Q9BT40 (INP5K_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Inositol polyphosphate 5-phosphatase K
EC=3.1.3.56

Alternative name(s):
Skeletal muscle and kidney-enriched inositol phosphatase

Gene names

Name:	INPP5K
Synonyms:	PPS, SKIP

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	448 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. May negatively regulate assembly of the actin cytoskeleton. Ref.1
Catalytic activity	D-myo-inositol 1,4,5-trisphosphate + H2O = myo-inositol 1,4-bisphosphate + phosphate. Ref.1
Subcellular location	Endoplasmic reticulum. Note: Following stimulation with EGF, translocates to membrane ruffles. Ref.6
Tissue specificity	Ubiquitously expressed with highest levels in skeletal muscle, heart and kidney. Ref.1
Sequence similarities	Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase type II family.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum
Coding sequence diversity	Alternative splicing Polymorphism
Molecular function	Hydrolase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	actin cytoskeleton organization Non-traceable author statement Ref.1. Source: UniProtKB cellular response to cAMP Inferred from sequence or structural similarity. Source: UniProtKB cellular response to epidermal growth factor stimulus Inferred from direct assay PubMed 21712384. Source: UniProtKB cellular response to insulin stimulus Inferred from direct assay PubMed 12556481. Source: UniProtKB cellular response to tumor necrosis factor Inferred from direct assay PubMed 21712384. Source: UniProtKB glucose homeostasis Inferred from sequence or structural similarity. Source: UniProtKB in utero embryonic development Inferred from electronic annotation. Source: Compara inositol phosphate dephosphorylation Inferred from direct assay Ref.6. Source: MGI negative regulation by host of viral transcription Inferred from direct assay PubMed 18774950. Source: UniProtKB negative regulation of MAP kinase activity Inferred from direct assay PubMed 12556481. Source: UniProtKB negative regulation of calcium ion transport Inferred from direct assay PubMed 12556481. Source: UniProtKB negative regulation of dephosphorylation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of glucose transport Inferred from direct assay PubMed 12556481. Source: UniProtKB negative regulation of glycogen (starch) synthase activity Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of glycogen biosynthetic process Inferred from direct assay PubMed 12556481. Source: UniProtKB negative regulation of insulin receptor signaling pathway Inferred from direct assay PubMed 12556481. Source: UniProtKB negative regulation of peptidyl-serine phosphorylation Inferred from direct assay PubMed 12556481. Source: UniProtKB negative regulation of peptidyl-threonine phosphorylation Inferred from direct assay PubMed 12556481. Source: UniProtKB negative regulation of protein kinase B signaling cascade Inferred from direct assay PubMed 12556481. Source: UniProtKB negative regulation of protein targeting to membrane Inferred from direct assay PubMed 12556481. Source: UniProtKB negative regulation of retroviral genome replication Inferred from direct assay PubMed 18774950. Source: UniProtKB negative regulation of stress fiber assembly Inferred from direct assay PubMed 12556481. Source: UniProtKB negative regulation of transcription, DNA-dependent Inferred from sequence or structural similarity. Source: UniProtKB phosphatidylinositol biosynthetic process Traceable author statement. Source: Reactome phosphatidylinositol dephosphorylation Inferred from direct assay PubMed 12556481. Source: UniProtKB phosphatidylinositol phosphorylation Inferred from electronic annotation. Source: InterPro positive regulation of renal water transport Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription, DNA-dependent Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of urine volume Inferred from sequence or structural similarity. Source: UniProtKB protein targeting to plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB ruffle assembly Inferred from direct assay PubMed 12556481. Source: UniProtKB
Cellular_component	cytosol Inferred from direct assay Ref.1PubMed 21712384. Source: UniProtKB endoplasmic reticulum Inferred from direct assay PubMed 18774950. Source: UniProtKB neuron projection Inferred from direct assay Ref.1. Source: UniProtKB nucleus Inferred from direct assay PubMed 18774950. Source: UniProtKB perinuclear region of cytoplasm Inferred from direct assay PubMed 18774950PubMed 21712384. Source: UniProtKB ruffle membrane Inferred from direct assay PubMed 12556481. Source: UniProtKB trans-Golgi network Inferred from direct assay PubMed 12556481. Source: UniProtKB
Molecular_function	inositol bisphosphate phosphatase activity Inferred from direct assay PubMed 18573875. Source: MGI inositol trisphosphate phosphatase activity Inferred from direct assay PubMed 18573875. Source: MGI inositol-1,3,4,5-tetrakisphosphate 5-phosphatase activity Inferred from electronic annotation. Source: EC inositol-1,4,5-trisphosphate 5-phosphatase activity Inferred from electronic annotation. Source: EC inositol-polyphosphate 5-phosphatase activity Inferred from electronic annotation. Source: EC lipid phosphatase activity Non-traceable author statement Ref.1. Source: UniProtKB phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase activity Inferred from direct assay PubMed 21712384. Source: UniProtKB vasopressin receptor activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
LNX1	Q8TBB1	3	EBI-749162,EBI-739832

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 Ref.1 (identifier: Q9BT40-1)

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 Ref.1 (identifier: Q9BT40-2)

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 448	448	Inositol polyphosphate 5-phosphatase K		PRO_0000209727
Regions
	Region	16 – 318	303	Catalytic Potential
	Region	321 – 448	128	Required for ruffle localization Ref.6
Natural variations
	Alternative sequence	1 – 76	76	Missing in isoform 2. Ref.1		VSP_050612
	Natural variant	315	1	S → F in a breast cancer sample; somatic mutation. Ref.7		VAR_036497
Experimental info
	Mutagenesis	349	1	Y → A or F: No effect on EGF-induced ruffle localization. Ref.6
	Mutagenesis	361	1	D → A: Significant decrease in EGF-induced ruffle localization. Ref.6
	Mutagenesis	362	1	W → A: Significant decrease in EGF-induced ruffle localization. Ref.6
	Mutagenesis	376	1	Y → A or F: No effect on EGF-induced ruffle localization. Ref.6
	Sequence conflict	120	1	T → A in AAB03214. Ref.5
	Sequence conflict	416	1	S → R in BAA92340. Ref.1
	Sequence conflict	416	1	S → R in BAA92341. Ref.1
	Sequence conflict	416	1	S → R in BAA92342. Ref.1
	Sequence conflict	416	1	S → R in AAB03214. Ref.5
	Sequence conflict	426	1	S → R in BAA92340. Ref.1
	Sequence conflict	426	1	S → R in BAA92341. Ref.1
	Sequence conflict	426	1	S → R in BAA92342. Ref.1
	Sequence conflict	426	1	S → R in AAB03214. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 17, 2006. Version 3. Checksum: 46FAA48C6E2EEAD4	FASTA	448	51,090
	10 20 30 40 50 60 MSSRKLSGPK GRRLSIHVVT WNVASAAPPL DLSDLLQLNN RNLNLDIYVI GLQELNSGII 70 80 90 100 110 120 SLLSDAAFND SWSSFLMDVL SPLSFIKVSH VRMQGILLLV FAKYQHLPYI QILSTKSTPT 130 140 150 160 170 180 GLFGYWGNKG GVNICLKLYG YYVSIINCHL PPHISNNYQR LEHFDRILEM QNCEGRDIPN 190 200 210 220 230 240 ILDHDLIIWF GDMNFRIEDF GLHFVRESIK NRCYGGLWEK DQLSIAKKHD PLLREFQEGR 250 260 270 280 290 300 LLFPPTYKFD RNSNDYDTSE KKRKPAWTDR ILWRLKRQPC AGPDTPIPPA SHFSLSLRGY 310 320 330 340 350 360 SSHMTYGISD HKPVSGTFDL ELKPLVSAPL IVLMPEDLWT VENDMMVSYS STSDFPSSPW 370 380 390 400 410 420 DWIGLYKVGL RDVNDYVSYA WVGDSKVSCS DNLNQVYIDI SNIPTTEDEF LLCYYSNSLR 430 440 SVVGISRPFQ IPPGSLREDP LGEAQPQI
	Isoform 2 [UniParc]. Checksum: E257B4890DCD44F3	FASTA	372	42,784
	10 20 30 40 50 60 MDVLSPLSFI KVSHVRMQGI LLLVFAKYQH LPYIQILSTK STPTGLFGYW GNKGGVNICL 70 80 90 100 110 120 KLYGYYVSII NCHLPPHISN NYQRLEHFDR ILEMQNCEGR DIPNILDHDL IIWFGDMNFR 130 140 150 160 170 180 IEDFGLHFVR ESIKNRCYGG LWEKDQLSIA KKHDPLLREF QEGRLLFPPT YKFDRNSNDY 190 200 210 220 230 240 DTSEKKRKPA WTDRILWRLK RQPCAGPDTP IPPASHFSLS LRGYSSHMTY GISDHKPVSG 250 260 270 280 290 300 TFDLELKPLV SAPLIVLMPE DLWTVENDMM VSYSSTSDFP SSPWDWIGLY KVGLRDVNDY 310 320 330 340 350 360 VSYAWVGDSK VSCSDNLNQV YIDISNIPTT EDEFLLCYYS NSLRSVVGIS RPFQIPPGSL 370 REDPLGEAQP QI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification and characterization of a novel inositol polyphosphate 5-phosphatase." Ijuin T., Mochizuki Y., Fukami K., Funaki M., Asano T., Takenawa T. J. Biol. Chem. 275:10870-10875(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), FUNCTION, TISSUE SPECIFICITY. Tissue: Testis.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Brain and Thymus.
[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 (SEP-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: Eye.
[5]	Nussbaum R.L. Submitted (JAN-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 120-448. Tissue: Brain.
[6]	"Identification of a novel domain in two mammalian inositol-polyphosphate 5-phosphatases that mediates membrane ruffle localization. The inositol 5-phosphatase SKIP localizes to the endoplasmic reticulum and translocates to membrane ruffles following epidermal growth factor stimulation." Gurung R., Tan A., Ooms L.M., McGrath M.J., Huysmans R.D., Munday A.D., Prescott M., Whisstock J.C., Mitchell C.A. J. Biol. Chem. 278:11376-11385(2003) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF TYR-349; ASP-361; TRP-362 AND TYR-376.
[7]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] PHE-315.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00374574. IPI00374575.
RefSeq	NP_001129114.1. NM_001135642.1. NP_057616.2. NM_016532.3. NP_570122.1. NM_130766.2.
UniGene	Hs.632238.
3D structure databases
ProteinModelPortal	Q9BT40.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9BT40. 6 interactions.
MINT	MINT-1445023.
STRING	9606.ENSP00000254712.
PTM databases
PhosphoSite	Q9BT40.
Polymorphism databases
DMDM	116242791.
Proteomic databases
PaxDb	Q9BT40.
PRIDE	Q9BT40.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000320345; ENSP00000318476; ENSG00000132376. ENST00000406424; ENSP00000385177; ENSG00000132376. ENST00000421807; ENSP00000413937; ENSG00000132376.
GeneID	51763.
KEGG	hsa:51763.
UCSC	uc002fsq.3. human.
Organism-specific databases
CTD	51763.
GeneCards	GC17M001397.
HGNC	HGNC:33882. INPP5K.
HPA	HPA031044.
MIM	607875. gene.
neXtProt	NX_Q9BT40.
PharmGKB	PA164720951.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5411.
HOGENOM	HOG000046051.
HOVERGEN	HBG082135.
InParanoid	Q9BT40.
KO	K01106.
OMA	TEDQFLL.
PhylomeDB	Q9BT40.
Enzyme and pathway databases
BioCyc	MetaCyc:HS05626-MONOMER.
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	Q9BT40.
Bgee	Q9BT40.
CleanEx	HS_INPP5K.
Genevestigator	Q9BT40.
GermOnline	ENSG00000132376. 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	51763.
NextBio	55878.
SOURCE	Search...

Entry information

Entry name

INP5K_HUMAN

Accession

Primary (citable) accession number: Q9BT40
Secondary accession number(s): B2R6I2 , B2R750, D3DTH8, Q15733, Q9NPJ5, Q9P2R5

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 26, 2003
Last sequence update:	October 17, 2006
Last modified:	May 1, 2013
This is version 101 of the entry and version 3 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.