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Protein

Vacuolar protein sorting-associated protein 33A

Gene

VPS33A

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:23351085, PubMed:24554770, PubMed:25266290, PubMed:25783203). Required for fusion of endosomes and autophagosomes with lysosomes; the function is dependent on its association with VPS16 but not VIPAS39 (PubMed:25783203). The function in autophagosome-lysosome fusion implicates STX17 but not UVRAG (PubMed:24554770).3 Publications2 Publications

GO - Biological processi

  • autophagosome maturation Source: UniProtKB
  • endosome to lysosome transport Source: UniProtKB
  • lysosome localization Source: UniProtKB
  • melanosome localization Source: UniProtKB
  • platelet formation Source: UniProtKB
  • protein transport Source: UniProtKB-KW
  • regulation of developmental pigmentation Source: UniProtKB
  • vesicle docking involved in exocytosis Source: InterPro
  • vesicle-mediated transport Source: MGI
Complete GO annotation...

Keywords - Biological processi

Autophagy, Protein transport, Transport

Enzyme and pathway databases

BioCyciZFISH:ENSG00000139719-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
Vacuolar protein sorting-associated protein 33A
Short name:
hVPS33A
Gene namesi
Name:VPS33A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:18179. VPS33A.

Subcellular locationi

GO - Cellular componenti

  • autophagosome Source: UniProtKB-SubCell
  • clathrin-coated vesicle Source: UniProtKB-SubCell
  • early endosome Source: UniProtKB
  • HOPS complex Source: UniProtKB
  • late endosome Source: UniProtKB
  • late endosome membrane Source: UniProtKB-SubCell
  • lysosomal membrane Source: UniProtKB
  • perinuclear region of cytoplasm Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasmic vesicle, Endosome, Lysosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi429K → D: Disrupts interaction with VPS16. Disrupts interaction with VPS18 and impairs endosome-lysosome fusion; when associated with K-438. Disrupts interaction with VPS18 and impairs endosome-lysosome fusion; when associated with K-441. 2 Publications1
Mutagenesisi438Y → D: Disrupts interaction with VPS16. Disrupts interaction with VPS18 and impairs endosome-lysosome fusion; when associated with D-429. Disrupts interaction with VPS18 and impairs endosome-lysosome fusion; when associated with K-441. 2 Publications1
Mutagenesisi441I → K: Disrupts interaction with VPS16. Disrupts interaction with VPS18 and impairs endosome-lysosome fusion; when associated with D-429. Disrupts interaction with VPS18 and impairs endosome-lysosome fusion; when associated with D-438. 2 Publications1

Organism-specific databases

DisGeNETi65082.
OpenTargetsiENSG00000139719.
PharmGKBiPA38306.

Polymorphism and mutation databases

BioMutaiVPS33A.
DMDMi23396917.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002063021 – 596Vacuolar protein sorting-associated protein 33AAdd BLAST596

Proteomic databases

EPDiQ96AX1.
MaxQBiQ96AX1.
PaxDbiQ96AX1.
PeptideAtlasiQ96AX1.
PRIDEiQ96AX1.
TopDownProteomicsiQ96AX1.

PTM databases

iPTMnetiQ96AX1.
PhosphoSitePlusiQ96AX1.

Expressioni

Gene expression databases

BgeeiENSG00000139719.
CleanExiHS_VPS33A.
ExpressionAtlasiQ96AX1. baseline and differential.
GenevisibleiQ96AX1. HS.

Organism-specific databases

HPAiHPA038701.
HPA038702.
HPA053209.

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:25266290 PubMed:23901104). Interacts with RAB5C (By similarity). Interacts with UVRAG, STX17, MON1A and MON1B (PubMed:18552835, PubMed:20434987, PubMed:24554770). Interacts with VIPAS39; however, this interaction is debated (PubMed:19109425, PubMed:23901104). Associates with adaptor protein complex 3 (AP-3) and clathrin (PubMed:21411634).By similarity2 Publications6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
STX17P569624EBI-2527283,EBI-2797775
UVRAGQ9P2Y54EBI-2527283,EBI-2952704
VPS16Q9H26913EBI-2527283,EBI-2655929
VPS18Q9P2536EBI-2527283,EBI-1053363

Protein-protein interaction databases

BioGridi122390. 27 interactors.
IntActiQ96AX1. 13 interactors.
MINTiMINT-2813690.
STRINGi9606.ENSP00000267199.

Structurei

Secondary structure

1596
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi3 – 5Combined sources3
Beta strandi7 – 10Combined sources4
Helixi13 – 29Combined sources17
Beta strandi34 – 38Combined sources5
Helixi40 – 42Combined sources3
Helixi43 – 46Combined sources4
Turni47 – 49Combined sources3
Helixi52 – 57Combined sources6
Beta strandi60 – 65Combined sources6
Beta strandi68 – 70Combined sources3
Beta strandi77 – 83Combined sources7
Helixi87 – 98Combined sources12
Beta strandi102 – 104Combined sources3
Beta strandi108 – 115Combined sources8
Helixi119 – 128Combined sources10
Helixi130 – 133Combined sources4
Beta strandi134 – 139Combined sources6
Beta strandi144 – 148Combined sources5
Beta strandi151 – 153Combined sources3
Helixi159 – 165Combined sources7
Helixi170 – 186Combined sources17
Beta strandi190 – 196Combined sources7
Helixi197 – 211Combined sources15
Beta strandi225 – 231Combined sources7
Helixi232 – 234Combined sources3
Helixi238 – 240Combined sources3
Helixi246 – 253Combined sources8
Beta strandi260 – 263Combined sources4
Beta strandi274 – 276Combined sources3
Beta strandi285 – 288Combined sources4
Helixi294 – 299Combined sources6
Helixi304 – 306Combined sources3
Helixi307 – 326Combined sources20
Helixi337 – 365Combined sources29
Helixi368 – 381Combined sources14
Helixi391 – 398Combined sources8
Helixi403 – 417Combined sources15
Helixi422 – 436Combined sources15
Helixi440 – 449Combined sources10
Helixi463 – 469Combined sources7
Beta strandi479 – 481Combined sources3
Helixi485 – 489Combined sources5
Helixi495 – 504Combined sources10
Helixi508 – 511Combined sources4
Helixi512 – 516Combined sources5
Beta strandi518 – 520Combined sources3
Beta strandi522 – 526Combined sources5
Beta strandi543 – 551Combined sources9
Helixi555 – 565Combined sources11
Beta strandi568 – 570Combined sources3
Beta strandi572 – 579Combined sources8
Helixi584 – 589Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4BX8X-ray2.40A/B1-596[»]
4BX9X-ray2.60A/B1-596[»]
ProteinModelPortaliQ96AX1.
SMRiQ96AX1.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG1302. Eukaryota.
COG5158. LUCA.
GeneTreeiENSGT00530000063488.
HOGENOMiHOG000166771.
HOVERGENiHBG054244.
InParanoidiQ96AX1.
KOiK20182.
OMAiRHVANMM.
OrthoDBiEOG091G0AK0.
PhylomeDBiQ96AX1.
TreeFamiTF315126.

Family and domain databases

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

Sequencei

Sequence statusi: Complete.

Q96AX1-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAAHLSYGRV NLNVLREAVR RELREFLDKC AGSKAIVWDE YLTGPFGLIA
60 70 80 90 100
QYSLLKEHEV EKMFTLKGNR LPAADVKNII FFVRPRLELM DIIAENVLSE
110 120 130 140 150
DRRGPTRDFH ILFVPRRSLL CEQRLKDLGV LGSFIHREEY SLDLIPFDGD
160 170 180 190 200
LLSMESEGAF KECYLEGDQT SLYHAAKGLM TLQALYGTIP QIFGKGECAR
210 220 230 240 250
QVANMMIRMK REFTGSQNSI FPVFDNLLLL DRNVDLLTPL ATQLTYEGLI
260 270 280 290 300
DEIYGIQNSY VKLPPEKFAP KKQGDGGKDL PTEAKKLQLN SAEELYAEIR
310 320 330 340 350
DKNFNAVGSV LSKKAKIISA AFEERHNAKT VGEIKQFVSQ LPHMQAARGS
360 370 380 390 400
LANHTSIAEL IKDVTTSEDF FDKLTVEQEF MSGIDTDKVN NYIEDCIAQK
410 420 430 440 450
HSLIKVLRLV CLQSVCNSGL KQKVLDYYKR EILQTYGYEH ILTLHNLEKA
460 470 480 490 500
GLLKPQTGGR NNYPTIRKTL RLWMDDVNEQ NPTDISYVYS GYAPLSVRLA
510 520 530 540 550
QLLSRPGWRS IEEVLRILPG PHFEERQPLP TGLQKKRQPG ENRVTLIFFL
560 570 580 590
GGVTFAEIAA LRFLSQLEDG GTEYVIATTK LMNGTSWIEA LMEKPF
Length:596
Mass (Da):67,611
Last modified:December 1, 2001 - v1
Checksum:i12442A1D9A223F56
GO

Sequence cautioni

The sequence BAB15570 differs from that shown. Reason: Frameshift at position 140.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_052471256I → L.Corresponds to variant rs34996966dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF439857 mRNA. Translation: AAL33577.1.
AK026840 mRNA. Translation: BAB15570.1. Frameshift.
CH471054 Genomic DNA. Translation: EAW98319.1.
BC016617 mRNA. Translation: AAH16617.1.
CCDSiCCDS9231.1.
RefSeqiNP_075067.2. NM_022916.4.
UniGeneiHs.592009.

Genome annotation databases

EnsembliENST00000267199; ENSP00000267199; ENSG00000139719.
GeneIDi65082.
KEGGihsa:65082.
UCSCiuc001ucd.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF439857 mRNA. Translation: AAL33577.1.
AK026840 mRNA. Translation: BAB15570.1. Frameshift.
CH471054 Genomic DNA. Translation: EAW98319.1.
BC016617 mRNA. Translation: AAH16617.1.
CCDSiCCDS9231.1.
RefSeqiNP_075067.2. NM_022916.4.
UniGeneiHs.592009.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4BX8X-ray2.40A/B1-596[»]
4BX9X-ray2.60A/B1-596[»]
ProteinModelPortaliQ96AX1.
SMRiQ96AX1.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122390. 27 interactors.
IntActiQ96AX1. 13 interactors.
MINTiMINT-2813690.
STRINGi9606.ENSP00000267199.

PTM databases

iPTMnetiQ96AX1.
PhosphoSitePlusiQ96AX1.

Polymorphism and mutation databases

BioMutaiVPS33A.
DMDMi23396917.

Proteomic databases

EPDiQ96AX1.
MaxQBiQ96AX1.
PaxDbiQ96AX1.
PeptideAtlasiQ96AX1.
PRIDEiQ96AX1.
TopDownProteomicsiQ96AX1.

Protocols and materials databases

DNASUi65082.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000267199; ENSP00000267199; ENSG00000139719.
GeneIDi65082.
KEGGihsa:65082.
UCSCiuc001ucd.4. human.

Organism-specific databases

CTDi65082.
DisGeNETi65082.
GeneCardsiVPS33A.
H-InvDBHIX0079486.
HGNCiHGNC:18179. VPS33A.
HPAiHPA038701.
HPA038702.
HPA053209.
MIMi610034. gene.
neXtProtiNX_Q96AX1.
OpenTargetsiENSG00000139719.
PharmGKBiPA38306.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1302. Eukaryota.
COG5158. LUCA.
GeneTreeiENSGT00530000063488.
HOGENOMiHOG000166771.
HOVERGENiHBG054244.
InParanoidiQ96AX1.
KOiK20182.
OMAiRHVANMM.
OrthoDBiEOG091G0AK0.
PhylomeDBiQ96AX1.
TreeFamiTF315126.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000139719-MONOMER.

Miscellaneous databases

GeneWikiiVPS33A.
GenomeRNAii65082.
PROiQ96AX1.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000139719.
CleanExiHS_VPS33A.
ExpressionAtlasiQ96AX1. baseline and differential.
GenevisibleiQ96AX1. HS.

Family and domain databases

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

Entry informationi

Entry nameiVP33A_HUMAN
AccessioniPrimary (citable) accession number: Q96AX1
Secondary accession number(s): Q547V4, Q9H5Q0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 19, 2002
Last sequence update: December 1, 2001
Last modified: November 30, 2016
This is version 127 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 12
    Human chromosome 12: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.