VPS25_HUMAN
ID VPS25_HUMAN Reviewed; 176 AA.
AC Q9BRG1; B2R581;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Vacuolar protein-sorting-associated protein 25;
DE Short=hVps25;
DE AltName: Full=Dermal papilla-derived protein 9;
DE AltName: Full=ELL-associated protein of 20 kDa;
DE AltName: Full=ESCRT-II complex subunit VPS25;
GN Name=VPS25; Synonyms=DERP9, EAP20;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Hair follicle dermal papilla;
RA Ikeda A., Ukai Y., Yamashita M., Yoshimoto M.;
RT "Molecular cloning of a dermal papilla derived gene.";
RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cerebellum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP INTERACTION WITH SNF8; VPS36 AND CHMP6.
RX PubMed=14505570; DOI=10.1016/s0092-8674(03)00714-1;
RA von Schwedler U.K., Stuchell M., Mueller B., Ward D.M., Chung H.-Y.,
RA Morita E., Wang H.E., Davis T., He G.P., Cimbora D.M., Scott A.,
RA Kraeusslich H.-G., Kaplan J., Morham S.G., Sundquist W.I.;
RT "The protein network of HIV budding.";
RL Cell 114:701-713(2003).
RN [6]
RP IDENTIFICATION IN THE ESCRT-II COMPLEX, AND INTERACTION WITH VPS36; SNF8
RP AND CHMP6.
RX PubMed=14519844; DOI=10.1073/pnas.2133846100;
RA Martin-Serrano J., Yarovoy A., Perez-Caballero D., Bieniasz P.D.;
RT "Divergent retroviral late-budding domains recruit vacuolar protein sorting
RT factors by using alternative adaptor proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:12414-12419(2003).
RN [7]
RP ERRATUM OF PUBMED:14519844.
RA Martin-Serrano J., Yarovoy A., Perez-Caballero D., Bieniasz P.D.;
RL Proc. Natl. Acad. Sci. U.S.A. 100:152845-152845(2003).
RN [8]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH CHMP6.
RX PubMed=15511219; DOI=10.1042/bj20041227;
RA Yorikawa C., Shibata H., Waguri S., Hatta K., Horii M., Katoh K.,
RA Kobayashi T., Uchiyama Y., Maki M.;
RT "Human CHMP6, a myristoylated ESCRT-III protein, interacts directly with an
RT ESCRT-II component EAP20 and regulates endosomal cargo sorting.";
RL Biochem. J. 387:17-26(2005).
RN [9]
RP INTERACTION WITH MISFOLDED CFTR.
RX PubMed=15007060; DOI=10.1083/jcb.200312018;
RA Sharma M., Pampinella F., Nemes C., Benharouga M., So J., Du K.,
RA Bache K.G., Papsin B., Zerangue N., Stenmark H., Lukacs G.L.;
RT "Misfolding diverts CFTR from recycling to degradation: quality control at
RT early endosomes.";
RL J. Cell Biol. 164:923-933(2004).
RN [10]
RP TISSUE SPECIFICITY.
RX PubMed=16889659; DOI=10.1186/1471-2148-6-59;
RA Slater R., Bishop N.E.;
RT "Genetic structure and evolution of the Vps25 family, a yeast ESCRT-II
RT component.";
RL BMC Evol. Biol. 6:59-59(2006).
RN [11]
RP INTERACTION WITH SNF8; VPS36 AND CHMP6, AND SUBCELLULAR LOCATION.
RX PubMed=16973552; DOI=10.1128/jvi.01049-06;
RA Langelier C., von Schwedler U.K., Fisher R.D., De Domenico I., White P.L.,
RA Hill C.P., Kaplan J., Ward D., Sundquist W.I.;
RT "Human ESCRT-II complex and its role in human immunodeficiency virus type 1
RT release.";
RL J. Virol. 80:9465-9480(2006).
RN [12]
RP FUNCTION.
RX PubMed=18723511; DOI=10.1074/jbc.m804157200;
RA Pincetic A., Medina G., Carter C., Leis J.;
RT "Avian sarcoma virus and human immunodeficiency virus, type 1 use different
RT subsets of ESCRT proteins to facilitate the budding process.";
RL J. Biol. Chem. 283:29822-29830(2008).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.61 ANGSTROMS) IN COMPLEX WITH SNF8 AND VPS36.
RX PubMed=18539118; DOI=10.1016/j.devcel.2008.04.004;
RA Im Y.J., Hurley J.H.;
RT "Integrated structural model and membrane targeting mechanism of the human
RT ESCRT-II complex.";
RL Dev. Cell 14:902-913(2008).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 102-176 IN COMPLEX WITH CHMP6, AND
RP MUTAGENESIS OF VAL-124 AND THR-126.
RX PubMed=19686684; DOI=10.1016/j.devcel.2009.07.008;
RA Im Y.J., Wollert T., Boura E., Hurley J.H.;
RT "Structure and function of the ESCRT-II-III interface in multivesicular
RT body biogenesis.";
RL Dev. Cell 17:234-243(2009).
CC -!- FUNCTION: Component of the ESCRT-II complex (endosomal sorting complex
CC required for transport II), which is required for multivesicular body
CC (MVB) formation and sorting of endosomal cargo proteins into MVBs. The
CC MVB pathway mediates delivery of transmembrane proteins into the lumen
CC of the lysosome for degradation. The ESCRT-II complex is probably
CC involved in the recruitment of the ESCRT-III complex. The ESCRT-II
CC complex may also play a role in transcription regulation, possibly via
CC its interaction with ELL. The ESCRT-II complex may be involved in
CC facilitating the budding of certain RNA viruses.
CC {ECO:0000269|PubMed:18723511}.
CC -!- SUBUNIT: Component of a complex at least composed of ELL, SNF8/EAP30,
CC VPS25/EAP20 and VPS36/EAP45 (By similarity). Component of the endosomal
CC sorting complex required for transport II (ESCRT-II), composed of SNF8,
CC VPS36 and 2 copies of VPS25. Interacts with CFTR; the interaction
CC requires misfolded CFTR. Interacts (via C-terminal half) with the
CC ESCRT-III subunit CHMP6 (via N-terminal half). {ECO:0000250,
CC ECO:0000269|PubMed:14505570, ECO:0000269|PubMed:14519844,
CC ECO:0000269|PubMed:15007060, ECO:0000269|PubMed:15511219,
CC ECO:0000269|PubMed:16973552, ECO:0000269|PubMed:18539118,
CC ECO:0000269|PubMed:19686684}.
CC -!- INTERACTION:
CC Q9BRG1; Q86U10: ASPG; NbExp=5; IntAct=EBI-741945, EBI-19946665;
CC Q9BRG1; Q9BPU9: B9D2; NbExp=3; IntAct=EBI-741945, EBI-6958971;
CC Q9BRG1; Q7L4P6: BEND5; NbExp=3; IntAct=EBI-741945, EBI-724373;
CC Q9BRG1; Q9NP55: BPIFA1; NbExp=3; IntAct=EBI-741945, EBI-953896;
CC Q9BRG1; Q96FZ7: CHMP6; NbExp=7; IntAct=EBI-741945, EBI-1049648;
CC Q9BRG1; Q8IUI8: CRLF3; NbExp=12; IntAct=EBI-741945, EBI-2872414;
CC Q9BRG1; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-741945, EBI-79165;
CC Q9BRG1; Q04864: REL; NbExp=4; IntAct=EBI-741945, EBI-307352;
CC Q9BRG1; Q9H190: SDCBP2; NbExp=3; IntAct=EBI-741945, EBI-742426;
CC Q9BRG1; Q6ZU15: SEPTIN14; NbExp=3; IntAct=EBI-741945, EBI-2009297;
CC Q9BRG1; Q96H20: SNF8; NbExp=16; IntAct=EBI-741945, EBI-747719;
CC Q9BRG1; Q9NZD8: SPG21; NbExp=3; IntAct=EBI-741945, EBI-742688;
CC Q9BRG1; Q8N0S2: SYCE1; NbExp=3; IntAct=EBI-741945, EBI-6872807;
CC Q9BRG1; O75478: TADA2A; NbExp=3; IntAct=EBI-741945, EBI-742268;
CC Q9BRG1; P14373: TRIM27; NbExp=7; IntAct=EBI-741945, EBI-719493;
CC Q9BRG1; Q86VN1: VPS36; NbExp=6; IntAct=EBI-741945, EBI-4401822;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Endosome membrane. Nucleus,
CC nucleoplasm. Note=Distributes diffusely throughout the cytoplasm and
CC nucleoplasm, but exhibits a punctate distribution on coexpression with
CC CHMP6.
CC -!- TISSUE SPECIFICITY: Expressed at the mRNA level in kidney, liver,
CC pancreas, and placenta. Lower levels of expression are found in heart,
CC skeletal muscle, brain and lung. {ECO:0000269|PubMed:16889659}.
CC -!- SIMILARITY: Belongs to the VPS25 family. {ECO:0000305}.
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DR EMBL; AB014763; BAB87804.1; -; mRNA.
DR EMBL; AK312092; BAG35028.1; -; mRNA.
DR EMBL; CH471152; EAW60879.1; -; Genomic_DNA.
DR EMBL; BC006282; AAH06282.1; -; mRNA.
DR CCDS; CCDS11438.1; -.
DR RefSeq; NP_115729.1; NM_032353.3.
DR PDB; 2ZME; X-ray; 2.90 A; C/D=1-102.
DR PDB; 3CUQ; X-ray; 2.61 A; C/D=1-176.
DR PDB; 3HTU; X-ray; 2.00 A; A/C/E/G=102-176.
DR PDBsum; 2ZME; -.
DR PDBsum; 3CUQ; -.
DR PDBsum; 3HTU; -.
DR AlphaFoldDB; Q9BRG1; -.
DR SMR; Q9BRG1; -.
DR BioGRID; 124039; 57.
DR ComplexPortal; CPX-2506; ESCRT-II complex.
DR CORUM; Q9BRG1; -.
DR IntAct; Q9BRG1; 25.
DR MINT; Q9BRG1; -.
DR STRING; 9606.ENSP00000253794; -.
DR iPTMnet; Q9BRG1; -.
DR PhosphoSitePlus; Q9BRG1; -.
DR BioMuta; VPS25; -.
DR DMDM; 73920459; -.
DR EPD; Q9BRG1; -.
DR jPOST; Q9BRG1; -.
DR MassIVE; Q9BRG1; -.
DR MaxQB; Q9BRG1; -.
DR PaxDb; Q9BRG1; -.
DR PeptideAtlas; Q9BRG1; -.
DR PRIDE; Q9BRG1; -.
DR ProteomicsDB; 78762; -.
DR Antibodypedia; 29407; 231 antibodies from 31 providers.
DR DNASU; 84313; -.
DR Ensembl; ENST00000253794.7; ENSP00000253794.1; ENSG00000131475.7.
DR GeneID; 84313; -.
DR KEGG; hsa:84313; -.
DR MANE-Select; ENST00000253794.7; ENSP00000253794.1; NM_032353.4; NP_115729.1.
DR UCSC; uc002ibi.5; human.
DR CTD; 84313; -.
DR DisGeNET; 84313; -.
DR GeneCards; VPS25; -.
DR HGNC; HGNC:28122; VPS25.
DR HPA; ENSG00000131475; Low tissue specificity.
DR MIM; 610907; gene.
DR neXtProt; NX_Q9BRG1; -.
DR OpenTargets; ENSG00000131475; -.
DR PharmGKB; PA142670614; -.
DR VEuPathDB; HostDB:ENSG00000131475; -.
DR eggNOG; KOG4068; Eukaryota.
DR GeneTree; ENSGT00390000014892; -.
DR HOGENOM; CLU_087657_0_1_1; -.
DR InParanoid; Q9BRG1; -.
DR OMA; SQEFHGM; -.
DR OrthoDB; 1094121at2759; -.
DR PhylomeDB; Q9BRG1; -.
DR TreeFam; TF317731; -.
DR PathwayCommons; Q9BRG1; -.
DR Reactome; R-HSA-917729; Endosomal Sorting Complex Required For Transport (ESCRT).
DR Reactome; R-HSA-9610379; HCMV Late Events.
DR SignaLink; Q9BRG1; -.
DR BioGRID-ORCS; 84313; 794 hits in 1083 CRISPR screens.
DR ChiTaRS; VPS25; human.
DR EvolutionaryTrace; Q9BRG1; -.
DR GeneWiki; VPS25; -.
DR GenomeRNAi; 84313; -.
DR Pharos; Q9BRG1; Tbio.
DR PRO; PR:Q9BRG1; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q9BRG1; protein.
DR Bgee; ENSG00000131475; Expressed in mucosa of transverse colon and 176 other tissues.
DR ExpressionAtlas; Q9BRG1; baseline and differential.
DR Genevisible; Q9BRG1; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0010008; C:endosome membrane; IDA:UniProtKB.
DR GO; GO:0000814; C:ESCRT II complex; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR GO; GO:0047485; F:protein N-terminus binding; IPI:UniProtKB.
DR GO; GO:0005198; F:structural molecule activity; IBA:GO_Central.
DR GO; GO:0016236; P:macroautophagy; TAS:ParkinsonsUK-UCL.
DR GO; GO:0090148; P:membrane fission; IC:ComplexPortal.
DR GO; GO:0036258; P:multivesicular body assembly; TAS:ParkinsonsUK-UCL.
DR GO; GO:0007175; P:negative regulation of epidermal growth factor-activated receptor activity; IMP:UniProtKB.
DR GO; GO:0043328; P:protein transport to vacuole involved in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway; IBA:GO_Central.
DR DisProt; DP01598; -.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 1.10.10.570; -; 1.
DR InterPro; IPR008570; ESCRT-II_cplx_Vps25-sub.
DR InterPro; IPR014041; ESCRT-II_cplx_Vps25-sub_N.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR PANTHER; PTHR13149; PTHR13149; 1.
DR Pfam; PF05871; ESCRT-II; 1.
DR SUPFAM; SSF46785; SSF46785; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Endosome; Membrane; Nucleus; Protein transport;
KW Reference proteome; Transcription; Transcription regulation; Transport.
FT CHAIN 1..176
FT /note="Vacuolar protein-sorting-associated protein 25"
FT /id="PRO_0000215216"
FT VARIANT 76
FT /note="I -> V (in dbSNP:rs34494804)"
FT /id="VAR_048940"
FT MUTAGEN 124
FT /note="V->E: Abolishes binding to CHMP6."
FT /evidence="ECO:0000269|PubMed:19686684"
FT MUTAGEN 126
FT /note="T->K: Abolishes binding to CHMP6."
FT /evidence="ECO:0000269|PubMed:19686684"
FT HELIX 9..12
FT /evidence="ECO:0007829|PDB:3CUQ"
FT HELIX 14..17
FT /evidence="ECO:0007829|PDB:3CUQ"
FT HELIX 23..44
FT /evidence="ECO:0007829|PDB:3CUQ"
FT STRAND 48..50
FT /evidence="ECO:0007829|PDB:3CUQ"
FT HELIX 51..55
FT /evidence="ECO:0007829|PDB:3CUQ"
FT STRAND 60..62
FT /evidence="ECO:0007829|PDB:3CUQ"
FT TURN 63..66
FT /evidence="ECO:0007829|PDB:3CUQ"
FT HELIX 71..84
FT /evidence="ECO:0007829|PDB:3CUQ"
FT STRAND 86..89
FT /evidence="ECO:0007829|PDB:3CUQ"
FT STRAND 91..99
FT /evidence="ECO:0007829|PDB:3CUQ"
FT HELIX 104..116
FT /evidence="ECO:0007829|PDB:3HTU"
FT TURN 117..119
FT /evidence="ECO:0007829|PDB:3CUQ"
FT STRAND 123..125
FT /evidence="ECO:0007829|PDB:3HTU"
FT HELIX 127..132
FT /evidence="ECO:0007829|PDB:3HTU"
FT TURN 135..138
FT /evidence="ECO:0007829|PDB:3HTU"
FT TURN 140..143
FT /evidence="ECO:0007829|PDB:3HTU"
FT HELIX 146..158
FT /evidence="ECO:0007829|PDB:3HTU"
FT STRAND 161..165
FT /evidence="ECO:0007829|PDB:3HTU"
FT TURN 167..169
FT /evidence="ECO:0007829|PDB:3CUQ"
FT STRAND 172..175
FT /evidence="ECO:0007829|PDB:3HTU"
SQ SEQUENCE 176 AA; 20748 MW; 34963A53C3DA4DD5 CRC64;
MAMSFEWPWQ YRFPPFFTLQ PNVDTRQKQL AAWCSLVLSF CRLHKQSSMT VMEAQESPLF
NNVKLQRKLP VESIQIVLEE LRKKGNLEWL DKSKSSFLIM WRRPEEWGKL IYQWVSRSGQ
NNSVFTLYEL TNGEDTEDEE FHGLDEATLL RALQALQQEH KAEIITVSDG RGVKFF
