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Protein

Vacuolar protein sorting-associated protein 33B

Gene

VPS33B

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

GO - Biological processi

  • endosome organization Source: UniProtKB
  • lysosome localization Source: UniProtKB
  • megakaryocyte development Source: Ensembl
  • melanosome localization Source: UniProtKB
  • membrane fusion Source: UniProtKB
  • platelet alpha granule organization Source: UniProtKB
  • protein transport Source: UniProtKB
  • regulation of platelet aggregation Source: Ensembl
  • vesicle docking involved in exocytosis Source: InterPro
  • vesicle-mediated transport Source: MGI
Complete GO annotation...

Keywords - Biological processi

Protein 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

HGNCiHGNC:12712. VPS33B.

Subcellular locationi

GO - Cellular componenti

  • clathrin-coated vesicle Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • early endosome membrane Source: UniProtKB
  • late endosome Source: UniProtKB
  • late endosome membrane Source: UniProtKB-SubCell
  • lysosomal membrane Source: UniProtKB-SubCell
  • lysosome Source: UniProtKB
  • perinuclear region of cytoplasm Source: UniProtKB
  • platelet alpha granule Source: UniProtKB
  • recycling endosome Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasmic vesicle, Endosome, Lysosome, Membrane

Pathology & Biotechi

Involvement in diseasei

Arthrogryposis, renal dysfunction and cholestasis syndrome 1 (ARCS1)2 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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti30 – 301L → 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 Publications
Corresponds to variant rs121434385 [ dbSNP | Ensembl ].
VAR_018983
Natural varianti243 – 2431S → F in ARCS1; no effect on interaction with VIPAS39; impairs localization to VIPAS39-containing endosomal compartment. 2 Publications
Corresponds to variant rs139829189 [ dbSNP | Ensembl ].
VAR_057901

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi133 – 1331Y → 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 Publication
Mutagenesisi232 – 2343DRD → AAA: Disrupts interaction with VIPAS39. 1 Publication
Mutagenesisi234 – 2341D → 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 Publication
Mutagenesisi235 – 2373VDF → AAA: Disrupts interaction with VIPAS39. 1 Publication
Mutagenesisi249 – 2491G → V: Disrupts interaction with VIPAS39; no effect on interaction with STX7; impairs localization to VIPAS39-containing endosomal compartment. 1 Publication
Mutagenesisi251 – 2533VDD → AAA: Disrupts interaction with VIPAS39. 1 Publication
Mutagenesisi252 – 2521D → E: No effect on interaction with VIPAS39 and STX7; impairs localization to VIPAS39-containing endosomal compartment. 1 Publication
Mutagenesisi382 – 3821Y → 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 Publication
Mutagenesisi511 – 5111Y → 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 Publication
Mutagenesisi517 – 5171Y → 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 Publication

Keywords - Diseasei

Disease mutation

Organism-specific databases

MalaCardsiVPS33B.
MIMi208085. phenotype.
Orphaneti2697. Arthrogryposis - renal dysfunction - cholestasis.
PharmGKBiPA37327.

Polymorphism and mutation databases

BioMutaiVPS33B.
DMDMi313104046.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedCombined sources
Chaini2 – 617616Vacuolar protein sorting-associated protein 33BPRO_0000206305Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineCombined sources

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.
PhosphoSiteiQ9H267.

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

WithEntry#Exp.IntActNotes
C14orf133Q6IA613EBI-749072,EBI-10305835
TNIP1Q150253EBI-749072,EBI-357849
VIPAS39Q9H9C129EBI-749072,EBI-749080

Protein-protein interaction databases

BioGridi117659. 36 interactions.
IntActiQ9H267. 14 interactions.
MINTiMINT-1451069.
STRINGi9606.ENSP00000327650.

Structurei

3D structure databases

ProteinModelPortaliQ9H267.
SMRiQ9H267. Positions 14-614.
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.
InterProiIPR027482. Sec-1-like_dom2.
IPR001619. Sec1-like.
IPR027121. VPS33.
[Graphical view]
PANTHERiPTHR11679. PTHR11679. 2 hits.
PTHR11679:SF1. PTHR11679:SF1. 2 hits.
PfamiPF00995. Sec1. 1 hit.
[Graphical view]
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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti293 – 2931H → Y in BAB55345 (PubMed:14702039).Curated
Sequence conflicti466 – 4661K → E in BAB55345 (PubMed:14702039).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti30 – 301L → 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 Publications
Corresponds to variant rs121434385 [ dbSNP | Ensembl ].
VAR_018983
Natural varianti243 – 2431S → F in ARCS1; no effect on interaction with VIPAS39; impairs localization to VIPAS39-containing endosomal compartment. 2 Publications
Corresponds to variant rs139829189 [ dbSNP | Ensembl ].
VAR_057901
Natural varianti513 – 5131F → S.
Corresponds to variant rs3177428 [ dbSNP | Ensembl ].
VAR_057330
Natural varianti514 – 5141G → S.3 Publications
Corresponds to variant rs11073964 [ dbSNP | Ensembl ].
VAR_013828

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 9191Missing in isoform 2. 1 PublicationVSP_056567Add
BLAST

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

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ9H267.
SMRiQ9H267. Positions 14-614.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117659. 36 interactions.
IntActiQ9H267. 14 interactions.
MINTiMINT-1451069.
STRINGi9606.ENSP00000327650.

PTM databases

iPTMnetiQ9H267.
PhosphoSiteiQ9H267.

Polymorphism and mutation databases

BioMutaiVPS33B.
DMDMi313104046.

Proteomic databases

EPDiQ9H267.
MaxQBiQ9H267.
PaxDbiQ9H267.
PeptideAtlasiQ9H267.
PRIDEiQ9H267.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi26276.
GeneCardsiVPS33B.
H-InvDBHIX0202153.
HGNCiHGNC:12712. VPS33B.
HPAiHPA040415.
MalaCardsiVPS33B.
MIMi208085. phenotype.
608552. gene.
neXtProtiNX_Q9H267.
Orphaneti2697. Arthrogryposis - renal dysfunction - cholestasis.
PharmGKBiPA37327.
GenAtlasiSearch...

Phylogenomic databases

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

Miscellaneous databases

ChiTaRSiVPS33B. human.
GeneWikiiVPS33B.
GenomeRNAii26276.
PROiQ9H267.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000184056.
CleanExiHS_VPS33B.
ExpressionAtlasiQ9H267. baseline and differential.
GenevisibleiQ9H267. HS.

Family and domain databases

Gene3Di3.40.50.1910. 2 hits.
InterProiIPR027482. Sec-1-like_dom2.
IPR001619. Sec1-like.
IPR027121. VPS33.
[Graphical view]
PANTHERiPTHR11679. PTHR11679. 2 hits.
PTHR11679:SF1. PTHR11679:SF1. 2 hits.
PfamiPF00995. Sec1. 1 hit.
[Graphical view]
SUPFAMiSSF56815. SSF56815. 2 hits.
ProtoNetiSearch...

Entry informationi

Entry nameiVP33B_HUMAN
AccessioniPrimary (citable) accession number: Q9H267
Secondary accession number(s): B3KQF6
, Q96K14, Q9NRP6, Q9NSF3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 19, 2002
Last sequence update: November 30, 2010
Last modified: September 7, 2016
This is version 139 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

Caution

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

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.