O14773 (TPP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	563 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	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	Neuronal ceroid lipofuscinosis 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
Sequence similarities	Belongs to the peptidase S53 family.
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 component	Lysosome
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Epilepsy Neurodegeneration Neuronal ceroid lipofuscinosis
Domain	Signal
Ligand	Calcium Metal-binding
Molecular function	Hydrolase Protease Serine protease
PTM	Autocatalytic cleavage Disulfide bond Glycoprotein Zymogen
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	activation 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 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_component	lysosomal lumen Traceable author statement. Source: Reactome melanosome Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrion Inferred from electronic annotation. Source: Compara
Molecular_function	endopeptidase activity Inferred from direct assay PubMed 10965052. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW peptide binding Inferred from sequence or structural similarity. Source: UniProtKB serine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 19

19

Ref.8

Propeptide

20 – 195

176

Removed in mature form

PRO_0000027374

Chain

196 – 563

368

Tripeptidyl-peptidase 1

PRO_0000027375

Sites

Active site

272

1

Charge relay system Ref.15 Ref.16

Active site

276

1

Charge relay system Ref.15 Ref.16

Active site

475

1

Charge relay system Ref.15 Ref.16

Metal binding

517

1

Calcium

Metal binding

518

1

Calcium; via carbonyl oxygen

Metal binding

539

1

Calcium; via carbonyl oxygen

Metal binding

541

1

Calcium; via carbonyl oxygen

Metal binding

543

1

Calcium

Amino acid modifications

Glycosylation

210

1

N-linked (GlcNAc...) Ref.13 Ref.15 Ref.16

Glycosylation

222

1

N-linked (GlcNAc...) Ref.13

Glycosylation

286

1

N-linked (GlcNAc...) Ref.15 Ref.16

Glycosylation

313

1

N-linked (GlcNAc...) Ref.13 Ref.15 Ref.16

Glycosylation

443

1

N-linked (GlcNAc...) Ref.10 Ref.13 Ref.15 Ref.16

Disulfide bond

111 ↔ 122

Ref.15 Ref.16

Disulfide bond

365 ↔ 526

Ref.15 Ref.16

Disulfide bond

522 ↔ 537

Ref.15 Ref.16

Natural variations

Alternative sequence

1 – 243

243

Missing in isoform 2.

VSP_013118

Natural variant

62

1

S → L.
Corresponds to variant rs2734715 [ dbSNP | Ensembl ].

VAR_037572

Natural variant

62

1

S → T in CLN2. Ref.29

VAR_066883

Natural variant

77

1

G → 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 variant

100

1

Q → R. Ref.17 Ref.22
Corresponds to variant rs1800746 [ dbSNP | Ensembl ].

VAR_009604

Natural variant

127

1

R → 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 variant

153

1

S → P in CLN2.

VAR_016791

Natural variant

175

1

R → H. Ref.1

VAR_005642

Natural variant

185

1

R → C.
Corresponds to variant rs34758634 [ dbSNP | Ensembl ].

VAR_037573

Natural variant

202

1

P → L in CLN2; displays no residual enzyme activity; altered intracellular trafficking. Ref.21 Ref.28
Corresponds to variant rs121908205 [ dbSNP | Ensembl ].

VAR_063640

Natural variant

206

1

R → C in CLN2; displays no residual enzyme activity; altered intracellular trafficking. Ref.18 Ref.28
Corresponds to variant rs28940573 [ dbSNP | Ensembl ].

VAR_009605

Natural variant

206

1

R → H in CLN2. Ref.25
Corresponds to variant rs121908209 [ dbSNP | Ensembl ].

VAR_016792

Natural variant

209

1

Y → H in CLN2. Ref.29

VAR_066884

Natural variant

266

1

R → Q in CLN2. Ref.29

VAR_066885

Natural variant

277

1

V → 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 variant

278

1

Q → P in CLN2. Ref.24

VAR_016794

Natural variant

284

1

G → 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 variant

286

1

N → 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 variant

287

1

I → N in CLN2; displays no residual enzyme activity; altered intracellular trafficking. Ref.17 Ref.28
Corresponds to variant rs121908196 [ dbSNP | Ensembl ].

VAR_009606

Natural variant

339

1

R → Q in CLN2. Ref.29

VAR_066886

Natural variant

343

1

E → K in CLN2; displays no residual enzyme activity; altered intracellular trafficking. Ref.17 Ref.28
Corresponds to variant rs121908197 [ dbSNP | Ensembl ].

VAR_009607

Natural variant

353

1

T → P in CLN2. Ref.23
Corresponds to variant rs121908206 [ dbSNP | Ensembl ].

VAR_016797

Natural variant

365

1

C → 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 variant

365

1

C → Y in CLN2. Ref.1 Ref.17
Corresponds to variant rs119455954 [ dbSNP | Ensembl ].

VAR_005644

Natural variant

382

1

S → R in CLN2. Ref.29

VAR_066887

Natural variant

385

1

V → D in CLN2. Ref.17
Corresponds to variant rs121908198 [ dbSNP | Ensembl ].

VAR_009608

Natural variant

389

1

G → E in CLN2. Ref.17 Ref.22
Corresponds to variant rs121908199 [ dbSNP | Ensembl ].

VAR_009609

Natural variant

422

1

Q → H in CLN2; displays no residual enzyme activity; altered intracellular trafficking. Ref.17 Ref.28
Corresponds to variant rs121908200 [ dbSNP | Ensembl ].

VAR_009610

Natural variant

428

1

K → N in CLN2. Ref.19

VAR_016798

Natural variant

447

1

R → 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 variant

448

1

A → V in CLN2. Ref.29

VAR_066888

Natural variant

454

1

A → E in CLN2. Ref.17
Corresponds to variant rs121908201 [ dbSNP | Ensembl ].

VAR_009611

Natural variant

473

1

G → R in CLN2. Ref.19 Ref.20
Corresponds to variant rs121908203 [ dbSNP | Ensembl ].

VAR_016799

Natural variant

475

1

S → 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 variant

481

1

F → C in CLN2. Ref.24

VAR_016800

Natural variant

482

1

G → R in CLN2. Ref.27
Corresponds to variant rs121908208 [ dbSNP | Ensembl ].

VAR_058435

Natural variant

501

1

G → C in CLN2. Ref.29

VAR_066889

Natural variant

504

1

N → Y in CLN2. Ref.29

VAR_066890

Natural variant

544

1

P → S in CLN2; displays residual enzyme activity; effectively transported to the lysosome. Ref.28
Corresponds to variant rs121908210 [ dbSNP | Ensembl ].

VAR_063641

Natural variant

548

1

W → R in CLN2. Ref.29

VAR_066891

Experimental info

Mutagenesis

236

1

H → A: No effect.

Mutagenesis

360

1

D → A: Inactive. Impaired processing.

Mutagenesis

475

1

S → A: Inactive. Impaired processing.

Mutagenesis

517

1

D → A: Inactive. Impaired processing.

Sequence conflict

115

1

I → N in BAD96219. Ref.6

Sequence conflict

373

1

Q → E in AAH14863. Ref.7

Secondary structure

1

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563

Helix Strand Turn

Details...

Beta strand

35 – 40

6

Beta strand

46 – 53

8

Helix

58 – 69

12

Turn

74 – 77

4

Helix

82 – 89

8

Helix

93 – 106

14

Beta strand

109 – 113

5

Beta strand

119 – 125

7

Helix

126 – 132

7

Beta strand

139 – 143

5

Turn

144 – 147

4

Beta strand

148 – 152

5

Helix

161 – 163

3

Turn

164 – 166

3

Beta strand

167 – 170

4

Helix

202 – 208

7

Beta strand

219 – 221

3

Beta strand

224 – 229

6

Helix

237 – 247

11

Beta strand

258 – 262

5

Helix

271 – 283

13

Turn

284 – 286

3

Beta strand

287 – 292

6

Turn

295 – 300

6

Helix

303 – 311

9

Beta strand

319 – 324

6

Helix

329 – 331

3

Helix

334 – 349

16

Beta strand

353 – 357

5

Beta strand

366 – 368

3

Beta strand

371 – 373

3

Turn

379 – 381

3

Beta strand

385 – 397

13

Beta strand

402 – 404

3

Beta strand

411 – 417

7

Helix

420 – 422

3

Helix

423 – 432

10

Helix

439 – 441

3

Beta strand

446 – 449

4

Beta strand

451 – 455

5

Beta strand

457 – 463

7

Beta strand

466 – 471

6

Helix

474 – 494

21

Helix

504 – 509

6

Turn

510 – 514

5

Beta strand

522 – 525

4

Turn

529 – 533

5

Beta strand

534 – 537

4

Turn

544 – 546

3

Helix

553 – 558

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 30, 2006. Version 2. Checksum: 7299D902F6AE8555	FASTA	563	61,248
	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
	Isoform 2 [UniParc]. Checksum: 707AE6D4A90B0FBC	FASTA	320	34,464
	10 20 30 40 50 60 MRLFGGNFAH QASVARVVGQ QGRGRAGIEA SLDVQYLMSA GANISTWVYS SPGRHEGQEP 70 80 90 100 110 120 FLQWLMLLSN ESALPHVHTV SYGDDEDSLS SAYIQRVNTE LMKAAARGLT LLFASGDSGA 130 140 150 160 170 180 GCWSVSGRHQ FRPTFPASSP YVTTVGGTSF QEPFLITNEI VDYISGGGFS NVFPRPSYQE 190 200 210 220 230 240 EAVTKFLSSS PHLPPSSYFN ASGRAYPDVA ALSDGYWVVS NRVPIPWVSG TSASTPVFGG 250 260 270 280 290 300 ILSLINEHRI LSGRPPLGFL NPRLYQQHGA GLFDVTRGCH ESCLDEEVEG QGFCSGPGWD 310 320 PVTGWGTPNF PALLKTLLNP

References

	« Hide 'large scale' referencesShow '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. , 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], MASS SPECTROMETRY. 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], MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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.
+	Additional computationally mapped references.

Web resources

NCL CLN2

Neural Ceroid Lipofuscinoses mutation db

GeneReviews

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.

IPI

IPI00298237.
IPI00909516.

RefSeq

NP_000382.3. NM_000391.3.

UniGene

Hs.523454.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1R60	model	-	A	196-563	[»]
3EDY	X-ray	1.85	A	20-563	[»]
3EE6	X-ray	2.35	A/B	1-563	[»]

ProteinModelPortal

O14773.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-47434N.

IntAct

O14773. 16 interactions.

MINT

MINT-5002180.

STRING

9606.ENSP00000299427.

Protein family/group databases

MEROPS

S53.003.

PTM databases

PhosphoSite

O14773.

Proteomic databases

PaxDb

O14773.

PRIDE

O14773.

Protocols and materials databases

DNASU

1200.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000299427; ENSP00000299427; ENSG00000166340.
ENST00000533371; ENSP00000437066; ENSG00000166340.

GeneID

1200.

KEGG

hsa:1200.

UCSC

uc001mek.1. human.

Organism-specific databases

CTD

1200.

GeneCards

GC11M006634.

H-InvDB

HIX0009410.

HGNC

HGNC:2073. TPP1.

HPA

HPA037709.

MIM

204500. phenotype.
607998. gene.

neXtProt

NX_O14773.

Orphanet

228349. CLN2 disease.

PharmGKB

PA26600.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG4934.

HOGENOM

HOG000171253.

HOVERGEN

HBG004449.

InParanoid

O14773.

KO

K01279.

OMA

WVVSNRV.

OrthoDB

EOG42Z4PZ.

PhylomeDB

O14773.

Enzyme and pathway databases

BRENDA

3.4.14.9. 2681.

Reactome

REACT_116125. Disease.

SABIO-RK

O14773.

Gene expression databases

ArrayExpress

O14773.

Bgee

O14773.

CleanEx

HS_TPP1.

Genevestigator

O14773.

GermOnline

ENSG00000166340. Homo sapiens.

Family and domain databases

Gene3D

3.40.50.200. 1 hit.

InterPro

IPR015366. Peptidase_S53_propep.
IPR000209. Peptidase_S8/S53_dom.
IPR009020. Prot_inh_propept.
[Graphical view]

Pfam

PF00082. Peptidase_S8. 1 hit.
PF09286. Pro-kuma_activ. 1 hit.
[Graphical view]

SMART

SM00944. Pro-kuma_activ. 1 hit.
[Graphical view]

SUPFAM

SSF52743. Pept_S8_S53. 1 hit.
SSF54897. Prot_inh_propept. 1 hit.

ProtoNet

Search...

Other

ChiTaRS

TPP1. human.

EvolutionaryTrace

O14773.

GenomeRNAi

1200.

NextBio

4955.

PMAP-CutDB

O14773.

SOURCE

Search...

Entry information

Entry name

TPP1_HUMAN

Accession

Primary (citable) accession number: O14773
Secondary accession number(s): Q53HT1 , Q5JAK6, Q6UX56, Q71JP6, Q96C37

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 15, 1998
Last sequence update:	May 30, 2006
Last modified:	May 1, 2013
This is version 141 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.