ID   TOM1_MOUSE              Reviewed;         492 AA.
AC   O88746; Q3V4C6; Q9D120;
DT   15-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1998, sequence version 1.
DT   24-JAN-2024, entry version 171.
DE   RecName: Full=Target of Myb1 membrane trafficking protein {ECO:0000250|UniProtKB:O60784};
DE   AltName: Full=Target of Myb protein 1 {ECO:0000305};
GN   Name=Tom1 {ECO:0000312|MGI:MGI:1338026};
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=10329004; DOI=10.1006/geno.1998.5739;
RA   Seroussi E., Kedra D., Kost-Alimova M., Sandberg-Nordqvist A.-C.,
RA   Fransson I., Jacobs J.F.M., Fu Y., Pan H.-Q., Roe B.A., Imreh S.,
RA   Dumanski J.P.;
RT   "TOM1 genes map to human chromosome 22q13.1 and mouse chromosome 8C1 and
RT   encode proteins similar to the endosomal proteins HGS and STAM.";
RL   Genomics 57:380-388(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   STRAIN=C57BL/6J; TISSUE=Thymus;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Colon;
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   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-176, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA   Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT   "Large-scale phosphorylation analysis of mouse liver.";
RL   Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN   [5]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-160; THR-164; SER-176;
RP   SER-180 AND SER-208, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP   ANALYSIS].
RC   TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung,
RC   Pancreas, Spleen, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [6]
RP   FUNCTION, SUBCELLULAR LOCATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=25588840; DOI=10.1242/jcs.166314;
RA   Boal F., Mansour R., Gayral M., Saland E., Chicanne G., Xuereb J.M.,
RA   Marcellin M., Burlet-Schiltz O., Sansonetti P.J., Payrastre B.,
RA   Tronchere H.;
RT   "TOM1 is a PI5P effector involved in the regulation of endosomal
RT   maturation.";
RL   J. Cell Sci. 128:815-827(2015).
CC   -!- FUNCTION: Adapter protein that plays a role in the intracellular
CC       membrane trafficking of ubiquitinated proteins, thereby participating
CC       in autophagy, ubiquitination-dependent signaling and receptor recycling
CC       pathways (By similarity). Acts as a MYO6/Myosin VI adapter protein that
CC       targets MYO6 to endocytic structures (By similarity). Together with
CC       MYO6, required for autophagosomal delivery of endocytic cargo, the
CC       maturation of autophagosomes and their fusion with lysosomes (By
CC       similarity). MYO6 links TOM1 with autophagy receptors, such as TAX1BP1;
CC       CALCOCO2/NDP52 and OPTN (By similarity). Binds to polyubiquitinated
CC       proteins via its GAT domain (By similarity). In a complex with TOLLIP,
CC       recruits ubiquitin-conjugated proteins onto early endosomes (By
CC       similarity). The Tom1-Tollip complex may regulate endosomal trafficking
CC       by linking polyubiquitinated proteins to clathrin (By similarity).
CC       Mediates clathrin recruitment to early endosomes by ZFYVE16 (By
CC       similarity). Modulates binding of TOLLIP to phosphatidylinositol 3-
CC       phosphate (PtdIns(3)P) via binding competition; the association with
CC       TOLLIP may favor the release of TOLLIP from endosomal membranes,
CC       allowing TOLLIP to commit to cargo trafficking (By similarity). Acts as
CC       a phosphatidylinositol 5-phosphate (PtdIns(5)P) effector by binding to
CC       PtdIns(5)P, thereby regulating endosomal maturation (PubMed:25588840).
CC       PtdIns(5)P-dependent recruitment to signaling endosomes may block
CC       endosomal maturation (PubMed:25588840). Also inhibits Toll-like
CC       receptor (TLR) signaling and participates in immune receptor recycling
CC       (By similarity). {ECO:0000250|UniProtKB:O60784,
CC       ECO:0000269|PubMed:25588840}.
CC   -!- SUBUNIT: Found in a complex with TOLLIP; interacts (via GAT domain)
CC       with TOLLIP (via N-terminus); the interactions leads to TOM1-
CC       recruitment to endosomes and inhibition of TOLLIP binding to PtdIns(3)P
CC       (By similarity). Interacts (via GAT domain and the C-terminal part of
CC       the VHS domain) with UBC/ubiquitin (By similarity). Interacts (via
CC       clathrin box and C-terminus) with clathrin heavy chain (By similarity).
CC       Interacts with MYO6 (By similarity). Interacts with TAX1BP1;
CC       CALCOCO2/NDP52 and OPTN; the interaction is indirect and is mediated by
CC       MYO6, which acts as a bridge between TOM1 and the three autophagy
CC       receptors (By similarity). Interacts (via C-terminus) with ZFYVE16 (via
CC       C-terminus); interaction is required to target TOM1 and clathrin to
CC       endosomes (By similarity). Interacts with LRBA (By similarity).
CC       {ECO:0000250|UniProtKB:O60784}.
CC   -!- INTERACTION:
CC       O88746; Q9QZ06: Tollip; NbExp=2; IntAct=EBI-74264, EBI-74272;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:25588840}. Endosome
CC       membrane {ECO:0000269|PubMed:25588840}; Peripheral membrane protein
CC       {ECO:0000305}. Early endosome membrane {ECO:0000250|UniProtKB:O60784};
CC       Peripheral membrane protein {ECO:0000305}. Note=Localized to
CC       endo/exosomal vesicles (PubMed:25588840). Enriched on signaling
CC       endosomes (PubMed:25588840). Recruited to early endosomes by TOLLIP and
CC       by PtdIns(5)P (By similarity). {ECO:0000250|UniProtKB:O60784,
CC       ECO:0000269|PubMed:25588840}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=O88746-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=O88746-2; Sequence=VSP_003991, VSP_003992;
CC   -!- TISSUE SPECIFICITY: Ubiquitous. In adult brain, it is highly expressed
CC       at the mesencephalic level, in the hippocampal formation and medial
CC       lemniscus. In cerebellum, it is highly expressed in Purkinje cells and
CC       granular layers.
CC   -!- DEVELOPMENTAL STAGE: Ubiquitously expressed in the embryo, with a
CC       higher expression in the intestines.
CC   -!- DOMAIN: The GAT domain and the VHS domain are required for the
CC       interaction with polyubiquitinated proteins.
CC       {ECO:0000250|UniProtKB:O60784}.
CC   -!- DOMAIN: The VHS domain binds to phosphatidylinositol monophosphates (By
CC       similarity). The KRKK motif within the VHS domain is required for
CC       binding to phosphatidylinositol monophosphates, with a preference for
CC       phosphatidylinositol 5-phosphate (PtdIns(5)P) (By similarity).
CC       {ECO:0000250|UniProtKB:O60784}.
CC   -!- PTM: Monoubiquitinated. {ECO:0000250|UniProtKB:O60784}.
CC   -!- SIMILARITY: Belongs to the TOM1 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; AJ006972; CAA07361.1; -; mRNA.
DR   EMBL; AK004063; BAE43160.1; -; mRNA.
DR   EMBL; AK028398; BAC25932.1; -; mRNA.
DR   EMBL; BC021633; AAH21633.1; -; mRNA.
DR   CCDS; CCDS52601.1; -. [O88746-1]
DR   RefSeq; NP_035752.1; NM_011622.3. [O88746-1]
DR   AlphaFoldDB; O88746; -.
DR   SMR; O88746; -.
DR   BioGRID; 204274; 8.
DR   IntAct; O88746; 3.
DR   STRING; 10090.ENSMUSP00000077891; -.
DR   GlyGen; O88746; 3 sites, 1 O-linked glycan (3 sites).
DR   iPTMnet; O88746; -.
DR   PhosphoSitePlus; O88746; -.
DR   SwissPalm; O88746; -.
DR   EPD; O88746; -.
DR   jPOST; O88746; -.
DR   MaxQB; O88746; -.
DR   PaxDb; 10090-ENSMUSP00000036849; -.
DR   PeptideAtlas; O88746; -.
DR   ProteomicsDB; 258813; -. [O88746-1]
DR   ProteomicsDB; 258814; -. [O88746-2]
DR   Pumba; O88746; -.
DR   Antibodypedia; 208; 232 antibodies from 27 providers.
DR   DNASU; 21968; -.
DR   Ensembl; ENSMUST00000165630.3; ENSMUSP00000130854.2; ENSMUSG00000042870.16. [O88746-1]
DR   GeneID; 21968; -.
DR   KEGG; mmu:21968; -.
DR   UCSC; uc009mha.2; mouse. [O88746-1]
DR   UCSC; uc009mhb.2; mouse. [O88746-2]
DR   AGR; MGI:1338026; -.
DR   CTD; 10043; -.
DR   MGI; MGI:1338026; Tom1.
DR   VEuPathDB; HostDB:ENSMUSG00000042870; -.
DR   eggNOG; KOG1087; Eukaryota.
DR   GeneTree; ENSGT00940000156865; -.
DR   HOGENOM; CLU_043812_3_0_1; -.
DR   InParanoid; O88746; -.
DR   OMA; GNHKSDM; -.
DR   OrthoDB; 609735at2759; -.
DR   PhylomeDB; O88746; -.
DR   TreeFam; TF314105; -.
DR   Reactome; R-MMU-6798695; Neutrophil degranulation.
DR   BioGRID-ORCS; 21968; 1 hit in 77 CRISPR screens.
DR   ChiTaRS; Tom1; mouse.
DR   PRO; PR:O88746; -.
DR   Proteomes; UP000000589; Chromosome 8.
DR   RNAct; O88746; Protein.
DR   Bgee; ENSMUSG00000042870; Expressed in lens of camera-type eye and 69 other cell types or tissues.
DR   ExpressionAtlas; O88746; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR   GO; GO:0005769; C:early endosome; ISS:UniProtKB.
DR   GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005768; C:endosome; ISS:UniProtKB.
DR   GO; GO:0010008; C:endosome membrane; ISS:UniProtKB.
DR   GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR   GO; GO:0030276; F:clathrin binding; ISO:MGI.
DR   GO; GO:0032050; F:clathrin heavy chain binding; ISS:UniProtKB.
DR   GO; GO:0070853; F:myosin VI binding; ISS:UniProtKB.
DR   GO; GO:0010314; F:phosphatidylinositol-5-phosphate binding; ISS:UniProtKB.
DR   GO; GO:0031593; F:polyubiquitin modification-dependent protein binding; ISS:UniProtKB.
DR   GO; GO:0043130; F:ubiquitin binding; ISS:UniProtKB.
DR   GO; GO:0061909; P:autophagosome-lysosome fusion; ISS:UniProtKB.
DR   GO; GO:0016197; P:endosomal transport; ISS:UniProtKB.
DR   GO; GO:1901098; P:positive regulation of autophagosome maturation; ISS:UniProtKB.
DR   GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR   GO; GO:1904978; P:regulation of endosome organization; ISS:UniProtKB.
DR   GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR   GO; GO:0061753; P:substrate localization to autophagosome; ISS:UniProtKB.
DR   CDD; cd14236; GAT_TOM1; 1.
DR   CDD; cd16995; VHS_Tom1; 1.
DR   Gene3D; 1.20.58.160; -; 1.
DR   Gene3D; 1.25.40.90; -; 1.
DR   InterPro; IPR008942; ENTH_VHS.
DR   InterPro; IPR004152; GAT_dom.
DR   InterPro; IPR038425; GAT_sf.
DR   InterPro; IPR014645; TOM1.
DR   InterPro; IPR002014; VHS_dom.
DR   PANTHER; PTHR13856:SF32; TARGET OF MYB PROTEIN 1; 1.
DR   PANTHER; PTHR13856; VHS DOMAIN CONTAINING PROTEIN FAMILY; 1.
DR   Pfam; PF03127; GAT; 1.
DR   Pfam; PF00790; VHS; 1.
DR   PIRSF; PIRSF036948; TOM1; 1.
DR   SMART; SM00288; VHS; 1.
DR   SUPFAM; SSF48464; ENTH/VHS domain; 1.
DR   SUPFAM; SSF89009; GAT-like domain; 1.
DR   PROSITE; PS50909; GAT; 1.
DR   PROSITE; PS50179; VHS; 1.
DR   Genevisible; O88746; MM.
PE   1: Evidence at protein level;
KW   Acetylation; Alternative splicing; Cytoplasm; Endosome; Isopeptide bond;
KW   Membrane; Phosphoprotein; Protein transport; Reference proteome; Transport;
KW   Ubl conjugation.
FT   CHAIN           1..492
FT                   /note="Target of Myb1 membrane trafficking protein"
FT                   /id="PRO_0000072629"
FT   DOMAIN          20..152
FT                   /note="VHS"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00218"
FT   DOMAIN          215..303
FT                   /note="GAT"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00373"
FT   REGION          167..215
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          321..326
FT                   /note="Clathrin box"
FT                   /evidence="ECO:0000250|UniProtKB:O60784"
FT   REGION          392..463
FT                   /note="Interaction with MYO6"
FT                   /evidence="ECO:0000250|UniProtKB:O60784"
FT   REGION          450..492
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           48..56
FT                   /note="KRKK"
FT                   /evidence="ECO:0000250|UniProtKB:O60784"
FT   COMPBIAS        167..194
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        477..492
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         1
FT                   /note="N-acetylmethionine"
FT                   /evidence="ECO:0000250|UniProtKB:O60784"
FT   MOD_RES         11
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:O60784"
FT   MOD_RES         160
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         164
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         176
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:17242355,
FT                   ECO:0007744|PubMed:21183079"
FT   MOD_RES         180
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         208
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         355
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:O60784"
FT   MOD_RES         376
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:O60784"
FT   MOD_RES         462
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:O60784"
FT   CROSSLNK        385
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:O60784"
FT   VAR_SEQ         1..324
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:16141072"
FT                   /id="VSP_003991"
FT   VAR_SEQ         325..343
FT                   /note="MGPDPAATNNLSSQLAGMN -> MGRANGTAGLLPGPSVSAD (in
FT                   isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:16141072"
FT                   /id="VSP_003992"
SQ   SEQUENCE   492 AA;  54325 MW;  A15F24FD9B4D31C3 CRC64;
     MDFLLGNPFS SPVGQRIEKA TDGSLQSEDW ALNMEICDII NETEEGPKDA FRAVKKRIMG
     NKNFHEVMLA LTVLETCVKN CGHRFHVLVA NQDFVENVLV RTILPKNNPP TIVHDKVLNL
     IQSWADAFRS SPDLTGVVAV YEDLRRKGLE FPMTDLDMLS PIHTPQRTVF NSETPSRQNS
     VSSNTSQRGD LSQHATPLPT PAVLPGDSPI TPTPEQIGKL RSELEMVSGN VRVMSEMLTE
     LVPTQVEPAD LELLQELNRT CRAMQQRILE LIPRISNEQL TEELLMINDN LNNVFLRHER
     FERFRTGQTA KASSEAELAT DLIDMGPDPA ATNNLSSQLA GMNLGSRSVR AGLQSLETSG
     HLEDDFDMFA LTRGSSLADQ RKGVKYEAPQ TTDGLAGALD ARQQSTGAIP ATQARIMEDI
     EQWLSTDVGN SAEEPSGVTS EEFDKFLEER AKAADRLPNL ASPSAEGPPR PSPGTAPRRK
     TQEKDDDMLF AL
//