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Protein

Tripeptidyl-peptidase 1

Gene

TPP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity

Catalytic activityi

Release of an N-terminal tripeptide from a polypeptide, but also has endopeptidase activity.

Cofactori

Ca2+2 PublicationsNote: Binds 1 Ca2+ ion per subunit.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei272Charge relay system2 Publications1
Active sitei276Charge relay system2 Publications1
Active sitei475Charge relay system2 Publications1
Metal bindingi517Calcium2 Publications1
Metal bindingi518Calcium; via carbonyl oxygen2 Publications1
Metal bindingi539Calcium; via carbonyl oxygen2 Publications1
Metal bindingi541Calcium; via carbonyl oxygen2 Publications1
Metal bindingi543Calcium2 Publications1

GO - Molecular functioni

  • endopeptidase activity Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • peptidase activity Source: UniProtKB
  • peptide binding Source: UniProtKB
  • serine-type endopeptidase activity Source: InterPro
  • serine-type peptidase activity Source: UniProtKB
  • tripeptidyl-peptidase activity Source: UniProtKB

GO - Biological processi

  • bone resorption Source: UniProtKB
  • central nervous system development Source: GO_Central
  • epithelial cell differentiation Source: UniProtKB
  • IRE1-mediated unfolded protein response Source: Reactome
  • lipid metabolic process Source: ProtInc
  • lysosome organization Source: UniProtKB
  • nervous system development Source: UniProtKB
  • neuromuscular process controlling balance Source: UniProtKB
  • peptide catabolic process Source: UniProtKB
  • protein catabolic process Source: UniProtKB
  • proteolysis Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Keywords - Ligandi

Calcium, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:HS09379-MONOMER.
BRENDAi3.4.14.9. 2681.
ReactomeiR-HSA-381038. XBP1(S) activates chaperone genes.
SABIO-RKO14773.
SignaLinkiO14773.

Protein family/group databases

MEROPSiS53.003.

Names & Taxonomyi

Protein namesi
Recommended name:
Tripeptidyl-peptidase 1 (EC:3.4.14.9)
Short name:
TPP-1
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 namesi
Name:TPP1
Synonyms:CLN2
ORF Names:GIG1, UNQ267/PRO304
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:2073. TPP1.

Subcellular locationi

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • lysosomal lumen Source: Reactome
  • lysosome Source: UniProtKB
  • melanosome Source: UniProtKB-SubCell
  • mitochondrion Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Lysosome

Pathology & Biotechi

Involvement in diseasei

Ceroid lipofuscinosis, neuronal, 2 (CLN2)13 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:204500
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06688362S → T in CLN2. 1 Publication1
Natural variantiVAR_00960377G → R in CLN2; displays very low residual enzyme activity; altered intracellular trafficking. 2 PublicationsCorresponds to variant rs121908195dbSNPEnsembl.1
Natural variantiVAR_016790127R → Q in CLN2; displays residual enzyme activity; effectively transported to the lysosome. 3 PublicationsCorresponds to variant rs121908204dbSNPEnsembl.1
Natural variantiVAR_016791153S → P in CLN2. 1
Natural variantiVAR_063640202P → L in CLN2; displays no residual enzyme activity; altered intracellular trafficking. 2 PublicationsCorresponds to variant rs121908205dbSNPEnsembl.1
Natural variantiVAR_009605206R → C in CLN2; displays no residual enzyme activity; altered intracellular trafficking. 2 PublicationsCorresponds to variant rs28940573dbSNPEnsembl.1
Natural variantiVAR_016792206R → H in CLN2. 1 PublicationCorresponds to variant rs121908209dbSNPEnsembl.1
Natural variantiVAR_066884209Y → H in CLN2. 1 Publication1
Natural variantiVAR_066885266R → Q in CLN2. 1 PublicationCorresponds to variant rs757953998dbSNPEnsembl.1
Natural variantiVAR_016793277V → M in CLN2; displays no residual enzyme activity; altered intracellular trafficking; demonstrates enhanced processing in response to folding improvement treatment. 2 PublicationsCorresponds to variant rs121908207dbSNPEnsembl.1
Natural variantiVAR_016794278Q → P in CLN2. 1 Publication1
Natural variantiVAR_072749278Q → R in CLN2. 1 PublicationCorresponds to variant rs796053439dbSNPEnsembl.1
Natural variantiVAR_016795284G → V in CLN2; displays no residual enzyme activity; altered intracellular trafficking. 3 PublicationsCorresponds to variant rs119455957dbSNPEnsembl.1
Natural variantiVAR_016796286N → S in CLN2; enzymatically inactive; lacks one oligosaccharide chain resulting in enzymatic inactivation and possibly prelysosomal protein degradation; altered intracellular trafficking. 3 PublicationsCorresponds to variant rs119455958dbSNPEnsembl.1
Natural variantiVAR_009606287I → N in CLN2; displays no residual enzyme activity; altered intracellular trafficking. 2 PublicationsCorresponds to variant rs121908196dbSNPEnsembl.1
Natural variantiVAR_066886339R → Q in CLN2. 1 PublicationCorresponds to variant rs765380155dbSNPEnsembl.1
Natural variantiVAR_009607343E → K in CLN2; displays no residual enzyme activity; altered intracellular trafficking. 2 PublicationsCorresponds to variant rs121908197dbSNPEnsembl.1
Natural variantiVAR_016797353T → P in CLN2. 1 PublicationCorresponds to variant rs121908206dbSNPEnsembl.1
Natural variantiVAR_005643365C → R in CLN2; displays no residual enzyme activity; altered intracellular trafficking. 3 PublicationsCorresponds to variant rs119455953dbSNPEnsembl.1
Natural variantiVAR_005644365C → Y in CLN2. 2 PublicationsCorresponds to variant rs119455954dbSNPEnsembl.1
Natural variantiVAR_066887382S → R in CLN2. 1 Publication1
Natural variantiVAR_009608385V → D in CLN2. 1 PublicationCorresponds to variant rs121908198dbSNPEnsembl.1
Natural variantiVAR_009609389G → E in CLN2. 2 PublicationsCorresponds to variant rs121908199dbSNPEnsembl.1
Natural variantiVAR_009610422Q → H in CLN2; displays no residual enzyme activity; altered intracellular trafficking;. 3 PublicationsCorresponds to variant rs121908200dbSNPEnsembl.1
Natural variantiVAR_016798428K → N in CLN2. 1 Publication1
Natural variantiVAR_005645447R → 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. 3 PublicationsCorresponds to variant rs119455956dbSNPEnsembl.1
Natural variantiVAR_066888448A → V in CLN2. 1 Publication1
Natural variantiVAR_009611454A → E in CLN2. 1 PublicationCorresponds to variant rs121908201dbSNPEnsembl.1
Natural variantiVAR_016799473G → R in CLN2. 2 PublicationsCorresponds to variant rs121908203dbSNPEnsembl.1
Natural variantiVAR_009612475S → L in CLN2; displays no residual enzyme activity; effectively transported to the lysosome. 2 PublicationsCorresponds to variant rs121908202dbSNPEnsembl.1
Natural variantiVAR_016800481F → C in CLN2. 1 Publication1
Natural variantiVAR_058435482G → R in CLN2. 1 PublicationCorresponds to variant rs121908208dbSNPEnsembl.1
Natural variantiVAR_066889501G → C in CLN2. 1 Publication1
Natural variantiVAR_066890504N → Y in CLN2. 1 Publication1
Natural variantiVAR_063641544P → S in CLN2; displays residual enzyme activity; effectively transported to the lysosome. 1 PublicationCorresponds to variant rs121908210dbSNPEnsembl.1
Natural variantiVAR_066891548W → R in CLN2. 1 Publication1
Spinocerebellar ataxia, autosomal recessive, 7 (SCAR7)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionSpinocerebellar 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.
See also OMIM:609270
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_070917466V → G in SCAR7. 1 PublicationCorresponds to variant rs398122959dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi236H → A: No effect. 1 Publication1
Mutagenesisi360D → A: Inactive. Impaired processing. 1 Publication1
Mutagenesisi475S → A: Inactive. Impaired processing. 1 Publication1
Mutagenesisi517D → A: Inactive. Impaired processing. 1 Publication1

Keywords - Diseasei

Disease mutation, Epilepsy, Neurodegeneration, Neuronal ceroid lipofuscinosis, Spinocerebellar ataxia

Organism-specific databases

DisGeNETi1200.
MalaCardsiTPP1.
MIMi204500. phenotype.
609270. phenotype.
OpenTargetsiENSG00000166340.
Orphaneti284324. Childhood-onset autosomal recessive slowly progressive spinocerebellar ataxia.
228349. CLN2 disease.
PharmGKBiPA26600.

Polymorphism and mutation databases

BioMutaiTPP1.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 191 PublicationAdd BLAST19
PropeptideiPRO_000002737420 – 195Removed in mature formCombined sources1 PublicationAdd BLAST176
ChainiPRO_0000027375196 – 563Tripeptidyl-peptidase 1Add BLAST368

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi111 ↔ 1222 Publications
Glycosylationi210N-linked (GlcNAc...)3 Publications1
Glycosylationi222N-linked (GlcNAc...)1 Publication1
Glycosylationi286N-linked (GlcNAc...)2 Publications1
Glycosylationi313N-linked (GlcNAc...)3 Publications1
Disulfide bondi365 ↔ 5262 Publications
Glycosylationi443N-linked (GlcNAc...)4 Publications1
Disulfide bondi522 ↔ 5372 Publications

Post-translational modificationi

Activated by autocatalytic proteolytical processing upon acidification. N-glycosylation is required for processing and activity.4 Publications

Keywords - PTMi

Autocatalytic cleavage, Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

EPDiO14773.
MaxQBiO14773.
PaxDbiO14773.
PeptideAtlasiO14773.
PRIDEiO14773.

PTM databases

iPTMnetiO14773.
PhosphoSitePlusiO14773.

Miscellaneous databases

PMAP-CutDBO14773.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000166340.
CleanExiHS_TPP1.
ExpressionAtlasiO14773. baseline and differential.
GenevisibleiO14773. HS.

Organism-specific databases

HPAiHPA037709.
HPA044868.

Interactioni

Subunit structurei

Monomer (PubMed:19038967). Interacts with CLN5 (PubMed:19941651).2 Publications

Protein-protein interaction databases

BioGridi107611. 20 interactors.
DIPiDIP-47434N.
IntActiO14773. 24 interactors.
MINTiMINT-5002180.
STRINGi9606.ENSP00000299427.

Structurei

Secondary structure

1563
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi35 – 40Combined sources6
Beta strandi46 – 53Combined sources8
Helixi58 – 69Combined sources12
Turni74 – 77Combined sources4
Helixi82 – 89Combined sources8
Helixi93 – 106Combined sources14
Beta strandi109 – 113Combined sources5
Beta strandi119 – 125Combined sources7
Helixi126 – 132Combined sources7
Beta strandi139 – 143Combined sources5
Turni144 – 147Combined sources4
Beta strandi148 – 152Combined sources5
Helixi161 – 163Combined sources3
Turni164 – 166Combined sources3
Beta strandi167 – 170Combined sources4
Helixi202 – 208Combined sources7
Beta strandi219 – 221Combined sources3
Beta strandi224 – 229Combined sources6
Helixi237 – 247Combined sources11
Beta strandi258 – 262Combined sources5
Helixi271 – 283Combined sources13
Turni284 – 286Combined sources3
Beta strandi287 – 292Combined sources6
Turni295 – 300Combined sources6
Helixi303 – 311Combined sources9
Beta strandi319 – 324Combined sources6
Helixi329 – 331Combined sources3
Helixi334 – 349Combined sources16
Beta strandi353 – 357Combined sources5
Beta strandi366 – 368Combined sources3
Beta strandi371 – 373Combined sources3
Turni379 – 381Combined sources3
Beta strandi385 – 397Combined sources13
Beta strandi402 – 404Combined sources3
Beta strandi411 – 417Combined sources7
Helixi420 – 422Combined sources3
Helixi423 – 432Combined sources10
Helixi439 – 441Combined sources3
Beta strandi446 – 449Combined sources4
Beta strandi451 – 455Combined sources5
Beta strandi457 – 463Combined sources7
Beta strandi466 – 471Combined sources6
Helixi474 – 494Combined sources21
Helixi504 – 509Combined sources6
Turni510 – 514Combined sources5
Beta strandi522 – 525Combined sources4
Turni529 – 533Combined sources5
Beta strandi534 – 537Combined sources4
Turni544 – 546Combined sources3
Helixi553 – 558Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1R60model-A196-563[»]
3EDYX-ray1.85A20-563[»]
3EE6X-ray2.35A/B1-563[»]
ProteinModelPortaliO14773.
SMRiO14773.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO14773.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini199 – 563Peptidase S53Add BLAST365

Sequence similaritiesi

Contains 1 peptidase S53 domain.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IICY. Eukaryota.
COG4934. LUCA.
GeneTreeiENSGT00390000008684.
HOGENOMiHOG000171253.
HOVERGENiHBG004449.
InParanoidiO14773.
KOiK01279.
OMAiGNFAHQA.
OrthoDBiEOG091G059I.
PhylomeDBiO14773.
TreeFamiTF333497.

Family and domain databases

CDDicd04056. Peptidases_S53. 1 hit.
cd11377. Pro-peptidase_S53. 1 hit.
Gene3Di3.40.50.200. 1 hit.
InterProiIPR000209. Peptidase_S8/S53_dom.
IPR009020. Propept_inh.
IPR015366. S53_propep.
IPR030400. Sedolisin_dom.
[Graphical view]
PfamiPF09286. Pro-kuma_activ. 1 hit.
[Graphical view]
SMARTiSM00944. Pro-kuma_activ. 1 hit.
[Graphical view]
SUPFAMiSSF52743. SSF52743. 1 hit.
SSF54897. SSF54897. 1 hit.
PROSITEiPS51695. SEDOLISIN. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O14773-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MGLQACLLGL FALILSGKCS YSPEPDQRRT LPPGWVSLGR ADPEEELSLT
60 70 80 90 100
FALRQQNVER LSELVQAVSD PSSPQYGKYL TLENVADLVR PSPLTLHTVQ
110 120 130 140 150
KWLLAAGAQK CHSVITQDFL TCWLSIRQAE LLLPGAEFHH YVGGPTETHV
160 170 180 190 200
VRSPHPYQLP QALAPHVDFV GGLHRFPPTS SLRQRPEPQV TGTVGLHLGV
210 220 230 240 250
TPSVIRKRYN LTSQDVGSGT SNNSQACAQF LEQYFHDSDL AQFMRLFGGN
260 270 280 290 300
FAHQASVARV VGQQGRGRAG IEASLDVQYL MSAGANISTW VYSSPGRHEG
310 320 330 340 350
QEPFLQWLML LSNESALPHV HTVSYGDDED SLSSAYIQRV NTELMKAAAR
360 370 380 390 400
GLTLLFASGD SGAGCWSVSG RHQFRPTFPA SSPYVTTVGG TSFQEPFLIT
410 420 430 440 450
NEIVDYISGG GFSNVFPRPS YQEEAVTKFL SSSPHLPPSS YFNASGRAYP
460 470 480 490 500
DVAALSDGYW VVSNRVPIPW VSGTSASTPV FGGILSLINE HRILSGRPPL
510 520 530 540 550
GFLNPRLYQQ HGAGLFDVTR GCHESCLDEE VEGQGFCSGP GWDPVTGWGT
560
PNFPALLKTL LNP
Length:563
Mass (Da):61,248
Last modified:May 30, 2006 - v2
Checksum:i7299D902F6AE8555
GO
Isoform 2 (identifier: O14773-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-243: Missing.

Note: No experimental confirmation available.
Show »
Length:320
Mass (Da):34,464
Checksum:i707AE6D4A90B0FBC
GO

Sequence cautioni

The sequence AAM08412 differs from that shown. Incorrectly indicated as originating from bovine.Curated
The sequence AAQ88866 differs from that shown. Reason: Frameshift at position 551.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti115I → N in BAD96219 (Ref. 6) Curated1
Sequence conflicti373Q → E in AAH14863 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03757262S → L.Corresponds to variant rs2734715dbSNPEnsembl.1
Natural variantiVAR_06688362S → T in CLN2. 1 Publication1
Natural variantiVAR_00960377G → R in CLN2; displays very low residual enzyme activity; altered intracellular trafficking. 2 PublicationsCorresponds to variant rs121908195dbSNPEnsembl.1
Natural variantiVAR_009604100Q → R.2 PublicationsCorresponds to variant rs1800746dbSNPEnsembl.1
Natural variantiVAR_016790127R → Q in CLN2; displays residual enzyme activity; effectively transported to the lysosome. 3 PublicationsCorresponds to variant rs121908204dbSNPEnsembl.1
Natural variantiVAR_016791153S → P in CLN2. 1
Natural variantiVAR_005642175R → H.1 PublicationCorresponds to variant rs764922748dbSNPEnsembl.1
Natural variantiVAR_037573185R → C.Corresponds to variant rs34758634dbSNPEnsembl.1
Natural variantiVAR_063640202P → L in CLN2; displays no residual enzyme activity; altered intracellular trafficking. 2 PublicationsCorresponds to variant rs121908205dbSNPEnsembl.1
Natural variantiVAR_009605206R → C in CLN2; displays no residual enzyme activity; altered intracellular trafficking. 2 PublicationsCorresponds to variant rs28940573dbSNPEnsembl.1
Natural variantiVAR_016792206R → H in CLN2. 1 PublicationCorresponds to variant rs121908209dbSNPEnsembl.1
Natural variantiVAR_066884209Y → H in CLN2. 1 Publication1
Natural variantiVAR_066885266R → Q in CLN2. 1 PublicationCorresponds to variant rs757953998dbSNPEnsembl.1
Natural variantiVAR_016793277V → M in CLN2; displays no residual enzyme activity; altered intracellular trafficking; demonstrates enhanced processing in response to folding improvement treatment. 2 PublicationsCorresponds to variant rs121908207dbSNPEnsembl.1
Natural variantiVAR_016794278Q → P in CLN2. 1 Publication1
Natural variantiVAR_072749278Q → R in CLN2. 1 PublicationCorresponds to variant rs796053439dbSNPEnsembl.1
Natural variantiVAR_016795284G → V in CLN2; displays no residual enzyme activity; altered intracellular trafficking. 3 PublicationsCorresponds to variant rs119455957dbSNPEnsembl.1
Natural variantiVAR_016796286N → S in CLN2; enzymatically inactive; lacks one oligosaccharide chain resulting in enzymatic inactivation and possibly prelysosomal protein degradation; altered intracellular trafficking. 3 PublicationsCorresponds to variant rs119455958dbSNPEnsembl.1
Natural variantiVAR_009606287I → N in CLN2; displays no residual enzyme activity; altered intracellular trafficking. 2 PublicationsCorresponds to variant rs121908196dbSNPEnsembl.1
Natural variantiVAR_066886339R → Q in CLN2. 1 PublicationCorresponds to variant rs765380155dbSNPEnsembl.1
Natural variantiVAR_009607343E → K in CLN2; displays no residual enzyme activity; altered intracellular trafficking. 2 PublicationsCorresponds to variant rs121908197dbSNPEnsembl.1
Natural variantiVAR_016797353T → P in CLN2. 1 PublicationCorresponds to variant rs121908206dbSNPEnsembl.1
Natural variantiVAR_005643365C → R in CLN2; displays no residual enzyme activity; altered intracellular trafficking. 3 PublicationsCorresponds to variant rs119455953dbSNPEnsembl.1
Natural variantiVAR_005644365C → Y in CLN2. 2 PublicationsCorresponds to variant rs119455954dbSNPEnsembl.1
Natural variantiVAR_066887382S → R in CLN2. 1 Publication1
Natural variantiVAR_009608385V → D in CLN2. 1 PublicationCorresponds to variant rs121908198dbSNPEnsembl.1
Natural variantiVAR_009609389G → E in CLN2. 2 PublicationsCorresponds to variant rs121908199dbSNPEnsembl.1
Natural variantiVAR_009610422Q → H in CLN2; displays no residual enzyme activity; altered intracellular trafficking;. 3 PublicationsCorresponds to variant rs121908200dbSNPEnsembl.1
Natural variantiVAR_016798428K → N in CLN2. 1 Publication1
Natural variantiVAR_005645447R → 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. 3 PublicationsCorresponds to variant rs119455956dbSNPEnsembl.1
Natural variantiVAR_066888448A → V in CLN2. 1 Publication1
Natural variantiVAR_009611454A → E in CLN2. 1 PublicationCorresponds to variant rs121908201dbSNPEnsembl.1
Natural variantiVAR_070917466V → G in SCAR7. 1 PublicationCorresponds to variant rs398122959dbSNPEnsembl.1
Natural variantiVAR_016799473G → R in CLN2. 2 PublicationsCorresponds to variant rs121908203dbSNPEnsembl.1
Natural variantiVAR_009612475S → L in CLN2; displays no residual enzyme activity; effectively transported to the lysosome. 2 PublicationsCorresponds to variant rs121908202dbSNPEnsembl.1
Natural variantiVAR_016800481F → C in CLN2. 1 Publication1
Natural variantiVAR_058435482G → R in CLN2. 1 PublicationCorresponds to variant rs121908208dbSNPEnsembl.1
Natural variantiVAR_066889501G → C in CLN2. 1 Publication1
Natural variantiVAR_066890504N → Y in CLN2. 1 Publication1
Natural variantiVAR_063641544P → S in CLN2; displays residual enzyme activity; effectively transported to the lysosome. 1 PublicationCorresponds to variant rs121908210dbSNPEnsembl.1
Natural variantiVAR_066891548W → R in CLN2. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0131181 – 243Missing in isoform 2. 1 PublicationAdd BLAST243

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF017456 mRNA. Translation: AAB80725.1.
AF039704 Genomic DNA. Translation: AAC98480.1.
AF491290 mRNA. Translation: AAM08412.1. Sequence problems.
AY268890 mRNA. Translation: AAQ72732.1.
AY358502 mRNA. Translation: AAQ88866.1. Frameshift.
AK222499 mRNA. Translation: BAD96219.1.
BC014863 mRNA. Translation: AAH14863.1.
CCDSiCCDS7770.1. [O14773-1]
RefSeqiNP_000382.3. NM_000391.3. [O14773-1]
UniGeneiHs.523454.

Genome annotation databases

EnsembliENST00000299427; ENSP00000299427; ENSG00000166340. [O14773-1]
ENST00000533371; ENSP00000437066; ENSG00000166340. [O14773-2]
GeneIDi1200.
KEGGihsa:1200.
UCSCiuc001mek.2. human. [O14773-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NCL CLN2

Neural Ceroid Lipofuscinoses mutation db

Mendelian genes trieptidyl peptidase I (TPP1)

Leiden Open Variation Database (LOVD)

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF017456 mRNA. Translation: AAB80725.1.
AF039704 Genomic DNA. Translation: AAC98480.1.
AF491290 mRNA. Translation: AAM08412.1. Sequence problems.
AY268890 mRNA. Translation: AAQ72732.1.
AY358502 mRNA. Translation: AAQ88866.1. Frameshift.
AK222499 mRNA. Translation: BAD96219.1.
BC014863 mRNA. Translation: AAH14863.1.
CCDSiCCDS7770.1. [O14773-1]
RefSeqiNP_000382.3. NM_000391.3. [O14773-1]
UniGeneiHs.523454.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1R60model-A196-563[»]
3EDYX-ray1.85A20-563[»]
3EE6X-ray2.35A/B1-563[»]
ProteinModelPortaliO14773.
SMRiO14773.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107611. 20 interactors.
DIPiDIP-47434N.
IntActiO14773. 24 interactors.
MINTiMINT-5002180.
STRINGi9606.ENSP00000299427.

Protein family/group databases

MEROPSiS53.003.

PTM databases

iPTMnetiO14773.
PhosphoSitePlusiO14773.

Polymorphism and mutation databases

BioMutaiTPP1.

Proteomic databases

EPDiO14773.
MaxQBiO14773.
PaxDbiO14773.
PeptideAtlasiO14773.
PRIDEiO14773.

Protocols and materials databases

DNASUi1200.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000299427; ENSP00000299427; ENSG00000166340. [O14773-1]
ENST00000533371; ENSP00000437066; ENSG00000166340. [O14773-2]
GeneIDi1200.
KEGGihsa:1200.
UCSCiuc001mek.2. human. [O14773-1]

Organism-specific databases

CTDi1200.
DisGeNETi1200.
GeneCardsiTPP1.
GeneReviewsiTPP1.
H-InvDBHIX0009410.
HGNCiHGNC:2073. TPP1.
HPAiHPA037709.
HPA044868.
MalaCardsiTPP1.
MIMi204500. phenotype.
607998. gene.
609270. phenotype.
neXtProtiNX_O14773.
OpenTargetsiENSG00000166340.
Orphaneti284324. Childhood-onset autosomal recessive slowly progressive spinocerebellar ataxia.
228349. CLN2 disease.
PharmGKBiPA26600.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IICY. Eukaryota.
COG4934. LUCA.
GeneTreeiENSGT00390000008684.
HOGENOMiHOG000171253.
HOVERGENiHBG004449.
InParanoidiO14773.
KOiK01279.
OMAiGNFAHQA.
OrthoDBiEOG091G059I.
PhylomeDBiO14773.
TreeFamiTF333497.

Enzyme and pathway databases

BioCyciZFISH:HS09379-MONOMER.
BRENDAi3.4.14.9. 2681.
ReactomeiR-HSA-381038. XBP1(S) activates chaperone genes.
SABIO-RKO14773.
SignaLinkiO14773.

Miscellaneous databases

ChiTaRSiTPP1. human.
EvolutionaryTraceiO14773.
GeneWikiiTripeptidyl_peptidase_I.
GenomeRNAii1200.
PMAP-CutDBO14773.
PROiO14773.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000166340.
CleanExiHS_TPP1.
ExpressionAtlasiO14773. baseline and differential.
GenevisibleiO14773. HS.

Family and domain databases

CDDicd04056. Peptidases_S53. 1 hit.
cd11377. Pro-peptidase_S53. 1 hit.
Gene3Di3.40.50.200. 1 hit.
InterProiIPR000209. Peptidase_S8/S53_dom.
IPR009020. Propept_inh.
IPR015366. S53_propep.
IPR030400. Sedolisin_dom.
[Graphical view]
PfamiPF09286. Pro-kuma_activ. 1 hit.
[Graphical view]
SMARTiSM00944. Pro-kuma_activ. 1 hit.
[Graphical view]
SUPFAMiSSF52743. SSF52743. 1 hit.
SSF54897. SSF54897. 1 hit.
PROSITEiPS51695. SEDOLISIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTPP1_HUMAN
AccessioniPrimary (citable) accession number: O14773
Secondary accession number(s): Q53HT1
, Q5JAK6, Q6UX56, Q71JP6, Q96C37
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: May 30, 2006
Last modified: November 2, 2016
This is version 178 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.