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Q9NRR6 (INP5E_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 104. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
72 kDa inositol polyphosphate 5-phosphatase

EC=3.1.3.36
Alternative name(s):
Phosphatidylinositol 4,5-bisphosphate 5-phosphatase
Phosphatidylinositol polyphosphate 5-phosphatase type IV
Gene names
Name:INPP5E
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length644 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Converts phosphatidylinositol 3,4,5-trisphosphate (PtdIns 3,4,5-P3) to PtdIns-P2. Specific for lipid substrates, inactive towards water soluble inositol phosphates. Ref.1

Catalytic activity

1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H2O = 1-phosphatidyl-1D-myo-inositol 4-phosphate + phosphate.

Enzyme regulation

Active in the presence of octyl-glucoside or Triton X-100, but completely inhibited by CTAB.

Subcellular location

Cytoplasmcytoskeletoncilium axoneme. Golgi apparatusGolgi stack membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Note: Peripheral membrane protein associated with Golgi stacks By similarity. Ref.7 Ref.8

Tissue specificity

Detected in brain, heart, pancreas, testis and spleen. Ref.1

Involvement in disease

Joubert syndrome 1 (JBTS1) [MIM:213300]: A disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy and renal disease.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8

Mental retardation, truncal obesity, retinal dystrophy, and micropenis (MORMS) [MIM:610156]: An autosomal recessive disorder characterized by moderate mental retardation, truncal obesity, congenital non-progressive retinal dystrophy, and micropenis in males. The phenotype is similar to Bardet-Biedl syndrome and Cohen syndrome Distinguishing features are the age of onset, the non-progressive nature of the visual impairment, lack of dysmorphic facies, skin or gingival infection, microcephaly, mottled retina, polydactyly, and testicular anomalies.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7

Sequence similarities

Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase type IV family.

Sequence caution

The sequence AAB03215.1 differs from that shown. Reason: Several sequencing problems.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9NRR6-1)

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.
Isoform 2 (identifier: Q9NRR6-2)

The sequence of this isoform differs from the canonical sequence as follows:
     346-379: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 64464472 kDa inositol polyphosphate 5-phosphatase
PRO_0000209747

Regions

Repeat10 – 1341
Repeat15 – 1842
Repeat28 – 3143
Repeat39 – 4244
Repeat55 – 5845
Repeat69 – 7136
Repeat72 – 7437
Repeat75 – 7848
Repeat121 – 12449
Repeat169 – 172410
Repeat183 – 185311
Repeat190 – 193412
Repeat236 – 239413
Region10 – 24223313 X 4 AA repeats of P-X-X-P
Compositional bias92 – 976Poly-Arg

Amino acid modifications

Modified residue991Phosphoserine Ref.6

Natural variations

Alternative sequence346 – 37934Missing in isoform 2.
VSP_009799
Natural variant2011I → M.
Corresponds to variant rs36064831 [ dbSNP | Ensembl ].
VAR_047078
Natural variant3781R → C in JBTS1; slightly reduced activity. Ref.8
VAR_063012
Natural variant4351R → Q in JBTS1; severe reduction of activity. Ref.8
VAR_063013
Natural variant5121R → W in JBTS1; associated with W-515; severe reduction of activity. Ref.8
VAR_063014
Natural variant5151R → W in JBTS1; associated with W-512; severe reduction of activity. Ref.8
VAR_063015
Natural variant5631R → H in JBTS1; slightly reduced activity. Ref.8
VAR_063016
Natural variant5801K → E in JBTS1; severe reduction of activity. Ref.8
VAR_063017

Experimental info

Sequence conflict3451R → T in AAF81404. Ref.1

Secondary structure

..................................................... 644
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 4, 2008. Version 2.
Checksum: 5B6CFB75CD0ADC9A

FASTA64470,205
        10         20         30         40         50         60 
MPSKAENLRP SEPAPQPPEG RTLQGQLPGA PPAQRAGSPP DAPGSESPAL ACSTPATPSG 

        70         80         90        100        110        120 
EDPPARAAPI APRPPARPRL ERALSLDDKG WRRRRFRGSQ EDLEARNGTS PSRGSVQSEG 

       130        140        150        160        170        180 
PGAPAHSCSP PCLSTSLQEI PKSRGVLSSE RGSPSSGGNP LSGVASSSPN LPHRDAAVAG 

       190        200        210        220        230        240 
SSPRLPSLLP PRPPPALSLD IASDSLRTAN KVDSDLADYK LRAQPLLVRA HSSLGPGRPR 

       250        260        270        280        290        300 
SPLACDDCSL RSAKSSFSLL APIRSKDVRS RSYLEGSLLA SGALLGADEL ARYFPDRNVA 

       310        320        330        340        350        360 
LFVATWNMQG QKELPPSLDE FLLPAEADYA QDLYVIGVQE GCSDRREWET RLQETLGPHY 

       370        380        390        400        410        420 
VLLSSAAHGV LYMSLFIRRD LIWFCSEVEC STVTTRIVSQ IKTKGALGIS FTFFGTSFLF 

       430        440        450        460        470        480 
ITSHFTSGDG KVAERLLDYT RTVQALVLPR NVPDTNPYRS SAADVTTRFD EVFWFGDFNF 

       490        500        510        520        530        540 
RLSGGRTVVD ALLCQGLVVD VPALLQHDQL IREMRKGSIF KGFQEPDIHF LPSYKFDIGK 

       550        560        570        580        590        600 
DTYDSTSKQR TPSYTDRVLY RSRHKGDICP VSYSSCPGIK TSDHRPVYGL FRVKVRPGRD 

       610        620        630        640 
NIPLAAGKFD RELYLLGIKR RISKEIQRQQ ALQSQNSSTI CSVS 

« Hide

Isoform 2 [UniParc].

Checksum: 093CCDE3EBB9DD9A
Show »

FASTA61066,193

References

« Hide 'large scale' references
[1]"The isolation and characterization of a cDNA encoding phospholipid-specific inositol polyphosphate 5-phosphatase."
Kisseleva M.V., Wilson M.P., Majerus P.W.
J. Biol. Chem. 275:20110-20116(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, TISSUE SPECIFICITY.
Tissue: Fetal brain.
[2]"DNA sequence and analysis of human chromosome 9."
Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. expand/collapse author list , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[5]Nussbaum R.L.
Submitted (JAN-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 469-644 (ISOFORM 1).
[6]"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage."
Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.
Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-99, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic kidney.
[7]"INPP5E mutations cause primary cilium signaling defects, ciliary instability and ciliopathies in human and mouse."
Jacoby M., Cox J.J., Gayral S., Hampshire D.J., Ayub M., Blockmans M., Pernot E., Kisseleva M.V., Compere P., Schiffmann S.N., Gergely F., Riley J.H., Perez-Morga D., Woods C.G., Schurmans S.
Nat. Genet. 41:1027-1031(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INVOLVEMENT IN MORMS.
[8]"Mutations in INPP5E, encoding inositol polyphosphate-5-phosphatase E, link phosphatidyl inositol signaling to the ciliopathies."
Bielas S.L., Silhavy J.L., Brancati F., Kisseleva M.V., Al-Gazali L., Sztriha L., Bayoumi R.A., Zaki M.S., Abdel-Aleem A., Rosti R.O., Kayserili H., Swistun D., Scott L.C., Bertini E., Boltshauser E., Fazzi E., Travaglini L., Field S.J. expand/collapse author list , Gayral S., Jacoby M., Schurmans S., Dallapiccola B., Majerus P.W., Valente E.M., Gleeson J.G.
Nat. Genet. 41:1032-1036(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, VARIANTS JBTS1 CYS-378; GLN-435; TRP-512; TRP-515; HIS-563 AND GLU-580, CHARACTERIZATION OF VARIANTS JBTS1 CYS-378; GLN-435; TRP-512; TRP-515; HIS-563 AND GLU-580.
[9]"Crystal structure of human INPP5E."
Structural genomics consortium (SGC)
Submitted (NOV-2010) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 275-623.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF187891 mRNA. Translation: AAF81404.1.
AL592301 Genomic DNA. Translation: CAI13947.1.
CH471090 Genomic DNA. Translation: EAW88234.1.
BC028032 mRNA. Translation: AAH28032.1.
U45974 mRNA. Translation: AAB03215.1. Sequence problems.
RefSeqNP_063945.2. NM_019892.4.
UniGeneHs.120998.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2XSWX-ray1.90A/B275-623[»]
ProteinModelPortalQ9NRR6.
SMRQ9NRR6. Positions 282-623.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid121159. 1 interaction.
STRING9606.ENSP00000360777.

PTM databases

PhosphoSiteQ9NRR6.

Polymorphism databases

DMDM212276439.

Proteomic databases

PaxDbQ9NRR6.
PRIDEQ9NRR6.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000371712; ENSP00000360777; ENSG00000148384. [Q9NRR6-1]
GeneID56623.
KEGGhsa:56623.
UCSCuc004cho.3. human. [Q9NRR6-1]

Organism-specific databases

CTD56623.
GeneCardsGC09M139323.
H-InvDBHIX0125641.
HGNCHGNC:21474. INPP5E.
MIM213300. phenotype.
610156. phenotype.
613037. gene.
neXtProtNX_Q9NRR6.
Orphanet475. Joubert syndrome.
220493. Joubert syndrome with ocular defect.
75858. MORM syndrome.
PharmGKBPA164741785.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5411.
HOGENOMHOG000231541.
HOVERGENHBG052132.
InParanoidQ9NRR6.
KOK01099.
OMASCSPPCL.
OrthoDBEOG70KGPF.
PhylomeDBQ9NRR6.
TreeFamTF323475.

Enzyme and pathway databases

BioCycMetaCyc:HS09270-MONOMER.
ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressQ9NRR6.
BgeeQ9NRR6.
CleanExHS_INPP5E.
GenevestigatorQ9NRR6.

Family and domain databases

Gene3D3.60.10.10. 1 hit.
InterProIPR005135. Endo/exonuclease/phosphatase.
IPR000300. IPPc.
[Graphical view]
PfamPF03372. Exo_endo_phos. 1 hit.
[Graphical view]
SMARTSM00128. IPPc. 1 hit.
[Graphical view]
SUPFAMSSF56219. SSF56219. 1 hit.
ProtoNetSearch...

Other

GenomeRNAi56623.
NextBio62067.
PROQ9NRR6.
SOURCESearch...

Entry information

Entry nameINP5E_HUMAN
AccessionPrimary (citable) accession number: Q9NRR6
Secondary accession number(s): Q15734, Q6PIV5
Entry history
Integrated into UniProtKB/Swiss-Prot: March 29, 2004
Last sequence update: November 4, 2008
Last modified: April 16, 2014
This is version 104 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM