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Protein

Phosphoinositide 3-kinase regulatory subunit 4

Gene

PIK3R4

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 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

  • cellular response to glucose starvation Source: UniProtKB
  • late endosome to vacuole transport Source: GO_Central
  • macroautophagy Source: GO_Central
  • pexophagy Source: GO_Central
  • phosphatidylinositol biosynthetic process Source: Reactome
  • positive regulation of phosphatidylinositol 3-kinase activity Source: UniProtKB
  • protein phosphorylation Source: UniProtKB
  • 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
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS03788-MONOMER.
ZFISH: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

HGNCiHGNC:8982. PIK3R4.

Subcellular locationi

  • Late endosome 1 Publication
  • Cytoplasmic vesicleautophagosome Curated
  • Membrane Curated; Lipid-anchor Curated

  • Note: As component of the PI3K complex I localized to pre-autophagosome structures. As component of the PI3K complex II localized predominantly to endosomes. Localizes also to discrete punctae along the ciliary axoneme (By similarity).By similarityCurated

GO - Cellular componenti

Complete GO annotation...

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.

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

WithEntry#Exp.IntActNotes
NRBF2Q96F248EBI-1046979,EBI-2362014

Protein-protein interaction databases

BioGridi119059. 23 interactors.
DIPiDIP-42310N.
IntActiQ99570. 18 interactors.
MINTiMINT-1631706.
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
Contains 3 HEAT repeats.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 7 WD repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, WD repeat

Phylogenomic databases

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

Family and domain databases

Gene3Di1.25.10.10. 1 hit.
2.130.10.10. 1 hit.
InterProiIPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR021133. HEAT_type_2.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR019775. WD40_repeat_CS.
IPR017986. WD40_repeat_dom.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
PF00400. WD40. 2 hits.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
SM00320. WD40. 6 hits.
[Graphical view]
SUPFAMiSSF48371. SSF48371. 2 hits.
SSF50978. SSF50978. 2 hits.
SSF56112. SSF56112. 2 hits.
PROSITEiPS50077. 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.
[Graphical view]

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 → L.1 PublicationCorresponds to variant rs55951445dbSNPEnsembl.1
Natural variantiVAR_040998342R → H.1 PublicationCorresponds to variant rs56295394dbSNPEnsembl.1
Natural variantiVAR_040999347R → W.1 PublicationCorresponds to variant rs34797184dbSNPEnsembl.1
Natural variantiVAR_041000388T → I.1 PublicationCorresponds to variant rs34663155dbSNPEnsembl.1
Natural variantiVAR_041001393D → N.1 PublicationCorresponds to variant rs34633532dbSNPEnsembl.1
Natural variantiVAR_041002699L → V.1 PublicationCorresponds to variant rs56369596dbSNPEnsembl.1
Natural variantiVAR_035632936R → Q in a breast cancer sample; somatic mutation. 1 PublicationCorresponds to variant rs181132426dbSNPEnsembl.1
Natural variantiVAR_0410031043G → V.1 PublicationCorresponds to variant rs56160735dbSNPEnsembl.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

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ99570.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119059. 23 interactors.
DIPiDIP-42310N.
IntActiQ99570. 18 interactors.
MINTiMINT-1631706.
STRINGi9606.ENSP00000349205.

Chemistry databases

BindingDBiQ99570.
ChEMBLiCHEMBL2189144.

PTM databases

iPTMnetiQ99570.
PhosphoSitePlusiQ99570.

Polymorphism and mutation databases

BioMutaiPIK3R4.
DMDMi74762700.

Proteomic databases

EPDiQ99570.
MaxQBiQ99570.
PaxDbiQ99570.
PeptideAtlasiQ99570.
PRIDEiQ99570.

Protocols and materials databases

DNASUi30849.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi30849.
DisGeNETi30849.
GeneCardsiPIK3R4.
HGNCiHGNC:8982. PIK3R4.
HPAiHPA036032.
HPA036033.
MIMi602610. gene.
neXtProtiNX_Q99570.
OpenTargetsiENSG00000196455.
PharmGKBiPA33315.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciMetaCyc:HS03788-MONOMER.
ZFISH: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.

Miscellaneous databases

ChiTaRSiPIK3R4. human.
GeneWikiiPIK3R4.
GenomeRNAii30849.
PROiQ99570.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000196455.
CleanExiHS_PIK3R4.
ExpressionAtlasiQ99570. baseline and differential.
GenevisibleiQ99570. HS.

Family and domain databases

Gene3Di1.25.10.10. 1 hit.
2.130.10.10. 1 hit.
InterProiIPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR021133. HEAT_type_2.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR019775. WD40_repeat_CS.
IPR017986. WD40_repeat_dom.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
PF00400. WD40. 2 hits.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
SM00320. WD40. 6 hits.
[Graphical view]
SUPFAMiSSF48371. SSF48371. 2 hits.
SSF50978. SSF50978. 2 hits.
SSF56112. SSF56112. 2 hits.
PROSITEiPS50077. 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.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPI3R4_HUMAN
AccessioniPrimary (citable) accession number: Q99570
Secondary accession number(s): Q2TBF4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 6, 2005
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 160 of the entry and version 3 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, 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

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 one 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.