Full text data of VPS36
VPS36
(C13orf9, EAP45)
[Confidence: low (only semi-automatic identification from reviews)]
Vacuolar protein-sorting-associated protein 36 (ELL-associated protein of 45 kDa; ESCRT-II complex subunit VPS36)
Vacuolar protein-sorting-associated protein 36 (ELL-associated protein of 45 kDa; ESCRT-II complex subunit VPS36)
UniProt
Q86VN1
ID VPS36_HUMAN Reviewed; 386 AA.
AC Q86VN1; A8K125; Q3ZCV7; Q5H9S1; Q5VXB6; Q9H8Z5; Q9Y3E3;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUN-2003, sequence version 1.
DT 22-JAN-2014, entry version 108.
DE RecName: Full=Vacuolar protein-sorting-associated protein 36;
DE AltName: Full=ELL-associated protein of 45 kDa;
DE AltName: Full=ESCRT-II complex subunit VPS36;
GN Name=VPS36; Synonyms=C13orf9, EAP45; ORFNames=CGI-145;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=10810093; DOI=10.1101/gr.10.5.703;
RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.;
RT "Identification of novel human genes evolutionarily conserved in
RT Caenorhabditis elegans by comparative proteomics.";
RL Genome Res. 10:703-713(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 68-386.
RC TISSUE=Brain, and Teratocarcinoma;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 MRNA] (ISOFORM 2).
RC TISSUE=Retina;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E.,
RA Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T.,
RA Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R.,
RA Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S.,
RA Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M.,
RA Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J.,
RA Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E.,
RA Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L.,
RA Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J.,
RA Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S.,
RA Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J.,
RA Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M.,
RA King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A.,
RA Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S.,
RA Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S.,
RA Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A.,
RA Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L.,
RA Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M.,
RA Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP INTERACTION WITH VPS25; SNF8 AND TSG101.
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 [8]
RP IDENTIFICATION IN THE ESCRT-II COMPLEX, AND INTERACTION WITH VPS36;
RP SNF8 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
RT sorting factors by using alternative adaptor proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:12414-12419(2003).
RN [9]
RP ERRATUM.
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 [10]
RP FUNCTION, SUBCELLULAR LOCATION, DOMAIN, LIPID-BINDING, AND INTERACTION
RP WITH UBIQUITIN.
RX PubMed=15755741; DOI=10.1074/jbc.M501510200;
RA Slagsvold T., Aasland R., Hirano S., Bache K.G., Raiborg C.,
RA Trambaiolo D., Wakatsuki S., Stenmark H.;
RT "Eap45 in mammalian ESCRT-II binds ubiquitin via a phosphoinositide-
RT interacting GLUE domain.";
RL J. Biol. Chem. 280:19600-19606(2005).
RN [11]
RP INTERACTION WITH VPS25 AND RILPL1, AND SUBCELLULAR LOCATION.
RX PubMed=17010938; DOI=10.1016/j.bbrc.2006.09.064;
RA Wang T., Hong W.;
RT "RILP interacts with VPS22 and VPS36 of ESCRT-II and regulates their
RT membrane recruitment.";
RL Biochem. Biophys. Res. Commun. 350:413-423(2006).
RN [12]
RP INTERACTION WITH VPS25; SNF8 AND TSG101, UBIQUITIN-BINDING, AND
RP SUBCELLULAR LOCATION.
RX PubMed=16973552; DOI=10.1128/JVI.01049-06;
RA Langelier C., von Schwedler U.K., Fisher R.D., De Domenico I.,
RA White P.L., Hill C.P., Kaplan J., Ward D., Sundquist W.I.;
RT "Human ESCRT-II complex and its role in human immunodeficiency virus
RT type 1 release.";
RL J. Virol. 80:9465-9480(2006).
RN [13]
RP SUBCELLULAR LOCATION.
RX PubMed=17714434; DOI=10.1111/j.1600-0854.2007.00630.x;
RA Maleroed L., Stuffers S., Brech A., Stenmark H.;
RT "Vps22/EAP30 in ESCRT-II mediates endosomal sorting of growth factor
RT and chemokine receptors destined for lysosomal degradation.";
RL Traffic 8:1617-1629(2007).
RN [14]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH ECM29.
RX PubMed=20682791; DOI=10.1074/jbc.M110.154120;
RA Gorbea C., Pratt G., Ustrell V., Bell R., Sahasrabudhe S.,
RA Hughes R.E., Rechsteiner M.;
RT "A protein interaction network for Ecm29 links the 26 S proteasome to
RT molecular motors and endosomal components.";
RL J. Biol. Chem. 285:31616-31633(2010).
RN [15]
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.,
RA Buerckstuemmer T., 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 [16]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 1-138 IN COMPLEX WITH
RP UBIQUITIN, AND MUTAGENESIS OF LEU-10; VAL-67; PHE-68 AND GLU-70.
RX PubMed=17057716; DOI=10.1038/nsmb1160;
RA Alam S.L., Langelier C., Whitby F.G., Koirala S., Robinson H.,
RA Hill C.P., Sundquist W.I.;
RT "Structural basis for ubiquitin recognition by the human ESCRT-II
RT EAP45 GLUE domain.";
RL Nat. Struct. Mol. Biol. 13:1029-1030(2006).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.61 ANGSTROMS) OF 169-386 IN COMPLEX WITH
RP VPS25 AND SNF8.
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
RT human ESCRT-II complex.";
RL Dev. Cell 14:902-913(2008).
CC -!- FUNCTION: Component of the ESCRT-II complex (endosomal sorting
CC complex required for transport II), which is required for
CC multivesicular bodies (MVBs) formation and sorting of endosomal
CC cargo proteins into MVBs. The MVB pathway mediates delivery of
CC transmembrane proteins into the lumen of the lysosome for
CC degradation. The ESCRT-II complex is probably involved in the
CC recruitment of the ESCRT-III complex. Its ability to bind
CC ubiquitin probably plays a role in endosomal sorting of
CC ubiquitinated cargo proteins by ESCRT complexes. The ESCRT-II
CC complex may also play a role in transcription regulation, possibly
CC via its interaction with ELL. Binds phosphoinosides such as
CC PtdIns(3,4,5)P3.
CC -!- SUBUNIT: Component of a complex at least composed of ELL,
CC SNF8/EAP30, VPS25/EAP20 and VPS36/EAP45 (By similarity). Component
CC of the endosomal sorting complex required for transport II (ESCRT-
CC II), composed of SNF8, VPS36 and two copies of VPS25. Interacts
CC with VPS25, SNF8, TSG101 and VPS36. Interacts (via GLUE domain)
CC with ubiquitin. Interacts with RILPL1 (via the C-terminal domain);
CC which recruits ESCRT-II to the endosome membranes. Interacts with
CC ECM29.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Endosome. Late endosome.
CC Membrane. Nucleus (Probable). Note=Colocalizes with ubiquitinated
CC proteins on late endosomes. Recruited to the endosome membrane to
CC participate in vesicle formation.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q86VN1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q86VN1-2; Sequence=VSP_015342;
CC Note=No experimental confirmation available;
CC -!- DOMAIN: The GLUE domain (GRAM-like ubiquitin-binding in EAP45)
CC mediates the binding to ubiquitin and phosphoinosides.
CC -!- SIMILARITY: Belongs to the VPS36 family.
CC -!- SIMILARITY: Contains 1 GLUE C-terminal domain.
CC -!- SIMILARITY: Contains 1 GLUE N-terminal domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB14451.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
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DR EMBL; AF151903; AAD34140.1; -; mRNA.
DR EMBL; AK023182; BAB14451.1; ALT_INIT; mRNA.
DR EMBL; AK289740; BAF82429.1; -; mRNA.
DR EMBL; CR933653; CAI45953.1; -; mRNA.
DR EMBL; AL359513; CAH71658.1; -; Genomic_DNA.
DR EMBL; CH471274; EAW55895.1; -; Genomic_DNA.
DR EMBL; BC037279; AAH37279.1; -; mRNA.
DR EMBL; BC050439; AAH50439.1; -; mRNA.
DR RefSeq; NP_001269098.1; NM_001282169.1.
DR RefSeq; NP_057159.2; NM_016075.3.
DR UniGene; Hs.109520; -.
DR PDB; 2HTH; X-ray; 2.70 A; B=1-138.
DR PDB; 2ZME; X-ray; 2.90 A; B=149-386.
DR PDB; 3CUQ; X-ray; 2.61 A; B=169-386.
DR PDBsum; 2HTH; -.
DR PDBsum; 2ZME; -.
DR PDBsum; 3CUQ; -.
DR ProteinModelPortal; Q86VN1; -.
DR SMR; Q86VN1; 3-131, 172-386.
DR DIP; DIP-29249N; -.
DR IntAct; Q86VN1; 2.
DR MINT; MINT-3085996; -.
DR STRING; 9606.ENSP00000367299; -.
DR PhosphoSite; Q86VN1; -.
DR DMDM; 73920464; -.
DR PaxDb; Q86VN1; -.
DR PRIDE; Q86VN1; -.
DR DNASU; 51028; -.
DR Ensembl; ENST00000378060; ENSP00000367299; ENSG00000136100.
DR GeneID; 51028; -.
DR KEGG; hsa:51028; -.
DR UCSC; uc001vgq.3; human.
DR CTD; 51028; -.
DR GeneCards; GC13M052986; -.
DR HGNC; HGNC:20312; VPS36.
DR HPA; HPA039734; -.
DR HPA; HPA043947; -.
DR MIM; 610903; gene.
DR neXtProt; NX_Q86VN1; -.
DR PharmGKB; PA134990943; -.
DR eggNOG; NOG262969; -.
DR HOVERGEN; HBG083632; -.
DR InParanoid; Q86VN1; -.
DR KO; K12190; -.
DR OMA; CCIAIPL; -.
DR OrthoDB; EOG7VB2FM; -.
DR PhylomeDB; Q86VN1; -.
DR Reactome; REACT_11123; Membrane Trafficking.
DR ChiTaRS; VPS36; human.
DR EvolutionaryTrace; Q86VN1; -.
DR GeneWiki; VPS36; -.
DR GenomeRNAi; 51028; -.
DR NextBio; 53573; -.
DR PRO; PR:Q86VN1; -.
DR Bgee; Q86VN1; -.
DR CleanEx; HS_VPS36; -.
DR Genevestigator; Q86VN1; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005768; C:endosome; IDA:UniProtKB.
DR GO; GO:0005770; C:late endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; IEA:Ensembl.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0032266; F:phosphatidylinositol-3-phosphate binding; IEA:InterPro.
DR GO; GO:0016197; P:endosomal transport; TAS:Reactome.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0006355; P:regulation of transcription, DNA-dependent; IEA:UniProtKB-KW.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR Gene3D; 1.10.10.10; -; 2.
DR InterPro; IPR007286; EAP30.
DR InterPro; IPR021648; VPS36_GLUE.
DR InterPro; IPR011991; WHTH_DNA-bd_dom.
DR Pfam; PF04157; EAP30; 1.
DR Pfam; PF11605; Vps36_ESCRT-II; 1.
DR PROSITE; PS51495; GLUE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Coiled coil; Complete proteome;
KW Cytoplasm; Endosome; Lipid-binding; Membrane; Nucleus;
KW Protein transport; Reference proteome; Transcription;
KW Transcription regulation; Transport.
FT CHAIN 1 386 Vacuolar protein-sorting-associated
FT protein 36.
FT /FTId=PRO_0000215222.
FT DOMAIN 1 88 GLUE N-terminal.
FT DOMAIN 105 138 GLUE C-terminal.
FT COILED 160 185 Potential.
FT VAR_SEQ 1 58 Missing (in isoform 2).
FT /FTId=VSP_015342.
FT MUTAGEN 10 10 L->D: No effect on interaction with
FT ubiquitin.
FT MUTAGEN 67 67 V->A: Reduces affinity for ubiquitin up
FT to 10-fold.
FT MUTAGEN 68 68 F->A: Reduces affinity for ubiquitin up
FT to 10-fold.
FT MUTAGEN 70 70 E->A: Reduces affinity for ubiquitin up
FT to 10-fold.
FT CONFLICT 185 185 M -> V (in Ref. 3; CAI45953).
FT CONFLICT 223 223 S -> R (in Ref. 1; AAD34140).
FT STRAND 17 28
FT STRAND 38 51
FT STRAND 59 62
FT HELIX 63 65
FT STRAND 66 72
FT STRAND 81 86
FT STRAND 93 95
FT STRAND 105 110
FT HELIX 115 128
FT HELIX 175 193
FT HELIX 197 199
FT HELIX 215 224
FT HELIX 229 232
FT HELIX 233 235
FT HELIX 240 259
FT STRAND 262 265
FT HELIX 266 275
FT STRAND 278 280
FT HELIX 284 292
FT TURN 293 298
FT STRAND 300 305
FT STRAND 309 315
FT HELIX 320 323
FT HELIX 324 333
FT HELIX 339 346
FT HELIX 350 362
FT STRAND 365 373
FT STRAND 375 379
FT HELIX 381 383
SQ SEQUENCE 386 AA; 43817 MW; 21E1E66F71BA7764 CRC64;
MDRFVWTSGL LEINETLVIQ QRGVRIYDGE EKIKFDAGTL LLSTHRLIWR DQKNHECCMA
ILLSQIVFIE EQAAGIGKSA KIVVHLHPAP PNKEPGPFQS SKNSYIKLSF KEHGQIEFYR
RLSEEMTQRR WENMPVSQSL QTNRGPQPGR IRAVGIVGIE RKLEEKRKET DKNISEAFED
LSKLMIKAKE MVELSKSIAN KIKDKQGDIT EDETIRFKSY LLSMGIANPV TRETYGSGTQ
YHMQLAKQLA GILQVPLEER GGIMSLTEVY CLVNRARGME LLSPEDLVNA CKMLEALKLP
LRLRVFDSGV MVIELQSHKE EEMVASALET VSEKGSLTSE EFAKLVGMSV LLAKERLLLA
EKMGHLCRDD SVEGLRFYPN LFMTQS
//
ID VPS36_HUMAN Reviewed; 386 AA.
AC Q86VN1; A8K125; Q3ZCV7; Q5H9S1; Q5VXB6; Q9H8Z5; Q9Y3E3;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUN-2003, sequence version 1.
DT 22-JAN-2014, entry version 108.
DE RecName: Full=Vacuolar protein-sorting-associated protein 36;
DE AltName: Full=ELL-associated protein of 45 kDa;
DE AltName: Full=ESCRT-II complex subunit VPS36;
GN Name=VPS36; Synonyms=C13orf9, EAP45; ORFNames=CGI-145;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=10810093; DOI=10.1101/gr.10.5.703;
RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.;
RT "Identification of novel human genes evolutionarily conserved in
RT Caenorhabditis elegans by comparative proteomics.";
RL Genome Res. 10:703-713(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 68-386.
RC TISSUE=Brain, and Teratocarcinoma;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 MRNA] (ISOFORM 2).
RC TISSUE=Retina;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E.,
RA Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T.,
RA Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R.,
RA Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S.,
RA Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M.,
RA Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J.,
RA Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E.,
RA Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L.,
RA Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J.,
RA Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S.,
RA Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J.,
RA Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M.,
RA King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A.,
RA Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S.,
RA Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S.,
RA Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A.,
RA Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L.,
RA Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M.,
RA Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP INTERACTION WITH VPS25; SNF8 AND TSG101.
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 [8]
RP IDENTIFICATION IN THE ESCRT-II COMPLEX, AND INTERACTION WITH VPS36;
RP SNF8 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
RT sorting factors by using alternative adaptor proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:12414-12419(2003).
RN [9]
RP ERRATUM.
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 [10]
RP FUNCTION, SUBCELLULAR LOCATION, DOMAIN, LIPID-BINDING, AND INTERACTION
RP WITH UBIQUITIN.
RX PubMed=15755741; DOI=10.1074/jbc.M501510200;
RA Slagsvold T., Aasland R., Hirano S., Bache K.G., Raiborg C.,
RA Trambaiolo D., Wakatsuki S., Stenmark H.;
RT "Eap45 in mammalian ESCRT-II binds ubiquitin via a phosphoinositide-
RT interacting GLUE domain.";
RL J. Biol. Chem. 280:19600-19606(2005).
RN [11]
RP INTERACTION WITH VPS25 AND RILPL1, AND SUBCELLULAR LOCATION.
RX PubMed=17010938; DOI=10.1016/j.bbrc.2006.09.064;
RA Wang T., Hong W.;
RT "RILP interacts with VPS22 and VPS36 of ESCRT-II and regulates their
RT membrane recruitment.";
RL Biochem. Biophys. Res. Commun. 350:413-423(2006).
RN [12]
RP INTERACTION WITH VPS25; SNF8 AND TSG101, UBIQUITIN-BINDING, AND
RP SUBCELLULAR LOCATION.
RX PubMed=16973552; DOI=10.1128/JVI.01049-06;
RA Langelier C., von Schwedler U.K., Fisher R.D., De Domenico I.,
RA White P.L., Hill C.P., Kaplan J., Ward D., Sundquist W.I.;
RT "Human ESCRT-II complex and its role in human immunodeficiency virus
RT type 1 release.";
RL J. Virol. 80:9465-9480(2006).
RN [13]
RP SUBCELLULAR LOCATION.
RX PubMed=17714434; DOI=10.1111/j.1600-0854.2007.00630.x;
RA Maleroed L., Stuffers S., Brech A., Stenmark H.;
RT "Vps22/EAP30 in ESCRT-II mediates endosomal sorting of growth factor
RT and chemokine receptors destined for lysosomal degradation.";
RL Traffic 8:1617-1629(2007).
RN [14]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH ECM29.
RX PubMed=20682791; DOI=10.1074/jbc.M110.154120;
RA Gorbea C., Pratt G., Ustrell V., Bell R., Sahasrabudhe S.,
RA Hughes R.E., Rechsteiner M.;
RT "A protein interaction network for Ecm29 links the 26 S proteasome to
RT molecular motors and endosomal components.";
RL J. Biol. Chem. 285:31616-31633(2010).
RN [15]
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.,
RA Buerckstuemmer T., 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 [16]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 1-138 IN COMPLEX WITH
RP UBIQUITIN, AND MUTAGENESIS OF LEU-10; VAL-67; PHE-68 AND GLU-70.
RX PubMed=17057716; DOI=10.1038/nsmb1160;
RA Alam S.L., Langelier C., Whitby F.G., Koirala S., Robinson H.,
RA Hill C.P., Sundquist W.I.;
RT "Structural basis for ubiquitin recognition by the human ESCRT-II
RT EAP45 GLUE domain.";
RL Nat. Struct. Mol. Biol. 13:1029-1030(2006).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.61 ANGSTROMS) OF 169-386 IN COMPLEX WITH
RP VPS25 AND SNF8.
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
RT human ESCRT-II complex.";
RL Dev. Cell 14:902-913(2008).
CC -!- FUNCTION: Component of the ESCRT-II complex (endosomal sorting
CC complex required for transport II), which is required for
CC multivesicular bodies (MVBs) formation and sorting of endosomal
CC cargo proteins into MVBs. The MVB pathway mediates delivery of
CC transmembrane proteins into the lumen of the lysosome for
CC degradation. The ESCRT-II complex is probably involved in the
CC recruitment of the ESCRT-III complex. Its ability to bind
CC ubiquitin probably plays a role in endosomal sorting of
CC ubiquitinated cargo proteins by ESCRT complexes. The ESCRT-II
CC complex may also play a role in transcription regulation, possibly
CC via its interaction with ELL. Binds phosphoinosides such as
CC PtdIns(3,4,5)P3.
CC -!- SUBUNIT: Component of a complex at least composed of ELL,
CC SNF8/EAP30, VPS25/EAP20 and VPS36/EAP45 (By similarity). Component
CC of the endosomal sorting complex required for transport II (ESCRT-
CC II), composed of SNF8, VPS36 and two copies of VPS25. Interacts
CC with VPS25, SNF8, TSG101 and VPS36. Interacts (via GLUE domain)
CC with ubiquitin. Interacts with RILPL1 (via the C-terminal domain);
CC which recruits ESCRT-II to the endosome membranes. Interacts with
CC ECM29.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Endosome. Late endosome.
CC Membrane. Nucleus (Probable). Note=Colocalizes with ubiquitinated
CC proteins on late endosomes. Recruited to the endosome membrane to
CC participate in vesicle formation.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q86VN1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q86VN1-2; Sequence=VSP_015342;
CC Note=No experimental confirmation available;
CC -!- DOMAIN: The GLUE domain (GRAM-like ubiquitin-binding in EAP45)
CC mediates the binding to ubiquitin and phosphoinosides.
CC -!- SIMILARITY: Belongs to the VPS36 family.
CC -!- SIMILARITY: Contains 1 GLUE C-terminal domain.
CC -!- SIMILARITY: Contains 1 GLUE N-terminal domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB14451.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
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DR EMBL; AF151903; AAD34140.1; -; mRNA.
DR EMBL; AK023182; BAB14451.1; ALT_INIT; mRNA.
DR EMBL; AK289740; BAF82429.1; -; mRNA.
DR EMBL; CR933653; CAI45953.1; -; mRNA.
DR EMBL; AL359513; CAH71658.1; -; Genomic_DNA.
DR EMBL; CH471274; EAW55895.1; -; Genomic_DNA.
DR EMBL; BC037279; AAH37279.1; -; mRNA.
DR EMBL; BC050439; AAH50439.1; -; mRNA.
DR RefSeq; NP_001269098.1; NM_001282169.1.
DR RefSeq; NP_057159.2; NM_016075.3.
DR UniGene; Hs.109520; -.
DR PDB; 2HTH; X-ray; 2.70 A; B=1-138.
DR PDB; 2ZME; X-ray; 2.90 A; B=149-386.
DR PDB; 3CUQ; X-ray; 2.61 A; B=169-386.
DR PDBsum; 2HTH; -.
DR PDBsum; 2ZME; -.
DR PDBsum; 3CUQ; -.
DR ProteinModelPortal; Q86VN1; -.
DR SMR; Q86VN1; 3-131, 172-386.
DR DIP; DIP-29249N; -.
DR IntAct; Q86VN1; 2.
DR MINT; MINT-3085996; -.
DR STRING; 9606.ENSP00000367299; -.
DR PhosphoSite; Q86VN1; -.
DR DMDM; 73920464; -.
DR PaxDb; Q86VN1; -.
DR PRIDE; Q86VN1; -.
DR DNASU; 51028; -.
DR Ensembl; ENST00000378060; ENSP00000367299; ENSG00000136100.
DR GeneID; 51028; -.
DR KEGG; hsa:51028; -.
DR UCSC; uc001vgq.3; human.
DR CTD; 51028; -.
DR GeneCards; GC13M052986; -.
DR HGNC; HGNC:20312; VPS36.
DR HPA; HPA039734; -.
DR HPA; HPA043947; -.
DR MIM; 610903; gene.
DR neXtProt; NX_Q86VN1; -.
DR PharmGKB; PA134990943; -.
DR eggNOG; NOG262969; -.
DR HOVERGEN; HBG083632; -.
DR InParanoid; Q86VN1; -.
DR KO; K12190; -.
DR OMA; CCIAIPL; -.
DR OrthoDB; EOG7VB2FM; -.
DR PhylomeDB; Q86VN1; -.
DR Reactome; REACT_11123; Membrane Trafficking.
DR ChiTaRS; VPS36; human.
DR EvolutionaryTrace; Q86VN1; -.
DR GeneWiki; VPS36; -.
DR GenomeRNAi; 51028; -.
DR NextBio; 53573; -.
DR PRO; PR:Q86VN1; -.
DR Bgee; Q86VN1; -.
DR CleanEx; HS_VPS36; -.
DR Genevestigator; Q86VN1; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005768; C:endosome; IDA:UniProtKB.
DR GO; GO:0005770; C:late endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; IEA:Ensembl.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0032266; F:phosphatidylinositol-3-phosphate binding; IEA:InterPro.
DR GO; GO:0016197; P:endosomal transport; TAS:Reactome.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0006355; P:regulation of transcription, DNA-dependent; IEA:UniProtKB-KW.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR Gene3D; 1.10.10.10; -; 2.
DR InterPro; IPR007286; EAP30.
DR InterPro; IPR021648; VPS36_GLUE.
DR InterPro; IPR011991; WHTH_DNA-bd_dom.
DR Pfam; PF04157; EAP30; 1.
DR Pfam; PF11605; Vps36_ESCRT-II; 1.
DR PROSITE; PS51495; GLUE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Coiled coil; Complete proteome;
KW Cytoplasm; Endosome; Lipid-binding; Membrane; Nucleus;
KW Protein transport; Reference proteome; Transcription;
KW Transcription regulation; Transport.
FT CHAIN 1 386 Vacuolar protein-sorting-associated
FT protein 36.
FT /FTId=PRO_0000215222.
FT DOMAIN 1 88 GLUE N-terminal.
FT DOMAIN 105 138 GLUE C-terminal.
FT COILED 160 185 Potential.
FT VAR_SEQ 1 58 Missing (in isoform 2).
FT /FTId=VSP_015342.
FT MUTAGEN 10 10 L->D: No effect on interaction with
FT ubiquitin.
FT MUTAGEN 67 67 V->A: Reduces affinity for ubiquitin up
FT to 10-fold.
FT MUTAGEN 68 68 F->A: Reduces affinity for ubiquitin up
FT to 10-fold.
FT MUTAGEN 70 70 E->A: Reduces affinity for ubiquitin up
FT to 10-fold.
FT CONFLICT 185 185 M -> V (in Ref. 3; CAI45953).
FT CONFLICT 223 223 S -> R (in Ref. 1; AAD34140).
FT STRAND 17 28
FT STRAND 38 51
FT STRAND 59 62
FT HELIX 63 65
FT STRAND 66 72
FT STRAND 81 86
FT STRAND 93 95
FT STRAND 105 110
FT HELIX 115 128
FT HELIX 175 193
FT HELIX 197 199
FT HELIX 215 224
FT HELIX 229 232
FT HELIX 233 235
FT HELIX 240 259
FT STRAND 262 265
FT HELIX 266 275
FT STRAND 278 280
FT HELIX 284 292
FT TURN 293 298
FT STRAND 300 305
FT STRAND 309 315
FT HELIX 320 323
FT HELIX 324 333
FT HELIX 339 346
FT HELIX 350 362
FT STRAND 365 373
FT STRAND 375 379
FT HELIX 381 383
SQ SEQUENCE 386 AA; 43817 MW; 21E1E66F71BA7764 CRC64;
MDRFVWTSGL LEINETLVIQ QRGVRIYDGE EKIKFDAGTL LLSTHRLIWR DQKNHECCMA
ILLSQIVFIE EQAAGIGKSA KIVVHLHPAP PNKEPGPFQS SKNSYIKLSF KEHGQIEFYR
RLSEEMTQRR WENMPVSQSL QTNRGPQPGR IRAVGIVGIE RKLEEKRKET DKNISEAFED
LSKLMIKAKE MVELSKSIAN KIKDKQGDIT EDETIRFKSY LLSMGIANPV TRETYGSGTQ
YHMQLAKQLA GILQVPLEER GGIMSLTEVY CLVNRARGME LLSPEDLVNA CKMLEALKLP
LRLRVFDSGV MVIELQSHKE EEMVASALET VSEKGSLTSE EFAKLVGMSV LLAKERLLLA
EKMGHLCRDD SVEGLRFYPN LFMTQS
//
MIM
610903
*RECORD*
*FIELD* NO
610903
*FIELD* TI
*610903 VACUOLAR PROTEIN SORTING 36, S. CEREVISIAE, HOMOLOG OF; VPS36
;;ELL-ASSOCIATED PROTEIN, 45-KD; EAP45
read more*FIELD* TX
DESCRIPTION
VPS36, VPS22 (SNF8; 610904), and VPS25 (610907) form ESCRT-II (endosomal
sorting complex required for transport II), a complex involved in
endocytosis of ubiquitinated membrane proteins. VPS36, VPS22, and VPS25
are also associated in a multiprotein complex with RNA polymerase II
elongation factor (ELL; 600284) (Slagsvold et al., 2005; Kamura et al.,
2001).
CLONING
Kamura et al. (2001) purified an Ell-containing complex from rat liver
extracts, and by peptide sequencing and database analysis, they
identified mouse and human VPS36, which they called EAP45. The deduced
386-amino acid human protein shares 97% identity with mouse Eap45.
GENE FUNCTION
Using mouse proteins expressed in mammalian and insect cells, Kamura et
al. (2001) found that Eap30 (SNF8) and Eap20 (VPS25) could be
coimmunoprecipitated in the absence of Eap45, and that Eap20 and Eap45
could be coimmunoprecipitated in the absence of Eap30. However, little
Eap30 was coimmunoprecipitated with Eap45 in the absence of Eap20.
Kamura et al. (2001) concluded that EAP20 bridges EAP30 and EAP45 and
thereby nucleates assembly of the EAP complex.
Slagsvold et al. (2005) found that mouse Eap45 contains a novel
N-terminal ubiquitin-binding domain that they called the GLUE (GRAM-like
ubiquitin binding in Eap45) domain. The Eap45 GLUE domain shares primary
and secondary structures with those of the phosphoinositide-binding GRAM
and pleckstrin (PLEK; 173570) homology (PH) domains. Slagsvold et al.
(2005) showed that the GLUE domain of Eap45 bound ubiquitin with similar
affinity and specificity as other ubiquitin-binding domains. The GLUE
domain of Eap45 also bound specifically to phosphatidylinositol
3,4,5-trisphosphate (PtdIns(3,4,5)P3) and more weakly to PtdIns(3,4)P2
and PtdIns(3,5)P2. Eap45 colocalized with ubiquitinated proteins on late
endosomes. Slagsvold et al. (2005) concluded that binding of
phosphoinositides on endosomal membranes by EAP45 may control the
localization and/or activity of EAP45.
BIOCHEMICAL FEATURES
Alam et al. (2006) solved the crystal structure of the human EAP45 GLUE
domain complexed with ubiquitin. The GLUE domain adopted a PH domain
fold, with a 7-stranded beta sandwich capped by a C-terminal alpha
helix. The PH domain fold was split by a 16-residue insertion that
formed an exposed loop. Ubiquitin bound along one edge of the beta
sandwich, and Alam et al. (2006) predicted that phosphoinositides would
bind a noncanonical binding site on the other side at the apex of the
beta sandwich.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the VPS36
gene to chromosome 13 (TMAP RH183).
*FIELD* RF
1. Alam, S. L.; Langelier, C.; Whitby, F. G.; Koirala, S.; Robinson,
H.; Hill, C. P.; Sundquist, W. I.: Structural basis for ubiquitin
recognition by the human ESCRT-II EAP45 GLUE domain. Nature Struct.
Biol. 13: 1029-1030, 2006.
2. Kamura, T.; Burian, D.; Khalili, H.; Schmidt, S. L.; Sato, S.;
Liu, W.-J.; Conrad, M. N.; Conaway, R. C.; Conaway, J. W.; Shilatifard,
A.: Cloning and characterization of ELL-associated proteins EAP45
and EAP20: a role for yeast EAP-like proteins in regulation of gene
expression by glucose. J. Biol. Chem. 276: 16528-16533, 2001.
3. Slagsvold, T.; Aasland, R.; Hirano, S.; Bache, K. G.; Raiborg,
C.; Trambaiolo, D.; Wakatsuki, S.; Stenmark, H.: Eap45 in mammalian
ESCRT-II binds ubiquitin via a phosphoinositide-interacting GLUE domain. J.
Biol. Chem. 280: 19600-19606, 2005.
*FIELD* CD
Patricia A. Hartz: 4/2/2007
*FIELD* ED
mgross: 04/02/2007
mgross: 4/2/2007
*RECORD*
*FIELD* NO
610903
*FIELD* TI
*610903 VACUOLAR PROTEIN SORTING 36, S. CEREVISIAE, HOMOLOG OF; VPS36
;;ELL-ASSOCIATED PROTEIN, 45-KD; EAP45
read more*FIELD* TX
DESCRIPTION
VPS36, VPS22 (SNF8; 610904), and VPS25 (610907) form ESCRT-II (endosomal
sorting complex required for transport II), a complex involved in
endocytosis of ubiquitinated membrane proteins. VPS36, VPS22, and VPS25
are also associated in a multiprotein complex with RNA polymerase II
elongation factor (ELL; 600284) (Slagsvold et al., 2005; Kamura et al.,
2001).
CLONING
Kamura et al. (2001) purified an Ell-containing complex from rat liver
extracts, and by peptide sequencing and database analysis, they
identified mouse and human VPS36, which they called EAP45. The deduced
386-amino acid human protein shares 97% identity with mouse Eap45.
GENE FUNCTION
Using mouse proteins expressed in mammalian and insect cells, Kamura et
al. (2001) found that Eap30 (SNF8) and Eap20 (VPS25) could be
coimmunoprecipitated in the absence of Eap45, and that Eap20 and Eap45
could be coimmunoprecipitated in the absence of Eap30. However, little
Eap30 was coimmunoprecipitated with Eap45 in the absence of Eap20.
Kamura et al. (2001) concluded that EAP20 bridges EAP30 and EAP45 and
thereby nucleates assembly of the EAP complex.
Slagsvold et al. (2005) found that mouse Eap45 contains a novel
N-terminal ubiquitin-binding domain that they called the GLUE (GRAM-like
ubiquitin binding in Eap45) domain. The Eap45 GLUE domain shares primary
and secondary structures with those of the phosphoinositide-binding GRAM
and pleckstrin (PLEK; 173570) homology (PH) domains. Slagsvold et al.
(2005) showed that the GLUE domain of Eap45 bound ubiquitin with similar
affinity and specificity as other ubiquitin-binding domains. The GLUE
domain of Eap45 also bound specifically to phosphatidylinositol
3,4,5-trisphosphate (PtdIns(3,4,5)P3) and more weakly to PtdIns(3,4)P2
and PtdIns(3,5)P2. Eap45 colocalized with ubiquitinated proteins on late
endosomes. Slagsvold et al. (2005) concluded that binding of
phosphoinositides on endosomal membranes by EAP45 may control the
localization and/or activity of EAP45.
BIOCHEMICAL FEATURES
Alam et al. (2006) solved the crystal structure of the human EAP45 GLUE
domain complexed with ubiquitin. The GLUE domain adopted a PH domain
fold, with a 7-stranded beta sandwich capped by a C-terminal alpha
helix. The PH domain fold was split by a 16-residue insertion that
formed an exposed loop. Ubiquitin bound along one edge of the beta
sandwich, and Alam et al. (2006) predicted that phosphoinositides would
bind a noncanonical binding site on the other side at the apex of the
beta sandwich.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the VPS36
gene to chromosome 13 (TMAP RH183).
*FIELD* RF
1. Alam, S. L.; Langelier, C.; Whitby, F. G.; Koirala, S.; Robinson,
H.; Hill, C. P.; Sundquist, W. I.: Structural basis for ubiquitin
recognition by the human ESCRT-II EAP45 GLUE domain. Nature Struct.
Biol. 13: 1029-1030, 2006.
2. Kamura, T.; Burian, D.; Khalili, H.; Schmidt, S. L.; Sato, S.;
Liu, W.-J.; Conrad, M. N.; Conaway, R. C.; Conaway, J. W.; Shilatifard,
A.: Cloning and characterization of ELL-associated proteins EAP45
and EAP20: a role for yeast EAP-like proteins in regulation of gene
expression by glucose. J. Biol. Chem. 276: 16528-16533, 2001.
3. Slagsvold, T.; Aasland, R.; Hirano, S.; Bache, K. G.; Raiborg,
C.; Trambaiolo, D.; Wakatsuki, S.; Stenmark, H.: Eap45 in mammalian
ESCRT-II binds ubiquitin via a phosphoinositide-interacting GLUE domain. J.
Biol. Chem. 280: 19600-19606, 2005.
*FIELD* CD
Patricia A. Hartz: 4/2/2007
*FIELD* ED
mgross: 04/02/2007
mgross: 4/2/2007