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Protein

Phosphatidylinositol 4-phosphate 5-kinase type-1 alpha

Gene

PIP5K1A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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 (PubMed:18288197, PubMed:19158393, PubMed:20660631). Positively regulates insulin-induced translocation of SLC2A4 to the cell membrane in adipocytes (By similarity).By similarity3 Publications

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.Curated

Catalytic activityi

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

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Transferase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS07047-MONOMER
BRENDAi2.7.1.68 2681
ReactomeiR-HSA-1660499 Synthesis of PIPs at the plasma membrane
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
SignaLinkiQ99755
SIGNORiQ99755

Chemistry databases

SwissLipidsiSLP:000000553 [Q99755-3]
SLP:000000554

Names & Taxonomyi

Protein namesi
Recommended name:
Phosphatidylinositol 4-phosphate 5-kinase type-1 alpha (EC:2.7.1.68)
Short name:
PIP5K1-alpha
Short name:
PtdIns(4)P-5-kinase 1 alpha
Alternative name(s):
68 kDa type I phosphatidylinositol 4-phosphate 5-kinase alpha
Phosphatidylinositol 4-phosphate 5-kinase type I alpha
Short name:
PIP5KIalpha
Gene namesi
Name:PIP5K1A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000143398.19
HGNCiHGNC:8994 PIP5K1A
MIMi603275 gene
neXtProtiNX_Q99755

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi322D → N: Does not affect targeting of RAC1 to the plasma membrane; when associated with Q-440. 1 Publication1
Mutagenesisi440R → Q: Does not affect targeting of RAC1 to the plasma membrane; when associated with N-322. 1 Publication1

Organism-specific databases

DisGeNETi8394
OpenTargetsiENSG00000143398
PharmGKBiPA33327

Chemistry databases

ChEMBLiCHEMBL5969

Polymorphism and mutation databases

BioMutaiPIP5K1A
DMDMi74752158

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001854561 – 562Phosphatidylinositol 4-phosphate 5-kinase type-1 alphaAdd BLAST562

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki103Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Modified residuei486PhosphoserineCombined sources1

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ99755
MaxQBiQ99755
PaxDbiQ99755
PeptideAtlasiQ99755
PRIDEiQ99755
ProteomicsDBi78458
78459 [Q99755-2]
78460 [Q99755-3]
78461 [Q99755-4]

PTM databases

iPTMnetiQ99755
PhosphoSitePlusiQ99755
SwissPalmiQ99755

Miscellaneous databases

PMAP-CutDBiQ99755

Expressioni

Tissue specificityi

Highly expressed in heart, placenta, skeletal muscle, kidney and pancreas. Detected at lower levels in brain, lung and liver.

Gene expression databases

BgeeiENSG00000143398 Expressed in 224 organ(s), highest expression level in esophagogastric junction muscularis propria
CleanExiHS_PIP5K1A
ExpressionAtlasiQ99755 baseline and differential
GenevisibleiQ99755 HS

Organism-specific databases

HPAiHPA029366

Interactioni

Subunit structurei

Interacts with RAC1 (By similarity). Interacts with TUT1. Forms a complex with CDH1/E-cadherin, CTNNB1/beta-catenin and CTNND1 at the plasma membrane upon calcium stimulation (PubMed:18288197, PubMed:19158393). Found in a ternary complex with IRS1 and DGKZ in the absence of insulin stimulation (By similarity). Interacts with DGKZ (PubMed:15157668).By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
TUT1Q9H6E53EBI-726414,EBI-2511680

GO - Molecular functioni

Protein-protein interaction databases

BioGridi113983, 58 interactors
DIPiDIP-60649N
IntActiQ99755, 9 interactors
STRINGi9606.ENSP00000357883

Chemistry databases

BindingDBiQ99755

Structurei

3D structure databases

ProteinModelPortaliQ99755
SMRiQ99755
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini81 – 449PIPKPROSITE-ProRule annotationAdd BLAST369

Phylogenomic databases

eggNOGiKOG0229 Eukaryota
COG5253 LUCA
GeneTreeiENSGT00760000119184
HOGENOMiHOG000193876
HOVERGENiHBG052818
InParanoidiQ99755
KOiK00889
OMAiMQDIPDG
OrthoDBiEOG091G0A6L
PhylomeDBiQ99755
TreeFamiTF319618

Family and domain databases

Gene3Di3.30.800.10, 1 hit
3.30.810.10, 2 hits
InterProiView protein in InterPro
IPR023610 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
PANTHERiPTHR23086 PTHR23086, 1 hit
PfamiView protein in Pfam
PF01504 PIP5K, 1 hit
SMARTiView protein in SMART
SM00330 PIPKc, 1 hit
PROSITEiView protein in PROSITE
PS51455 PIPK, 1 hit

Sequences (4+)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q99755-1) [UniParc]FASTAAdd to basket
Also known as: PIP5KIalpha2

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.

« Hide
        10         20         30         40         50
MASASSGPSS SVGFSSFDPA VPSCTLSSAA SGIKRPMASE VLEARQDSYI
60 70 80 90 100
SLVPYASGMP IKKIGHRSVD SSGETTYKKT TSSALKGAIQ LGITHTVGSL
110 120 130 140 150
STKPERDVLM QDFYVVESIF FPSEGSNLTP AHHYNDFRFK TYAPVAFRYF
160 170 180 190 200
RELFGIRPDD YLYSLCSEPL IELCSSGASG SLFYVSSDDE FIIKTVQHKE
210 220 230 240 250
AEFLQKLLPG YYMNLNQNPR TLLPKFYGLY CVQAGGKNIR IVVMNNLLPR
260 270 280 290 300
SVKMHIKYDL KGSTYKRRAS QKEREKPLPT FKDLDFLQDI PDGLFLDADM
310 320 330 340 350
YNALCKTLQR DCLVLQSFKI MDYSLLMSIH NIDHAQREPL SSETQYSVDT
360 370 380 390 400
RRPAPQKALY STAMESIQGE ARRGGTMETD DHMGGIPARN SKGERLLLYI
410 420 430 440 450
GIIDILQSYR FVKKLEHSWK ALVHDGDTVS VHRPGFYAER FQRFMCNTVF
460 470 480 490 500
KKIPLKPSPS KKFRSGSSFS RRAGSSGNSC ITYQPSVSGE HKAQVTTKAE
510 520 530 540 550
VEPGVHLGRP DVLPQTPPLE EISEGSPIPD PSFSPLVGET LQMLTTSTTL
560
EKLEVAESEF TH
Length:562
Mass (Da):62,633
Last modified:May 1, 1997 - v1
Checksum:iA8F7988EB73506A0
GO
Isoform 2 (identifier: Q99755-2) [UniParc]FASTAAdd to basket
Also known as: PIP5KIalpha3

The sequence of this isoform differs from the canonical sequence as follows:
     30-52: ASGIKRPMASEVLEARQDSYISL → SGIKRPMASE
     455-504: LKPSPSKKFRSGSSFSRRAGSSGNSCITYQPSVSGEHKAQVTTKAEVEPG → C

Show »
Length:500
Mass (Da):56,053
Checksum:i684F0C9C2DBE9EC4
GO
Isoform 3 (identifier: Q99755-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     30-52: ASGIKRPMASEVLEARQDSYISL → SGIKRPMASE

Show »
Length:549
Mass (Da):61,187
Checksum:i7CD48BFE175564A0
GO
Isoform 4 (identifier: Q99755-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     41-52: Missing.
     382-410: HMGGIPARNSKGERLLLYIGIIDILQSYR → Q

Show »
Length:522
Mass (Da):58,119
Checksum:i693CE47DBFC72B5F
GO

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A6PW57A6PW57_HUMAN
Phosphatidylinositol 4-phosphate 5-...
PIP5K1A
550Annotation score:
A6PW58A6PW58_HUMAN
Phosphatidylinositol 4-phosphate 5-...
PIP5K1A
86Annotation score:
A2A5X0A2A5X0_HUMAN
Phosphatidylinositol 4-phosphate 5-...
PIP5K1A
101Annotation score:
A6PW56A6PW56_HUMAN
Phosphatidylinositol 4-phosphate 5-...
PIP5K1A
41Annotation score:
E9PSF8E9PSF8_HUMAN
Phosphatidylinositol 4-phosphate 5-...
PIP5K1A
39Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti257K → E in BAG58542 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_01600730 – 52ASGIK…SYISL → SGIKRPMASE in isoform 2 and isoform 3. 3 PublicationsAdd BLAST23
Alternative sequenceiVSP_04191241 – 52Missing in isoform 4. 1 PublicationAdd BLAST12
Alternative sequenceiVSP_041913382 – 410HMGGI…LQSYR → Q in isoform 4. 1 PublicationAdd BLAST29
Alternative sequenceiVSP_016008455 – 504LKPSP…EVEPG → C in isoform 2. 2 PublicationsAdd BLAST50

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U78575 mRNA Translation: AAC50910.1
U78576 mRNA Translation: AAC50911.1
U78577 mRNA Translation: AAC50912.1
AK291015 mRNA Translation: BAF83704.1
AK295691 mRNA Translation: BAG58542.1
AL592424 Genomic DNA No translation available.
CH471121 Genomic DNA Translation: EAW53461.1
BC007833 mRNA Translation: AAH07833.1
CCDSiCCDS44219.1 [Q99755-1]
CCDS44220.1 [Q99755-4]
CCDS44221.1 [Q99755-2]
CCDS990.1 [Q99755-3]
RefSeqiNP_001129108.1, NM_001135636.1 [Q99755-4]
NP_001129109.1, NM_001135637.1 [Q99755-2]
NP_001129110.1, NM_001135638.1 [Q99755-1]
NP_001317618.1, NM_001330689.1
NP_003548.1, NM_003557.2 [Q99755-3]
UniGeneiHs.655131
Hs.661888

Genome annotation databases

EnsembliENST00000349792; ENSP00000271663; ENSG00000143398 [Q99755-3]
ENST00000368888; ENSP00000357883; ENSG00000143398 [Q99755-1]
ENST00000368890; ENSP00000357885; ENSG00000143398 [Q99755-2]
ENST00000441902; ENSP00000415648; ENSG00000143398 [Q99755-4]
GeneIDi8394
KEGGihsa:8394
UCSCiuc001exi.4 human [Q99755-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U78575 mRNA Translation: AAC50910.1
U78576 mRNA Translation: AAC50911.1
U78577 mRNA Translation: AAC50912.1
AK291015 mRNA Translation: BAF83704.1
AK295691 mRNA Translation: BAG58542.1
AL592424 Genomic DNA No translation available.
CH471121 Genomic DNA Translation: EAW53461.1
BC007833 mRNA Translation: AAH07833.1
CCDSiCCDS44219.1 [Q99755-1]
CCDS44220.1 [Q99755-4]
CCDS44221.1 [Q99755-2]
CCDS990.1 [Q99755-3]
RefSeqiNP_001129108.1, NM_001135636.1 [Q99755-4]
NP_001129109.1, NM_001135637.1 [Q99755-2]
NP_001129110.1, NM_001135638.1 [Q99755-1]
NP_001317618.1, NM_001330689.1
NP_003548.1, NM_003557.2 [Q99755-3]
UniGeneiHs.655131
Hs.661888

3D structure databases

ProteinModelPortaliQ99755
SMRiQ99755
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113983, 58 interactors
DIPiDIP-60649N
IntActiQ99755, 9 interactors
STRINGi9606.ENSP00000357883

Chemistry databases

BindingDBiQ99755
ChEMBLiCHEMBL5969
SwissLipidsiSLP:000000553 [Q99755-3]
SLP:000000554

PTM databases

iPTMnetiQ99755
PhosphoSitePlusiQ99755
SwissPalmiQ99755

Polymorphism and mutation databases

BioMutaiPIP5K1A
DMDMi74752158

Proteomic databases

EPDiQ99755
MaxQBiQ99755
PaxDbiQ99755
PeptideAtlasiQ99755
PRIDEiQ99755
ProteomicsDBi78458
78459 [Q99755-2]
78460 [Q99755-3]
78461 [Q99755-4]

Protocols and materials databases

DNASUi8394
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000349792; ENSP00000271663; ENSG00000143398 [Q99755-3]
ENST00000368888; ENSP00000357883; ENSG00000143398 [Q99755-1]
ENST00000368890; ENSP00000357885; ENSG00000143398 [Q99755-2]
ENST00000441902; ENSP00000415648; ENSG00000143398 [Q99755-4]
GeneIDi8394
KEGGihsa:8394
UCSCiuc001exi.4 human [Q99755-1]

Organism-specific databases

CTDi8394
DisGeNETi8394
EuPathDBiHostDB:ENSG00000143398.19
GeneCardsiPIP5K1A
HGNCiHGNC:8994 PIP5K1A
HPAiHPA029366
MIMi603275 gene
neXtProtiNX_Q99755
OpenTargetsiENSG00000143398
PharmGKBiPA33327
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0229 Eukaryota
COG5253 LUCA
GeneTreeiENSGT00760000119184
HOGENOMiHOG000193876
HOVERGENiHBG052818
InParanoidiQ99755
KOiK00889
OMAiMQDIPDG
OrthoDBiEOG091G0A6L
PhylomeDBiQ99755
TreeFamiTF319618

Enzyme and pathway databases

BioCyciMetaCyc:HS07047-MONOMER
BRENDAi2.7.1.68 2681
ReactomeiR-HSA-1660499 Synthesis of PIPs at the plasma membrane
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
SignaLinkiQ99755
SIGNORiQ99755

Miscellaneous databases

ChiTaRSiPIP5K1A human
GeneWikiiPIP5K1A
GenomeRNAii8394
PMAP-CutDBiQ99755
PROiPR:Q99755
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000143398 Expressed in 224 organ(s), highest expression level in esophagogastric junction muscularis propria
CleanExiHS_PIP5K1A
ExpressionAtlasiQ99755 baseline and differential
GenevisibleiQ99755 HS

Family and domain databases

Gene3Di3.30.800.10, 1 hit
3.30.810.10, 2 hits
InterProiView protein in InterPro
IPR023610 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
PANTHERiPTHR23086 PTHR23086, 1 hit
PfamiView protein in Pfam
PF01504 PIP5K, 1 hit
SMARTiView protein in SMART
SM00330 PIPKc, 1 hit
PROSITEiView protein in PROSITE
PS51455 PIPK, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiPI51A_HUMAN
AccessioniPrimary (citable) accession number: Q99755
Secondary accession number(s): A8K4Q0
, B4DIN0, Q99754, Q99756
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 25, 2005
Last sequence update: May 1, 1997
Last modified: November 7, 2018
This is version 161 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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