UniProtKB - Q8TBX8 (PI42C_HUMAN)
Protein
Phosphatidylinositol 5-phosphate 4-kinase type-2 gamma
Gene
PIP4K2C
Organism
Homo sapiens (Human)
Status
Functioni
Phosphatidylinositol 5-phosphate 4-kinase with low enzymatic activity. May be a GTP sensor, has higher GTP-dependent kinase activity than ATP-dependent kinase activity. PIP4Ks negatively regulate insulin signaling through a catalytic-independent mechanism. They interact with PIP5Ks and suppress PIP5K-mediated PtdIns(4,5)P2 synthesis and insulin-dependent conversion to PtdIns(3,4,5)P3 (PubMed:31091439).2 Publications
Catalytic activityi
- a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-5-phosphate) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + ADP + H+1 PublicationEC:2.7.1.1491 PublicationThis reaction proceeds in the forward1 Publication direction.
- 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol-5-phosphate) + ATP = 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + ADP + H+1 PublicationThis reaction proceeds in the forward1 Publication direction.
- 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol-5-phosphate) + GTP = 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + GDP + H+1 PublicationThis reaction proceeds in the forward1 Publication direction.
Kineticsi
- KM=31 µM for ATP1 Publication
- KM=389 µM for GTP1 Publication
GO - Molecular functioni
- 1-phosphatidylinositol-4-phosphate 5-kinase activity Source: UniProtKB
- 1-phosphatidylinositol-5-phosphate 4-kinase activity Source: UniProtKB-EC
- ATP binding Source: UniProtKB-KW
- identical protein binding Source: IntAct
GO - Biological processi
- 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate biosynthetic process Source: UniProtKB
- negative regulation of 1-phosphatidylinositol-4-phosphate 5-kinase activity Source: UniProtKB
- negative regulation of insulin receptor signaling pathway Source: UniProtKB
- phosphatidylinositol biosynthetic process Source: Reactome
- positive regulation of autophagosome assembly Source: ParkinsonsUK-UCL
- regulation of autophagy Source: ParkinsonsUK-UCL
- regulation of phosphatidylinositol 3-kinase signaling Source: Reactome
Keywordsi
Molecular function | Kinase, Transferase |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.1.149, 2681 |
PathwayCommonsi | Q8TBX8 |
Reactomei | R-HSA-1660499, Synthesis of PIPs at the plasma membrane R-HSA-6811555, PI5P Regulates TP53 Acetylation R-HSA-6811558, PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling R-HSA-8847453, Synthesis of PIPs in the nucleus |
Names & Taxonomyi
Protein namesi | Recommended name: Phosphatidylinositol 5-phosphate 4-kinase type-2 gammaCurated (EC:2.7.1.1491 Publication)Alternative name(s): Phosphatidylinositol 5-phosphate 4-kinase type II gamma Short name: PI(5)P 4-kinase type II gamma Short name: PIP4KII-gamma |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:23786, PIP4K2C |
neXtProti | NX_Q8TBX8 |
VEuPathDBi | HostDB:ENSG00000166908.17 |
Subcellular locationi
Endoplasmic reticulum
- Endoplasmic reticulum By similarity
Cytoplasm and Cytosol
- Cytoplasm By similarity
Cytosol
- cytosol Source: HPA
Endoplasmic reticulum
- endoplasmic reticulum Source: UniProtKB-SubCell
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
Nucleus
- nucleoplasm Source: HPA
Plasma Membrane
- plasma membrane Source: HPA
Other locations
- autophagosome Source: ParkinsonsUK-UCL
- intracellular organelle Source: FlyBase
Keywords - Cellular componenti
Cytoplasm, Endoplasmic reticulumPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 69 – 75 | VMLLPDD → EIFLPNN: Loss of interaction with PIP5K1A. Loss of inhibition of PIP5K1A activity. 1 Publication | 7 |
Organism-specific databases
DisGeNETi | 79837 |
OpenTargetsi | ENSG00000166908 |
PharmGKBi | PA162399665 |
Miscellaneous databases
Pharosi | Q8TBX8, Tchem |
Chemistry databases
ChEMBLi | CHEMBL1770034 |
DrugBanki | DB12010, Fostamatinib |
DrugCentrali | Q8TBX8 |
Genetic variation databases
BioMutai | PIP4K2C |
DMDMi | 317373532 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedCombined sources | |||
ChainiPRO_0000285750 | 2 – 421 | Phosphatidylinositol 5-phosphate 4-kinase type-2 gammaAdd BLAST | 420 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylalanineCombined sources | 1 | |
Modified residuei | 26 | PhosphoserineCombined sources | 1 | |
Modified residuei | 349 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Phosphorylated, phosphorylation is induced by EGF.By similarity
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
EPDi | Q8TBX8 |
jPOSTi | Q8TBX8 |
MassIVEi | Q8TBX8 |
MaxQBi | Q8TBX8 |
PaxDbi | Q8TBX8 |
PeptideAtlasi | Q8TBX8 |
PRIDEi | Q8TBX8 |
ProteomicsDBi | 74044 [Q8TBX8-1] 74045 [Q8TBX8-2] 74046 [Q8TBX8-3] |
PTM databases
iPTMneti | Q8TBX8 |
PhosphoSitePlusi | Q8TBX8 |
Expressioni
Gene expression databases
Bgeei | ENSG00000166908, Expressed in vagina and 241 other tissues |
ExpressionAtlasi | Q8TBX8, baseline and differential |
Genevisiblei | Q8TBX8, HS |
Organism-specific databases
HPAi | ENSG00000166908, Low tissue specificity |
Interactioni
Subunit structurei
Interacts with PIP5K1A; the interaction inhibits PIP5K1A kinase activity.
1 PublicationBinary interactionsi
Q8TBX8
With | #Exp. | IntAct |
---|---|---|
itself | 2 | EBI-1383637,EBI-1383637 |
GO - Molecular functioni
- identical protein binding Source: IntAct
Protein-protein interaction databases
BioGRIDi | 122928, 55 interactors |
IntActi | Q8TBX8, 25 interactors |
STRINGi | 9606.ENSP00000347032 |
Chemistry databases
BindingDBi | Q8TBX8 |
Miscellaneous databases
RNActi | Q8TBX8, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q8TBX8 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q8TBX8 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 43 – 420 | PIPKPROSITE-ProRule annotationAdd BLAST | 378 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 69 – 75 | Required for interaction with PIP5K1A1 Publication | 7 |
Phylogenomic databases
eggNOGi | KOG0229, Eukaryota |
GeneTreei | ENSGT00940000156890 |
HOGENOMi | CLU_004312_7_0_1 |
InParanoidi | Q8TBX8 |
OMAi | SEWDGDC |
OrthoDBi | 1562683at2759 |
PhylomeDBi | Q8TBX8 |
TreeFami | TF354315 |
Family and domain databases
Gene3Di | 3.30.800.10, 1 hit 3.30.810.10, 2 hits |
InterProi | View 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 |
PANTHERi | PTHR23086, PTHR23086, 1 hit |
Pfami | View protein in Pfam PF01504, PIP5K, 1 hit |
SMARTi | View protein in SMART SM00330, PIPKc, 1 hit |
PROSITEi | View protein in PROSITE PS51455, PIPK, 1 hit |
s (3+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q8TBX8-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MASSSVPPAT VSAATAGPGP GFGFASKTKK KHFVQQKVKV FRAADPLVGV
60 70 80 90 100
FLWGVAHSIN ELSQVPPPVM LLPDDFKASS KIKVNNHLFH RENLPSHFKF
110 120 130 140 150
KEYCPQVFRN LRDRFGIDDQ DYLVSLTRNP PSESEGSDGR FLISYDRTLV
160 170 180 190 200
IKEVSSEDIA DMHSNLSNYH QYIVKCHGNT LLPQFLGMYR VSVDNEDSYM
210 220 230 240 250
LVMRNMFSHR LPVHRKYDLK GSLVSREASD KEKVKELPTL KDMDFLNKNQ
260 270 280 290 300
KVYIGEEEKK IFLEKLKRDV EFLVQLKIMD YSLLLGIHDI IRGSEPEEEA
310 320 330 340 350
PVREDESEVD GDCSLTGPPA LVGSYGTSPE GIGGYIHSHR PLGPGEFESF
360 370 380 390 400
IDVYAIRSAE GAPQKEVYFM GLIDILTQYD AKKKAAHAAK TVKHGAGAEI
410 420
STVHPEQYAK RFLDFITNIF A
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketH0YIJ6 | H0YIJ6_HUMAN | Phosphatidylinositol 5-phosphate 4-... | PIP4K2C | 134 | Annotation score: | ||
F8VNT5 | F8VNT5_HUMAN | Phosphatidylinositol 5-phosphate 4-... | PIP4K2C | 160 | Annotation score: | ||
F8VU68 | F8VU68_HUMAN | Phosphatidylinositol 5-phosphate 4-... | PIP4K2C | 171 | Annotation score: | ||
F8VVB2 | F8VVB2_HUMAN | Phosphatidylinositol 5-phosphate 4-... | PIP4K2C | 50 | Annotation score: |
Sequence cautioni
The sequence BAB15223 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_032049 | 84 | V → A. Corresponds to variant dbSNP:rs17550713Ensembl. | 1 | |
Natural variantiVAR_032050 | 241 | K → R1 PublicationCorresponds to variant dbSNP:rs17852569Ensembl. | 1 | |
Natural variantiVAR_032051 | 300 | A → G. Corresponds to variant dbSNP:rs2277319Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_043369 | 83 – 100 | Missing in isoform 3. 1 PublicationAdd BLAST | 18 | |
Alternative sequenceiVSP_042929 | 124 – 171 | Missing in isoform 2. 1 PublicationAdd BLAST | 48 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK025708 mRNA Translation: BAB15223.1 Different initiation. AK297243 mRNA Translation: BAG59723.1 AK302254 mRNA Translation: BAG63606.1 AK315588 mRNA Translation: BAG37960.1 AC022506 Genomic DNA No translation available. CH471054 Genomic DNA Translation: EAW97031.1 BC028596 mRNA Translation: AAH28596.1 |
CCDSi | CCDS53808.1 [Q8TBX8-2] CCDS55839.1 [Q8TBX8-3] CCDS8946.1 [Q8TBX8-1] |
RefSeqi | NP_001139730.1, NM_001146258.1 [Q8TBX8-1] NP_001139731.1, NM_001146259.1 [Q8TBX8-3] NP_001139732.1, NM_001146260.1 [Q8TBX8-2] NP_079055.3, NM_024779.4 [Q8TBX8-1] |
Genome annotation databases
Ensembli | ENST00000354947; ENSP00000347032; ENSG00000166908 [Q8TBX8-1] ENST00000422156; ENSP00000412035; ENSG00000166908 [Q8TBX8-2] ENST00000540759; ENSP00000439878; ENSG00000166908 [Q8TBX8-1] ENST00000550465; ENSP00000447390; ENSG00000166908 [Q8TBX8-3] |
GeneIDi | 79837 |
KEGGi | hsa:79837 |
UCSCi | uc001sot.4, human [Q8TBX8-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK025708 mRNA Translation: BAB15223.1 Different initiation. AK297243 mRNA Translation: BAG59723.1 AK302254 mRNA Translation: BAG63606.1 AK315588 mRNA Translation: BAG37960.1 AC022506 Genomic DNA No translation available. CH471054 Genomic DNA Translation: EAW97031.1 BC028596 mRNA Translation: AAH28596.1 |
CCDSi | CCDS53808.1 [Q8TBX8-2] CCDS55839.1 [Q8TBX8-3] CCDS8946.1 [Q8TBX8-1] |
RefSeqi | NP_001139730.1, NM_001146258.1 [Q8TBX8-1] NP_001139731.1, NM_001146259.1 [Q8TBX8-3] NP_001139732.1, NM_001146260.1 [Q8TBX8-2] NP_079055.3, NM_024779.4 [Q8TBX8-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2GK9 | X-ray | 2.80 | A/B/C/D | 32-421 | [»] | |
SMRi | Q8TBX8 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 122928, 55 interactors |
IntActi | Q8TBX8, 25 interactors |
STRINGi | 9606.ENSP00000347032 |
Chemistry databases
BindingDBi | Q8TBX8 |
ChEMBLi | CHEMBL1770034 |
DrugBanki | DB12010, Fostamatinib |
DrugCentrali | Q8TBX8 |
PTM databases
iPTMneti | Q8TBX8 |
PhosphoSitePlusi | Q8TBX8 |
Genetic variation databases
BioMutai | PIP4K2C |
DMDMi | 317373532 |
Proteomic databases
EPDi | Q8TBX8 |
jPOSTi | Q8TBX8 |
MassIVEi | Q8TBX8 |
MaxQBi | Q8TBX8 |
PaxDbi | Q8TBX8 |
PeptideAtlasi | Q8TBX8 |
PRIDEi | Q8TBX8 |
ProteomicsDBi | 74044 [Q8TBX8-1] 74045 [Q8TBX8-2] 74046 [Q8TBX8-3] |
Protocols and materials databases
Antibodypediai | 28802, 106 antibodies |
DNASUi | 79837 |
Genome annotation databases
Ensembli | ENST00000354947; ENSP00000347032; ENSG00000166908 [Q8TBX8-1] ENST00000422156; ENSP00000412035; ENSG00000166908 [Q8TBX8-2] ENST00000540759; ENSP00000439878; ENSG00000166908 [Q8TBX8-1] ENST00000550465; ENSP00000447390; ENSG00000166908 [Q8TBX8-3] |
GeneIDi | 79837 |
KEGGi | hsa:79837 |
UCSCi | uc001sot.4, human [Q8TBX8-1] |
Organism-specific databases
CTDi | 79837 |
DisGeNETi | 79837 |
GeneCardsi | PIP4K2C |
HGNCi | HGNC:23786, PIP4K2C |
HPAi | ENSG00000166908, Low tissue specificity |
neXtProti | NX_Q8TBX8 |
OpenTargetsi | ENSG00000166908 |
PharmGKBi | PA162399665 |
VEuPathDBi | HostDB:ENSG00000166908.17 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0229, Eukaryota |
GeneTreei | ENSGT00940000156890 |
HOGENOMi | CLU_004312_7_0_1 |
InParanoidi | Q8TBX8 |
OMAi | SEWDGDC |
OrthoDBi | 1562683at2759 |
PhylomeDBi | Q8TBX8 |
TreeFami | TF354315 |
Enzyme and pathway databases
BRENDAi | 2.7.1.149, 2681 |
PathwayCommonsi | Q8TBX8 |
Reactomei | R-HSA-1660499, Synthesis of PIPs at the plasma membrane R-HSA-6811555, PI5P Regulates TP53 Acetylation R-HSA-6811558, PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling R-HSA-8847453, Synthesis of PIPs in the nucleus |
Miscellaneous databases
BioGRID-ORCSi | 79837, 13 hits in 997 CRISPR screens |
ChiTaRSi | PIP4K2C, human |
EvolutionaryTracei | Q8TBX8 |
GenomeRNAii | 79837 |
Pharosi | Q8TBX8, Tchem |
PROi | PR:Q8TBX8 |
RNActi | Q8TBX8, protein |
Gene expression databases
Bgeei | ENSG00000166908, Expressed in vagina and 241 other tissues |
ExpressionAtlasi | Q8TBX8, baseline and differential |
Genevisiblei | Q8TBX8, HS |
Family and domain databases
Gene3Di | 3.30.800.10, 1 hit 3.30.810.10, 2 hits |
InterProi | View 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 |
PANTHERi | PTHR23086, PTHR23086, 1 hit |
Pfami | View protein in Pfam PF01504, PIP5K, 1 hit |
SMARTi | View protein in SMART SM00330, PIPKc, 1 hit |
PROSITEi | View protein in PROSITE PS51455, PIPK, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | PI42C_HUMAN | |
Accessioni | Q8TBX8Primary (citable) accession number: Q8TBX8 Secondary accession number(s): B2RDL3 Q9H6N2 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 1, 2007 |
Last sequence update: | January 11, 2011 | |
Last modified: | April 7, 2021 | |
This is version 154 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 12
Human chromosome 12: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - PDB cross-references
Index of Protein Data Bank (PDB) cross-references