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Protein

Phosphoinositide 3-kinase regulatory subunit 4

Gene

Pik3r4

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Protein inferred from homologyi

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 (By similarity).By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mn2+By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei53 – 531ATPPROSITE-ProRule annotation
Active sitei148 – 1481Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi32 – 409ATPPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-RNO-109704. PI3K Cascade.
R-RNO-1632852. Macroautophagy.
R-RNO-1660514. Synthesis of PIPs at the Golgi membrane.
R-RNO-1660516. Synthesis of PIPs at the early endosome membrane.
R-RNO-1660517. Synthesis of PIPs at the late endosome membrane.
R-RNO-168138. Toll Like Receptor 9 (TLR9) Cascade.
R-RNO-5668599. RHO GTPases Activate NADPH Oxidases.

Names & Taxonomyi

Protein namesi
Recommended name:
Phosphoinositide 3-kinase regulatory subunit 4 (EC:2.7.11.1)
Short name:
PI3-kinase regulatory subunit 4
Gene namesi
Name:Pik3r4
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 8

Organism-specific databases

RGDi1311809. Pik3r4.

Subcellular locationi

  • Late endosome By similarity
  • Cytoplasmic vesicleautophagosome Curated
  • Membrane By similarity; Lipid-anchor By similarity

  • 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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 13581357Phosphoinositide 3-kinase regulatory subunit 4PRO_0000086527Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi2 – 21N-myristoyl glycineBy similarity
Modified residuei808 – 8081PhosphoserineBy similarity
Modified residuei813 – 8131PhosphoserineBy similarity
Modified residuei853 – 8531PhosphoserineBy similarity
Modified residuei865 – 8651PhosphoserineBy similarity
Modified residuei1316 – 13161PhosphothreonineBy similarity

Post-translational modificationi

Myristoylated.By similarity
Probably autophosphorylated.By similarity

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein

Proteomic databases

PaxDbiP0C0R5.
PRIDEiP0C0R5.

PTM databases

iPTMnetiP0C0R5.
PhosphoSiteiP0C0R5.

Expressioni

Gene expression databases

ExpressionAtlasiP0C0R5. baseline.
GenevisibleiP0C0R5. RN.

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. PI3KC3-C1 displays a V-shaped architecture with PIK3R4 serving as a bridge between PIK3C3 and the ATG14:BECN1 subcomplex. Both, PI3KC3-C1 and PI3KC3-C2, can associate with further regulatory subunits, such as RUBCN, SH3GLB1/Bif-1, AMBRA1 and NRBF2. PI3KC3-C1 probably associates with PIK3CB. Interacts with RAB7A in the presence of PIK3C3/VPS34. Interacts with NRBF2 (By similarity).By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000018654.

Structurei

3D structure databases

ProteinModelPortaliP0C0R5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini26 – 324299Protein kinasePROSITE-ProRule annotationAdd
BLAST
Repeati413 – 45038HEAT 1Add
BLAST
Repeati458 – 49538HEAT 2Add
BLAST
Repeati572 – 61039HEAT 3Add
BLAST
Repeati612 – 64837HEAT 4Add
BLAST
Repeati991 – 103040WD 1Add
BLAST
Repeati1040 – 107940WD 2Add
BLAST
Repeati1093 – 113442WD 3Add
BLAST
Repeati1139 – 117840WD 4Add
BLAST
Repeati1182 – 122342WD 5Add
BLAST
Repeati1237 – 127842WD 6Add
BLAST
Repeati1327 – 135832WD 7Add
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi781 – 7844Poly-Glu
Compositional biasi974 – 9774Poly-Pro

Sequence similaritiesi

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.PROSITE-ProRule annotation
Contains 4 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.
InParanoidiP0C0R5.
OMAiFQDIHHF.
OrthoDBiEOG7HMS08.
PhylomeDBiP0C0R5.
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. 1 hit.
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. 3 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.

P0C0R5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGNQLAGIAP SQILSVESYF SDIHDFEYDK SLGSTRFFKV ARAKHREGLV
60 70 80 90 100
VVKVFAIQDP TLPLTSYKQE LEELKIRLHS AQNCLPFQKA AEKASEKAAM
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 IEDRSIRELV TQMIQREPGQ
310 320 330 340 350
RLEADDYLKQ QRGNAFPEVF YTFLQPYMAQ FAKETFLSAD ERILVIRKDL
360 370 380 390 400
GNIIHNLCGH DLPEKAEGES KASGLVVLVS VITSCLQTLK SCDSKLAALE
410 420 430 440 450
LILHLAPRLS VEILLDRITP YLLHFSNNSV PRVRAEALRT LTKVLALVQE
460 470 480 490 500
VPRNDVNIYP EYILPGIAHL AQDDATIVRL AYAENIALLA ETALRFLELV
510 520 530 540 550
QLKTLNMENE PDSEEVDEAT RPNGDYDTEL QALHEMVQQK VVTLLSDPEN
560 570 580 590 600
IVKQTLMENG ITRLCVFFGR QKANDVLLSH MITFLNDKND WHLRGAFFDS
610 620 630 640 650
IVGVAAYVGW QSSSILKPLL QQGLSDAEEF VIVKALNALT CMCQLGLLQK
660 670 680 690 700
PHVYEFASDI APFLCHPNLW IRYGAVGFIT VVAHQISTAD VYCKLMPYLD
710 720 730 740 750
PYITQPVIQI ERKLVLLSVL KEPVSRSIFD YALRSKDIAS LFRHLHMRQK
760 770 780 790 800
KRNGSLLDCP PPEDPAIAQL LKKLLSQGMT EEEEDKLLAL KDFMMKSNRA
810 820 830 840 850
KANAVDQSHL HDSSQKGVID LAALGITGRQ VDLVKTKQEP DEKRARKHVK
860 870 880 890 900
QDSNVNEEWK SMFGSLEPPN IPQALPKTSD HEVVPTGKSP RSESSAGVCV
910 920 930 940 950
PLSTSPQVSE AAHIPSKKPV IPVVSSTVLP STYQIRITTC KTELQQLIQQ
960 970 980 990 1000
KREQCNAERI AKQMMENAEW ESKPPPPGWR PKGLLVAHLH EHKSAVNRIR
1010 1020 1030 1040 1050
VSDEHLLFAT 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 SSGAMACWDM RFQLPISSHC HPSRARIRRL SMHPLYQSWV
1210 1220 1230 1240 1250
IAAVQGNNEV SMWDMETGDR RLTLWASSAP PLSELQPSPH SVHGIYCSPA
1260 1270 1280 1290 1300
DGNPILLTAG SDMKIRFWDL VSPERSYVVA GSTGSPSVSY YKKIIEGTEV
1310 1320 1330 1340 1350
VQEIQNKQKV GPSDDTPRRG PESLPVGHHD IITDIATFQT TQGFIVTASR

DGIVKVWK
Length:1,358
Mass (Da):152,447
Last modified:January 23, 2007 - v2
Checksum:iDBA44A399F3DC9EE
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR03062590 Genomic DNA. No translation available.
AABR03066737 Genomic DNA. No translation available.
AABR03063719 Genomic DNA. No translation available.
RefSeqiXP_006243862.1. XM_006243800.1.
XP_006243863.1. XM_006243801.2.
UniGeneiRn.8917.

Genome annotation databases

EnsembliENSRNOT00000018654; ENSRNOP00000018654; ENSRNOG00000013669.
ENSRNOT00000090707; ENSRNOP00000070282; ENSRNOG00000013669.
GeneIDi363131.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR03062590 Genomic DNA. No translation available.
AABR03066737 Genomic DNA. No translation available.
AABR03063719 Genomic DNA. No translation available.
RefSeqiXP_006243862.1. XM_006243800.1.
XP_006243863.1. XM_006243801.2.
UniGeneiRn.8917.

3D structure databases

ProteinModelPortaliP0C0R5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000018654.

PTM databases

iPTMnetiP0C0R5.
PhosphoSiteiP0C0R5.

Proteomic databases

PaxDbiP0C0R5.
PRIDEiP0C0R5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000018654; ENSRNOP00000018654; ENSRNOG00000013669.
ENSRNOT00000090707; ENSRNOP00000070282; ENSRNOG00000013669.
GeneIDi363131.

Organism-specific databases

CTDi30849.
RGDi1311809. Pik3r4.

Phylogenomic databases

eggNOGiKOG1240. Eukaryota.
ENOG410XPDN. LUCA.
GeneTreeiENSGT00390000016225.
HOGENOMiHOG000216566.
HOVERGENiHBG079542.
InParanoidiP0C0R5.
OMAiFQDIHHF.
OrthoDBiEOG7HMS08.
PhylomeDBiP0C0R5.
TreeFamiTF102034.

Enzyme and pathway databases

ReactomeiR-RNO-109704. PI3K Cascade.
R-RNO-1632852. Macroautophagy.
R-RNO-1660514. Synthesis of PIPs at the Golgi membrane.
R-RNO-1660516. Synthesis of PIPs at the early endosome membrane.
R-RNO-1660517. Synthesis of PIPs at the late endosome membrane.
R-RNO-168138. Toll Like Receptor 9 (TLR9) Cascade.
R-RNO-5668599. RHO GTPases Activate NADPH Oxidases.

Miscellaneous databases

PROiP0C0R5.

Gene expression databases

ExpressionAtlasiP0C0R5. baseline.
GenevisibleiP0C0R5. RN.

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. 1 hit.
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. 3 hits.
PS50294. WD_REPEATS_REGION. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Genome sequence of the Brown Norway rat yields insights into mammalian evolution."
    Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., Morgan M.
    , Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S., Collins F.S.
    Nature 428:493-521(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].

Entry informationi

Entry nameiPI3R4_RAT
AccessioniPrimary (citable) accession number: P0C0R5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 6, 2005
Last sequence update: January 23, 2007
Last modified: July 6, 2016
This is version 95 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 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.