Q8NEB9 (PK3C3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	887 AA.
Sequence status	Complete.
Protein existence	Evidence 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. Ref.1 Ref.3 Ref.5 Ref.7
Subcellular location	Midbody. Late endosome 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 process	Autophagy Cell cycle Cell division
Cellular component	Endosome
Ligand	ATP-binding Manganese Nucleotide-binding
Molecular function	Kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	autophagic vacuole assembly Inferred from electronic annotation. Source: Compara cell cycle Inferred from electronic annotation. Source: UniProtKB-KW 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: Compara innate immune response Traceable author statement. Source: Reactome insulin receptor signaling pathway Traceable author statement. Source: Reactome phosphatidylinositol-mediated signaling Inferred from electronic annotation. Source: Compara protein processing Inferred from electronic annotation. Source: Compara regulation of protein secretion Inferred from electronic annotation. Source: Compara response to leucine Inferred from electronic annotation. Source: Compara small molecule metabolic process Traceable author statement. Source: Reactome
Cellular_component	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_function	1-phosphatidylinositol-3-kinase activity Inferred from mutant phenotype Ref.8. Source: UniProtKB ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein kinase activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BECN1	Q14457	6	EBI-1056470,EBI-949378

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 887

887

Phosphatidylinositol 3-kinase catalytic subunit type 3

PRO_0000088802

Regions

Domain

35 – 184

150

C2 PI3K-type

Domain

283 – 520

238

PIK helical

Domain

631 – 885

255

PI3K/PI4K

Amino acid modifications

Modified residue

261

1

Phosphoserine Ref.6

Modified residue

525

1

Phosphoserine By similarity

Experimental info

Sequence conflict

36

1

K → N in CAA87094. Ref.1

Sequence conflict

70

1

L → S in CAA87094. Ref.1

Sequence conflict

136

1

F → S in CAA87094. Ref.1

Sequence conflict

158

1

K → N in CAA87094. Ref.1

Sequence conflict

208

1

E → V in CAA87094. Ref.1

Sequence conflict

219 – 220

2

VE → GG in CAA87094. Ref.1

Sequence conflict

262

1

M → L in CAA87094. Ref.1

Sequence conflict

272 – 274

3

KLA → NLP in CAA87094. Ref.1

Sequence conflict

289 – 292

4

NAAT → YPSP in CAA87094. Ref.1

Sequence conflict

297 – 298

2

NI → KN in CAA87094. Ref.1

Sequence conflict

305 – 308

4

TKQL → SKPP in CAA87094. Ref.1

Sequence conflict

318

1

K → E in CAA87094. Ref.1

Sequence conflict

327

1

E → D in CAA87094. Ref.1

Sequence conflict

333 – 338

6

FLKCVN → ILTSVI in CAA87094. Ref.1

Sequence conflict

344

1

E → G in CAA87094. Ref.1

Sequence conflict

350

1

E → A in CAA87094. Ref.1

Sequence conflict

356

1

K → N in CAA87094. Ref.1

Sequence conflict

367

1

L → I in CAA87094. Ref.1

Sequence conflict

397

1

L → S in CAA87094. Ref.1

Sequence conflict

428

1

E → G in CAA87094. Ref.1

Sequence conflict

484

1

C → S in CAA87094. Ref.1

Sequence conflict

750

1

L → V in CAA87094. Ref.1

Sequence conflict

826

1

A → P in CAA87094. Ref.1

Secondary structure

1

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887

Helix Strand Turn

Details...

Helix

283 – 285

3

Helix

290 – 301

12

Helix

310 – 318

9

Helix

320 – 323

4

Helix

327 – 329

3

Helix

330 – 334

5

Helix

342 – 354

13

Helix

360 – 363

4

Helix

364 – 367

4

Helix

374 – 384

11

Helix

389 – 394

6

Helix

396 – 402

7

Helix

403 – 405

3

Helix

408 – 413

6

Helix

442 – 444

3

Helix

475 – 484

10

Helix

487 – 502

16

Helix

504 – 509

6

Helix

511 – 530

20

Helix

533 – 561

29

Helix

566 – 578

13

Helix

580 – 583

4

Beta strand

589 – 593

5

Beta strand

596 – 604

9

Helix

606 – 608

3

Beta strand

619 – 625

7

Beta strand

630 – 639

10

Helix

642 – 660

19

Beta strand

672 – 683

12

Helix

690 – 696

7

Helix

700 – 707

8

Helix

714 – 716

3

Helix

719 – 739

21

Beta strand

748 – 751

4

Beta strand

757 – 759

3

Beta strand

770 – 773

4

Helix

781 – 786

6

Helix

793 – 811

19

Helix

813 – 821

9

Turn

822 – 825

4

Helix

829 – 832

4

Helix

835 – 837

3

Helix

838 – 845

8

Turn

846 – 849

4

Helix

852 – 870

19

Sequences

	Sequence		Length	Mass (Da)
	Q8NEB9 [UniParc]. Last modified October 1, 2002. Version 1. Checksum: 1C03D97338E44976	FASTA	887	101,549
	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

References

	« Hide 'large scale' referencesShow '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, MASS SPECTROMETRY.
[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].
+	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.

IPI

IPI00299755.

PIR

S57219.

RefSeq

NP_002638.2. NM_002647.2.

UniGene

Hs.464971.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3IHY	X-ray	2.80	A/B/C/D/E	282-879	[»]
3LS8	X-ray	2.25	A/B	268-879	[»]

ProteinModelPortal

Q8NEB9.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-42272N.

IntAct

Q8NEB9. 9 interactions.

MINT

MINT-1682773.

STRING

9606.ENSP00000262039.

PTM databases

PhosphoSite

Q8NEB9.

Polymorphism databases

DMDM

74730233.

Proteomic databases

PaxDb

Q8NEB9.

PeptideAtlas

Q8NEB9.

PRIDE

Q8NEB9.

Protocols and materials databases

DNASU

5289.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000262039; ENSP00000262039; ENSG00000078142.

GeneID

5289.

KEGG

hsa:5289.

UCSC

uc002lap.3. human.

Organism-specific databases

CTD

5289.

GeneCards

GC18P039535.

HGNC

HGNC:8974. PIK3C3.

HPA

HPA040718.

MIM

602609. gene.

neXtProt

NX_Q8NEB9.

PharmGKB

PA33307.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5032.

HOGENOM

HOG000174003.

HOVERGEN

HBG082145.

KO

K00914.

OMA

YLMVEFP.

OrthoDB

EOG46T30T.

PhylomeDB

Q8NEB9.

Enzyme and pathway databases

BioCyc

MetaCyc:HS01275-MONOMER.

Reactome

REACT_111102. Signal Transduction.
REACT_111217. Metabolism.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

Q8NEB9.

Bgee

Q8NEB9.

CleanEx

HS_PIK3C3.

Genevestigator

Q8NEB9.

GermOnline

ENSG00000078142. Homo sapiens.

Family and domain databases

Gene3D

1.10.1070.11. 1 hit.
1.25.40.70. 2 hits.

InterPro

IPR016024. ARM-type_fold.
IPR000008. C2_Ca-dep.
IPR008973. C2_Ca/lipid-bd_dom_CaLB.
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]

PANTHER

PTHR10048. PTHR10048. 1 hit.

Pfam

PF00454. PI3_PI4_kinase. 1 hit.
PF00792. PI3K_C2. 1 hit.
PF00613. PI3Ka. 1 hit.
[Graphical view]

PIRSF

PIRSF000587. PI3K_Vps34. 1 hit.

SMART

SM00239. C2. 1 hit.
SM00142. PI3K_C2. 1 hit.
SM00145. PI3Ka. 1 hit.
SM00146. PI3Kc. 1 hit.
[Graphical view]

SUPFAM

SSF48371. ARM-type_fold. 1 hit.
SSF49562. C2_CaLB. 1 hit.
SSF56112. Kinase_like. 1 hit.

PROSITE

PS00915. 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]

ProtoNet

Search...

Other

BindingDB

Q8NEB9.

ChEMBL

CHEMBL1075165.

ChiTaRS

PIK3C3. human.

EvolutionaryTrace

Q8NEB9.

GenomeRNAi

5289.

NextBio

20438.

SOURCE

Search...

Entry information

Entry name

PK3C3_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 103 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.