UniProtKB - Q9NQH7 (XPP3_HUMAN)
Xaa-Pro aminopeptidase 3
XPNPEP3
Functioni
Catalyzes the removal of a penultimate prolyl residue from the N-termini of peptides, such as Leu-Pro-Ala (PubMed:25609706, PubMed:28476889).
Also shows low activity towards peptides with Ala or Ser at the P1 position (PubMed:28476889).
2 PublicationsPromotes TNFRSF1B-mediated phosphorylation of MAPK8/JNK1 and MAPK9/JNK2, suggesting a function as an adapter protein for TNFRSF1B; the effect is independent of XPNPEP3 peptidase activity. May inhibit apoptotic cell death induced via TNF-TNFRSF1B signaling.
1 PublicationCatalytic activityi
- Release of any N-terminal amino acid, including proline, that is linked to proline, even from a dipeptide or tripeptide.2 Publications EC:3.4.11.9
Cofactori
Kineticsi
- KM=1.62 mM for Met-Pro-Ala1 Publication
- KM=2.45 mM for Leu-Pro-Ala1 Publication
- KM=3.06 mM for Phe-Pro-Ala1 Publication
- KM=0.55 mM for Tyr-Pro-Ala1 Publication
- KM=4.91 mM for Tyr-Ser-Ser1 Publication
- KM=4.20 mM for Tyr-Ala-Ala1 Publication
- KM=3.74 mM for Tyr-Ser-Ser-Ala-Ala-Ala-Ala1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 300 | SubstrateCombined sources1 Publication | 1 | |
Metal bindingi | 331 | Manganese 2Combined sources1 Publication | 1 | |
Binding sitei | 331 | SubstrateCombined sources1 Publication | 1 | |
Metal bindingi | 342 | Manganese 1Combined sources1 Publication | 1 | |
Metal bindingi | 342 | Manganese 2Combined sources1 Publication | 1 | |
Binding sitei | 342 | SubstrateCombined sources1 Publication1 Publication | 1 | |
Metal bindingi | 424 | Manganese 1Combined sources1 Publication | 1 | |
Binding sitei | 424 | SubstrateCombined sources1 Publication | 1 | |
Binding sitei | 431 | SubstrateCombined sources1 Publication | 1 | |
Metal bindingi | 451 | Manganese 1Combined sources1 Publication | 1 | |
Binding sitei | 451 | SubstrateCombined sources1 Publication | 1 | |
Metal bindingi | 475 | Manganese 1Combined sources1 Publication | 1 | |
Metal bindingi | 475 | Manganese 2Combined sources1 Publication | 1 | |
Binding sitei | 475 | SubstrateCombined sources1 Publication1 Publication | 1 |
GO - Molecular functioni
- aminopeptidase activity Source: MGI
- manganese ion binding Source: UniProtKB
- metalloaminopeptidase activity Source: UniProtKB
- peptidase activity Source: GO_Central
- protein homodimerization activity Source: UniProtKB
GO - Biological processi
- glomerular filtration Source: MGI
- protein processing Source: MGI
- proteolysis Source: UniProtKB
Keywordsi
Molecular function | Aminopeptidase, Hydrolase, Metalloprotease, Protease |
Ligand | Manganese, Metal-binding |
Enzyme and pathway databases
BRENDAi | 3.4.11.9, 2681 |
PathwayCommonsi | Q9NQH7 |
SignaLinki | Q9NQH7 |
Protein family/group databases
MEROPSi | M24.026 |
Names & Taxonomyi
Protein namesi | Recommended name: Xaa-Pro aminopeptidase 3Imported (EC:3.4.11.92 Publications)Short name: X-Pro aminopeptidase 3 Alternative name(s): Aminopeptidase P3 Short name: APP3 |
Gene namesi | Name:XPNPEP3 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:28052, XPNPEP3 |
MIMi | 613553, gene |
neXtProti | NX_Q9NQH7 |
VEuPathDBi | HostDB:ENSG00000196236 |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm 1 Publication
Mitochondrion
- Mitochondrion 2 Publications
Note: Mainly mitochondrial. Translocates to the cytoplasm following TNFRSF1B activation.1 Publication
Cytoplasm and Cytosol
- Cytoplasm 1 Publication
Cytosol
- cytosol Source: HPA
Mitochondrion
- mitochondrion Source: UniProtKB
Other locations
- cytoplasm Source: UniProtKB
Keywords - Cellular componenti
Cytoplasm, MitochondrionPathology & Biotechi
Involvement in diseasei
Nephronophthisis-like nephropathy 1 (NPHPL1)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_063820 | 453 | G → C in NPHPL1. 1 PublicationCorresponds to variant dbSNP:rs267607179EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 18 | R → A: Prevents cleavage of N-terminal transit peptide; when associated with A-29-30-A; A-39-40-A and A-44. 1 Publication | 1 | |
Mutagenesisi | 29 – 30 | RR → AA: Prevents cleavage of N-terminal transit peptide; when associated with A-18; A-39-40-A and A-44. 1 Publication | 2 | |
Mutagenesisi | 39 – 40 | RR → AA: Prevents cleavage of N-terminal transit peptide; when associated with A-18; A-29-30-A and A-44. 1 Publication | 2 | |
Mutagenesisi | 44 | R → A: Prevents cleavage of N-terminal transit peptide; when associated with A-18; A-29-30-A and A-39-40-A. 1 Publication | 1 | |
Mutagenesisi | 314 | H → A: Impairs catalytic activity. 1 Publication | 1 | |
Mutagenesisi | 342 | D → A: Impairs catalytic activity. 1 Publication | 1 | |
Mutagenesisi | 475 | E → A: Impairs catalytic activity. 1 Publication | 1 |
Keywords - Diseasei
Disease variant, NephronophthisisOrganism-specific databases
DisGeNETi | 63929 |
GeneReviewsi | XPNPEP3 |
MalaCardsi | XPNPEP3 |
MIMi | 613159, phenotype |
OpenTargetsi | ENSG00000196236 |
Orphaneti | 93589, Late-onset nephronophthisis |
PharmGKBi | PA147357130 |
Miscellaneous databases
Pharosi | Q9NQH7, Tbio |
Chemistry databases
ChEMBLi | CHEMBL3831223 |
Genetic variation databases
BioMutai | XPNPEP3 |
DMDMi | 74761652 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transit peptidei | 1 – 31 | MitochondrionSequence analysis1 PublicationAdd BLAST | 31 | |
ChainiPRO_0000255654 | 32 – 507 | Xaa-Pro aminopeptidase 3Add BLAST | 476 |
Proteomic databases
EPDi | Q9NQH7 |
jPOSTi | Q9NQH7 |
MassIVEi | Q9NQH7 |
MaxQBi | Q9NQH7 |
PaxDbi | Q9NQH7 |
PeptideAtlasi | Q9NQH7 |
PRIDEi | Q9NQH7 |
ProteomicsDBi | 82154 [Q9NQH7-1] 82155 [Q9NQH7-2] 82156 [Q9NQH7-3] 82157 [Q9NQH7-4] 82158 [Q9NQH7-5] |
PTM databases
iPTMneti | Q9NQH7 |
PhosphoSitePlusi | Q9NQH7 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000196236, Expressed in testis and 216 other tissues |
ExpressionAtlasi | Q9NQH7, baseline and differential |
Genevisiblei | Q9NQH7, HS |
Organism-specific databases
HPAi | ENSG00000196236, Low tissue specificity |
Interactioni
Subunit structurei
GO - Molecular functioni
- protein homodimerization activity Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 121997, 62 interactors |
CORUMi | Q9NQH7 |
IntActi | Q9NQH7, 44 interactors |
MINTi | Q9NQH7 |
STRINGi | 9606.ENSP00000349658 |
Miscellaneous databases
RNActi | Q9NQH7, protein |
Structurei
Secondary structure
3D structure databases
SMRi | Q9NQH7 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 54 – 79 | Interaction with TNFRSF1B1 PublicationAdd BLAST | 26 |
Sequence similaritiesi
Keywords - Domaini
Transit peptidePhylogenomic databases
eggNOGi | KOG2414, Eukaryota |
GeneTreei | ENSGT00940000153657 |
HOGENOMi | CLU_017266_1_1_1 |
InParanoidi | Q9NQH7 |
OMAi | HHVGHYI |
OrthoDBi | 352329at2759 |
PhylomeDBi | Q9NQH7 |
TreeFami | TF314484 |
Family and domain databases
Gene3Di | 3.40.350.10, 1 hit 3.90.230.10, 1 hit |
InterProi | View protein in InterPro IPR007865, Aminopep_P_N IPR029149, Creatin/AminoP/Spt16_NTD IPR036005, Creatinase/aminopeptidase-like IPR000994, Pept_M24 |
Pfami | View protein in Pfam PF05195, AMP_N, 1 hit PF00557, Peptidase_M24, 1 hit |
SMARTi | View protein in SMART SM01011, AMP_N, 1 hit |
SUPFAMi | SSF53092, SSF53092, 1 hit SSF55920, SSF55920, 1 hit |
s (5+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 5 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 5 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MPWLLSAPKL VPAVANVRGL SGCMLCSQRR YSLQPVPERR IPNRYLGQPS
60 70 80 90 100
PFTHPHLLRP GEVTPGLSQV EYALRRHKLM SLIQKEAQGQ SGTDQTVVVL
110 120 130 140 150
SNPTYYMSND IPYTFHQDNN FLYLCGFQEP DSILVLQSLP GKQLPSHKAI
160 170 180 190 200
LFVPRRDPSR ELWDGPRSGT DGAIALTGVD EAYTLEEFQH LLPKMKAETN
210 220 230 240 250
MVWYDWMRPS HAQLHSDYMQ PLTEAKAKSK NKVRGVQQLI QRLRLIKSPA
260 270 280 290 300
EIERMQIAGK LTSQAFIETM FTSKAPVEEA FLYAKFEFEC RARGADILAY
310 320 330 340 350
PPVVAGGNRS NTLHYVKNNQ LIKDGEMVLL DGGCESSCYV SDITRTWPVN
360 370 380 390 400
GRFTAPQAEL YEAVLEIQRD CLALCFPGTS LENIYSMMLT LIGQKLKDLG
410 420 430 440 450
IMKNIKENNA FKAARKYCPH HVGHYLGMDV HDTPDMPRSL PLQPGMVITI
460 470 480 490 500
EPGIYIPEDD KDAPEKFRGL GVRIEDDVVV TQDSPLILSA DCPKEMNDIE
QICSQAS
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A087X0Z2 | A0A087X0Z2_HUMAN | Xaa-Pro aminopeptidase 3 | XPNPEP3 LOC63929, hCG_41117 | 55 | Annotation score: | ||
F2Z316 | F2Z316_HUMAN | Xaa-Pro aminopeptidase 3 | XPNPEP3 | 69 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 340 | V → A in CAG33677 (Ref. 1) Curated | 1 | |
Sequence conflicti | 486 | L → F in AAH01681 (PubMed:15489334).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_051573 | 450 | I → L. Corresponds to variant dbSNP:rs17002243Ensembl. | 1 | |
Natural variantiVAR_063820 | 453 | G → C in NPHPL1. 1 PublicationCorresponds to variant dbSNP:rs267607179EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_021296 | 1 – 79 | Missing in isoform 2. 1 PublicationAdd BLAST | 79 | |
Alternative sequenceiVSP_040142 | 1 – 23 | Missing in isoform 4. 1 PublicationAdd BLAST | 23 | |
Alternative sequenceiVSP_040143 | 265 – 288 | AFIET…AKFEF → KSVLLARHGGSRLYSHHFGR PRLS in isoform 5. 1 PublicationAdd BLAST | 24 | |
Alternative sequenceiVSP_021297 | 265 – 278 | AFIET…KAPVE → RQGFSVLSRLVSNS in isoform 3. 1 PublicationAdd BLAST | 14 | |
Alternative sequenceiVSP_021298 | 279 – 507 | Missing in isoform 3. 1 PublicationAdd BLAST | 229 | |
Alternative sequenceiVSP_040144 | 289 – 507 | Missing in isoform 5. 1 PublicationAdd BLAST | 219 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | CR457396 mRNA Translation: CAG33677.1 AL365514 mRNA Translation: CAB97210.1 CR456442 mRNA Translation: CAG30328.1 AK301635 mRNA Translation: BAH13526.1 AK301758 mRNA Translation: BAH13548.1 AK313770 mRNA Translation: BAG36508.1 AL834310 mRNA Translation: CAD38980.1 AL035450 Genomic DNA No translation available. Z98048 Genomic DNA No translation available. CH471095 Genomic DNA Translation: EAW60399.1 BC001208 mRNA Translation: AAH01208.1 BC001681 mRNA Translation: AAH01681.1 BC004989 mRNA Translation: AAH04989.1 |
CCDSi | CCDS14007.1 [Q9NQH7-1] |
RefSeqi | NP_071381.1, NM_022098.3 [Q9NQH7-1] |
Genome annotation databases
Ensembli | ENST00000357137; ENSP00000349658; ENSG00000196236 |
GeneIDi | 63929 |
KEGGi | hsa:63929 |
MANE-Selecti | ENST00000357137.9; ENSP00000349658.4; NM_022098.4; NP_071381.1 |
UCSCi | uc003azh.4, human [Q9NQH7-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | CR457396 mRNA Translation: CAG33677.1 AL365514 mRNA Translation: CAB97210.1 CR456442 mRNA Translation: CAG30328.1 AK301635 mRNA Translation: BAH13526.1 AK301758 mRNA Translation: BAH13548.1 AK313770 mRNA Translation: BAG36508.1 AL834310 mRNA Translation: CAD38980.1 AL035450 Genomic DNA No translation available. Z98048 Genomic DNA No translation available. CH471095 Genomic DNA Translation: EAW60399.1 BC001208 mRNA Translation: AAH01208.1 BC001681 mRNA Translation: AAH01681.1 BC004989 mRNA Translation: AAH04989.1 |
CCDSi | CCDS14007.1 [Q9NQH7-1] |
RefSeqi | NP_071381.1, NM_022098.3 [Q9NQH7-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
5X49 | X-ray | 1.65 | A/B | 54-507 | [»] | |
SMRi | Q9NQH7 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 121997, 62 interactors |
CORUMi | Q9NQH7 |
IntActi | Q9NQH7, 44 interactors |
MINTi | Q9NQH7 |
STRINGi | 9606.ENSP00000349658 |
Chemistry databases
ChEMBLi | CHEMBL3831223 |
Protein family/group databases
MEROPSi | M24.026 |
PTM databases
iPTMneti | Q9NQH7 |
PhosphoSitePlusi | Q9NQH7 |
Genetic variation databases
BioMutai | XPNPEP3 |
DMDMi | 74761652 |
Proteomic databases
EPDi | Q9NQH7 |
jPOSTi | Q9NQH7 |
MassIVEi | Q9NQH7 |
MaxQBi | Q9NQH7 |
PaxDbi | Q9NQH7 |
PeptideAtlasi | Q9NQH7 |
PRIDEi | Q9NQH7 |
ProteomicsDBi | 82154 [Q9NQH7-1] 82155 [Q9NQH7-2] 82156 [Q9NQH7-3] 82157 [Q9NQH7-4] 82158 [Q9NQH7-5] |
Protocols and materials databases
Antibodypediai | 259, 146 antibodies from 27 providers |
DNASUi | 63929 |
Genome annotation databases
Ensembli | ENST00000357137; ENSP00000349658; ENSG00000196236 |
GeneIDi | 63929 |
KEGGi | hsa:63929 |
MANE-Selecti | ENST00000357137.9; ENSP00000349658.4; NM_022098.4; NP_071381.1 |
UCSCi | uc003azh.4, human [Q9NQH7-1] |
Organism-specific databases
CTDi | 63929 |
DisGeNETi | 63929 |
GeneCardsi | XPNPEP3 |
GeneReviewsi | XPNPEP3 |
HGNCi | HGNC:28052, XPNPEP3 |
HPAi | ENSG00000196236, Low tissue specificity |
MalaCardsi | XPNPEP3 |
MIMi | 613159, phenotype 613553, gene |
neXtProti | NX_Q9NQH7 |
OpenTargetsi | ENSG00000196236 |
Orphaneti | 93589, Late-onset nephronophthisis |
PharmGKBi | PA147357130 |
VEuPathDBi | HostDB:ENSG00000196236 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2414, Eukaryota |
GeneTreei | ENSGT00940000153657 |
HOGENOMi | CLU_017266_1_1_1 |
InParanoidi | Q9NQH7 |
OMAi | HHVGHYI |
OrthoDBi | 352329at2759 |
PhylomeDBi | Q9NQH7 |
TreeFami | TF314484 |
Enzyme and pathway databases
BRENDAi | 3.4.11.9, 2681 |
PathwayCommonsi | Q9NQH7 |
SignaLinki | Q9NQH7 |
Miscellaneous databases
BioGRID-ORCSi | 63929, 21 hits in 1046 CRISPR screens |
ChiTaRSi | XPNPEP3, human |
GeneWikii | XPNPEP3 |
GenomeRNAii | 63929 |
Pharosi | Q9NQH7, Tbio |
PROi | PR:Q9NQH7 |
RNActi | Q9NQH7, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000196236, Expressed in testis and 216 other tissues |
ExpressionAtlasi | Q9NQH7, baseline and differential |
Genevisiblei | Q9NQH7, HS |
Family and domain databases
Gene3Di | 3.40.350.10, 1 hit 3.90.230.10, 1 hit |
InterProi | View protein in InterPro IPR007865, Aminopep_P_N IPR029149, Creatin/AminoP/Spt16_NTD IPR036005, Creatinase/aminopeptidase-like IPR000994, Pept_M24 |
Pfami | View protein in Pfam PF05195, AMP_N, 1 hit PF00557, Peptidase_M24, 1 hit |
SMARTi | View protein in SMART SM01011, AMP_N, 1 hit |
SUPFAMi | SSF53092, SSF53092, 1 hit SSF55920, SSF55920, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | XPP3_HUMAN | |
Accessioni | Q9NQH7Primary (citable) accession number: Q9NQH7 Secondary accession number(s): B2R9G1 Q9BVH0 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 31, 2006 |
Last sequence update: | October 1, 2000 | |
Last modified: | February 23, 2022 | |
This is version 177 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Peptidase families
Classification of peptidase families and list of entries - Human chromosome 22
Human chromosome 22: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families