P70182 (PI51A_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Phosphatidylinositol 4-phosphate 5-kinase type-1 alpha
Short name=PIP5K1-alpha
Short name=PtdIns(4)P-5-kinase 1 alpha
EC=2.7.1.68

Alternative name(s):
68 kDa type I phosphatidylinositol 4-phosphate 5-kinase
Phosphatidylinositol 4-phosphate 5-kinase type I alpha
Short name=PIP5KIalpha
Phosphatidylinositol 4-phosphate 5-kinase type I beta
Short name=PI4P5KIbeta

Gene names

Name:	Pip5k1a
Synonyms:	Pip5k1b

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	546 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns4P) to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). PtdIns(4,5)P2 is involved in a variety of cellular processes and is the substrate to form phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3), another second messenger. The majority of PtdIns(4,5)P2 is thought to occur via type I phosphatidylinositol 4-phosphate 5-kinases given the abundance of PtdIns4P. Participates in a variety of cellular processes such as actin cytoskeleton organization, cell adhesion, migration and phagocytosis. Required for membrane ruffling formation, actin organization and focal adhesion formation during directional cell migration by controlling integrin-induced translocation of RAC1 to the plasma membrane. Together with PIP5K1C is required for phagocytosis, but they regulate different types of actin remodeling at sequential steps. Promotes particle ingestion by activating WAS that induces Arp2/3 dependent actin polymerization at the nascent phagocytic cup. Together with PIP5K1B is required after stimulation of G-protein coupled receptors for stable platelet adhesion. Plays a role during calcium-induced keratinocyte differentiation. Recruited to the plasma membrane by the E-cadherin/beta-catenin complex where it provides the substrate PtdIns(4,5)P2 for the production of PtdIns(3,4,5)P3, diacylglycerol and inositol 1,4,5-trisphosphate that mobilize internal calcium and drive keratinocyte differentiation. Together with PIP5K1C have a role during embryogenesis. Functions also in the nucleus where acts as an activator of TUT1 adenylyltransferase activity in nuclear speckles, thereby regulating mRNA polyadenylation of a select set of mRNAs. Ref.1 Ref.5 Ref.6 Ref.7 Ref.8
Catalytic activity	ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate = ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate.
Enzyme regulation	Activated by phosphatidic acid. Ref.1 Ref.4
Subunit structure	Interacts with RAC1. Interacts with TUT1 By similarity. Forms a complex with CDH1/E-cadherin, CTNNB1/beta-catenin and CTNND1 at the plasma membrane upon calcium stimulation By similarity. Ref.5
Subcellular location	Cell membrane. Nucleus speckle By similarity. Cytoplasm. Cell projection › ruffle By similarity. Note: Colocalizes with RAC1 at actin-rich membrane ruffles By similarity. Localizes to nuclear speckles and associates with TUT1 to regulate polyadenylation of selected mRNAs By similarity. Ref.8
Tissue specificity	Highest expression in brain. Also detected in skeletal muscle, testis, brain and lung. Ref.1 Ref.8
Developmental stage	Expression is highest during early embryogenesis and slightly decreases over time. Ref.8
Disruption phenotype	Survive to adulthood, but bred poorly and display reduced fertility. Failed to form any vessel occlusion after chemical-induced carotid injury. Platelets have defective aggregation. Bone marrow-derived macrophages (BMM) are defective in actin polymerization during phagocytosis. Double mutant mice carrying both PIP5K1A and PIP5K1C mutations are embryonic lethal. Ref.6 Ref.7 Ref.8
Sequence similarities	Contains 1 PIPK domain.
Caution	There is confusion in the literature with phosphatidylinositol 4-phosphate 5-kinase type I nomenclature due to the fact that frequently mouse PIP5K1B is named Phosphatidylinositol 4-phosphate 5-kinase type I alpha.
Biophysicochemical properties	Kinetic parameters: KM=26 µM for PtdIns4P Ref.4 KM=33 µM for ATP

Ontologies

Keywords
Cellular component	Cell membrane Cell projection Cytoplasm Membrane Nucleus
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase
PTM	Isopeptide bond Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	actin cytoskeleton reorganization Inferred from sequence or structural similarity. Source: UniProtKB activation of Rac GTPase activity Inferred from sequence or structural similarity. Source: UniProtKB cell chemotaxis Inferred from sequence or structural similarity. Source: UniProtKB fibroblast migration Inferred from mutant phenotype PubMed 15870270. Source: MGI focal adhesion assembly Inferred from sequence or structural similarity. Source: UniProtKB phospholipid biosynthetic process Inferred from electronic annotation. Source: Compara protein targeting to plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB ruffle assembly Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell lamellipodium Inferred from electronic annotation. Source: Compara mRNA cleavage and polyadenylation specificity factor complex Inferred from electronic annotation. Source: Compara nuclear speck Inferred from sequence or structural similarity. Source: UniProtKB ruffle membrane Inferred from direct assay PubMed 15870270. Source: MGI
Molecular_function	1-phosphatidylinositol-4-phosphate 5-kinase activity Inferred from direct assay Ref.1. Source: MGI ATP binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: P70182-1)

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: P70182-2)

The sequence of this isoform differs from the canonical sequence as follows:
     238-431: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 546	546	Phosphatidylinositol 4-phosphate 5-kinase type-1 alpha		PRO_0000185457
Regions
	Domain	66 – 434	369	PIPK
Amino acid modifications
	Cross-link	88		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Natural variations
	Alternative sequence	238 – 431	194	Missing in isoform 2.		VSP_016009
Experimental info
	Sequence conflict	28	1	S → AS in AAH03763. Ref.3
	Sequence conflict	120	1	N → S in AAH03763. Ref.3
	Sequence conflict	258	1	E → D in BAA13031. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 25, 2005. Version 2. Checksum: 6E895F22A75B7140	FASTA	546	60,485
	10 20 30 40 50 60 MASASSGPAA AGFSSLDAGA PAGTAAASGI KRATVSEGPS ASVMPVKKIG HRSVDSSGET 70 80 90 100 110 120 TYKKTTSSAL KGAIQLGITH TVGSLSTKPE RDVLMQDFYV VESIFFPSEG SNLTPAHHYN 130 140 150 160 170 180 DFRFKTYAPV AFRYFRELFG IRPDDYLYSL CSEPLIELSN SGASGSLFYV SSDDEFIIKT 190 200 210 220 230 240 VQHKEAEFLQ KLLPGYYMNL NQNPRTLLPK FYGLYCVQAG GKNIRIVVMN NLLPRSVKMH 250 260 270 280 290 300 MKYDLKGSTY KRRASQKERE KTLPTFKDLD FLQDIPDGLF LDADMYSALC KTLQRDCLVL 310 320 330 340 350 360 QSFKIMDYSL LMSIHNMDHA QREPTSNDTQ YSADTRRPAP QKALYSTAME SIQGEARRGG 370 380 390 400 410 420 TVETEDHMGG IPARNNKGER LLLYIGIIDI LQSYRFVKKL EHSWKALVHD GDTVSVHRPG 430 440 450 460 470 480 FYAERFQRFM CNTVFKKIPL KPSPTKKFRS GPSFSRRSGP SGNSCTSQLM ASGEHRAQVT 490 500 510 520 530 540 TKAEVEPDVH LGRPDVLPQT PPLEEISEGS PVPGPSFSPV VGQPLQILNL SSTLEKLDVA ESEFTH
	Isoform 2 [UniParc]. Checksum: 6090D9F312A32B99	FASTA	352	38,027
	10 20 30 40 50 60 MASASSGPAA AGFSSLDAGA PAGTAAASGI KRATVSEGPS ASVMPVKKIG HRSVDSSGET 70 80 90 100 110 120 TYKKTTSSAL KGAIQLGITH TVGSLSTKPE RDVLMQDFYV VESIFFPSEG SNLTPAHHYN 130 140 150 160 170 180 DFRFKTYAPV AFRYFRELFG IRPDDYLYSL CSEPLIELSN SGASGSLFYV SSDDEFIIKT 190 200 210 220 230 240 VQHKEAEFLQ KLLPGYYMNL NQNPRTLLPK FYGLYCVQAG GKNIRIVVMN NLLPRSVNTV 250 260 270 280 290 300 FKKIPLKPSP TKKFRSGPSF SRRSGPSGNS CTSQLMASGE HRAQVTTKAE VEPDVHLGRP 310 320 330 340 350 DVLPQTPPLE EISEGSPVPG PSFSPVVGQP LQILNLSSTL EKLDVAESEF TH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of cDNAs encoding two isoforms of 68-kDa type I phosphatidylinositol 4-phosphate 5-kinase." Ishihara H., Shibasaki Y., Kizuki N., Katagiri H., Yazaki Y., Asano T., Oka Y. J. Biol. Chem. 271:23611-23614(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, ENZYME REGULATION, TISSUE SPECIFICITY. Tissue: Insulinoma.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Strain: C57BL/6J. Tissue: Inner ear.
[3]	"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] (ISOFORMS 1 AND 2). Tissue: Eye and Mammary gland.
[4]	"Type I phosphatidylinositol-4-phosphate 5-kinases. Cloning of the third isoform and deletion/substitution analysis of members of this novel lipid kinase family." Ishihara H., Shibasaki Y., Kizuki N., Wada T., Yazaki Y., Asano T., Oka Y. J. Biol. Chem. 273:8741-8748(1998) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES.
[5]	"Type Ialpha phosphatidylinositol-4-phosphate 5-kinase mediates Rac-dependent actin assembly." Tolias K.F., Hartwig J.H., Ishihara H., Shibasaki Y., Cantley L.C., Carpenter C.L. Curr. Biol. 10:153-156(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH RAC1.
[6]	"Loss of PIP5KIbeta demonstrates that PIP5KI isoform-specific PIP2 synthesis is required for IP3 formation." Wang Y., Chen X., Lian L., Tang T., Stalker T.J., Sasaki T., Kanaho Y., Brass L.F., Choi J.K., Hartwig J.H., Abrams C.S. Proc. Natl. Acad. Sci. U.S.A. 105:14064-14069(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PLATELETS, DISRUPTION PHENOTYPE.
[7]	"Essential and unique roles of PIP5K-gamma and -alpha in Fcgamma receptor-mediated phagocytosis." Mao Y.S., Yamaga M., Zhu X., Wei Y., Sun H.-Q., Wang J., Yun M., Wang Y., Di Paolo G., Bennett M., Mellman I., Abrams C.S., De Camilli P., Lu C.Y., Yin H.L. J. Cell Biol. 184:281-296(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHAGOCYTOSIS, DISRUPTION PHENOTYPE.
[8]	"Phosphatidylinositol-4-phosphate 5-kinases and phosphatidylinositol 4,5-bisphosphate synthesis in the brain." Volpicelli-Daley L.A., Lucast L., Gong L.-W., Liu L., Sasaki J., Sasaki T., Abrams C.S., Kanaho Y., De Camilli P. J. Biol. Chem. 285:28708-28714(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN EMBRYOGENESIS, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D86177 mRNA. Translation: BAA13031.1. AK158062 mRNA. Translation: BAE34344.1. BC003763 mRNA. Translation: AAH03763.1. BC031774 mRNA. Translation: AAH31774.1.
IPI	IPI00331736. IPI00475262.
RefSeq	NP_032873.2. NM_008847.2.
UniGene	Mm.296409.
3D structure databases
ProteinModelPortal	P70182.
SMR	P70182. Positions 67-352.
ModBase	Search...
PTM databases
PhosphoSite	P70182.
Proteomic databases
PaxDb	P70182.
PRIDE	P70182.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000107236; ENSMUSP00000102855; ENSMUSG00000028126.
GeneID	18720.
KEGG	mmu:18720.
UCSC	uc008qhx.1. mouse.
Organism-specific databases
CTD	8394.
MGI	MGI:107929. Pip5k1a.
Phylogenomic databases
eggNOG	COG5253.
GeneTree	ENSGT00690000101870.
HOGENOM	HOG000193876.
HOVERGEN	HBG052818.
KO	K00889.
OrthoDB	EOG4JQ3Z0.
Gene expression databases
ArrayExpress	P70182.
Bgee	P70182.
Genevestigator	P70182.
GermOnline	ENSMUSG00000028126. Mus musculus.
Family and domain databases
InterPro	IPR023610. PInositol-4-P-5-kinase. IPR002498. PInositol-4-P-5-kinase_core. IPR016034. PInositol-4P-5-kinase_core_sub. [Graphical view]
PANTHER	PTHR23086. PTHR23086. 1 hit.
Pfam	PF01504. PIP5K. 1 hit. [Graphical view]
SMART	SM00330. PIPKc. 1 hit. [Graphical view]
PROSITE	PS51455. PIPK. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	PIP5K1A. mouse.
NextBio	294821.
SOURCE	Search...

Entry information

Entry name

PI51A_MOUSE

Accession

Primary (citable) accession number: P70182
Secondary accession number(s): Q8K0D3, Q99L80

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 25, 2005
Last sequence update:	October 25, 2005
Last modified:	May 1, 2013
This is version 94 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program