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Protein

Phosphoinositide 3-kinase regulatory subunit 4

Gene

PIK3R4

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

Functioni

Regulatory subunit of the PI3K complex that mediates formation of phosphatidylinositol 3-phosphate; different complex forms are believed to play a role in multiple membrane trafficking pathways: PI3KC3-C1 is involved in initiation of autophagosomes and PI3KC3-C2 in maturation of autophagosomes and endocytosis. Involved in regulation of degradative endocytic trafficking and cytokinesis, probably in the context of PI3KC3-C2 (PubMed:20643123).1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mn2+1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei53ATPPROSITE-ProRule annotation1
Active sitei148Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi32 – 40ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

  • autophagy of peroxisome Source: GO_Central
  • cellular response to glucose starvation Source: UniProtKB
  • late endosome to vacuole transport Source: GO_Central
  • macroautophagy Source: GO_Central
  • positive regulation of phosphatidylinositol 3-kinase activity Source: UniProtKB
  • protein phosphorylation Source: GO_Central
  • protein targeting to vacuole Source: GO_Central
  • receptor catabolic process Source: UniProtKB
  • regulation of cytokinesis Source: UniProtKB
  • toll-like receptor 9 signaling pathway Source: Reactome

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS03788-MONOMER
ReactomeiR-HSA-109704 PI3K Cascade
R-HSA-1632852 Macroautophagy
R-HSA-1660514 Synthesis of PIPs at the Golgi membrane
R-HSA-1660516 Synthesis of PIPs at the early endosome membrane
R-HSA-1660517 Synthesis of PIPs at the late endosome membrane
R-HSA-168138 Toll Like Receptor 9 (TLR9) Cascade
R-HSA-5668599 RHO GTPases Activate NADPH Oxidases
SignaLinkiQ99570
SIGNORiQ99570

Names & Taxonomyi

Protein namesi
Recommended name:
Phosphoinositide 3-kinase regulatory subunit 4 (EC:2.7.11.1)
Short name:
PI3-kinase regulatory subunit 4
Alternative name(s):
PI3-kinase p150 subunit
Phosphoinositide 3-kinase adaptor protein
Gene namesi
Name:PIK3R4
Synonyms:VPS151 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000196455.7
HGNCiHGNC:8982 PIK3R4
MIMi602610 gene
neXtProtiNX_Q99570

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasmic vesicle, Endosome, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi30849
OpenTargetsiENSG00000196455
PharmGKBiPA33315

Chemistry databases

ChEMBLiCHEMBL2189144

Polymorphism and mutation databases

BioMutaiPIK3R4
DMDMi74762700

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00000865242 – 1358Phosphoinositide 3-kinase regulatory subunit 4Add BLAST1357

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycine2 Publications1
Modified residuei808PhosphoserineCombined sources1
Modified residuei813PhosphoserineCombined sources1
Modified residuei853PhosphoserineCombined sources1
Modified residuei865PhosphoserineCombined sources1
Modified residuei1316PhosphothreonineCombined sources1

Post-translational modificationi

Myristoylated.1 Publication
Probably autophosphorylated.1 Publication

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein

Proteomic databases

EPDiQ99570
MaxQBiQ99570
PaxDbiQ99570
PeptideAtlasiQ99570
PRIDEiQ99570
ProteomicsDBi78330

PTM databases

iPTMnetiQ99570
PhosphoSitePlusiQ99570

Expressioni

Tissue specificityi

Ubiquitously expressed.1 Publication

Gene expression databases

BgeeiENSG00000196455
CleanExiHS_PIK3R4
ExpressionAtlasiQ99570 baseline and differential
GenevisibleiQ99570 HS

Organism-specific databases

HPAiHPA036032
HPA036033

Interactioni

Subunit structurei

Component of the PI3K (PI3KC3/PI3K-III/class III phosphatidylinositol 3-kinase) complex the core of which is composed of the catalytic subunit PIK3C3, the regulatory subunit PIK3R4 and BECN1 associating with additional regulatory/auxilliary subunits to form alternative complex forms. Alternative complex forms containing a forth regulatory subunit in a mutually exclusive manner are PI3K complex I (PI3KC3-C1) containing ATG14, and PI3K complex II (PI3KC3-C2) containing UVRAG (PubMed:8999962, PubMed:19270696, PubMed:23878393, PubMed:25490155). PI3KC3-C1 displays a V-shaped architecture with PIK3R4 serving as a bridge between PIK3C3 and the ATG14:BECN1 subcomplex (PubMed:25490155). Both, PI3KC3-C1 and PI3KC3-C2, can associate with further regulatory subunits, such as RUBCN, SH3GLB1/Bif-1, AMBRA1 and NRBF2 (PubMed:19270696, PubMed:20643123, PubMed:24785657). PI3KC3-C1 probably associates with PIK3CB (By similarity). Interacts with RAB7A in the presence of PIK3C3/VPS34 (PubMed:14617358). Interacts with NRBF2 (PubMed:24785657).By similarity7 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi119059, 24 interactors
ComplexPortaliCPX-73 Phosphatidylinositol 3-kinase complex, class III, ATG14 variant
CPX-74 Phosphatidylinositol 3-kinase complex, class III, UVRAG variant
CORUMiQ99570
DIPiDIP-42310N
ELMiQ99570
IntActiQ99570, 22 interactors
MINTiQ99570
STRINGi9606.ENSP00000349205

Chemistry databases

BindingDBiQ99570

Structurei

3D structure databases

ProteinModelPortaliQ99570
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini26 – 324Protein kinasePROSITE-ProRule annotationAdd BLAST299
Repeati413 – 450HEAT 1Add BLAST38
Repeati458 – 495HEAT 2Add BLAST38
Repeati572 – 610HEAT 3Add BLAST39
Repeati991 – 1030WD 1Add BLAST40
Repeati1040 – 1079WD 2Add BLAST40
Repeati1093 – 1134WD 3Add BLAST42
Repeati1139 – 1178WD 4Add BLAST40
Repeati1182 – 1223WD 5Add BLAST42
Repeati1237 – 1278WD 6Add BLAST42
Repeati1327 – 1358WD 7Add BLAST32

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi781 – 784Poly-Glu4
Compositional biasi974 – 977Poly-Pro4

Sequence similaritiesi

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, WD repeat

Phylogenomic databases

eggNOGiKOG1240 Eukaryota
ENOG410XPDN LUCA
GeneTreeiENSGT00390000016225
HOGENOMiHOG000216566
HOVERGENiHBG079542
InParanoidiQ99570
KOiK08333
OMAiWCILYPS
OrthoDBiEOG091G00QT
PhylomeDBiQ99570
TreeFamiTF102034

Family and domain databases

Gene3Di1.25.10.10, 2 hits
2.130.10.10, 1 hit
InterProiView protein in InterPro
IPR011989 ARM-like
IPR016024 ARM-type_fold
IPR021133 HEAT_type_2
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR008271 Ser/Thr_kinase_AS
IPR015943 WD40/YVTN_repeat-like_dom_sf
IPR001680 WD40_repeat
IPR019775 WD40_repeat_CS
IPR017986 WD40_repeat_dom
IPR036322 WD40_repeat_dom_sf
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PF00400 WD40, 2 hits
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SM00320 WD40, 6 hits
SUPFAMiSSF48371 SSF48371, 2 hits
SSF50978 SSF50978, 2 hits
SSF56112 SSF56112, 2 hits
PROSITEiView protein in PROSITE
PS50077 HEAT_REPEAT, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
PS00678 WD_REPEATS_1, 2 hits
PS50082 WD_REPEATS_2, 2 hits
PS50294 WD_REPEATS_REGION, 2 hits

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q99570-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGNQLAGIAP SQILSVESYF SDIHDFEYDK SLGSTRFFKV ARAKHREGLV
60 70 80 90 100
VVKVFAIQDP TLPLTSYKQE LEELKIRLNS AQNCLPFQKA SEKASEKAAM
110 120 130 140 150
LFRQYVRDNL YDRISTRPFL NNIEKRWIAF QILTAVDQAH KSGVRHGDIK
160 170 180 190 200
TENVMVTSWN WVLLTDFASF KPTYLPEDNP ADFNYFFDTS RRRTCYIAPE
210 220 230 240 250
RFVDGGMFAT ELEYMRDPST PLVDLNSNQR TRGELKRAMD IFSAGCVIAE
260 270 280 290 300
LFTEGVPLFD LSQLLAYRNG HFFPEQVLNK IEDHSIRELV TQMIHREPDK
310 320 330 340 350
RLEAEDYLKQ QRGNAFPEIF YTFLQPYMAQ FAKETFLSAD ERILVIRKDL
360 370 380 390 400
GNIIHNLCGH DLPEKAEGEP KENGLVILVS VITSCLQTLK YCDSKLAALE
410 420 430 440 450
LILHLAPRLS VEILLDRITP YLLHFSNDSV PRVRAEALRT LTKVLALVKE
460 470 480 490 500
VPRNDINIYP EYILPGIAHL AQDDATIVRL AYAENIALLA ETALRFLELV
510 520 530 540 550
QLKNLNMEND PNNEEIDEVT HPNGNYDTEL QALHEMVQQK VVTLLSDPEN
560 570 580 590 600
IVKQTLMENG ITRLCVFFGR QKANDVLLSH MITFLNDKND WHLRGAFFDS
610 620 630 640 650
IVGVAAYVGW QSSSILKPLL QQGLSDAEEF VIVKALYALT CMCQLGLLQK
660 670 680 690 700
PHVYEFASDI APFLCHPNLW IRYGAVGFIT VVARQISTAD VYCKLMPYLD
710 720 730 740 750
PYITQPIIQI ERKLVLLSVL KEPVSRSIFD YALRSKDITS LFRHLHMRQK
760 770 780 790 800
KRNGSLPDCP PPEDPAIAQL LKKLLSQGMT EEEEDKLLAL KDFMMKSNKA
810 820 830 840 850
KANIVDQSHL HDSSQKGVID LAALGITGRQ VDLVKTKQEP DDKRARKHVK
860 870 880 890 900
QDSNVNEEWK SMFGSLDPPN MPQALPKGSD QEVIQTGKPP RSESSAGICV
910 920 930 940 950
PLSTSSQVPE VTTVQNKKPV IPVLSSTILP STYQIRITTC KTELQQLIQQ
960 970 980 990 1000
KREQCNAERI AKQMMENAEW ESKPPPPGWR PKGLLVAHLH EHKSAVNRIR
1010 1020 1030 1040 1050
VSDEHSLFAT CSNDGTVKIW NSQKMEGKTT TTRSILTYSR IGGRVKTLTF
1060 1070 1080 1090 1100
CQGSHYLAIA SDNGAVQLLG IEASKLPKSP KIHPLQSRIL DQKEDGCVVD
1110 1120 1130 1140 1150
MHHFNSGAQS VLAYATVNGS LVGWDLRSSS NAWTLKHDLK SGLITSFAVD
1160 1170 1180 1190 1200
IHQCWLCIGT SSGTMACWDM RFQLPISSHC HPSRARIRRL SMHPLYQSWV
1210 1220 1230 1240 1250
IAAVQGNNEV SMWDMETGDR RFTLWASSAP PLSELQPSPH SVHGIYCSPA
1260 1270 1280 1290 1300
DGNPILLTAG SDMKIRFWDL AYPERSYVVA GSTSSPSVSY YRKIIEGTEV
1310 1320 1330 1340 1350
VQEIQNKQKV GPSDDTPRRG PESLPVGHHD IITDVATFQT TQGFIVTASR

DGIVKVWK
Length:1,358
Mass (Da):153,103
Last modified:January 23, 2007 - v3
Checksum:i5B402175265B21F7
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti342 – 343RI → EK AA sequence (PubMed:8999962).Curated2
Sequence conflicti553 – 554KQ → FK AA sequence (PubMed:8999962).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_040997273F → L1 PublicationCorresponds to variant dbSNP:rs55951445Ensembl.1
Natural variantiVAR_040998342R → H1 PublicationCorresponds to variant dbSNP:rs56295394Ensembl.1
Natural variantiVAR_040999347R → W1 PublicationCorresponds to variant dbSNP:rs34797184Ensembl.1
Natural variantiVAR_041000388T → I1 PublicationCorresponds to variant dbSNP:rs34663155Ensembl.1
Natural variantiVAR_041001393D → N1 PublicationCorresponds to variant dbSNP:rs34633532Ensembl.1
Natural variantiVAR_041002699L → V1 PublicationCorresponds to variant dbSNP:rs56369596Ensembl.1
Natural variantiVAR_035632936R → Q in a breast cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs181132426Ensembl.1
Natural variantiVAR_0410031043G → V1 PublicationCorresponds to variant dbSNP:rs56160735Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y08991 mRNA Translation: CAA70176.1
BC110318 mRNA Translation: AAI10319.1
BC127106 mRNA Translation: AAI27107.1
CCDSiCCDS3067.1
RefSeqiNP_055417.1, NM_014602.2
UniGeneiHs.149032

Genome annotation databases

EnsembliENST00000356763; ENSP00000349205; ENSG00000196455
GeneIDi30849
KEGGihsa:30849
UCSCiuc003enj.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiPI3R4_HUMAN
AccessioniPrimary (citable) accession number: Q99570
Secondary accession number(s): Q2TBF4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 6, 2005
Last sequence update: January 23, 2007
Last modified: July 18, 2018
This is version 174 of the entry and version 3 of the sequence. See 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, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: 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
  5. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. SIMILARITY comments
    Index of protein domains and families

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