ID   MIL1_YEAST              Reviewed;        1073 AA.
AC   P43564; D6VTJ7;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   21-SEP-2011, sequence version 2.
DT   02-SEP-2026, entry version 174.
DE   RecName: Full=Probable lipase MIL1 {ECO:0000303|PubMed:26658609};
DE            EC=3.1.1.- {ECO:0000305|PubMed:26658609};
DE   AltName: Full=Medium adaptin-interacting ligand 1 {ECO:0000303|PubMed:26658609};
GN   Name=MIL1 {ECO:0000303|PubMed:26658609}; OrderedLocusNames=YFL034W;
OS   Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC   Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX   NCBI_TaxID=559292;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=7670463; DOI=10.1038/ng0795-261;
RA   Murakami Y., Naitou M., Hagiwara H., Shibata T., Ozawa M., Sasanuma S.,
RA   Sasanuma M., Tsuchiya Y., Soeda E., Yokoyama K., Yamazaki M., Tashiro H.,
RA   Eki T.;
RT   "Analysis of the nucleotide sequence of chromosome VI from Saccharomyces
RT   cerevisiae.";
RL   Nat. Genet. 10:261-268(1995).
RN   [2]
RP   GENOME REANNOTATION, AND SEQUENCE REVISION TO 323.
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=24374639; DOI=10.1534/g3.113.008995;
RA   Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA   Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA   Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT   "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL   G3 (Bethesda) 4:389-398(2014).
RN   [3]
RP   LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX   PubMed=14562106; DOI=10.1038/nature02046;
RA   Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA   O'Shea E.K., Weissman J.S.;
RT   "Global analysis of protein expression in yeast.";
RL   Nature 425:737-741(2003).
RN   [4]
RP   INTERACTION WITH RPP0.
RX   PubMed=15286401; DOI=10.1007/bf02702559;
RA   Aruna K., Chakraborty T., Nambeesan S., Mannan A.B., Sehgal A.,
RA   Balachandara S.R., Sharma S.;
RT   "Identification of a hypothetical membrane protein interactor of ribosomal
RT   phosphoprotein P0.";
RL   J. Biosci. 29:33-43(2004).
RN   [5]
RP   TOPOLOGY [LARGE SCALE ANALYSIS].
RC   STRAIN=ATCC 208353 / W303-1A;
RX   PubMed=16847258; DOI=10.1073/pnas.0604075103;
RA   Kim H., Melen K., Oesterberg M., von Heijne G.;
RT   "A global topology map of the Saccharomyces cerevisiae membrane proteome.";
RL   Proc. Natl. Acad. Sci. U.S.A. 103:11142-11147(2006).
RN   [6]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   STRAIN=ADR376;
RX   PubMed=17330950; DOI=10.1021/pr060559j;
RA   Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J.,
RA   Elias J.E., Gygi S.P.;
RT   "Large-scale phosphorylation analysis of alpha-factor-arrested
RT   Saccharomyces cerevisiae.";
RL   J. Proteome Res. 6:1190-1197(2007).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1037, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA   Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT   "A multidimensional chromatography technology for in-depth phosphoproteome
RT   analysis.";
RL   Mol. Cell. Proteomics 7:1389-1396(2008).
RN   [8]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-435, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19779198; DOI=10.1126/science.1172867;
RA   Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT   "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT   into evolution.";
RL   Science 325:1682-1686(2009).
RN   [9]
RP   FUNCTION, INTERACTION WITH APM2, DOMAIN, AND MUTAGENESIS OF
RP   143-TRP--PRO-147; SER-759; ASP-817 AND HIS-858.
RX   PubMed=26658609; DOI=10.1091/mbc.e15-09-0621;
RA   Whitfield S.T., Burston H.E., Bean B.D., Raghuram N., Maldonado-Baez L.,
RA   Davey M., Wendland B., Conibear E.;
RT   "The alternate AP-1 adaptor subunit Apm2 interacts with the Mil1 regulatory
RT   protein and confers differential cargo sorting.";
RL   Mol. Biol. Cell 27:588-598(2016).
CC   -!- FUNCTION: Probable lipase that recruits the AP-1-related (AP-1R)
CC       complex to membranes via interaction with APM2 (PubMed:26658609). The
CC       AP-1R complex is an adapter protein complex that mediates of cargo
CC       protein SNC1 sorting in clathrin-coated vesicles (PubMed:26658609).
CC       {ECO:0000269|PubMed:26658609}.
CC   -!- SUBUNIT: Interacts with RPP0 (PubMed:15286401). Interacts with APM2
CC       (PubMed:26658609). {ECO:0000269|PubMed:15286401,
CC       ECO:0000269|PubMed:26658609}.
CC   -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC       {ECO:0000269|PubMed:26658609}; Multi-pass membrane protein
CC       {ECO:0000255}. Early endosome membrane {ECO:0000269|PubMed:26658609};
CC       Multi-pass membrane protein {ECO:0000255}. Cytoplasmic vesicle,
CC       clathrin-coated vesicle membrane {ECO:0000269|PubMed:26658609}; Multi-
CC       pass membrane protein {ECO:0000255}.
CC   -!- MISCELLANEOUS: Present with 1110 molecules/cell in log phase SD medium.
CC       {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the TMCO4 family. {ECO:0000305}.
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DR   EMBL; D50617; BAA09205.1; -; Genomic_DNA.
DR   EMBL; BK006940; DAA12407.2; -; Genomic_DNA.
DR   PIR; S56220; S56220.
DR   RefSeq; NP_116583.2; NM_001179932.2.
DR   AlphaFoldDB; P43564; -.
DR   BioGRID; 31113; 87.
DR   DIP; DIP-6508N; -.
DR   FunCoup; P43564; 115.
DR   IntAct; P43564; 8.
DR   MINT; P43564; -.
DR   STRING; 4932.YFL034W; -.
DR   ESTHER; yeast-yfd4; Duf_726.
DR   GlyCosmos; P43564; 8 sites, No reported glycans.
DR   GlyGen; P43564; 8 sites.
DR   iPTMnet; P43564; -.
DR   PaxDb; 4932-YFL034W; -.
DR   PeptideAtlas; P43564; -.
DR   EnsemblFungi; YFL034W_mRNA; YFL034W; YFL034W.
DR   GeneID; 850510; -.
DR   KEGG; sce:YFL034W; -.
DR   AGR; SGD:S000001860; -.
DR   SGD; S000001860; MIL1.
DR   VEuPathDB; FungiDB:YFL034W; -.
DR   eggNOG; KOG2385; Eukaryota.
DR   HOGENOM; CLU_001695_2_1_1; -.
DR   InParanoid; P43564; -.
DR   OMA; KEVGWEV; -.
DR   OrthoDB; 277931at2759; -.
DR   BioCyc; YEAST:G3O-30428-MONOMER; -.
DR   BioGRID-ORCS; 850510; 0 hits in 10 CRISPR screens.
DR   PRO; PR:P43564; -.
DR   Proteomes; UP000002311; Chromosome VI.
DR   RNAct; P43564; protein.
DR   GO; GO:0030665; C:clathrin-coated vesicle membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0031901; C:early endosome membrane; EXP:UniProtKB.
DR   GO; GO:0000139; C:Golgi membrane; EXP:UniProtKB.
DR   GO; GO:0016020; C:membrane; IDA:SGD.
DR   GO; GO:0035650; F:AP-1 adaptor complex binding; IDA:SGD.
DR   GO; GO:0035652; P:clathrin-coated vesicle cargo loading; IMP:SGD.
DR   InterPro; IPR029058; AB_hydrolase_fold.
DR   InterPro; IPR007941; DUF726.
DR   PANTHER; PTHR17920:SF3; TRANSMEMBRANE AND COILED-COIL DOMAIN-CONTAINING PROTEIN 4; 1.
DR   PANTHER; PTHR17920; TRANSMEMBRANE AND COILED-COIL DOMAIN-CONTAINING PROTEIN 4 TMCO4; 1.
DR   Pfam; PF05277; DUF726; 1.
DR   SUPFAM; SSF53474; alpha/beta-Hydrolases; 1.
PE   1: Evidence at protein level;
KW   Cytoplasmic vesicle; Endosome; Glycoprotein; Golgi apparatus; Hydrolase;
KW   Membrane; Phosphoprotein; Reference proteome; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..1073
FT                   /note="Probable lipase MIL1"
FT                   /id="PRO_0000202674"
FT   TRANSMEM        292..312
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        457..477
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        553..573
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        577..597
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        818..838
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   REGION          1..151
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          163..190
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          230..267
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          385..448
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          942..968
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1010..1073
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           143..147
FT                   /note="APM2-interacting WQEMP motif"
FT                   /evidence="ECO:0000269|PubMed:26658609"
FT   COMPBIAS        54..81
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        101..121
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        233..249
FT                   /note="Low complexity"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        252..267
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        404..427
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1027..1037
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         435
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19779198"
FT   MOD_RES         1037
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18407956"
FT   CARBOHYD        190
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        229
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        236
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        280
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        411
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        495
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        726
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        850
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   MUTAGEN         143..147
FT                   /note="WQEMP->AAEAA: Impairs the interaction with APM2 and
FT                   its recruitment to membranes, and leads to sertraline
FT                   sensitivity."
FT                   /evidence="ECO:0000269|PubMed:26658609"
FT   MUTAGEN         759
FT                   /note="S->A: Increases sensitivity to sertraline."
FT                   /evidence="ECO:0000269|PubMed:26658609"
FT   MUTAGEN         817
FT                   /note="D->A: Increases sensitivity to sertraline."
FT                   /evidence="ECO:0000269|PubMed:26658609"
FT   MUTAGEN         858
FT                   /note="H->A: Increases sensitivity to sertraline."
FT                   /evidence="ECO:0000269|PubMed:26658609"
FT   CONFLICT        323
FT                   /note="K -> N (in Ref. 1; BAA09205)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1073 AA;  119510 MW;  2CB2CAB4F9E24DA2 CRC64;
     MSDSEEDLGV QLKGLKIARH LKESGEHTDE ESNSSPEHDC GLSNQDDLTV MHTQAKEEVF
     KRREEDGTRT EDALHEGEAG KEGTGFPSSQ SVCSPNEADS GIDRADKPIL LDPFKSVHDT
     DPVPGTKSRS NSDSDSDSDD GGWQEMPAVS SFNIYNHRGE LELTSKVRNS EQASETSPTV
     PPGKNCKSVN DSRFDYTKMA AEQQAQRSYR TNKKTDFLFD HKVLKKKINS SQTSVNLTSS
     PSTTSLNNEK NNDDDDDDSY DEYEDDVEPV NDLNRDSQLN ITKNLLSDME KFAYVGAINI
     LANQMCTNLA TLCLCIDIKS HKKLAHRLQF TQKDMAAWKT VVLSRLYDHL GISQEEIVMI
     EKLSLHKIQL EDLCKCLKTT QSIDNPWEND RDHEEDGIEE TTERMSPNEQ NGSVQASTPD
     PEQSATPETP KAKQSPLSSD VPGKVLDPEN VKSQDKLNID VAWTIICDLF LICLQSSTYD
     SRSRTLLINF AKVLNMTSLE ICEFERRVTD SLDMEQSTED QVWDEQDHMR NRRRSKRRKK
     MAYVALAMVG GSLVLGLSGG LLAPVIGGGI AAGLSTIGIT GATSFLTGVG GTTVVAVSST
     AIGANIGARG MSKRMGSVRT FEFRPLHNNR RVNLILTVSG WMVGNEDDVR LPFSTVDPVE
     GDLYSLYWEP EMLKSIGQTV SIVATEIFTT SLQQILGATV LTALISSIQW PMALSKLGYI
     LDNPWNVSLD RAWSAGKILA DTLIARNLGA RPITLVGFSI GARVIFSCLI ELCKKKALGL
     IENVYLFGTP AVMKKEQLVM ARSVVSGRFV NGYSDKDWFL AYLFRAAAGG FSAVMGISTI
     ENVEGIENIN CTEFVDGHLN YRKSMPKLLK RIGIAVLSEE FVEIEEMMNP EEVKRKRKLI
     NDVDAAQKKL SERKKHNSWV PKWLKPKKSK WKVMVEEAVE EGRDMQDLPE NDVNNNENEN
     PDEHEGIARQ KRRDAALVDH GALMHELQLI KQAMHEDEIK NKACLPGEDK EVESSNDFLG
     ESHYKPPSTP KINPPQSPNN FQLLSAGRTI LPEDDDFDPR GKKKVEFSFP DDI
//