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Protein

Phosphoinositide 3-kinase regulatory subunit 5

Gene

PIK3R5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Regulatory subunit of the PI3K gamma complex. Required for recruitment of the catalytic subunit to the plasma membrane via interaction with beta-gamma G protein dimers. Required for G protein-mediated activation of PIK3CG (By similarity).By similarity

Enzyme regulationi

Greatly activated by G gamma proteins.By similarity

GO - Molecular functioni

  1. 1-phosphatidylinositol-3-kinase regulator activity Source: InterPro
  2. G-protein beta/gamma-subunit complex binding Source: UniProtKB

GO - Biological processi

  1. blood coagulation Source: Reactome
  2. G-protein coupled receptor signaling pathway Source: UniProtKB
  3. phosphatidylinositol 3-kinase signaling Source: UniProtKB
  4. phosphatidylinositol biosynthetic process Source: Reactome
  5. phospholipid metabolic process Source: Reactome
  6. platelet activation Source: Reactome
  7. positive regulation of MAP kinase activity Source: UniProtKB
  8. positive regulation of protein kinase B signaling Source: UniProtKB
  9. small molecule metabolic process Source: Reactome
Complete GO annotation...

Enzyme and pathway databases

BioCyciMetaCyc:HS13887-MONOMER.
ReactomeiREACT_121025. Synthesis of PIPs at the plasma membrane.
REACT_1695. GPVI-mediated activation cascade.
REACT_19290. G beta:gamma signalling through PI3Kgamma.

Names & Taxonomyi

Protein namesi
Recommended name:
Phosphoinositide 3-kinase regulatory subunit 5
Short name:
PI3-kinase regulatory subunit 5
Alternative name(s):
PI3-kinase p101 subunit
Phosphatidylinositol 4,5-bisphosphate 3-kinase regulatory subunit
Short name:
PtdIns-3-kinase regulatory subunit
Protein FOAP-2
PtdIns-3-kinase p101
p101-PI3K
Gene namesi
Name:PIK3R5
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 17

Organism-specific databases

HGNCiHGNC:30035. PIK3R5.

Subcellular locationi

Nucleus By similarity. Cytoplasm By similarity. Membrane By similarity; Peripheral membrane protein By similarity

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. cytosol Source: Reactome
  3. membrane Source: UniProtKB
  4. nucleus Source: UniProtKB-SubCell
  5. phosphatidylinositol 3-kinase complex, class IB Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

Ataxia-oculomotor apraxia 31 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionAn autosomal recessive disease characterized by cerebellar ataxia, oculomotor apraxia, areflexia and peripheral neuropathy.

See also OMIM:615217
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti629 – 6291P → S in AOA3. 1 Publication
Corresponds to variant rs61761068 [ dbSNP | Ensembl ].
VAR_067052

Keywords - Diseasei

Disease mutation, Neurodegeneration

Organism-specific databases

MIMi615217. phenotype.
Orphaneti64753. Spinocerebellar ataxia with axonal neuropathy type 2.
PharmGKBiPA134890823.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 880880Phosphoinositide 3-kinase regulatory subunit 5PRO_0000058421Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionineBy similarity
Modified residuei458 – 4581Phosphoserine1 Publication
Modified residuei507 – 5071Phosphoserine1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiQ8WYR1.
PaxDbiQ8WYR1.
PRIDEiQ8WYR1.

PTM databases

PhosphoSiteiQ8WYR1.

Expressioni

Tissue specificityi

Ubiquitously expressed with high expression in fetal brain compared to adult brain. Abundant expression is observed in cerebellum, cerebral cortex, cerebral meninges, and vermis cerebelli.2 Publications

Gene expression databases

BgeeiQ8WYR1.
CleanExiHS_PIK3R5.
ExpressionAtlasiQ8WYR1. baseline and differential.
GenevestigatoriQ8WYR1.

Organism-specific databases

HPAiHPA052247.

Interactioni

Subunit structurei

Heterodimer of a catalytic subunit (PIK3CG/p120) and a regulatory (PIK3R5a/p101) subunit. Interacts with beta-gamma G protein dimers.1 Publication

Protein-protein interaction databases

BioGridi117079. 5 interactions.
IntActiQ8WYR1. 7 interactions.
STRINGi9606.ENSP00000269300.

Structurei

3D structure databases

ProteinModelPortaliQ8WYR1.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni25 – 10177HeterodimerizationBy similarityAdd
BLAST
Regioni653 – 753101Interaction with beta-gamma G protein dimersBy similarityAdd
BLAST

Domaini

The heterodimerization region allows the binding to the catalytic subunit.

Phylogenomic databases

eggNOGiNOG27692.
GeneTreeiENSGT00530000063753.
HOVERGENiHBG079651.
InParanoidiQ8WYR1.
KOiK02649.
OMAiIYSKGAI.
OrthoDBiEOG7RV9FH.
PhylomeDBiQ8WYR1.
TreeFamiTF102035.

Family and domain databases

InterProiIPR019522. PIK3R5/6.
[Graphical view]
PfamiPF10486. PI3K_1B_p101. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8WYR1-1) [UniParc]FASTAAdd to basket

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
MQPGATTCTE DRIQHALERC LHGLSLSRRS TSWSAGLCLN CWSLQELVSR
60 70 80 90 100
DPGHFLILLE QILQKTREVQ EKGTYDLLTP LALLFYSTVL CTPHFPPDSD
110 120 130 140 150
LLLKAASTYH RFLTWPVPYC SICQELLTFI DAELKAPGIS YQRLVRAEQG
160 170 180 190 200
LPIRSHRSST VTVLLLNPVE VQAEFLAVAN KLSTPGHSPH SAYTTLLLHA
210 220 230 240 250
FQATFGAHCD VPGLHCRLQA KTLAELEDIF TETAEAQELA SGIGDAAEAR
260 270 280 290 300
RWLRTKLQAV GEKAGFPGVL DTAKPGKLHT IPIPVARCYT YSWSQDSFDI
310 320 330 340 350
LQEILLKEQE LLQPGILGDD EEEEEEEEEV EEDLETDGHC AERDSLLSTS
360 370 380 390 400
SLASHDSTLS LASSQASGPA LSRHLLTSFV SGLSDGMDSG YVEDSEESSS
410 420 430 440 450
EWPWRRGSQE RRGHRRPGQK FIRIYKLFKS TSQLVLRRDS RSLEGSSDTA
460 470 480 490 500
LPLRRAGSLC SPLDEPVSPP SRAQRSRSLP QPKLGTQLPS WLLAPASRPQ
510 520 530 540 550
RRRPFLSGDE DPKASTLRVV VFGSDRISGK VARAYSNLRR LENNRPLLTR
560 570 580 590 600
FFKLQFFYVP VKRSHGTSPG ACPPPRSQTP SPPTDSPRHA SPGELGTTPW
610 620 630 640 650
EESTNDISHY LGMLDPWYER NVLGLMHLPP EVLCQQSLKA EAQALEGSPT
660 670 680 690 700
QLPILADMLL YYCRFAARPV LLQVYQTELT FITGEKTTEI FIHSLELGHS
710 720 730 740 750
AATRAIKASG PGSKRLGIDG DREAVPLTLQ IIYSKGAISG RSRWSNLEKV
760 770 780 790 800
CTSVNLNKAC RKQEELDSSM EALTLNLTEV VKRQNSKSKK GFNQISTSQI
810 820 830 840 850
KVDKVQIIGS NSCPFAVCLD QDERKILQSV VRCEVSPCYK PEKSDLSSPP
860 870 880
QTPPDLPAQA APDLCSLLCL PIMTFSGALP
Length:880
Mass (Da):97,348
Last modified:March 1, 2002 - v1
Checksum:i70E356773B148A8A
GO
Isoform 2 (identifier: Q8WYR1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-386: Missing.

Note: No experimental confirmation available.

Show »
Length:494
Mass (Da):54,878
Checksum:iC8962DD01304C8C3
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti15 – 151H → L in AAW63122 (Ref. 6) Curated
Sequence conflicti29 – 291R → C in AAW63122 (Ref. 6) Curated
Sequence conflicti47 – 471L → Q in AAW63122 (Ref. 6) Curated
Sequence conflicti95 – 951F → L in AAW63122 (Ref. 6) Curated
Sequence conflicti171 – 1711V → E in AAW63122 (Ref. 6) Curated
Sequence conflicti220 – 29778AKTLA…WSQDS → TLQNQGSSIPSPSLSPGATP TAGARTALTSCRKSCSRNRS CSSQGSWEMMKRRKRRRRRW RRTWKLMGTVPREIPCSP in AAW63122 (Ref. 6) CuratedAdd
BLAST
Sequence conflicti299 – 36870DILQE…SQASG → GNIEGDPGPRRPDSAGLASL QTSCRKSCSRNRSYSSQGSW EMMKRRERRRRRWRRTWKLT GTVPREIPCS in AAW63121 (Ref. 6) CuratedAdd
BLAST
Sequence conflicti674 – 6741V → L in AAD33397 (Ref. 2) Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti28 – 281R → C in a colorectal cancer sample; somatic mutation. 1 Publication
VAR_036227
Natural varianti629 – 6291P → S in AOA3. 1 Publication
Corresponds to variant rs61761068 [ dbSNP | Ensembl ].
VAR_067052

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 386386Missing in isoform 2. 1 PublicationVSP_016388Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB028925 mRNA. Translation: BAB82464.1.
AF128881 mRNA. Translation: AAD33397.1.
EU332864 Genomic DNA. Translation: ABY87553.1.
CH471108 Genomic DNA. Translation: EAW90035.1.
CH471108 Genomic DNA. Translation: EAW90036.1.
BC028212 mRNA. Translation: AAH28212.1.
AY725851 mRNA. Translation: AAW63121.1.
AY725852 mRNA. Translation: AAW63122.1.
AY725853 mRNA. Translation: AAW63123.1.
AY725854 mRNA. Translation: AAW63124.1.
CCDSiCCDS11147.1. [Q8WYR1-1]
CCDS73986.1. [Q8WYR1-2]
RefSeqiNP_001136105.1. NM_001142633.2. [Q8WYR1-1]
NP_001238780.1. NM_001251851.1. [Q8WYR1-2]
NP_001238781.1. NM_001251852.1. [Q8WYR1-2]
NP_001238782.1. NM_001251853.1. [Q8WYR1-2]
NP_001238784.1. NM_001251855.1. [Q8WYR1-2]
NP_055123.2. NM_014308.3. [Q8WYR1-1]
XP_005256636.1. XM_005256579.2. [Q8WYR1-1]
UniGeneiHs.278901.
Hs.738684.

Genome annotation databases

EnsembliENST00000447110; ENSP00000392812; ENSG00000141506. [Q8WYR1-1]
ENST00000581552; ENSP00000462433; ENSG00000141506. [Q8WYR1-1]
ENST00000611902; ENSP00000477795; ENSG00000141506. [Q8WYR1-2]
ENST00000616147; ENSP00000484211; ENSG00000141506. [Q8WYR1-2]
ENST00000623421; ENSP00000485280; ENSG00000141506. [Q8WYR1-2]
GeneIDi23533.
KEGGihsa:23533.
UCSCiuc002glt.3. human. [Q8WYR1-1]

Polymorphism databases

DMDMi74716480.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB028925 mRNA. Translation: BAB82464.1.
AF128881 mRNA. Translation: AAD33397.1.
EU332864 Genomic DNA. Translation: ABY87553.1.
CH471108 Genomic DNA. Translation: EAW90035.1.
CH471108 Genomic DNA. Translation: EAW90036.1.
BC028212 mRNA. Translation: AAH28212.1.
AY725851 mRNA. Translation: AAW63121.1.
AY725852 mRNA. Translation: AAW63122.1.
AY725853 mRNA. Translation: AAW63123.1.
AY725854 mRNA. Translation: AAW63124.1.
CCDSiCCDS11147.1. [Q8WYR1-1]
CCDS73986.1. [Q8WYR1-2]
RefSeqiNP_001136105.1. NM_001142633.2. [Q8WYR1-1]
NP_001238780.1. NM_001251851.1. [Q8WYR1-2]
NP_001238781.1. NM_001251852.1. [Q8WYR1-2]
NP_001238782.1. NM_001251853.1. [Q8WYR1-2]
NP_001238784.1. NM_001251855.1. [Q8WYR1-2]
NP_055123.2. NM_014308.3. [Q8WYR1-1]
XP_005256636.1. XM_005256579.2. [Q8WYR1-1]
UniGeneiHs.278901.
Hs.738684.

3D structure databases

ProteinModelPortaliQ8WYR1.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117079. 5 interactions.
IntActiQ8WYR1. 7 interactions.
STRINGi9606.ENSP00000269300.

Chemistry

BindingDBiQ8WYR1.

PTM databases

PhosphoSiteiQ8WYR1.

Polymorphism databases

DMDMi74716480.

Proteomic databases

MaxQBiQ8WYR1.
PaxDbiQ8WYR1.
PRIDEiQ8WYR1.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000447110; ENSP00000392812; ENSG00000141506. [Q8WYR1-1]
ENST00000581552; ENSP00000462433; ENSG00000141506. [Q8WYR1-1]
ENST00000611902; ENSP00000477795; ENSG00000141506. [Q8WYR1-2]
ENST00000616147; ENSP00000484211; ENSG00000141506. [Q8WYR1-2]
ENST00000623421; ENSP00000485280; ENSG00000141506. [Q8WYR1-2]
GeneIDi23533.
KEGGihsa:23533.
UCSCiuc002glt.3. human. [Q8WYR1-1]

Organism-specific databases

CTDi23533.
GeneCardsiGC17M008724.
H-InvDBHIX0027111.
HGNCiHGNC:30035. PIK3R5.
HPAiHPA052247.
MIMi611317. gene.
615217. phenotype.
neXtProtiNX_Q8WYR1.
Orphaneti64753. Spinocerebellar ataxia with axonal neuropathy type 2.
PharmGKBiPA134890823.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG27692.
GeneTreeiENSGT00530000063753.
HOVERGENiHBG079651.
InParanoidiQ8WYR1.
KOiK02649.
OMAiIYSKGAI.
OrthoDBiEOG7RV9FH.
PhylomeDBiQ8WYR1.
TreeFamiTF102035.

Enzyme and pathway databases

BioCyciMetaCyc:HS13887-MONOMER.
ReactomeiREACT_121025. Synthesis of PIPs at the plasma membrane.
REACT_1695. GPVI-mediated activation cascade.
REACT_19290. G beta:gamma signalling through PI3Kgamma.

Miscellaneous databases

ChiTaRSiPIK3R5. human.
GeneWikiiPIK3R5.
GenomeRNAii23533.
NextBioi46026.
PROiQ8WYR1.
SOURCEiSearch...

Gene expression databases

BgeeiQ8WYR1.
CleanExiHS_PIK3R5.
ExpressionAtlasiQ8WYR1. baseline and differential.
GenevestigatoriQ8WYR1.

Family and domain databases

InterProiIPR019522. PIK3R5/6.
[Graphical view]
PfamiPF10486. PI3K_1B_p101. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning of a human novel gene, FOAP-2, which are highly expressed in macrophages."
    Yazaki M., Fujii Y., Tsuritani K., Yajima Y., Amemiya T., Ukai Y., Naito K., Kawaguchi A., Takayama K.
    Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  2. "G-beta gamma regulated phosphatidylinositol 3-kinase."
    Stephens L., Hawkins P.T., Braselmann S.
    Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  3. SeattleSNPs variation discovery resource
    Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "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] (ISOFORM 2).
    Tissue: Blood.
  6. "Identification of alternative transcripts of human P101-PI3K."
    Reichwald K., Gausmann U., Karagyozov L., Platzer M.
    Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-369 (ISOFORM 1).
    Tissue: Peripheral blood leukocyte and Spleen.
  7. "p84, a new Gbetagamma-activated regulatory subunit of the type IB phosphoinositide 3-kinase p110gamma."
    Suire S., Coadwell J., Ferguson G.J., Davidson K., Hawkins P., Stephens L.
    Curr. Biol. 15:566-570(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PIK3CG, TISSUE SPECIFICITY.
  8. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-458 AND SER-507, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  9. Cited for: TISSUE SPECIFICITY, VARIANT AOA3 SER-629.
  10. Cited for: VARIANT [LARGE SCALE ANALYSIS] CYS-28.

Entry informationi

Entry nameiPI3R5_HUMAN
AccessioniPrimary (citable) accession number: Q8WYR1
Secondary accession number(s): B0LPH4
, D3DTS3, Q5G936, Q5G938, Q5G939, Q8IZ23, Q9Y2Y2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 6, 2005
Last sequence update: March 1, 2002
Last modified: March 4, 2015
This is version 95 of the entry and version 1 of the sequence. [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 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.