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Protein

Vacuolar protein sorting-associated protein 16 homolog

Gene

VPS16

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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:25266290, PubMed:25783203). Required for recruitment of VPS33A to the HOPS complex (PubMed:23901104). Required for fusion of endosomes and autophagosomes with lysosomes; the function is dependent on its association with VPS33A but not VPS33B (PubMed:25783203). The function in autophagosome-lysosome fusion implicates STX17 but not UVRAG (PubMed:24554770).4 Publications3 Publications

GO - Molecular functioni

GO - Biological processi

  • autophagosome maturation Source: UniProtKB
  • endosome to lysosome transport Source: UniProtKB
  • intracellular protein transport Source: InterPro
  • regulation of SNARE complex assembly Source: GO_Central
  • regulation of vacuole fusion, non-autophagic Source: GO_Central
  • vacuole organization Source: InterPro

Keywordsi

Biological processAutophagy, Protein transport, Transport

Names & Taxonomyi

Protein namesi
Recommended name:
Vacuolar protein sorting-associated protein 16 homolog
Short name:
hVPS16
Gene namesi
Name:VPS16
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

EuPathDBiHostDB:ENSG00000215305.9
HGNCiHGNC:14584 VPS16
MIMi608550 gene
neXtProtiNX_Q9H269

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasmic vesicle, Endosome, Lysosome, Membrane

Pathology & Biotechi

Involvement in diseasei

VSP16 mutation have been found in one familly with adolescent-onset primary dystonia. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi669A → D: Disrupts interaction with VPS33A, no effect on interaction with VPS18 and impairs endosome-lysosome fusion; when associated with E-725. 2 Publications1
Mutagenesisi725R → E: Disrupts interaction with VPS33A, no effect on interaction with VPS18 and impairs endosome-lysosome fusion; when associated with D-669. 2 Publications1

Keywords - Diseasei

Disease mutation

Organism-specific databases

PharmGKBiPA37903

Polymorphism and mutation databases

DMDMi23396927

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000658881 – 839Vacuolar protein sorting-associated protein 16 homologAdd BLAST839

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei4Nitrated tyrosineBy similarity1

Keywords - PTMi

Nitration

Proteomic databases

EPDiQ9H269
MaxQBiQ9H269
PaxDbiQ9H269
PeptideAtlasiQ9H269
PRIDEiQ9H269
ProteomicsDBi80507
80508 [Q9H269-2]

PTM databases

iPTMnetiQ9H269
PhosphoSitePlusiQ9H269

Expressioni

Tissue specificityi

Ubiquitous.

Gene expression databases

BgeeiENSG00000215305
ExpressionAtlasiQ9H269 baseline and differential
GenevisibleiQ9H269 HS

Organism-specific databases

HPAiHPA043229
HPA048661

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 vacuole/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:11382755, PubMed:25783203, PubMed:23901104, PubMed:25266290). Interacts with RAB5C (By similarity). Interacts with STX17, MON1B (PubMed:20434987, PubMed:24554770). Associates with adaptor protein complex 3 (AP-3) and clathrin:AP-3 complexes (By similarity).By similarity2 Publications4 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi122220, 58 interactors
CORUMiQ9H269
IntActiQ9H269, 31 interactors
STRINGi9606.ENSP00000369810

Structurei

Secondary structure

1839
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi645 – 660Combined sources16
Helixi664 – 687Combined sources24
Helixi696 – 705Combined sources10
Helixi709 – 718Combined sources10
Helixi723 – 734Combined sources12

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4BX9X-ray2.60C642-736[»]
ProteinModelPortaliQ9H269
SMRiQ9H269
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni642 – 736Interaction with VPS33A1 PublicationAdd BLAST95

Sequence similaritiesi

Belongs to the VPS16 family.Curated

Phylogenomic databases

eggNOGiKOG2280 Eukaryota
ENOG410XQ8X LUCA
GeneTreeiENSGT00390000003896
HOVERGENiHBG056306
InParanoidiQ9H269
KOiK20180
OMAiSYCLLGR
OrthoDBiEOG091G01XD
PhylomeDBiQ9H269
TreeFamiTF105673

Family and domain databases

Gene3Di1.10.150.780, 1 hit
InterProiView protein in InterPro
IPR016534 VPS16
IPR006925 Vps16_C
IPR038132 Vps16_C_sf
IPR006926 Vps16_N
PANTHERiPTHR12811 PTHR12811, 1 hit
PfamiView protein in Pfam
PF04840 Vps16_C, 1 hit
PF04841 Vps16_N, 1 hit
PIRSFiPIRSF007949 VPS16, 1 hit

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q9H269-1) [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
MDCYTANWNP LGDSAFYRKY ELYSMDWDLK EELRDCLVAA APYGGPIALL
60 70 80 90 100
RNPWRKEKAA SVRPVLDIYS ASGMPLASLL WKSGPVVSLG WSAEEELLCV
110 120 130 140 150
QEDGAVLVYG LHGDFRRHFS MGNEVLQNRV LDARIFHTEF GSGVAILTGA
160 170 180 190 200
HRFTLSANVG DLKLRRMPEV PGLQSAPSCW TVLCQDRVAH ILLAVGPDLY
210 220 230 240 250
LLDHAACSAV TPPGLAPGVS SFLQMAVSFT YRHLALFTDT GYIWMGTASL
260 270 280 290 300
KEKLCEFNCN IRAPPKQMVW CSRPRSKERA VVVAWERRLM VVGDAPESIQ
310 320 330 340 350
FVLDEDSYLV PELDGVRIFS RSTHEFLHEV PAASEEIFKI ASMAPGALLL
360 370 380 390 400
EAQKEYEKES QKADEYLREI QELGQLTQAV QQCIEAAGHE HQPDMQKSLL
410 420 430 440 450
RAASFGKCFL DRFPPDSFVH MCQDLRVLNA VRDYHIGIPL TYSQYKQLTI
460 470 480 490 500
QVLLDRLVLR RLYPLAIQIC EYLRLPEVQG VSRILAHWAC YKVQQKDVSD
510 520 530 540 550
EDVARAINQK LGDTPGVSYS DIAARAYGCG RTELAIKLLE YEPRSGEQVP
560 570 580 590 600
LLLKMKRSKL ALSKAIESGD TDLVFTVLLH LKNELNRGDF FMTLRNQPMA
610 620 630 640 650
LSLYRQFCKH QELETLKDLY NQDDNHQELG SFHIRASYAA EERIEGRVAA
660 670 680 690 700
LQTAADAFYK AKNEFAAKAT EDQMRLLRLQ RRLEDELGGQ FLDLSLHDTV
710 720 730 740 750
TTLILGGHNK RAEQLARDFR IPDKRLWWLK LTALADLEDW EELEKFSKSK
760 770 780 790 800
KSPIGYLPFV EICMKQHNKY EAKKYASRVG PEQKVKALLL VGDVAQAADV
810 820 830
AIEHRNEAEL SLVLSHCTGA TDGATADKIQ RARAQAQKK
Length:839
Mass (Da):94,694
Last modified:September 19, 2002 - v2
Checksum:i9C4292D455C19A60
GO
Isoform 2 (identifier: Q9H269-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     300-443: Missing.

Note: No experimental confirmation available.
Show »
Length:695
Mass (Da):78,300
Checksum:i13D27C230E5CFFCD
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti87V → A in BAB71013 (PubMed:14702039).Curated1
Sequence conflicti612E → G in BAB71013 (PubMed:14702039).Curated1
Sequence conflicti690 – 691QF → LQ in AAH12422 (PubMed:15489334).Curated2
Sequence conflicti768N → T in AAG34678 (PubMed:11250079).Curated1
Sequence conflicti809E → D in AAH12422 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07652052N → K Probable disease associated mutation found in patients with adolescent-onset primary dystonia. 1 PublicationCorresponds to variant dbSNP:rs367642720Ensembl.1
Natural variantiVAR_053776637S → I. Corresponds to variant dbSNP:rs35773586Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_004018300 – 443Missing in isoform 2. 1 PublicationAdd BLAST144

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF308801 mRNA Translation: AAG34678.1
AK055787 mRNA Translation: BAB71013.1
AL161656 Genomic DNA No translation available.
AL834401 mRNA Translation: CAD39063.1
BC012422 mRNA Translation: AAH12422.1
BC021291 mRNA Translation: AAH21291.2
BC064406 mRNA Translation: AAH64406.1
CCDSiCCDS13036.1 [Q9H269-1]
CCDS13037.1 [Q9H269-2]
RefSeqiNP_072097.2, NM_022575.3 [Q9H269-1]
NP_536338.1, NM_080413.2 [Q9H269-2]
UniGeneiHs.269577

Genome annotation databases

EnsembliENST00000380445; ENSP00000369810; ENSG00000215305 [Q9H269-1]
ENST00000380469; ENSP00000369836; ENSG00000215305 [Q9H269-2]
GeneIDi64601
KEGGihsa:64601
UCSCiuc002whe.5 human [Q9H269-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiVPS16_HUMAN
AccessioniPrimary (citable) accession number: Q9H269
Secondary accession number(s): Q5JUB1
, Q8WU31, Q96EE7, Q96N92, Q9H1Q4, Q9H1Q5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 19, 2002
Last sequence update: September 19, 2002
Last modified: June 20, 2018
This is version 149 of the entry and version 2 of the sequence. See 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

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