PI3R4_PONAB
ID PI3R4_PONAB Reviewed; 1358 AA.
AC Q5R9I3;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 103.
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 Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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 -!- FUNCTION: Regulatory subunit of the PI3K complex. May regulate membrane
CC trafficking late in the endocytic pathway (By similarity).
CC {ECO:0000250}.
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; CR859405; CAH91577.1; -; mRNA.
DR RefSeq; NP_001125926.1; NM_001132454.1.
DR AlphaFoldDB; Q5R9I3; -.
DR SMR; Q5R9I3; -.
DR STRING; 9601.ENSPPYP00000015770; -.
DR GeneID; 100172860; -.
DR KEGG; pon:100172860; -.
DR CTD; 30849; -.
DR eggNOG; KOG1240; Eukaryota.
DR InParanoid; Q5R9I3; -.
DR OrthoDB; 1312453at2759; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0005776; C:autophagosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005930; C:axoneme; ISS:UniProtKB.
DR GO; GO:0005770; C:late endosome; ISS:UniProtKB.
DR GO; GO:0035032; C:phosphatidylinositol 3-kinase complex, class III; ISS:UniProtKB.
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; IEA:UniProtKB-KW.
DR GO; GO:0042149; P:cellular response to glucose starvation; ISS:UniProtKB.
DR GO; GO:0045324; P:late endosome to vacuole transport; IEA:InterPro.
DR GO; GO:0016236; P:macroautophagy; IEA:InterPro.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
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; 2.
DR PROSITE; PS50294; WD_REPEATS_REGION; 2.
PE 2: Evidence at transcript level;
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_0000086526"
FT DOMAIN 26..324
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REPEAT 373..411
FT /note="HEAT 1"
FT REPEAT 413..450
FT /note="HEAT 2"
FT REPEAT 458..495
FT /note="HEAT 3"
FT REPEAT 531..570
FT /note="HEAT 4"
FT REPEAT 572..610
FT /note="HEAT 5"
FT REPEAT 612..648
FT /note="HEAT 6"
FT REPEAT 690..726
FT /note="HEAT 7"
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 COMPBIAS 885..899
FT /note="Polar residues"
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; 153183 MW; 4F253B0E39844772 CRC64;
MGNQLAGIAP SQILSVESYF SDIHDFEYDK SLGSTRFFKV ARAKHREGLV VVKVFAIQDP
TLPLTSYKQE LEELKIRLNS AQNCLPFQKA SEKASEKAAM LFRQYVRDNL YDRISTRPFL
NNIENRWIAF QILTAVDQAH KPGVRHGDIK TENVMVTSWN WVLLTDFASF KPTYLPEDNP
ADFNYFFDTS RRRTCYIAPE RFVDGGMFAT ELEYMRDPST PLVDLNSNQR TRGELKRAMD
IFSAGCVIAE LFTEGVPLFD LSQLLAYRNG HFFPEQVLNK IEDHSIRELV TQMIHREPDK
RLEAEDYLKQ QRGNAFPEIF YTFLQPYMAQ FAKETFLSAD ERILVIRKDL GNIIHNLCGH
DLPEKTEEEP KENGLVILVS VITSCLQTLK YYDSKLAALE LILHLAPRLG VEILLDRITP
YLLHFSNDSV PRVRAEALRT LTKVLALVKE VPRNDINIYP EYILPGIAHL AQDDATIVRL
AYAENIALLA ETALRFLELV QLKNLNMEND PNNEEIDEVT HPNGNYDTEL QALHEMVQQK
VVTLLSDPEN IVKQTLMENG ITRLCVFFGR QKANDVLLSH MITFLNDKND WHLRGAFFDS
IVGVAAYVGW QSSSILKPLL QQGLSDAEEF VIVKALYALT CMCQLGLLQK PHVYEFASDI
APFLCHPNLW IRYGAVGFVT VVARQISTAD VYCKLMPYLD PYITQPIIQI ERKLVLLSVL
KEPVSRSIFD YALRSKDITS LFRHLHMRQK KRNGSLPDCP PPEDPAIAQL LKKLLSQGMT
EDEEDKLLAL KDFMMKSNKA KANIVDQSHL HDSSQKGVID LAALGITGRQ VDLVKTKQEP
DDKRARKHVK QDSNVNEEWK SMFGSLDPPN MPQALPKGSD QEVIQTGKPP RSESSAGICV
PLSTSPQVPE VTTIQNKKPV IPVLSSTILP STYQIRITTC KTELQQLIQQ KREQCNAERI
AKQMMENAEW ESKPPPPGWR PKGLLVAHLH EHKSAVNRIR VSDEHSLFAT CSNDGTVKIR
NSQKMEGKTT TTRSILTYSR VGGRVKTLTF CQGSHYLAIA SDNGAVQLLG IEASKLPKSP
KIHPLQSRIL DQKEDGCVVD MHHFNSGAQS VLAYATVNGS LVGWDLRSSS NAWTLKHDLK
SGLITSFAVD IHQCWLCIGT SSGTMACWDM RFQLPISSHC HPSRARIRRL SMHPLYQSWV
IAAVQGNNEV SMWDMETGDR RFTLWASSAP PLSELQPSPH SVHGIYCSPA DGNPILLTAG
SDMKIRFWDL AYPERSYVVA GSTSSPSVSY YRKIIEGTEV VQEIQNKQKV GPSDDTPRRG
PESLPVGHHD IITDVATFQT TQGFIVTASR DGIVKVWK
