PI3R4_RAT
ID PI3R4_RAT Reviewed; 1358 AA.
AC P0C0R5;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=Phosphoinositide 3-kinase regulatory subunit 4;
DE Short=PI3-kinase regulatory subunit 4;
DE EC=2.7.11.1;
GN Name=Pik3r4;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
CC -!- FUNCTION: Regulatory subunit of the PI3K complex that mediates
CC formation of phosphatidylinositol 3-phosphate; different complex forms
CC are believed to play a role in multiple membrane trafficking pathways:
CC PI3KC3-C1 is involved in initiation of autophagosomes and PI3KC3-C2 in
CC maturation of autophagosomes and endocytosis. Involved in regulation of
CC degradative endocytic trafficking and cytokinesis, probably in the
CC context of PI3KC3-C2 (By similarity). {ECO:0000250|UniProtKB:Q99570}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC -!- SUBUNIT: Component of the PI3K (PI3KC3/PI3K-III/class III
CC phosphatidylinositol 3-kinase) complex the core of which is composed of
CC the catalytic subunit PIK3C3, the regulatory subunit PIK3R4 and BECN1
CC associating with additional regulatory/auxilliary subunits to form
CC alternative complex forms. Alternative complex forms containing a forth
CC regulatory subunit in a mutually exclusive manner are PI3K complex I
CC (PI3KC3-C1) containing ATG14, and PI3K complex II (PI3KC3-C2)
CC containing UVRAG. PI3KC3-C1 displays a V-shaped architecture with
CC PIK3R4 serving as a bridge between PIK3C3 and the ATG14:BECN1
CC subcomplex. Both, PI3KC3-C1 and PI3KC3-C2, can associate with further
CC regulatory subunits, such as RUBCN, SH3GLB1/Bif-1, AMBRA1 and NRBF2.
CC PI3KC3-C1 probably associates with PIK3CB. Interacts with RAB7A in the
CC presence of PIK3C3/VPS34. Interacts with NRBF2 (By similarity).
CC {ECO:0000250|UniProtKB:Q8VD65, ECO:0000250|UniProtKB:Q99570}.
CC -!- SUBCELLULAR LOCATION: Late endosome {ECO:0000250}. Cytoplasmic vesicle,
CC autophagosome {ECO:0000305}. Membrane {ECO:0000250|UniProtKB:Q99570};
CC Lipid-anchor {ECO:0000250|UniProtKB:Q99570}. Note=As component of the
CC PI3K complex I localized to pre-autophagosome structures. As component
CC of the PI3K complex II localized predominantly to endosomes. Localizes
CC also to discrete punctae along the ciliary axoneme (By similarity).
CC {ECO:0000250|UniProtKB:Q8VD65, ECO:0000305}.
CC -!- PTM: Myristoylated. {ECO:0000250}.
CC -!- PTM: Probably autophosphorylated. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; AABR03062590; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03066737; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03063719; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_006243862.1; XM_006243800.1.
DR RefSeq; XP_006243863.1; XM_006243801.3.
DR AlphaFoldDB; P0C0R5; -.
DR SMR; P0C0R5; -.
DR STRING; 10116.ENSRNOP00000018654; -.
DR iPTMnet; P0C0R5; -.
DR PhosphoSitePlus; P0C0R5; -.
DR jPOST; P0C0R5; -.
DR PaxDb; P0C0R5; -.
DR PRIDE; P0C0R5; -.
DR Ensembl; ENSRNOT00000018654; ENSRNOP00000018654; ENSRNOG00000013669.
DR GeneID; 363131; -.
DR CTD; 30849; -.
DR RGD; 1311809; Pik3r4.
DR eggNOG; KOG1240; Eukaryota.
DR GeneTree; ENSGT00390000016225; -.
DR InParanoid; P0C0R5; -.
DR OMA; RELILHM; -.
DR OrthoDB; 1312453at2759; -.
DR PhylomeDB; P0C0R5; -.
DR TreeFam; TF102034; -.
DR Reactome; R-RNO-109704; PI3K Cascade.
DR Reactome; R-RNO-1632852; Macroautophagy.
DR Reactome; R-RNO-1660514; Synthesis of PIPs at the Golgi membrane.
DR Reactome; R-RNO-1660516; Synthesis of PIPs at the early endosome membrane.
DR Reactome; R-RNO-1660517; Synthesis of PIPs at the late endosome membrane.
DR Reactome; R-RNO-168138; Toll Like Receptor 9 (TLR9) Cascade.
DR Reactome; R-RNO-5668599; RHO GTPases Activate NADPH Oxidases.
DR PRO; PR:P0C0R5; -.
DR Proteomes; UP000002494; Chromosome 8.
DR Bgee; ENSRNOG00000013669; Expressed in Ammon's horn and 20 other tissues.
DR ExpressionAtlas; P0C0R5; baseline and differential.
DR Genevisible; P0C0R5; RN.
DR GO; GO:0005776; C:autophagosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005930; C:axoneme; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:GOC.
DR GO; GO:0005770; C:late endosome; ISS:UniProtKB.
DR GO; GO:0015630; C:microtubule cytoskeleton; IEA:Ensembl.
DR GO; GO:0071561; C:nucleus-vacuole junction; IBA:GO_Central.
DR GO; GO:0035032; C:phosphatidylinositol 3-kinase complex, class III; ISS:UniProtKB.
DR GO; GO:0034271; C:phosphatidylinositol 3-kinase complex, class III, type I; IBA:GO_Central.
DR GO; GO:0034272; C:phosphatidylinositol 3-kinase complex, class III, type II; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0097352; P:autophagosome maturation; ISO:RGD.
DR GO; GO:0030242; P:autophagy of peroxisome; IBA:GO_Central.
DR GO; GO:0042149; P:cellular response to glucose starvation; ISS:UniProtKB.
DR GO; GO:0045022; P:early endosome to late endosome transport; ISO:RGD.
DR GO; GO:0045324; P:late endosome to vacuole transport; IBA:GO_Central.
DR GO; GO:0016236; P:macroautophagy; IBA:GO_Central.
DR GO; GO:0036092; P:phosphatidylinositol-3-phosphate biosynthetic process; ISO:RGD.
DR GO; GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; ISO:RGD.
DR GO; GO:0006468; P:protein phosphorylation; ISO:RGD.
DR GO; GO:0006623; P:protein targeting to vacuole; IBA:GO_Central.
DR GO; GO:0032801; P:receptor catabolic process; ISO:RGD.
DR GO; GO:0010506; P:regulation of autophagy; ISO:RGD.
DR GO; GO:0032465; P:regulation of cytokinesis; ISO:RGD.
DR GO; GO:0016241; P:regulation of macroautophagy; ISO:RGD.
DR Gene3D; 1.25.10.10; -; 2.
DR Gene3D; 2.130.10.10; -; 2.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR021133; HEAT_type_2.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR045162; Vps15-like.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR PANTHER; PTHR17583; PTHR17583; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00400; WD40; 2.
DR SMART; SM00220; S_TKc; 1.
DR SMART; SM00320; WD40; 6.
DR SUPFAM; SSF48371; SSF48371; 1.
DR SUPFAM; SSF50978; SSF50978; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50077; HEAT_REPEAT; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 2.
DR PROSITE; PS50082; WD_REPEATS_2; 3.
DR PROSITE; PS50294; WD_REPEATS_REGION; 2.
PE 3: Inferred from homology;
KW ATP-binding; Cytoplasmic vesicle; Endosome; Kinase; Lipoprotein; Membrane;
KW Myristate; Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Transferase; WD repeat.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q99570"
FT CHAIN 2..1358
FT /note="Phosphoinositide 3-kinase regulatory subunit 4"
FT /id="PRO_0000086527"
FT DOMAIN 26..324
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REPEAT 413..450
FT /note="HEAT 1"
FT REPEAT 458..495
FT /note="HEAT 2"
FT REPEAT 572..610
FT /note="HEAT 3"
FT REPEAT 612..648
FT /note="HEAT 4"
FT REPEAT 991..1030
FT /note="WD 1"
FT REPEAT 1040..1079
FT /note="WD 2"
FT REPEAT 1093..1134
FT /note="WD 3"
FT REPEAT 1139..1178
FT /note="WD 4"
FT REPEAT 1182..1223
FT /note="WD 5"
FT REPEAT 1237..1278
FT /note="WD 6"
FT REPEAT 1327..1358
FT /note="WD 7"
FT REGION 875..899
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1307..1326
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 148
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 32..40
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 53
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 808
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99570"
FT MOD_RES 813
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99570"
FT MOD_RES 853
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99570"
FT MOD_RES 865
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99570"
FT MOD_RES 1316
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q99570"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000250|UniProtKB:Q99570"
SQ SEQUENCE 1358 AA; 152447 MW; DBA44A399F3DC9EE CRC64;
MGNQLAGIAP SQILSVESYF SDIHDFEYDK SLGSTRFFKV ARAKHREGLV VVKVFAIQDP
TLPLTSYKQE LEELKIRLHS AQNCLPFQKA AEKASEKAAM LFRQYVRDNL YDRISTRPFL
NNIEKRWIAF QILTAVDQAH KSGVRHGDIK TENVMVTSWN WVLLTDFASF KPTYLPEDNP
ADFNYFFDTS RRRTCYIAPE RFVDGGMFAT ELEYMRDPST PLVDLNSNQR TRGELKRAMD
IFSAGCVIAE LFTEGVPLFD LSQLLAYRNG HFFPEQVLNK IEDRSIRELV TQMIQREPGQ
RLEADDYLKQ QRGNAFPEVF YTFLQPYMAQ FAKETFLSAD ERILVIRKDL GNIIHNLCGH
DLPEKAEGES KASGLVVLVS VITSCLQTLK SCDSKLAALE LILHLAPRLS VEILLDRITP
YLLHFSNNSV PRVRAEALRT LTKVLALVQE VPRNDVNIYP EYILPGIAHL AQDDATIVRL
AYAENIALLA ETALRFLELV QLKTLNMENE PDSEEVDEAT RPNGDYDTEL QALHEMVQQK
VVTLLSDPEN IVKQTLMENG ITRLCVFFGR QKANDVLLSH MITFLNDKND WHLRGAFFDS
IVGVAAYVGW QSSSILKPLL QQGLSDAEEF VIVKALNALT CMCQLGLLQK PHVYEFASDI
APFLCHPNLW IRYGAVGFIT VVAHQISTAD VYCKLMPYLD PYITQPVIQI ERKLVLLSVL
KEPVSRSIFD YALRSKDIAS LFRHLHMRQK KRNGSLLDCP PPEDPAIAQL LKKLLSQGMT
EEEEDKLLAL KDFMMKSNRA KANAVDQSHL HDSSQKGVID LAALGITGRQ VDLVKTKQEP
DEKRARKHVK QDSNVNEEWK SMFGSLEPPN IPQALPKTSD HEVVPTGKSP RSESSAGVCV
PLSTSPQVSE AAHIPSKKPV IPVVSSTVLP STYQIRITTC KTELQQLIQQ KREQCNAERI
AKQMMENAEW ESKPPPPGWR PKGLLVAHLH EHKSAVNRIR VSDEHLLFAT CSNDGTVKIW
NSQKMEGKTT TTRSILTYSR IGGRVKTLTF CQGSHYLAIA SDNGAVQLLG IEASKLPKSP
KIHPLQSRIL DQKEDGCVVD MHHFNSGAQS VLAYATVNGS LVGWDLRSSS NAWTLKHDLK
SGLITSFAVD IHQCWLCIGT SSGAMACWDM RFQLPISSHC HPSRARIRRL SMHPLYQSWV
IAAVQGNNEV SMWDMETGDR RLTLWASSAP PLSELQPSPH SVHGIYCSPA DGNPILLTAG
SDMKIRFWDL VSPERSYVVA GSTGSPSVSY YKKIIEGTEV VQEIQNKQKV GPSDDTPRRG
PESLPVGHHD IITDIATFQT TQGFIVTASR DGIVKVWK
