VPS35_HUMAN
ID VPS35_HUMAN Reviewed; 796 AA.
AC Q96QK1; Q561W2; Q9H016; Q9H096; Q9H4P3; Q9H8J0; Q9NRS7; Q9NVG2; Q9NX80;
AC Q9NZK2;
DT 25-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2002, sequence version 2.
DT 03-AUG-2022, entry version 200.
DE RecName: Full=Vacuolar protein sorting-associated protein 35;
DE Short=hVPS35;
DE AltName: Full=Maternal-embryonic 3;
DE AltName: Full=Vesicle protein sorting 35;
GN Name=VPS35 {ECO:0000303|PubMed:28397838, ECO:0000312|HGNC:HGNC:13487};
GN Synonyms=MEM3; ORFNames=TCCCTA00141;
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=Lung;
RX PubMed=11062004; DOI=10.1006/bbrc.2000.3727;
RA Edgar A.J., Polak J.M.;
RT "Human homologues of yeast vacuolar protein sorting 29 and 35.";
RL Biochem. Biophys. Res. Commun. 277:622-630(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Testis;
RX PubMed=11112353; DOI=10.1006/geno.2000.6380;
RA Zhang P., Yu L., Gao J., Fu Q., Dai F., Zhao Y., Zheng L., Zhao S.;
RT "Cloning and characterization of human VPS35 and mouse Vps35 and mapping of
RT VPS35 to human chromosome 16q13-q21.";
RL Genomics 70:253-257(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND INTERACTION WITH VPS29; VPS26A; SNX1 AND
RP SNX2.
RC TISSUE=Colon;
RX PubMed=11102511; DOI=10.1091/mbc.11.12.4105;
RA Renfrew Haft C., de la Luz Sierra M., Bafford R., Lesniak M.A., Barr V.A.,
RA Taylor S.I.;
RT "Human orthologs of yeast vacuolar protein sorting proteins Vps26, 29, and
RT 35: assembly into multimeric complexes.";
RL Mol. Biol. Cell 11:4105-4116(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pheochromocytoma;
RA Peng Y., Li Y., Tu Y., Xu S., Han Z., Fu G., Chen Z.;
RT "A novel gene expressed in human pheochromocytoma.";
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ileal mucosa, Placenta, 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., 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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Placenta, and Prostate;
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 469-796.
RC TISSUE=Leukemia;
RA Zhou J., Yu W., Tang H., Mei G., Tsang Y.T.M., Bouck J., Gibbs R.A.,
RA Margolin J.F.;
RT "Pediatric leukemia cDNA sequencing project.";
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH IGF2R.
RX PubMed=15078903; DOI=10.1083/jcb.200312055;
RA Arighi C.N., Hartnell L.M., Aguilar R.C., Haft C.R., Bonifacino J.S.;
RT "Role of the mammalian retromer in sorting of the cation-independent
RT mannose 6-phosphate receptor.";
RL J. Cell Biol. 165:123-133(2004).
RN [10]
RP FUNCTION.
RX PubMed=15247922; DOI=10.1038/ncb1153;
RA Verges M., Luton F., Gruber C., Tiemann F., Reinders L.G., Huang L.,
RA Burlingame A.L., Haft C.R., Mostov K.E.;
RT "The mammalian retromer regulates transcytosis of the polymeric
RT immunoglobulin receptor.";
RL Nat. Cell Biol. 6:763-769(2004).
RN [11]
RP INTERACTION WITH EHD1.
RX PubMed=17868075; DOI=10.1111/j.1600-0854.2007.00652.x;
RA Gokool S., Tattersall D., Seaman M.N.;
RT "EHD1 interacts with retromer to stabilize SNX1 tubules and facilitate
RT endosome-to-Golgi retrieval.";
RL Traffic 8:1873-1886(2007).
RN [12]
RP INTERACTION WITH RAB7A.
RX PubMed=19531583; DOI=10.1242/jcs.048686;
RA Seaman M.N., Harbour M.E., Tattersall D., Read E., Bright N.;
RT "Membrane recruitment of the cargo-selective retromer subcomplex is
RT catalysed by the small GTPase Rab7 and inhibited by the Rab-GAP TBC1D5.";
RL J. Cell Sci. 122:2371-2382(2009).
RN [13]
RP INTERACTION WITH GOLPH3.
RX PubMed=19553991; DOI=10.1038/nature08109;
RA Scott K.L., Kabbarah O., Liang M.C., Ivanova E., Anagnostou V., Wu J.,
RA Dhakal S., Wu M., Chen S., Feinberg T., Huang J., Saci A., Widlund H.R.,
RA Fisher D.E., Xiao Y., Rimm D.L., Protopopov A., Wong K.K., Chin L.;
RT "GOLPH3 modulates mTOR signalling and rapamycin sensitivity in cancer.";
RL Nature 459:1085-1090(2009).
RN [14]
RP FUNCTION.
RX PubMed=20923837; DOI=10.1242/jcs.071472;
RA Harbour M.E., Breusegem S.Y., Antrobus R., Freeman C., Reid E.,
RA Seaman M.N.;
RT "The cargo-selective retromer complex is a recruiting hub for protein
RT complexes that regulate endosomal tubule dynamics.";
RL J. Cell Sci. 123:3703-3717(2010).
RN [15]
RP FUNCTION.
RX PubMed=20164305; DOI=10.1242/jcs.060574;
RA Tabuchi M., Yanatori I., Kawai Y., Kishi F.;
RT "Retromer-mediated direct sorting is required for proper endosomal
RT recycling of the mammalian iron transporter DMT1.";
RL J. Cell Sci. 123:756-766(2010).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-7, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
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 [18]
RP FUNCTION OF THE SNX3-RETROMER, AND SUBUNIT.
RX PubMed=21725319; DOI=10.1038/ncb2281;
RA Harterink M., Port F., Lorenowicz M.J., McGough I.J., Silhankova M.,
RA Betist M.C., van Weering J.R., van Heesbeen R.G., Middelkoop T.C.,
RA Basler K., Cullen P.J., Korswagen H.C.;
RT "A SNX3-dependent retromer pathway mediates retrograde transport of the Wnt
RT sorting receptor Wntless and is required for Wnt secretion.";
RL Nat. Cell Biol. 13:914-923(2011).
RN [19]
RP FUNCTION, AND INTERACTION WITH WASHC2C; FKBP15 AND WASHC1.
RX PubMed=22070227; DOI=10.1042/bj20111761;
RA Harbour M.E., Breusegem S.Y., Seaman M.N.;
RT "Recruitment of the endosomal WASH complex is mediated by the extended
RT 'tail' of Fam21 binding to the retromer protein Vps35.";
RL Biochem. J. 442:209-220(2012).
RN [20]
RP FUNCTION, AND INTERACTION WITH WASHC2C.
RX PubMed=22513087; DOI=10.1091/mbc.e11-12-1059;
RA Jia D., Gomez T.S., Billadeau D.D., Rosen M.K.;
RT "Multiple repeat elements within the FAM21 tail link the WASH actin
RT regulatory complex to the retromer.";
RL Mol. Biol. Cell 23:2352-2361(2012).
RN [21]
RP INTERACTION WITH VPS29 AND VPS26, AND MUTAGENESIS OF LEU-108 AND HIS-675.
RX PubMed=23331060; DOI=10.1111/boc.201200038;
RA Helfer E., Harbour M.E., Henriot V., Lakisic G., Sousa-Blin C.,
RA Volceanov L., Seaman M.N., Gautreau A.;
RT "Endosomal recruitment of the WASH complex: active sequences and mutations
RT impairing interaction with the retromer.";
RL Biol. Cell 105:191-207(2013).
RN [22]
RP INTERACTION WITH MAGEL2.
RX PubMed=23452853; DOI=10.1016/j.cell.2013.01.051;
RA Hao Y.H., Doyle J.M., Ramanathan S., Gomez T.S., Jia D., Xu M., Chen Z.J.,
RA Billadeau D.D., Rosen M.K., Potts P.R.;
RT "Regulation of WASH-dependent actin polymerization and protein trafficking
RT by ubiquitination.";
RL Cell 152:1051-1064(2013).
RN [23]
RP FUNCTION OF THE SNX27-RETROMER, SUBUNIT, AND INTERACTION WITH SNX27 AND
RP WASHC5.
RX PubMed=23563491; DOI=10.1038/ncb2721;
RA Steinberg F., Gallon M., Winfield M., Thomas E.C., Bell A.J., Heesom K.J.,
RA Tavare J.M., Cullen P.J.;
RT "A global analysis of SNX27-retromer assembly and cargo specificity reveals
RT a function in glucose and metal ion transport.";
RL Nat. Cell Biol. 15:461-471(2013).
RN [24]
RP FUNCTION IN RETROGRADE TRANSPORT, INTERACTION WITH LRRK2, AND
RP CHARACTERIZATION OF VARIANT PARK17 ASN-620.
RX PubMed=23395371; DOI=10.1016/j.neuron.2012.11.033;
RA MacLeod D.A., Rhinn H., Kuwahara T., Zolin A., Di Paolo G., McCabe B.D.,
RA MacCabe B.D., Marder K.S., Honig L.S., Clark L.N., Small S.A.,
RA Abeliovich A.;
RT "RAB7L1 interacts with LRRK2 to modify intraneuronal protein sorting and
RT Parkinson's disease risk.";
RL Neuron 77:425-439(2013).
RN [25]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [26]
RP INTERACTION WITH SNX3 AND SLC11A2.
RX PubMed=24344282; DOI=10.1073/pnas.1316482111;
RA Harrison M.S., Hung C.S., Liu T.T., Christiano R., Walther T.C., Burd C.G.;
RT "A mechanism for retromer endosomal coat complex assembly with cargo.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:267-272(2014).
RN [27]
RP FUNCTION, INTERACTION WITH WASHC2C, AND CHARACTERIZATION OF VARIANT PARK17
RP ASN-620.
RX PubMed=24980502; DOI=10.1016/j.cub.2014.06.024;
RA McGough I.J., Steinberg F., Jia D., Barbuti P.A., McMillan K.J.,
RA Heesom K.J., Whone A.L., Caldwell M.A., Billadeau D.D., Rosen M.K.,
RA Cullen P.J.;
RT "Retromer binding to FAM21 and the WASH complex is perturbed by the
RT Parkinson disease-linked VPS35(D620N) mutation.";
RL Curr. Biol. 24:1670-1676(2014).
RN [28]
RP FUNCTION, AND CHARACTERIZATION OF VARIANT PARK17 ASN-620.
RX PubMed=24819384; DOI=10.1038/ncomms4828;
RA Zavodszky E., Seaman M.N., Moreau K., Jimenez-Sanchez M., Breusegem S.Y.,
RA Harbour M.E., Rubinsztein D.C.;
RT "Mutation in VPS35 associated with Parkinson's disease impairs WASH complex
RT association and inhibits autophagy.";
RL Nat. Commun. 5:3828-3828(2014).
RN [29]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [30]
RP INTERACTION WITH HUMAN PAPILLOMAVIRUS 16 MINOR CAPSID PROTEIN L2 (MICROBIAL
RP INFECTION), AND FUNCTION (MICROBIAL INFECTION).
RX PubMed=25693203; DOI=10.1371/journal.ppat.1004699;
RA Popa A., Zhang W., Harrison M.S., Goodner K., Kazakov T., Goodwin E.C.,
RA Lipovsky A., Burd C.G., DiMaio D.;
RT "Direct binding of retromer to human papillomavirus type 16 minor capsid
RT protein L2 mediates endosome exit during viral infection.";
RL PLoS Pathog. 11:E1004699-E1004699(2015).
RN [31]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH VPS26A AND VPS29.
RX PubMed=28892079; DOI=10.1038/ncb3610;
RA McNally K.E., Faulkner R., Steinberg F., Gallon M., Ghai R., Pim D.,
RA Langton P., Pearson N., Danson C.M., Naegele H., Morris L.L., Singla A.,
RA Overlee B.L., Heesom K.J., Sessions R., Banks L., Collins B.M., Berger I.,
RA Billadeau D.D., Burstein E., Cullen P.J.;
RT "Retriever is a multiprotein complex for retromer-independent endosomal
RT cargo recycling.";
RL Nat. Cell Biol. 19:1214-1225(2017).
RN [32]
RP INTERACTION WITH HUMAN PAPILLOMAVIRUS 16 MINOR CAPSID PROTEIN L2 (MICROBIAL
RP INFECTION).
RX PubMed=30122350; DOI=10.1016/j.cell.2018.07.031;
RA Zhang P., Monteiro da Silva G., Deatherage C., Burd C., DiMaio D.;
RT "Cell-Penetrating Peptide Mediates Intracellular Membrane Passage of Human
RT Papillomavirus L2 Protein to Trigger Retrograde Trafficking.";
RL Cell 0:0-0(2018).
RN [33]
RP FUNCTION, INTERACTION WITH SNX3, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=30213940; DOI=10.1038/s41467-018-06114-3;
RA McGough I.J., de Groot R.E.A., Jellett A.P., Betist M.C., Varandas K.C.,
RA Danson C.M., Heesom K.J., Korswagen H.C., Cullen P.J.;
RT "SNX3-retromer requires an evolutionary conserved MON2:DOPEY2:ATP9A complex
RT to mediate Wntless sorting and Wnt secretion.";
RL Nat. Commun. 9:3737-3737(2018).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 483-780 IN COMPLEX WITH VPS29, AND
RP ELECTRON MICROSCOPY OF THE RETROMER COMPLEX CONTAINING VPS29; VPS35 AND
RP VPS26.
RX PubMed=17891154; DOI=10.1038/nature06216;
RA Hierro A., Rojas A.L., Rojas R., Murthy N., Effantin G., Kajava A.V.,
RA Steven A.C., Bonifacino J.S., Hurley J.H.;
RT "Functional architecture of the retromer cargo-recognition complex.";
RL Nature 449:1063-1067(2007).
RN [35]
RP VARIANT PARK17 ASN-620, AND VARIANTS SER-316 AND VAL-737.
RX PubMed=21763482; DOI=10.1016/j.ajhg.2011.06.001;
RA Vilarino-Guell C., Wider C., Ross O.A., Dachsel J.C., Kachergus J.M.,
RA Lincoln S.J., Soto-Ortolaza A.I., Cobb S.A., Wilhoite G.J., Bacon J.A.,
RA Behrouz B., Melrose H.L., Hentati E., Puschmann A., Evans D.M.,
RA Conibear E., Wasserman W.W., Aasly J.O., Burkhard P.R., Djaldetti R.,
RA Ghika J., Hentati F., Krygowska-Wajs A., Lynch T., Melamed E., Rajput A.,
RA Rajput A.H., Solida A., Wu R.M., Uitti R.J., Wszolek Z.K., Vingerhoets F.,
RA Farrer M.J.;
RT "VPS35 mutations in Parkinson disease.";
RL Am. J. Hum. Genet. 89:162-167(2011).
RN [36]
RP VARIANT PARK17 ASN-620, AND VARIANTS SER-51; ILE-57; ARG-82; MET-241;
RP TRP-524 AND MET-774.
RX PubMed=21763483; DOI=10.1016/j.ajhg.2011.06.008;
RA Zimprich A., Benet-Pages A., Struhal W., Graf E., Eck S.H., Offman M.N.,
RA Haubenberger D., Spielberger S., Schulte E.C., Lichtner P., Rossle S.C.,
RA Klopp N., Wolf E., Seppi K., Pirker W., Reinthaler E., Harutyunyan A.,
RA Kralovics R., Peters A., Zimprich F., Brucke T., Poewe W., Auff E.,
RA Trenkwalder C., Rost B., Ransmayr G., Winkelmann J., Meitinger T.,
RA Strom T.M.;
RT "A mutation in VPS35, encoding a subunit of the retromer complex, causes
RT late-onset Parkinson disease.";
RL Am. J. Hum. Genet. 89:168-175(2011).
RN [37]
RP VARIANT PARK17 ASN-620.
RX PubMed=22517097; DOI=10.1212/wnl.0b013e318253d5f2;
RA Lesage S., Condroyer C., Klebe S., Honore A., Tison F., Brefel-Courbon C.,
RA Durr A., Brice A.;
RT "Identification of VPS35 mutations replicated in French families with
RT Parkinson disease.";
RL Neurology 78:1449-1450(2012).
RN [38]
RP VARIANT PRO-469.
RX PubMed=28397838; DOI=10.1038/mp.2017.60;
RA Harripaul R., Vasli N., Mikhailov A., Rafiq M.A., Mittal K.,
RA Windpassinger C., Sheikh T.I., Noor A., Mahmood H., Downey S., Johnson M.,
RA Vleuten K., Bell L., Ilyas M., Khan F.S., Khan V., Moradi M., Ayaz M.,
RA Naeem F., Heidari A., Ahmed I., Ghadami S., Agha Z., Zeinali S., Qamar R.,
RA Mozhdehipanah H., John P., Mir A., Ansar M., French L., Ayub M.,
RA Vincent J.B.;
RT "Mapping autosomal recessive intellectual disability: combined microarray
RT and exome sequencing identifies 26 novel candidate genes in 192
RT consanguineous families.";
RL Mol. Psychiatry 23:973-984(2018).
CC -!- FUNCTION: Acts as component of the retromer cargo-selective complex
CC (CSC). The CSC is believed to be the core functional component of
CC retromer or respective retromer complex variants acting to prevent
CC missorting of selected transmembrane cargo proteins into the lysosomal
CC degradation pathway. The recruitment of the CSC to the endosomal
CC membrane involves RAB7A and SNX3. The CSC seems to associate with the
CC cytoplasmic domain of cargo proteins predominantly via VPS35; however,
CC these interactions seem to be of low affinity and retromer SNX proteins
CC may also contribute to cargo selectivity thus questioning the classical
CC function of the CSC. The SNX-BAR retromer mediates retrograde transport
CC of cargo proteins from endosomes to the trans-Golgi network (TGN) and
CC is involved in endosome-to-plasma membrane transport for cargo protein
CC recycling. The SNX3-retromer mediates the retrograde endosome-to-TGN
CC transport of WLS distinct from the SNX-BAR retromer pathway
CC (PubMed:30213940). The SNX27-retromer is believed to be involved in
CC endosome-to-plasma membrane trafficking and recycling of a broad
CC spectrum of cargo proteins. The CSC seems to act as recruitment hub for
CC other proteins, such as the WASH complex and TBC1D5 (Probable).
CC Required for retrograde transport of lysosomal enzyme receptor IGF2R
CC and SLC11A2. Required to regulate transcytosis of the polymeric
CC immunoglobulin receptor (pIgR-pIgA) (PubMed:15078903, PubMed:15247922,
CC PubMed:20164305). Required for endosomal localization of WASHC2C
CC (PubMed:22070227, PubMed:28892079). Mediates the association of the CSC
CC with the WASH complex via WASHC2 (PubMed:22070227, PubMed:24980502,
CC PubMed:24819384). Required for the endosomal localization of TBC1D5
CC (PubMed:20923837). {ECO:0000269|PubMed:15078903,
CC ECO:0000269|PubMed:15247922, ECO:0000269|PubMed:20164305,
CC ECO:0000269|PubMed:20923837, ECO:0000269|PubMed:22070227,
CC ECO:0000269|PubMed:23395371, ECO:0000269|PubMed:24819384,
CC ECO:0000269|PubMed:24980502, ECO:0000269|PubMed:28892079,
CC ECO:0000269|PubMed:30213940, ECO:0000303|PubMed:21725319,
CC ECO:0000303|PubMed:22070227, ECO:0000303|PubMed:22513087,
CC ECO:0000303|PubMed:23563491}.
CC -!- FUNCTION: (Microbial infection) The heterotrimeric retromer cargo-
CC selective complex (CSC) mediates the exit of human papillomavirus from
CC the early endosome and the delivery to the Golgi apparatus.
CC {ECO:0000269|PubMed:25693203, ECO:0000269|PubMed:30122350}.
CC -!- SUBUNIT: Component of the heterotrimeric retromer cargo-selective
CC complex (CSC), also decribed as vacuolar protein sorting subcomplex
CC (VPS), formed by VPS26 (VPS26A or VPS26B), VPS29 and VPS35
CC (PubMed:11102511, PubMed:28892079). The CSC has a highly elongated
CC structure with VPS26 and VPS29 binding independently at opposite distal
CC ends of VPS35 as central platform (By similarity). The CSC is believed
CC to associate with variable sorting nexins to form functionally distinct
CC retromer complex variants. The originally described retromer complex
CC (also called SNX-BAR retromer) is a pentamer containing the CSC and a
CC heterodimeric membrane-deforming subcomplex formed between SNX1 or SNX2
CC and SNX5 or SNX6 (also called SNX-BAR subcomplex); the respective CSC
CC and SNX-BAR subcomplexes associate with low affinity. The CSC
CC associates with SNX3 to form a SNX3-retromer complex. The CSC
CC associates with SNX27, the WASH complex and the SNX-BAR subcomplex to
CC form the SNX27-retromer complex (Probable). Interacts with VPS26A,
CC VPS26B, VPS29, SNX1, SNX2, IGF2R, SNX3, GOLPH3, LRRK2, SLC11A2,
CC WASHC2A, WASHC2C, FKBP15, WASHC1, RAB7A, SNX27, WASHC5, EHD1
CC (PubMed:11102511, PubMed:15078903, PubMed:17868075PubMed:22070227,
CC PubMed:19553991, PubMed:21725319, PubMed:22070227, PubMed:22513087,
CC PubMed:23331060, PubMed:23563491, PubMed:23395371, PubMed:24344282,
CC PubMed:24980502, PubMed:17891154, PubMed:19531583, PubMed:30213940).
CC Interacts with MAGEL2; leading to recruitment of the TRIM27:MAGEL2 E3
CC ubiquitin ligase complex retromer-containing endosomes
CC (PubMed:23452853). Interacts with SORCS2 (By similarity).
CC {ECO:0000250|UniProtKB:Q9EQH3, ECO:0000269|PubMed:11102511,
CC ECO:0000269|PubMed:15078903, ECO:0000269|PubMed:17868075,
CC ECO:0000269|PubMed:17891154, ECO:0000269|PubMed:19553991,
CC ECO:0000269|PubMed:21725319, ECO:0000269|PubMed:22070227,
CC ECO:0000269|PubMed:22513087, ECO:0000269|PubMed:23331060,
CC ECO:0000269|PubMed:23395371, ECO:0000269|PubMed:23452853,
CC ECO:0000269|PubMed:23563491, ECO:0000269|PubMed:24344282,
CC ECO:0000269|PubMed:24980502, ECO:0000269|PubMed:28892079,
CC ECO:0000303|PubMed:21725319, ECO:0000303|PubMed:23563491}.
CC -!- SUBUNIT: (Microbial infection) Interacts with human papillomavirus 16
CC minor capsid protein L2 (via C-terminus); this interaction mediates the
CC transport of the capsid from the early endosome to the Golgi apparatus.
CC {ECO:0000269|PubMed:25693203}.
CC -!- INTERACTION:
CC Q96QK1; P05067: APP; NbExp=3; IntAct=EBI-1054634, EBI-77613;
CC Q96QK1; Q13596: SNX1; NbExp=2; IntAct=EBI-1054634, EBI-2822329;
CC Q96QK1; Q92609: TBC1D5; NbExp=6; IntAct=EBI-1054634, EBI-742381;
CC Q96QK1; O75436: VPS26A; NbExp=23; IntAct=EBI-1054634, EBI-1043891;
CC Q96QK1; Q4G0F5: VPS26B; NbExp=9; IntAct=EBI-1054634, EBI-6151831;
CC Q96QK1; Q9UBQ0: VPS29; NbExp=17; IntAct=EBI-1054634, EBI-718596;
CC Q96QK1; Q9UBQ0-2: VPS29; NbExp=4; IntAct=EBI-1054634, EBI-11141397;
CC Q96QK1; Q9Y4E1: WASHC2C; NbExp=7; IntAct=EBI-1054634, EBI-948957;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Membrane; Peripheral membrane protein.
CC Endosome {ECO:0000269|PubMed:15078903, ECO:0000269|PubMed:28892079}.
CC Early endosome {ECO:0000305}. Late endosome {ECO:0000305}.
CC Note=Localizes to tubular profiles adjacent to endosomes.
CC {ECO:0000269|PubMed:15078903}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. Highly expressed in heart, brain,
CC placenta, skeletal muscle, spleen, thymus, testis, ovary, small
CC intestine, kidney and colon.
CC -!- DISEASE: Parkinson disease 17 (PARK17) [MIM:614203]: An autosomal
CC dominant, adult-onset form of Parkinson disease. Parkinson disease is a
CC complex neurodegenerative disorder characterized by bradykinesia,
CC resting tremor, muscular rigidity and postural instability, as well as
CC by a clinically significant response to treatment with levodopa. The
CC pathology involves the loss of dopaminergic neurons in the substantia
CC nigra and the presence of Lewy bodies (intraneuronal accumulations of
CC aggregated proteins), in surviving neurons in various areas of the
CC brain. {ECO:0000269|PubMed:21763482, ECO:0000269|PubMed:21763483,
CC ECO:0000269|PubMed:22517097, ECO:0000269|PubMed:23395371,
CC ECO:0000269|PubMed:24819384, ECO:0000269|PubMed:24980502}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the VPS35 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAG01989.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA91137.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB14626.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF191298; AAF02778.2; -; mRNA.
DR EMBL; AF186382; AAG40619.1; -; mRNA.
DR EMBL; AF175265; AAF89953.1; -; mRNA.
DR EMBL; AF183418; AAG09687.1; -; mRNA.
DR EMBL; AK001614; BAA91790.1; -; mRNA.
DR EMBL; AK023650; BAB14626.1; ALT_INIT; mRNA.
DR EMBL; AK000395; BAA91137.1; ALT_INIT; mRNA.
DR EMBL; AL136888; CAB66822.1; -; mRNA.
DR EMBL; AL512769; CAC21686.1; -; mRNA.
DR EMBL; BC002414; AAH02414.1; -; mRNA.
DR EMBL; BC010362; AAH10362.1; -; mRNA.
DR EMBL; BC093036; AAH93036.1; -; mRNA.
DR EMBL; AY007112; AAG01989.1; ALT_INIT; mRNA.
DR CCDS; CCDS10721.1; -.
DR PIR; JC7516; JC7516.
DR RefSeq; NP_060676.2; NM_018206.5.
DR PDB; 2R17; X-ray; 2.80 A; C/D=483-780.
DR PDB; 5F0J; X-ray; 2.70 A; A=14-470.
DR PDB; 5F0K; X-ray; 3.07 A; A/B/C/D/E=14-470.
DR PDB; 5F0L; X-ray; 3.20 A; A=14-470.
DR PDB; 5F0M; X-ray; 3.10 A; A=14-470.
DR PDB; 5F0P; X-ray; 2.78 A; A=14-470.
DR PDB; 5OSH; X-ray; 4.30 A; B/E/H/K=482-780.
DR PDB; 5OSI; X-ray; 2.52 A; B/E/H/K=471-781.
DR PDB; 7BLN; EM; 8.90 A; A/C=1-796.
DR PDB; 7BLO; EM; 9.50 A; A/C=12-363.
DR PDBsum; 2R17; -.
DR PDBsum; 5F0J; -.
DR PDBsum; 5F0K; -.
DR PDBsum; 5F0L; -.
DR PDBsum; 5F0M; -.
DR PDBsum; 5F0P; -.
DR PDBsum; 5OSH; -.
DR PDBsum; 5OSI; -.
DR PDBsum; 7BLN; -.
DR PDBsum; 7BLO; -.
DR AlphaFoldDB; Q96QK1; -.
DR SMR; Q96QK1; -.
DR BioGRID; 120855; 217.
DR CORUM; Q96QK1; -.
DR DIP; DIP-29076N; -.
DR IntAct; Q96QK1; 107.
DR MINT; Q96QK1; -.
DR STRING; 9606.ENSP00000299138; -.
DR BindingDB; Q96QK1; -.
DR ChEMBL; CHEMBL2216744; -.
DR TCDB; 9.A.3.1.1; the sorting nexin27 (snx27)-retromer assembly apparatus (retromeraa) family.
DR GlyGen; Q96QK1; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q96QK1; -.
DR PhosphoSitePlus; Q96QK1; -.
DR SwissPalm; Q96QK1; -.
DR BioMuta; VPS35; -.
DR DMDM; 25453321; -.
DR CPTAC; CPTAC-605; -.
DR EPD; Q96QK1; -.
DR jPOST; Q96QK1; -.
DR MassIVE; Q96QK1; -.
DR MaxQB; Q96QK1; -.
DR PaxDb; Q96QK1; -.
DR PeptideAtlas; Q96QK1; -.
DR PRIDE; Q96QK1; -.
DR ProteomicsDB; 77884; -.
DR Antibodypedia; 28023; 257 antibodies from 41 providers.
DR DNASU; 55737; -.
DR Ensembl; ENST00000299138.12; ENSP00000299138.7; ENSG00000069329.18.
DR GeneID; 55737; -.
DR KEGG; hsa:55737; -.
DR MANE-Select; ENST00000299138.12; ENSP00000299138.7; NM_018206.6; NP_060676.2.
DR UCSC; uc002eef.5; human.
DR CTD; 55737; -.
DR DisGeNET; 55737; -.
DR GeneCards; VPS35; -.
DR GeneReviews; VPS35; -.
DR HGNC; HGNC:13487; VPS35.
DR HPA; ENSG00000069329; Low tissue specificity.
DR MalaCards; VPS35; -.
DR MIM; 601501; gene.
DR MIM; 614203; phenotype.
DR neXtProt; NX_Q96QK1; -.
DR OpenTargets; ENSG00000069329; -.
DR Orphanet; 411602; Hereditary late-onset Parkinson disease.
DR PharmGKB; PA37783; -.
DR VEuPathDB; HostDB:ENSG00000069329; -.
DR eggNOG; KOG1107; Eukaryota.
DR GeneTree; ENSGT00390000007315; -.
DR HOGENOM; CLU_005836_1_0_1; -.
DR InParanoid; Q96QK1; -.
DR OMA; WWVVENP; -.
DR OrthoDB; 316875at2759; -.
DR PhylomeDB; Q96QK1; -.
DR TreeFam; TF105659; -.
DR PathwayCommons; Q96QK1; -.
DR Reactome; R-HSA-3238698; WNT ligand biogenesis and trafficking.
DR SignaLink; Q96QK1; -.
DR SIGNOR; Q96QK1; -.
DR BioGRID-ORCS; 55737; 385 hits in 1092 CRISPR screens.
DR ChiTaRS; VPS35; human.
DR EvolutionaryTrace; Q96QK1; -.
DR GeneWiki; VPS35; -.
DR GenomeRNAi; 55737; -.
DR Pharos; Q96QK1; Tbio.
DR PRO; PR:Q96QK1; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q96QK1; protein.
DR Bgee; ENSG00000069329; Expressed in ventricular zone and 111 other tissues.
DR ExpressionAtlas; Q96QK1; baseline and differential.
DR Genevisible; Q96QK1; HS.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR GO; GO:0005768; C:endosome; IDA:UniProtKB.
DR GO; GO:0010008; C:endosome membrane; IDA:ParkinsonsUK-UCL.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0005770; C:late endosome; IBA:GO_Central.
DR GO; GO:0005765; C:lysosomal membrane; HDA:UniProtKB.
DR GO; GO:0005764; C:lysosome; IDA:HPA.
DR GO; GO:0099073; C:mitochondrion-derived vesicle; IDA:ParkinsonsUK-UCL.
DR GO; GO:0043005; C:neuron projection; IEA:Ensembl.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl.
DR GO; GO:0098793; C:presynapse; IEA:Ensembl.
DR GO; GO:0030904; C:retromer complex; IDA:UniProtKB.
DR GO; GO:0030906; C:retromer, cargo-selective complex; IDA:UniProtKB.
DR GO; GO:0097422; C:tubular endosome; IDA:UniProtKB.
DR GO; GO:0031748; F:D1 dopamine receptor binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0032456; P:endocytic recycling; IMP:UniProtKB.
DR GO; GO:0006886; P:intracellular protein transport; IBA:GO_Central.
DR GO; GO:0007040; P:lysosome organization; IEA:Ensembl.
DR GO; GO:0043653; P:mitochondrial fragmentation involved in apoptotic process; IMP:ParkinsonsUK-UCL.
DR GO; GO:0099074; P:mitochondrion to lysosome transport; IMP:ParkinsonsUK-UCL.
DR GO; GO:0060548; P:negative regulation of cell death; IGI:ParkinsonsUK-UCL.
DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IGI:ParkinsonsUK-UCL.
DR GO; GO:1902823; P:negative regulation of late endosome to lysosome transport; IMP:UniProtKB.
DR GO; GO:1905166; P:negative regulation of lysosomal protein catabolic process; IEA:Ensembl.
DR GO; GO:1901215; P:negative regulation of neuron death; IGI:ParkinsonsUK-UCL.
DR GO; GO:0032463; P:negative regulation of protein homooligomerization; IEA:Ensembl.
DR GO; GO:1903828; P:negative regulation of protein localization; IEA:Ensembl.
DR GO; GO:0099639; P:neurotransmitter receptor transport, endosome to plasma membrane; IDA:ParkinsonsUK-UCL.
DR GO; GO:0098887; P:neurotransmitter receptor transport, endosome to postsynaptic membrane; IEA:Ensembl.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IEA:Ensembl.
DR GO; GO:1903181; P:positive regulation of dopamine biosynthetic process; IEA:Ensembl.
DR GO; GO:0060161; P:positive regulation of dopamine receptor signaling pathway; IDA:ParkinsonsUK-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:ParkinsonsUK-UCL.
DR GO; GO:0090326; P:positive regulation of locomotion involved in locomotory behavior; IEA:Ensembl.
DR GO; GO:0090141; P:positive regulation of mitochondrial fission; IMP:ParkinsonsUK-UCL.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; IGI:ParkinsonsUK-UCL.
DR GO; GO:0061357; P:positive regulation of Wnt protein secretion; IEA:Ensembl.
DR GO; GO:0031648; P:protein destabilization; IEA:Ensembl.
DR GO; GO:0036010; P:protein localization to endosome; IMP:UniProtKB.
DR GO; GO:0032268; P:regulation of cellular protein metabolic process; IDA:ParkinsonsUK-UCL.
DR GO; GO:1902950; P:regulation of dendritic spine maintenance; IMP:ParkinsonsUK-UCL.
DR GO; GO:0016241; P:regulation of macroautophagy; TAS:ParkinsonsUK-UCL.
DR GO; GO:0010821; P:regulation of mitochondrion organization; IGI:ParkinsonsUK-UCL.
DR GO; GO:1905606; P:regulation of presynapse assembly; ISS:ParkinsonsUK-UCL.
DR GO; GO:0031647; P:regulation of protein stability; IMP:ParkinsonsUK-UCL.
DR GO; GO:2000331; P:regulation of terminal button organization; IMP:ParkinsonsUK-UCL.
DR GO; GO:0042147; P:retrograde transport, endosome to Golgi; IMP:UniProtKB.
DR GO; GO:0007416; P:synapse assembly; IEA:Ensembl.
DR GO; GO:0045056; P:transcytosis; IDA:UniProtKB.
DR GO; GO:0099003; P:vesicle-mediated transport in synapse; IEA:Ensembl.
DR GO; GO:0050882; P:voluntary musculoskeletal movement; IEA:Ensembl.
DR GO; GO:0016055; P:Wnt signaling pathway; NAS:ParkinsonsUK-UCL.
DR Gene3D; 1.25.40.660; -; 1.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR005378; Vps35.
DR InterPro; IPR042491; Vps35_C.
DR PANTHER; PTHR11099; PTHR11099; 1.
DR Pfam; PF03635; Vps35; 1.
DR PIRSF; PIRSF009375; Retromer_Vps35; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Endosome; Host-virus interaction; Membrane;
KW Neurodegeneration; Parkinson disease; Parkinsonism; Phosphoprotein;
KW Protein transport; Reference proteome; Transport.
FT CHAIN 1..796
FT /note="Vacuolar protein sorting-associated protein 35"
FT /id="PRO_0000065896"
FT REGION 25..44
FT /note="Interaction with SNX3"
FT /evidence="ECO:0000269|PubMed:24344282"
FT REGION 205..215
FT /note="Interaction with SNX3"
FT /evidence="ECO:0000269|PubMed:24344282"
FT REGION 438..796
FT /note="Interaction with SLC11A2"
FT /evidence="ECO:0000269|PubMed:24344282"
FT REGION 500..693
FT /note="Interaction with IGF2R cytoplasmic domain"
FT /evidence="ECO:0000269|PubMed:15078903"
FT MOD_RES 7
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 783
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9EQH3"
FT MOD_RES 791
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9EQH3"
FT VARIANT 51
FT /note="G -> S (in dbSNP:rs193077277)"
FT /evidence="ECO:0000269|PubMed:21763483"
FT /id="VAR_066653"
FT VARIANT 57
FT /note="M -> I (in dbSNP:rs183554824)"
FT /evidence="ECO:0000269|PubMed:21763483"
FT /id="VAR_066654"
FT VARIANT 82
FT /note="T -> R (in dbSNP:rs188245364)"
FT /evidence="ECO:0000269|PubMed:21763483"
FT /id="VAR_066655"
FT VARIANT 241
FT /note="I -> M (found in a patient with Parkinson disease;
FT dbSNP:rs192783364)"
FT /evidence="ECO:0000269|PubMed:21763483"
FT /id="VAR_066656"
FT VARIANT 316
FT /note="P -> S (found in a patient with Parkinson disease;
FT dbSNP:rs770029606)"
FT /evidence="ECO:0000269|PubMed:21763482"
FT /id="VAR_066657"
FT VARIANT 469
FT /note="Q -> P (found in a consanguineous family with
FT intellectual disability; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:28397838"
FT /id="VAR_080769"
FT VARIANT 524
FT /note="R -> W (found in a patient with Parkinson disease;
FT dbSNP:rs184277092)"
FT /evidence="ECO:0000269|PubMed:21763483"
FT /id="VAR_066658"
FT VARIANT 602
FT /note="V -> D (in dbSNP:rs34687100)"
FT /id="VAR_054046"
FT VARIANT 620
FT /note="D -> N (in PARK17; decreases interaction with
FT WASHC2C, FKBP15 and the WASH complex; impairs recruitment
FT of the WASH complex to endosomes; shows reduced retrograde
FT transport of selective cargo between lysosomes and the
FT Golgi apparatus; shows a progressive reduction in neurite
FT length and branching; dbSNP:rs188286943)"
FT /evidence="ECO:0000269|PubMed:21763482,
FT ECO:0000269|PubMed:21763483, ECO:0000269|PubMed:22517097,
FT ECO:0000269|PubMed:23395371, ECO:0000269|PubMed:24819384,
FT ECO:0000269|PubMed:24980502"
FT /id="VAR_066659"
FT VARIANT 737
FT /note="A -> V (in dbSNP:rs749516404)"
FT /evidence="ECO:0000269|PubMed:21763482"
FT /id="VAR_066660"
FT VARIANT 774
FT /note="L -> M (in dbSNP:rs192419029)"
FT /evidence="ECO:0000269|PubMed:21763483"
FT /id="VAR_066661"
FT MUTAGEN 108
FT /note="L->P: Disrupts interaction with VPS26; no effect on
FT interaction with VPS29."
FT /evidence="ECO:0000269|PubMed:23331060"
FT MUTAGEN 675
FT /note="H->R: Disrupts interaction with VPS29. Does not
FT effect interaction with VPS26."
FT /evidence="ECO:0000269|PubMed:23331060"
FT CONFLICT 42
FT /note="A -> S (in Ref. 6; CAB66822)"
FT /evidence="ECO:0000305"
FT CONFLICT 160
FT /note="I -> T (in Ref. 5; BAB14626)"
FT /evidence="ECO:0000305"
FT CONFLICT 168
FT /note="T -> P (in Ref. 3; AAF89953)"
FT /evidence="ECO:0000305"
FT CONFLICT 453
FT /note="S -> F (in Ref. 7; AAH10362)"
FT /evidence="ECO:0000305"
FT CONFLICT 526
FT /note="R -> G (in Ref. 5; BAA91790)"
FT /evidence="ECO:0000305"
FT CONFLICT 694
FT /note="K -> E (in Ref. 5; BAA91790)"
FT /evidence="ECO:0000305"
FT CONFLICT 796
FT /note="L -> H (in Ref. 5; BAA91137)"
FT /evidence="ECO:0000305"
FT HELIX 14..35
FT /evidence="ECO:0007829|PDB:5F0J"
FT HELIX 39..50
FT /evidence="ECO:0007829|PDB:5F0J"
FT HELIX 51..54
FT /evidence="ECO:0007829|PDB:5F0J"
FT STRAND 56..58
FT /evidence="ECO:0007829|PDB:5F0J"
FT HELIX 60..86
FT /evidence="ECO:0007829|PDB:5F0J"
FT HELIX 94..97
FT /evidence="ECO:0007829|PDB:5F0J"
FT HELIX 98..100
FT /evidence="ECO:0007829|PDB:5F0J"
FT HELIX 104..121
FT /evidence="ECO:0007829|PDB:5F0J"
FT HELIX 123..125
FT /evidence="ECO:0007829|PDB:5F0J"
FT HELIX 126..136
FT /evidence="ECO:0007829|PDB:5F0J"
FT HELIX 137..139
FT /evidence="ECO:0007829|PDB:5F0J"
FT HELIX 143..156
FT /evidence="ECO:0007829|PDB:5F0J"
FT TURN 157..160
FT /evidence="ECO:0007829|PDB:5F0J"
FT HELIX 176..196
FT /evidence="ECO:0007829|PDB:5F0J"
FT HELIX 197..199
FT /evidence="ECO:0007829|PDB:5F0J"
FT HELIX 206..229
FT /evidence="ECO:0007829|PDB:5F0J"
FT HELIX 235..240
FT /evidence="ECO:0007829|PDB:5F0J"
FT HELIX 242..252
FT /evidence="ECO:0007829|PDB:5F0J"
FT HELIX 256..269
FT /evidence="ECO:0007829|PDB:5F0J"
FT HELIX 272..277
FT /evidence="ECO:0007829|PDB:5F0J"
FT HELIX 279..286
FT /evidence="ECO:0007829|PDB:5F0J"
FT HELIX 295..310
FT /evidence="ECO:0007829|PDB:5F0J"
FT STRAND 313..315
FT /evidence="ECO:0007829|PDB:5F0J"
FT STRAND 320..322
FT /evidence="ECO:0007829|PDB:5F0J"
FT HELIX 324..338
FT /evidence="ECO:0007829|PDB:5F0J"
FT HELIX 344..361
FT /evidence="ECO:0007829|PDB:5F0J"
FT HELIX 366..382
FT /evidence="ECO:0007829|PDB:5F0J"
FT STRAND 390..392
FT /evidence="ECO:0007829|PDB:5F0P"
FT HELIX 393..408
FT /evidence="ECO:0007829|PDB:5F0J"
FT HELIX 413..416
FT /evidence="ECO:0007829|PDB:5F0J"
FT TURN 419..422
FT /evidence="ECO:0007829|PDB:5F0P"
FT HELIX 423..427
FT /evidence="ECO:0007829|PDB:5F0J"
FT HELIX 430..446
FT /evidence="ECO:0007829|PDB:5F0J"
FT HELIX 454..468
FT /evidence="ECO:0007829|PDB:5F0J"
FT HELIX 485..498
FT /evidence="ECO:0007829|PDB:5OSI"
FT HELIX 503..518
FT /evidence="ECO:0007829|PDB:5OSI"
FT HELIX 521..528
FT /evidence="ECO:0007829|PDB:5OSI"
FT HELIX 530..545
FT /evidence="ECO:0007829|PDB:5OSI"
FT TURN 546..549
FT /evidence="ECO:0007829|PDB:5OSI"
FT HELIX 553..573
FT /evidence="ECO:0007829|PDB:5OSI"
FT HELIX 578..594
FT /evidence="ECO:0007829|PDB:5OSI"
FT HELIX 599..617
FT /evidence="ECO:0007829|PDB:5OSI"
FT HELIX 621..637
FT /evidence="ECO:0007829|PDB:5OSI"
FT HELIX 643..657
FT /evidence="ECO:0007829|PDB:5OSI"
FT HELIX 663..672
FT /evidence="ECO:0007829|PDB:5OSI"
FT HELIX 674..678
FT /evidence="ECO:0007829|PDB:5OSI"
FT STRAND 685..687
FT /evidence="ECO:0007829|PDB:5OSI"
FT HELIX 693..708
FT /evidence="ECO:0007829|PDB:5OSI"
FT HELIX 713..732
FT /evidence="ECO:0007829|PDB:5OSI"
FT HELIX 740..753
FT /evidence="ECO:0007829|PDB:5OSI"
FT HELIX 754..756
FT /evidence="ECO:0007829|PDB:5OSI"
FT HELIX 761..778
FT /evidence="ECO:0007829|PDB:5OSI"
SQ SEQUENCE 796 AA; 91707 MW; 28D2DD1C6B920A0A CRC64;
MPTTQQSPQD EQEKLLDEAI QAVKVQSFQM KRCLDKNKLM DALKHASNML GELRTSMLSP
KSYYELYMAI SDELHYLEVY LTDEFAKGRK VADLYELVQY AGNIIPRLYL LITVGVVYVK
SFPQSRKDIL KDLVEMCRGV QHPLRGLFLR NYLLQCTRNI LPDEGEPTDE ETTGDISDSM
DFVLLNFAEM NKLWVRMQHQ GHSRDREKRE RERQELRILV GTNLVRLSQL EGVNVERYKQ
IVLTGILEQV VNCRDALAQE YLMECIIQVF PDEFHLQTLN PFLRACAELH QNVNVKNIII
ALIDRLALFA HREDGPGIPA DIKLFDIFSQ QVATVIQSRQ DMPSEDVVSL QVSLINLAMK
CYPDRVDYVD KVLETTVEIF NKLNLEHIAT SSAVSKELTR LLKIPVDTYN NILTVLKLKH
FHPLFEYFDY ESRKSMSCYV LSNVLDYNTE IVSQDQVDSI MNLVSTLIQD QPDQPVEDPD
PEDFADEQSL VGRFIHLLRS EDPDQQYLIL NTARKHFGAG GNQRIRFTLP PLVFAAYQLA
FRYKENSKVD DKWEKKCQKI FSFAHQTISA LIKAELAELP LRLFLQGALA AGEIGFENHE
TVAYEFMSQA FSLYEDEISD SKAQLAAITL IIGTFERMKC FSEENHEPLR TQCALAASKL
LKKPDQGRAV STCAHLFWSG RNTDKNGEEL HGGKRVMECL KKALKIANQC MDPSLQVQLF
IEILNRYIYF YEKENDAVTI QVLNQLIQKI REDLPNLESS EETEQINKHF HNTLEHLRLR
RESPESEGPI YEGLIL
