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Protein

Vacuolar protein sorting-associated protein 33B

Gene

VPS33B

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

Functioni

May play a role in vesicle-mediated protein trafficking to lysosomal compartments and in membrane docking/fusion reactions of late endosomes/lysosomes. Mediates phagolysosomal fusion in macrophages (PubMed:18474358). Proposed to be involved in endosomal maturation implicating VIPAS39. In epithelial cells, the VPS33B:VIPAS39 complex may play a role in the apical recycling pathway and in the maintenance of the apical-basolateral polarity (PubMed:20190753). Seems to be involved in the sorting of specific cargos from the trans-Golgi network to alpha-granule-destined multivesicular bodies (MVBs) promoting MVBs maturation in megakaryocytes (By similarity).By similarity2 Publications1 Publication

Caution

According to PubMed:18474358, it is autophosphorylated. However, it is not related with protein kinases, suggesting it is phosphorylated by another protein.Curated

GO - Biological processi

  • collagen metabolic process Source: MGI
  • endosome organization Source: UniProtKB
  • lysosome localization Source: UniProtKB
  • melanosome localization Source: UniProtKB
  • membrane fusion Source: UniProtKB
  • peptidyl-lysine hydroxylation Source: MGI
  • platelet alpha granule organization Source: UniProtKB
  • protein transport Source: UniProtKB
  • vesicle docking involved in exocytosis Source: InterPro
  • vesicle-mediated transport Source: MGI

Keywordsi

Biological processProtein transport, Transport

Names & Taxonomyi

Protein namesi
Recommended name:
Vacuolar protein sorting-associated protein 33B
Short name:
hVPS33B
Gene namesi
Name:VPS33B
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

EuPathDBiHostDB:ENSG00000184056.14
HGNCiHGNC:12712 VPS33B
MIMi608552 gene
neXtProtiNX_Q9H267

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

Arthrogryposis, renal dysfunction and cholestasis syndrome 1 (ARCS1)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA multisystem disorder, characterized by neurogenic arthrogryposis multiplex congenita, renal tubular dysfunction and neonatal cholestasis with bile duct hypoplasia and low gamma glutamyl transpeptidase activity. Platelet dysfunction is common.
See also OMIM:208085
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01898330L → P in ARCS1; effect on interaction with VIPAS39 is reported conflictingly but disrupts colocalization with VIPAS39 at cytoplasmic organelle; impairs localization to VIPAS39-containing endosomal compartment; and induces fragmentation of the VIPAS39-containing endosomal compartment; no effect on interaction with STX7 and association with the HOPS complex. 4 PublicationsCorresponds to variant dbSNP:rs121434385EnsemblClinVar.1
Natural variantiVAR_057901243S → F in ARCS1; no effect on interaction with VIPAS39; impairs localization to VIPAS39-containing endosomal compartment. 2 PublicationsCorresponds to variant dbSNP:rs139829189Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi133Y → E: Reduces phosphorylation activity, but does not impair phagolysosomal fusion in M.tuberculosis-infected macrophages; when associated with E-382; E-511 and E-517. 1 Publication1
Mutagenesisi232 – 234DRD → AAA: Disrupts interaction with VIPAS39. 1 Publication3
Mutagenesisi234D → H: No effect on interaction with VIPAS39; no effect on interaction with STX7 and association with the HOPS complex; impairs localization to VIPAS39-containing endosomal compartment. 1 Publication1
Mutagenesisi235 – 237VDF → AAA: Disrupts interaction with VIPAS39. 1 Publication3
Mutagenesisi249G → V: Disrupts interaction with VIPAS39; no effect on interaction with STX7; impairs localization to VIPAS39-containing endosomal compartment. 1 Publication1
Mutagenesisi251 – 253VDD → AAA: Disrupts interaction with VIPAS39. 1 Publication3
Mutagenesisi252D → E: No effect on interaction with VIPAS39 and STX7; impairs localization to VIPAS39-containing endosomal compartment. 1 Publication1
Mutagenesisi382Y → E: Reduces phosphorylation activity, but does not impair phagolysosomal fusion in M.tuberculosis-infected macrophages; when associated with E-133; E-511 and E-517. 1 Publication1
Mutagenesisi511Y → E: Reduces phosphorylation activity, but does not impair phagolysosomal fusion in M.tuberculosis-infected macrophages; when associated with E-133; E-382 and E-517. 1 Publication1
Mutagenesisi517Y → E: Reduces phosphorylation activity, but does not impair phagolysosomal fusion in M.tuberculosis-infected macrophages; when associated with E-133; E-382 and E-511. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi26276
MalaCardsiVPS33B
MIMi208085 phenotype
OpenTargetsiENSG00000184056
Orphaneti2697 Arthrogryposis - renal dysfunction - cholestasis
PharmGKBiPA37327

Polymorphism and mutation databases

BioMutaiVPS33B
DMDMi313104046

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00002063052 – 617Vacuolar protein sorting-associated protein 33BAdd BLAST616

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1

Post-translational modificationi

Phosphorylated on tyrosine residues. Dephosphorylation by M.tuberculosis PtpA is necessary to induce the reduction of host phagolysosome fusion in M.tuberculosis-infected macrophages.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9H267
MaxQBiQ9H267
PaxDbiQ9H267
PeptideAtlasiQ9H267
PRIDEiQ9H267

PTM databases

iPTMnetiQ9H267
PhosphoSitePlusiQ9H267

Expressioni

Tissue specificityi

Ubiquitous; highly expressed in testis and low expression in the lung.

Gene expression databases

BgeeiENSG00000184056
CleanExiHS_VPS33B
ExpressionAtlasiQ9H267 baseline and differential
GenevisibleiQ9H267 HS

Organism-specific databases

HPAiHPA040415

Interactioni

Subunit structurei

Interacts with RAB11A and VIPAS39. Associates with adaptor protein complex 3 (AP-3), clathrin:AP-3 and clathrin:HGS complexes (PubMed:21411634). Interacts with M.tuberculosis PtpA.4 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi117659, 39 interactors
CORUMiQ9H267
IntActiQ9H267, 16 interactors
MINTiQ9H267
STRINGi9606.ENSP00000327650

Structurei

3D structure databases

ProteinModelPortaliQ9H267
SMRiQ9H267
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the STXBP/unc-18/SEC1 family.Curated

Phylogenomic databases

eggNOGiKOG1302 Eukaryota
COG5158 LUCA
GeneTreeiENSGT00530000063488
HOGENOMiHOG000166771
HOVERGENiHBG106182
InParanoidiQ9H267
OMAiSCDEWAF
OrthoDBiEOG091G0AK0
PhylomeDBiQ9H267
TreeFamiTF315126

Family and domain databases

Gene3Di3.40.50.1910, 2 hits
InterProiView protein in InterPro
IPR027482 Sec-1-like_dom2
IPR001619 Sec1-like
IPR036045 Sec1-like_sf
IPR027121 VPS33
PANTHERiPTHR11679 PTHR11679, 1 hit
PTHR11679:SF1 PTHR11679:SF1, 1 hit
PfamiView protein in Pfam
PF00995 Sec1, 1 hit
SUPFAMiSSF56815 SSF56815, 2 hits

Sequences (2)i

Sequence statusi: Complete.

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

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

Isoform 1 (identifier: Q9H267-1) [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
MAFPHRPDAP ELPDFSMLKR LARDQLIYLL EQLPGKKDLF IEADLMSPLD
60 70 80 90 100
RIANVSILKQ HEVDKLYKVE NKPALSSNEQ LCFLVRPRIK NMRYIASLVN
110 120 130 140 150
ADKLAGRTRK YKVIFSPQKF YACEMVLEEE GIYGDVSCDE WAFSLLPLDV
160 170 180 190 200
DLLSMELPEF FRDYFLEGDQ RWINTVAQAL HLLSTLYGPF PNCYGIGRCA
210 220 230 240 250
KMAYELWRNL EEEEDGETKG RRPEIGHIFL LDRDVDFVTA LCSQVVYEGL
260 270 280 290 300
VDDTFRIKCG SVDFGPEVTS SDKSLKVLLN AEDKVFNEIR NEHFSNVFGF
310 320 330 340 350
LSQKARNLQA QYDRRRGMDI KQMKNFVSQE LKGLKQEHRL LSLHIGACES
360 370 380 390 400
IMKKKTKQDF QELIKTEHAL LEGFNIREST SYIEEHIDRQ VSPIESLRLM
410 420 430 440 450
CLLSITENGL IPKDYRSLKT QYLQSYGPEH LLTFSNLRRA GLLTEQAPGD
460 470 480 490 500
TLTAVESKVS KLVTDKAAGK ITDAFSSLAK RSNFRAISKK LNLIPRVDGE
510 520 530 540 550
YDLKVPRDMA YVFGGAYVPL SCRIIEQVLE RRSWQGLDEV VRLLNCSDFA
560 570 580 590 600
FTDMTKEDKA SSESLRLILV VFLGGCTFSE ISALRFLGRE KGYRFIFLTT
610
AVTNSARLME AMSEVKA
Length:617
Mass (Da):70,585
Last modified:November 30, 2010 - v2
Checksum:iBD7DB97E1FEB1D32
GO
Isoform 2 (identifier: Q9H267-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-91: Missing.

Note: No experimental confirmation available.
Show »
Length:526
Mass (Da):60,032
Checksum:iA614FE0EFCBF8BE2
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti293H → Y in BAB55345 (PubMed:14702039).Curated1
Sequence conflicti466K → E in BAB55345 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01898330L → P in ARCS1; effect on interaction with VIPAS39 is reported conflictingly but disrupts colocalization with VIPAS39 at cytoplasmic organelle; impairs localization to VIPAS39-containing endosomal compartment; and induces fragmentation of the VIPAS39-containing endosomal compartment; no effect on interaction with STX7 and association with the HOPS complex. 4 PublicationsCorresponds to variant dbSNP:rs121434385EnsemblClinVar.1
Natural variantiVAR_057901243S → F in ARCS1; no effect on interaction with VIPAS39; impairs localization to VIPAS39-containing endosomal compartment. 2 PublicationsCorresponds to variant dbSNP:rs139829189Ensembl.1
Natural variantiVAR_057330513F → S. Corresponds to variant dbSNP:rs3177428Ensembl.1
Natural variantiVAR_013828514G → S3 PublicationsCorresponds to variant dbSNP:rs11073964EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0565671 – 91Missing in isoform 2. 1 PublicationAdd BLAST91

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF201694 mRNA Translation: AAF91174.1
AL357472 mRNA Translation: CAB93109.1
AF308803 mRNA Translation: AAG34680.1
AK027754 mRNA Translation: BAB55345.1
AK074863 mRNA Translation: BAG52018.1
AC068831 Genomic DNA No translation available.
CH471101 Genomic DNA Translation: EAX02140.1
BC016445 mRNA Translation: AAH16445.1
CCDSiCCDS10369.1 [Q9H267-1]
RefSeqiNP_001276077.1, NM_001289148.1
NP_001276078.1, NM_001289149.1 [Q9H267-2]
NP_061138.3, NM_018668.4 [Q9H267-1]
XP_005254944.1, XM_005254887.1 [Q9H267-2]
XP_011519750.1, XM_011521448.1 [Q9H267-2]
UniGeneiHs.745007

Genome annotation databases

EnsembliENST00000333371; ENSP00000327650; ENSG00000184056 [Q9H267-1]
GeneIDi26276
KEGGihsa:26276
UCSCiuc002bqp.3 human [Q9H267-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiVP33B_HUMAN
AccessioniPrimary (citable) accession number: Q9H267
Secondary accession number(s): B3KQF6
, Q96K14, Q9NRP6, Q9NSF3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 19, 2002
Last sequence update: November 30, 2010
Last modified: May 23, 2018
This is version 155 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

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

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