UniProtKB - Q86TP1 (PRUN1_HUMAN)
Protein
Exopolyphosphatase PRUNE1
Gene
PRUNE1
Organism
Homo sapiens (Human)
Status
Functioni
Phosphodiesterase (PDE) that has higher activity toward cAMP than cGMP, as substrate. Plays a role in cell proliferation, migration and differentiation, and acts as a negative regulator of NME1. Plays a role in the regulation of neurogenesis (PubMed:28334956). Involved in the regulation of microtubule polymerization (PubMed:28334956).6 Publications
Catalytic activityi
- EC:3.6.1.1
Cofactori
Mn2+By similarityNote: Binds 2 manganese ions per subunit.By similarity
Activity regulationi
Activated by magnesium ions and inhibited by manganese ions. Inhibited by dipyridamole, moderately sensitive to IBMX and inhibited by vinpocetine.1 Publication
Kineticsi
- KM=0.91 µM for cAMP2 Publications
- KM=2.3 µM for cGMP2 Publications
- Vmax=12.8 pmol/min/µg enzyme with cAMP as substrate2 Publications
- Vmax=0.8 pmol/min/µg enzyme with cGMP as substrate2 Publications
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 28 | Manganese 1By similarity | 1 | |
Metal bindingi | 30 | Manganese 2By similarity | 1 | |
Metal bindingi | 106 | Manganese 1By similarity | 1 | |
Metal bindingi | 106 | Manganese 2By similarity | 1 | |
Metal bindingi | 179 | Manganese 2By similarity | 1 |
GO - Molecular functioni
- exopolyphosphatase activity Source: GO_Central
- inorganic diphosphatase activity Source: UniProtKB-EC
- metal ion binding Source: UniProtKB-KW
- phosphatase activity Source: UniProtKB
- tubulin binding Source: UniProtKB
GO - Biological processi
- polyphosphate catabolic process Source: GO_Central
- regulation of microtubule polymerization Source: UniProtKB
- regulation of neurogenesis Source: UniProtKB
Keywordsi
Molecular function | Hydrolase |
Ligand | Manganese, Metal-binding |
Enzyme and pathway databases
PathwayCommonsi | Q86TP1 |
SABIO-RKi | Q86TP1 |
Names & Taxonomyi
Protein namesi | Recommended name: Exopolyphosphatase PRUNE1 (EC:3.6.1.1)Alternative name(s): Drosophila-related expressed sequence 17 Short name: DRES-17 Short name: DRES17 HTcD37 Protein prune homolog 1 Short name: hPrune |
Gene namesi | |
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:13420, PRUNE1 |
MIMi | 617413, gene |
neXtProti | NX_Q86TP1 |
VEuPathDBi | HostDB:ENSG00000143363.15 |
Subcellular locationi
Cytoplasm and Cytosol
Nucleus
Other locations
Note: In some transfected cells a nuclear staining is also observed.
Cytosol
- cytosol Source: HPA
Nucleus
- nucleus Source: UniProtKB-SubCell
Other locations
- cytoplasm Source: GO_Central
- focal adhesion Source: UniProtKB-SubCell
Keywords - Cellular componenti
Cell junction, Cytoplasm, NucleusPathology & Biotechi
Involvement in diseasei
Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies (NMIHBA)3 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive neurodevelopmental and degenerative disorder characterized by primary microcephaly, profound global developmental delay, and severe intellectual disability. Additional clinical features include dysmorphic features, truncal hypotonia, peripheral spasticity, and lack of independent ambulation or speech acquisition. Brain imaging shows cortical atrophy, thin corpus callosum, cerebellar hypoplasia, and delayed myelination.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_078986 | 30 | D → N in NMIHBA; loss of function in regulation of cell proliferation and migration; loss of function in neurogenesis; impaired regulation of microtubule polymerization; increased phosphatase activity; no effect on interaction with tubulin beta. 2 PublicationsCorresponds to variant dbSNP:rs1057521927EnsemblClinVar. | 1 | |
Natural variantiVAR_078987 | 54 | P → T in NMIHBA; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1085308033EnsemblClinVar. | 1 | |
Natural variantiVAR_078988 | 106 | D → N in NMIHBA. 2 PublicationsCorresponds to variant dbSNP:rs773618224EnsemblClinVar. | 1 | |
Natural variantiVAR_078989 | 128 | R → Q in NMIHBA. 1 PublicationCorresponds to variant dbSNP:rs767769359EnsemblClinVar. | 1 | |
Natural variantiVAR_078990 | 174 – 453 | Missing in NMIHBA. 1 PublicationAdd BLAST | 280 | |
Natural variantiVAR_078991 | 297 | R → W in NMIHBA; loss of function in regulation of cell proliferation and migration; loss of function in neurogenesis; impaired regulation of microtubule polymerization; increased phosphatase activity; decreased interaction with tubulin beta. 1 PublicationCorresponds to variant dbSNP:rs752599948EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 28 | D → A: Partial loss of cAMP PDE activity. Partial loss of cAMP PDE activity; when associated with D-106. Partial loss of cAMP PDE activity; when associated with D-106 and D-179. 1 Publication | 1 | |
Mutagenesisi | 106 | D → A: No change in cAMP PDE activity. Partial loss of cAMP PDE activity; when associated with D-28. Partial loss of cAMP PDE activity; when associated with D-28 and D-179. 1 Publication | 1 | |
Mutagenesisi | 126 – 129 | DHRP → AAAA: Partial loss of cAMP PDE activity. 1 Publication | 4 | |
Mutagenesisi | 179 | D → A: Partial loss of cAMP PDE activity. Partial loss of cAMP PDE activity; when associated with D-28 and D-106. 1 Publication | 1 |
Keywords - Diseasei
Disease variant, Mental retardation, Neurodegeneration, Primary microcephalyOrganism-specific databases
DisGeNETi | 58497 |
MalaCardsi | PRUNE1 |
MIMi | 617481, phenotype |
OpenTargetsi | ENSG00000143363 |
Orphaneti | 544469, PRUNE1-related neurological syndrome |
PharmGKBi | PA134939749 |
Miscellaneous databases
Pharosi | Q86TP1, Tchem |
Chemistry databases
ChEMBLi | CHEMBL2079850 |
DrugCentrali | Q86TP1 |
Genetic variation databases
BioMutai | PRUNE1 |
DMDMi | 229462737 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000337987 | 1 – 453 | Exopolyphosphatase PRUNE1Add BLAST | 453 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 1 | N-acetylmethionineCombined sources | 1 | |
Modified residuei | 399 | PhosphoserineBy similarity | 1 | |
Modified residuei | 410 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 414 | PhosphoserineBy similarity | 1 |
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
EPDi | Q86TP1 |
jPOSTi | Q86TP1 |
MassIVEi | Q86TP1 |
MaxQBi | Q86TP1 |
PaxDbi | Q86TP1 |
PeptideAtlasi | Q86TP1 |
PRIDEi | Q86TP1 |
ProteomicsDBi | 69719 [Q86TP1-1] 69720 [Q86TP1-2] 69721 [Q86TP1-3] 69722 [Q86TP1-4] 69723 [Q86TP1-5] 69724 [Q86TP1-6] 69725 [Q86TP1-7] |
PTM databases
iPTMneti | Q86TP1 |
PhosphoSitePlusi | Q86TP1 |
Expressioni
Tissue specificityi
Ubiquitously expressed. Seems to be overexpressed in aggressive sarcoma subtypes, such as leiomyosarcomas and malignant fibrous histiocytomas (MFH) as well as in the less malignant liposarcomas.3 Publications
Gene expression databases
Bgeei | ENSG00000143363, Expressed in secondary oocyte and 253 other tissues |
ExpressionAtlasi | Q86TP1, baseline and differential |
Genevisiblei | Q86TP1, HS |
Organism-specific databases
HPAi | ENSG00000143363, Low tissue specificity |
Interactioni
Subunit structurei
Homooligomer. Able to homodimerize via its C-terminal domain.
Interacts with NME1.
Interacts with GSK3; at focal adhesion complexes where paxillin and vinculin are colocalized.
Interacts with alpha and beta tubulin (PubMed:28334956).
6 PublicationsBinary interactionsi
Q86TP1
With | #Exp. | IntAct |
---|---|---|
NME1 [P15531] | 2 | EBI-2127112,EBI-741141 |
GO - Molecular functioni
- tubulin binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 121827, 21 interactors |
CORUMi | Q86TP1 |
IntActi | Q86TP1, 10 interactors |
STRINGi | 9606.ENSP00000271620 |
Chemistry databases
BindingDBi | Q86TP1 |
Miscellaneous databases
RNActi | Q86TP1, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 393 – 420 | Essential for homodimerizationAdd BLAST | 28 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 106 – 108 | DHH motif | 3 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG4129, Eukaryota |
GeneTreei | ENSGT00450000040262 |
HOGENOMi | CLU_019358_2_0_1 |
InParanoidi | Q86TP1 |
OMAi | RHLLVWG |
OrthoDBi | 1545660at2759 |
PhylomeDBi | Q86TP1 |
TreeFami | TF323914 |
Family and domain databases
Gene3Di | 3.10.310.20, 1 hit |
InterProi | View protein in InterPro IPR001667, DDH_dom IPR038763, DHH_sf IPR004097, DHHA2 IPR038222, DHHA2_dom_sf |
Pfami | View protein in Pfam PF01368, DHH, 1 hit PF02833, DHHA2, 1 hit |
SMARTi | View protein in SMART SM01131, DHHA2, 1 hit |
SUPFAMi | SSF64182, SSF64182, 1 hit |
s (7+)i Sequence
Sequence statusi: Complete.
This entry describes 7 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 7 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q86TP1-1) [UniParc]FASTAAdd to basket
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
MEDYLQGCRA ALQESRPLHV VLGNEACDLD STVSALALAF YLAKTTEAEE
60 70 80 90 100
VFVPVLNIKR SELPLRGDIV FFLQKVHIPE SILIFRDEID LHALYQAGQL
110 120 130 140 150
TLILVDHHIL SKSDTALEEA VAEVLDHRPI EPKHCPPCHV SVELVGSCAT
160 170 180 190 200
LVTERILQGA PEILDRQTAA LLHGTIILDC VNMDLKIGKA TPKDSKYVEK
210 220 230 240 250
LEALFPDLPK RNDIFDSLQK AKFDVSGLTT EQMLRKDQKT IYRQGVKVAI
260 270 280 290 300
SAIYMDLEAF LQRSNLLADL HAFCQAHSYD VLVAMTIFFN THNEPVRQLA
310 320 330 340 350
IFCPHVALQT TICEVLERSH SPPLKLTPAS STHPNLHAYL QGNTQVSRKK
360 370 380 390 400
LLPLLQEALS AYFDSMKIPS GQPETADVSR EQVDKELDRA SNSLISGLSQ
410 420 430 440 450
DEEDPPLPPT PMNSLVDECP LDQGLPKLSA EAVFEKCSQI SLSQSTTASL
SKK
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketQ5SZG1 | Q5SZG1_HUMAN | Exopolyphosphatase PRUNE1 | PRUNE1 | 178 | Annotation score: | ||
A0A3B3ITN0 | A0A3B3ITN0_HUMAN | Exopolyphosphatase PRUNE1 | PRUNE1 | 454 | Annotation score: | ||
Q5SZF2 | Q5SZF2_HUMAN | Exopolyphosphatase PRUNE1 | PRUNE1 | 139 | Annotation score: |
Sequence cautioni
The sequence BAB55423 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAG60534 differs from that shown. Reason: Erroneous initiation.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 14 | E → A in AAK00592 (Ref. 2) Curated | 1 | |
Sequence conflicti | 19 – 22 | HVVL → AWHE in AAF04914 (PubMed:10524757).Curated | 4 | |
Sequence conflicti | 221 | A → V in AAC95290 (PubMed:10602478).Curated | 1 | |
Sequence conflicti | 221 | A → V in AAF04914 (PubMed:10524757).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_078986 | 30 | D → N in NMIHBA; loss of function in regulation of cell proliferation and migration; loss of function in neurogenesis; impaired regulation of microtubule polymerization; increased phosphatase activity; no effect on interaction with tubulin beta. 2 PublicationsCorresponds to variant dbSNP:rs1057521927EnsemblClinVar. | 1 | |
Natural variantiVAR_078987 | 54 | P → T in NMIHBA; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1085308033EnsemblClinVar. | 1 | |
Natural variantiVAR_078988 | 106 | D → N in NMIHBA. 2 PublicationsCorresponds to variant dbSNP:rs773618224EnsemblClinVar. | 1 | |
Natural variantiVAR_078989 | 128 | R → Q in NMIHBA. 1 PublicationCorresponds to variant dbSNP:rs767769359EnsemblClinVar. | 1 | |
Natural variantiVAR_078990 | 174 – 453 | Missing in NMIHBA. 1 PublicationAdd BLAST | 280 | |
Natural variantiVAR_078991 | 297 | R → W in NMIHBA; loss of function in regulation of cell proliferation and migration; loss of function in neurogenesis; impaired regulation of microtubule polymerization; increased phosphatase activity; decreased interaction with tubulin beta. 1 PublicationCorresponds to variant dbSNP:rs752599948EnsemblClinVar. | 1 | |
Natural variantiVAR_059559 | 397 | G → R. Corresponds to variant dbSNP:rs3738477Ensembl. | 1 | |
Natural variantiVAR_043728 | 397 | G → S. Corresponds to variant dbSNP:rs3738477Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_034013 | 1 – 232 | Missing in isoform 6 and isoform 7. 2 PublicationsAdd BLAST | 232 | |
Alternative sequenceiVSP_034014 | 1 – 182 | Missing in isoform 3 and isoform 5. 2 PublicationsAdd BLAST | 182 | |
Alternative sequenceiVSP_034015 | 15 – 174 | Missing in isoform 4. 1 PublicationAdd BLAST | 160 | |
Alternative sequenceiVSP_034016 | 45 – 112 | TTEAE…HILSK → A in isoform 2. 1 PublicationAdd BLAST | 68 | |
Alternative sequenceiVSP_034017 | 259 – 311 | Missing in isoform 4, isoform 5 and isoform 6. 3 PublicationsAdd BLAST | 53 |
Sequence databases
Genome annotation databases
Ensembli | ENST00000271620; ENSP00000271620; ENSG00000143363 [Q86TP1-1] ENST00000368934; ENSP00000357930; ENSG00000143363 [Q86TP1-5] ENST00000368935; ENSP00000357931; ENSG00000143363 [Q86TP1-6] ENST00000368936; ENSP00000357932; ENSG00000143363 [Q86TP1-3] ENST00000368937; ENSP00000357933; ENSG00000143363 [Q86TP1-5] |
GeneIDi | 58497 |
KEGGi | hsa:58497 |
UCSCi | uc001ewh.2, human [Q86TP1-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
3D structure databases
BMRBi | Q86TP1 |
SMRi | Q86TP1 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 121827, 21 interactors |
CORUMi | Q86TP1 |
IntActi | Q86TP1, 10 interactors |
STRINGi | 9606.ENSP00000271620 |
Chemistry databases
BindingDBi | Q86TP1 |
ChEMBLi | CHEMBL2079850 |
DrugCentrali | Q86TP1 |
PTM databases
iPTMneti | Q86TP1 |
PhosphoSitePlusi | Q86TP1 |
Genetic variation databases
BioMutai | PRUNE1 |
DMDMi | 229462737 |
Proteomic databases
EPDi | Q86TP1 |
jPOSTi | Q86TP1 |
MassIVEi | Q86TP1 |
MaxQBi | Q86TP1 |
PaxDbi | Q86TP1 |
PeptideAtlasi | Q86TP1 |
PRIDEi | Q86TP1 |
ProteomicsDBi | 69719 [Q86TP1-1] 69720 [Q86TP1-2] 69721 [Q86TP1-3] 69722 [Q86TP1-4] 69723 [Q86TP1-5] 69724 [Q86TP1-6] 69725 [Q86TP1-7] |
Protocols and materials databases
Antibodypediai | 34044, 209 antibodies |
DNASUi | 58497 |
Genome annotation databases
Ensembli | ENST00000271620; ENSP00000271620; ENSG00000143363 [Q86TP1-1] ENST00000368934; ENSP00000357930; ENSG00000143363 [Q86TP1-5] ENST00000368935; ENSP00000357931; ENSG00000143363 [Q86TP1-6] ENST00000368936; ENSP00000357932; ENSG00000143363 [Q86TP1-3] ENST00000368937; ENSP00000357933; ENSG00000143363 [Q86TP1-5] |
GeneIDi | 58497 |
KEGGi | hsa:58497 |
UCSCi | uc001ewh.2, human [Q86TP1-1] |
Organism-specific databases
CTDi | 58497 |
DisGeNETi | 58497 |
GeneCardsi | PRUNE1 |
HGNCi | HGNC:13420, PRUNE1 |
HPAi | ENSG00000143363, Low tissue specificity |
MalaCardsi | PRUNE1 |
MIMi | 617413, gene 617481, phenotype |
neXtProti | NX_Q86TP1 |
OpenTargetsi | ENSG00000143363 |
Orphaneti | 544469, PRUNE1-related neurological syndrome |
PharmGKBi | PA134939749 |
VEuPathDBi | HostDB:ENSG00000143363.15 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4129, Eukaryota |
GeneTreei | ENSGT00450000040262 |
HOGENOMi | CLU_019358_2_0_1 |
InParanoidi | Q86TP1 |
OMAi | RHLLVWG |
OrthoDBi | 1545660at2759 |
PhylomeDBi | Q86TP1 |
TreeFami | TF323914 |
Enzyme and pathway databases
PathwayCommonsi | Q86TP1 |
SABIO-RKi | Q86TP1 |
Miscellaneous databases
BioGRID-ORCSi | 58497, 70 hits in 1000 CRISPR screens |
ChiTaRSi | PRUNE1, human |
GenomeRNAii | 58497 |
Pharosi | Q86TP1, Tchem |
PROi | PR:Q86TP1 |
RNActi | Q86TP1, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000143363, Expressed in secondary oocyte and 253 other tissues |
ExpressionAtlasi | Q86TP1, baseline and differential |
Genevisiblei | Q86TP1, HS |
Family and domain databases
Gene3Di | 3.10.310.20, 1 hit |
InterProi | View protein in InterPro IPR001667, DDH_dom IPR038763, DHH_sf IPR004097, DHHA2 IPR038222, DHHA2_dom_sf |
Pfami | View protein in Pfam PF01368, DHH, 1 hit PF02833, DHHA2, 1 hit |
SMARTi | View protein in SMART SM01131, DHHA2, 1 hit |
SUPFAMi | SSF64182, SSF64182, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | PRUN1_HUMAN | |
Accessioni | Q86TP1Primary (citable) accession number: Q86TP1 Secondary accession number(s): B2RCH8 Q9UIV0 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | June 10, 2008 |
Last sequence update: | May 5, 2009 | |
Last modified: | April 7, 2021 | |
This is version 143 of the entry and version 2 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
Reference proteomeDocuments
- Human chromosome 1
Human chromosome 1: 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 - SIMILARITY comments
Index of protein domains and families