SNF8_HUMAN
ID SNF8_HUMAN Reviewed; 258 AA.
AC Q96H20; Q8IXY3; Q9UN50;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Vacuolar-sorting protein SNF8;
DE AltName: Full=ELL-associated protein of 30 kDa;
DE AltName: Full=ESCRT-II complex subunit VPS22;
DE Short=hVps22;
GN Name=SNF8; Synonyms=EAP30;
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].
RX PubMed=10419521; DOI=10.1074/jbc.274.31.21981;
RA Schmidt A.E., Miller T., Schmidt S.L., Shiekhattar R., Shilatifard A.;
RT "Cloning and characterization of the EAP30 subunit of the ELL complex that
RT confers derepression of transcription by RNA polymerase II.";
RL J. Biol. Chem. 274:21981-21985(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Pancreas, and Placenta;
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 [3]
RP SELF-ASSOCIATION, AND INTERACTION WITH VPS25; VPS36 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 [4]
RP IDENTIFICATION IN THE ESCRT-II COMPLEX, AND INTERACTION WITH VPS36 AND
RP VPS25.
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 [5]
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 [6]
RP INTERACTION WITH RILPL1, AND SUBCELLULAR LOCATION.
RX PubMed=16857164; DOI=10.1016/j.bbrc.2006.07.007;
RA Progida C., Spinosa M.R., De Luca A., Bucci C.;
RT "RILP interacts with the VPS22 component of the ESCRT-II complex.";
RL Biochem. Biophys. Res. Commun. 347:1074-1079(2006).
RN [7]
RP INTERACTION WITH VPS25; VPS36 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 [8]
RP INTERACTION WITH 14-3-3 PROTEINS.
RX PubMed=16260042; DOI=10.1016/j.jneumeth.2005.09.015;
RA Satoh J., Nanri Y., Yamamura T.;
RT "Rapid identification of 14-3-3-binding proteins by protein microarray
RT analysis.";
RL J. Neurosci. Methods 152:278-288(2006).
RN [9]
RP INTERACTION WITH VPS25; VPS36 AND TSG101, 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 [10]
RP FUNCTION.
RX PubMed=17959629; DOI=10.1242/jcs.017301;
RA Progida C., Malerod L., Stuffers S., Brech A., Bucci C., Stenmark H.;
RT "RILP is required for the proper morphology and function of late
RT endosomes.";
RL J. Cell Sci. 120:3729-3737(2007).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, AND SUBUNIT.
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 and
RT chemokine receptors destined for lysosomal degradation.";
RL Traffic 8:1617-1629(2007).
RN [12]
RP FUNCTION.
RX PubMed=18031739; DOI=10.1016/j.yexcr.2007.10.014;
RA Raiborg C., Malerod L., Pedersen N.M., Stenmark H.;
RT "Differential functions of Hrs and ESCRT proteins in endocytic membrane
RT trafficking.";
RL Exp. Cell Res. 314:801-813(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 FUNCTION.
RX PubMed=22660413; DOI=10.1038/ncb2502;
RA Baietti M.F., Zhang Z., Mortier E., Melchior A., Degeest G., Geeraerts A.,
RA Ivarsson Y., Depoortere F., Coomans C., Vermeiren E., Zimmermann P.,
RA David G.;
RT "Syndecan-syntenin-ALIX regulates the biogenesis of exosomes.";
RL Nat. Cell Biol. 14:677-685(2012).
RN [15]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-4, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.61 ANGSTROMS) OF 25-258 IN COMPLEX WITH VPS25 AND
RP 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).
CC -!- FUNCTION: Component of the endosomal sorting complex required for
CC transport II (ESCRT-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 by
CC participating in derepression of transcription by RNA polymerase II,
CC possibly via its interaction with ELL. Required for degradation of both
CC endocytosed EGF and EGFR, but not for the EGFR ligand-mediated
CC internalization. It is also required for the degradation of CXCR4.
CC Required for the exosomal release of SDCBP, CD63 and syndecan
CC (PubMed:22660413). {ECO:0000269|PubMed:17714434,
CC ECO:0000269|PubMed:17959629, ECO:0000269|PubMed:18031739,
CC ECO:0000269|PubMed:22660413}.
CC -!- SUBUNIT: Component of the endosomal sorting complex required for
CC transport II (ESCRT-II), composed of SNF8, VPS25 and VPS36. SNF8 is
CC essential for the stability of the ESCRT-II complex. ESCRT-II interacts
CC with ELL. Interacts with TSG101 (via the C-terminal domain). Interacts
CC with RILPL1 (via the N-terminal domain); which recruits ESCRT-II to the
CC endosome membranes. Interacts with 14-3-3 proteins.
CC {ECO:0000269|PubMed:14505570, ECO:0000269|PubMed:14519844,
CC ECO:0000269|PubMed:16260042, ECO:0000269|PubMed:16857164,
CC ECO:0000269|PubMed:16973552, ECO:0000269|PubMed:17010938,
CC ECO:0000269|PubMed:17714434, ECO:0000269|PubMed:18539118}.
CC -!- INTERACTION:
CC Q96H20; Q6PJH3: AKAP9; NbExp=3; IntAct=EBI-747719, EBI-11745576;
CC Q96H20; P55212: CASP6; NbExp=3; IntAct=EBI-747719, EBI-718729;
CC Q96H20; Q92989: CLP1; NbExp=3; IntAct=EBI-747719, EBI-2559831;
CC Q96H20; Q8WUE5: CT55; NbExp=3; IntAct=EBI-747719, EBI-6873363;
CC Q96H20; O75190-2: DNAJB6; NbExp=3; IntAct=EBI-747719, EBI-12593112;
CC Q96H20; P55199: ELL; NbExp=3; IntAct=EBI-747719, EBI-1245868;
CC Q96H20; Q9NW38: FANCL; NbExp=3; IntAct=EBI-747719, EBI-2339898;
CC Q96H20; Q8IVS8: GLYCTK; NbExp=5; IntAct=EBI-747719, EBI-748515;
CC Q96H20; Q08379: GOLGA2; NbExp=3; IntAct=EBI-747719, EBI-618309;
CC Q96H20; O60341: KDM1A; NbExp=2; IntAct=EBI-747719, EBI-710124;
CC Q96H20; O14901: KLF11; NbExp=3; IntAct=EBI-747719, EBI-948266;
CC Q96H20; P13473-2: LAMP2; NbExp=3; IntAct=EBI-747719, EBI-21591415;
CC Q96H20; P49736: MCM2; NbExp=8; IntAct=EBI-747719, EBI-374819;
CC Q96H20; P24928: POLR2A; NbExp=2; IntAct=EBI-747719, EBI-295301;
CC Q96H20; Q96LA8: PRMT6; NbExp=2; IntAct=EBI-747719, EBI-912440;
CC Q96H20; O75400-2: PRPF40A; NbExp=3; IntAct=EBI-747719, EBI-5280197;
CC Q96H20; P62826: RAN; NbExp=3; IntAct=EBI-747719, EBI-286642;
CC Q96H20; Q96GM5: SMARCD1; NbExp=3; IntAct=EBI-747719, EBI-358489;
CC Q96H20; O95793-2: STAU1; NbExp=3; IntAct=EBI-747719, EBI-358189;
CC Q96H20; P51687: SUOX; NbExp=5; IntAct=EBI-747719, EBI-3921347;
CC Q96H20; Q9BYV2: TRIM54; NbExp=6; IntAct=EBI-747719, EBI-2130429;
CC Q96H20; P40222: TXLNA; NbExp=3; IntAct=EBI-747719, EBI-359793;
CC Q96H20; Q08AM6: VAC14; NbExp=4; IntAct=EBI-747719, EBI-2107455;
CC Q96H20; Q9BRG1: VPS25; NbExp=16; IntAct=EBI-747719, EBI-741945;
CC Q96H20; Q86VN1: VPS36; NbExp=6; IntAct=EBI-747719, EBI-4401822;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Endosome membrane. Nucleus
CC {ECO:0000305}. Late endosome membrane. Note=Recruited to the endosome
CC membrane to participate in vesicle formation.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96H20-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96H20-2; Sequence=VSP_015340;
CC -!- SIMILARITY: Belongs to the SNF8 family. {ECO:0000305}.
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DR EMBL; AF156102; AAD46560.1; -; mRNA.
DR EMBL; BC008976; AAH08976.1; -; mRNA.
DR EMBL; BC038830; AAH38830.1; -; mRNA.
DR CCDS; CCDS11541.1; -. [Q96H20-1]
DR CCDS; CCDS82156.1; -. [Q96H20-2]
DR RefSeq; NP_001304121.1; NM_001317192.1. [Q96H20-2]
DR RefSeq; NP_001304122.1; NM_001317193.1.
DR RefSeq; NP_001304123.1; NM_001317194.1.
DR RefSeq; NP_009172.2; NM_007241.3. [Q96H20-1]
DR PDB; 2ZME; X-ray; 2.90 A; A=1-258.
DR PDB; 3CUQ; X-ray; 2.61 A; A=25-258.
DR PDBsum; 2ZME; -.
DR PDBsum; 3CUQ; -.
DR AlphaFoldDB; Q96H20; -.
DR SMR; Q96H20; -.
DR BioGRID; 116425; 72.
DR ComplexPortal; CPX-2506; ESCRT-II complex.
DR CORUM; Q96H20; -.
DR IntAct; Q96H20; 32.
DR MINT; Q96H20; -.
DR STRING; 9606.ENSP00000421380; -.
DR iPTMnet; Q96H20; -.
DR MetOSite; Q96H20; -.
DR PhosphoSitePlus; Q96H20; -.
DR BioMuta; SNF8; -.
DR DMDM; 73919323; -.
DR EPD; Q96H20; -.
DR jPOST; Q96H20; -.
DR MassIVE; Q96H20; -.
DR MaxQB; Q96H20; -.
DR PaxDb; Q96H20; -.
DR PeptideAtlas; Q96H20; -.
DR PRIDE; Q96H20; -.
DR ProteomicsDB; 76695; -. [Q96H20-1]
DR ProteomicsDB; 76696; -. [Q96H20-2]
DR Antibodypedia; 30335; 197 antibodies from 23 providers.
DR DNASU; 11267; -.
DR Ensembl; ENST00000290330.7; ENSP00000290330.3; ENSG00000159210.10. [Q96H20-2]
DR Ensembl; ENST00000502492.6; ENSP00000421380.1; ENSG00000159210.10. [Q96H20-1]
DR GeneID; 11267; -.
DR KEGG; hsa:11267; -.
DR MANE-Select; ENST00000502492.6; ENSP00000421380.1; NM_007241.4; NP_009172.2.
DR UCSC; uc002ioj.5; human. [Q96H20-1]
DR CTD; 11267; -.
DR DisGeNET; 11267; -.
DR GeneCards; SNF8; -.
DR HGNC; HGNC:17028; SNF8.
DR HPA; ENSG00000159210; Low tissue specificity.
DR MIM; 610904; gene.
DR neXtProt; NX_Q96H20; -.
DR OpenTargets; ENSG00000159210; -.
DR PharmGKB; PA142670892; -.
DR VEuPathDB; HostDB:ENSG00000159210; -.
DR eggNOG; KOG3341; Eukaryota.
DR GeneTree; ENSGT00390000007843; -.
DR HOGENOM; CLU_070147_2_0_1; -.
DR InParanoid; Q96H20; -.
DR OMA; SNTEQGC; -.
DR OrthoDB; 869548at2759; -.
DR PhylomeDB; Q96H20; -.
DR TreeFam; TF105950; -.
DR PathwayCommons; Q96H20; -.
DR Reactome; R-HSA-917729; Endosomal Sorting Complex Required For Transport (ESCRT).
DR Reactome; R-HSA-9610379; HCMV Late Events.
DR SignaLink; Q96H20; -.
DR BioGRID-ORCS; 11267; 659 hits in 1090 CRISPR screens.
DR ChiTaRS; SNF8; human.
DR EvolutionaryTrace; Q96H20; -.
DR GeneWiki; SNF8; -.
DR GenomeRNAi; 11267; -.
DR Pharos; Q96H20; Tbio.
DR PRO; PR:Q96H20; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q96H20; protein.
DR Bgee; ENSG00000159210; Expressed in apex of heart and 202 other tissues.
DR ExpressionAtlas; Q96H20; baseline and differential.
DR Genevisible; Q96H20; 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:0031902; C:late endosome membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0055037; C:recycling endosome; IDA:UniProtKB.
DR GO; GO:0005667; C:transcription regulator complex; IDA:MGI.
DR GO; GO:0016247; F:channel regulator activity; IDA:UniProtKB.
DR GO; GO:0008022; F:protein C-terminus binding; IPI: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:0045022; P:early endosome to late endosome transport; IMP:UniProtKB.
DR GO; GO:0032456; P:endocytic recycling; IMP:UniProtKB.
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:0071985; P:multivesicular body sorting pathway; TAS:ParkinsonsUK-UCL.
DR GO; GO:1903543; P:positive regulation of exosomal secretion; IMP:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; 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 GO; GO:0042176; P:regulation of protein catabolic process; IMP:UniProtKB.
DR GO; GO:0061635; P:regulation of protein complex stability; IMP:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:1903772; P:regulation of viral budding via host ESCRT complex; IMP:UniProtKB.
DR DisProt; DP02598; -.
DR Gene3D; 1.10.10.10; -; 2.
DR InterPro; IPR016689; ESCRT-2_cplx_Snf8.
DR InterPro; IPR040608; Snf8/Vps36.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR PANTHER; PTHR12806; PTHR12806; 1.
DR Pfam; PF04157; EAP30; 1.
DR PIRSF; PIRSF017215; ESCRT2_Vps22; 1.
DR SUPFAM; SSF46785; SSF46785; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Coiled coil; Cytoplasm; Endosome;
KW Membrane; Methylation; Nucleus; Protein transport; Reference proteome;
KW Transcription; Transcription regulation; Transport.
FT CHAIN 1..258
FT /note="Vacuolar-sorting protein SNF8"
FT /id="PRO_0000215209"
FT COILED 27..53
FT /evidence="ECO:0000255"
FT MOD_RES 4
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT VAR_SEQ 189
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_015340"
FT CONFLICT 250
FT /note="A -> P (in Ref. 1; AAD46560)"
FT /evidence="ECO:0000305"
FT HELIX 37..60
FT /evidence="ECO:0007829|PDB:3CUQ"
FT HELIX 62..75
FT /evidence="ECO:0007829|PDB:3CUQ"
FT HELIX 86..91
FT /evidence="ECO:0007829|PDB:3CUQ"
FT HELIX 93..115
FT /evidence="ECO:0007829|PDB:3CUQ"
FT STRAND 116..120
FT /evidence="ECO:0007829|PDB:3CUQ"
FT HELIX 121..130
FT /evidence="ECO:0007829|PDB:3CUQ"
FT TURN 131..134
FT /evidence="ECO:0007829|PDB:3CUQ"
FT HELIX 141..151
FT /evidence="ECO:0007829|PDB:3CUQ"
FT HELIX 152..154
FT /evidence="ECO:0007829|PDB:3CUQ"
FT STRAND 155..157
FT /evidence="ECO:0007829|PDB:3CUQ"
FT STRAND 159..163
FT /evidence="ECO:0007829|PDB:3CUQ"
FT STRAND 166..170
FT /evidence="ECO:0007829|PDB:3CUQ"
FT HELIX 178..187
FT /evidence="ECO:0007829|PDB:3CUQ"
FT TURN 188..190
FT /evidence="ECO:0007829|PDB:3CUQ"
FT STRAND 191..193
FT /evidence="ECO:0007829|PDB:3CUQ"
FT HELIX 195..202
FT /evidence="ECO:0007829|PDB:3CUQ"
FT HELIX 206..218
FT /evidence="ECO:0007829|PDB:3CUQ"
FT STRAND 223..231
FT /evidence="ECO:0007829|PDB:3CUQ"
FT STRAND 233..235
FT /evidence="ECO:0007829|PDB:3CUQ"
FT HELIX 249..251
FT /evidence="ECO:0007829|PDB:3CUQ"
SQ SEQUENCE 258 AA; 28864 MW; FD6CBA6BC0A4485E CRC64;
MHRRGVGAGA IAKKKLAEAK YKERGTVLAE DQLAQMSKQL DMFKTNLEEF ASKHKQEIRK
NPEFRVQFQD MCATIGVDPL ASGKGFWSEM LGVGDFYYEL GVQIIEVCLA LKHRNGGLIT
LEELHQQVLK GRGKFAQDVS QDDLIRAIKK LKALGTGFGI IPVGGTYLIQ SVPAELNMDH
TVVLQLAEKN GYVTVSEIKA SLKWETERAR QVLEHLLKEG LAWLDLQAPG EAHYWLPALF
TDLYSQEITA EEAREALP
