Incorrectly indicated as originating from bovine.

The sequence AAQ88866.1 differs from that shown. Reason: Frameshift at position 551.

Ontologies

Keywords
   Cellular componentLysosome
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
Epilepsy
Neurodegeneration
Neuronal ceroid lipofuscinosis
Spinocerebellar ataxia
   DomainSignal
   LigandCalcium
Metal-binding
   Molecular functionHydrolase
Protease
Serine protease
   PTMAutocatalytic cleavage
Disulfide bond
Glycoprotein
Zymogen
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of signaling protein activity involved in unfolded protein response

Traceable author statement. Source: Reactome

bone resorption

Inferred from mutant phenotype PubMed 8215436. Source: UniProtKB

cell death

Inferred from electronic annotation. Source: UniProtKB-KW

cellular protein metabolic process

Traceable author statement. Source: Reactome

endoplasmic reticulum unfolded protein response

Traceable author statement. Source: Reactome

epithelial cell differentiation

Inferred from expression pattern PubMed 21492153. Source: UniProt

lipid metabolic process

Traceable author statement Ref.1. Source: ProtInc

lysosome organization

Inferred from sequence or structural similarity. Source: UniProtKB

nervous system development

Inferred from mutant phenotype Ref.1. Source: UniProtKB

neuromuscular process controlling balance

Inferred from sequence or structural similarity. Source: UniProtKB

peptide catabolic process

Inferred from mutant phenotype PubMed 15158442PubMed 9989590. Source: UniProtKB

protein catabolic process

Non-traceable author statement PubMed 10740217. Source: UniProtKB

proteolysis

Inferred from mutant phenotype PubMed 10965052Ref.1. Source: UniProtKB

   Cellular_componentextracellular vesicular exosome

Inferred from direct assay PubMed 19056867PubMed 23376485. Source: UniProt

lysosomal lumen

Traceable author statement. Source: Reactome

lysosome

Inferred from direct assay PubMed 15317752. Source: UniProtKB

melanosome

Inferred from electronic annotation. Source: UniProtKB-SubCell

mitochondrion

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionendopeptidase activity

Inferred from direct assay PubMed 10965052. Source: UniProtKB

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

peptidase activity

Inferred from mutant phenotype Ref.1. Source: UniProtKB

peptide binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 12134079. Source: UniProtKB

serine-type endopeptidase activity

Inferred from electronic annotation. Source: InterPro

serine-type peptidase activity

Inferred from mutant phenotype Ref.8. Source: UniProtKB

tripeptidyl-peptidase activity

Inferred from direct assay PubMed 10965052Ref.8PubMed 12134079. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O14773-1)

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.
Isoform 2 (identifier: O14773-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-243: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1919 Ref.8
Propeptide20 – 195176Removed in mature form
PRO_0000027374
Chain196 – 563368Tripeptidyl-peptidase 1
PRO_0000027375

Regions

Domain199 – 563365Peptidase S53

Sites

Active site2721Charge relay system Ref.15 Ref.16
Active site2761Charge relay system Ref.15 Ref.16
Active site4751Charge relay system Ref.15 Ref.16
Metal binding5171Calcium
Metal binding5181Calcium; via carbonyl oxygen
Metal binding5391Calcium; via carbonyl oxygen
Metal binding5411Calcium; via carbonyl oxygen
Metal binding5431Calcium

Amino acid modifications

Glycosylation2101N-linked (GlcNAc...) Ref.13 Ref.15 Ref.16
Glycosylation2221N-linked (GlcNAc...) Ref.13
Glycosylation2861N-linked (GlcNAc...) Ref.15 Ref.16
Glycosylation3131N-linked (GlcNAc...) Ref.13 Ref.15 Ref.16
Glycosylation4431N-linked (GlcNAc...) Ref.10 Ref.13 Ref.15 Ref.16
Disulfide bond111 ↔ 122 Ref.15 Ref.16
Disulfide bond365 ↔ 526 Ref.15 Ref.16
Disulfide bond522 ↔ 537 Ref.15 Ref.16

Natural variations

Alternative sequence1 – 243243Missing in isoform 2.
VSP_013118
Natural variant621S → L.
Corresponds to variant rs2734715 [ dbSNP | Ensembl ].
VAR_037572
Natural variant621S → T in CLN2. Ref.29
VAR_066883
Natural variant771G → R in CLN2; displays very low residual enzyme activity; altered intracellular trafficking. Ref.17 Ref.28
Corresponds to variant rs121908195 [ dbSNP | Ensembl ].
VAR_009603
Natural variant1001Q → R. Ref.17 Ref.22
Corresponds to variant rs1800746 [ dbSNP | Ensembl ].
VAR_009604
Natural variant1271R → Q in CLN2; displays residual enzyme activity; effectively transported to the lysosome. Ref.19 Ref.23 Ref.28
Corresponds to variant rs121908204 [ dbSNP | Ensembl ].
VAR_016790
Natural variant1531S → P in CLN2.
VAR_016791
Natural variant1751R → H. Ref.1
VAR_005642
Natural variant1851R → C.
Corresponds to variant rs34758634 [ dbSNP | Ensembl ].
VAR_037573
Natural variant2021P → L in CLN2; displays no residual enzyme activity; altered intracellular trafficking. Ref.21 Ref.28
Corresponds to variant rs121908205 [ dbSNP | Ensembl ].
VAR_063640
Natural variant2061R → C in CLN2; displays no residual enzyme activity; altered intracellular trafficking. Ref.18 Ref.28
Corresponds to variant rs28940573 [ dbSNP | Ensembl ].
VAR_009605
Natural variant2061R → H in CLN2. Ref.25
Corresponds to variant rs121908209 [ dbSNP | Ensembl ].
VAR_016792
Natural variant2091Y → H in CLN2. Ref.29
VAR_066884
Natural variant2661R → Q in CLN2. Ref.29
VAR_066885
Natural variant2771V → M in CLN2; displays no residual enzyme activity; altered intracellular trafficking; demonstrates enhanced processing in response to folding improvement treatment. Ref.24 Ref.28
Corresponds to variant rs121908207 [ dbSNP | Ensembl ].
VAR_016793
Natural variant2781Q → P in CLN2. Ref.24
VAR_016794
Natural variant2841G → V in CLN2; displays no residual enzyme activity; altered intracellular trafficking. Ref.19 Ref.24 Ref.28
Corresponds to variant rs119455957 [ dbSNP | Ensembl ].
VAR_016795
Natural variant2861N → S in CLN2; enzymatically inactive; lacks one oligosaccharide chain resulting in enzymatic inactivation and possibly prelysosomal protein degradation; altered intracellular trafficking. Ref.23 Ref.26 Ref.28
Corresponds to variant rs119455958 [ dbSNP | Ensembl ].
VAR_016796
Natural variant2871I → N in CLN2; displays no residual enzyme activity; altered intracellular trafficking. Ref.17 Ref.28
Corresponds to variant rs121908196 [ dbSNP | Ensembl ].
VAR_009606
Natural variant3391R → Q in CLN2. Ref.29
VAR_066886
Natural variant3431E → K in CLN2; displays no residual enzyme activity; altered intracellular trafficking. Ref.17 Ref.28
Corresponds to variant rs121908197 [ dbSNP | Ensembl ].
VAR_009607
Natural variant3531T → P in CLN2. Ref.23
Corresponds to variant rs121908206 [ dbSNP | Ensembl ].
VAR_016797
Natural variant3651C → R in CLN2; displays no residual enzyme activity; altered intracellular trafficking. Ref.1 Ref.17 Ref.28
Corresponds to variant rs119455953 [ dbSNP | Ensembl ].
VAR_005643
Natural variant3651C → Y in CLN2. Ref.1 Ref.17
Corresponds to variant rs119455954 [ dbSNP | Ensembl ].
VAR_005644
Natural variant3821S → R in CLN2. Ref.29
VAR_066887
Natural variant3851V → D in CLN2. Ref.17
Corresponds to variant rs121908198 [ dbSNP | Ensembl ].
VAR_009608
Natural variant3891G → E in CLN2. Ref.17 Ref.22
Corresponds to variant rs121908199 [ dbSNP | Ensembl ].
VAR_009609
Natural variant4221Q → H in CLN2; displays no residual enzyme activity; altered intracellular trafficking. Ref.17 Ref.28
Corresponds to variant rs121908200 [ dbSNP | Ensembl ].
VAR_009610
Natural variant4281K → N in CLN2. Ref.19
VAR_016798
Natural variant4471R → H in CLN2; displays very low residual enzyme activity; altered intracellular trafficking; demonstrates enhanced processing in response to folding improvement treatment; shows a five fold increase under permissive temperature conditions. Ref.17 Ref.22 Ref.28
Corresponds to variant rs119455956 [ dbSNP | Ensembl ].
VAR_005645
Natural variant4481A → V in CLN2. Ref.29
VAR_066888
Natural variant4541A → E in CLN2. Ref.17
Corresponds to variant rs121908201 [ dbSNP | Ensembl ].
VAR_009611
Natural variant4661V → G in SCAR7. Ref.30
VAR_070917
Natural variant4731G → R in CLN2. Ref.19 Ref.20
Corresponds to variant rs121908203 [ dbSNP | Ensembl ].
VAR_016799
Natural variant4751S → L in CLN2; displays no residual enzyme activity; effectively transported to the lysosome. Ref.17 Ref.28
Corresponds to variant rs121908202 [ dbSNP | Ensembl ].
VAR_009612
Natural variant4811F → C in CLN2. Ref.24
VAR_016800
Natural variant4821G → R in CLN2. Ref.27
Corresponds to variant rs121908208 [ dbSNP | Ensembl ].
VAR_058435
Natural variant5011G → C in CLN2. Ref.29
VAR_066889
Natural variant5041N → Y in CLN2. Ref.29
VAR_066890
Natural variant5441P → S in CLN2; displays residual enzyme activity; effectively transported to the lysosome. Ref.28
Corresponds to variant rs121908210 [ dbSNP | Ensembl ].
VAR_063641
Natural variant5481W → R in CLN2. Ref.29
VAR_066891

Experimental info

Mutagenesis2361H → A: No effect.
Mutagenesis3601D → A: Inactive. Impaired processing.
Mutagenesis4751S → A: Inactive. Impaired processing.
Mutagenesis5171D → A: Inactive. Impaired processing.
Sequence conflict1151I → N in BAD96219. Ref.6
Sequence conflict3731Q → E in AAH14863. Ref.7

Secondary structure

........................................................................................... 563
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 30, 2006. Version 2.
Checksum: 7299D902F6AE8555

FASTA56361,248
        10         20         30         40         50         60 
MGLQACLLGL FALILSGKCS YSPEPDQRRT LPPGWVSLGR ADPEEELSLT FALRQQNVER 

        70         80         90        100        110        120 
LSELVQAVSD PSSPQYGKYL TLENVADLVR PSPLTLHTVQ KWLLAAGAQK CHSVITQDFL 

       130        140        150        160        170        180 
TCWLSIRQAE LLLPGAEFHH YVGGPTETHV VRSPHPYQLP QALAPHVDFV GGLHRFPPTS 

       190        200        210        220        230        240 
SLRQRPEPQV TGTVGLHLGV TPSVIRKRYN LTSQDVGSGT SNNSQACAQF LEQYFHDSDL 

       250        260        270        280        290        300 
AQFMRLFGGN FAHQASVARV VGQQGRGRAG IEASLDVQYL MSAGANISTW VYSSPGRHEG 

       310        320        330        340        350        360 
QEPFLQWLML LSNESALPHV HTVSYGDDED SLSSAYIQRV NTELMKAAAR GLTLLFASGD 

       370        380        390        400        410        420 
SGAGCWSVSG RHQFRPTFPA SSPYVTTVGG TSFQEPFLIT NEIVDYISGG GFSNVFPRPS 

       430        440        450        460        470        480 
YQEEAVTKFL SSSPHLPPSS YFNASGRAYP DVAALSDGYW VVSNRVPIPW VSGTSASTPV 

       490        500        510        520        530        540 
FGGILSLINE HRILSGRPPL GFLNPRLYQQ HGAGLFDVTR GCHESCLDEE VEGQGFCSGP 

       550        560 
GWDPVTGWGT PNFPALLKTL LNP 

« Hide

Isoform 2 [UniParc].

Checksum: 707AE6D4A90B0FBC
Show »

FASTA32034,464

References

« Hide 'large scale' references
[1]"Association of mutations in a lysosomal protein with classical late-infantile neuronal ceroid lipofuscinosis."
Sleat D.E., Donnelly R.J., Lackland H., Liu C.-G., Sohar I., Pullarkat R.K., Lobel P.
Science 277:1802-1805(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, VARIANTS CLN2 ARG-365 AND TYR-365, VARIANT HIS-175.
Tissue: Placenta.
[2]"Structural organization and sequence of CLN2, the defective gene in classical late infantile neuronal ceroid lipofuscinosis."
Liu C.-G., Sleat D.E., Donnelly R.J., Lobel P.
Genomics 50:206-212(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Placenta.
[3]"Bovine brain homolog of the tripeptidyl peptidase I which is deficient in the human classic late-infantile neuronal ceroid lipofuscinosis."
Junaid M.A., Barua M., Pullarkat R.K.
Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Brain cortex.
[4]"Identification of a human growth inhibition gene 1 (GIG1)."
Kim J.W.
Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[5]"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. expand/collapse author list , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.
Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Adipose tissue.
[7]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Lymph.
[8]"The human CLN2 protein/tripeptidyl-peptidase I is a serine protease that autoactivates at acidic pH."
Lin L., Sohar I., Lackland H., Lobel P.
J. Biol. Chem. 276:2249-2255(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 20-24; 196-200 AND 466-492, MUTAGENESIS, CHARACTERIZATION.
[9]"Proteomic analysis of early melanosomes: identification of novel melanosomal proteins."
Basrur V., Yang F., Kushimoto T., Higashimoto Y., Yasumoto K., Valencia J., Muller J., Vieira W.D., Watabe H., Shabanowitz J., Hearing V.J., Hunt D.F., Appella E.
J. Proteome Res. 2:69-79(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
Tissue: Melanoma.
[10]"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] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-443.
[11]"Molecular basis of the neuronal ceroid lipofuscinoses: mutations in CLN1, CLN2, CLN3, and CLN5."
Mole S.E., Mitchison H.M., Munroe P.B.
Hum. Mutat. 14:199-215(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON VARIANTS.
[12]"Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes."
Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F.
J. Proteome Res. 5:3135-3144(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
Tissue: Melanoma.
[13]"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] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-210; ASN-222; ASN-313 AND ASN-443.
Tissue: Liver.
[14]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]"Structure of tripeptidyl-peptidase I provides insight into the molecular basis of late infantile neuronal ceroid lipofuscinosis."
Pal A., Kraetzner R., Gruene T., Grapp M., Schreiber K., Gronborg M., Urlaub H., Becker S., Asif A.R., Gartner J., Sheldrick G.M., Steinfeld R.
J. Biol. Chem. 284:3976-3984(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS), ACTIVE SITE, CALCIUM-BINDING SITES, DISULFIDE BONDS, GLYCOSYLATION AT ASN-210; ASN-286; ASN-313 AND ASN-443.
[16]"Crystal structure and autoactivation pathway of the precursor form of human tripeptidyl-peptidase 1, the enzyme deficient in late infantile ceroid lipofuscinosis."
Guhaniyogi J., Sohar I., Das K., Stock A.M., Lobel P.
J. Biol. Chem. 284:3985-3997(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 20-563, ACTIVE SITE, DISULFIDE BONDS, CALCIUM-BINDING SITES, SUBUNIT, AUTOPROTEOLYTIC CLEAVAGE, GLYCOSYLATION AT ASN-210; ASN-286; ASN-313 AND ASN-443.
[17]"Mutational analysis of the defective protease in classic late-infantile neuronal ceroid lipofuscinosis, a neurodegenerative lysosomal storage disorder."
Sleat D.E., Gin R.M., Sohar I., Wisniewski K., Sklower-Brooks S., Pullarkat R.K., Palmer D.N., Lerner T.J., Boustany R.-M.N., Uldall P., Siakotos A.N., Donnelly R.J., Lobel P.
Am. J. Hum. Genet. 64:1511-1523(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CLN2 ARG-77; ASN-287; LYS-343; ARG-365; TYR-365; ASP-385; GLU-389; HIS-422; HIS-447; GLU-454 AND LEU-475, VARIANT ARG-100.
[18]"Prenatal testing for late infantile neuronal ceroid lipofuscinosis."
Berry-Kravis E., Sleat D.E., Sohar I., Meyer P., Donnelly R., Lobel P.
Ann. Neurol. 47:254-257(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CLN2 CYS-206.
[19]"Heterogeneity of late-infantile neuronal ceroid lipofuscinosis."
Zhong N., Moroziewicz D.N., Ju W., Jurkiewicz A., Johnston L., Wisniewski K.E., Brown W.T.
Genet. Med. 2:312-318(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CLN2 GLN-127; VAL-284; ASN-428 AND ARG-473.
[20]"Two novel CLN2 gene mutations in a Chinese patient with classical late-infantile neuronal ceroid lipofuscinosis."
Lam C.W., Poon P.M., Tong S.F., Ko C.H.
Am. J. Med. Genet. 99:161-163(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CLN2 ARG-473.
[21]"New mutations in the neuronal ceroid lipofuscinosis genes."
Mole S.E., Zhong N.A., Sarpong A., Logan W.P., Hofmann S., Yi W., Franken P.F., van Diggelen O.P., Breuning M.H., Moroziewicz D., Ju W., Salonen T., Holmberg V., Jaervelae I., Taschner P.E.M.
Eur. J. Paediatr. Neurol. 5:7-10(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CLN2 LEU-202.
[22]"Expression and analysis of CLN2 variants in CHO cells: Q100R represents a polymorphism, and G389E and R447H represent loss-of-function mutations."
Lin L., Lobel P.
Hum. Mutat. 18:165-165(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS ARG-100; GLU-389 AND HIS-447.
[23]"Late infantile neuronal ceroid lipofuscinosis: quantitative description of the clinical course in patients with CLN2 mutations."
Steinfeld R., Heim P., von Gregory H., Meyer K., Ullrich K., Goebel H.H., Kohlschutter A.
Am. J. Med. Genet. 112:347-354(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CLN2 GLN-127; SER-286 AND PRO-353.
[24]"Identification of novel CLN2 mutations shows Canadian specific NCL2 alleles."
Ju W., Zhong R., Moore S., Moroziewicz D., Currie J.R., Parfrey P., Brown W.T., Zhong N.
J. Med. Genet. 39:822-825(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CLN2 MET-277; PRO-278; VAL-284 AND CYS-481.
[25]"Tripeptidyl peptidase 1 deficiency in neuronal ceroid lipofuscinosis. A novel mutation."
Bukina A.M., Tsvetkova I.V., Semiachkina A.N., Il'ina E.S.
Vopr. Med. Khim. 48:594-598(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CLN2 HIS-206.
[26]"Mutation of the glycosylated asparagine residue 286 in human CLN2 protein results in loss of enzymatic activity."
Tsiakas K., Steinfeld R., Storch S., Ezaki J., Lukacs Z., Kominami E., Kohlschuetter A., Ullrich K., Braulke T.
Glycobiology 14:1C-5C(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT CLN2 SER-286.
[27]"Mutations in CLN7/MFSD8 are a common cause of variant late-infantile neuronal ceroid lipofuscinosis."
Kousi M., Siintola E., Dvorakova L., Vlaskova H., Turnbull J., Topcu M., Yuksel D., Gokben S., Minassian B.A., Elleder M., Mole S.E., Lehesjoki A.-E.
Brain 132:810-819(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CLN2 ARG-482.
[28]"Functional consequences and rescue potential of pathogenic missense mutations in tripeptidyl peptidase I."
Walus M., Kida E., Golabek A.A.
Hum. Mutat. 31:710-721(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CLN2 SER-544, CHARACTERIZATION OF VARIANTS CLN2 ARG-77; GLN-127; LEU-202; CYS-206; MET-277; VAL-284; SER-286; ASN-287; LYS-343; ARG-365; HIS-422; HIS-447; LEU-475 AND SER-544.
[29]"Update of the mutation spectrum and clinical correlations of over 360 mutations in eight genes that underlie the neuronal ceroid lipofuscinoses."
Kousi M., Lehesjoki A.E., Mole S.E.
Hum. Mutat. 33:42-63(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CLN2 THR-62; HIS-209; GLN-266; GLN-339; ARG-382; VAL-448; CYS-501; TYR-504 AND ARG-548.
[30]"Autosomal recessive spinocerebellar ataxia 7 (SCAR7) is caused by variants in TPP1, the gene involved in classic late-infantile neuronal ceroid lipofuscinosis 2 disease (CLN2 disease)."
Sun Y., Almomani R., Breedveld G.J., Santen G.W., Aten E., Lefeber D.J., Hoff J.I., Brusse E., Verheijen F.W., Verdijk R.M., Kriek M., Oostra B., Breuning M.H., Losekoot M., den Dunnen J.T., van de Warrenburg B.P., Maat-Kievit A.J.
Hum. Mutat. 34:706-713(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SCAR7 GLY-466.
+Additional computationally mapped references.

Web resources

NCL CLN2

Neural Ceroid Lipofuscinoses mutation db

Mendelian genes trieptidyl peptidase I (TPP1)

Leiden Open Variation Database (LOVD)

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF017456 mRNA. Translation: AAB80725.1.
AF039704 Genomic DNA. Translation: AAC98480.1.
AF491290 mRNA. Translation: AAM08412.1.
AY268890 mRNA. Translation: AAQ72732.1.
AY358502 mRNA. Translation: AAQ88866.1. Frameshift.
AK222499 mRNA. Translation: BAD96219.1.
BC014863 mRNA. Translation: AAH14863.1.
CCDSCCDS7770.1. [O14773-1]
RefSeqNP_000382.3. NM_000391.3. [O14773-1]
UniGeneHs.523454.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1R60model-A196-563[»]
3EDYX-ray1.85A20-563[»]
3EE6X-ray2.35A/B1-563[»]
ProteinModelPortalO14773.
SMRO14773. Positions 20-563.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107611. 6 interactions.
DIPDIP-47434N.
IntActO14773. 18 interactions.
MINTMINT-5002180.
STRING9606.ENSP00000299427.

Protein family/group databases

MEROPSS53.003.

PTM databases

PhosphoSiteO14773.

Proteomic databases

MaxQBO14773.
PaxDbO14773.
PRIDEO14773.

Protocols and materials databases

DNASU1200.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000299427; ENSP00000299427; ENSG00000166340. [O14773-1]
ENST00000533371; ENSP00000437066; ENSG00000166340. [O14773-2]
GeneID1200.
KEGGhsa:1200.
UCSCuc001mek.1. human. [O14773-1]

Organism-specific databases

CTD1200.
GeneCardsGC11M006634.
GeneReviewsTPP1.
H-InvDBHIX0009410.
HGNCHGNC:2073. TPP1.
HPAHPA037709.
MIM204500. phenotype.
607998. gene.
609270. phenotype.
neXtProtNX_O14773.
Orphanet284324. Childhood-onset autosomal recessive slowly progressive spinocerebellar ataxia.
228349. CLN2 disease.
PharmGKBPA26600.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG4934.
HOGENOMHOG000171253.
HOVERGENHBG004449.
InParanoidO14773.
KOK01279.
OMACRVRSAR.
OrthoDBEOG7RNJZW.
PhylomeDBO14773.
TreeFamTF333497.

Enzyme and pathway databases

BRENDA3.4.14.9. 2681.
ReactomeREACT_17015. Metabolism of proteins.
SABIO-RKO14773.
SignaLinkO14773.

Gene expression databases

ArrayExpressO14773.
BgeeO14773.
CleanExHS_TPP1.
GenevestigatorO14773.

Family and domain databases

Gene3D3.40.50.200. 1 hit.
InterProIPR015366. Peptidase_S53_propep.
IPR000209. Peptidase_S8/S53_dom.
IPR009020. Prot_inh_propept.
[Graphical view]
PfamPF00082. Peptidase_S8. 1 hit.
PF09286. Pro-kuma_activ. 1 hit.
[Graphical view]
SMARTSM00944. Pro-kuma_activ. 1 hit.
[Graphical view]
SUPFAMSSF52743. SSF52743. 1 hit.
SSF54897. SSF54897. 1 hit.
PROSITEPS51695. SEDOLISIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTPP1. human.
EvolutionaryTraceO14773.
GeneWikiTripeptidyl_peptidase_I.
GenomeRNAi1200.
NextBio4955.
PMAP-CutDBO14773.
PROO14773.
SOURCESearch...

Entry information

Entry nameTPP1_HUMAN
AccessionPrimary (citable) accession number: O14773
Secondary accession number(s): Q53HT1 expand/collapse secondary AC list , Q5JAK6, Q6UX56, Q71JP6, Q96C37
Entry history
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: May 30, 2006
Last modified: July 9, 2014
This is version 154 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM