Reactome | UniProt:O00459 PIK3R2

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UniProt:O00459 PIK3R2 Show undefined attributes

chain	chain:1-728
checksum	ADAC3E4B61F3F44A
comment	FUNCTION Regulatory subunit of phosphoinositide-3-kinase (PI3K), a kinase that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Binds to activated (phosphorylated) protein-tyrosine kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Indirectly regulates autophagy (PubMed:23604317). Promotes nuclear translocation of XBP1 isoform 2 in a ER stress- and/or insulin-dependent manner during metabolic overloading in the liver and hence plays a role in glucose tolerance improvement (By similarity).SUBUNIT Heterodimer of a regulatory subunit PIK3R2 and a p110 catalytic subunit (PIK3CA, PIK3CB or PIK3CD) (PubMed:23604317). Interacts with AXL (PubMed:9178760). Interacts with FLT1 (tyrosine-phosphorylated) and FLT4 (tyrosine-phosphorylated) (PubMed:15102829, PubMed:9600074). Interacts with NYAP1, NYAP2 and MYO16 (By similarity). Interacts with FBXL2; PIK3R2 is a substrate of the SCF(FBXL2) complex (PubMed:23604317). Interacts with PTPN13; dephosphorylates PIK3R2 (PubMed:23604317). Interacts with XBP1 isoform 2; the interaction is direct and induces translocation of XBP1 isoform 2 into the nucleus in a ER stress- and/or insulin-dependent but PI3K-independent manner (By similarity). Interacts with PIK3R1; the interaction is dissociated in an insulin-dependent manner (By similarity). Interacts with SRC (PubMed:28903391).INTERACTION The SH2 2 domain is required for interaction with FBXL2 and PTPN13.PTM Phosphorylated in response to signaling from activated receptor-type protein kinases (PubMed:19690332, PubMed:20068231). Dephosphorylated by PTPRJ (PubMed:18348712). Dephosphorylated at Tyr-655 by PTPN13. Phosphorylation of Tyr-655 impairs while its dephosphorylation promotes interaction with FBXL2 and SCF(FBXL2)-mediated polyubiquitination (PubMed:23604317).PTM Ubiquitinated. Polyubiquitination by the SCF(FBXL2) complex probably promotes proteasomal degradation of PIK3R2.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the PI3K p85 subunit family.
crossReference	[DatabaseIdentifier:12205410] PDB:7RNU [DatabaseIdentifier:12424613] RefSeq:NP_005018.2 [DatabaseIdentifier:12289105] Pharos - Targets:O00459 [DatabaseIdentifier:12250573] PRO:O00459 [DatabaseIdentifier:12207343] PDB:6U28 [DatabaseIdentifier:11498156] ENSEMBL:ENSG00000105647 [DatabaseIdentifier:11607326] ENSEMBL:ENSP00000222254 [DatabaseIdentifier:11730025] ENSEMBL:ENST00000222254 [DatabaseIdentifier:11779460] Guide to Pharmacology - Targets:2504 [DatabaseIdentifier:11791266] GeneCards:PIK3R2 [DatabaseIdentifier:11832699] HMDB Protein:HMDBP03980 [DatabaseIdentifier:11844268] HPA:ENSG00000105647-PIK3R2 [DatabaseIdentifier:12128893] OpenTargets:ENSG00000105647 [DatabaseIdentifier:12137090] Orphanet:PIK3R2 [DatabaseIdentifier:12207341] PDB:3O5Z [DatabaseIdentifier:12207342] PDB:7RCH [DatabaseIdentifier:12207338] PDB:2XS6 [DatabaseIdentifier:12207337] PDB:2KT1 [DatabaseIdentifier:12207339] PDB:6OX7 [DatabaseIdentifier:12207340] PDB:3MTT
databaseName	UniProt
dbId	61194
description	recommendedName: Phosphatidylinositol 3-kinase regulatory subunit beta shortName: PI3-kinase regulatory subunit beta shortName: PI3K regulatory subunit beta shortName: PtdIns-3-kinase regulatory subunit beta alternativeName: Phosphatidylinositol 3-kinase 85 kDa regulatory subunit beta shortName: PI3-kinase subunit p85-beta shortName: PtdIns-3-kinase regulatory subunit p85-beta
displayName	UniProt:O00459 PIK3R2
geneName	PIK3R2
identifier	O00459
isSequenceChanged	false
keyword	3D-structure Disease variant GTPase activation Phosphoprotein Protein transport Proteomics identification Reference proteome Repeat SH2 domain SH3 domain Stress response Transport Ubl conjugation
modified	[InstanceEdit:9963647] Weiser, Joel, 2025-08-15
moleculeType	Protein
name	PIK3R2
otherIdentifier	11744004_at 1568629_PM_s_at 1568629_s_at 16859740 207105_PM_s_at 207105_s_at 2826532 33223_at 34197_at 3824839 3824840 3824841 3824842 3824843 3824844 3824846 3824847 3824848 3824850 3824851 3824852 3824853 3824854 3824855 3824856 3824857 3824858 3824859 3824860 3824861 3824862 3824864 3824865 3824866 3824867 3824868 3824869 3824870 3824871 3824872 3824873 388_at 5296 8026954 A_14_P103501 A_14_P127707 A_14_P133175 A_23_P142361 A_33_P3367855 GE53279 GE61807 GE880167 GO:0001678 GO:0001784 GO:0002376 GO:0005096 GO:0005515 GO:0005634 GO:0005829 GO:0005925 GO:0005943 GO:0006355 GO:0006955 GO:0007165 GO:0008286 GO:0010506 GO:0015031 GO:0019903 GO:0030154 GO:0030183 GO:0030217 GO:0030833 GO:0030971 GO:0032869 GO:0034976 GO:0036312 GO:0042307 GO:0043409 GO:0043491 GO:0045785 GO:0045944 GO:0046935 GO:0046982 GO:0051492 GO:0098772 GO:1903076 HMNXSV003008493 HMNXSV003049156 Hs2.390523.1.S1_3p_s_at ILMN_1726565 PH_hs_0012270 PH_hs_0041093 TC19002628.hg X80907_at g4826907_3p_a_at
physicalEntity	[EntityWithAccessionedSequence:R-HSA-74791] PIK3R2 [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-3080554] K63polyUb-PIK3R2 [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9860512] p-Y464-PIK3R2 [cytosol] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:ensembl:ENSG00000105647] ENSEMBL:ENSG00000105647 PIK3R2 [ReferenceDNASequence:12701598] UCSC:O00459 PIK3R2 [ReferenceDNASequence:11363666] BioGPS Gene:5296 PIK3R2 [ReferenceDNASequence:11394407] COSMIC - genes:PIK3R2 PIK3R2 [ReferenceDNASequence:11418925] CTD Gene:5296 PIK3R2 [ReferenceDNASequence:11430474] dbSNP Gene:5296 PIK3R2 [ReferenceDNASequence:11822936] HGNC:8980 PIK3R2 [ReferenceDNASequence:11902394] KEGG:hsa:5296 PIK3R2 [ReferenceDNASequence:11993455] Monarch:5296 PIK3R2 [ReferenceDNASequence:12077548] NCBI Gene:5296 PIK3R2 [ReferenceDNASequence:12113601] OMIM:603157 PIK3R2
referenceTranscript	[ReferenceRNASequence:12606186] RefSeq:NM_005027.4 PIK3R2
schemaClass	ReferenceGeneProduct
secondaryIdentifier	P85B_HUMAN Q5EAT5 Q9UPH9
sequenceLength	728
species	[Species:48887] Homo sapiens
stId	uniprot:O00459
url	http://purl.uniprot.org/uniprot/O00459

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-74791] PIK3R2 [cytosol] [EntityWithAccessionedSequence:R-HSA-3080554] K63polyUb-PIK3R2 [cytosol] [EntityWithAccessionedSequence:R-HSA-9860512] p-Y464-PIK3R2 [cytosol]
(referenceSequence)	[GroupModifiedResidue:3080566] ubiquitinylated lysine (K63-polyubiquitin [cytosol]) at unknown position [ModifiedResidue:9860492] O4'-phospho-L-tyrosine at 464
(interactor)	[UndirectedInteraction:11138723] UniProt:P37173 <-> UniProt:O00459 (IntAct) [UndirectedInteraction:11159463] UniProt:P10721 <-> UniProt:O00459 (IntAct) [UndirectedInteraction:11164045] UniProt:P46108 <-> UniProt:O00459 (IntAct) [UndirectedInteraction:11174095] UniProt:Q9UQC2 <-> UniProt:O00459 (IntAct) [UndirectedInteraction:11182373] UniProt:P27986 <-> UniProt:O00459 (IntAct) [UndirectedInteraction:11189525] UniProt:P62993 <-> UniProt:O00459 (IntAct) [UndirectedInteraction:11195301] UniProt:Q06124 <-> UniProt:O00459 (IntAct) [UndirectedInteraction:11198715] UniProt:Q08379 <-> UniProt:O00459 (IntAct) [UndirectedInteraction:11204593] UniProt:Q8TDQ0 <-> UniProt:O00459 (IntAct) [UndirectedInteraction:11210165] UniProt:P42336 <-> UniProt:O00459 (IntAct) [UndirectedInteraction:11234095] UniProt:P00533 <-> UniProt:O00459 (IntAct) [UndirectedInteraction:11276845] UniProt:O15431 <-> UniProt:O00459 (IntAct) [UndirectedInteraction:11282841] UniProt:P43115 <-> UniProt:O00459 (IntAct) [UndirectedInteraction:11289883] UniProt:P03496 <-> UniProt:O00459 (IntAct) [UndirectedInteraction:11292027] UniProt:P49407 <-> UniProt:O00459 (IntAct) [UndirectedInteraction:11297277] UniProt:P22681 <-> UniProt:O00459 (IntAct) [UndirectedInteraction:11306799] UniProt:P04626 <-> UniProt:O00459 (IntAct)