Q9NRR6 (INP5E_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	644 AA.
Sequence status	Complete.
Protein existence	Evidence 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	Cytoplasm › cytoskeleton › cilium axoneme. Golgi apparatus › Golgi 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.

Ontologies

Keywords
Biological process	Lipid metabolism
Cellular component	Cell projection Cilium Cytoplasm Cytoskeleton Golgi apparatus Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Ciliopathy Disease mutation Joubert syndrome Mental retardation Obesity
Domain	Repeat
Molecular function	Hydrolase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	inositol phosphate dephosphorylation Inferred from electronic annotation. Source: Compara phosphatidylinositol biosynthetic process Traceable author statement. Source: Reactome phosphatidylinositol dephosphorylation Inferred from electronic annotation. Source: Compara phosphatidylinositol phosphorylation Inferred from electronic annotation. Source: InterPro small molecule metabolic process Traceable author statement. Source: Reactome
Cellular_component	Golgi cisterna membrane Inferred from electronic annotation. Source: UniProtKB-SubCell cilium axoneme Inferred from direct assay Ref.7. Source: UniProtKB cytoskeleton Inferred from electronic annotation. Source: UniProtKB-KW cytosol Traceable author statement. Source: Reactome
Molecular_function	inositol-polyphosphate 5-phosphatase activity Traceable author statement Ref.1. Source: UniProtKB phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 644

644

72 kDa inositol polyphosphate 5-phosphatase

PRO_0000209747

Regions

Repeat

10 – 13

4

1

Repeat

15 – 18

4

2

Repeat

28 – 31

4

3

Repeat

39 – 42

4

4

Repeat

55 – 58

4

5

Repeat

69 – 71

3

6

Repeat

72 – 74

3

7

Repeat

75 – 78

4

8

Repeat

121 – 124

4

9

Repeat

169 – 172

4

10

Repeat

183 – 185

3

11

Repeat

190 – 193

4

12

Repeat

236 – 239

4

13

Region

10 – 242

233

13 X 4 AA repeats of P-X-X-P

Compositional bias

92 – 97

6

Poly-Arg

Amino acid modifications

Modified residue

99

1

Phosphoserine Ref.6

Modified residue

241

1

Phosphoserine By similarity

Natural variations

Alternative sequence

346 – 379

34

Missing in isoform 2.

VSP_009799

Natural variant

201

1

I → M.
Corresponds to variant rs36064831 [ dbSNP | Ensembl ].

VAR_047078

Natural variant

378

1

R → C in JBTS1; slightly reduced activity. Ref.8

VAR_063012

Natural variant

435

1

R → Q in JBTS1; severe reduction of activity. Ref.8

VAR_063013

Natural variant

512

1

R → W in JBTS1; associated with W-515; severe reduction of activity. Ref.8

VAR_063014

Natural variant

515

1

R → W in JBTS1; associated with W-512; severe reduction of activity. Ref.8

VAR_063015

Natural variant

563

1

R → H in JBTS1; slightly reduced activity. Ref.8

VAR_063016

Natural variant

580

1

K → E in JBTS1; severe reduction of activity. Ref.8

VAR_063017

Experimental info

Sequence conflict

345

1

R → T in AAF81404. Ref.1

Secondary structure

1

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644

Helix Strand Turn

Details...

Helix

287 – 293

7

Beta strand

298 – 307

10

Helix

319 – 322

4

Beta strand

332 – 340

9

Helix

345 – 356

12

Beta strand

360 – 368

9

Beta strand

371 – 378

8

Helix

379 – 384

6

Beta strand

389 – 399

11

Beta strand

402 – 413

12

Beta strand

416 – 424

9

Helix

432 – 445

14

Beta strand

450 – 452

3

Helix

457 – 459

3

Helix

465 – 467

3

Beta strand

468 – 477

10

Beta strand

482 – 484

3

Helix

486 – 493

8

Helix

501 – 505

5

Helix

509 – 515

7

Beta strand

518 – 520

3

Beta strand

540 – 543

4

Beta strand

556 – 564

9

Beta strand

567 – 575

9

Beta strand

581 – 584

4

Beta strand

587 – 594

8

Helix

611 – 623

13

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 4, 2008. Version 2. Checksum: 5B6CFB75CD0ADC9A	FASTA	644	70,205
	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
	Isoform 2 [UniParc]. Checksum: 093CCDE3EBB9DD9A	FASTA	610	66,193
	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 GCSDRDLIWF CSEVECSTVT 370 380 390 400 410 420 TRIVSQIKTK GALGISFTFF GTSFLFITSH FTSGDGKVAE RLLDYTRTVQ ALVLPRNVPD 430 440 450 460 470 480 TNPYRSSAAD VTTRFDEVFW FGDFNFRLSG GRTVVDALLC QGLVVDVPAL LQHDQLIREM 490 500 510 520 530 540 RKGSIFKGFQ EPDIHFLPSY KFDIGKDTYD STSKQRTPSY TDRVLYRSRH KGDICPVSYS 550 560 570 580 590 600 SCPGIKTSDH RPVYGLFRVK VRPGRDNIPL AAGKFDRELY LLGIKRRISK EIQRQQALQS 610 QNSSTICSVS

References

	« Hide 'large scale' referencesShow '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. , 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. , 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, MASS SPECTROMETRY. 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. , 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.

IPI

IPI00181799.
IPI00409719.

RefSeq

NP_063945.2. NM_019892.4.

UniGene

Hs.120998.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2XSW	X-ray	1.90	A/B	275-623	[»]

ProteinModelPortal

Q9NRR6.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000360777.

PTM databases

PhosphoSite

Q9NRR6.

Polymorphism databases

DMDM

212276439.

Proteomic databases

PaxDb

Q9NRR6.

PRIDE

Q9NRR6.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000371712; ENSP00000360777; ENSG00000148384.

GeneID

56623.

KEGG

hsa:56623.

UCSC

uc004cho.3. human.

Organism-specific databases

CTD

56623.

GeneCards

GC09M139323.

H-InvDB

HIX0125641.

HGNC

HGNC:21474. INPP5E.

MIM

213300. phenotype.
610156. phenotype.
613037. gene.

neXtProt

NX_Q9NRR6.

Orphanet

475. Joubert syndrome.
75858. MORM syndrome.

PharmGKB

PA164741785.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5411.

HOGENOM

HOG000231541.

HOVERGEN

HBG052132.

InParanoid

Q9NRR6.

KO

K01099.

OMA

SCSPPCL.

OrthoDB

EOG4CVG6H.

PhylomeDB

Q9NRR6.

Enzyme and pathway databases

BioCyc

MetaCyc:HS09270-MONOMER.

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

Q9NRR6.

Bgee

Q9NRR6.

CleanEx

HS_INPP5E.

Genevestigator

Q9NRR6.

GermOnline

ENSG00000148384. Homo sapiens.

Family and domain databases

InterPro

IPR005135. Endo/exonuclease/phosphatase.
IPR000300. IPPc.
[Graphical view]

Pfam

PF03372. Exo_endo_phos. 1 hit.
[Graphical view]

SMART

SM00128. IPPc. 1 hit.
[Graphical view]

SUPFAM

SSF56219. Exo_endo_phos. 1 hit.

ProtoNet

Search...

Other

GenomeRNAi

56623.

NextBio

62067.

SOURCE

Search...

Entry information

Entry name

INP5E_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 95 of the entry and version 2 of the sequence. [Complete history]

Entry status

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.