O89023 (TPP1_MOUSE) 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):
Lysosomal pepstatin-insensitive protease
Short name=LPIC
Tripeptidyl aminopeptidase
Tripeptidyl-peptidase I
Short name=TPP-I

Gene names

Name:	Tpp1
Synonyms:	Cln2

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	562 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 By similarity.
Subunit structure	Monomer By similarity.
Subcellular location	Lysosome. Melanosome By similarity.
Post-translational modification	Activated by autocatalytic proteolytical processing upon acidification. N-glycosylation is required for processing and activity By similarity.
Sequence similarities	Belongs to the peptidase S53 family.
Sequence caution	The sequence CAA09863.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Lysosome
Domain	Signal
Ligand	Calcium Metal-binding
Molecular function	Hydrolase Protease Serine protease
PTM	Autocatalytic cleavage Disulfide bond Glycoprotein Zymogen
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	bone resorption Inferred from sequence or structural similarity PubMed 14609438. Source: UniProtKB lysosome organization Inferred from mutant phenotype PubMed 15483130. Source: MGI nervous system development Inferred from sequence or structural similarity PubMed 14609438. Source: UniProtKB neuromuscular process controlling balance Inferred from mutant phenotype PubMed 15483130. Source: MGI peptide catabolic process Inferred from sequence or structural similarity PubMed 14609438. Source: UniProtKB proteolysis Inferred from sequence or structural similarity PubMed 14609438. Source: UniProtKB
Cellular_component	lysosome Inferred from sequence or structural similarity PubMed 14609438. Source: UniProtKB melanosome Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrion Inferred from direct assay PubMed 14651853. Source: MGI
Molecular_function	endopeptidase activity Inferred from sequence or structural similarity PubMed 14609438. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW serine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro tripeptidyl-peptidase activity Inferred from sequence or structural similarity PubMed 14609438. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 19	19	By similarity
	Propeptide	20 – 194	175	Removed in mature form By similarity		PRO_0000027378
	Chain	195 – 562	368	Tripeptidyl-peptidase 1		PRO_0000027379
Sites
	Active site	271	1	Charge relay system By similarity
	Active site	275	1	Charge relay system By similarity
	Active site	474	1	Charge relay system By similarity
	Metal binding	516	1	Calcium By similarity
	Metal binding	517	1	Calcium; via carbonyl oxygen By similarity
	Metal binding	538	1	Calcium; via carbonyl oxygen By similarity
	Metal binding	540	1	Calcium; via carbonyl oxygen By similarity
	Metal binding	542	1	Calcium By similarity
Amino acid modifications
	Glycosylation	209	1	N-linked (GlcNAc...) Potential
	Glycosylation	221	1	N-linked (GlcNAc...) (high mannose) Ref.6
	Glycosylation	285	1	N-linked (GlcNAc...) Potential
	Glycosylation	312	1	N-linked (GlcNAc...) Potential
	Glycosylation	442	1	N-linked (GlcNAc...) Potential
	Disulfide bond	111 ↔ 122		By similarity
	Disulfide bond	364 ↔ 525		By similarity
	Disulfide bond	521 ↔ 536		By similarity
Experimental info
	Sequence conflict	1	1	M → V Ref.1
	Sequence conflict	562	1	P → LDPFVP Ref.1

Sequences

	Sequence		Length	Mass (Da)
	O89023 [UniParc]. Last modified December 1, 2000. Version 2. Checksum: 0AF8163EA1A66396	FASTA	562	61,342
	10 20 30 40 50 60 MGLQARLLGL LALVIAGKCT YNPEPDQRWM LPPGWVSLGR VDPEEELSLT FALKQRNLER 70 80 90 100 110 120 LSELVQAVSD PSSPQYGKYL TLEDVAELVQ PSPLTLLTVQ KWLSAAGARN CDSVTTQDFL 130 140 150 160 170 180 TCWLSVRQAE LLLPGAEFHR YVGGPTKTHV IRSPHPYQLP QALAPHVDFV GGLHRFPPSS 190 200 210 220 230 240 PRQRPEPQQV GTVSLHLGVT PSVLRQRYNL TAKDVGSGTT NNSQACAQFL EQYFHNSDLT 250 260 270 280 290 300 EFMRLFGGSF THQASVAKVV GKQGRGRAGI EASLDVEYLM SAGANISTWV YSSPGRHEAQ 310 320 330 340 350 360 EPFLQWLLLL SNESSLPHVH TVSYGDDEDS LSSIYIQRVN TEFMKAAARG LTLLFASGDT 370 380 390 400 410 420 GAGCWSVSGR HKFRPSFPAS SPYVTTVGGT SFKNPFLITD EVVDYISGGG FSNVFPRPPY 430 440 450 460 470 480 QEEAVAQFLK SSSHLPPSSY FNASGRAYPD VAALSDGYWV VSNMVPIPWV SGTSASTPVF 490 500 510 520 530 540 GGILSLINEH RILNGRPPLG FLNPRLYQQH GTGLFDVTHG CHESCLNEEV EGQGFCSGPG 550 560 WDPVTGWGTP NFPALLKTLL NP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Classical late infantile neuronal ceroid lipofuscinosis fibroblasts are deficient in lysosomal tripeptidyl peptidase I." Vines D.J., Warburton M.J. FEBS Lett. 443:131-135(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Characterization and chromosomal mapping of a mouse ortholog of the late-infantile ceroid-lipofuscinosis gene CLN2." Katz M.L., Liu P.-C., Grob-Nunn S.E., Shibuya H., Johnson G.S. Mamm. Genome 10:1050-1053(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Murine homologue of the lysosomal pepstatin insensitive protease which is deficient in human classical late infantile neuronal ceroid lipofuscinosis." Sleat D.E., Lobel P. Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE.
[4]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J and NOD. Tissue: Head and Kidney.
[5]	"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]. Strain: C57BL/6. Tissue: Retina.
[6]	"High throughput quantitative glycomics and glycoform-focused proteomics of murine dermis and epidermis." Uematsu R., Furukawa J., Nakagawa H., Shinohara Y., Deguchi K., Monde K., Nishimura S. Mol. Cell. Proteomics 4:1977-1989(2005) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-221, MASS SPECTROMETRY. Tissue: Epidermis.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ011912 mRNA. Translation: CAA09863.1. Different initiation. AF124599 Genomic DNA. Translation: AAD32573.1. AF111172 mRNA. Translation: AAD03083.1. AK002418 mRNA. Translation: BAB22085.1. AK048279 mRNA. Translation: BAC33293.1. AK170781 mRNA. Translation: BAE42026.1. BC024820 mRNA. Translation: AAH24820.1.
IPI	IPI00130661.
RefSeq	NP_034036.1. NM_009906.5.
UniGene	Mm.20837.
3D structure databases
ProteinModelPortal	O89023.
SMR	O89023. Positions 20-562.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-3379633.
Protein family/group databases
MEROPS	S53.003.
PTM databases
PhosphoSite	O89023.
Proteomic databases
PaxDb	O89023.
PRIDE	O89023.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000033184; ENSMUSP00000033184; ENSMUSG00000030894.
GeneID	12751.
KEGG	mmu:12751.
UCSC	uc009izg.1. mouse.
Organism-specific databases
CTD	1200.
MGI	MGI:1336194. Tpp1.
Phylogenomic databases
eggNOG	COG4934.
GeneTree	ENSGT00390000008684.
HOGENOM	HOG000171253.
HOVERGEN	HBG004449.
InParanoid	O89023.
KO	K01279.
OMA	WVVSNRV.
OrthoDB	EOG42Z4PZ.
Gene expression databases
ArrayExpress	O89023.
Bgee	O89023.
CleanEx	MM_TPP1.
Genevestigator	O89023.
GermOnline	ENSMUSG00000030894. Mus musculus.
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
NextBio	282084.
SOURCE	Search...

Entry information

Entry name

TPP1_MOUSE

Accession

Primary (citable) accession number: O89023
Secondary accession number(s): Q543Q8, Q9QUS7

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 15, 1998
Last sequence update:	December 1, 2000
Last modified:	April 3, 2013
This is version 106 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program