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Q8NEB9 (PK3C3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 116. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Phosphatidylinositol 3-kinase catalytic subunit type 3

Short name=PI3-kinase type 3
Short name=PI3K type 3
Short name=PtdIns-3-kinase type 3
EC=2.7.1.137
Alternative name(s):
Phosphatidylinositol 3-kinase p100 subunit
Phosphoinositide-3-kinase class 3
hVps34
Gene names
Name:PIK3C3
Synonyms:VPS34
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length887 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalytic subunit of the PI3K complex that mediates formation of phosphatidylinositol 3-phosphate which plays a key role in initiation and maturation of autophagosomes. Involved in the transport of lysosomal enzyme precursors to lysosomes. Required for the abcission step in cytokinesis. Required for transport from early to late endosomes. Ref.1 Ref.3 Ref.8

Catalytic activity

ATP + 1-phosphatidyl-1D-myo-inositol = ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate.

Cofactor

Manganese. Ref.1

Subunit structure

Heterodimer. This subunit, part of a complex composed of regulatory and catalytic subunits, associates with regulatory subunit PIK3R4. Forms a complex with BECN1, PIK3R4 and either UVRAG and KIAA0226/Rubicon, or with ATG14. In this complex, presence of UVRAG and ATG14 are mutually exclusive. Part of a complex composed of PIK3R4 and PIK3CB By similarity. Interacts with RAB7A in the presence of PIK3R4. Interacts with BECN1P1/BECN2. Ref.1 Ref.3 Ref.5 Ref.7 Ref.10

Subcellular location

Midbody. Late endosome. Note: Localizes also to discrete punctae along the ciliary axoneme and to the base of the ciliary axoneme By similarity. Ref.3 Ref.8

Tissue specificity

Ubiquitously expressed, with a highest expression in skeletal muscle. Ref.1

Sequence similarities

Belongs to the PI3/PI4-kinase family.

Contains 1 C2 PI3K-type domain.

Contains 1 PI3K/PI4K domain.

Contains 1 PIK helical domain.

Ontologies

Keywords
   Biological processAutophagy
Cell cycle
Cell division
   Cellular componentEndosome
   LigandATP-binding
Manganese
Nucleotide-binding
   Molecular functionKinase
Transferase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processautophagic vacuole assembly

Inferred from electronic annotation. Source: Ensembl

cytokinesis

Inferred from mutant phenotype Ref.8. Source: UniProtKB

early endosome to late endosome transport

Inferred from mutant phenotype Ref.3. Source: UniProtKB

endosome organization

Inferred from electronic annotation. Source: Ensembl

innate immune response

Traceable author statement. Source: Reactome

insulin receptor signaling pathway

Traceable author statement. Source: Reactome

phosphatidylinositol biosynthetic process

Traceable author statement. Source: Reactome

phosphatidylinositol-3-phosphate biosynthetic process

Inferred from mutant phenotype Ref.8. Source: GOC

phosphatidylinositol-mediated signaling

Inferred from electronic annotation. Source: Ensembl

phospholipid metabolic process

Traceable author statement. Source: Reactome

protein processing

Inferred from electronic annotation. Source: Ensembl

regulation of protein secretion

Inferred from electronic annotation. Source: Ensembl

response to leucine

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

toll-like receptor 9 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

   Cellular_componentaxoneme

Inferred from sequence or structural similarity. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

late endosome

Inferred from direct assay Ref.3. Source: UniProtKB

midbody

Inferred from direct assay Ref.8. Source: UniProtKB

phosphatidylinositol 3-kinase complex

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Molecular_function1-phosphatidylinositol-3-kinase activity

Inferred from mutant phenotype Ref.8. Source: UniProtKB

ATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction Ref.3PubMed 16417406Ref.7Ref.10PubMed 7504174. Source: UniProtKB

protein kinase activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

BECN1Q1445712EBI-1056470,EBI-949378

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 887887Phosphatidylinositol 3-kinase catalytic subunit type 3
PRO_0000088802

Regions

Domain35 – 184150C2 PI3K-type
Domain283 – 520238PIK helical
Domain631 – 885255PI3K/PI4K

Amino acid modifications

Modified residue2611Phosphoserine Ref.6

Experimental info

Sequence conflict361K → N in CAA87094. Ref.1
Sequence conflict701L → S in CAA87094. Ref.1
Sequence conflict1361F → S in CAA87094. Ref.1
Sequence conflict1581K → N in CAA87094. Ref.1
Sequence conflict2081E → V in CAA87094. Ref.1
Sequence conflict219 – 2202VE → GG in CAA87094. Ref.1
Sequence conflict2621M → L in CAA87094. Ref.1
Sequence conflict272 – 2743KLA → NLP in CAA87094. Ref.1
Sequence conflict289 – 2924NAAT → YPSP in CAA87094. Ref.1
Sequence conflict297 – 2982NI → KN in CAA87094. Ref.1
Sequence conflict305 – 3084TKQL → SKPP in CAA87094. Ref.1
Sequence conflict3181K → E in CAA87094. Ref.1
Sequence conflict3271E → D in CAA87094. Ref.1
Sequence conflict333 – 3386FLKCVN → ILTSVI in CAA87094. Ref.1
Sequence conflict3441E → G in CAA87094. Ref.1
Sequence conflict3501E → A in CAA87094. Ref.1
Sequence conflict3561K → N in CAA87094. Ref.1
Sequence conflict3671L → I in CAA87094. Ref.1
Sequence conflict3971L → S in CAA87094. Ref.1
Sequence conflict4281E → G in CAA87094. Ref.1
Sequence conflict4841C → S in CAA87094. Ref.1
Sequence conflict7501L → V in CAA87094. Ref.1
Sequence conflict8261A → P in CAA87094. Ref.1

Secondary structure

..................................................................................... 887
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q8NEB9 [UniParc].

Last modified October 1, 2002. Version 1.
Checksum: 1C03D97338E44976

FASTA887101,549
        10         20         30         40         50         60 
MGEAEKFHYI YSCDLDINVQ LKIGSLEGKR EQKSYKAVLE DPMLKFSGLY QETCSDLYVT 

        70         80         90        100        110        120 
CQVFAEGKPL ALPVRTSYKA FSTRWNWNEW LKLPVKYPDL PRNAQVALTI WDVYGPGKAV 

       130        140        150        160        170        180 
PVGGTTVSLF GKYGMFRQGM HDLKVWPNVE ADGSEPTKTP GRTSSTLSED QMSRLAKLTK 

       190        200        210        220        230        240 
AHRQGHMVKV DWLDRLTFRE IEMINESEKR SSNFMYLMVE FRCVKCDDKE YGIVYYEKDG 

       250        260        270        280        290        300 
DESSPILTSF ELVKVPDPQM SMENLVESKH HKLARSLRSG PSDHDLKPNA ATRDQLNIIV 

       310        320        330        340        350        360 
SYPPTKQLTY EEQDLVWKFR YYLTNQEKAL TKFLKCVNWD LPQEAKQALE LLGKWKPMDV 

       370        380        390        400        410        420 
EDSLELLSSH YTNPTVRRYA VARLRQADDE DLLMYLLQLV QALKYENFDD IKNGLEPTKK 

       430        440        450        460        470        480 
DSQSSVSENV SNSGINSAEI DSSQIITSPL PSVSSPPPAS KTKEVPDGEN LEQDLCTFLI 

       490        500        510        520        530        540 
SRACKNSTLA NYLYWYVIVE CEDQDTQQRD PKTHEMYLNV MRRFSQALLK GDKSVRVMRS 

       550        560        570        580        590        600 
LLAAQQTFVD RLVHLMKAVQ RESGNRKKKN ERLQALLGDN EKMNLSDVEL IPLPLEPQVK 

       610        620        630        640        650        660 
IRGIIPETAT LFKSALMPAQ LFFKTEDGGK YPVIFKHGDD LRQDQLILQI ISLMDKLLRK 

       670        680        690        700        710        720 
ENLDLKLTPY KVLATSTKHG FMQFIQSVPV AEVLDTEGSI QNFFRKYAPS ENGPNGISAE 

       730        740        750        760        770        780 
VMDTYVKSCA GYCVITYILG VGDRHLDNLL LTKTGKLFHI DFGYILGRDP KPLPPPMKLN 

       790        800        810        820        830        840 
KEMVEGMGGT QSEQYQEFRK QCYTAFLHLR RYSNLILNLF SLMVDANIPD IALEPDKTVK 

       850        860        870        880 
KVQDKFRLDL SDEEAVHYMQ SLIDESVHAL FAAVVEQIHK FAQYWRK 

« Hide

References

« Hide 'large scale' references
[1]"A human phosphatidylinositol 3-kinase complex related to the yeast Vps34p-Vps15p protein sorting system."
Volinia S., Dhand R., Vanhaesebroeck B., MacDougall L.K., Zvelebil M.J., Domin J., Panaretou C., Waterfield M.D.
EMBO J. 14:3339-3348(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, COFACTOR, SUBUNIT, TISSUE SPECIFICITY, INTERACTION WITH PIK3R4.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Testis and Uterus.
[3]"Human VPS34 and p150 are Rab7 interacting partners."
Stein M.P., Feng Y., Cooper K.L., Welford A.M., Wandinger-Ness A.
Traffic 4:754-771(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH RAB7A AND PIK3R4, SUBCELLULAR LOCATION.
[4]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[5]"Identification of Barkor as a mammalian autophagy-specific factor for Beclin 1 and class III phosphatidylinositol 3-kinase."
Sun Q., Fan W., Chen K., Ding X., Chen S., Zhong Q.
Proc. Natl. Acad. Sci. U.S.A. 105:19211-19216(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH BECN1 AND ATG14.
[6]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-261, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]"Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages."
Matsunaga K., Saitoh T., Tabata K., Omori H., Satoh T., Kurotori N., Maejima I., Shirahama-Noda K., Ichimura T., Isobe T., Akira S., Noda T., Yoshimori T.
Nat. Cell Biol. 11:385-396(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH BECN1; KIAA0226; ATG14; PIK3R4 AND UVRAG.
[8]"PtdIns(3)P controls cytokinesis through KIF13A-mediated recruitment of FYVE-CENT to the midbody."
Sagona A.P., Nezis I.P., Pedersen N.M., Liestol K., Poulton J., Rusten T.E., Skotheim R.I., Raiborg C., Stenmark H.
Nat. Cell Biol. 12:362-371(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[9]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"Beclin 2 functions in autophagy, degradation of G protein-coupled receptors, and metabolism."
He C., Wei Y., Sun K., Li B., Dong X., Zou Z., Liu Y., Kinch L.N., Khan S., Sinha S., Xavier R.J., Grishin N.V., Xiao G., Eskelinen E.L., Scherer P.E., Whistler J.L., Levine B.
Cell 154:1085-1099(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH BECN1P1/BECN2.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Z46973 mRNA. Translation: CAA87094.1.
BC033004 mRNA. Translation: AAH33004.1.
BC053651 mRNA. Translation: AAH53651.1.
CCDSCCDS11920.1.
PIRS57219.
RefSeqNP_002638.2. NM_002647.2.
UniGeneHs.464971.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3IHYX-ray2.80A/B/C/D/E282-879[»]
3LS8X-ray2.25A/B268-879[»]
ProteinModelPortalQ8NEB9.
SMRQ8NEB9. Positions 57-147, 230-871.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111307. 26 interactions.
DIPDIP-42272N.
IntActQ8NEB9. 12 interactions.
MINTMINT-1682773.
STRING9606.ENSP00000262039.

Chemistry

BindingDBQ8NEB9.
ChEMBLCHEMBL1075165.

PTM databases

PhosphoSiteQ8NEB9.

Polymorphism databases

DMDM74730233.

Proteomic databases

MaxQBQ8NEB9.
PaxDbQ8NEB9.
PeptideAtlasQ8NEB9.
PRIDEQ8NEB9.

Protocols and materials databases

DNASU5289.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000262039; ENSP00000262039; ENSG00000078142.
GeneID5289.
KEGGhsa:5289.
UCSCuc002lap.3. human.

Organism-specific databases

CTD5289.
GeneCardsGC18P039535.
HGNCHGNC:8974. PIK3C3.
HPAHPA040718.
MIM602609. gene.
neXtProtNX_Q8NEB9.
PharmGKBPA33307.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5032.
HOGENOMHOG000174003.
HOVERGENHBG082145.
KOK00914.
OMAYLMVEFP.
OrthoDBEOG7PP55Z.
PhylomeDBQ8NEB9.
TreeFamTF102032.

Enzyme and pathway databases

BioCycMetaCyc:HS01275-MONOMER.
ReactomeREACT_111102. Signal Transduction.
REACT_111217. Metabolism.
REACT_6900. Immune System.

Gene expression databases

ArrayExpressQ8NEB9.
BgeeQ8NEB9.
CleanExHS_PIK3C3.
GenevestigatorQ8NEB9.

Family and domain databases

Gene3D1.10.1070.11. 1 hit.
1.25.40.70. 2 hits.
2.60.40.150. 1 hit.
InterProIPR016024. ARM-type_fold.
IPR000008. C2_dom.
IPR011009. Kinase-like_dom.
IPR000403. PI3/4_kinase_cat_dom.
IPR018936. PI3/4_kinase_CS.
IPR002420. PI3K_C2_dom.
IPR008290. PI3K_Vps34.
IPR015433. PI_Kinase.
IPR001263. PInositide-3_kin_accessory_dom.
[Graphical view]
PANTHERPTHR10048. PTHR10048. 1 hit.
PfamPF00454. PI3_PI4_kinase. 1 hit.
PF00792. PI3K_C2. 1 hit.
PF00613. PI3Ka. 1 hit.
[Graphical view]
PIRSFPIRSF000587. PI3K_Vps34. 1 hit.
SMARTSM00239. C2. 1 hit.
SM00142. PI3K_C2. 1 hit.
SM00145. PI3Ka. 1 hit.
SM00146. PI3Kc. 1 hit.
[Graphical view]
SUPFAMSSF48371. SSF48371. 2 hits.
SSF49562. SSF49562. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS00915. PI3_4_KINASE_1. 1 hit.
PS00916. PI3_4_KINASE_2. 1 hit.
PS50290. PI3_4_KINASE_3. 1 hit.
PS51547. PI3K_C2. 1 hit.
PS51545. PIK_HELICAL. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPIK3C3. human.
EvolutionaryTraceQ8NEB9.
GeneWikiPIK3C3.
GenomeRNAi5289.
NextBio20438.
PROQ8NEB9.
SOURCESearch...

Entry information

Entry namePK3C3_HUMAN
AccessionPrimary (citable) accession number: Q8NEB9
Secondary accession number(s): Q15134
Entry history
Integrated into UniProtKB/Swiss-Prot: December 6, 2005
Last sequence update: October 1, 2002
Last modified: July 9, 2014
This is version 116 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 18

Human chromosome 18: entries, gene names and cross-references to MIM