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Protein

Vacuolar protein sorting-associated protein 18 homolog

Gene

VPS18

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport and autophagic pathways. Believed to act as a core component of the putative HOPS and CORVET endosomal tethering complexes which are proposed to be involved in the Rab5-to-Rab7 endosome conversion probably implicating MON1A/B, and via binding SNAREs and SNARE complexes to mediate tethering and docking events during SNARE-mediated membrane fusion. The HOPS complex is proposed to be recruited to Rab7 on the late endosomal membrane and to regulate late endocytic, phagocytic and autophagic traffic towards lysosomes. The CORVET complex is proposed to function as a Rab5 effector to mediate early endosome fusion probably in specific endosome subpopulations (PubMed:11382755, PubMed:23351085, PubMed:24554770, PubMed:25783203). Required for fusion of endosomes and autophagosomes with lysosomes (PubMed:25783203). Involved in dendrite development of Pukinje cells (By similarity).By similarity3 Publications1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri853 – 947RING-typeAdd BLAST95

GO - Molecular functioni

  • metal ion binding Source: UniProtKB-KW
  • protein binding, bridging Source: GO_Central
  • syntaxin binding Source: UniProtKB

GO - Biological processi

  • autophagy Source: UniProtKB-KW
  • endosome organization Source: UniProtKB
  • endosome to lysosome transport Source: UniProtKB
  • intracellular protein transport Source: InterPro
  • lysosome organization Source: UniProtKB
  • regulation of SNARE complex assembly Source: GO_Central
  • vesicle docking involved in exocytosis Source: GO_Central
  • viral entry into host cell Source: Ensembl
Complete GO annotation...

Keywords - Biological processi

Autophagy, Protein transport, Transport

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000104142-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
Vacuolar protein sorting-associated protein 18 homolog
Short name:
hVPS18
Gene namesi
Name:VPS18
Synonyms:KIAA1475
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

HGNCiHGNC:15972. VPS18.

Subcellular locationi

GO - Cellular componenti

  • actin filament Source: Ensembl
  • AP-3 adaptor complex Source: Ensembl
  • autophagosome Source: UniProtKB-SubCell
  • clathrin-coated vesicle Source: UniProtKB-SubCell
  • CORVET complex Source: Ensembl
  • early endosome Source: UniProtKB-SubCell
  • HOPS complex Source: UniProtKB
  • late endosome Source: UniProtKB
  • late endosome membrane Source: UniProtKB-SubCell
  • lysosomal membrane Source: UniProtKB
  • lysosome Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasmic vesicle, Endosome, Lysosome, Membrane

Pathology & Biotechi

Organism-specific databases

OpenTargetsiENSG00000104142.
PharmGKBiPA38069.

Polymorphism and mutation databases

BioMutaiVPS18.
DMDMi23396938.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000559062 – 973Vacuolar protein sorting-associated protein 18 homologAdd BLAST972

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei3PhosphoserineCombined sources1
Modified residuei11PhosphoserineCombined sources1
Modified residuei13PhosphoserineCombined sources1
Modified residuei362N6-acetyllysineCombined sources1
Modified residuei689PhosphoserineCombined sources1
Modified residuei912PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9P253.
MaxQBiQ9P253.
PaxDbiQ9P253.
PeptideAtlasiQ9P253.
PRIDEiQ9P253.

PTM databases

iPTMnetiQ9P253.
PhosphoSitePlusiQ9P253.

Expressioni

Tissue specificityi

Ubiquitous. Expression was highest in heart and low in lung.1 Publication

Gene expression databases

BgeeiENSG00000104142.
CleanExiHS_VPS18.
ExpressionAtlasiQ9P253. baseline and differential.
GenevisibleiQ9P253. HS.

Organism-specific databases

HPAiHPA040701.

Interactioni

Subunit structurei

Core component of at least two putative endosomal tethering complexes, the homotypic fusion and vacuole protein sorting (HOPS) complex and the class C core vacuaole/endosome tethering (CORVET) complex. Their common core is composed of the class C Vps proteins VPS11, VPS16, VPS18 and VPS33A, which in HOPS further associates with VPS39 and VPS41 and in CORVET with VPS8 and TGFBRAP1 (PubMed:23351085, PubMed:25783203, PubMed:23901104). Interacts with RAB5C (By similarity). Interacts with HOOK1 (By similarity). Interacts with STX7, MON1B (PubMed:20434987, PubMed:24554770). Associates with adaptor protein complex 3 (AP-3) and clathrin:AP-3 complexes Associates with adaptor protein complex 3 (AP-3) and clathrin:AP-3 complexes (By similarity).By similarity1 Publication5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
MON1BQ7L1V22EBI-1053363,EBI-2655311
STX7O154002EBI-1053363,EBI-3221827
VPS11Q9H2708EBI-1053363,EBI-373380
VPS16Q9H26915EBI-1053363,EBI-2655929
VPS33AQ96AX16EBI-1053363,EBI-2527283
Vps33aQ636152EBI-1053363,EBI-918669From a different organism.
VPS41P497543EBI-1053363,EBI-2130459

GO - Molecular functioni

  • protein binding, bridging Source: GO_Central
  • syntaxin binding Source: UniProtKB

Protein-protein interaction databases

BioGridi121664. 54 interactors.
IntActiQ9P253. 36 interactors.
STRINGi9606.ENSP00000220509.

Structurei

3D structure databases

ProteinModelPortaliQ9P253.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati618 – 772CHCRAdd BLAST155

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili454 – 481Sequence analysisAdd BLAST28
Coiled coili802 – 848Sequence analysisAdd BLAST47

Sequence similaritiesi

Belongs to the VPS18 family.Curated
Contains 1 CHCR (clathrin heavy-chain) repeat.PROSITE-ProRule annotation
Contains 1 RING-type zinc finger.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri853 – 947RING-typeAdd BLAST95

Keywords - Domaini

Coiled coil, Zinc-finger

Phylogenomic databases

eggNOGiKOG2034. Eukaryota.
ENOG410XRSD. LUCA.
GeneTreeiENSGT00390000015233.
HOGENOMiHOG000172497.
HOVERGENiHBG057876.
InParanoidiQ9P253.
KOiK20181.
OMAiHIYTSMG.
OrthoDBiEOG091G01XI.
PhylomeDBiQ9P253.
TreeFamiTF105704.

Family and domain databases

InterProiIPR000547. Clathrin_H-chain/VPS_repeat.
IPR007810. Pep3_Vps18.
[Graphical view]
PfamiPF00637. Clathrin. 1 hit.
PF05131. Pep3_Vps18. 1 hit.
[Graphical view]
PROSITEiPS50236. CHCR. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q9P253-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASILDEYEN SLSRSAVLQP GCPSVGIPHS GYVNAQLEKE VPIFTKQRID
60 70 80 90 100
FTPSERITSL VVSSNQLCMS LGKDTLLRID LGKANEPNHV ELGRKDDAKV
110 120 130 140 150
HKMFLDHTGS HLLIALSSTE VLYVNRNGQK VRPLARWKGQ LVESVGWNKA
160 170 180 190 200
LGTESSTGPI LVGTAQGHIF EAELSASEGG LFGPAPDLYF RPLYVLNEEG
210 220 230 240 250
GPAPVCSLEA ERGPDGRSFV IATTRQRLFQ FIGRAAEGAE AQGFSGLFAA
260 270 280 290 300
YTDHPPPFRE FPSNLGYSEL AFYTPKLRSA PRAFAWMMGD GVLYGALDCG
310 320 330 340 350
RPDSLLSEER VWEYPEGVGP GASPPLAIVL TQFHFLLLLA DRVEAVCTLT
360 370 380 390 400
GQVVLRDHFL EKFGPLKHMV KDSSTGQLWA YTERAVFRYH VQREARDVWR
410 420 430 440 450
TYLDMNRFDL AKEYCRERPD CLDTVLAREA DFCFRQRRYL ESARCYALTQ
460 470 480 490 500
SYFEEIALKF LEARQEEALA EFLQRKLASL KPAERTQATL LTTWLTELYL
510 520 530 540 550
SRLGALQGDP EALTLYRETK ECFRTFLSSP RHKEWLFASR ASIHELLASH
560 570 580 590 600
GDTEHMVYFA VIMQDYERVV AYHCQHEAYE EALAVLARHR DPQLFYKFSP
610 620 630 640 650
ILIRHIPRQL VDAWIEMGSR LDARQLIPAL VNYSQGGEVQ QVSQAIRYME
660 670 680 690 700
FCVNVLGETE QAIHNYLLSL YARGRPDSLL AYLEQAGASP HRVHYDLKYA
710 720 730 740 750
LRLCAEHGHH RACVHVYKVL ELYEEAVDLA LQVDVDLAKQ CADLPEEDEE
760 770 780 790 800
LRKKLWLKIA RHVVQEEEDV QTAMACLASC PLLKIEDVLP FFPDFVTIDH
810 820 830 840 850
FKEAICSSLK AYNHHIQELQ REMEEATASA QRIRRDLQEL RGRYGTVEPQ
860 870 880 890 900
DKCATCDFPL LNRPFYLFLC GHMFHADCLL QAVRPGLPAY KQARLEELQR
910 920 930 940 950
KLGAAPPPAK GSARAKEAEG GAATAGPSRE QLKADLDELV AAECVYCGEL
960 970
MIRSIDRPFI DPQRYEEEQL SWL
Length:973
Mass (Da):110,186
Last modified:September 19, 2002 - v2
Checksum:i0008E21D66E8CFEC
GO

Sequence cautioni

The sequence AAH01513 differs from that shown. Unlikely isoform. Aberrant splice sites.Curated
The sequence BAA95999 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_035950913A → S in a colorectal cancer sample; somatic mutation. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF308802 mRNA. Translation: AAG34679.1.
AB040908 mRNA. Translation: BAA95999.1. Different initiation.
AL713725 mRNA. Translation: CAD28515.1.
BC001513 mRNA. Translation: AAH01513.1. Sequence problems.
CCDSiCCDS10069.1.
RefSeqiNP_065908.1. NM_020857.2.
UniGeneiHs.23876.

Genome annotation databases

EnsembliENST00000220509; ENSP00000220509; ENSG00000104142.
GeneIDi57617.
KEGGihsa:57617.
UCSCiuc001zne.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF308802 mRNA. Translation: AAG34679.1.
AB040908 mRNA. Translation: BAA95999.1. Different initiation.
AL713725 mRNA. Translation: CAD28515.1.
BC001513 mRNA. Translation: AAH01513.1. Sequence problems.
CCDSiCCDS10069.1.
RefSeqiNP_065908.1. NM_020857.2.
UniGeneiHs.23876.

3D structure databases

ProteinModelPortaliQ9P253.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121664. 54 interactors.
IntActiQ9P253. 36 interactors.
STRINGi9606.ENSP00000220509.

PTM databases

iPTMnetiQ9P253.
PhosphoSitePlusiQ9P253.

Polymorphism and mutation databases

BioMutaiVPS18.
DMDMi23396938.

Proteomic databases

EPDiQ9P253.
MaxQBiQ9P253.
PaxDbiQ9P253.
PeptideAtlasiQ9P253.
PRIDEiQ9P253.

Protocols and materials databases

DNASUi57617.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000220509; ENSP00000220509; ENSG00000104142.
GeneIDi57617.
KEGGihsa:57617.
UCSCiuc001zne.3. human.

Organism-specific databases

CTDi57617.
GeneCardsiVPS18.
HGNCiHGNC:15972. VPS18.
HPAiHPA040701.
MIMi608551. gene.
neXtProtiNX_Q9P253.
OpenTargetsiENSG00000104142.
PharmGKBiPA38069.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2034. Eukaryota.
ENOG410XRSD. LUCA.
GeneTreeiENSGT00390000015233.
HOGENOMiHOG000172497.
HOVERGENiHBG057876.
InParanoidiQ9P253.
KOiK20181.
OMAiHIYTSMG.
OrthoDBiEOG091G01XI.
PhylomeDBiQ9P253.
TreeFamiTF105704.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000104142-MONOMER.

Miscellaneous databases

ChiTaRSiVPS18. human.
GeneWikiiVPS18.
GenomeRNAii57617.
PROiQ9P253.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000104142.
CleanExiHS_VPS18.
ExpressionAtlasiQ9P253. baseline and differential.
GenevisibleiQ9P253. HS.

Family and domain databases

InterProiIPR000547. Clathrin_H-chain/VPS_repeat.
IPR007810. Pep3_Vps18.
[Graphical view]
PfamiPF00637. Clathrin. 1 hit.
PF05131. Pep3_Vps18. 1 hit.
[Graphical view]
PROSITEiPS50236. CHCR. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiVPS18_HUMAN
AccessioniPrimary (citable) accession number: Q9P253
Secondary accession number(s): Q8TCG0, Q96DI3, Q9H268
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 19, 2002
Last sequence update: September 19, 2002
Last modified: November 30, 2016
This is version 144 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

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.