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Protein

Inositol polyphosphate 5-phosphatase K

Gene

INPP5K

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

Functioni

Inositol 5-phosphatase which acts on inositol 1,4,5-trisphosphate, inositol 1,3,4,5-tetrakisphosphate, phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate. Has 6-fold higher affinity for phosphatidylinositol 4,5-bisphosphate than for inositol 1,4,5-trisphosphate (PubMed:10753883). Negatively regulates assembly of the actin cytoskeleton. Controls insulin-dependent glucose uptake among inositol 3,4,5-trisphosphate phosphatases; therefore, is the specific regulator for insulin signaling in skeletal muscle (By similarity).By similarity3 Publications

Catalytic activityi

D-myo-inositol 1,4,5-trisphosphate + H2O = myo-inositol 1,4-bisphosphate + phosphate.3 Publications

GO - Molecular functioni

  • inositol-1,3,4,5-tetrakisphosphate 5-phosphatase activity Source: UniProtKB-EC
  • inositol-1,4,5-trisphosphate 5-phosphatase activity Source: UniProtKB-EC
  • inositol bisphosphate phosphatase activity Source: MGI
  • inositol-polyphosphate 5-phosphatase activity Source: UniProtKB-EC
  • inositol trisphosphate phosphatase activity Source: MGI
  • lipid phosphatase activity Source: UniProtKB
  • phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase activity Source: UniProtKB
  • phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity Source: UniProtKB
  • phosphatidylinositol phosphate 5-phosphatase activity Source: UniProtKB
  • phosphatidylinositol trisphosphate phosphatase activity Source: UniProtKB
  • vasopressin receptor activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionHydrolase

Enzyme and pathway databases

BioCyciMetaCyc:HS05626-MONOMER.
ReactomeiR-HSA-1660499. Synthesis of PIPs at the plasma membrane.

Chemistry databases

SwissLipidsiSLP:000000957.

Names & Taxonomyi

Protein namesi
Recommended name:
Inositol polyphosphate 5-phosphatase KCurated (EC:3.1.3.563 Publications)
Alternative name(s):
Skeletal muscle and kidney-enriched inositol phosphatase1 Publication
Gene namesi
Name:INPP5KImported
Synonyms:PPS, SKIP1 Publication
OrganismiHomo sapiens (Human)Imported
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000132376.19.
HGNCiHGNC:33882. INPP5K.

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

Endoplasmic reticulum

Pathology & Biotechi

Involvement in diseasei

Muscular dystrophy, congenital, with cataracts and intellectual disability (MDCCAID)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive form of muscular dystrophy with onset in early childhood and characterized by progressive muscle weakness. Almost all patients also have early-onset cataracts and intellectual disability of varying severity. Some patients have seizures.
See also OMIM:617404
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07899823V → M in MDCCAID; decreased phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity. 1 Publication1
Natural variantiVAR_07899950I → T in MDCCAID; decreased phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity; shows normal localization indistinguishable from the wild-type. 1 Publication1
Natural variantiVAR_07900093M → V in MDCCAID; decreased phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity. 1 Publication1
Natural variantiVAR_079001140G → S in MDCCAID; no phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity. 1 Publication1
Natural variantiVAR_079002269D → N in MDCCAID; no phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity. 1 Publication1
Natural variantiVAR_079003294Missing in MDCCAID; decreased phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity; shows normal localization indistinguishable from the wild-type. 1 Publication1
Natural variantiVAR_079004300Y → C in MDCCAID; no phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity; shows normal localization indistinguishable from the wild-type. 1 Publication1
Natural variantiVAR_079005363I → T in MDCCAID; shows a diffuse perinuclear mislocalization. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi310D → G: No phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity. 2 Publications1
Mutagenesisi349Y → A or F: No effect on EGF-induced ruffle localization. 1 Publication1
Mutagenesisi361D → A: Significant decrease in EGF-induced ruffle localization. 1 Publication1
Mutagenesisi362W → A: Significant decrease in EGF-induced ruffle localization. 1 Publication1
Mutagenesisi376Y → A or F: No effect on EGF-induced ruffle localization. 1 Publication1

Keywords - Diseasei

Cataract, Congenital muscular dystrophy, Disease mutation, Mental retardation

Organism-specific databases

DisGeNETi51763.
MIMi617404. phenotype.
OpenTargetsiENSG00000132376.
PharmGKBiPA164720951.

Polymorphism and mutation databases

BioMutaiINPP5K.
DMDMi116242791.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002097271 – 448Inositol polyphosphate 5-phosphatase KAdd BLAST448

Proteomic databases

EPDiQ9BT40.
MaxQBiQ9BT40.
PaxDbiQ9BT40.
PeptideAtlasiQ9BT40.
PRIDEiQ9BT40.

PTM databases

DEPODiQ9BT40.
iPTMnetiQ9BT40.
PhosphoSitePlusiQ9BT40.

Expressioni

Tissue specificityi

Ubiquitously expressed with highest levels in skeletal muscle, heart and kidney.1 Publication

Gene expression databases

BgeeiENSG00000132376.
CleanExiHS_INPP5K.
ExpressionAtlasiQ9BT40. baseline and differential.
GenevisibleiQ9BT40. HS.

Organism-specific databases

HPAiHPA031044.

Interactioni

Subunit structurei

Interacts with GPR78; necessary for INPP5K localization at the endoplasmic reticulum. Interacts with PAK1; competes with GPR78.1 Publication

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi119720. 34 interactors.
CORUMiQ9BT40.
IntActiQ9BT40. 22 interactors.
MINTiMINT-1445023.
STRINGi9606.ENSP00000413937.

Structurei

3D structure databases

ProteinModelPortaliQ9BT40.
SMRiQ9BT40.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni16 – 318CatalyticSequence analysisAdd BLAST303
Regioni318 – 448Required for interaction with GPR78 and PAK11 PublicationAdd BLAST131
Regioni321 – 448Required for ruffle localizationAdd BLAST128

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0565. Eukaryota.
COG5411. LUCA.
GeneTreeiENSGT00760000119075.
HOGENOMiHOG000046051.
HOVERGENiHBG082135.
InParanoidiQ9BT40.
KOiK01106.
OMAiPEGLWTM.
OrthoDBiEOG091G055L.
PhylomeDBiQ9BT40.
TreeFamiTF317034.

Family and domain databases

Gene3Di3.60.10.10. 1 hit.
InterProiView protein in InterPro
IPR036691. Endo/exonu/phosph_ase_sf.
IPR005135. Endo/exonuclease/phosphatase.
IPR000300. IPPc.
PfamiView protein in Pfam
PF03372. Exo_endo_phos. 1 hit.
SMARTiView protein in SMART
SM00128. IPPc. 1 hit.
SUPFAMiSSF56219. SSF56219. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 11 Publication (identifier: Q9BT40-1) [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
MSSRKLSGPK GRRLSIHVVT WNVASAAPPL DLSDLLQLNN RNLNLDIYVI
60 70 80 90 100
GLQELNSGII SLLSDAAFND SWSSFLMDVL SPLSFIKVSH VRMQGILLLV
110 120 130 140 150
FAKYQHLPYI QILSTKSTPT GLFGYWGNKG GVNICLKLYG YYVSIINCHL
160 170 180 190 200
PPHISNNYQR LEHFDRILEM QNCEGRDIPN ILDHDLIIWF GDMNFRIEDF
210 220 230 240 250
GLHFVRESIK NRCYGGLWEK DQLSIAKKHD PLLREFQEGR LLFPPTYKFD
260 270 280 290 300
RNSNDYDTSE KKRKPAWTDR ILWRLKRQPC AGPDTPIPPA SHFSLSLRGY
310 320 330 340 350
SSHMTYGISD HKPVSGTFDL ELKPLVSAPL IVLMPEDLWT VENDMMVSYS
360 370 380 390 400
STSDFPSSPW DWIGLYKVGL RDVNDYVSYA WVGDSKVSCS DNLNQVYIDI
410 420 430 440
SNIPTTEDEF LLCYYSNSLR SVVGISRPFQ IPPGSLREDP LGEAQPQI
Length:448
Mass (Da):51,090
Last modified:October 17, 2006 - v3
Checksum:i46FAA48C6E2EEAD4
GO
Isoform 21 Publication (identifier: Q9BT40-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-76: Missing.

Show »
Length:372
Mass (Da):42,784
Checksum:iE257B4890DCD44F3
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti120T → A in AAB03214 (Ref. 5) Curated1
Sequence conflicti416S → R in BAA92340 (PubMed:10753883).Curated1
Sequence conflicti416S → R in BAA92341 (PubMed:10753883).Curated1
Sequence conflicti416S → R in BAA92342 (PubMed:10753883).Curated1
Sequence conflicti416S → R in AAB03214 (Ref. 5) Curated1
Sequence conflicti426S → R in BAA92340 (PubMed:10753883).Curated1
Sequence conflicti426S → R in BAA92341 (PubMed:10753883).Curated1
Sequence conflicti426S → R in BAA92342 (PubMed:10753883).Curated1
Sequence conflicti426S → R in AAB03214 (Ref. 5) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07899823V → M in MDCCAID; decreased phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity. 1 Publication1
Natural variantiVAR_07899950I → T in MDCCAID; decreased phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity; shows normal localization indistinguishable from the wild-type. 1 Publication1
Natural variantiVAR_07900093M → V in MDCCAID; decreased phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity. 1 Publication1
Natural variantiVAR_079001140G → S in MDCCAID; no phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity. 1 Publication1
Natural variantiVAR_079002269D → N in MDCCAID; no phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity. 1 Publication1
Natural variantiVAR_079003294Missing in MDCCAID; decreased phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity; shows normal localization indistinguishable from the wild-type. 1 Publication1
Natural variantiVAR_079004300Y → C in MDCCAID; no phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity; shows normal localization indistinguishable from the wild-type. 1 Publication1
Natural variantiVAR_036497315S → F in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_079005363I → T in MDCCAID; shows a diffuse perinuclear mislocalization. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0506121 – 76Missing in isoform 2. 2 PublicationsAdd BLAST76

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB036829 mRNA. Translation: BAA92340.1.
AB036830 mRNA. Translation: BAA92341.1.
AB036831 Genomic DNA. Translation: BAA92342.1.
AK312585 mRNA. Translation: BAG35479.1.
AK312844 mRNA. Translation: BAG35697.1.
CH471108 Genomic DNA. Translation: EAW90614.1.
CH471108 Genomic DNA. Translation: EAW90615.1.
CH471108 Genomic DNA. Translation: EAW90618.1.
BC004362 mRNA. Translation: AAH04362.1.
U45973 mRNA. Translation: AAB03214.1.
CCDSiCCDS11004.1. [Q9BT40-1]
CCDS11005.1. [Q9BT40-2]
RefSeqiNP_001129114.1. NM_001135642.1. [Q9BT40-2]
NP_057616.2. NM_016532.3. [Q9BT40-1]
NP_570122.1. NM_130766.2. [Q9BT40-2]
XP_005256740.1. XM_005256683.2. [Q9BT40-2]
XP_011522236.1. XM_011523934.1. [Q9BT40-2]
XP_016880244.1. XM_017024755.1. [Q9BT40-2]
XP_016880245.1. XM_017024756.1. [Q9BT40-2]
UniGeneiHs.632238.

Genome annotation databases

EnsembliENST00000320345; ENSP00000318476; ENSG00000132376. [Q9BT40-2]
ENST00000406424; ENSP00000385177; ENSG00000132376. [Q9BT40-2]
ENST00000421807; ENSP00000413937; ENSG00000132376. [Q9BT40-1]
GeneIDi51763.
KEGGihsa:51763.
UCSCiuc002fsr.4. human. [Q9BT40-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiINP5K_HUMAN
AccessioniPrimary (citable) accession number: Q9BT40
Secondary accession number(s): B2R6I2
, B2R750, D3DTH8, Q15733, Q9NPJ5, Q9P2R5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 26, 2003
Last sequence update: October 17, 2006
Last modified: October 25, 2017
This is version 145 of the entry and version 3 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: 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. SIMILARITY comments
    Index of protein domains and families