VPS29_HUMAN
ID VPS29_HUMAN Reviewed; 182 AA.
AC Q9UBQ0; Q502Y5; Q6FIF8; Q6IAH3; Q9H0W0; Q9NRP1; Q9NRU7;
DT 25-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=Vacuolar protein sorting-associated protein 29;
DE Short=hVPS29;
DE AltName: Full=PEP11 homolog;
DE AltName: Full=Vesicle protein sorting 29;
GN Name=VPS29 {ECO:0000303|PubMed:30213940, ECO:0000312|HGNC:HGNC:14340};
GN ORFNames=DC15, DC7, MDS007;
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] (ISOFORMS 1 AND 2).
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] (ISOFORM 1), AND INTERACTION WITH VPS26A; VPS35;
RP SNX1 AND SNX2.
RC TISSUE=Parathyroid;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Hematopoietic stem cell;
RA Huang C., Zhang C., Tu Y., Gu W., Wang Y., Han Z., Chen Z., Zhou J., Gu J.,
RA Huang Q., Yu Y., Xu S., Ren S., Fu G., Li N.;
RT "Novel genes expressed in hematopoietic stem/progenitor cells from
RT myelodysplastic syndrome patients.";
RL Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Dendritic cell;
RA Peng Y., Li Y., Tu Y., Xu S., Han Z., Fu G., Chen Z.;
RT "Novel genes expressed in human dendritic cells.";
RL Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Fetal brain;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Cervix;
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 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 [9]
RP CAUTION, MUTAGENESIS OF ASP-8; ASN-39; ASP-62; HIS-86 AND HIS-117, AND
RP SUBUNIT.
RX PubMed=16737443; DOI=10.1042/bj20060033;
RA Damen E., Krieger E., Nielsen J.E., Eygensteyn J., van Leeuwen J.E.M.;
RT "The human Vps29 retromer component is a metallo-phosphoesterase for a
RT cation-independent mannose 6-phosphate receptor substrate peptide.";
RL Biochem. J. 398:399-409(2006).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-50, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [11]
RP INTERACTION WITH TBC1D5, AND MUTAGENESIS OF LEU-152.
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 [12]
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 [13]
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 [14]
RP LACK OF PHOSPHATASE ACTIVITY.
RX PubMed=21629666; DOI=10.1371/journal.pone.0020420;
RA Swarbrick J.D., Shaw D.J., Chhabra S., Ghai R., Valkov E., Norwood S.J.,
RA Seaman M.N., Collins B.M.;
RT "VPS29 is not an active metallo-phosphatase but is a rigid scaffold
RT required for retromer interaction with accessory proteins.";
RL PLoS ONE 6:E20420-E20420(2011).
RN [15]
RP INTERACTION WITH VPS35, AND MUTAGENESIS OF VAL-90 AND ILE-91.
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 [16]
RP INTERACTION WITH SNX27 AND WASHC5, SUBUNIT, AND FUNCTION OF THE
RP SNX27-RETROMER.
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 [17]
RP FUNCTION.
RX PubMed=24856514; DOI=10.1016/j.devcel.2014.04.010;
RA Hesketh G.G., Perez-Dorado I., Jackson L.P., Wartosch L., Schafer I.B.,
RA Gray S.R., McCoy A.J., Zeldin O.B., Garman E.F., Harbour M.E., Evans P.R.,
RA Seaman M.N., Luzio J.P., Owen D.J.;
RT "VARP is recruited on to endosomes by direct interaction with retromer,
RT where together they function in export to the cell surface.";
RL Dev. Cell 29:591-606(2014).
RN [18]
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 [19]
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 [20]
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 [21]
RP FUNCTION, IDENTIFICATION IN THE RETROMER COMPLEX, AND IDENTIFICATION IN THE
RP RETRIEVER COMPLEX.
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 [22]
RP 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 [23]
RP INTERACTION WITH VPS35L.
RX PubMed=31712251; DOI=10.1136/jmedgenet-2019-106213;
RA Kato K., Oka Y., Muramatsu H., Vasilev F.F., Otomo T., Oishi H., Kawano Y.,
RA Kidokoro H., Nakazawa Y., Ogi T., Takahashi Y., Saitoh S.;
RT "Biallelic VPS35L pathogenic variants cause 3C/Ritscher-Schinzel-like
RT syndrome through dysfunction of retriever complex.";
RL J. Med. Genet. 57:245-253(2020).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS), AND METAL-BINDING.
RX PubMed=15788412; DOI=10.1074/jbc.m500464200;
RA Wang D., Guo M., Liang Z., Fan J., Zhu Z., Zang J., Zhu Z., Li X., Teng M.,
RA Niu L., Dong Y., Liu P.;
RT "Crystal structure of human vacuolar protein sorting protein 29 reveals a
RT phosphodiesterase/nuclease-like fold and two protein-protein interaction
RT sites.";
RL J. Biol. Chem. 280:22962-22967(2005).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) IN COMPLEX WITH VPS35, AND ELECTRON
RP MICROSCOPY OF THE RETROMER COMPLEX CONTAINING VPS29; VPS35 AND 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).
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 SNX-BAR retromer mediates
CC retrograde transport of cargo proteins from endosomes to the trans-
CC Golgi network (TGN) and is involved in endosome-to-plasma membrane
CC transport for cargo protein recycling. The SNX3-retromer mediates the
CC retrograde endosome-to-TGN transport of WLS distinct from the SNX-BAR
CC retromer pathway. 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. Required to
CC regulate transcytosis of the polymeric immunoglobulin receptor (pIgR-
CC pIgA) (PubMed:15247922, PubMed:21725319, PubMed:23563491). Acts also as
CC component of the retriever complex. The retriever complex is a
CC heterotrimeric complex related to retromer cargo-selective complex
CC (CSC) and essential for retromer-independent retrieval and recycling of
CC numerous cargos such as integrin alpha-5/beta-1 (ITGA5:ITGB1)
CC (PubMed:28892079). In the endosomes, retriever complex drives the
CC retrieval and recycling of NxxY-motif-containing cargo proteins by
CC coupling to SNX17, a cargo essential for the homeostatic maintenance of
CC numerous cell surface proteins associated with processes that include
CC cell migration, cell adhesion, nutrient supply and cell signaling
CC (PubMed:28892079). The recruitment of the retriever complex to the
CC endosomal membrane involves CCC and WASH complexes (PubMed:28892079).
CC Involved in GLUT1 endosome-to-plasma membrane trafficking; the function
CC is dependent of association with ANKRD27 (PubMed:24856514).
CC {ECO:0000269|PubMed:24856514, ECO:0000269|PubMed:28892079,
CC ECO:0000303|PubMed:15247922, ECO:0000303|PubMed:21725319,
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}.
CC -!- SUBUNIT: Component of the heterotrimeric retromer cargo-selective
CC complex (CSC), also described as vacuolar protein sorting subcomplex
CC (VPS), formed by VPS26 (VPS26A or VPS26B), VPS29 and VPS35
CC (PubMed:11102511, PubMed:16737443, PubMed:17891154, PubMed:28892079).
CC The CSC has a highly elongated structure with VPS26 and VPS29 binding
CC independently at opposite distal ends of VPS35 as central platform (By
CC similarity). The CSC is believed to associate with variable sorting
CC nexins to form functionally distinct retromer complex variants. The
CC originally described retromer complex (also called SNX-BAR retromer) is
CC a pentamer containing the CSC and a heterodimeric membrane-deforming
CC subcomplex formed between SNX1 or SNX2 and SNX5 or SNX6 (also called
CC SNX-BAR subcomplex); the respective CSC and SNX-BAR subcomplexes
CC associate with low affinity. The CSC associates with SNX3 to form a
CC SNX3-retromer complex. The CSC associates with SNX27, the WASH complex
CC and the SNX-BAR subcomplex to form the SNX27-retromer complex
CC (PubMed:21725319, PubMed:23563491). Component of the heterotrimeric
CC retriever complex formed by VPS26C, VPS29 and VPS35L (PubMed:28892079).
CC Interacts with VPS35L (PubMed:31712251). Interacts with VPS26A, VPS35,
CC SNX1, SNX2, SNX3, SNX27, WASHC5, TBC1D5 (PubMed:11102511,
CC PubMed:20923837, PubMed:23331060, PubMed:23563491, PubMed:28892079,
CC PubMed:30213940). Interacts with VPS26B and ANKRD27 (By similarity).
CC {ECO:0000250|UniProtKB:Q9QZ88, ECO:0000269|PubMed:11102511,
CC ECO:0000269|PubMed:16737443, ECO:0000269|PubMed:17891154,
CC ECO:0000269|PubMed:20923837, ECO:0000269|PubMed:23331060,
CC ECO:0000269|PubMed:23563491, ECO:0000269|PubMed:28892079,
CC ECO:0000269|PubMed:31712251, ECO:0000303|PubMed:21725319,
CC 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 Q9UBQ0; B9A6K1: TBC1D5; NbExp=3; IntAct=EBI-718596, EBI-10217641;
CC Q9UBQ0; Q92609: TBC1D5; NbExp=4; IntAct=EBI-718596, EBI-742381;
CC Q9UBQ0; O75436: VPS26A; NbExp=9; IntAct=EBI-718596, EBI-1043891;
CC Q9UBQ0; Q96QK1: VPS35; NbExp=17; IntAct=EBI-718596, EBI-1054634;
CC Q9UBQ0-2; P01023: A2M; NbExp=3; IntAct=EBI-11141397, EBI-640741;
CC Q9UBQ0-2; P60709: ACTB; NbExp=3; IntAct=EBI-11141397, EBI-353944;
CC Q9UBQ0-2; P51693: APLP1; NbExp=3; IntAct=EBI-11141397, EBI-74648;
CC Q9UBQ0-2; P21810: BGN; NbExp=3; IntAct=EBI-11141397, EBI-762076;
CC Q9UBQ0-2; Q13867: BLMH; NbExp=3; IntAct=EBI-11141397, EBI-718504;
CC Q9UBQ0-2; Q9UQM7: CAMK2A; NbExp=3; IntAct=EBI-11141397, EBI-1383687;
CC Q9UBQ0-2; P29466-3: CASP1; NbExp=3; IntAct=EBI-11141397, EBI-12248206;
CC Q9UBQ0-2; P48730-2: CSNK1D; NbExp=3; IntAct=EBI-11141397, EBI-9087876;
CC Q9UBQ0-2; O14576-2: DYNC1I1; NbExp=3; IntAct=EBI-11141397, EBI-25840445;
CC Q9UBQ0-2; P06241: FYN; NbExp=3; IntAct=EBI-11141397, EBI-515315;
CC Q9UBQ0-2; P10809: HSPD1; NbExp=3; IntAct=EBI-11141397, EBI-352528;
CC Q9UBQ0-2; Q07954-2: LRP1; NbExp=3; IntAct=EBI-11141397, EBI-25833471;
CC Q9UBQ0-2; Q99683: MAP3K5; NbExp=3; IntAct=EBI-11141397, EBI-476263;
CC Q9UBQ0-2; I6L9F6: NEFL; NbExp=3; IntAct=EBI-11141397, EBI-10178578;
CC Q9UBQ0-2; Q99497: PARK7; NbExp=3; IntAct=EBI-11141397, EBI-1164361;
CC Q9UBQ0-2; P27986-2: PIK3R1; NbExp=3; IntAct=EBI-11141397, EBI-9090282;
CC Q9UBQ0-2; Q9BXM7: PINK1; NbExp=3; IntAct=EBI-11141397, EBI-2846068;
CC Q9UBQ0-2; P17612: PRKACA; NbExp=3; IntAct=EBI-11141397, EBI-476586;
CC Q9UBQ0-2; Q05655: PRKCD; NbExp=3; IntAct=EBI-11141397, EBI-704279;
CC Q9UBQ0-2; O60260-5: PRKN; NbExp=3; IntAct=EBI-11141397, EBI-21251460;
CC Q9UBQ0-2; P63000: RAC1; NbExp=3; IntAct=EBI-11141397, EBI-413628;
CC Q9UBQ0-2; P01011: SERPINA3; NbExp=3; IntAct=EBI-11141397, EBI-296557;
CC Q9UBQ0-2; P37840: SNCA; NbExp=3; IntAct=EBI-11141397, EBI-985879;
CC Q9UBQ0-2; Q99523: SORT1; NbExp=3; IntAct=EBI-11141397, EBI-1057058;
CC Q9UBQ0-2; Q13501: SQSTM1; NbExp=3; IntAct=EBI-11141397, EBI-307104;
CC Q9UBQ0-2; Q9UNE7: STUB1; NbExp=3; IntAct=EBI-11141397, EBI-357085;
CC Q9UBQ0-2; Q15583: TGIF1; NbExp=3; IntAct=EBI-11141397, EBI-714215;
CC Q9UBQ0-2; Q5TGY1: TMCO4; NbExp=5; IntAct=EBI-11141397, EBI-6530446;
CC Q9UBQ0-2; Q96QK1: VPS35; NbExp=4; IntAct=EBI-11141397, EBI-1054634;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Membrane; Peripheral membrane protein.
CC Endosome membrane {ECO:0000250|UniProtKB:Q9QZ88}; Peripheral membrane
CC protein {ECO:0000250|UniProtKB:Q9QZ88}. Early endosome {ECO:0000305}.
CC Late endosome {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9UBQ0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UBQ0-2; Sequence=VSP_004073;
CC -!- TISSUE SPECIFICITY: Ubiquitous. Highly expressed in heart, lung,
CC placenta, spleen, peripheral blood leukocytes, thymus, colon skeletal
CC muscle, kidney and brain.
CC -!- SIMILARITY: Belongs to the VPS29 family. {ECO:0000305}.
CC -!- CAUTION: Was originally believed to be a metal-dependent phosphatase
CC but shown to lack catalytic activity; can bind metals with very low
CC affinity suggesting that metal binding is not required for its
CC function. {ECO:0000303|PubMed:16737443, ECO:0000303|PubMed:21629666}.
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DR EMBL; AF193795; AAF04596.1; -; mRNA.
DR EMBL; AF175264; AAF89952.1; -; mRNA.
DR EMBL; AF168716; AAF87318.1; -; mRNA.
DR EMBL; AF201936; AAF86872.1; -; mRNA.
DR EMBL; AF201946; AAF17238.1; -; mRNA.
DR EMBL; AL136614; CAB66549.1; -; mRNA.
DR EMBL; CR457182; CAG33463.1; -; mRNA.
DR EMBL; CR533468; CAG38499.1; -; mRNA.
DR EMBL; BC000880; AAH00880.1; -; mRNA.
DR EMBL; BC095446; AAH95446.1; -; mRNA.
DR CCDS; CCDS41832.1; -. [Q9UBQ0-1]
DR CCDS; CCDS53832.1; -. [Q9UBQ0-2]
DR PIR; JC7515; JC7515.
DR RefSeq; NP_057310.1; NM_016226.4. [Q9UBQ0-1]
DR RefSeq; NP_476528.1; NM_057180.2. [Q9UBQ0-2]
DR PDB; 1W24; X-ray; 2.10 A; A=1-182.
DR PDB; 2R17; X-ray; 2.80 A; A/B=1-182.
DR PDB; 5GTU; X-ray; 1.50 A; A=2-182.
DR PDB; 5OSH; X-ray; 4.30 A; A/D/G/J=1-182.
DR PDB; 5OSI; X-ray; 2.52 A; A/D/G/J=1-182.
DR PDB; 5WYH; X-ray; 2.46 A; A/C=2-182.
DR PDB; 6XS5; X-ray; 2.01 A; A=1-182.
DR PDB; 6XS7; X-ray; 1.58 A; A=1-182.
DR PDB; 6XS9; X-ray; 2.69 A; A/B=1-182.
DR PDB; 6XSA; X-ray; 1.83 A; A=1-182.
DR PDB; 7BLN; EM; 8.90 A; B/D=1-182.
DR PDBsum; 1W24; -.
DR PDBsum; 2R17; -.
DR PDBsum; 5GTU; -.
DR PDBsum; 5OSH; -.
DR PDBsum; 5OSI; -.
DR PDBsum; 5WYH; -.
DR PDBsum; 6XS5; -.
DR PDBsum; 6XS7; -.
DR PDBsum; 6XS9; -.
DR PDBsum; 6XSA; -.
DR PDBsum; 7BLN; -.
DR AlphaFoldDB; Q9UBQ0; -.
DR SMR; Q9UBQ0; -.
DR BioGRID; 119683; 104.
DR CORUM; Q9UBQ0; -.
DR DIP; DIP-29077N; -.
DR IntAct; Q9UBQ0; 67.
DR MINT; Q9UBQ0; -.
DR STRING; 9606.ENSP00000480853; -.
DR TCDB; 9.A.3.1.1; the sorting nexin27 (snx27)-retromer assembly apparatus (retromeraa) family.
DR TCDB; 9.A.3.1.2; the sorting nexin27 (snx27)-retromer assembly apparatus (retromeraa) family.
DR DEPOD; VPS29; -.
DR iPTMnet; Q9UBQ0; -.
DR MetOSite; Q9UBQ0; -.
DR PhosphoSitePlus; Q9UBQ0; -.
DR SwissPalm; Q9UBQ0; -.
DR BioMuta; VPS29; -.
DR DMDM; 25453325; -.
DR EPD; Q9UBQ0; -.
DR jPOST; Q9UBQ0; -.
DR MassIVE; Q9UBQ0; -.
DR MaxQB; Q9UBQ0; -.
DR PaxDb; Q9UBQ0; -.
DR PeptideAtlas; Q9UBQ0; -.
DR PRIDE; Q9UBQ0; -.
DR ProteomicsDB; 84030; -. [Q9UBQ0-1]
DR ProteomicsDB; 84031; -. [Q9UBQ0-2]
DR TopDownProteomics; Q9UBQ0-1; -. [Q9UBQ0-1]
DR TopDownProteomics; Q9UBQ0-2; -. [Q9UBQ0-2]
DR Antibodypedia; 31016; 212 antibodies from 32 providers.
DR DNASU; 51699; -.
DR Ensembl; ENST00000360579.11; ENSP00000353786.7; ENSG00000111237.19. [Q9UBQ0-2]
DR Ensembl; ENST00000549578.6; ENSP00000447058.1; ENSG00000111237.19. [Q9UBQ0-1]
DR GeneID; 51699; -.
DR KEGG; hsa:51699; -.
DR MANE-Select; ENST00000549578.6; ENSP00000447058.1; NM_016226.5; NP_057310.1.
DR UCSC; uc001tqx.5; human. [Q9UBQ0-1]
DR CTD; 51699; -.
DR DisGeNET; 51699; -.
DR GeneCards; VPS29; -.
DR HGNC; HGNC:14340; VPS29.
DR HPA; ENSG00000111237; Low tissue specificity.
DR MIM; 606932; gene.
DR neXtProt; NX_Q9UBQ0; -.
DR OpenTargets; ENSG00000111237; -.
DR PharmGKB; PA37875; -.
DR VEuPathDB; HostDB:ENSG00000111237; -.
DR eggNOG; KOG3325; Eukaryota.
DR GeneTree; ENSGT00390000012669; -.
DR HOGENOM; CLU_063749_0_1_1; -.
DR InParanoid; Q9UBQ0; -.
DR OMA; IVVYVYE; -.
DR PhylomeDB; Q9UBQ0; -.
DR TreeFam; TF300880; -.
DR PathwayCommons; Q9UBQ0; -.
DR Reactome; R-HSA-3238698; WNT ligand biogenesis and trafficking.
DR SignaLink; Q9UBQ0; -.
DR BioGRID-ORCS; 51699; 308 hits in 1097 CRISPR screens.
DR ChiTaRS; VPS29; human.
DR EvolutionaryTrace; Q9UBQ0; -.
DR GeneWiki; VPS29; -.
DR GenomeRNAi; 51699; -.
DR Pharos; Q9UBQ0; Tbio.
DR PRO; PR:Q9UBQ0; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q9UBQ0; protein.
DR Bgee; ENSG00000111237; Expressed in monocyte and 180 other tissues.
DR ExpressionAtlas; Q9UBQ0; baseline and differential.
DR Genevisible; Q9UBQ0; HS.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005768; C:endosome; IDA:LIFEdb.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005770; C:late endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0030904; C:retromer complex; IDA:UniProtKB.
DR GO; GO:0030906; C:retromer, cargo-selective complex; IDA:ParkinsonsUK-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0032456; P:endocytic recycling; IMP:UniProtKB.
DR GO; GO:0006886; P:intracellular protein transport; IBA:GO_Central.
DR GO; GO:0042147; P:retrograde transport, endosome to Golgi; IBA:GO_Central.
DR CDD; cd07394; MPP_Vps29; 1.
DR Gene3D; 3.60.21.10; -; 1.
DR InterPro; IPR024654; Calcineurin-like_PHP_lpxH.
DR InterPro; IPR029052; Metallo-depent_PP-like.
DR InterPro; IPR000979; Phosphodiesterase_MJ0936/Vps29.
DR InterPro; IPR028661; Vps29.
DR PANTHER; PTHR11124; PTHR11124; 1.
DR PANTHER; PTHR11124:SF12; PTHR11124:SF12; 1.
DR Pfam; PF12850; Metallophos_2; 1.
DR SUPFAM; SSF56300; SSF56300; 1.
DR TIGRFAMs; TIGR00040; yfcE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm; Endosome;
KW Host-virus interaction; Membrane; Metal-binding; Protein transport;
KW Reference proteome; Transport; Zinc.
FT CHAIN 1..182
FT /note="Vacuolar protein sorting-associated protein 29"
FT /id="PRO_0000065894"
FT BINDING 8
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 10
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 39
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 39
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 62
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 86
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 115
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 117
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT MOD_RES 50
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT VAR_SEQ 1
FT /note="M -> MAGHR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11062004,
FT ECO:0000303|PubMed:15489334, ECO:0000303|Ref.3,
FT ECO:0000303|Ref.6"
FT /id="VSP_004073"
FT MUTAGEN 8
FT /note="D->A: Loss of in vitro protein phosphatase
FT activity."
FT /evidence="ECO:0000269|PubMed:16737443"
FT MUTAGEN 39
FT /note="N->A: Loss of in vitro protein phosphatase
FT activity."
FT /evidence="ECO:0000269|PubMed:16737443"
FT MUTAGEN 39
FT /note="N->D: No effect on in vitro protein phosphatase
FT activity."
FT /evidence="ECO:0000269|PubMed:16737443"
FT MUTAGEN 62
FT /note="D->A,N: Loss of in vitro protein phosphatase
FT activity."
FT /evidence="ECO:0000269|PubMed:16737443"
FT MUTAGEN 86
FT /note="H->A: Loss of in vitro protein phosphatase
FT activity."
FT /evidence="ECO:0000269|PubMed:16737443"
FT MUTAGEN 90
FT /note="V->D: Decreases interaction with VPS35."
FT MUTAGEN 91
FT /note="I->D: Disrupts interaction with VPS35."
FT MUTAGEN 117
FT /note="H->A: Loss of in vitro protein phosphatase
FT activity."
FT /evidence="ECO:0000269|PubMed:16737443"
FT MUTAGEN 152
FT /note="L->E: Disrupts interaction with TBC1D5."
FT /evidence="ECO:0000269|PubMed:20923837"
FT CONFLICT 1..2
FT /note="ML -> MKIVLYPV (in Ref. 4; AAF86872)"
FT /evidence="ECO:0000305"
FT CONFLICT 119
FT /note="F -> S (in Ref. 5; CAB66549 and 6; CAG38499)"
FT /evidence="ECO:0000305"
FT STRAND 2..6
FT /evidence="ECO:0007829|PDB:5GTU"
FT TURN 11..14
FT /evidence="ECO:0007829|PDB:5GTU"
FT STRAND 16..18
FT /evidence="ECO:0007829|PDB:6XS9"
FT HELIX 20..25
FT /evidence="ECO:0007829|PDB:5GTU"
FT TURN 28..30
FT /evidence="ECO:0007829|PDB:6XS7"
FT STRAND 32..36
FT /evidence="ECO:0007829|PDB:5GTU"
FT HELIX 43..52
FT /evidence="ECO:0007829|PDB:5GTU"
FT STRAND 54..58
FT /evidence="ECO:0007829|PDB:5GTU"
FT STRAND 67..69
FT /evidence="ECO:0007829|PDB:5OSI"
FT STRAND 71..77
FT /evidence="ECO:0007829|PDB:5GTU"
FT STRAND 80..85
FT /evidence="ECO:0007829|PDB:5GTU"
FT STRAND 90..92
FT /evidence="ECO:0007829|PDB:5GTU"
FT HELIX 96..106
FT /evidence="ECO:0007829|PDB:5GTU"
FT STRAND 109..113
FT /evidence="ECO:0007829|PDB:5GTU"
FT STRAND 115..118
FT /evidence="ECO:0007829|PDB:1W24"
FT STRAND 119..124
FT /evidence="ECO:0007829|PDB:5GTU"
FT STRAND 127..132
FT /evidence="ECO:0007829|PDB:5GTU"
FT STRAND 134..136
FT /evidence="ECO:0007829|PDB:6XS9"
FT STRAND 141..145
FT /evidence="ECO:0007829|PDB:6XSA"
FT STRAND 149..156
FT /evidence="ECO:0007829|PDB:5GTU"
FT STRAND 159..168
FT /evidence="ECO:0007829|PDB:5GTU"
FT STRAND 171..180
FT /evidence="ECO:0007829|PDB:5GTU"
SQ SEQUENCE 182 AA; 20506 MW; 6E0CDE6B720C9BF8 CRC64;
MLVLVLGDLH IPHRCNSLPA KFKKLLVPGK IQHILCTGNL CTKESYDYLK TLAGDVHIVR
GDFDENLNYP EQKVVTVGQF KIGLIHGHQV IPWGDMASLA LLQRQFDVDI LISGHTHKFE
AFEHENKFYI NPGSATGAYN ALETNIIPSF VLMDIQASTV VTYVYQLIGD DVKVERIEYK
KP
