PIK3C2A phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha [Homo sapiens (human)] - Gene

Summary

Official Symbol: PIK3C2Aprovided by HGNC
Official Full Name: phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alphaprovided by HGNC
Primary source: HGNC:HGNC:8971
See related: Ensembl:ENSG00000011405 MIM:603601; AllianceGenome:HGNC:8971
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CPK; OCSKD; PI3-K-C2A; PI3K-C2alpha; PI3K-C2-alpha; PI3-K-C2(ALPHA)
Summary: The protein encoded by this gene belongs to the phosphoinositide 3-kinase (PI3K) family. PI3-kinases play roles in signaling pathways involved in cell proliferation, oncogenic transformation, cell survival, cell migration, and intracellular protein trafficking. This protein contains a lipid kinase catalytic domain as well as a C-terminal C2 domain, a characteristic of class II PI3-kinases. C2 domains act as calcium-dependent phospholipid binding motifs that mediate translocation of proteins to membranes, and may also mediate protein-protein interactions. The PI3-kinase activity of this protein is not sensitive to nanomolar levels of the inhibitor wortmanin. This protein was shown to be able to be activated by insulin and may be involved in integrin-dependent signaling. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in thyroid (RPKM 18.0), testis (RPKM 13.1) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 11p15.1

Exon count:: 35

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (17086575..17207986, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (17184463..17305651, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (17108122..17229533, complement)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Various Expressions of PIK3C2A and TXNIP Genes and Their Potential Role as Independent Risk Factors for Chronic Stable Angina and Acute Coronary Syndrome.
Title: Various Expressions of PIK3C2A and TXNIP Genes and Their Potential Role as Independent Risk Factors for Chronic Stable Angina and Acute Coronary Syndrome.
The molecular mechanisms mediating class II PI 3-kinase function in cell physiology.
Title: The molecular mechanisms mediating class II PI 3-kinase function in cell physiology.
PI(3,4)P2-mediated cytokinetic abscission prevents early senescence and cataract formation.
Title: PI(3,4)P2-mediated cytokinetic abscission prevents early senescence and cataract formation.
Class II phosphatidylinositol 3-kinase-C2alpha is essential for Notch signaling by regulating the endocytosis of gamma-secretase in endothelial cells.
Title: Class II phosphatidylinositol 3-kinase-C2α is essential for Notch signaling by regulating the endocytosis of γ-secretase in endothelial cells.
TGFbeta receptor endocytosis and Smad signaling require synaptojanin1, PI3K-C2alpha-, and INPP4B-mediated phosphoinositide conversions.
Title: TGFβ receptor endocytosis and Smad signaling require synaptojanin1, PI3K-C2α-, and INPP4B-mediated phosphoinositide conversions.
MiR-31 suppressed cell proliferation, migration, and invasion of osteosarcoma by targeting PIK3C2A expression.
Title: MicroRNA-31 inhibits osteosarcoma cell proliferation, migration and invasion by targeting PIK3C2A.
the identification of the first patients with PIK3C2A deficiency establishes a role for PIK3C2A in neurological and skeletal development, as well as vision, and growth and implicates loss-of-function PIK3C2A mutations as a potentially new cause of a cilia-associated disease.
Title: Mutations in PIK3C2A cause syndromic short stature, skeletal abnormalities, and cataracts associated with ciliary dysfunction.
Study illustrates that the C-terminal PX-C2 module of PI3K-C2a plays an important role in membrane anchoring, with the C2 domain providing the primary site of membrane affinity, and suggests a possible role for Ca2+ in regulating PI3K-C2a activity through perturbation of C2 domain membrane interaction.
Title: Molecular Basis for Membrane Recruitment by the PX and C2 Domains of Class II Phosphoinositide 3-Kinase-C2α.
PI3K-C2alpha and PI3K-C2beta play differential, indispensable roles in clathrin-mediated pinocytosis.
Title: The class II phosphoinositide 3-kinases PI3K-C2α and PI3K-C2β differentially regulate clathrin-dependent pinocytosis in human vascular endothelial cells.
The level of PIK3C2A gene expression in patients with acute myocardial infarction is significantly lower than that of healthy people.
Title: Low expression of PIK3C2A gene: A potential biomarker to predict the risk of acute myocardial infarction.

Submit: New GeneRIF Correction See all GeneRIFs (38)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Oculocerebrodental syndrome MedGen: C5193101 OMIM: 618440 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Genome-wide association study identifies five new schizophrenia loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Polygenic dissection of diagnosis and clinical dimensions of bipolar disorder and schizophrenia. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120 upregulates the expression of IL-6 and IL-8 via the p38 signaling pathway and the PI3K/Akt signaling pathway in astrocytes	PubMed
	env	HIV-1 gp120-induced PI3-kinase activity and calcium mobilization are inhibited by pertussis toxin and blocking antibodies directed against CCR5 and CXCR4, suggesting that this signaling is mediated through these chemokine receptors	PubMed
	env	CD45 modulates HIV-1 gp120-induced apoptosis by regulating Fas ligand induction and activation of the phosphoinositide 3-kinase/Akt pathway	PubMed
	env	HIV-1 gp120-induced TNF-alpha production by primary human macrophages is mediated by phosphatidylinositol-3 (PI-3) kinase and mitogen-activated protein (MAP) kinase pathways	PubMed
	env	CCR5 activation by gp120 triggers the assembly of endogenous Lyn, PI3K, and Pyk2 and is associated with PI3K and Pyk2 translocation from the cytoplasm to the membrane where they colocalized with Lyn	PubMed
	env	Concomitant activation of Lyn, Pyk2, and class IA PI3K are required for gp120-induced IL-1beta production	PubMed
	env	Insulin-like growth factor-I (IGF-I) and erythropoietin treatment protect against HIV/gp120-mediated neuronal damage in culture and in vivo, in part, through cooperative activation of phosphatidylinositol 3-kinase/Akt/GSK-3beta signaling	PubMed
	env	Pre-treatment of endothelial cells with fibroblast growth factor 2 (FGF2) protects cells from HIV-1 gp120 angiotoxicity; this protection is regulated by crosstalk among the ERK, PI3K-AKT and PKC signaling pathways	PubMed
Envelope surface glycoprotein gp160, precursor	env	HIV-1 gp160 disrupts the association between phospholipase C gamma-1 and phosphoinositide 3 kinase (PI3-kinase), and this effect is dependent on PI3-kinase activity	PubMed
	env	PI3-kinase activation induced by HIV-1 gp160 leads to downregulation of LFA-1-mediated T cell adhesion to B cells	PubMed
Nef	nef	Downregulation of cell surface major histocompatibility complex class I (MHC-I) protein expression by HIV-1 Nef depends on a phosphoinositide 3-kinase (PI3K)-regulated signaling pathway, suggesting an interaction between Nef and PI3K	PubMed
	nef	In the context of Nef-associated kinase complex (NAKC), hnRNP-K interacts with HIV-1 Nef and recruits LCK, PKCdelta, and PI-3 kinase	PubMed
	nef	The presence of HIV-1 Nef in Jurkat cells stimulated with a combination of PMA and anti-CD28 upregulates the levels of PI3K production	PubMed
	nef	The association of phosphatidylinositol (PI) 3-kinase with platelet-derived growth factor (PDGF) activated receptor was downregulated by HIV-1 nef expression	PubMed
Tat	tat	HIV-1 Tat induces phosphorylation of PI3K, AKT, PTEN, and GSK-3beta activating PI3K and AKT and inactivating PTEN and GSK-3beta in vIL-6 expressing cells	PubMed
	tat	HIV-1 Tat-induced upregulation of IDO production requires the activity of IFN-gamma signaling pathway such as JAK and PI3K in human monocyte derived-dendritic cells	PubMed
	tat	Pro-survival effects of intracellular HIV-1 Tat in a microglial cell line is attributed to activation of the PI-3-kinase (PI3K)/Akt pathway via decreasing expression of PTEN, a negative regulator of the PI-3-K pathway	PubMed
	tat	Phosphatidylinositol 3-kinase/Akt signaling pathway is involved in HIV-1 Tat-induced NADPH oxidase stimulation and LTR transactivation	PubMed
	tat	HIV-1 Tat in combination with KSHV kaposin A activates the MEK/ERK, STAT3, and PI3K/Akt signals in NIH3T3 cells	PubMed
	tat	HIV-1 Tat activates phosphatidylinositol 3-kinase (PI3K), leading to the activation of Akt/PKB, decreased levels of cAMP and CREB phosphorylation, and the protection of cells from apoptosis	PubMed
	tat	Phosphatidylinositol 3-kinase inhibits HIV-1 Tat-mediated transactivation of the HIV-1 LTR promoter by affecting the formation of the Tat-associated kinase transactivating complex	PubMed
	tat	HIV-1 Tat induced release of MCP-1 from human lung microvascular endothelial cells involves an interaction between Tat and PI3 kinase	PubMed
	tat	Activation of protein kinase C-epsilon by HIV-1 Tat involves an interaction with PI 3-kinase	PubMed
	tat	HIV-1 Tat-mediated cytopathic changes in human brain micro vascular endothelial cells involves its interaction with phosphatidylinositol 3-kinase (PI3K)	PubMed
reverse transcriptase	gag-pol	HIV-1 RT heterodimer expressed in bacteria can be phosphorylated in vitro by several purified mammalian protein kinases including auto-activated protein kinase (PK), CKII, cytosolic protamine kinase (CPK), myelin basic protein kinase 1 (MBPK1), and PRKC	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-112334 (e-PCR)
- UniSTS:168539

D11S4711 (e-PCR)
- UniSTS:42396

RH79759 (e-PCR)
- UniSTS:85974

D11S4677 (e-PCR)
- UniSTS:67035

RH102150 (e-PCR)
- UniSTS:96484

RH102427 (e-PCR)
- UniSTS:96761

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables 1-phosphatidylinositol-3-kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables 1-phosphatidylinositol-3-kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables 1-phosphatidylinositol-3-kinase activity	TAS Traceable Author Statement more info	PubMed
enables 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables 1-phosphatidylinositol-4-phosphate 3-kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables 1-phosphatidylinositol-4-phosphate 3-kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables 1-phosphatidylinositol-4-phosphate 3-kinase activity	TAS Traceable Author Statement more info
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables clathrin binding	IDA Inferred from Direct Assay more info	PubMed
enables phosphatidylinositol binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in cell migration	IBA Inferred from Biological aspect of Ancestor more info
involved_in clathrin coat assembly	TAS Traceable Author Statement more info	PubMed
involved_in endocytosis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in epidermal growth factor receptor signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in exocytosis	TAS Traceable Author Statement more info	PubMed
involved_in insulin receptor signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in membrane organization	TAS Traceable Author Statement more info
involved_in phosphatidylinositol 3-kinase/protein kinase B signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in phosphatidylinositol biosynthetic process	TAS Traceable Author Statement more info	PubMed
involved_in phosphatidylinositol-3-phosphate biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in phosphatidylinositol-mediated signaling	IBA Inferred from Biological aspect of Ancestor more info
involved_in phosphorylation	IEA Inferred from Electronic Annotation more info
involved_in platelet-derived growth factor receptor signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of autophagy	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cell migration involved in sprouting angiogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in vascular associated smooth muscle contraction	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in clathrin-coated vesicle	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
located_in membrane	HDA more info	PubMed
located_in nucleoplasm	IDA Inferred from Direct Assay more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in trans-Golgi network	IDA Inferred from Direct Assay more info	PubMed
located_in vesicle	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha

Names: C2-containing phosphatidylinositol kinase; phosphatidylinositol-4-phosphate 3-kinase C2 domain-containing subunit alpha; phosphoinositide 3-kinase-C2-alpha; phosphoinositide-3-kinase, class 2, alpha polypeptide; ptdIns-3-kinase C2 subunit alpha

NP_001308307.1

EC 2.7.1.137

EC 2.7.1.153

EC 2.7.1.154

NP_001308309.1

EC 2.7.1.137

EC 2.7.1.153

EC 2.7.1.154

NP_001373799.1

EC 2.7.1.137

EC 2.7.1.153

EC 2.7.1.154

NP_002636.2

EC 2.7.1.137

EC 2.7.1.153

EC 2.7.1.154

XP_047283083.1

EC 2.7.1.137

EC 2.7.1.153

EC 2.7.1.154

XP_047283084.1

EC 2.7.1.137

EC 2.7.1.153

EC 2.7.1.154

XP_054225106.1

EC 2.7.1.137

EC 2.7.1.153

EC 2.7.1.154

XP_054225107.1

EC 2.7.1.137

EC 2.7.1.153

EC 2.7.1.154

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001321378.2 → NP_001308307.1 phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha isoform 1

Status: VALIDATED

Source sequence(s)

AC107956, AC116533, AC126389

Consensus CDS

CCDS7824.1

UniProtKB/Swiss-Prot

B0LPH2, B4E2G4, O00443, Q14CQ9

UniProtKB/TrEMBL

L7RRS0

Conserved Domains (6) summary

cd07289
Location:1426 → 1534

PX_PI3K_C2_alpha; The phosphoinositide binding Phox Homology Domain of the Alpha Isoform of Class II Phosphoinositide 3-Kinases

cd04012
Location:677 → 849

C2A_PI3K_class_II; C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks)

cd08381
Location:1560 → 1681

C2B_PI3K_class_II; C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks)

cd00869
Location:870 → 1038

PI3Ka_II; Phosphoinositide 3-kinase (PI3K) class II, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation. In general, class II PI3-kinases ...

cd05176
Location:1043 → 1395

PI3Kc_C2_alpha; Catalytic domain of Class II Phosphoinositide 3-kinase alpha

pfam00794
Location:409 → 512

PI3K_rbd; PI3-kinase family, ras-binding domain
NM_001321380.2 → NP_001308309.1 phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha isoform 2

Status: VALIDATED

Source sequence(s)

AC126389, AK294416, AL049998, AL832699, BG548448, BX642731, BX648778

UniProtKB/TrEMBL

B4DG55

Conserved Domains (6) summary

cd07289
Location:1046 → 1154

PX_PI3K_C2_alpha; The phosphoinositide binding Phox Homology Domain of the Alpha Isoform of Class II Phosphoinositide 3-Kinases

cd04012
Location:297 → 469

C2A_PI3K_class_II; C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks)

cd08381
Location:1180 → 1301

C2B_PI3K_class_II; C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks)

cd00869
Location:490 → 658

PI3Ka_II; Phosphoinositide 3-kinase (PI3K) class II, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation. In general, class II PI3-kinases ...

cd05176
Location:663 → 1015

PI3Kc_C2_alpha; Catalytic domain of Class II Phosphoinositide 3-kinase alpha

pfam00794
Location:29 → 132

PI3K_rbd; PI3-kinase family, ras-binding domain
NM_001386870.1 → NP_001373799.1 phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha isoform 3

Status: VALIDATED

Source sequence(s)

AC107956, AC116533, AC126389

Conserved Domains (6) summary

cd07289
Location:1370 → 1478

PX_PI3K_C2_alpha; The phosphoinositide binding Phox Homology Domain of the Alpha Isoform of Class II Phosphoinositide 3-Kinases

cd04012
Location:677 → 793

C2A_PI3K_class_II; C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks)

cd08381
Location:1504 → 1625

C2B_PI3K_class_II; C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks)

cd00869
Location:814 → 982

PI3Ka_II; Phosphoinositide 3-kinase (PI3K) class II, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation. In general, class II PI3-kinases ...

cd05176
Location:987 → 1339

PI3Kc_C2_alpha; Catalytic domain of Class II Phosphoinositide 3-kinase alpha

pfam00794
Location:409 → 512

PI3K_rbd; PI3-kinase family, ras-binding domain
NM_002645.4 → NP_002636.2 phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha isoform 1

See identical proteins and their annotated locations for NP_002636.2

Status: VALIDATED

Source sequence(s)

AC116533, AL049998, BC040952, BC113658, BX642731

Consensus CDS

CCDS7824.1

UniProtKB/Swiss-Prot

B0LPH2, B4E2G4, O00443, Q14CQ9

UniProtKB/TrEMBL

L7RRS0

Related

ENSP00000509400.1, ENST00000691414.1

Conserved Domains (6) summary

cd07289
Location:1426 → 1534

PX_PI3K_C2_alpha; The phosphoinositide binding Phox Homology Domain of the Alpha Isoform of Class II Phosphoinositide 3-Kinases

cd04012
Location:677 → 849

C2A_PI3K_class_II; C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks)

cd08381
Location:1560 → 1681

C2B_PI3K_class_II; C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks)

cd00869
Location:870 → 1038

PI3Ka_II; Phosphoinositide 3-kinase (PI3K) class II, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation. In general, class II PI3-kinases ...

cd05176
Location:1043 → 1395

PI3Kc_C2_alpha; Catalytic domain of Class II Phosphoinositide 3-kinase alpha

pfam00794
Location:409 → 512

PI3K_rbd; PI3-kinase family, ras-binding domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000011.10 Reference GRCh38.p14 Primary Assembly

Range

17086575..17207986 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047427128.1 → XP_047283084.1 phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha isoform X2
XM_047427127.1 → XP_047283083.1 phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha isoform X1

UniProtKB/Swiss-Prot

B0LPH2, B4E2G4, O00443, Q14CQ9

UniProtKB/TrEMBL

L7RRS0

Alternate T2T-CHM13v2.0

Genomic

NC_060935.1 Alternate T2T-CHM13v2.0

Range

17184463..17305651 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054369132.1 → XP_054225107.1 phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha isoform X2
XM_054369131.1 → XP_054225106.1 phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha isoform X1

UniProtKB/Swiss-Prot

B0LPH2, B4E2G4, O00443, Q14CQ9

UniProtKB/TrEMBL

L7RRS0