VPS41_HUMAN
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 03-AUG-2022, entry version 184.
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:9159129, PubMed:23167963, PubMed:25445562,
CC PubMed:25908847). 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:25445562,
CC PubMed:25908847, PubMed:21802320). 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:28325809, PubMed:25908847).
CC {ECO:0000269|PubMed:20434987, ECO:0000269|PubMed:21411634,
CC ECO:0000269|PubMed:21802320, ECO:0000269|PubMed:25908847,
CC ECO:0000269|PubMed:28325809, ECO:0000269|PubMed:31806350,
CC ECO:0000269|PubMed:33422265, ECO:0000269|PubMed:33851776,
CC ECO:0000305|PubMed:23351085, ECO:0000305|PubMed:24210660,
CC ECO:0000305|PubMed:25445562, 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; 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; Q9P253: VPS18; NbExp=4; 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}.
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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; 71.
DR ComplexPortal; CPX-6212; HOPS tethering complex.
DR CORUM; P49754; -.
DR IntAct; P49754; 26.
DR MINT; P49754; -.
DR STRING; 9606.ENSP00000309457; -.
DR iPTMnet; P49754; -.
DR PhosphoSitePlus; P49754; -.
DR BioMuta; VPS41; -.
DR DMDM; 218512109; -.
DR EPD; P49754; -.
DR jPOST; P49754; -.
DR MassIVE; P49754; -.
DR MaxQB; P49754; -.
DR PaxDb; P49754; -.
DR PeptideAtlas; P49754; -.
DR PRIDE; P49754; -.
DR ProteomicsDB; 20017; -.
DR ProteomicsDB; 56068; -. [P49754-1]
DR ProteomicsDB; 56069; -. [P49754-2]
DR Antibodypedia; 13056; 131 antibodies from 30 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 CTD; 27072; -.
DR DisGeNET; 27072; -.
DR GeneCards; VPS41; -.
DR HGNC; HGNC:12713; VPS41.
DR HPA; ENSG00000006715; Low tissue specificity.
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; KFKYQRI; -.
DR OrthoDB; 722805at2759; -.
DR PhylomeDB; P49754; -.
DR TreeFam; TF300451; -.
DR PathwayCommons; P49754; -.
DR Reactome; R-HSA-9754560; SARS-CoV-2 modulates autophagy.
DR SignaLink; P49754; -.
DR BioGRID-ORCS; 27072; 403 hits in 1126 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 183 other tissues.
DR ExpressionAtlas; P49754; baseline and differential.
DR Genevisible; P49754; HS.
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; IC:ComplexPortal.
DR GO; GO:0016192; P:vesicle-mediated transport; IMP:UniProtKB.
DR Gene3D; 1.25.40.10; -; 1.
DR Gene3D; 2.130.10.10; -; 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; PTHR12616; 1.
DR Pfam; PF00637; Clathrin; 1.
DR PIRSF; PIRSF028921; VPS41; 1.
DR SMART; SM00299; CLH; 1.
DR SUPFAM; SSF50978; SSF50978; 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; Reference proteome;
KW Spinocerebellar ataxia; 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; unknown pathological
FT significance; no effect 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; unknown pathological
FT significance; decreased 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
