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P70182 (PI51A_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 107. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | 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:
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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length546 AA.
Sequence statusComplete.
Protein existenceEvidence 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.6 Ref.7 Ref.8 Ref.9

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.5

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.6

Subcellular location

Cell membrane. Nucleus speckle By similarity. Cytoplasm. Cell projectionruffle 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.9

Tissue specificity

Highest expression in brain. Also detected in skeletal muscle, testis, brain and lung. Ref.1 Ref.9

Developmental stage

Expression is highest during early embryogenesis and slightly decreases over time. Ref.9

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 are defective in actin polymerization during phagocytosis. PIP5K1A and PIP5K1C double mutant mice are embryonic lethal. Ref.7 Ref.8 Ref.9

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.5

KM=33 µM for ATP

Ontologies

Keywords
   Cellular componentCell membrane
Cell projection
Cytoplasm
Membrane
Nucleus
   Coding sequence diversityAlternative splicing
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
   PTMIsopeptide bond
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactin 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

phosphatidylinositol metabolic process

Inferred from direct assay Ref.1. Source: MGI

phosphatidylinositol phosphorylation

Inferred from direct assay Ref.1. Source: GOC

phospholipid biosynthetic process

Inferred from electronic annotation. Source: Ensembl

protein targeting to plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

ruffle assembly

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

lamellipodium

Inferred from electronic annotation. Source: Ensembl

mRNA cleavage and polyadenylation specificity factor complex

Inferred from electronic annotation. Source: Ensembl

nuclear speck

Inferred from sequence or structural similarity. Source: UniProtKB

nucleus

Inferred from direct assay PubMed 15870270. Source: MGI

plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

ruffle membrane

Inferred from direct assay PubMed 15870270. Source: MGI

   Molecular_function1-phosphatidylinositol-4-phosphate 5-kinase activity

Inferred from direct assay Ref.1. Source: MGI

ATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction PubMed 15870270. Source: MGI

Complete GO annotation...

Alternative products

This entry describes 3 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:
     27-27: A → AA
     238-431: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: P70182-3)

The sequence of this isoform differs from the canonical sequence as follows:
     27-27: A → AA
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 546546Phosphatidylinositol 4-phosphate 5-kinase type-1 alpha
PRO_0000185457

Regions

Domain66 – 434369PIPK

Amino acid modifications

Cross-link88Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Natural variations

Alternative sequence271A → AA in isoform 2 and isoform 3.
VSP_053437
Alternative sequence238 – 431194Missing in isoform 2.
VSP_016009

Experimental info

Sequence conflict1071P → R in BAE29943. Ref.2
Sequence conflict1071P → R in BAE30850. Ref.2
Sequence conflict1201N → S in AAH03763. Ref.4
Sequence conflict2581E → D in BAA13031. Ref.1

Sequences

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

Last modified October 25, 2005. Version 2.
Checksum: 6E895F22A75B7140

FASTA54660,485
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 99BDCE9D767BE901
Show »

FASTA35338,098
Isoform 3 [UniParc].

Checksum: 65889A83CE3F2B32
Show »

FASTA54760,556

References

« Hide '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. expand/collapse author list , 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] (ISOFORMS 1 AND 3).
Strain: C57BL/6J.
Tissue: Inner ear and Macrophage.
[3]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[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] (ISOFORMS 1 AND 2).
Tissue: Eye and Mammary tumor.
[5]"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.
[6]"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.
[7]"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.
[8]"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.
[9]"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.
AK150898 mRNA. Translation: BAE29943.1.
AK151984 mRNA. Translation: BAE30850.1.
AK158062 mRNA. Translation: BAE34344.1.
AC087062 Genomic DNA. No translation available.
AC131769 Genomic DNA. No translation available.
BC003763 mRNA. Translation: AAH03763.1.
BC031774 mRNA. Translation: AAH31774.1.
CCDSCCDS38542.1. [P70182-1]
RefSeqNP_032873.2. NM_008847.2. [P70182-1]
XP_006501193.1. XM_006501130.1. [P70182-3]
UniGeneMm.296409.

3D structure databases

ProteinModelPortalP70182.
SMRP70182. Positions 67-352.
ModBaseSearch...
MobiDBSearch...

PTM databases

PhosphoSiteP70182.

Proteomic databases

PaxDbP70182.
PRIDEP70182.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000107233; ENSMUSP00000102852; ENSMUSG00000028126. [P70182-3]
ENSMUST00000107236; ENSMUSP00000102855; ENSMUSG00000028126. [P70182-1]
GeneID18720.
KEGGmmu:18720.
UCSCuc008qhx.2. mouse. [P70182-1]
uc008qhy.2. mouse.

Organism-specific databases

CTD8394.
MGIMGI:107929. Pip5k1a.

Phylogenomic databases

eggNOGCOG5253.
GeneTreeENSGT00690000101870.
HOGENOMHOG000193876.
HOVERGENHBG052818.
KOK00889.
OMAETEDHMG.
OrthoDBEOG70W3DM.
PhylomeDBP70182.
TreeFamTF319618.

Gene expression databases

ArrayExpressP70182.
BgeeP70182.
GenevestigatorP70182.

Family and domain databases

Gene3D3.30.800.10. 1 hit.
3.30.810.10. 1 hit.
InterProIPR023610. PInositol-4-P-5-kinase.
IPR027483. PInositol-4-P-5-kinase_C.
IPR002498. PInositol-4-P-5-kinase_core.
IPR027484. PInositol-4-P-5-kinase_N.
IPR016034. PInositol-4P-5-kinase_core_sub.
[Graphical view]
PANTHERPTHR23086. PTHR23086. 1 hit.
PfamPF01504. PIP5K. 1 hit.
[Graphical view]
SMARTSM00330. PIPKc. 1 hit.
[Graphical view]
PROSITEPS51455. PIPK. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPIP5K1A. mouse.
NextBio294821.
PROP70182.
SOURCESearch...

Entry information

Entry namePI51A_MOUSE
AccessionPrimary (citable) accession number: P70182
Secondary accession number(s): F8WIX5 expand/collapse secondary AC list , Q3U917, Q8K0D3, Q99L80
Entry history
Integrated into UniProtKB/Swiss-Prot: October 25, 2005
Last sequence update: October 25, 2005
Last modified: July 9, 2014
This is version 107 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot