Q8WYR1 (PI3R5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:

PIK3R5

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	880 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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.
Enzyme regulation	Greatly activated by G gamma proteins By similarity.
Subunit structure	Heterodimer of a catalytic subunit (PIK3CG/p120) and a regulatory (PIK3R5a/p101) subunit. Interacts with beta-gamma G protein dimers. Ref.7
Subcellular location	Nucleus By similarity. Cytoplasm By similarity. Membrane; Peripheral membrane protein By similarity.
Tissue specificity	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. Ref.7 Ref.9
Domain	The heterodimerization region allows the binding to the catalytic subunit.
Involvement in disease	Defects in PIK3R5 may be a cause of autosomal recessive ataxia with oculomotor apraxia (AOA). A PIK3R5 mutation segregates with the disease phenotype in a family affected by gait ataxia, cerebellar dysarthric speech, and impaired ocular movement. Additional features include reduced or absent tendon reflexes, severe cerebellar atrophy, marked vermal atrophy, moderately severe axonal sensory polyneuropathy with absent sensory nerve action potential in the lower extremities, and persistently elevated alpha-fetoprotein levels.

Ontologies

Keywords
Cellular component	Cytoplasm Membrane Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G-protein coupled receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB phosphatidylinositol 3-kinase cascade Inferred from sequence or structural similarity. Source: UniProtKB phosphatidylinositol biosynthetic process Traceable author statement. Source: Reactome platelet activation Traceable author statement. Source: Reactome positive regulation of MAP kinase activity Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of protein kinase B signaling cascade Inferred from sequence or structural similarity. Source: UniProtKB small molecule metabolic process Traceable author statement. Source: Reactome
Cellular_component	1-phosphatidylinositol-4-phosphate 3-kinase, class IB complex Inferred from sequence or structural similarity. Source: UniProtKB membrane Inferred from sequence or structural similarity. Source: UniProtKB nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	1-phosphatidylinositol-3-kinase regulator activity Inferred from electronic annotation. Source: Compara G-protein beta/gamma-subunit complex binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8WYR1-1)

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.

Isoform 2 (identifier: Q8WYR1-2)

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

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 880	880	Phosphoinositide 3-kinase regulatory subunit 5		PRO_0000058421
Regions
	Region	25 – 101	77	Heterodimerization By similarity
	Region	653 – 753	101	Interaction with beta-gamma G protein dimers By similarity
Amino acid modifications
	Modified residue	1	1	N-acetylmethionine By similarity
	Modified residue	458	1	Phosphoserine Ref.8
	Modified residue	507	1	Phosphoserine Ref.8
Natural variations
	Alternative sequence	1 – 386	386	Missing in isoform 2.		VSP_016388
	Natural variant	28	1	R → C in a colorectal cancer sample; somatic mutation. Ref.10		VAR_036227
	Natural variant	629	1	P → S Probable disease-associated mutation found in a family affected by autosomal recessive ataxia with oculomotor apraxia. Ref.9 Corresponds to variant rs61761068 [ dbSNP | Ensembl ].		VAR_067052
Experimental info
	Sequence conflict	15	1	H → L in AAW63122. Ref.6
	Sequence conflict	29	1	R → C in AAW63122. Ref.6
	Sequence conflict	47	1	L → Q in AAW63122. Ref.6
	Sequence conflict	95	1	F → L in AAW63122. Ref.6
	Sequence conflict	171	1	V → E in AAW63122. Ref.6
	Sequence conflict	220 – 297	78	AKTLA…WSQDS → TLQNQGSSIPSPSLSPGATP TAGARTALTSCRKSCSRNRS CSSQGSWEMMKRRKRRRRRW RRTWKLMGTVPREIPCSP in AAW63122. Ref.6
	Sequence conflict	299 – 368	70	DILQE…SQASG → GNIEGDPGPRRPDSAGLASL QTSCRKSCSRNRSYSSQGSW EMMKRRERRRRRWRRTWKLT GTVPREIPCS in AAW63121. Ref.6
	Sequence conflict	674	1	V → L in AAD33397. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2002. Version 1. Checksum: 70E356773B148A8A	FASTA	880	97,348
	10 20 30 40 50 60 MQPGATTCTE DRIQHALERC LHGLSLSRRS TSWSAGLCLN CWSLQELVSR DPGHFLILLE 70 80 90 100 110 120 QILQKTREVQ EKGTYDLLTP LALLFYSTVL CTPHFPPDSD LLLKAASTYH RFLTWPVPYC 130 140 150 160 170 180 SICQELLTFI DAELKAPGIS YQRLVRAEQG LPIRSHRSST VTVLLLNPVE VQAEFLAVAN 190 200 210 220 230 240 KLSTPGHSPH SAYTTLLLHA FQATFGAHCD VPGLHCRLQA KTLAELEDIF TETAEAQELA 250 260 270 280 290 300 SGIGDAAEAR RWLRTKLQAV GEKAGFPGVL DTAKPGKLHT IPIPVARCYT YSWSQDSFDI 310 320 330 340 350 360 LQEILLKEQE LLQPGILGDD EEEEEEEEEV EEDLETDGHC AERDSLLSTS SLASHDSTLS 370 380 390 400 410 420 LASSQASGPA LSRHLLTSFV SGLSDGMDSG YVEDSEESSS EWPWRRGSQE RRGHRRPGQK 430 440 450 460 470 480 FIRIYKLFKS TSQLVLRRDS RSLEGSSDTA LPLRRAGSLC SPLDEPVSPP SRAQRSRSLP 490 500 510 520 530 540 QPKLGTQLPS WLLAPASRPQ RRRPFLSGDE DPKASTLRVV VFGSDRISGK VARAYSNLRR 550 560 570 580 590 600 LENNRPLLTR FFKLQFFYVP VKRSHGTSPG ACPPPRSQTP SPPTDSPRHA SPGELGTTPW 610 620 630 640 650 660 EESTNDISHY LGMLDPWYER NVLGLMHLPP EVLCQQSLKA EAQALEGSPT QLPILADMLL 670 680 690 700 710 720 YYCRFAARPV LLQVYQTELT FITGEKTTEI FIHSLELGHS AATRAIKASG PGSKRLGIDG 730 740 750 760 770 780 DREAVPLTLQ IIYSKGAISG RSRWSNLEKV CTSVNLNKAC RKQEELDSSM EALTLNLTEV 790 800 810 820 830 840 VKRQNSKSKK GFNQISTSQI KVDKVQIIGS NSCPFAVCLD QDERKILQSV VRCEVSPCYK 850 860 870 880 PEKSDLSSPP QTPPDLPAQA APDLCSLLCL PIMTFSGALP
	Isoform 2 [UniParc]. Checksum: C8962DD01304C8C3	FASTA	494	54,878
	10 20 30 40 50 60 MDSGYVEDSE ESSSEWPWRR GSQERRGHRR PGQKFIRIYK LFKSTSQLVL RRDSRSLEGS 70 80 90 100 110 120 SDTALPLRRA GSLCSPLDEP VSPPSRAQRS RSLPQPKLGT QLPSWLLAPA SRPQRRRPFL 130 140 150 160 170 180 SGDEDPKAST LRVVVFGSDR ISGKVARAYS NLRRLENNRP LLTRFFKLQF FYVPVKRSHG 190 200 210 220 230 240 TSPGACPPPR SQTPSPPTDS PRHASPGELG TTPWEESTND ISHYLGMLDP WYERNVLGLM 250 260 270 280 290 300 HLPPEVLCQQ SLKAEAQALE GSPTQLPILA DMLLYYCRFA ARPVLLQVYQ TELTFITGEK 310 320 330 340 350 360 TTEIFIHSLE LGHSAATRAI KASGPGSKRL GIDGDREAVP LTLQIIYSKG AISGRSRWSN 370 380 390 400 410 420 LEKVCTSVNL NKACRKQEEL DSSMEALTLN LTEVVKRQNS KSKKGFNQIS TSQIKVDKVQ 430 440 450 460 470 480 IIGSNSCPFA VCLDQDERKI LQSVVRCEVS PCYKPEKSDL SSPPQTPPDL PAQAAPDLCS 490 LLCLPIMTFS GALP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases 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]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-458 AND SER-507, MASS SPECTROMETRY.
[9]	"A missense mutation in PIK3R5 gene in a family with ataxia and oculomotor apraxia." Tassan N.A., Khalil D., Shinwari J., Sharif L.A., Bavi P., Abduljaleel Z., Abu Dhaim N., Magrashi A., Bobis S., Ahmed H., Alahmed S., Bohlega S. Hum. Mutat. 33:351-354(2012) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, PROBABLE INVOLVEMENT IN AUTOSOMAL RECESSIVE ATAXIA WITH OCULOMOTOR APRAXIA, VARIANT SER-629.
[10]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] CYS-28.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00292380. IPI00552269.
RefSeq	NP_001136105.1. NM_001142633.2. NP_001238780.1. NM_001251851.1. NP_001238781.1. NM_001251852.1. NP_001238782.1. NM_001251853.1. NP_001238784.1. NM_001251855.1. NP_055123.2. NM_014308.3.
UniGene	Hs.278901. Hs.738684.
3D structure databases
ProteinModelPortal	Q8WYR1.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8WYR1. 6 interactions.
STRING	9606.ENSP00000269300.
PTM databases
PhosphoSite	Q8WYR1.
Polymorphism databases
DMDM	74716480.
Proteomic databases
PaxDb	Q8WYR1.
PRIDE	Q8WYR1.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000447110; ENSP00000392812; ENSG00000141506. ENST00000581552; ENSP00000462433; ENSG00000141506.
GeneID	23533.
KEGG	hsa:23533.
UCSC	uc002glt.3. human.
Organism-specific databases
CTD	23533.
GeneCards	GC17M008724.
H-InvDB	HIX0027111.
HGNC	HGNC:30035. PIK3R5.
HPA	HPA052247.
MIM	611317. gene.
neXtProt	NX_Q8WYR1.
Orphanet	64753. Spinocerebellar ataxia with axonal neuropathy type 2.
PharmGKB	PA134890823.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG27692.
HOVERGEN	HBG079651.
InParanoid	Q8WYR1.
KO	K02649.
OMA	TLQIIYS.
OrthoDB	EOG4Z0B56.
PhylomeDB	Q8WYR1.
Enzyme and pathway databases
BioCyc	MetaCyc:HS13887-MONOMER.
Pathway_Interaction_DB	pi3kcipathway. Class I PI3K signaling events. pi3kcibpathway. Class IB PI3K non-lipid kinase events. epha_fwdpathway. EPHA forward signaling. txa2pathway. Thromboxane A2 receptor signaling.
Reactome	REACT_111102. Signal Transduction. REACT_111217. Metabolism. REACT_604. Hemostasis.
Gene expression databases
Bgee	Q8WYR1.
CleanEx	HS_PIK3R5.
Genevestigator	Q8WYR1.
GermOnline	ENSG00000141506. Homo sapiens.
Family and domain databases
InterPro	IPR019522. PI3K_1B_gamma_p101_su. [Graphical view]
PANTHER	PTHR15593. PTHR15593. 1 hit.
Pfam	PF10486. PI3K_1B_p101. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q8WYR1.
ChiTaRS	PIK3R5. human.
GenomeRNAi	23533.
NextBio	46026.
SOURCE	Search...

Entry information

Entry name

PI3R5_HUMAN

Accession

Primary (citable) accession number: Q8WYR1
Secondary accession number(s): B0LPH4 , D3DTS3, Q5G936, Q5G938, Q5G939, Q8IZ23, Q9Y2Y2

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 6, 2005
Last sequence update:	March 1, 2002
Last modified:	May 1, 2013
This is version 77 of the entry and version 1 of the sequence. [Complete history]

Entry status

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.