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Protein

Tripeptidyl-peptidase 1

Gene

TPP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Keywordsi

Molecular functionHydrolase, Protease, Serine protease
LigandCalcium, Metal-binding

Enzyme and pathway databases

BRENDAi3.4.14.9 2681
ReactomeiR-HSA-381038 XBP1(S) activates chaperone genes
SABIO-RKiO14773
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

EuPathDBiHostDB:ENSG00000166340.14
HGNCiHGNC:2073 TPP1
MIMi607998 gene
neXtProtiNX_O14773

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Lysosome

Pathology & Biotechi

Involvement in diseasei

Ceroid lipofuscinosis, neuronal, 2 (CLN2)14 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 dbSNP:rs121908195EnsemblClinVar.1
Natural variantiVAR_016790127R → Q in CLN2; displays residual enzyme activity; effectively transported to the lysosome. 3 PublicationsCorresponds to variant dbSNP:rs121908204EnsemblClinVar.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 dbSNP:rs121908205EnsemblClinVar.1
Natural variantiVAR_009605206R → C in CLN2; displays no residual enzyme activity; altered intracellular trafficking. 2 PublicationsCorresponds to variant dbSNP:rs28940573EnsemblClinVar.1
Natural variantiVAR_016792206R → H in CLN2. 1 PublicationCorresponds to variant dbSNP:rs121908209EnsemblClinVar.1
Natural variantiVAR_066884209Y → H in CLN2. 1 Publication1
Natural variantiVAR_066885266R → Q in CLN2. 1 PublicationCorresponds to variant dbSNP:rs757953998EnsemblClinVar.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 dbSNP:rs121908207EnsemblClinVar.1
Natural variantiVAR_016794278Q → P in CLN2. 1 Publication1
Natural variantiVAR_072749278Q → R in CLN2. 1 PublicationCorresponds to variant dbSNP:rs796053439EnsemblClinVar.1
Natural variantiVAR_016795284G → V in CLN2; displays no residual enzyme activity; altered intracellular trafficking. 3 PublicationsCorresponds to variant dbSNP:rs119455957EnsemblClinVar.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 dbSNP:rs119455958EnsemblClinVar.1
Natural variantiVAR_009606287I → N in CLN2; displays no residual enzyme activity; altered intracellular trafficking. 2 PublicationsCorresponds to variant dbSNP:rs121908196EnsemblClinVar.1
Natural variantiVAR_066886339R → Q in CLN2. 1 PublicationCorresponds to variant dbSNP:rs765380155EnsemblClinVar.1
Natural variantiVAR_009607343E → K in CLN2; displays no residual enzyme activity; altered intracellular trafficking. 2 PublicationsCorresponds to variant dbSNP:rs121908197EnsemblClinVar.1
Natural variantiVAR_016797353T → P in CLN2. 1 PublicationCorresponds to variant dbSNP:rs121908206EnsemblClinVar.1
Natural variantiVAR_005643365C → R in CLN2; displays no residual enzyme activity; altered intracellular trafficking. 3 PublicationsCorresponds to variant dbSNP:rs119455953EnsemblClinVar.1
Natural variantiVAR_005644365C → Y in CLN2. 2 PublicationsCorresponds to variant dbSNP:rs119455954EnsemblClinVar.1
Natural variantiVAR_066887382S → R in CLN2. 1 Publication1
Natural variantiVAR_009608385V → D in CLN2. 1 PublicationCorresponds to variant dbSNP:rs121908198EnsemblClinVar.1
Natural variantiVAR_009609389G → E in CLN2. 2 PublicationsCorresponds to variant dbSNP:rs121908199EnsemblClinVar.1
Natural variantiVAR_009610422Q → H in CLN2; displays no residual enzyme activity; altered intracellular trafficking;. 3 PublicationsCorresponds to variant dbSNP:rs121908200EnsemblClinVar.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 dbSNP:rs119455956EnsemblClinVar.1
Natural variantiVAR_066888448A → V in CLN2. 1 Publication1
Natural variantiVAR_009611454A → E in CLN2. 1 PublicationCorresponds to variant dbSNP:rs121908201EnsemblClinVar.1
Natural variantiVAR_016799473G → R in CLN2. 2 PublicationsCorresponds to variant dbSNP:rs121908203EnsemblClinVar.1
Natural variantiVAR_009612475S → L in CLN2; displays no residual enzyme activity; effectively transported to the lysosome. 2 PublicationsCorresponds to variant dbSNP:rs121908202EnsemblClinVar.1
Natural variantiVAR_016800481F → C in CLN2. 1 Publication1
Natural variantiVAR_058435482G → R in CLN2. 1 PublicationCorresponds to variant dbSNP:rs121908208EnsemblClinVar.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 dbSNP:rs121908210EnsemblClinVar.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 dbSNP:rs398122959EnsemblClinVar.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
GeneReviewsiTPP1
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...) asparagine3 Publications1
Glycosylationi222N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi286N-linked (GlcNAc...) asparagine2 Publications1
Glycosylationi313N-linked (GlcNAc...) asparagine3 Publications1
Disulfide bondi365 ↔ 5262 Publications
Glycosylationi443N-linked (GlcNAc...) asparagine4 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
ProteomicsDBi48224
48225 [O14773-2]

PTM databases

iPTMnetiO14773
PhosphoSitePlusiO14773

Miscellaneous databases

PMAP-CutDBiO14773

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 Expressed in 215 organ(s), highest expression level in right adrenal gland cortex
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

Binary interactionsi

Protein-protein interaction databases

BioGridi107611, 24 interactors
DIPiDIP-47434N
IntActiO14773, 33 interactors
MINTiO14773
STRINGi9606.ENSP00000299427

Structurei

Secondary structure

1563
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO14773
SMRiO14773
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO14773

Family & Domainsi

Domains and Repeats

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

Keywords - Domaini

Signal

Phylogenomic databases

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

Family and domain databases

CDDicd04056 Peptidases_S53, 1 hit
cd11377 Pro-peptidase_S53, 1 hit
Gene3Di3.40.50.200, 1 hit
InterProiView protein in InterPro
IPR036852 Peptidase_S8/S53_dom_sf
IPR015366 S53_propep
IPR030400 Sedolisin_dom
PfamiView protein in Pfam
PF09286 Pro-kuma_activ, 1 hit
SMARTiView protein in SMART
SM00944 Pro-kuma_activ, 1 hit
SUPFAMiSSF52743 SSF52743, 1 hit
PROSITEiView protein in PROSITE
PS51695 SEDOLISIN, 1 hit

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

This entry has 2 described isoforms and 12 potential isoforms that are computationally mapped.iShow all

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

Computationally mapped potential isoform sequencesi

There are 12 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A2R8YD45A0A2R8YD45_HUMAN
Tripeptidyl-peptidase 1
TPP1
500Annotation score:
A0A2R8YGD1A0A2R8YGD1_HUMAN
Tripeptidyl-peptidase 1
TPP1
470Annotation score:
A0A2R8Y7U1A0A2R8Y7U1_HUMAN
Tripeptidyl-peptidase 1
TPP1
400Annotation score:
A0A2R8YE64A0A2R8YE64_HUMAN
Tripeptidyl-peptidase 1
TPP1
162Annotation score:
A0A2R8YCK4A0A2R8YCK4_HUMAN
Tripeptidyl-peptidase 1
TPP1
81Annotation score:
A0A2R8Y7I4A0A2R8Y7I4_HUMAN
Tripeptidyl-peptidase 1
TPP1
162Annotation score:
E9PME9E9PME9_HUMAN
Tripeptidyl-peptidase 1
TPP1
30Annotation score:
E9PPA4E9PPA4_HUMAN
Tripeptidyl-peptidase 1
TPP1
39Annotation score:
E7EV34E7EV34_HUMAN
Tripeptidyl-peptidase 1
TPP1
170Annotation score:
A0A2R8YD72A0A2R8YD72_HUMAN
Tripeptidyl-peptidase 1
TPP1
92Annotation score:
There are more potential isoformsShow all

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 dbSNP:rs2734715EnsemblClinVar.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 dbSNP:rs121908195EnsemblClinVar.1
Natural variantiVAR_009604100Q → R2 PublicationsCorresponds to variant dbSNP:rs1800746EnsemblClinVar.1
Natural variantiVAR_016790127R → Q in CLN2; displays residual enzyme activity; effectively transported to the lysosome. 3 PublicationsCorresponds to variant dbSNP:rs121908204EnsemblClinVar.1
Natural variantiVAR_016791153S → P in CLN2. 1
Natural variantiVAR_005642175R → H1 PublicationCorresponds to variant dbSNP:rs764922748EnsemblClinVar.1
Natural variantiVAR_037573185R → C. Corresponds to variant dbSNP:rs34758634EnsemblClinVar.1
Natural variantiVAR_063640202P → L in CLN2; displays no residual enzyme activity; altered intracellular trafficking. 2 PublicationsCorresponds to variant dbSNP:rs121908205EnsemblClinVar.1
Natural variantiVAR_009605206R → C in CLN2; displays no residual enzyme activity; altered intracellular trafficking. 2 PublicationsCorresponds to variant dbSNP:rs28940573EnsemblClinVar.1
Natural variantiVAR_016792206R → H in CLN2. 1 PublicationCorresponds to variant dbSNP:rs121908209EnsemblClinVar.1
Natural variantiVAR_066884209Y → H in CLN2. 1 Publication1
Natural variantiVAR_066885266R → Q in CLN2. 1 PublicationCorresponds to variant dbSNP:rs757953998EnsemblClinVar.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 dbSNP:rs121908207EnsemblClinVar.1
Natural variantiVAR_016794278Q → P in CLN2. 1 Publication1
Natural variantiVAR_072749278Q → R in CLN2. 1 PublicationCorresponds to variant dbSNP:rs796053439EnsemblClinVar.1
Natural variantiVAR_016795284G → V in CLN2; displays no residual enzyme activity; altered intracellular trafficking. 3 PublicationsCorresponds to variant dbSNP:rs119455957EnsemblClinVar.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 dbSNP:rs119455958EnsemblClinVar.1
Natural variantiVAR_009606287I → N in CLN2; displays no residual enzyme activity; altered intracellular trafficking. 2 PublicationsCorresponds to variant dbSNP:rs121908196EnsemblClinVar.1
Natural variantiVAR_066886339R → Q in CLN2. 1 PublicationCorresponds to variant dbSNP:rs765380155EnsemblClinVar.1
Natural variantiVAR_009607343E → K in CLN2; displays no residual enzyme activity; altered intracellular trafficking. 2 PublicationsCorresponds to variant dbSNP:rs121908197EnsemblClinVar.1
Natural variantiVAR_016797353T → P in CLN2. 1 PublicationCorresponds to variant dbSNP:rs121908206EnsemblClinVar.1
Natural variantiVAR_005643365C → R in CLN2; displays no residual enzyme activity; altered intracellular trafficking. 3 PublicationsCorresponds to variant dbSNP:rs119455953EnsemblClinVar.1
Natural variantiVAR_005644365C → Y in CLN2. 2 PublicationsCorresponds to variant dbSNP:rs119455954EnsemblClinVar.1
Natural variantiVAR_066887382S → R in CLN2. 1 Publication1
Natural variantiVAR_009608385V → D in CLN2. 1 PublicationCorresponds to variant dbSNP:rs121908198EnsemblClinVar.1
Natural variantiVAR_009609389G → E in CLN2. 2 PublicationsCorresponds to variant dbSNP:rs121908199EnsemblClinVar.1
Natural variantiVAR_009610422Q → H in CLN2; displays no residual enzyme activity; altered intracellular trafficking;. 3 PublicationsCorresponds to variant dbSNP:rs121908200EnsemblClinVar.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 dbSNP:rs119455956EnsemblClinVar.1
Natural variantiVAR_066888448A → V in CLN2. 1 Publication1
Natural variantiVAR_009611454A → E in CLN2. 1 PublicationCorresponds to variant dbSNP:rs121908201EnsemblClinVar.1
Natural variantiVAR_070917466V → G in SCAR7. 1 PublicationCorresponds to variant dbSNP:rs398122959EnsemblClinVar.1
Natural variantiVAR_016799473G → R in CLN2. 2 PublicationsCorresponds to variant dbSNP:rs121908203EnsemblClinVar.1
Natural variantiVAR_009612475S → L in CLN2; displays no residual enzyme activity; effectively transported to the lysosome. 2 PublicationsCorresponds to variant dbSNP:rs121908202EnsemblClinVar.1
Natural variantiVAR_016800481F → C in CLN2. 1 Publication1
Natural variantiVAR_058435482G → R in CLN2. 1 PublicationCorresponds to variant dbSNP:rs121908208EnsemblClinVar.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 dbSNP:rs121908210EnsemblClinVar.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]
ENST00000642892; ENSP00000494165; ENSG00000166340 [O14773-2]
ENST00000645620; ENSP00000493657; ENSG00000166340 [O14773-2]
ENST00000647152; ENSP00000495893; ENSG00000166340 [O14773-2]
GeneIDi1200
KEGGihsa:1200
UCSCiuc001mek.2 human [O14773-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

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, 24 interactors
DIPiDIP-47434N
IntActiO14773, 33 interactors
MINTiO14773
STRINGi9606.ENSP00000299427

Protein family/group databases

MEROPSiS53.003

PTM databases

iPTMnetiO14773
PhosphoSitePlusiO14773

Polymorphism and mutation databases

BioMutaiTPP1

Proteomic databases

EPDiO14773
MaxQBiO14773
PaxDbiO14773
PeptideAtlasiO14773
PRIDEiO14773
ProteomicsDBi48224
48225 [O14773-2]

Protocols and materials databases

DNASUi1200
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000299427; ENSP00000299427; ENSG00000166340 [O14773-1]
ENST00000533371; ENSP00000437066; ENSG00000166340 [O14773-2]
ENST00000642892; ENSP00000494165; ENSG00000166340 [O14773-2]
ENST00000645620; ENSP00000493657; ENSG00000166340 [O14773-2]
ENST00000647152; ENSP00000495893; ENSG00000166340 [O14773-2]
GeneIDi1200
KEGGihsa:1200
UCSCiuc001mek.2 human [O14773-1]

Organism-specific databases

CTDi1200
DisGeNETi1200
EuPathDBiHostDB:ENSG00000166340.14
GeneCardsiTPP1
GeneReviewsiTPP1
H-InvDBiHIX0009410
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
OMAiISTWVYS
OrthoDBiEOG091G059I
PhylomeDBiO14773
TreeFamiTF333497

Enzyme and pathway databases

BRENDAi3.4.14.9 2681
ReactomeiR-HSA-381038 XBP1(S) activates chaperone genes
SABIO-RKiO14773
SignaLinkiO14773

Miscellaneous databases

ChiTaRSiTPP1 human
EvolutionaryTraceiO14773
GeneWikiiTripeptidyl_peptidase_I
GenomeRNAii1200
PMAP-CutDBiO14773
PROiPR:O14773
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000166340 Expressed in 215 organ(s), highest expression level in right adrenal gland cortex
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
InterProiView protein in InterPro
IPR036852 Peptidase_S8/S53_dom_sf
IPR015366 S53_propep
IPR030400 Sedolisin_dom
PfamiView protein in Pfam
PF09286 Pro-kuma_activ, 1 hit
SMARTiView protein in SMART
SM00944 Pro-kuma_activ, 1 hit
SUPFAMiSSF52743 SSF52743, 1 hit
PROSITEiView protein in PROSITE
PS51695 SEDOLISIN, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTPP1_HUMAN
AccessioniPrimary (citable) accession number: O14773
Secondary accession number(s): Q53HT1
, Q5JAK6, Q6UX56, Q71JP6, Q96C37
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: May 30, 2006
Last modified: September 12, 2018
This is version 190 of the entry and version 2 of the sequence. See 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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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