Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Serine/threonine-protein kinase VPS15

Gene

VPS15

Organism
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Serine/threonine-protein kinase required for cytoplasm to vacuole transport (Cvt) and autophagy as a part of the autophagy-specific VPS34 PI3-kinase complex I. This complex is essential to recruit the ATG8-phosphatidylinositol conjugate and the ATG12-ATG5 conjugate to the pre-autophagosomal structure. Is also involved in endosome-to-Golgi retrograde transport as part of the VPS34 PI3-kinase complex II. This second complex is required for the endosome-to-Golgi retrieval of PEP1 and KEX2, and the recruitment of VPS5 and VPS7, two components of the retromer complex, to endosomal membranes (probably through the synthesis of a specific pool of phosphatidylinositol 3-phosphate recruiting the retromer to the endosomes). By regulating VPS34 kinase activity, VPS15 appears to be essential for the efficient delivery of soluble hydrolases to the yeast vacuole.9 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei54 – 541ATPPROSITE-ProRule annotation
Active sitei147 – 1471Proton acceptor

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi33 – 419ATPPROSITE-ProRule annotation

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • protein serine/threonine kinase activity Source: SGD
  • ubiquitin binding Source: SGD

GO - Biological processi

  • inositol lipid-mediated signaling Source: SGD
  • late endosome to vacuole transport Source: SGD
  • macroautophagy Source: SGD
  • pexophagy Source: SGD
  • positive regulation of transcription elongation from RNA polymerase II promoter Source: SGD
  • protein phosphorylation Source: SGD
  • protein retention in Golgi apparatus Source: SGD
  • protein targeting to vacuole Source: SGD
  • vacuole inheritance Source: SGD
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Autophagy, Protein transport, Transport

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciYEAST:G3O-29061-MONOMER.
ReactomeiR-SCE-1632852. Macroautophagy.
R-SCE-1660514. Synthesis of PIPs at the Golgi membrane.
R-SCE-1660516. Synthesis of PIPs at the early endosome membrane.
R-SCE-1660517. Synthesis of PIPs at the late endosome membrane.
R-SCE-5668599. RHO GTPases Activate NADPH Oxidases.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase VPS15 (EC:2.7.11.1)
Alternative name(s):
Golgi-retention defective mutant protein 8
Vacuolar protein sorting-associated protein 15
Gene namesi
Name:VPS15
Synonyms:GRD8, VAC4, VPL19
Ordered Locus Names:YBR097W
ORF Names:YBR0825
OrganismiSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Taxonomic identifieri559292 [NCBI]
Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces
Proteomesi
  • UP000002311 Componenti: Chromosome II

Organism-specific databases

EuPathDBiFungiDB:YBR097W.
SGDiS000000301. VPS15.

Subcellular locationi

GO - Cellular componenti

  • endosome membrane Source: UniProtKB-SubCell
  • Golgi apparatus Source: UniProtKB-SubCell
  • late endosome Source: GO_Central
  • nucleus-vacuole junction Source: SGD
  • phosphatidylinositol 3-kinase complex, class III, type I Source: SGD
  • phosphatidylinositol 3-kinase complex, class III, type II Source: SGD
Complete GO annotation...

Keywords - Cellular componenti

Endosome, Golgi apparatus, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi2 – 21G → A or W: No myristoylation, but still membrane-association and normal activity. 1 Publication
Mutagenesisi54 – 541K → D: Loss of activity. 1 Publication
Mutagenesisi147 – 1471D → R: Loss of activity. 1 Publication
Mutagenesisi149 – 1491K → D: Loss of activity. 1 Publication
Mutagenesisi151 – 1511E → R: Modest effect on activity and normal CPY sorting. 1 Publication
Mutagenesisi165 – 1651D → R: Loss of activity. 1 Publication
Mutagenesisi200 – 2001E → R: Loss of activity. No activation of VPS34 kinase activity. 2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemoved
Chaini2 – 14541453Serine/threonine-protein kinase VPS15PRO_0000086802Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi2 – 21N-myristoyl glycine1 Publication

Post-translational modificationi

Autophosphorylated.

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein

Proteomic databases

MaxQBiP22219.

PTM databases

iPTMnetiP22219.

Interactioni

Subunit structurei

Component of the autophagy-specific VPS34 PI3-kinase complex I composed of VPS15, VPS30, VPS34, ATG14 and ATG38; and of the VPS34 PI3-kinase complex II composed of VPS15, VPS30, VPS34 and VPS38.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
GPA1P085392EBI-20347,EBI-7376

GO - Molecular functioni

  • ubiquitin binding Source: SGD

Protein-protein interaction databases

BioGridi32803. 72 interactions.
DIPiDIP-814N.
IntActiP22219. 8 interactions.
MINTiMINT-637747.

Structurei

Secondary structure

1
1454
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi1034 – 10363Combined sources
Helixi1046 – 10483Combined sources
Helixi1050 – 10523Combined sources
Helixi1064 – 10663Combined sources
Beta strandi1070 – 10756Combined sources
Turni1077 – 10804Combined sources
Beta strandi1083 – 10897Combined sources
Beta strandi1091 – 10933Combined sources
Beta strandi1095 – 11006Combined sources
Beta strandi1103 – 11097Combined sources
Helixi1110 – 11145Combined sources
Beta strandi1122 – 11265Combined sources
Beta strandi1131 – 11366Combined sources
Beta strandi1140 – 11478Combined sources
Beta strandi1150 – 116213Combined sources
Beta strandi1165 – 117814Combined sources
Helixi1179 – 11824Combined sources
Beta strandi1188 – 11958Combined sources
Beta strandi1200 – 12067Combined sources
Beta strandi1209 – 12157Combined sources
Turni1216 – 12183Combined sources
Beta strandi1221 – 12266Combined sources
Helixi1229 – 12313Combined sources
Beta strandi1234 – 12396Combined sources
Beta strandi1245 – 12506Combined sources
Beta strandi1255 – 12595Combined sources
Turni1260 – 12634Combined sources
Beta strandi1264 – 12707Combined sources
Beta strandi1275 – 12828Combined sources
Turni1284 – 12863Combined sources
Beta strandi1290 – 12978Combined sources
Beta strandi1300 – 13067Combined sources
Turni1307 – 13104Combined sources
Beta strandi1311 – 132111Combined sources
Helixi1325 – 13284Combined sources
Helixi1335 – 13373Combined sources
Helixi1346 – 13494Combined sources
Beta strandi1352 – 13554Combined sources
Beta strandi1358 – 13636Combined sources
Helixi1364 – 13663Combined sources
Beta strandi1368 – 13736Combined sources
Helixi1377 – 13793Combined sources
Beta strandi1381 – 13844Combined sources
Beta strandi1392 – 13998Combined sources
Beta strandi1402 – 14087Combined sources
Beta strandi1427 – 144519Combined sources
Beta strandi1450 – 14545Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3GREX-ray1.80A1027-1454[»]
5DFZX-ray4.40B1-1454[»]
ProteinModelPortaliP22219.
SMRiP22219. Positions 10-890, 1031-1454.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP22219.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini27 – 300274Protein kinasePROSITE-ProRule annotationAdd
BLAST
Repeati460 – 49738HEAT 1Add
BLAST
Repeati576 – 61338HEAT 2Add
BLAST
Repeati615 – 65238HEAT 3Add
BLAST
Repeati654 – 69138HEAT 4Add
BLAST
Repeati1078 – 111841WD 1Add
BLAST
Repeati1126 – 116540WD 2Add
BLAST
Repeati1229 – 126840WD 3Add
BLAST
Repeati1275 – 131541WD 4Add
BLAST
Repeati1344 – 138239WD 5Add
BLAST
Repeati1422 – 145332WD 6Add
BLAST

Domaini

Truncation of 30 residues from the C-terminus results in a temperature-conditional defect in protein sorting.

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 6 WD repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, WD repeat

Phylogenomic databases

GeneTreeiENSGT00390000016225.
HOGENOMiHOG000216566.
InParanoidiP22219.
KOiK08333.
OMAiCKALDPN.
OrthoDBiEOG092C1FQ2.

Family and domain databases

Gene3Di1.25.10.10. 2 hits.
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.
IPR017986. WD40_repeat_dom.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
SM00320. WD40. 5 hits.
[Graphical view]
SUPFAMiSSF48371. SSF48371. 2 hits.
SSF50978. SSF50978. 2 hits.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50077. HEAT_REPEAT. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50082. WD_REPEATS_2. 1 hit.
PS50294. WD_REPEATS_REGION. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P22219-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGAQLSLVVQ ASPSIAIFSY IDVLEEVHYV SQLNSSRFLK TCKALDPNGE
60 70 80 90 100
IVIKVFIKPK DQYSLRPFLQ RIRAQSFKLG QLPHVLNYSK LIETNRAGYM
110 120 130 140 150
IRQHLKNNLY DRLSLRPYLQ DIELKFIAFQ LLNALKDIHN LNIVHGDIKT
160 170 180 190 200
ENILVTSWNW CILTDFAAFI KPVYLPEDNP GEFLFYFDTS KRRTCYLAPE
210 220 230 240 250
RFNSKLYQDG KSNNGRLTKE MDIFSLGCVI AEIFAEGRPI FNLSQLFKYK
260 270 280 290 300
SNSYDVNREF LMEEMNSTDL RNLVLDMIQL DPSKRLSCDE LLNKYRGIFF
310 320 330 340 350
PDYFYTFIYD YFRNLVTMTT STPISDNTCT NSTLEDNVKL LDETTEKIYR
360 370 380 390 400
DFSQICHCLD FPLIKDGGEI GSDPPILESY KIEIEISRFL NTNLYFPQNY
410 420 430 440 450
HLVLQQFTKV SEKIKSVKEE CALLFISYLS HSIRSIVSTA TKLKNLELLA
460 470 480 490 500
VFAQFVSDEN KIDRVVPYFV CCFEDSDQDV QALSLLTLIQ VLTSVRKLNQ
510 520 530 540 550
LNENIFVDYL LPRLKRLLIS NRQNTNYLRI VFANCLSDLA IIINRFQEFT
560 570 580 590 600
FAQHCNDNSM DNNTEIMESS TKYSAKLIQS VEDLTVSFLT DNDTYVKMAL
610 620 630 640 650
LQNILPLCKF FGRERTNDII LSHLITYLND KDPALRVSLI QTISGISILL
660 670 680 690 700
GTVTLEQYIL PLLIQTITDS EELVVISVLQ SLKSLFKTGL IRKKYYIDIS
710 720 730 740 750
KTTSPLLLHP NNWIRQFTLM IIIEIINKLS KAEVYCILYP IIRPFFEFDV
760 770 780 790 800
EFNFKSMISC CKQPVSRSVY NLLCSWSVRA SKSLFWKKII TNHVDSFGNN
810 820 830 840 850
RIEFITKNYS SKNYGFNKRD TKSSSSLKGI KTSSTVYSHD NKEIPLTAED
860 870 880 890 900
RNWIDKFHII GLTEKDIWKI VALRGYVIRT ARVMAANPDF PYNNSNYRPL
910 920 930 940 950
VQNSPPNLNL TNIMPRNIFF DVEFAEESTS EGQDSNLENQ QIYKYDESEK
960 970 980 990 1000
DSNKLNINGS KQLSTVMDIN GSLIFKNKSI ATTTSNLKNV FVQLEPTSYH
1010 1020 1030 1040 1050
MHSPNHGLKD NANVKPERKV VVSNSYEGDV ESIEKFLSTF KILPPLRDYK
1060 1070 1080 1090 1100
EFGPIQEIVR SPNMGNLRGK LIATLMENEP NSITSSAVSP GETPYLITGS
1110 1120 1130 1140 1150
DQGVIKIWNL KEIIVGEVYS SSLTYDCSST VTQITMIPNF DAFAVSSKDG
1160 1170 1180 1190 1200
QIIVLKVNHY QQESEVKFLN CECIRKINLK NFGKNEYAVR MRAFVNEEKS
1210 1220 1230 1240 1250
LLVALTNLSR VIIFDIRTLE RLQIIENSPR HGAVSSICID EECCVLILGT
1260 1270 1280 1290 1300
TRGIIDIWDI RFNVLIRSWS FGDHAPITHV EVCQFYGKNS VIVVGGSSKT
1310 1320 1330 1340 1350
FLTIWNFVKG HCQYAFINSD EQPSMEHFLP IEKGLEELNF CGIRSLNALS
1360 1370 1380 1390 1400
TISVSNDKIL LTDEATSSIV MFSLNELSSS KAVISPSRFS DVFIPTQVTA
1410 1420 1430 1440 1450
NLTMLLRKMK RTSTHSVDDS LYHHDIINSI STCEVDETPL LVACDNSGLI

GIFQ
Length:1,454
Mass (Da):166,372
Last modified:July 27, 2011 - v4
Checksum:i247EBA5531E41FFB
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti134 – 1341A → T in CAA55602 (PubMed:7900426).Curated
Sequence conflicti134 – 1341A → T in CAA85050 (PubMed:7813418).Curated
Sequence conflicti443 – 4431L → PV in AAA35214 (PubMed:1988155).Curated
Sequence conflicti610 – 6101F → S in AAA35214 (PubMed:1988155).Curated
Sequence conflicti851 – 8511R → I in AAA35214 (PubMed:1988155).Curated
Sequence conflicti851 – 8511R → I in CAA55602 (PubMed:7900426).Curated
Sequence conflicti851 – 8511R → I in CAA85050 (PubMed:7813418).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M59835 Genomic DNA. Translation: AAA35214.1.
X78993 Genomic DNA. Translation: CAA55602.1.
Z35966 Genomic DNA. Translation: CAA85050.1.
BK006936 Genomic DNA. Translation: DAA07218.2.
PIRiS48264.
RefSeqiNP_009655.2. NM_001178445.2.

Genome annotation databases

EnsemblFungiiYBR097W; YBR097W; YBR097W.
GeneIDi852394.
KEGGisce:YBR097W.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M59835 Genomic DNA. Translation: AAA35214.1.
X78993 Genomic DNA. Translation: CAA55602.1.
Z35966 Genomic DNA. Translation: CAA85050.1.
BK006936 Genomic DNA. Translation: DAA07218.2.
PIRiS48264.
RefSeqiNP_009655.2. NM_001178445.2.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3GREX-ray1.80A1027-1454[»]
5DFZX-ray4.40B1-1454[»]
ProteinModelPortaliP22219.
SMRiP22219. Positions 10-890, 1031-1454.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi32803. 72 interactions.
DIPiDIP-814N.
IntActiP22219. 8 interactions.
MINTiMINT-637747.

PTM databases

iPTMnetiP22219.

Proteomic databases

MaxQBiP22219.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblFungiiYBR097W; YBR097W; YBR097W.
GeneIDi852394.
KEGGisce:YBR097W.

Organism-specific databases

EuPathDBiFungiDB:YBR097W.
SGDiS000000301. VPS15.

Phylogenomic databases

GeneTreeiENSGT00390000016225.
HOGENOMiHOG000216566.
InParanoidiP22219.
KOiK08333.
OMAiCKALDPN.
OrthoDBiEOG092C1FQ2.

Enzyme and pathway databases

BioCyciYEAST:G3O-29061-MONOMER.
ReactomeiR-SCE-1632852. Macroautophagy.
R-SCE-1660514. Synthesis of PIPs at the Golgi membrane.
R-SCE-1660516. Synthesis of PIPs at the early endosome membrane.
R-SCE-1660517. Synthesis of PIPs at the late endosome membrane.
R-SCE-5668599. RHO GTPases Activate NADPH Oxidases.

Miscellaneous databases

EvolutionaryTraceiP22219.
PROiP22219.

Family and domain databases

Gene3Di1.25.10.10. 2 hits.
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.
IPR017986. WD40_repeat_dom.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
SM00320. WD40. 5 hits.
[Graphical view]
SUPFAMiSSF48371. SSF48371. 2 hits.
SSF50978. SSF50978. 2 hits.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50077. HEAT_REPEAT. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50082. WD_REPEATS_2. 1 hit.
PS50294. WD_REPEATS_REGION. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiVPS15_YEAST
AccessioniPrimary (citable) accession number: P22219
Secondary accession number(s): D6VQ98
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: July 27, 2011
Last modified: September 7, 2016
This is version 171 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Miscellaneousi

Miscellaneous

Present with 279 molecules/cell in log phase SD medium.1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Yeast
    Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD
  4. Yeast chromosome II
    Yeast (Saccharomyces cerevisiae) chromosome II: entries and gene names

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.