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Protein

Vacuolar protein-sorting-associated protein 36

Gene

VPS36

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

Functioni

Component of the ESCRT-II complex (endosomal sorting complex required for transport II), which is required for multivesicular body (MVB) formation and sorting of endosomal cargo proteins into MVBs. The MVB pathway mediates delivery of transmembrane proteins into the lumen of the lysosome for degradation. The ESCRT-II complex is probably involved in the recruitment of the ESCRT-III complex. Its ability to bind ubiquitin probably plays a role in endosomal sorting of ubiquitinated cargo proteins by ESCRT complexes. The ESCRT-II complex may also play a role in transcription regulation, possibly via its interaction with ELL. Binds phosphoinosides such as PtdIns(3,4,5)P3.

GO - Molecular functioni

  • phosphatidylinositol-3-phosphate binding Source: InterPro
  • protein C-terminus binding Source: UniProtKB
  • ubiquitin binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Protein transport, Transcription, Transcription regulation, Transport

Keywords - Ligandi

Lipid-binding

Enzyme and pathway databases

ReactomeiR-HSA-917729. Endosomal Sorting Complex Required For Transport (ESCRT).

Names & Taxonomyi

Protein namesi
Recommended name:
Vacuolar protein-sorting-associated protein 36
Alternative name(s):
ELL-associated protein of 45 kDa
ESCRT-II complex subunit VPS36
Gene namesi
Name:VPS36
Synonyms:C13orf9, EAP45
ORF Names:CGI-145
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 13

Organism-specific databases

HGNCiHGNC:20312. VPS36.

Subcellular locationi

  • Cytoplasm
  • Endosome
  • Late endosome By similarity
  • Membrane
  • Nucleus Curated

  • Note: Colocalizes with ubiquitinated proteins on late endosomes. Recruited to the endosome membrane to participate in vesicle formation.By similarity

GO - Cellular componenti

  • cytosol Source: UniProtKB
  • endosome Source: UniProtKB
  • ESCRT II complex Source: ParkinsonsUK-UCL
  • extracellular exosome Source: UniProtKB
  • late endosome membrane Source: UniProtKB
  • lysosome Source: Ensembl
  • nucleus Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endosome, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi10L → D: No effect on interaction with ubiquitin. 1 Publication1
Mutagenesisi67V → A: Reduces affinity for ubiquitin up to 10-fold. 1 Publication1
Mutagenesisi68F → A: Reduces affinity for ubiquitin up to 10-fold. 1 Publication1
Mutagenesisi70E → A: Reduces affinity for ubiquitin up to 10-fold. 1 Publication1

Organism-specific databases

DisGeNETi51028.
OpenTargetsiENSG00000136100.
PharmGKBiPA134990943.

Polymorphism and mutation databases

DMDMi73920464.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002152221 – 386Vacuolar protein-sorting-associated protein 36Add BLAST386

Proteomic databases

EPDiQ86VN1.
MaxQBiQ86VN1.
PaxDbiQ86VN1.
PeptideAtlasiQ86VN1.
PRIDEiQ86VN1.

PTM databases

iPTMnetiQ86VN1.
PhosphoSitePlusiQ86VN1.

Expressioni

Gene expression databases

BgeeiENSG00000136100.
CleanExiHS_VPS36.
GenevisibleiQ86VN1. HS.

Organism-specific databases

HPAiHPA039734.
HPA043947.

Interactioni

Subunit structurei

Component of a complex at least composed of ELL, SNF8/EAP30, VPS25/EAP20 and VPS36/EAP45 (By similarity). Component of the endosomal sorting complex required for transport II (ESCRT-II), composed of SNF8, VPS36 and two copies of VPS25 (PubMed:14519844). Interacts with VPS25, SNF8, TSG101 and CHMP6 (PubMed:14505570, PubMed:14519844, PubMed:16973552, PubMed:18539118). Interacts (via GLUE domain) with ubiquitin (PubMed:17057716). Interacts with RILPL1 (via the C-terminal domain); which recruits ESCRT-II to the endosome membranes (PubMed:17010938). Interacts with ECM29 (PubMed:20682791).By similarity7 Publications

GO - Molecular functioni

  • protein C-terminus binding Source: UniProtKB
  • ubiquitin binding Source: UniProtKB

Protein-protein interaction databases

BioGridi119234. 41 interactors.
DIPiDIP-29249N.
IntActiQ86VN1. 4 interactors.
MINTiMINT-3085996.
STRINGi9606.ENSP00000367299.

Structurei

Secondary structure

1386
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi17 – 28Combined sources12
Beta strandi38 – 51Combined sources14
Beta strandi59 – 62Combined sources4
Helixi63 – 65Combined sources3
Beta strandi66 – 72Combined sources7
Beta strandi81 – 86Combined sources6
Beta strandi93 – 95Combined sources3
Beta strandi105 – 110Combined sources6
Helixi115 – 128Combined sources14
Helixi175 – 193Combined sources19
Helixi197 – 199Combined sources3
Helixi215 – 224Combined sources10
Helixi229 – 232Combined sources4
Helixi233 – 235Combined sources3
Helixi240 – 259Combined sources20
Beta strandi262 – 265Combined sources4
Helixi266 – 275Combined sources10
Beta strandi278 – 280Combined sources3
Helixi284 – 292Combined sources9
Turni293 – 298Combined sources6
Beta strandi300 – 305Combined sources6
Beta strandi309 – 315Combined sources7
Helixi320 – 323Combined sources4
Helixi324 – 333Combined sources10
Helixi339 – 346Combined sources8
Helixi350 – 362Combined sources13
Beta strandi365 – 373Combined sources9
Beta strandi375 – 379Combined sources5
Helixi381 – 383Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2HTHX-ray2.70B1-138[»]
2ZMEX-ray2.90B149-386[»]
3CUQX-ray2.61B169-386[»]
ProteinModelPortaliQ86VN1.
SMRiQ86VN1.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ86VN1.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 88GLUE N-terminalPROSITE-ProRule annotationAdd BLAST88
Domaini105 – 138GLUE C-terminalPROSITE-ProRule annotationAdd BLAST34

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili160 – 185Sequence analysisAdd BLAST26

Domaini

The GLUE domain (GRAM-like ubiquitin-binding in EAP45) mediates binding to ubiquitin and phosphoinosides.By similarity

Sequence similaritiesi

Belongs to the VPS36 family.Curated
Contains 1 GLUE C-terminal domain.PROSITE-ProRule annotation
Contains 1 GLUE N-terminal domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG2760. Eukaryota.
ENOG410XR74. LUCA.
GeneTreeiENSGT00390000017209.
HOVERGENiHBG083632.
InParanoidiQ86VN1.
KOiK12190.
OMAiCKMFESL.
OrthoDBiEOG091G09HR.
PhylomeDBiQ86VN1.
TreeFamiTF314770.

Family and domain databases

Gene3Di1.10.10.10. 2 hits.
InterProiIPR007286. EAP30.
IPR021648. GLUE_dom.
IPR011993. PH_dom-like.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF04157. EAP30. 1 hit.
PF11605. Vps36_ESCRT-II. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 2 hits.
SSF50729. SSF50729. 1 hit.
PROSITEiPS51495. GLUE. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q86VN1-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MDRFVWTSGL LEINETLVIQ QRGVRIYDGE EKIKFDAGTL LLSTHRLIWR
60 70 80 90 100
DQKNHECCMA ILLSQIVFIE EQAAGIGKSA KIVVHLHPAP PNKEPGPFQS
110 120 130 140 150
SKNSYIKLSF KEHGQIEFYR RLSEEMTQRR WENMPVSQSL QTNRGPQPGR
160 170 180 190 200
IRAVGIVGIE RKLEEKRKET DKNISEAFED LSKLMIKAKE MVELSKSIAN
210 220 230 240 250
KIKDKQGDIT EDETIRFKSY LLSMGIANPV TRETYGSGTQ YHMQLAKQLA
260 270 280 290 300
GILQVPLEER GGIMSLTEVY CLVNRARGME LLSPEDLVNA CKMLEALKLP
310 320 330 340 350
LRLRVFDSGV MVIELQSHKE EEMVASALET VSEKGSLTSE EFAKLVGMSV
360 370 380
LLAKERLLLA EKMGHLCRDD SVEGLRFYPN LFMTQS
Length:386
Mass (Da):43,817
Last modified:June 1, 2003 - v1
Checksum:i21E1E66F71BA7764
GO
Isoform 2 (identifier: Q86VN1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-58: Missing.

Note: No experimental confirmation available.
Show »
Length:328
Mass (Da):36,958
Checksum:iF6078BBD25CC0032
GO

Sequence cautioni

The sequence BAB14451 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti185M → V in CAI45953 (PubMed:17974005).Curated1
Sequence conflicti223S → R in AAD34140 (PubMed:10810093).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0153421 – 58Missing in isoform 2. 1 PublicationAdd BLAST58

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF151903 mRNA. Translation: AAD34140.1.
AK023182 mRNA. Translation: BAB14451.1. Different initiation.
AK289740 mRNA. Translation: BAF82429.1.
CR933653 mRNA. Translation: CAI45953.1.
AL359513 Genomic DNA. Translation: CAH71658.1.
CH471274 Genomic DNA. Translation: EAW55895.1.
BC037279 mRNA. Translation: AAH37279.1.
BC050439 mRNA. Translation: AAH50439.1.
CCDSiCCDS73577.1. [Q86VN1-2]
CCDS9434.1. [Q86VN1-1]
RefSeqiNP_001269098.1. NM_001282169.1. [Q86VN1-2]
NP_057159.2. NM_016075.3. [Q86VN1-1]
UniGeneiHs.109520.

Genome annotation databases

EnsembliENST00000378060; ENSP00000367299; ENSG00000136100. [Q86VN1-1]
ENST00000611132; ENSP00000484968; ENSG00000136100. [Q86VN1-2]
GeneIDi51028.
KEGGihsa:51028.
UCSCiuc001vgq.4. human. [Q86VN1-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF151903 mRNA. Translation: AAD34140.1.
AK023182 mRNA. Translation: BAB14451.1. Different initiation.
AK289740 mRNA. Translation: BAF82429.1.
CR933653 mRNA. Translation: CAI45953.1.
AL359513 Genomic DNA. Translation: CAH71658.1.
CH471274 Genomic DNA. Translation: EAW55895.1.
BC037279 mRNA. Translation: AAH37279.1.
BC050439 mRNA. Translation: AAH50439.1.
CCDSiCCDS73577.1. [Q86VN1-2]
CCDS9434.1. [Q86VN1-1]
RefSeqiNP_001269098.1. NM_001282169.1. [Q86VN1-2]
NP_057159.2. NM_016075.3. [Q86VN1-1]
UniGeneiHs.109520.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2HTHX-ray2.70B1-138[»]
2ZMEX-ray2.90B149-386[»]
3CUQX-ray2.61B169-386[»]
ProteinModelPortaliQ86VN1.
SMRiQ86VN1.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119234. 41 interactors.
DIPiDIP-29249N.
IntActiQ86VN1. 4 interactors.
MINTiMINT-3085996.
STRINGi9606.ENSP00000367299.

PTM databases

iPTMnetiQ86VN1.
PhosphoSitePlusiQ86VN1.

Polymorphism and mutation databases

DMDMi73920464.

Proteomic databases

EPDiQ86VN1.
MaxQBiQ86VN1.
PaxDbiQ86VN1.
PeptideAtlasiQ86VN1.
PRIDEiQ86VN1.

Protocols and materials databases

DNASUi51028.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000378060; ENSP00000367299; ENSG00000136100. [Q86VN1-1]
ENST00000611132; ENSP00000484968; ENSG00000136100. [Q86VN1-2]
GeneIDi51028.
KEGGihsa:51028.
UCSCiuc001vgq.4. human. [Q86VN1-1]

Organism-specific databases

CTDi51028.
DisGeNETi51028.
GeneCardsiVPS36.
HGNCiHGNC:20312. VPS36.
HPAiHPA039734.
HPA043947.
MIMi610903. gene.
neXtProtiNX_Q86VN1.
OpenTargetsiENSG00000136100.
PharmGKBiPA134990943.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2760. Eukaryota.
ENOG410XR74. LUCA.
GeneTreeiENSGT00390000017209.
HOVERGENiHBG083632.
InParanoidiQ86VN1.
KOiK12190.
OMAiCKMFESL.
OrthoDBiEOG091G09HR.
PhylomeDBiQ86VN1.
TreeFamiTF314770.

Enzyme and pathway databases

ReactomeiR-HSA-917729. Endosomal Sorting Complex Required For Transport (ESCRT).

Miscellaneous databases

ChiTaRSiVPS36. human.
EvolutionaryTraceiQ86VN1.
GeneWikiiVPS36.
GenomeRNAii51028.
PROiQ86VN1.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000136100.
CleanExiHS_VPS36.
GenevisibleiQ86VN1. HS.

Family and domain databases

Gene3Di1.10.10.10. 2 hits.
InterProiIPR007286. EAP30.
IPR021648. GLUE_dom.
IPR011993. PH_dom-like.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF04157. EAP30. 1 hit.
PF11605. Vps36_ESCRT-II. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 2 hits.
SSF50729. SSF50729. 1 hit.
PROSITEiPS51495. GLUE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiVPS36_HUMAN
AccessioniPrimary (citable) accession number: Q86VN1
Secondary accession number(s): A8K125
, Q3ZCV7, Q5H9S1, Q5VXB6, Q9H8Z5, Q9Y3E3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 30, 2005
Last sequence update: June 1, 2003
Last modified: November 2, 2016
This is version 135 of the entry and version 1 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 13
    Human chromosome 13: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.