Q9BRG1 (VPS25_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Vacuolar protein-sorting-associated protein 25
Short name=hVps25

Alternative name(s):
Dermal papilla-derived protein 9
ELL-associated protein of 20 kDa
ESCRT-II complex subunit VPS25

Gene names

Name:	VPS25
Synonyms:	DERP9, EAP20

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	176 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Component of the ESCRT-II complex (endosomal sorting complex required for transport II), which is required for multivesicular body (MVB) formation and sorting of endosomal cargo proteins into MVBs. The MVB pathway mediates delivery of transmembrane proteins into the lumen of the lysosome for degradation. The ESCRT-II complex is probably involved in the recruitment of the ESCRT-III complex. The ESCRT-II complex may also play a role in transcription regulation, possibly via its interaction with ELL. The ESCRT-II complex may be involved in facilitating the budding of certain RNA viruses. Ref.12
Subunit structure	Component of a complex at least composed of ELL, SNF8/EAP30, VPS25/EAP20 and VPS36/EAP45 By similarity. Component of the endosomal sorting complex required for transport II (ESCRT-II), composed of SNF8, VPS36 and 2 copies of VPS25. Interacts with CFTR; the interaction requires misfolded CFTR. Interacts (via C-terminal half) with the ESCRT-III subunit CHMP6 (via N-terminal half). Ref.5 Ref.6 Ref.8 Ref.9 Ref.11
Subcellular location	Cytoplasm. Endosome membrane. Nucleus › nucleoplasm. Note: Distributes diffusely throughout the cytoplasm and nucleoplasm, but exhibits a punctate distribution on coexpression with CHMP6. Ref.8 Ref.11
Tissue specificity	Expressed at the mRNA level in kidney, liver, pancreas, and placenta. Lower levels of expression are found in heart, skeletal muscle, brain and lung. Ref.10
Sequence similarities	Belongs to the VPS25 family.

Ontologies

Keywords
Biological process	Protein transport Transcription Transcription regulation Transport
Cellular component	Cytoplasm Endosome Membrane Nucleus
Coding sequence diversity	Polymorphism
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular membrane organization Traceable author statement. Source: Reactome endosomal transport Traceable author statement. Source: Reactome protein transport Inferred from electronic annotation. Source: UniProtKB-KW regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytosol Traceable author statement. Source: Reactome endosome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrion Inferred from electronic annotation. Source: Compara nucleoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 176

176

Vacuolar protein-sorting-associated protein 25

PRO_0000215216

Natural variations

Natural variant

76

1

I → V.
Corresponds to variant rs34494804 [ dbSNP | Ensembl ].

VAR_048940

Experimental info

Mutagenesis

124

1

V → E: Abolishes binding to CHMP6. Ref.15

Mutagenesis

126

1

T → K: Abolishes binding to CHMP6. Ref.15

Secondary structure

1

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176

Helix Strand Turn

Details...

Helix

9 – 12

4

Helix

14 – 17

4

Helix

23 – 44

22

Beta strand

48 – 50

3

Helix

51 – 55

5

Beta strand

60 – 62

3

Turn

63 – 66

4

Helix

71 – 84

14

Beta strand

86 – 89

4

Beta strand

91 – 99

9

Helix

104 – 116

13

Turn

117 – 119

3

Beta strand

123 – 125

3

Helix

127 – 132

6

Turn

135 – 138

4

Turn

140 – 143

4

Helix

146 – 158

13

Beta strand

161 – 165

5

Turn

167 – 169

3

Beta strand

172 – 175

4

Sequences

	Sequence		Length	Mass (Da)
	Q9BRG1 [UniParc]. Last modified June 1, 2001. Version 1. Checksum: 34963A53C3DA4DD5	FASTA	176	20,748
	10 20 30 40 50 60 MAMSFEWPWQ YRFPPFFTLQ PNVDTRQKQL AAWCSLVLSF CRLHKQSSMT VMEAQESPLF 70 80 90 100 110 120 NNVKLQRKLP VESIQIVLEE LRKKGNLEWL DKSKSSFLIM WRRPEEWGKL IYQWVSRSGQ 130 140 150 160 170 NNSVFTLYEL TNGEDTEDEE FHGLDEATLL RALQALQQEH KAEIITVSDG RGVKFF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of a dermal papilla derived gene." Ikeda A., Ukai Y., Yamashita M., Yoshimoto M. Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Hair follicle dermal papilla.
[2]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Cerebellum.
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Skin.
[5]	"The protein network of HIV budding." von Schwedler U.K., Stuchell M., Mueller B., Ward D.M., Chung H.-Y., Morita E., Wang H.E., Davis T., He G.P., Cimbora D.M., Scott A., Kraeusslich H.-G., Kaplan J., Morham S.G., Sundquist W.I. Cell 114:701-713(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SNF8; VPS36 AND CHMP6.
[6]	"Divergent retroviral late-budding domains recruit vacuolar protein sorting factors by using alternative adaptor proteins." Martin-Serrano J., Yarovoy A., Perez-Caballero D., Bieniasz P.D. Proc. Natl. Acad. Sci. U.S.A. 100:12414-12419(2003) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN THE ESCRT-II COMPLEX, INTERACTION WITH VPS36; SNF8 AND CHMP6.
[7]	Erratum Martin-Serrano J., Yarovoy A., Perez-Caballero D., Bieniasz P.D. Proc. Natl. Acad. Sci. U.S.A. 100:152845-152845(2003)
[8]	"Human CHMP6, a myristoylated ESCRT-III protein, interacts directly with an ESCRT-II component EAP20 and regulates endosomal cargo sorting." Yorikawa C., Shibata H., Waguri S., Hatta K., Horii M., Katoh K., Kobayashi T., Uchiyama Y., Maki M. Biochem. J. 387:17-26(2005) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH CHMP6.
[9]	"Misfolding diverts CFTR from recycling to degradation: quality control at early endosomes." Sharma M., Pampinella F., Nemes C., Benharouga M., So J., Du K., Bache K.G., Papsin B., Zerangue N., Stenmark H., Lukacs G.L. J. Cell Biol. 164:923-933(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MISFOLDED CFTR.
[10]	"Genetic structure and evolution of the Vps25 family, a yeast ESCRT-II component." Slater R., Bishop N.E. BMC Evol. Biol. 6:59-59(2006) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[11]	"Human ESCRT-II complex and its role in human immunodeficiency virus type 1 release." Langelier C., von Schwedler U.K., Fisher R.D., De Domenico I., White P.L., Hill C.P., Kaplan J., Ward D., Sundquist W.I. J. Virol. 80:9465-9480(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SNF8; VPS36 AND CHMP6, SUBCELLULAR LOCATION.
[12]	"Avian sarcoma virus and human immunodeficiency virus, type 1 use different subsets of ESCRT proteins to facilitate the budding process." Pincetic A., Medina G., Carter C., Leis J. J. Biol. Chem. 283:29822-29830(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[13]	"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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]	"Integrated structural model and membrane targeting mechanism of the human ESCRT-II complex." Im Y.J., Hurley J.H. Dev. Cell 14:902-913(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.61 ANGSTROMS) IN COMPLEX WITH SNF8 AND VPS36.
[15]	"Structure and function of the ESCRT-II-III interface in multivesicular body biogenesis." Im Y.J., Wollert T., Boura E., Hurley J.H. Dev. Cell 17:234-243(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 102-176 IN COMPLEX WITH CHMP6, MUTAGENESIS OF VAL-124 AND THR-126.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB014763 mRNA. Translation: BAB87804.1.
AK312092 mRNA. Translation: BAG35028.1.
CH471152 Genomic DNA. Translation: EAW60879.1.
BC006282 mRNA. Translation: AAH06282.1.

IPI

IPI00031655.

RefSeq

NP_115729.1. NM_032353.2.

UniGene

Hs.500165.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2ZME	X-ray	2.90	C/D	1-102	[»]
3CUQ	X-ray	2.61	C/D	1-176	[»]
3HTU	X-ray	2.00	A/C/E/G	102-176	[»]

ProteinModelPortal

Q9BRG1.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9BRG1. 4 interactions.

MINT

MINT-5003482.

STRING

9606.ENSP00000253794.

PTM databases

PhosphoSite

Q9BRG1.

Polymorphism databases

DMDM

73920459.

Proteomic databases

PaxDb

Q9BRG1.

PeptideAtlas

Q9BRG1.

PRIDE

Q9BRG1.

Protocols and materials databases

DNASU

84313.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000253794; ENSP00000253794; ENSG00000131475.

GeneID

84313.

KEGG

hsa:84313.

UCSC

uc002ibi.3. human.

Organism-specific databases

CTD

84313.

GeneCards

GC17P040925.

HGNC

HGNC:28122. VPS25.

MIM

610907. gene.

neXtProt

NX_Q9BRG1.

PharmGKB

PA142670614.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG270942.

HOGENOM

HOG000191978.

HOVERGEN

HBG080015.

InParanoid

Q9BRG1.

KO

K12189.

OMA

PPFFTIQ.

OrthoDB

EOG4RNB9H.

PhylomeDB

Q9BRG1.

Enzyme and pathway databases

Reactome

REACT_11123. Membrane Trafficking.

Gene expression databases

Bgee

Q9BRG1.

CleanEx

HS_VPS25.

Genevestigator

Q9BRG1.

GermOnline

ENSG00000131475. Homo sapiens.

Family and domain databases

Gene3D

1.10.10.10. 1 hit.
1.10.10.570. 1 hit.

InterPro

IPR008570. ESCRT-II_cplx_vps25-sub.
IPR014041. ESCRT-II_cplx_Vps25-sub_N.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]

PANTHER

PTHR13149. PTHR13149. 1 hit.

Pfam

PF05871. ESCRT-II. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q9BRG1.

GenomeRNAi

84313.

NextBio

74014.

SOURCE

Search...

Entry information

Entry name

VPS25_HUMAN

Accession

Primary (citable) accession number: Q9BRG1
Secondary accession number(s): B2R581

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 30, 2005
Last sequence update:	June 1, 2001
Last modified:	May 1, 2013
This is version 96 of the entry and version 1 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.