Q9H267 (VP33B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Vacuolar protein sorting-associated protein 33B
Short name=hVPS33B

Gene names

Name:

VPS33B

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	617 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.6
Subunit structure	Interacts with RAB11A and VIPAR. Interacts with M.tuberculosis PtpA. Ref.6 Ref.8
Subcellular location	Late endosome membrane; Peripheral membrane protein; Cytoplasmic side. Lysosome membrane; Peripheral membrane protein; Cytoplasmic side. Note: Cytoplasmic, peripheral membrane protein associated with late endosomes/lysosomes. Colocalizes with M.tuberculosis PtpA in the cytosol of tuberculosis-infected macrophages and associates with phagosomes. Ref.6 Ref.10
Tissue specificity	Ubiquitous; highly expressed in testis and low expression in the lung.
Post-translational modification	Phosphorylated on tyrosine residues. Dephosphorylation by M.tuberculosis PtpA is necessary to induce the reduction of host phagolysosome fusion in M.tuberculosis-infected macrophages. Ref.6
Involvement in disease	Defects in VPS33B are the cause of arthrogryposis-renal dysfunction-cholestasis syndrome type 1 (ARCS1) [MIM:208085]. ARCS1 is an autosomal recessive 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. Ref.10 Ref.11
Sequence similarities	Belongs to the STXBP/unc-18/SEC1 family.
Caution	Acccording to Ref.6, it is autophosphorylated. However, it is not related with protein kinases, suggesting it is phosphorylated by another protein.

Ontologies

Keywords
Biological process	Protein transport Transport
Cellular component	Endosome Lysosome Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cellular membrane fusion Inferred from mutant phenotype Ref.10. Source: UniProtKB lysosome localization Inferred from direct assay. Source: UniProtKB melanosome localization Inferred from direct assay. Source: UniProtKB platelet alpha granule organization Inferred from mutant phenotype. Source: UniProtKB protein transport Inferred from mutant phenotype Ref.10. Source: UniProtKB vesicle docking involved in exocytosis Inferred from electronic annotation. Source: InterPro
Cellular component	late endosome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell lysosomal membrane Inferred from electronic annotation. Source: UniProtKB-SubCell perinuclear region of cytoplasm Inferred from direct assay. Source: UniProtKB platelet alpha granule Inferred from direct assay. Source: UniProtKB
Molecular function	protein binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
VIPAR	Q9H9C1	17	EBI-749072,EBI-749080

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed
	Chain	2 – 617	616	Vacuolar protein sorting-associated protein 33B		PRO_0000206305
Amino acid modifications
	Modified residue	2	1	N-acetylalanine Ref.7
Natural variations
	Natural variant	30	1	L → P in ARCS1. Ref.10		VAR_018983
	Natural variant	243	1	S → F in ARCS1. Ref.11		VAR_057901
	Natural variant	513	1	F → S. Corresponds to variant rs3177428 [ dbSNP | Ensembl ].		VAR_057330
	Natural variant	514	1	G → S. Ref.1 Ref.3 Ref.5 Corresponds to variant rs11073964 [ dbSNP | Ensembl ].		VAR_013828
Experimental info
	Mutagenesis	133	1	Y → 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. Ref.6
	Mutagenesis	382	1	Y → 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. Ref.6
	Mutagenesis	511	1	Y → 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. Ref.6
	Mutagenesis	517	1	Y → 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. Ref.6
	Sequence conflict	293	1	H → Y in BAB55345. Ref.3
	Sequence conflict	466	1	K → E in BAB55345. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q9H267 [UniParc]. Last modified November 30, 2010. Version 2. Checksum: BD7DB97E1FEB1D32	FASTA	617	70,585
	10 20 30 40 50 60 MAFPHRPDAP ELPDFSMLKR LARDQLIYLL EQLPGKKDLF IEADLMSPLD RIANVSILKQ 70 80 90 100 110 120 HEVDKLYKVE NKPALSSNEQ LCFLVRPRIK NMRYIASLVN ADKLAGRTRK YKVIFSPQKF 130 140 150 160 170 180 YACEMVLEEE GIYGDVSCDE WAFSLLPLDV DLLSMELPEF FRDYFLEGDQ RWINTVAQAL 190 200 210 220 230 240 HLLSTLYGPF PNCYGIGRCA KMAYELWRNL EEEEDGETKG RRPEIGHIFL LDRDVDFVTA 250 260 270 280 290 300 LCSQVVYEGL VDDTFRIKCG SVDFGPEVTS SDKSLKVLLN AEDKVFNEIR NEHFSNVFGF 310 320 330 340 350 360 LSQKARNLQA QYDRRRGMDI KQMKNFVSQE LKGLKQEHRL LSLHIGACES IMKKKTKQDF 370 380 390 400 410 420 QELIKTEHAL LEGFNIREST SYIEEHIDRQ VSPIESLRLM CLLSITENGL IPKDYRSLKT 430 440 450 460 470 480 QYLQSYGPEH LLTFSNLRRA GLLTEQAPGD TLTAVESKVS KLVTDKAAGK ITDAFSSLAK 490 500 510 520 530 540 RSNFRAISKK LNLIPRVDGE YDLKVPRDMA YVFGGAYVPL SCRIIEQVLE RRSWQGLDEV 550 560 570 580 590 600 VRLLNCSDFA FTDMTKEDKA SSESLRLILV VFLGGCTFSE ISALRFLGRE KGYRFIFLTT 610 AVTNSARLME AMSEVKA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning, mapping and expression analysis of VPS33B, the human orthologue of rat Vps33b." Carim-Todd L., Sumoy L., Andreu N., Estivill X., Escarceller M. Cytogenet. Cell Genet. 89:92-95(2000) [PubMed: 10894945] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT SER-514.
[2]	"Molecular cloning and characterization of human VPS18, VPS11, VPS16, and VPS33." Huizing M., Didier A., Walenta J., Anikster Y., Gahl W.A., Kraemer H. Gene 264:241-247(2001) [PubMed: 11250079] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT SER-514. Tissue: Placenta.
[4]	"Analysis of the DNA sequence and duplication history of human chromosome 15." Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C. Nature 440:671-675(2006) [PubMed: 16572171] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT SER-514. Tissue: Placenta.
[6]	"Mycobacterium tuberculosis virulence is mediated by PtpA dephosphorylation of human vacuolar protein sorting 33B." Bach H., Papavinasasundaram K.G., Wong D., Hmama Z., Av-Gay Y. Cell Host Microbe 3:316-322(2008) [PubMed: 18474358] [Abstract] Cited for: FUNCTION, DEPHOSPHORYLATION, PHOSPHORYLATION, INTERACTION WITH MYCOBACTERIUM TUBERCULOSIS PTPA, MUTAGENESIS OF TYR-133; TYR-382; TYR-511 AND TYR-517, SUBCELLULAR LOCATION, MASS SPECTROMETRY.
[7]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[8]	"Mutations in VIPAR cause an arthrogryposis, renal dysfunction and cholestasis syndrome phenotype with defects in epithelial polarization." Cullinane A.R., Straatman-Iwanowska A., Zaucker A., Wakabayashi Y., Bruce C.K., Luo G., Rahman F., Gurakan F., Utine E., Ozkan T.B., Denecke J., Vukovic J., Di Rocco M., Mandel H., Cangul H., Matthews R.P., Thomas S.G., Rappoport J.Z. , Arias I.M., Wolburg H., Knisely A.S., Kelly D.A., Muller F., Maher E.R., Gissen P. Nat. Genet. 42:303-312(2010) [PubMed: 20190753] [Abstract] Cited for: INTERACTION WITH RAB11A AND VIPAR.
[9]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]	"Mutations in VPS33B, encoding a regulator of SNARE-dependent membrane fusion, cause arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome." Gissen P., Johnson C.A., Morgan N.V., Stapelbroek J.M., Forshew T., Cooper W.N., McKiernan P.J., Klomp L.W.J., Morris A.A.M., Wraith J.E., McClean P., Lynch S.A., Thompson R.J., Lo B., Quarrell O.W., Di Rocco M., Trembath R.C., Mandel H. , Wali S., Karet F.E., Knisely A.S., Houwen R.H.J., Kelly D.A., Maher E.R. Nat. Genet. 36:400-404(2004) [PubMed: 15052268] [Abstract] Cited for: VARIANT ARCS1 PRO-30, SUBCELLULAR LOCATION.
[11]	"Molecular investigations to improve diagnostic accuracy in patients with ARC syndrome." Cullinane A.R., Straatman-Iwanowska A., Seo J.K., Ko J.S., Song K.S., Gizewska M., Gruszfeld D., Gliwicz D., Tuysuz B., Erdemir G., Sougrat R., Wakabayashi Y., Hinds R., Barnicoat A., Mandel H., Chitayat D., Fischler B., Garcia-Cazorla A. , Knisely A.S., Kelly D.A., Maher E.R., Gissen P. Hum. Mutat. 30:E330-E337(2009) [PubMed: 18853461] [Abstract] Cited for: VARIANT ARCS1 PHE-243.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF201694 mRNA. Translation: AAF91174.1. AL357472 mRNA. Translation: CAB93109.1. AF308803 mRNA. Translation: AAG34680.1. AK027754 mRNA. Translation: BAB55345.1. AC068831 Genomic DNA. No translation available. BC016445 mRNA. Translation: AAH16445.1.
IPI	IPI00032905.
RefSeq	NP_061138.3. NM_018668.3.
UniGene	Hs.728254.
3D structure databases
ProteinModelPortal	Q9H267.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9H267. 1 interaction.
MINT	MINT-1451069.
STRING	Q9H267.
Polymorphism databases
DMDM	23396926.
Proteomic databases
PRIDE	Q9H267.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000333371; ENSP00000327650; ENSG00000184056.
GeneID	26276.
KEGG	hsa:26276.
UCSC	uc002bqp.1. human.
Organism-specific databases
CTD	26276.
GeneCards	GC15M091541.
H-InvDB	HIX0202153.
HGNC	HGNC:12712. VPS33B.
HPA	HPA040415.
MIM	208085. phenotype. 608552. gene.
neXtProt	NX_Q9H267.
Orphanet	2697. Arthrogryposis - renal dysfunction - cholestasis.
PharmGKB	PA37327.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG17090.
GeneTree	ENSGT00530000063488.
HOGENOM	HBG330900.
HOVERGEN	HBG106182.
InParanoid	Q9H267.
OMA	CFLVRPR.
OrthoDB	EOG4STS44.
PhylomeDB	Q9H267.
Gene expression databases
ArrayExpress	Q9H267.
Bgee	Q9H267.
CleanEx	HS_VPS33B.
Genevestigator	Q9H267.
GermOnline	ENSG00000184056. Homo sapiens.
Family and domain databases
InterPro	IPR001619. Sec1-like. [Graphical view]
PANTHER	PTHR11679. Sec1-like. 1 hit.
Pfam	PF00995. Sec1. 1 hit. [Graphical view]
SUPFAM	SSF56815. Sec1-like. 1 hit.
ProtoNet	Search...
Other
NextBio	48583.
SOURCE	Search...

Entry information

Entry name

VP33B_HUMAN

Accession

Primary (citable) accession number: Q9H267
Secondary accession number(s): Q96K14, Q9NRP6, Q9NSF3

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 19, 2002
Last sequence update:	November 30, 2010
Last modified:	January 25, 2012
This is version 96 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.