ID TM1L2_HUMAN Reviewed; 507 AA.
AC Q6ZVM7; B7Z2L7; B7Z7F4; Q86V61; Q8TDE7; Q96M88;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 27-MAR-2024, entry version 157.
DE RecName: Full=TOM1-like protein 2;
DE AltName: Full=Target of Myb-like protein 2;
GN Name=TOM1L2;
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] (ISOFORM 3), AND TISSUE SPECIFICITY.
RX PubMed=11997338; DOI=10.1101/gr.73702;
RA Bi W., Yan J., Stankiewicz P., Park S.-S., Walz K., Boerkoel C.F.,
RA Potocki L., Shaffer L.G., Devriendt K., Nowaczyk M.J.M., Inoue K.,
RA Lupski J.R.;
RT "Genes in a refined Smith-Magenis syndrome critical deletion interval on
RT chromosome 17p11.2 and the syntenic region of the mouse.";
RL Genome Res. 12:713-728(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3; 4 AND 5).
RC TISSUE=Brain, Testis, and Uterus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [5]
RP FUNCTION, AND INTERACTION WITH CLATHRIN AND TOLLIP.
RX PubMed=16412388; DOI=10.1016/j.bbrc.2005.12.156;
RA Katoh Y., Imakagura H., Futatsumori M., Nakayama K.;
RT "Recruitment of clathrin onto endosomes by the Tom1-Tollip complex.";
RL Biochem. Biophys. Res. Commun. 341:143-149(2006).
RN [6]
RP FUNCTION, AND INTERACTION WITH SRC.
RX PubMed=16479011; DOI=10.1128/mcb.26.5.1932-1947.2006;
RA Franco M., Furstoss O., Simon V., Benistant C., Hong W.J., Roche S.;
RT "The adaptor protein Tom1L1 is a negative regulator of Src mitogenic
RT signaling induced by growth factors.";
RL Mol. Cell. Biol. 26:1932-1947(2006).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-160 AND THR-164, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [9]
RP FUNCTION, AND INTERACTION WITH MYO6.
RX PubMed=23023224; DOI=10.1038/ncb2589;
RA Tumbarello D.A., Waxse B.J., Arden S.D., Bright N.A., Kendrick-Jones J.,
RA Buss F.;
RT "Autophagy receptors link myosin VI to autophagosomes to mediate Tom1-
RT dependent autophagosome maturation and fusion with the lysosome.";
RL Nat. Cell Biol. 14:1024-1035(2012).
RN [10]
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).
CC -!- FUNCTION: Acts as a MYO6/Myosin VI adapter protein that targets myosin
CC VI to endocytic structures (PubMed:23023224). May also play a role in
CC recruiting clathrin to endosomes (PubMed:16412388). May regulate growth
CC factor-induced mitogenic signaling (PubMed:16479011).
CC {ECO:0000269|PubMed:16412388, ECO:0000269|PubMed:16479011,
CC ECO:0000269|PubMed:23023224}.
CC -!- SUBUNIT: Interacts with clathrin, SRC and TOLLIP (PubMed:16412388,
CC PubMed:16479011). Interacts with MYO6 (PubMed:23023224).
CC {ECO:0000269|PubMed:16412388, ECO:0000269|PubMed:16479011,
CC ECO:0000269|PubMed:23023224}.
CC -!- INTERACTION:
CC Q6ZVM7-2; Q8IZU0: FAM9B; NbExp=5; IntAct=EBI-12147805, EBI-10175124;
CC Q6ZVM7-2; Q9H0E2: TOLLIP; NbExp=7; IntAct=EBI-12147805, EBI-74615;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q6ZVM7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6ZVM7-2; Sequence=VSP_023391;
CC Name=3;
CC IsoId=Q6ZVM7-3; Sequence=VSP_023392;
CC Name=4;
CC IsoId=Q6ZVM7-4; Sequence=VSP_023390;
CC Name=5;
CC IsoId=Q6ZVM7-5; Sequence=VSP_057214, VSP_057215;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed with higher expression in
CC heart and skeletal muscle. {ECO:0000269|PubMed:11997338}.
CC -!- DOMAIN: The GAT domain mediates interaction with TOLLIP.
CC -!- SIMILARITY: Belongs to the TOM1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAL78338.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF467441; AAL78338.1; ALT_SEQ; mRNA.
DR EMBL; AK057308; BAB71421.1; -; mRNA.
DR EMBL; AK124331; BAC85834.1; -; mRNA.
DR EMBL; AK294846; BAH11903.1; -; mRNA.
DR EMBL; AK301944; BAH13590.1; -; mRNA.
DR EMBL; AC087163; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC122129; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KF456255; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC051650; AAH51650.1; -; mRNA.
DR CCDS; CCDS32584.1; -. [Q6ZVM7-2]
DR CCDS; CCDS42270.1; -. [Q6ZVM7-1]
DR CCDS; CCDS74002.1; -. [Q6ZVM7-3]
DR CCDS; CCDS74003.1; -. [Q6ZVM7-5]
DR RefSeq; NP_001028723.1; NM_001033551.2. [Q6ZVM7-2]
DR RefSeq; NP_001076437.1; NM_001082968.1. [Q6ZVM7-1]
DR RefSeq; NP_001275715.1; NM_001288786.1. [Q6ZVM7-5]
DR RefSeq; NP_001275716.1; NM_001288787.1. [Q6ZVM7-3]
DR RefSeq; NP_001275717.1; NM_001288788.1.
DR RefSeq; NP_001275718.1; NM_001288789.1.
DR AlphaFoldDB; Q6ZVM7; -.
DR SMR; Q6ZVM7; -.
DR BioGRID; 127001; 61.
DR DIP; DIP-61860N; -.
DR IntAct; Q6ZVM7; 18.
DR MINT; Q6ZVM7; -.
DR STRING; 9606.ENSP00000368818; -.
DR GlyGen; Q6ZVM7; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q6ZVM7; -.
DR PhosphoSitePlus; Q6ZVM7; -.
DR SwissPalm; Q6ZVM7; -.
DR BioMuta; TOM1L2; -.
DR DMDM; 74712301; -.
DR EPD; Q6ZVM7; -.
DR jPOST; Q6ZVM7; -.
DR MassIVE; Q6ZVM7; -.
DR MaxQB; Q6ZVM7; -.
DR PaxDb; 9606-ENSP00000368818; -.
DR PeptideAtlas; Q6ZVM7; -.
DR ProteomicsDB; 6447; -.
DR ProteomicsDB; 68426; -. [Q6ZVM7-1]
DR ProteomicsDB; 68427; -. [Q6ZVM7-2]
DR ProteomicsDB; 68428; -. [Q6ZVM7-3]
DR ProteomicsDB; 68429; -. [Q6ZVM7-4]
DR Pumba; Q6ZVM7; -.
DR Antibodypedia; 13414; 167 antibodies from 25 providers.
DR DNASU; 146691; -.
DR Ensembl; ENST00000318094.14; ENSP00000312860.10; ENSG00000175662.18. [Q6ZVM7-3]
DR Ensembl; ENST00000379504.8; ENSP00000368818.3; ENSG00000175662.18. [Q6ZVM7-1]
DR Ensembl; ENST00000395739.8; ENSP00000379088.4; ENSG00000175662.18. [Q6ZVM7-3]
DR Ensembl; ENST00000478943.5; ENSP00000463313.1; ENSG00000175662.18. [Q6ZVM7-4]
DR Ensembl; ENST00000535933.5; ENSP00000438621.1; ENSG00000175662.18. [Q6ZVM7-5]
DR Ensembl; ENST00000581396.5; ENSP00000464297.1; ENSG00000175662.18. [Q6ZVM7-2]
DR GeneID; 146691; -.
DR KEGG; hsa:146691; -.
DR MANE-Select; ENST00000379504.8; ENSP00000368818.3; NM_001082968.2; NP_001076437.1.
DR UCSC; uc002gry.5; human. [Q6ZVM7-1]
DR AGR; HGNC:11984; -.
DR CTD; 146691; -.
DR DisGeNET; 146691; -.
DR GeneCards; TOM1L2; -.
DR HGNC; HGNC:11984; TOM1L2.
DR HPA; ENSG00000175662; Low tissue specificity.
DR MIM; 615519; gene.
DR neXtProt; NX_Q6ZVM7; -.
DR OpenTargets; ENSG00000175662; -.
DR PharmGKB; PA36668; -.
DR VEuPathDB; HostDB:ENSG00000175662; -.
DR eggNOG; KOG1087; Eukaryota.
DR GeneTree; ENSGT00940000156940; -.
DR HOGENOM; CLU_932372_0_0_1; -.
DR InParanoid; Q6ZVM7; -.
DR OMA; NYALHIE; -.
DR OrthoDB; 609735at2759; -.
DR PhylomeDB; Q6ZVM7; -.
DR TreeFam; TF314105; -.
DR PathwayCommons; Q6ZVM7; -.
DR SignaLink; Q6ZVM7; -.
DR SIGNOR; Q6ZVM7; -.
DR BioGRID-ORCS; 146691; 14 hits in 1154 CRISPR screens.
DR ChiTaRS; TOM1L2; human.
DR GeneWiki; TOM1L2; -.
DR GenomeRNAi; 146691; -.
DR Pharos; Q6ZVM7; Tbio.
DR PRO; PR:Q6ZVM7; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q6ZVM7; Protein.
DR Bgee; ENSG00000175662; Expressed in sural nerve and 179 other cell types or tissues.
DR ExpressionAtlas; Q6ZVM7; baseline and differential.
DR Genevisible; Q6ZVM7; HS.
DR GO; GO:0005768; C:endosome; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0030276; F:clathrin binding; IDA:UniProtKB.
DR GO; GO:0035091; F:phosphatidylinositol binding; IEA:InterPro.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0043130; F:ubiquitin binding; IEA:InterPro.
DR GO; GO:0045839; P:negative regulation of mitotic nuclear division; IDA:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0007165; P:signal transduction; IDA:UniProtKB.
DR CDD; cd14238; GAT_TM1L2; 1.
DR CDD; cd16996; VHS_Tom1L2; 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; IPR027429; TOM1L2_VHS_dom.
DR InterPro; IPR002014; VHS_dom.
DR PANTHER; PTHR13856:SF31; TOM1-LIKE PROTEIN 2; 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.
PE 1: Evidence at protein level;
KW Alternative splicing; Phosphoprotein; Protein transport;
KW Reference proteome; Transport.
FT CHAIN 1..507
FT /note="TOM1-like protein 2"
FT /id="PRO_0000278790"
FT DOMAIN 20..152
FT /note="VHS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00218"
FT DOMAIN 219..307
FT /note="GAT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00373"
FT REGION 162..210
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 467..507
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 329..334
FT /note="Clathrin-binding"
FT COMPBIAS 177..195
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 160
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 164
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT VAR_SEQ 1..267
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_023390"
FT VAR_SEQ 73..122
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_023391"
FT VAR_SEQ 123..167
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:11997338,
FT ECO:0000303|PubMed:14702039"
FT /id="VSP_023392"
FT VAR_SEQ 168..220
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_057214"
FT VAR_SEQ 426
FT /note="G -> GTFLSSAQKRGRGGESDLEPIDSWLITQGM (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_057215"
FT CONFLICT 12
FT /note="P -> A (in Ref. 1; AAL78338)"
FT /evidence="ECO:0000305"
FT CONFLICT 177
FT /note="T -> S (in Ref. 1; AAL78338)"
FT /evidence="ECO:0000305"
FT CONFLICT 323
FT /note="N -> S (in Ref. 1; AAL78338)"
FT /evidence="ECO:0000305"
FT CONFLICT 331
FT /note="I -> L (in Ref. 1; AAL78338)"
FT /evidence="ECO:0000305"
FT CONFLICT 347
FT /note="N -> S (in Ref. 1; AAL78338)"
FT /evidence="ECO:0000305"
FT CONFLICT 400
FT /note="K -> Q (in Ref. 1; AAL78338)"
FT /evidence="ECO:0000305"
FT CONFLICT 466
FT /note="E -> V (in Ref. 1; AAL78338)"
FT /evidence="ECO:0000305"
FT CONFLICT 475
FT /note="P -> H (in Ref. 1; AAL78338)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 507 AA; 55556 MW; 6CB4B4433076D8D0 CRC64;
MEFLLGNPFS TPVGQCLEKA TDGSLQSEDW TLNMEICDII NETEEGPKDA IRALKKRLNG
NRNYREVMLA LTVLETCVKN CGHRFHILVA NRDFIDSVLV KIISPKNNPP TIVQDKVLAL
IQAWADAFRS SPDLTGVVHI YEELKRKGVE FPMADLDALS PIHTPQRSVP EVDPAATMPR
SQSQQRTSAG SYSSPPPAPY SAPQAPALSV TGPITANSEQ IARLRSELDV VRGNTKVMSE
MLTEMVPGQE DSSDLELLQE LNRTCRAMQQ RIVELISRVS NEEVTEELLH VNDDLNNVFL
RYERFERYRS GRSVQNASNG VLNEVTEDNL IDLGPGSPAV VSPMVGNTAP PSSLSSQLAG
LDLGTESVSG TLSSLQQCNP RDGFDMFAQT RGNSLAEQRK TVTYEDPQAV GGLASALDNR
KQSSEGIPVA QPSVMDDIEV WLRTDLKGDD LEEGVTSEEF DKFLEERAKA AEMVPDLPSP
PMEAPAPASN PSGRKKPERS EDALFAL
//
