ID VPS41_HUMAN Reviewed; 854 AA. AC P49754; E9PF36; Q86TP8; Q99851; Q99852; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 16-DEC-2008, sequence version 3. DT 02-OCT-2024, entry version 196. DE RecName: Full=Vacuolar protein sorting-associated protein 41 homolog; DE AltName: Full=S53; GN Name=VPS41; 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), AND FUNCTION. RC TISSUE=Heart; RX PubMed=9159129; DOI=10.1073/pnas.94.11.5662; RA Radisky D.C., Snyder W.B., Emr S.D., Kaplan J.; RT "Characterization of VPS41, a gene required for vacuolar trafficking and RT high-affinity iron transport in yeast."; RL Proc. Natl. Acad. Sci. U.S.A. 94:5662-5666(1997). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Testis; 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 [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 615-744. RC TISSUE=Brain; RX PubMed=7596406; DOI=10.1038/375754a0; RA Sherrington R., Rogaev E.I., Liang Y., Rogaeva E.A., Levesque G., Ikeda M., RA Chi H., Lin C., Li G., Holman K., Tsuda T., Mar L., Foncin J.-F., RA Bruni A.C., Montesi M.P., Sorbi S., Rainero I., Pinessi L., Nee L., RA Chumakov I., Pollen D., Brookes A., Sanseau P., Polinsky R.J., Wasco W., RA da Silva H.A.R., Haines J.L., Pericak-Vance M.A., Tanzi R.E., Roses A.D., RA Fraser P.E., Rommens J.M., St George-Hyslop P.H.; RT "Cloning of a gene bearing missense mutations in early-onset familial RT Alzheimer's disease."; RL Nature 375:754-760(1995). RN [5] RP INTERACTION WITH MON1B. RX PubMed=20434987; DOI=10.1016/j.cell.2010.03.011; RA Poteryaev D., Datta S., Ackema K., Zerial M., Spang A.; RT "Identification of the switch in early-to-late endosome transition."; RL Cell 141:497-508(2010). RN [6] RP MISCELLANEOUS. RX PubMed=19850127; DOI=10.1016/j.nbd.2009.10.011; RA Ruan Q., Harrington A.J., Caldwell K.A., Caldwell G.A., Standaert D.G.; RT "VPS41, a protein involved in lysosomal trafficking, is protective in RT Caenorhabditis elegans and mammalian cellular models of Parkinson's RT disease."; RL Neurobiol. Dis. 37:330-338(2010). RN [7] RP FUNCTION, INTERACTION WITH ARL8B, AND SUBCELLULAR LOCATION. RX PubMed=21802320; DOI=10.1016/j.immuni.2011.06.009; RA Garg S., Sharma M., Ung C., Tuli A., Barral D.C., Hava D.L., Veerapen N., RA Besra G.S., Hacohen N., Brenner M.B.; RT "Lysosomal trafficking, antigen presentation, and microbial killing are RT controlled by the Arf-like GTPase Arl8b."; RL Immunity 35:182-193(2011). RN [8] RP SUBUNIT, AND SUBCELLULAR LOCATION. RX PubMed=21411634; DOI=10.1091/mbc.e10-10-0799; RA Zlatic S.A., Tornieri K., L'Hernault S.W., Faundez V.; RT "Clathrin-dependent mechanisms modulate the subcellular distribution of RT class C Vps/HOPS tether subunits in polarized and nonpolarized cells."; RL Mol. Biol. Cell 22:1699-1715(2011). RN [9] RP MISCELLANEOUS. RX PubMed=22323726; DOI=10.1523/jneurosci.2606-11.2012; RA Harrington A.J., Yacoubian T.A., Slone S.R., Caldwell K.A., Caldwell G.A.; RT "Functional analysis of VPS41-mediated neuroprotection in Caenorhabditis RT elegans and mammalian models of Parkinson's disease."; RL J. Neurosci. 32:2142-2153(2012). RN [10] RP FUNCTION, AND SUBUNIT. RX PubMed=24210660; DOI=10.1016/j.devcel.2013.10.007; RA Asensio C.S., Sirkis D.W., Maas J.W. Jr., Egami K., To T.L., Brodsky F.M., RA Shu X., Cheng Y., Edwards R.H.; RT "Self-assembly of VPS41 promotes sorting required for biogenesis of the RT regulated secretory pathway."; RL Dev. Cell 27:425-437(2013). RN [11] RP REVIEW ON THE HOPS AND CORVET COMPLEXES. RX PubMed=23351085; DOI=10.1111/febs.12151; RA Solinger J.A., Spang A.; RT "Tethering complexes in the endocytic pathway: CORVET and HOPS."; RL FEBS J. 280:2743-2757(2013). RN [12] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=23322049; DOI=10.1038/ncomms2360; RA Pols M.S., van Meel E., Oorschot V., ten Brink C., Fukuda M., Swetha M.G., RA Mayor S., Klumperman J.; RT "hVps41 and VAMP7 function in direct TGN to late endosome transport of RT lysosomal membrane proteins."; RL Nat. Commun. 4:1361-1361(2013). RN [13] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=23167963; DOI=10.1111/tra.12027; RA Pols M.S., ten Brink C., Gosavi P., Oorschot V., Klumperman J.; RT "The HOPS proteins hVps41 and hVps39 are required for homotypic and RT heterotypic late endosome fusion."; RL Traffic 14:219-232(2013). RN [14] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH RILP, AND SUBUNIT. RX PubMed=25445562; DOI=10.1038/srep07282; RA Lin X., Yang T., Wang S., Wang Z., Yun Y., Sun L., Zhou Y., Xu X., RA Akazawa C., Hong W., Wang T.; RT "RILP interacts with HOPS complex via VPS41 subunit to regulate endocytic RT trafficking."; RL Sci. Rep. 4:7282-7282(2014). RN [15] RP FUNCTION, SUBUNIT, INTERACTION WITH ARL8B, VARIANT PRO-146, AND RP CHARACTERIZATION OF VARIANT PRO-146. RX PubMed=25908847; DOI=10.1242/jcs.162651; RA Khatter D., Raina V.B., Dwivedi D., Sindhwani A., Bahl S., Sharma M.; RT "The small GTPase Arl8b regulates assembly of the mammalian HOPS complex on RT lysosomes."; RL J. Cell Sci. 128:1746-1761(2015). RN [16] RP FUNCTION, AND FUNCTION OF THE HOPS COMPLEX. RX PubMed=25783203; DOI=10.1111/tra.12283; RA Wartosch L., Guenesdogan U., Graham S.C., Luzio J.P.; RT "Recruitment of VPS33A to HOPS by VPS16 Is Required for Lysosome Fusion RT with Endosomes and Autophagosomes."; RL Traffic 16:727-742(2015). RN [17] RP INTERACTION WITH PLEKHM1. RX PubMed=28325809; DOI=10.1083/jcb.201607085; RA Marwaha R., Arya S.B., Jagga D., Kaur H., Tuli A., Sharma M.; RT "The Rab7 effector PLEKHM1 binds Arl8b to promote cargo traffic to RT lysosomes."; RL J. Cell Biol. 216:1051-1070(2017). RN [18] RP INTERACTION WITH STX17. RX PubMed=31806350; DOI=10.1016/j.molcel.2019.10.035; RA Miao G., Zhang Y., Chen D., Zhang H.; RT "The ER-Localized Transmembrane Protein TMEM39A/SUSR2 Regulates Autophagy RT by Controlling the Trafficking of the PtdIns(4)P Phosphatase SAC1."; RL Mol. Cell 0:0-0(2019). RN [19] RP INVOLVEMENT IN SCAR29. RX PubMed=32808683; DOI=10.1002/ana.25879; RG Genomics England Research Consortium; RA Steel D., Zech M., Zhao C., Barwick K.E.S., Burke D., Demailly D., RA Kumar K.R., Zorzi G., Nardocci N., Kaiyrzhanov R., Wagner M., Iuso A., RA Berutti R., Skorvanek M., Necpal J., Davis R., Wiethoff S., Mankad K., RA Sudhakar S., Ferrini A., Sharma S., Kamsteeg E.J., Tijssen M.A., RA Verschuuren C., van Egmond M.E., Flowers J.M., McEntagart M., Tucci A., RA Coubes P., Bustos B.I., Gonzalez-Latapi P., Tisch S., Darveniza P., RA Gorman K.M., Peall K.J., Boetzel K., Koch J.C., Kmiec T., Plecko B., RA Boesch S., Haslinger B., Jech R., Garavaglia B., Wood N., Houlden H., RA Gissen P., Lubbe S.J., Sue C.M., Cif L., Mencacci N.E., Anderson G., RA Kurian M.A., Winkelmann J.; RT "Loss-of-Function Variants in HOPS Complex Genes VPS16 and VPS41 Cause RT Early Onset Dystonia Associated with Lysosomal Abnormalities."; RL Ann. Neurol. 88:867-877(2020). RN [20] RP INTERACTION WITH STX17, AND SUBCELLULAR LOCATION. RX PubMed=33422265; DOI=10.1016/j.devcel.2020.12.010; RA Miao G., Zhao H., Li Y., Ji M., Chen Y., Shi Y., Bi Y., Wang P., Zhang H.; RT "ORF3a of the COVID-19 virus SARS-CoV-2 blocks HOPS complex-mediated RT assembly of the SNARE complex required for autolysosome formation."; RL Dev. Cell 56:427-442(2020). RN [21] RP INVOLVEMENT IN SCAR29, VARIANTS SCAR29 GLY-13; PRO-285; PRO-633 AND RP PHE-791, CHARACTERIZATION OF VARIANTS SCAR29 GLY-13; PRO-285; PRO-633 AND RP PHE-791, AND TISSUE SPECIFICITY. RX PubMed=33764426; DOI=10.1093/brain/awaa459; RA Sanderson L.E., Lanko K., Alsagob M., Almass R., Al-Ahmadi N., Najafi M., RA Al-Muhaizea M.A., Alzaidan H., AlDhalaan H., Perenthaler E., RA van der Linde H.C., Nikoncuk A., Kuehn N.A., Antony D., Owaidah T.M., RA Raskin S., Vieira L.G.D.R., Mombach R., Ahangari N., Silveira T.R.D., RA Ameziane N., Rolfs A., Alharbi A., Sabbagh R.M., AlAhmadi K., Alawam B., RA Ghebeh H., AlHargan A., Albader A.A., Binhumaid F.S., Goljan E., Monies D., RA Mustafa O.M., Aldosary M., AlBakheet A., Alyounes B., Almutairi F., RA Al-Odaib A., Aksoy D.B., Basak A.N., Palvadeau R., Trabzuni D., RA Rosenfeld J.A., Karimiani E.G., Meyer B.F., Karakas B., Al-Mohanna F., RA Arold S.T., Colak D., Maroofian R., Houlden H., Bertoli-Avella A.M., RA Schmidts M., Barakat T.S., van Ham T.J., Kaya N.; RT "Bi-allelic variants in HOPS complex subunit VPS41 cause cerebellar ataxia RT and abnormal membrane trafficking."; RL Brain 144:769-780(2021). RN [22] RP VARIANTS SCAR29 662-ARG--LYS-854 DEL AND PRO-285, CHARACTERIZATION OF RP VARIANTS SCAR29 662-ARG--LYS-854 DEL AND PRO-285, FUNCTION, SUBUNIT, AND RP SUBCELLULAR LOCATION. RX PubMed=33851776; DOI=10.15252/emmm.202013258; RA van der Welle R.E.N., Jobling R., Burns C., Sanza P., van der Beek J.A., RA Fasano A., Chen L., Zwartkruis F.J., Zwakenberg S., Griffin E.F., RA Ten Brink C., Veenendaal T., Liv N., van Ravenswaaij-Arts C.M.A., RA Lemmink H.H., Pfundt R., Blaser S., Sepulveda C., Lozano A.M., Yoon G., RA Santiago-Sim T., Asensio C.S., Caldwell G.A., Caldwell K.A., Chitayat D., RA Klumperman J.; RT "Neurodegenerative VPS41 variants inhibit HOPS function and mTORC1- RT dependent TFEB/TFE3 regulation."; RL EMBO Mol. Med. 13:e13258-e13258(2021). CC -!- FUNCTION: Plays a role in vesicle-mediated protein trafficking to CC lysosomal compartments including the endocytic membrane transport and CC autophagic pathways. Believed to act in part as a core component of the CC putative HOPS endosomal tethering complex is proposed to be involved in CC the Rab5-to-Rab7 endosome conversion probably implicating MON1A/B, and CC via binding SNAREs and SNARE complexes to mediate tethering and docking CC events during SNARE-mediated membrane fusion. The HOPS complex is CC proposed to be recruited to Rab7 on the late endosomal membrane and to CC regulate late endocytic, phagocytic and autophagic traffic towards CC lysosomes (PubMed:23351085, PubMed:33851776). Involved in homotypic CC vesicle fusions between late endosomes and in heterotypic fusions CC between late endosomes and lysosomes implicated in degradation of CC endocytosed cargo (PubMed:23167963, PubMed:25445562, PubMed:25908847, CC PubMed:9159129). Required for fusion of autophagosomes with lysosomes CC (PubMed:25783203). Links the HOPS complex to endosomal Rab7 via its CC association with RILP and to lysosomal membranes via its association CC with ARL8B, suggesting that these interactions may bring the CC compartments to close proximity for fusion (PubMed:21802320, CC PubMed:25445562, PubMed:25908847). Involved in the direct trans-Golgi CC network to late endosomes transport of lysosomal membrane proteins CC independently of HOPS (PubMed:23322049). Involved in sorting to the CC regulated secretory pathway presumably implicating the AP-3 adapter CC complex (By similarity). May play a role in HOPS-independent function CC in the regulated secretory pathway (PubMed:24210660). CC {ECO:0000250|UniProtKB:D3ZVH6, ECO:0000269|PubMed:21802320, CC ECO:0000269|PubMed:23167963, ECO:0000269|PubMed:23322049, CC ECO:0000269|PubMed:25445562, ECO:0000269|PubMed:25783203, CC ECO:0000269|PubMed:25908847, ECO:0000269|PubMed:33851776, CC ECO:0000269|PubMed:9159129, ECO:0000305|PubMed:23167963, CC ECO:0000305|PubMed:23351085, ECO:0000305|PubMed:24210660, CC ECO:0000305|PubMed:25445562}. CC -!- SUBUNIT: Component of the putative homotypic fusion and vacuole protein CC sorting (HOPS) complex; the core of which composed of the class C Vps CC proteins VPS11, VPS16, VPS18 and VPS33A, is associated with VPS39 and CC VPS41 (PubMed:23351085, PubMed:25445562, PubMed:25908847, CC PubMed:33851776). Interacts with RILP, MON1B (PubMed:20434987, CC PubMed:25445562). Interacts with ARL8B (GTP-bound form); involved in CC recruitment to lysosomes and probably hierarchial assembly of the HOPS CC complex at lysosomal membranes (PubMed:25908847). In vitro can self- CC assemble into a lattice (PubMed:24210660). Associates with adapter CC protein complex 3 (AP-3) and clathrin:AP-3 complexes (PubMed:21411634). CC Interacts with STX17; this interaction is increased in the absence of CC TMEM39A (PubMed:31806350, PubMed:33422265). Interacts with ARL8B and CC PLEKHM1; the interaction mediates the recruitment of the HOPS complex CC to lysosomes (PubMed:21802320, PubMed:25908847, PubMed:28325809). CC Interacts with RAB7, RAB2A and RAB2B (By similarity). CC {ECO:0000250|UniProtKB:Q5KU39, ECO:0000269|PubMed:20434987, CC ECO:0000269|PubMed:21411634, ECO:0000269|PubMed:21802320, CC ECO:0000269|PubMed:25908847, ECO:0000269|PubMed:28325809, CC ECO:0000269|PubMed:31806350, ECO:0000269|PubMed:33422265, CC ECO:0000269|PubMed:33851776, ECO:0000305|PubMed:23351085, CC ECO:0000305|PubMed:24210660, ECO:0000305|PubMed:25445562, CC ECO:0000305|PubMed:25908847}. CC -!- SUBUNIT: (Microbial infection) The interaction with STX17 is decreased CC in presence of SARS coronavirus-2/SARS-CoV-2 ORF3A protein. CC {ECO:0000269|PubMed:33422265}. CC -!- INTERACTION: CC P49754; Q9Y4G2: PLEKHM1; NbExp=9; IntAct=EBI-2130459, EBI-473814; CC P49754; Q96NA2: RILP; NbExp=4; IntAct=EBI-2130459, EBI-2856119; CC P49754; P56962: STX17; NbExp=2; IntAct=EBI-2130459, EBI-2797775; CC P49754; Q9H9C1: VIPAS39; NbExp=4; IntAct=EBI-2130459, EBI-749080; CC P49754; Q9H270: VPS11; NbExp=5; IntAct=EBI-2130459, EBI-373380; CC P49754; Q9P253: VPS18; NbExp=6; IntAct=EBI-2130459, EBI-1053363; CC P49754; P49754: VPS41; NbExp=2; IntAct=EBI-2130459, EBI-2130459; CC P49754; P0DTC3: 3a; Xeno; NbExp=4; IntAct=EBI-2130459, EBI-25475894; CC -!- SUBCELLULAR LOCATION: Endosome membrane {ECO:0000269|PubMed:21411634, CC ECO:0000269|PubMed:23322049, ECO:0000269|PubMed:25445562}; Peripheral CC membrane protein {ECO:0000269|PubMed:23167963, CC ECO:0000269|PubMed:25445562}. Late endosome membrane CC {ECO:0000269|PubMed:23322049, ECO:0000269|PubMed:33422265}; Peripheral CC membrane protein {ECO:0000269|PubMed:23167963, CC ECO:0000269|PubMed:25445562}. Early endosome membrane CC {ECO:0000269|PubMed:21411634}; Peripheral membrane protein CC {ECO:0000269|PubMed:23167963, ECO:0000269|PubMed:25445562}. Lysosome CC membrane {ECO:0000269|PubMed:21802320, ECO:0000269|PubMed:23322049, CC ECO:0000269|PubMed:33422265, ECO:0000269|PubMed:33851776}; Peripheral CC membrane protein {ECO:0000269|PubMed:23167963}. Golgi apparatus, trans- CC Golgi network {ECO:0000269|PubMed:23322049}. Cytoplasmic vesicle, CC clathrin-coated vesicle {ECO:0000269|PubMed:21411634}. Cytoplasm, CC cytosol {ECO:0000269|PubMed:23167963}. CC -!- SUBCELLULAR LOCATION: Note=(Microbial infection) Sequestrated at the CC late endosome by SARS coronavirus-2/SARS-CoV-2 ORF3A protein. CC {ECO:0000269|PubMed:33422265}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P49754-1; Sequence=Displayed; CC Name=2; CC IsoId=P49754-2; Sequence=VSP_006751, VSP_006752; CC Name=3; CC IsoId=P49754-3; Sequence=VSP_054169; CC -!- TISSUE SPECIFICITY: Expressed in cerebral cortex and cerebellum. Highly CC expressed in Purkinje cells. {ECO:0000269|PubMed:33764426}. CC -!- DISEASE: Spinocerebellar ataxia, autosomal recessive, 29 (SCAR29) CC [MIM:619389]: A form of spinocerebellar ataxia, a clinically and CC genetically heterogeneous group of cerebellar disorders due to CC degeneration of the cerebellum with variable involvement of the CC brainstem and spinal cord. SCAR29 is a progressive disease CC characterized by delayed motor development in early infancy followed by CC difficulty walking due to an ataxic gait or inability to walk, CC hypotonia, and variably impaired intellectual development. CC {ECO:0000269|PubMed:32808683, ECO:0000269|PubMed:33764426, CC ECO:0000269|PubMed:33851776}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: Protective against both alpha-synuclein and neurotoxic- CC mediated injury in invertebrate and cellular models of Parkinson's CC disease (PD); the function requires the AP-3 adapter complex and the CC HOPS complex. {ECO:0000269|PubMed:19850127, CC ECO:0000269|PubMed:22323726}. CC -!- SIMILARITY: Belongs to the VPS41 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U87281; AAB47758.1; -; mRNA. DR EMBL; U87309; AAB47563.1; -; mRNA. DR EMBL; AC004850; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC005247; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC011292; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC044851; AAH44851.1; -; mRNA. DR EMBL; L40398; AAC42004.1; -; mRNA. DR CCDS; CCDS5457.1; -. [P49754-1] DR CCDS; CCDS5458.2; -. [P49754-3] DR RefSeq; NP_055211.2; NM_014396.3. [P49754-1] DR RefSeq; NP_542198.2; NM_080631.3. [P49754-3] DR AlphaFoldDB; P49754; -. DR BioGRID; 117982; 76. DR ComplexPortal; CPX-6212; HOPS tethering complex. DR CORUM; P49754; -. DR IntAct; P49754; 46. DR MINT; P49754; -. DR STRING; 9606.ENSP00000309457; -. DR GlyGen; P49754; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P49754; -. DR PhosphoSitePlus; P49754; -. DR BioMuta; VPS41; -. DR DMDM; 218512109; -. DR jPOST; P49754; -. DR MassIVE; P49754; -. DR PaxDb; 9606-ENSP00000309457; -. DR PeptideAtlas; P49754; -. DR ProteomicsDB; 20017; -. DR ProteomicsDB; 56068; -. [P49754-1] DR ProteomicsDB; 56069; -. [P49754-2] DR Pumba; P49754; -. DR Antibodypedia; 13056; 151 antibodies from 31 providers. DR DNASU; 27072; -. DR Ensembl; ENST00000310301.9; ENSP00000309457.4; ENSG00000006715.16. [P49754-1] DR Ensembl; ENST00000395969.6; ENSP00000379297.2; ENSG00000006715.16. [P49754-3] DR GeneID; 27072; -. DR KEGG; hsa:27072; -. DR MANE-Select; ENST00000310301.9; ENSP00000309457.4; NM_014396.4; NP_055211.2. DR UCSC; uc003tgy.4; human. [P49754-1] DR AGR; HGNC:12713; -. DR CTD; 27072; -. DR DisGeNET; 27072; -. DR GeneCards; VPS41; -. DR HGNC; HGNC:12713; VPS41. DR HPA; ENSG00000006715; Low tissue specificity. DR MalaCards; VPS41; -. DR MIM; 605485; gene. DR MIM; 619389; phenotype. DR neXtProt; NX_P49754; -. DR OpenTargets; ENSG00000006715; -. DR Orphanet; 95434; Autosomal recessive cerebellar ataxia-movement disorder syndrome. DR PharmGKB; PA37328; -. DR VEuPathDB; HostDB:ENSG00000006715; -. DR eggNOG; KOG2066; Eukaryota. DR GeneTree; ENSGT00390000000481; -. DR HOGENOM; CLU_001285_2_2_1; -. DR InParanoid; P49754; -. DR OMA; PQLVWQD; -. DR OrthoDB; 8838at2759; -. DR PhylomeDB; P49754; -. DR TreeFam; TF300451; -. DR PathwayCommons; P49754; -. DR Reactome; R-HSA-9754560; SARS-CoV-2 modulates autophagy. DR SignaLink; P49754; -. DR SIGNOR; P49754; -. DR BioGRID-ORCS; 27072; 413 hits in 1204 CRISPR screens. DR ChiTaRS; VPS41; human. DR GenomeRNAi; 27072; -. DR Pharos; P49754; Tbio. DR PRO; PR:P49754; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; P49754; protein. DR Bgee; ENSG00000006715; Expressed in calcaneal tendon and 185 other cell types or tissues. DR ExpressionAtlas; P49754; baseline and differential. DR GO; GO:0030136; C:clathrin-coated vesicle; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0010008; C:endosome membrane; IDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell. DR GO; GO:0005798; C:Golgi-associated vesicle; IMP:UniProtKB. DR GO; GO:0030897; C:HOPS complex; IDA:UniProtKB. DR GO; GO:0005770; C:late endosome; IDA:UniProtKB. DR GO; GO:0031902; C:late endosome membrane; IDA:UniProtKB. DR GO; GO:1902501; C:lysosomal HOPS complex; IDA:UniProtKB. DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB. DR GO; GO:0005764; C:lysosome; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0015630; C:microtubule cytoskeleton; IEA:Ensembl. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0008017; F:microtubule binding; IEA:Ensembl. DR GO; GO:0009267; P:cellular response to starvation; IBA:GO_Central. DR GO; GO:0034058; P:endosomal vesicle fusion; IMP:UniProtKB. DR GO; GO:0008333; P:endosome to lysosome transport; IMP:UniProtKB. DR GO; GO:0048193; P:Golgi vesicle transport; IMP:UniProtKB. DR GO; GO:1902774; P:late endosome to lysosome transport; IMP:UniProtKB. DR GO; GO:0016236; P:macroautophagy; IBA:GO_Central. DR GO; GO:0006623; P:protein targeting to vacuole; IBA:GO_Central. DR GO; GO:0035542; P:regulation of SNARE complex assembly; NAS:ComplexPortal. DR GO; GO:0016192; P:vesicle-mediated transport; IMP:UniProtKB. DR CDD; cd16690; RING-H2_Vps41; 1. DR Gene3D; 1.25.40.10; Tetratricopeptide repeat domain; 1. DR Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 1. DR InterPro; IPR000547; Clathrin_H-chain/VPS_repeat. DR InterPro; IPR011990; TPR-like_helical_dom_sf. DR InterPro; IPR016902; VPS41. DR InterPro; IPR045111; Vps41/Vps8. DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf. DR InterPro; IPR036322; WD40_repeat_dom_sf. DR InterPro; IPR001841; Znf_RING. DR PANTHER; PTHR12616; VACUOLAR PROTEIN SORTING VPS41; 1. DR PANTHER; PTHR12616:SF1; VACUOLAR PROTEIN SORTING-ASSOCIATED PROTEIN 41 HOMOLOG; 1. DR Pfam; PF00637; Clathrin; 1. DR PIRSF; PIRSF028921; VPS41; 1. DR SMART; SM00299; CLH; 1. DR SUPFAM; SSF57850; RING/U-box; 1. DR SUPFAM; SSF50978; WD40 repeat-like; 1. DR PROSITE; PS50236; CHCR; 1. DR PROSITE; PS50089; ZF_RING_2; 1. PE 1: Evidence at protein level; KW Alternative splicing; Autophagy; Cytoplasm; Cytoplasmic vesicle; KW Disease variant; Endosome; Golgi apparatus; Lysosome; Membrane; KW Metal-binding; Neurodegeneration; Protein transport; KW Proteomics identification; Reference proteome; Spinocerebellar ataxia; KW Transport; Zinc; Zinc-finger. FT CHAIN 1..854 FT /note="Vacuolar protein sorting-associated protein 41 FT homolog" FT /id="PRO_0000212823" FT REPEAT 568..712 FT /note="CHCR" FT ZN_FING 791..839 FT /note="RING-type; atypical" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175" FT REGION 1..540 FT /note="Interaction with ARL8B" FT /evidence="ECO:0000269|PubMed:25908847" FT REGION 1..33 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1..26 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT VAR_SEQ 83..107 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000305" FT /id="VSP_054169" FT VAR_SEQ 802 FT /note="D -> E (in isoform 2)" FT /evidence="ECO:0000303|PubMed:9159129" FT /id="VSP_006751" FT VAR_SEQ 803..854 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:9159129" FT /id="VSP_006752" FT VARIANT 13 FT /note="E -> G (in SCAR29; uncertain significance; no effect FT on protein expression)" FT /evidence="ECO:0000269|PubMed:33764426" FT /id="VAR_085704" FT VARIANT 146 FT /note="T -> P (disrupts interaction with ARL8B; impairs FT lysosomal localization and degradation of endocytosed FT cargo; dbSNP:rs35693565)" FT /evidence="ECO:0000269|PubMed:25908847" FT /id="VAR_047914" FT VARIANT 285 FT /note="S -> P (in SCAR29; decreased protein abundance; FT cannot form a functional HOPS complex; causes a kinetic FT defect in the endosome-lysosome fusion process; FT dbSNP:rs544223875)" FT /evidence="ECO:0000269|PubMed:33764426, FT ECO:0000269|PubMed:33851776" FT /id="VAR_085705" FT VARIANT 633 FT /note="R -> P (in SCAR29; uncertain significance; decreased FT protein abundance)" FT /evidence="ECO:0000269|PubMed:33764426" FT /id="VAR_085706" FT VARIANT 647 FT /note="C -> R (in dbSNP:rs11762417)" FT /id="VAR_047915" FT VARIANT 662..854 FT /note="Missing (in SCAR29; loss of expression; cannot form FT a functional HOPS complex)" FT /evidence="ECO:0000269|PubMed:33851776" FT /id="VAR_085707" FT VARIANT 791 FT /note="C -> F (in SCAR29; decreased protein abundance)" FT /evidence="ECO:0000269|PubMed:33764426" FT /id="VAR_085708" FT VARIANT 843 FT /note="R -> H (in dbSNP:rs1059508)" FT /id="VAR_047916" FT CONFLICT 5 FT /note="E -> V (in Ref. 1; AAB47563)" FT /evidence="ECO:0000305" FT CONFLICT 615..618 FT /note="KQIS -> WHEG (in Ref. 4; AAC42004)" FT /evidence="ECO:0000305" FT CONFLICT 736..744 FT /note="IPNLRDSLV -> DPQFERFLG (in Ref. 4; AAC42004)" FT /evidence="ECO:0000305" SQ SEQUENCE 854 AA; 98566 MW; 037577D5FA3A18A0 CRC64; MAEAEEQETG SLEESTDESE EEESEEEPKL KYERLSNGVT EILQKDAASC MTVHDKFLAL GTHYGKVYLL DVQGNITQKF DVSPVKINQI SLDESGEHMG VCSEDGKVQV FGLYSGEEFH ETFDCPIKII AVHPHFVRSS CKQFVTGGKK LLLFERSWMN RWKSAVLHEG EGNIRSVKWR GHLIAWANNM GVKIFDIISK QRITNVPRDD ISLRPDMYPC SLCWKDNVTL IIGWGTSVKV CSVKERHASE MRDLPSRYVE IVSQFETEFY ISGLAPLCDQ LVVLSYVKEI SEKTEREYCA RPRLDIIQPL SETCEEISSD ALTVRGFQEN ECRDYHLEYS EGESLFYIVS PRDVVVAKER DQDDHIDWLL EKKKYEEALM AAEISQKNIK RHKILDIGLA YINHLVERGD YDIAARKCQK ILGKNAALWE YEVYKFKEIG QLKAISPYLP RGDPVLKPLI YEMILHEFLE SDYEGFATLI REWPGDLYNN SVIVQAVRDH LKKDSQNKTL LKTLAELYTY DKNYGNALEI YLTLRHKDVF QLIHKHNLFS SIKDKIVLLM DFDSEKAVDM LLDNEDKISI KKVVEELEDR PELQHVYLHK LFKRDHHKGQ RYHEKQISLY AEYDRPNLLP FLRDSTHCPL EKALEICQQR NFVEETVYLL SRMGNSRSAL KMIMEELHDV DKAIEFAKEQ DDGELWEDLI LYSIDKPPFI TGLLNNIGTH VDPILLIHRI KEGMEIPNLR DSLVKILQDY NLQILLREGC KKILVADSLS LLKKMHRTQM KGVLVDEENI CESCLSPILP SDAAKPFSVV VFHCRHMFHK ECLPMPSMNS AAQFCNICSA KNRGPGSAIL EMKK //