P29144 (TPP2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tripeptidyl-peptidase 2
Short name=TPP-2
EC=3.4.14.10

Alternative name(s):
Tripeptidyl aminopeptidase
Tripeptidyl-peptidase II
Short name=TPP-II

Gene names

Name:

TPP2

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	1249 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	Component of the proteolytic cascade acting downstream of the 26S proteasome in the ubiquitin-proteasome pathway. May be able to complement the 26S proteasome function to some extent under conditions in which the latter is inhibited By similarity.
Catalytic activity	Release of an N-terminal tripeptide from a polypeptide.
Subcellular location	Cytoplasm. Nucleus. Note: Translocates to the nucleus in responce to gamma-irradiation. Ref.10
Miscellaneous	The limitation of proteolytic products to tripeptides is achieved by tailoring the size of the substrate-binding cleft: the two negatively charged residues Glu-305 and Glu-331 that are blocking position P4 limit the number of residues that can be accommodated in the binding cleft and thus create a molecular ruler. At the same time, they orient substrates so that the tripeptides are removed exclusively from the N-terminus By similarity.
Sequence similarities	Belongs to the peptidase S8 family.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Molecular function	Aminopeptidase Hydrolase Protease Serine protease
PTM	Acetylation Isopeptide bond Ubl conjugation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	antigen processing and presentation of peptide antigen via MHC class I Traceable author statement. Source: Reactome protein polyubiquitination Traceable author statement. Source: Reactome proteolysis Inferred from Biological aspect of Ancestor. Source: RefGenome
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	aminopeptidase activity Inferred from electronic annotation. Source: UniProtKB-KW serine-type endopeptidase activity Inferred from Biological aspect of Ancestor. Source: RefGenome tripeptidyl-peptidase activity Traceable author statement PubMed 9974389. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.6
	Chain	2 – 1249	1248	Tripeptidyl-peptidase 2		PRO_0000076422
Sites
	Active site	44	1	Charge relay system By similarity
	Active site	264	1	Charge relay system By similarity
	Active site	449	1	Charge relay system By similarity
Amino acid modifications
	Modified residue	2	1	N-acetylalanine Ref.6
	Cross-link	1005		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.9
	Cross-link	1013		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.9
Experimental info
	Sequence conflict	252	1	G → R in AAA36760. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	P29144 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: A26A6249DBF7F3DD	FASTA	1,249	138,350
	10 20 30 40 50 60 MATAATEEPF PFHGLLPKKE TGAASFLCRY PEYDGRGVLI AVLDTGVDPG APGMQVTTDG 70 80 90 100 110 120 KPKIVDIIDT TGSGDVNTAT EVEPKDGEIV GLSGRVLKIP ASWTNPSGKY HIGIKNGYDF 130 140 150 160 170 180 YPKALKERIQ KERKEKIWDP VHRVALAEAC RKQEEFDVAN NGSSQANKLI KEELQSQVEL 190 200 210 220 230 240 LNSFEKKYSD PGPVYDCLVW HDGEVWRACI DSNEDGDLSK STVLRNYKEA QEYGSFGTAE 250 260 270 280 290 300 MLNYSVNIYD DGNLLSIVTS GGAHGTHVAS IAAGHFPEEP ERNGVAPGAQ ILSIKIGDTR 310 320 330 340 350 360 LSTMETGTGL IRAMIEVINH KCDLVNYSYG EATHWPNSGR ICEVINEAVW KHNIIYVSSA 370 380 390 400 410 420 GNNGPCLSTV GCPGGTTSSV IGVGAYVSPD MMVAEYSLRE KLPANQYTWS SRGPSADGAL 430 440 450 460 470 480 GVSISAPGGA IASVPNWTLR GTQLMNGTSM SSPNACGGIA LILSGLKANN IDYTVHSVRR 490 500 510 520 530 540 ALENTAVKAD NIEVFAQGHG IIQVDKAYDY LVQNTSFANK LGFTVTVGNN RGIYLRDPVQ 550 560 570 580 590 600 VAAPSDHGVG IEPVFPENTE NSEKISLQLH LALTSNSSWV QCPSHLELMN QCRHINIRVD 610 620 630 640 650 660 PRGLREGLHY TEVCGYDIAS PNAGPLFRVP ITAVIAAKVN ESSHYDLAFT DVHFKPGQIR 670 680 690 700 710 720 RHFIEVPEGA TWAEVTVCSC SSEVSAKFVL HAVQLVKQRA YRSHEFYKFC SLPEKGTLTE 730 740 750 760 770 780 AFPVLGGKAI EFCIARWWAS LSDVNIDYTI SFHGIVCTAP QLNIHASEGI NRFDVQSSLK 790 800 810 820 830 840 YEDLAPCITL KNWVQTLRPV SAKTKPLGSR DVLPNNRQLY EMVLTYNFHQ PKSGEVTPSC 850 860 870 880 890 900 PLLCELLYES EFDSQLWIIF DQNKRQMGSG DAYPHQYSLK LEKGDYTIRL QIRHEQISDL 910 920 930 940 950 960 ERLKDLPFIV SHRLSNTLSL DIHENHSFAL LGKKKSSNLT LPPKYNQPFF VTSLPDDKIP 970 980 990 1000 1010 1020 KGAGPGCYLA GSLTLSKTEL GKKADVIPVH YYLIPPPTKT KNGSKDKEKD SEKEKDLKEE 1030 1040 1050 1060 1070 1080 FTEALRDLKI QWMTKLDSSD IYNELKETYP NYLPLYVARL HQLDAEKERM KRLNEIVDAA 1090 1100 1110 1120 1130 1140 NAVISHIDQT ALAVYIAMKT DPRPDAATIK NDMDKQKSTL VDALCRKGCA LADHLLHTQA 1150 1160 1170 1180 1190 1200 QDGAISTDAE GKEEEGESPL DSLAETFWET TKWTDLFDNK VLTFAYKHAL VNKMYGRGLK 1210 1220 1230 1240 FATKLVEEKP TKENWKNCIQ LMKLLGWTHC ASFTENWLPI MYPPDYCVF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The DNA sequence and analysis of human chromosome 13." Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T. Nature 428:522-528(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"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]. Tissue: Testis.
[4]	"Nucleotide sequence of cDNA covering the N-terminus of human tripeptidyl peptidase II." Tomkinson B. Biomed. Biochim. Acta 50:727-729(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-55, PROTEIN SEQUENCE OF 6-26.
[5]	"Characterization of cDNA for human tripeptidyl peptidase II: the N-terminal part of the enzyme is similar to subtilisin." Tomkinson B., Jonsson A.-K. Biochemistry 30:168-174(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 56-1249. Tissue: Lymphocyte.
[6]	Bienvenut W.V., Quadroni M. Submitted (JUL-2005) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-18 AND 1036-1046, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, MASS SPECTROMETRY. Tissue: B-cell lymphoma.
[7]	"Immunological cross-reactivity between human tripeptidyl peptidase II and fibronectin." Tomkinson B., Zetterqvist O. Biochem. J. 267:149-154(1990) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 13-26; 1099-1118 AND 440-450.
[8]	"Active site of tripeptidyl peptidase II from human erythrocytes is of the subtilisin type." Tomkinson B., Wernstedt C., Hellman U., Zetterqvist O. Proc. Natl. Acad. Sci. U.S.A. 84:7508-7512(1987) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 441-450.
[9]	"Tryptic digestion of ubiquitin standards reveals an improved strategy for identifying ubiquitinated proteins by mass spectrometry." Denis N.J., Vasilescu J., Lambert J.-P., Smith J.C., Figeys D. Proteomics 7:868-874(2007) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-1005 AND LYS-1013, MASS SPECTROMETRY. Tissue: Mammary cancer.
[10]	"A role for nuclear translocation of tripeptidyl-peptidase II in reactive oxygen species-dependent DNA damage responses." Preta G., de Klark R., Glas R. Biochem. Biophys. Res. Commun. 389:575-579(2009) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[11]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]	"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].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AL158063 Genomic DNA. Translation: CAH72179.1. CH471085 Genomic DNA. Translation: EAX09059.1. BC039905 mRNA. Translation: AAH39905.1. M73047 mRNA. Translation: AAA36760.1. M55169 mRNA. Translation: AAA63263.1.
IPI	IPI00020416.
PIR	S54376.
RefSeq	NP_003282.2. NM_003291.2.
UniGene	Hs.432424.
3D structure databases
ProteinModelPortal	P29144.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-50761N.
STRING	9606.ENSP00000365233.
Protein family/group databases
MEROPS	S08.090.
PTM databases
PhosphoSite	P29144.
Polymorphism databases
DMDM	34223721.
Proteomic databases
PaxDb	P29144.
PeptideAtlas	P29144.
PRIDE	P29144.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000376065; ENSP00000365233; ENSG00000134900.
GeneID	7174.
KEGG	hsa:7174.
UCSC	uc001vpi.4. human.
Organism-specific databases
CTD	7174.
GeneCards	GC13P103249.
HGNC	HGNC:12016. TPP2.
HPA	HPA021069.
MIM	190470. gene.
neXtProt	NX_P29144.
PharmGKB	PA36695.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1404.
HOGENOM	HOG000008178.
HOVERGEN	HBG017992.
KO	K01280.
OrthoDB	EOG4H462Z.
PhylomeDB	P29144.
Enzyme and pathway databases
Reactome	REACT_6900. Immune System.
Gene expression databases
ArrayExpress	P29144.
Bgee	P29144.
CleanEx	HS_TPP2.
Genevestigator	P29144.
GermOnline	ENSG00000134900. Homo sapiens.
Family and domain databases
Gene3D	3.40.50.200. 2 hits.
InterPro	IPR000209. Peptidase_S8/S53_dom. IPR022398. Peptidase_S8_His-AS. IPR023828. Peptidase_S8_Ser-AS. IPR015500. Peptidase_S8_subtilisin-rel. IPR022229. Peptidase_S8A_TPPII. [Graphical view]
PANTHER	PTHR10795. PTHR10795. 1 hit.
Pfam	PF00082. Peptidase_S8. 1 hit. PF12580. TPPII. 1 hit. [Graphical view]
PRINTS	PR00723. SUBTILISIN.
SUPFAM	SSF52743. Pept_S8_S53. 1 hit.
PROSITE	PS00136. SUBTILASE_ASP. False negative. PS00137. SUBTILASE_HIS. 1 hit. PS00138. SUBTILASE_SER. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL6156.
GenomeRNAi	7174.
NextBio	28124.
SOURCE	Search...

Entry information

Entry name

TPP2_HUMAN

Accession

Primary (citable) accession number: P29144
Secondary accession number(s): Q5VZU8

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 1992
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 118 of the entry and version 4 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.