ID MD1L1_HUMAN Reviewed; 718 AA. AC Q9Y6D9; B3KR41; Q13312; Q75MI0; Q86UM4; Q9UNH0; DT 27-SEP-2004, integrated into UniProtKB/Swiss-Prot. DT 27-SEP-2004, sequence version 2. DT 27-MAR-2024, entry version 199. DE RecName: Full=Mitotic spindle assembly checkpoint protein MAD1; DE AltName: Full=Mitotic arrest deficient 1-like protein 1; DE Short=MAD1-like protein 1; DE AltName: Full=Mitotic checkpoint MAD1 protein homolog; DE Short=HsMAD1; DE Short=hMAD1; DE AltName: Full=Tax-binding protein 181; GN Name=MAD1L1; Synonyms=MAD1, TXBP181; 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 1), HOMODIMERIZATION, RP HETEROTETRAMERIZATION, SUBCELLULAR LOCATION, PHOSPHORYLATION, AND RP INTERACTION WITH MAD2L1 AND VIRAL TAX. RX PubMed=9546394; DOI=10.1016/s0092-8674(00)81148-4; RA Jin D.-Y., Spencer F., Jeang K.-T.; RT "Human T cell leukemia virus type 1 oncoprotein Tax targets the human RT mitotic checkpoint protein MAD1."; RL Cell 93:81-91(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PHOSPHORYLATION BY BUB1, AND RP INTERACTION WITH BUB1/BUB3 COMPLEX. RC TISSUE=Testis; RX PubMed=10198256; DOI=10.1006/bbrc.1999.0514; RA Seeley T.W., Wang L., Zhen J.Y.; RT "Phosphorylation of human MAD1 by the BUB1 kinase in vitro."; RL Biochem. Biophys. Res. Commun. 257:589-595(1999). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INDUCTION, AND FUNCTION. RX PubMed=10049595; DOI=10.1006/geno.1998.5654; RA Jin D.-Y., Kozak C.A., Pangilinan F., Spencer F., Green E.D., Jeang K.-T.; RT "Mitotic checkpoint locus MAD1L1 maps to human chromosome 7p22 and mouse RT chromosome 5."; RL Genomics 55:363-364(1999). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Amygdala; 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 [5] 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Pancreas; 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 [7] RP SUBCELLULAR LOCATION, AND INTERACTION WITH NEK2. RX PubMed=14978040; DOI=10.1074/jbc.m314205200; RA Lou Y., Yao J., Zereshki A., Dou Z., Ahmed K., Wang H., Hu J., Wang Y., RA Yao X.; RT "NEK2A interacts with MAD1 and possibly functions as a novel integrator of RT the spindle checkpoint signaling."; RL J. Biol. Chem. 279:20049-20057(2004). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-428, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=16964243; DOI=10.1038/nbt1240; RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.; RT "A probability-based approach for high-throughput protein phosphorylation RT analysis and site localization."; RL Nat. Biotechnol. 24:1285-1292(2006). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-214, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., RA Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [10] RP ALTERNATIVE SPLICING (ISOFORM 3), FUNCTION (ISOFORM 3), SUBCELLULAR RP LOCATION (ISOFORMS 1 AND 3), INTERACTION WITH MAD2L1 (ISOFORMS 1 AND 3), RP TISSUE SPECIFICITY (ISOFORMS 1 AND 3), NUCLEAR LOCALIZATION SIGNAL, AND RP MUTAGENESIS OF 79-LYS--ARG-82 AND 540-SER--ALA-551. RX PubMed=19010891; DOI=10.1158/0008-5472.can-08-2600; RA Sze K.M., Ching Y.P., Jin D.Y., Ng I.O.; RT "Role of a novel splice variant of mitotic arrest deficient 1 (MAD1), RT MAD1beta, in mitotic checkpoint control in liver cancer."; RL Cancer Res. 68:9194-9201(2008). RN [11] RP INTERACTION WITH TPR AND MAD2L1, IDENTIFICATION BY MASS SPECTROMETRY, AND RP SUBCELLULAR LOCATION. RX PubMed=18981471; DOI=10.1101/gad.1677208; RA Lee S.H., Sterling H., Burlingame A., McCormick F.; RT "Tpr directly binds to Mad1 and Mad2 and is important for the Mad1-Mad2- RT mediated mitotic spindle checkpoint."; RL Genes Dev. 22:2926-2931(2008). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-16 AND SER-428, AND 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 [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [15] RP INTERACTION WITH TPR. RX PubMed=19273613; DOI=10.1083/jcb.200811012; RA Lince-Faria M., Maffini S., Orr B., Ding Y., Florindo C., Sunkel C.E., RA Tavares A., Johansen J., Johansen K.M., Maiato H.; RT "Spatiotemporal control of mitosis by the conserved spindle matrix protein RT Megator."; RL J. Cell Biol. 184:647-657(2009). RN [16] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-61, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [17] RP FUNCTION, INTERACTION WITH TPR, AND SUBCELLULAR LOCATION. RX PubMed=20133940; DOI=10.1074/jbc.m110.105890; RA Nakano H., Funasaka T., Hashizume C., Wong R.W.; RT "Nucleoporin translocated promoter region (Tpr) associates with dynein RT complex, preventing chromosome lagging formation during mitosis."; RL J. Biol. Chem. 285:10841-10849(2010). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-428, AND IDENTIFICATION BY RP 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 [19] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [20] RP SUBCELLULAR LOCATION, AND INTERACTION WITH IK AND MAD2L1. RX PubMed=22351768; DOI=10.1074/jbc.m111.299131; RA Yeh P.C., Yeh C.C., Chen Y.C., Juang Y.L.; RT "RED, a spindle pole-associated protein, is required for kinetochore RT localization of MAD1, mitotic progression, and activation of the spindle RT assembly checkpoint."; RL J. Biol. Chem. 287:11704-11716(2012). RN [21] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [22] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [23] RP INTERACTION WITH PRAP1, AND TISSUE SPECIFICITY. RX PubMed=24374861; DOI=10.1002/path.4319; RA Sze K.M., Chu G.K., Mak Q.H., Lee J.M., Ng I.O.; RT "Proline-rich acidic protein 1 (PRAP1) is a novel interacting partner of RT MAD1 and has a suppressive role in mitotic checkpoint signalling in RT hepatocellular carcinoma."; RL J. Pathol. 233:51-60(2014). RN [24] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-16 AND SER-428, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [25] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-61, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25218447; DOI=10.1038/nsmb.2890; RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M., RA Vertegaal A.C.; RT "Uncovering global SUMOylation signaling networks in a site-specific RT manner."; RL Nat. Struct. Mol. Biol. 21:927-936(2014). RN [26] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-61, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [27] RP FUNCTION, SUBUNIT, INTERACTION WITH MAD2L1 AND TTK, SUBCELLULAR LOCATION, RP PHOSPHORYLATION AT SER-598; SER-610; TYR-634 AND THR-716, AND MUTAGENESIS RP OF 1-MET--SER-485; LYS-541; LEU-543; 597-SER--ALA-718; SER-598; SER-610; RP TYR-634 AND THR-716. RX PubMed=29162720; DOI=10.1074/jbc.ra117.000555; RA Ji W., Luo Y., Ahmad E., Liu S.T.; RT "Direct interactions of mitotic arrest deficient 1 (MAD1) domains with each RT other and MAD2 conformers are required for mitotic checkpoint signaling."; RL J. Biol. Chem. 293:484-496(2018). RN [28] RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 493-579 IN COMPLEX WITH MAD2L1, RP AND COMPETITIVE INHIBITOR OF MAD2L1-CDC20 INTERACTION. RX PubMed=12006501; DOI=10.1093/emboj/21.10.2496; RA Sironi L., Mapelli M., Knapp S., De Antoni A., Jeang K.-T., Musacchio A.; RT "Crystal structure of the tetrameric Mad1-Mad2 core complex: implications RT of a 'safety belt' binding mechanism for the spindle checkpoint."; RL EMBO J. 21:2496-2506(2002). RN [29] RP VARIANTS HIS-558 AND HIS-572. RX PubMed=10366450; DOI=10.1006/geno.1999.5831; RA Cahill D.P., da Costa L.T., Carson-Walter E.B., Kinzler K.W., RA Vogelstein B., Lengauer C.; RT "Characterization of MAD2B and other mitotic spindle checkpoint genes."; RL Genomics 58:181-187(1999). RN [30] RP VARIANT LUNG CANCER ALA-299, AND VARIANTS SER-160; MET-500; LYS-511; RP HIS-556 AND HIS-558. RX PubMed=10597320; DOI=10.1038/sj.onc.1203141; RA Nomoto S., Haruki N., Takahashi T., Masuda A., Koshikawa T., Takahashi T., RA Fujii Y., Osada H., Takahashi T.; RT "Search for in vivo somatic mutations in the mitotic checkpoint gene, RT hMAD1, in human lung cancers."; RL Oncogene 18:7180-7183(1999). RN [31] RP VARIANTS CANCER LEU-29; CYS-59; GLN-360; LYS-516; CYS-556 AND LYS-569, AND RP VARIANTS MET-500 AND HIS-558. RX PubMed=11423979; DOI=10.1038/sj.onc.1204421; RA Tsukasaki K., Miller C.W., Greenspun E., Eshaghian S., Kawabata H., RA Fujimoto T., Tomonaga M., Sawyers C., Said J.W., Koeffler H.P.; RT "Mutations in the mitotic check point gene, MAD1L1, in human cancers."; RL Oncogene 20:3301-3305(2001). RN [32] RP INVOLVEMENT IN MVA7, VARIANTS MVA7 66-GLN--ALA-718 DEL AND 628-GLU--ALA-718 RP DEL, CHARACTERIZATION OF VARIANTS MVA7 66-GLN--ALA-718 DEL AND RP 628-GLU--ALA-718 DEL, AND FUNCTION. RX PubMed=36322655; DOI=10.1126/sciadv.abq5914; RA Villarroya-Beltri C., Osorio A., Torres-Ruiz R., Gomez-Sanchez D., RA Trakala M., Sanchez-Belmonte A., Mercadillo F., Hurtado B., Pitarch B., RA Hernandez-Nunez A., Gomez-Caturla A., Rueda D., Perea J., RA Rodriguez-Perales S., Malumbres M., Urioste M.; RT "Biallelic germline mutations in MAD1L1 induce a syndrome of aneuploidy RT with high tumor susceptibility."; RL Sci. Adv. 8:eabq5914-eabq5914(2022). CC -!- FUNCTION: Component of the spindle-assembly checkpoint that prevents CC the onset of anaphase until all chromosomes are properly aligned at the CC metaphase plate (PubMed:10049595, PubMed:20133940, PubMed:29162720). CC Forms a heterotetrameric complex with the closed conformation form of CC MAD2L1 (C-MAD2) at unattached kinetochores during prometaphase, CC recruits an open conformation of MAD2L1 (O-MAD2) and promotes the CC conversion of O-MAD2 to C-MAD2, which ensures mitotic checkpoint CC signaling (PubMed:29162720). {ECO:0000269|PubMed:10049595, CC ECO:0000269|PubMed:20133940, ECO:0000269|PubMed:29162720, CC ECO:0000269|PubMed:36322655}. CC -!- FUNCTION: [Isoform 3]: Sequesters MAD2L1 in the cytoplasm preventing CC its function as an activator of the mitotic spindle assembly checkpoint CC (SAC) resulting in SAC impairment and chromosomal instability in CC hepatocellular carcinomas. {ECO:0000269|PubMed:19010891}. CC -!- SUBUNIT: Homodimer (PubMed:9546394, PubMed:29162720). Dimerizes via its CC N- and C- terminal regions (PubMed:29162720). Heterodimerizes with CC MAD2L1 in order to form a tetrameric MAD1L1-MAD2L1 core complex CC (PubMed:22351768, PubMed:9546394, PubMed:18981471, PubMed:12006501). CC Interacts with the closed conformation form of MAD2L1 (C-MAD2) and open CC conformation form of MAD2L1 (O-MAD2) (PubMed:29162720). It is unclear CC whether MAD1L1 dimerization promotes the conversion of closed to open CC conformation of MAD2L1 (PubMed:29162720). Formation of a CC heterotetrameric core complex containing two molecules each of MAD1L1 CC and of MAD2L1 promotes binding of another molecule of MAD2L1 to each CC MAD2L1, resulting in a heterohexamer (PubMed:12006501). Perturbation of CC the original MAD1L1-MAD2L1 structure by the spindle checkpoint may CC decrease MAD2L1 affinity for MAD1L1 (PubMed:12006501). CDC20 can CC compete with MAD1L1 for MAD2L1 binding, until the attachment and/or CC tension dampen the checkpoint signal, preventing further release of CC MAD2L1 on to CDC20 (PubMed:12006501). Also able to interact with the CC BUB1/BUB3 complex (PubMed:10198256). Interacts with NEK2 CC (PubMed:14978040). Interacts with TTK (PubMed:29162720). Interacts with CC TPR; the interactions occurs in a microtubule-independent manner CC (PubMed:18981471, PubMed:19273613, PubMed:20133940). Interacts with IK CC (PubMed:22351768). Interacts with the viral Tax protein CC (PubMed:9546394). Interacts with PRAP1 (PubMed:24374861). CC {ECO:0000269|PubMed:10198256, ECO:0000269|PubMed:12006501, CC ECO:0000269|PubMed:14978040, ECO:0000269|PubMed:18981471, CC ECO:0000269|PubMed:19010891, ECO:0000269|PubMed:19273613, CC ECO:0000269|PubMed:20133940, ECO:0000269|PubMed:22351768, CC ECO:0000269|PubMed:24374861, ECO:0000269|PubMed:29162720, CC ECO:0000269|PubMed:9546394}. CC -!- SUBUNIT: [Isoform 3]: Interacts with MAD2L1; this interaction leads to CC the cytoplasmic sequestration of MAD2L1 (PubMed:19010891). Interacts CC with PRAP1 (PubMed:24374861). {ECO:0000269|PubMed:19010891, CC ECO:0000269|PubMed:24374861}. CC -!- INTERACTION: CC Q9Y6D9; P09917: ALOX5; NbExp=9; IntAct=EBI-742610, EBI-79934; CC Q9Y6D9; Q9H1Y0: ATG5; NbExp=3; IntAct=EBI-742610, EBI-1047414; CC Q9Y6D9; Q9UL15: BAG5; NbExp=7; IntAct=EBI-742610, EBI-356517; CC Q9Y6D9; Q9Y6W3: CAPN7; NbExp=3; IntAct=EBI-742610, EBI-1765641; CC Q9Y6D9; Q2TAC2-2: CCDC57; NbExp=3; IntAct=EBI-742610, EBI-10961624; CC Q9Y6D9; Q8TD31-3: CCHCR1; NbExp=6; IntAct=EBI-742610, EBI-10175300; CC Q9Y6D9; Q16543: CDC37; NbExp=3; IntAct=EBI-742610, EBI-295634; CC Q9Y6D9; Q07002: CDK18; NbExp=3; IntAct=EBI-742610, EBI-746238; CC Q9Y6D9; Q02224: CENPE; NbExp=3; IntAct=EBI-742610, EBI-1375040; CC Q9Y6D9; O43247-2: CIMIP4; NbExp=3; IntAct=EBI-742610, EBI-12093053; CC Q9Y6D9; Q2TBE0: CWF19L2; NbExp=6; IntAct=EBI-742610, EBI-5453285; CC Q9Y6D9; Q86YD7: FAM90A1; NbExp=3; IntAct=EBI-742610, EBI-6658203; CC Q9Y6D9; O95995: GAS8; NbExp=3; IntAct=EBI-742610, EBI-1052570; CC Q9Y6D9; Q92917: GPKOW; NbExp=3; IntAct=EBI-742610, EBI-746309; CC Q9Y6D9; Q96CS2: HAUS1; NbExp=3; IntAct=EBI-742610, EBI-2514791; CC Q9Y6D9; Q9HAQ2: KIF9; NbExp=3; IntAct=EBI-742610, EBI-8472129; CC Q9Y6D9; Q96BZ8: LENG1; NbExp=3; IntAct=EBI-742610, EBI-726510; CC Q9Y6D9; Q3ZCW2: LGALSL; NbExp=6; IntAct=EBI-742610, EBI-10241423; CC Q9Y6D9; P25800: LMO1; NbExp=3; IntAct=EBI-742610, EBI-8639312; CC Q9Y6D9; Q8TAP4-4: LMO3; NbExp=3; IntAct=EBI-742610, EBI-11742507; CC Q9Y6D9; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-742610, EBI-739832; CC Q9Y6D9; Q9Y6D9: MAD1L1; NbExp=11; IntAct=EBI-742610, EBI-742610; CC Q9Y6D9; Q13257: MAD2L1; NbExp=39; IntAct=EBI-742610, EBI-78203; CC Q9Y6D9; P55081: MFAP1; NbExp=6; IntAct=EBI-742610, EBI-1048159; CC Q9Y6D9; O76041: NEBL; NbExp=7; IntAct=EBI-742610, EBI-2880203; CC Q9Y6D9; Q96HA8: NTAQ1; NbExp=3; IntAct=EBI-742610, EBI-741158; CC Q9Y6D9; Q4G0R1: PIBF1; NbExp=3; IntAct=EBI-742610, EBI-14066006; CC Q9Y6D9; Q6NYC8: PPP1R18; NbExp=3; IntAct=EBI-742610, EBI-2557469; CC Q9Y6D9; P25786: PSMA1; NbExp=3; IntAct=EBI-742610, EBI-359352; CC Q9Y6D9; O76064: RNF8; NbExp=7; IntAct=EBI-742610, EBI-373337; CC Q9Y6D9; Q8TC71: SPATA18; NbExp=3; IntAct=EBI-742610, EBI-11334239; CC Q9Y6D9; Q9UM82: SPATA2; NbExp=3; IntAct=EBI-742610, EBI-744066; CC Q9Y6D9; Q9BSW7: SYT17; NbExp=3; IntAct=EBI-742610, EBI-745392; CC Q9Y6D9; Q5T7P8-2: SYT6; NbExp=3; IntAct=EBI-742610, EBI-10246152; CC Q9Y6D9; Q9Y4C2-2: TCAF1; NbExp=3; IntAct=EBI-742610, EBI-11974855; CC Q9Y6D9; P09493: TPM1; NbExp=6; IntAct=EBI-742610, EBI-351158; CC Q9Y6D9; P09493-10: TPM1; NbExp=6; IntAct=EBI-742610, EBI-12123928; CC Q9Y6D9; P06753: TPM3; NbExp=10; IntAct=EBI-742610, EBI-355607; CC Q9Y6D9; Q5VU62: TPM3; NbExp=3; IntAct=EBI-742610, EBI-10184033; CC Q9Y6D9; P12270: TPR; NbExp=2; IntAct=EBI-742610, EBI-1048528; CC Q9Y6D9; Q14134: TRIM29; NbExp=7; IntAct=EBI-742610, EBI-702370; CC Q9Y6D9; Q99576: TSC22D3; NbExp=3; IntAct=EBI-742610, EBI-750174; CC Q9Y6D9; Q99576-3: TSC22D3; NbExp=3; IntAct=EBI-742610, EBI-10294415; CC Q9Y6D9; Q9BZW7: TSGA10; NbExp=3; IntAct=EBI-742610, EBI-744794; CC Q9Y6D9; Q63HK5: TSHZ3; NbExp=3; IntAct=EBI-742610, EBI-9053916; CC Q9Y6D9; Q9Y4E8: USP15; NbExp=3; IntAct=EBI-742610, EBI-1043104; CC Q9Y6D9; Q9Y4E8-2: USP15; NbExp=3; IntAct=EBI-742610, EBI-12041225; CC Q9Y6D9; Q9BW85: YJU2; NbExp=3; IntAct=EBI-742610, EBI-10300345; CC Q9Y6D9; Q9NX65: ZSCAN32; NbExp=3; IntAct=EBI-742610, EBI-739949; CC Q9Y6D9; PRO_0000449631 [P0DTD1]: rep; Xeno; NbExp=3; IntAct=EBI-742610, EBI-25475920; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:19010891, CC ECO:0000269|PubMed:9546394}. Chromosome, centromere, kinetochore CC {ECO:0000269|PubMed:14978040, ECO:0000269|PubMed:18981471, CC ECO:0000269|PubMed:22351768, ECO:0000269|PubMed:29162720}. Nucleus CC envelope {ECO:0000269|PubMed:18981471, ECO:0000269|PubMed:22351768}. CC Cytoplasm, cytoskeleton, microtubule organizing center, centrosome CC {ECO:0000269|PubMed:14978040, ECO:0000269|PubMed:9546394}. Cytoplasm, CC cytoskeleton, spindle {ECO:0000269|PubMed:9546394}. Cytoplasm, CC cytoskeleton, spindle pole {ECO:0000269|PubMed:22351768}. Note=Co- CC localizes with TPR at the nucleus envelope during interphase and CC throughout the cell cycle (PubMed:22351768, PubMed:18981471). From the CC beginning to the end of mitosis, it is seen to move from a diffusely CC nuclear distribution to the centrosome, to the spindle midzone and CC finally to the midbody (PubMed:9546394). Localizes to kinetochores CC during prometaphase (PubMed:22351768, PubMed:29162720). Does not CC localize to kinetochores during metaphase (PubMed:29162720). CC Colocalizes with NEK2 at the kinetochore (PubMed:14978040). Colocalizes CC with IK at spindle poles during metaphase and anaphase CC (PubMed:22351768). {ECO:0000269|PubMed:14978040, CC ECO:0000269|PubMed:18981471, ECO:0000269|PubMed:22351768, CC ECO:0000269|PubMed:29162720, ECO:0000269|PubMed:9546394}. CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm CC {ECO:0000269|PubMed:19010891}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; Synonyms=MAD1-alpha {ECO:0000303|PubMed:19010891}; CC IsoId=Q9Y6D9-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9Y6D9-3; Sequence=VSP_056160, VSP_056161; CC Name=3; Synonyms=MAD1-beta {ECO:0000303|PubMed:19010891}; CC IsoId=Q9Y6D9-4; Sequence=VSP_061075; CC -!- TISSUE SPECIFICITY: [Isoform 1]: Expressed in hepatocellular carcinomas CC and hepatoma cell lines (at protein level). CC {ECO:0000269|PubMed:19010891, ECO:0000269|PubMed:24374861}. CC -!- TISSUE SPECIFICITY: [Isoform 3]: Expressed in hepatocellular carcinomas CC and hepatoma cell lines (at protein level). CC {ECO:0000269|PubMed:19010891}. CC -!- INDUCTION: Increased by p53/TP53. {ECO:0000269|PubMed:10049595}. CC -!- PTM: Phosphorylated; by BUB1 (PubMed:10198256). Become CC hyperphosphorylated in late S through M phases or after mitotic spindle CC damage (PubMed:9546394). Phosphorylated; by TTK (PubMed:29162720). CC {ECO:0000269|PubMed:10198256, ECO:0000269|PubMed:29162720, CC ECO:0000269|PubMed:9546394}. CC -!- DISEASE: Mosaic variegated aneuploidy syndrome 7 with inflammation and CC tumor predisposition (MVA7) [MIM:620189]: A form of mosaic variegated CC aneuploidy syndrome, a severe disorder characterized by mosaic CC aneuploidies, predominantly trisomies and monosomies, involving CC multiple different chromosomes and tissues. Affected individuals CC typically present with severe intrauterine growth retardation and CC microcephaly. Eye anomalies, mild dysmorphism, variable developmental CC delay, and a broad spectrum of additional congenital abnormalities and CC medical conditions may also occur. The risk of malignancy is high, with CC rhabdomyosarcoma, Wilms tumor and leukemia reported in several cases. CC MVA7 is an autosomal recessive form characterized by increased CC susceptibility to benign and malignant neoplasms beginning in early CC childhood. Affected individuals show dysmorphic facies and may have CC early developmental delay. {ECO:0000269|PubMed:36322655}. Note=The CC disease may be caused by variants affecting the gene represented in CC this entry. CC -!- DISEASE: Note=Defects in MAD1L1 are involved in the development and/or CC progression of various types of cancer. {ECO:0000269|PubMed:10597320, CC ECO:0000269|PubMed:11423979}. CC -!- SIMILARITY: Belongs to the MAD1 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAC52059.1; Type=Frameshift; Evidence={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; U33822; AAC52059.1; ALT_FRAME; mRNA. DR EMBL; AF123318; AAD20359.1; -; mRNA. DR EMBL; AF083811; AAD24498.1; -; mRNA. DR EMBL; AK090959; BAG52253.1; -; mRNA. DR EMBL; AC005282; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC006433; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC069288; AAS07503.1; -; Genomic_DNA. DR EMBL; AC104129; AAP21876.1; -; Genomic_DNA. DR EMBL; AC110781; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC009964; AAH09964.1; -; mRNA. DR CCDS; CCDS43539.1; -. [Q9Y6D9-1] DR CCDS; CCDS78201.1; -. [Q9Y6D9-3] DR RefSeq; NP_001013858.1; NM_001013836.1. [Q9Y6D9-1] DR RefSeq; NP_001013859.1; NM_001013837.1. [Q9Y6D9-1] DR RefSeq; NP_001291452.1; NM_001304523.1. [Q9Y6D9-1] DR RefSeq; NP_001291453.1; NM_001304524.1. [Q9Y6D9-3] DR RefSeq; NP_003541.2; NM_003550.2. [Q9Y6D9-1] DR RefSeq; XP_005249934.1; XM_005249877.1. DR PDB; 1GO4; X-ray; 2.05 A; E/F/G/H=485-584. DR PDB; 4DZO; X-ray; 1.76 A; A/B=597-718. DR PDB; 7B1F; X-ray; 1.75 A; A/B=597-718. DR PDB; 7B1H; X-ray; 2.40 A; A/B/E/F=597-718. DR PDB; 7B1J; X-ray; 2.90 A; A/B=597-718. DR PDBsum; 1GO4; -. DR PDBsum; 4DZO; -. DR PDBsum; 7B1F; -. DR PDBsum; 7B1H; -. DR PDBsum; 7B1J; -. DR AlphaFoldDB; Q9Y6D9; -. DR SMR; Q9Y6D9; -. DR BioGRID; 113971; 147. DR ComplexPortal; CPX-82; Mitotic spindle assembly checkpoint Mad1 complex. DR ComplexPortal; CPX-85; Mitotic spindle assembly checkpoint MAD1-MAD2 complex. DR CORUM; Q9Y6D9; -. DR DIP; DIP-29654N; -. DR ELM; Q9Y6D9; -. DR IntAct; Q9Y6D9; 85. DR MINT; Q9Y6D9; -. DR STRING; 9606.ENSP00000385334; -. DR GlyGen; Q9Y6D9; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9Y6D9; -. DR MetOSite; Q9Y6D9; -. DR PhosphoSitePlus; Q9Y6D9; -. DR BioMuta; MAD1L1; -. DR DMDM; 52783153; -. DR EPD; Q9Y6D9; -. DR jPOST; Q9Y6D9; -. DR MassIVE; Q9Y6D9; -. DR MaxQB; Q9Y6D9; -. DR PaxDb; 9606-ENSP00000385334; -. DR PeptideAtlas; Q9Y6D9; -. DR ProteomicsDB; 3578; -. DR ProteomicsDB; 86656; -. [Q9Y6D9-1] DR Pumba; Q9Y6D9; -. DR Antibodypedia; 1135; 449 antibodies from 38 providers. DR DNASU; 8379; -. DR Ensembl; ENST00000265854.12; ENSP00000265854.7; ENSG00000002822.16. [Q9Y6D9-1] DR Ensembl; ENST00000399654.6; ENSP00000382562.2; ENSG00000002822.16. [Q9Y6D9-1] DR Ensembl; ENST00000402746.5; ENSP00000384155.1; ENSG00000002822.16. [Q9Y6D9-3] DR Ensembl; ENST00000406869.5; ENSP00000385334.1; ENSG00000002822.16. [Q9Y6D9-1] DR GeneID; 8379; -. DR KEGG; hsa:8379; -. DR MANE-Select; ENST00000265854.12; ENSP00000265854.7; NM_001013836.2; NP_001013858.1. DR UCSC; uc003slf.2; human. [Q9Y6D9-1] DR AGR; HGNC:6762; -. DR CTD; 8379; -. DR DisGeNET; 8379; -. DR GeneCards; MAD1L1; -. DR HGNC; HGNC:6762; MAD1L1. DR HPA; ENSG00000002822; Low tissue specificity. DR MalaCards; MAD1L1; -. DR MIM; 602686; gene. DR MIM; 620189; phenotype. DR neXtProt; NX_Q9Y6D9; -. DR OpenTargets; ENSG00000002822; -. DR PharmGKB; PA372; -. DR VEuPathDB; HostDB:ENSG00000002822; -. DR eggNOG; KOG4593; Eukaryota. DR GeneTree; ENSGT00390000001316; -. DR HOGENOM; CLU_023576_1_0_1; -. DR InParanoid; Q9Y6D9; -. DR OMA; YKLDFMP; -. DR OrthoDB; 8224at2759; -. DR PhylomeDB; Q9Y6D9; -. DR TreeFam; TF101083; -. DR PathwayCommons; Q9Y6D9; -. DR Reactome; R-HSA-141444; Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal. DR Reactome; R-HSA-2467813; Separation of Sister Chromatids. DR Reactome; R-HSA-2500257; Resolution of Sister Chromatid Cohesion. DR Reactome; R-HSA-5663220; RHO GTPases Activate Formins. DR Reactome; R-HSA-68877; Mitotic Prometaphase. DR Reactome; R-HSA-9648025; EML4 and NUDC in mitotic spindle formation. DR SignaLink; Q9Y6D9; -. DR SIGNOR; Q9Y6D9; -. DR BioGRID-ORCS; 8379; 53 hits in 1157 CRISPR screens. DR ChiTaRS; MAD1L1; human. DR EvolutionaryTrace; Q9Y6D9; -. DR GeneWiki; Mad1; -. DR GenomeRNAi; 8379; -. DR Pharos; Q9Y6D9; Tbio. DR PRO; PR:Q9Y6D9; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; Q9Y6D9; Protein. DR Bgee; ENSG00000002822; Expressed in sural nerve and 98 other cell types or tissues. DR ExpressionAtlas; Q9Y6D9; baseline and differential. DR GO; GO:0005813; C:centrosome; NAS:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0000776; C:kinetochore; IDA:UniProtKB. DR GO; GO:1990706; C:MAD1 complex; IPI:ComplexPortal. DR GO; GO:0072686; C:mitotic spindle; IDA:UniProtKB. DR GO; GO:1990728; C:mitotic spindle assembly checkpoint MAD1-MAD2 complex; IPI:ComplexPortal. DR GO; GO:0005635; C:nuclear envelope; IDA:UniProtKB. DR GO; GO:0044615; C:nuclear pore nuclear basket; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005819; C:spindle; NAS:UniProtKB. DR GO; GO:0000922; C:spindle pole; IEA:UniProtKB-SubCell. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0043515; F:kinetochore binding; IDA:UniProtKB. DR GO; GO:0051315; P:attachment of mitotic spindle microtubules to kinetochore; IBA:GO_Central. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0051220; P:cytoplasmic sequestering of protein; IDA:UniProtKB. DR GO; GO:1902426; P:deactivation of mitotic spindle assembly checkpoint; IDA:UniProtKB. DR GO; GO:0007094; P:mitotic spindle assembly checkpoint signaling; IDA:UniProtKB. DR GO; GO:0042130; P:negative regulation of T cell proliferation; IEA:Ensembl. DR GO; GO:0090267; P:positive regulation of mitotic cell cycle spindle assembly checkpoint; IDA:ComplexPortal. DR GO; GO:0090235; P:regulation of metaphase plate congression; IDA:UniProtKB. DR GO; GO:0048538; P:thymus development; IEA:Ensembl. DR Gene3D; 1.20.5.170; -; 1. DR Gene3D; 3.30.457.60; -; 1. DR Gene3D; 6.10.250.90; -; 1. DR InterPro; IPR008672; Mad1. DR PANTHER; PTHR23168:SF0; MITOTIC SPINDLE ASSEMBLY CHECKPOINT PROTEIN MAD1; 1. DR PANTHER; PTHR23168; MITOTIC SPINDLE ASSEMBLY CHECKPOINT PROTEIN MAD1 MITOTIC ARREST DEFICIENT-LIKE PROTEIN 1; 1. DR Pfam; PF05557; MAD; 1. DR SUPFAM; SSF75704; Mitotic arrest deficient-like 1, Mad1; 1. DR Genevisible; Q9Y6D9; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cell cycle; Cell division; KW Centromere; Chromosome; Coiled coil; Cytoplasm; Cytoskeleton; KW Disease variant; Isopeptide bond; Kinetochore; Mitosis; Nucleus; KW Phosphoprotein; Reference proteome; Ubl conjugation. FT CHAIN 1..718 FT /note="Mitotic spindle assembly checkpoint protein MAD1" FT /id="PRO_0000213800" FT REGION 301..340 FT /note="Important for interaction with IK" FT /evidence="ECO:0000269|PubMed:22351768" FT REGION 380..532 FT /note="Necessary for interaction with NEK2" FT /evidence="ECO:0000269|PubMed:14978040" FT REGION 439..480 FT /note="Important for interaction with IK" FT /evidence="ECO:0000269|PubMed:22351768" FT REGION 540..551 FT /note="Necessary for interaction with MAD2L1" FT /evidence="ECO:0000269|PubMed:19010891" FT COILED 46..632 FT /evidence="ECO:0000255" FT MOTIF 79..82 FT /note="Nuclear localization signal" FT /evidence="ECO:0000269|PubMed:19010891" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:22223895, FT ECO:0007744|PubMed:22814378" FT MOD_RES 16 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 61 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 214 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17525332" FT MOD_RES 428 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:16964243, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 598 FT /note="Phosphoserine" FT /evidence="ECO:0000305|PubMed:29162720" FT MOD_RES 610 FT /note="Phosphoserine" FT /evidence="ECO:0000305|PubMed:29162720" FT MOD_RES 634 FT /note="Phosphotyrosine" FT /evidence="ECO:0000305|PubMed:29162720" FT MOD_RES 716 FT /note="Phosphothreonine" FT /evidence="ECO:0000305|PubMed:29162720" FT CROSSLNK 61 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:25218447, FT ECO:0007744|PubMed:28112733" FT VAR_SEQ 1..65 FT /note="MEDLGENTMVLSTLRSLNNFISQRVEGGSGLDISTSAPGSLQMQYQQSMQLE FT ERAEQIRSKSHLI -> MLPARGCVRKRTVWPRLARVLIVTLLTLELSYAPLPCQLSGV FT PYNTGDPVGRWARPCIWPCPWHT (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_056160" FT VAR_SEQ 51..97 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:19010891" FT /id="VSP_061075" FT VAR_SEQ 66..157 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_056161" FT VARIANT 29 FT /note="S -> L (in a lymphoid cancer cell line; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:11423979" FT /id="VAR_019707" FT VARIANT 59 FT /note="R -> C (in a prostate cancer cell line; somatic FT mutation; dbSNP:rs121908982)" FT /evidence="ECO:0000269|PubMed:11423979" FT /id="VAR_019708" FT VARIANT 66..718 FT /note="Missing (in MVA7; decreased protein abundance in FT cells from the patient and from his heterozygous parents)" FT /evidence="ECO:0000269|PubMed:36322655" FT /id="VAR_087991" FT VARIANT 160 FT /note="N -> S (in dbSNP:rs550573452)" FT /evidence="ECO:0000269|PubMed:10597320" FT /id="VAR_019709" FT VARIANT 299 FT /note="T -> A (in lung cancer cell line; somatic mutation)" FT /evidence="ECO:0000269|PubMed:10597320" FT /id="VAR_019710" FT VARIANT 360 FT /note="R -> Q (in a prostate cancer cell line; somatic FT mutation; dbSNP:rs769418574)" FT /evidence="ECO:0000269|PubMed:11423979" FT /id="VAR_019711" FT VARIANT 500 FT /note="T -> M (in dbSNP:rs193231481)" FT /evidence="ECO:0000269|PubMed:10597320, FT ECO:0000269|PubMed:11423979" FT /id="VAR_019712" FT VARIANT 511 FT /note="E -> K (in dbSNP:rs377555260)" FT /evidence="ECO:0000269|PubMed:10597320" FT /id="VAR_019713" FT VARIANT 516 FT /note="E -> K (in a breast cancer cell line; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:11423979" FT /id="VAR_019714" FT VARIANT 556 FT /note="R -> C (in a prostate cancer cell line; somatic FT mutation; dbSNP:rs371561369)" FT /evidence="ECO:0000269|PubMed:11423979" FT /id="VAR_019715" FT VARIANT 556 FT /note="R -> H (in one individual with lung cancer; FT dbSNP:rs755012008)" FT /evidence="ECO:0000269|PubMed:10597320" FT /id="VAR_019716" FT VARIANT 558 FT /note="R -> H (in a cancer cell line; dbSNP:rs1801368)" FT /evidence="ECO:0000269|PubMed:10366450, FT ECO:0000269|PubMed:10597320, ECO:0000269|PubMed:11423979" FT /id="VAR_019717" FT VARIANT 569 FT /note="E -> K (in a breast cancer cell line; somatic FT mutation; dbSNP:rs201951163)" FT /evidence="ECO:0000269|PubMed:11423979" FT /id="VAR_019718" FT VARIANT 572 FT /note="R -> H (in a cancer cell line; dbSNP:rs1801500)" FT /evidence="ECO:0000269|PubMed:10366450" FT /id="VAR_019719" FT VARIANT 628..718 FT /note="Missing (in MVA7; decreased protein abundance in FT cells from the patient and from his heterozygous parents)" FT /evidence="ECO:0000269|PubMed:36322655" FT /id="VAR_087992" FT MUTAGEN 1..485 FT /note="Missing: Defective dimerization. Abolishes binding FT to the closed and open conformations of MAD2L1. Impairs FT mitotic checkpoint signaling abolishing mitotic arrest, and FT shortens the duration of mitosis." FT /evidence="ECO:0000269|PubMed:29162720" FT MUTAGEN 79..82 FT /note="KRAR->LLAL: Loss of nuclear localization." FT /evidence="ECO:0000269|PubMed:19010891" FT MUTAGEN 540..551 FT /note="Missing: Loss of interaction with MAD2L1." FT /evidence="ECO:0000269|PubMed:19010891" FT MUTAGEN 541 FT /note="K->A: Abolishes binding to closed and open FT conformations of MAD2L1 and impairs mitotic checkpint FT signaling abolishing mitotic arrest, and shortens the FT duration of mitosis; in association with A-543." FT /evidence="ECO:0000269|PubMed:29162720" FT MUTAGEN 543 FT /note="L->A: Abolishes binding to closed and open FT conformations of MAD2L1 and impairs mitotic checkpoint FT signaling abolishing mitotic arrest, and shortens the FT duration of mitosis; in association with A-541." FT /evidence="ECO:0000269|PubMed:29162720" FT MUTAGEN 597..718 FT /note="Missing: Defective dimerization. Reduces binding to FT the closed and open conformations of MAD2L1. Impairs FT mitotic checkpoint signaling abolishing mitotic arrest, and FT shortens the duration of mitosis." FT /evidence="ECO:0000269|PubMed:29162720" FT MUTAGEN 598 FT /note="S->A,E: Does not impact the duration of mitosis." FT /evidence="ECO:0000269|PubMed:29162720" FT MUTAGEN 610 FT /note="S->A,E: Impairs mitotic checkpoint signaling and FT shortens the duration of mitosis." FT /evidence="ECO:0000269|PubMed:29162720" FT MUTAGEN 634 FT /note="Y->E: Reduces binding to closed and open FT conformations of MAD2L1. Impairs mitotic checkpoint FT signaling abolishing mitotic arrest, and shortens the FT duration of mitosis." FT /evidence="ECO:0000269|PubMed:29162720" FT MUTAGEN 634 FT /note="Y->F: Reduces binding to closed and open FT conformations of MAD2L1. Does not impact the duration of FT mitosis." FT /evidence="ECO:0000269|PubMed:29162720" FT MUTAGEN 716 FT /note="T->A,E: Reduces binding to closed and open FT conformations of MAD2L1. Impairs mitotic checkpoint FT signaling and shortens the duration of mitosis." FT /evidence="ECO:0000269|PubMed:29162720" FT CONFLICT 189..190 FT /note="EL -> DV (in Ref. 1; AAC52059 and 3; AAD24498)" FT /evidence="ECO:0000305" FT CONFLICT 260 FT /note="K -> E (in Ref. 1; AAC52059 and 3; AAD24498)" FT /evidence="ECO:0000305" FT CONFLICT 268 FT /note="Missing (in Ref. 1; AAC52059)" FT /evidence="ECO:0000305" FT HELIX 487..492 FT /evidence="ECO:0007829|PDB:1GO4" FT HELIX 494..528 FT /evidence="ECO:0007829|PDB:1GO4" FT TURN 537..539 FT /evidence="ECO:0007829|PDB:1GO4" FT STRAND 540..547 FT /evidence="ECO:0007829|PDB:1GO4" FT HELIX 549..575 FT /evidence="ECO:0007829|PDB:1GO4" FT TURN 580..582 FT /evidence="ECO:0007829|PDB:1GO4" FT HELIX 598..637 FT /evidence="ECO:0007829|PDB:7B1F" FT STRAND 638..643 FT /evidence="ECO:0007829|PDB:7B1F" FT STRAND 647..653 FT /evidence="ECO:0007829|PDB:7B1F" FT STRAND 657..660 FT /evidence="ECO:0007829|PDB:7B1J" FT STRAND 663..667 FT /evidence="ECO:0007829|PDB:7B1F" FT STRAND 670..672 FT /evidence="ECO:0007829|PDB:7B1H" FT STRAND 675..677 FT /evidence="ECO:0007829|PDB:7B1F" FT HELIX 681..685 FT /evidence="ECO:0007829|PDB:7B1F" FT HELIX 687..693 FT /evidence="ECO:0007829|PDB:7B1F" FT TURN 694..696 FT /evidence="ECO:0007829|PDB:7B1F" FT HELIX 700..715 FT /evidence="ECO:0007829|PDB:7B1F" SQ SEQUENCE 718 AA; 83067 MW; DA65529856A37EE3 CRC64; MEDLGENTMV LSTLRSLNNF ISQRVEGGSG LDISTSAPGS LQMQYQQSMQ LEERAEQIRS KSHLIQVERE KMQMELSHKR ARVELERAAS TSARNYEREV DRNQELLTRI RQLQEREAGA EEKMQEQLER NRQCQQNLDA ASKRLREKED SLAQAGETIN ALKGRISELQ WSVMDQEMRV KRLESEKQEL QEQLDLQHKK CQEANQKIQE LQASQEARAD HEQQIKDLEQ KLSLQEQDAA IVKNMKSELV RLPRLERELK QLREESAHLR EMRETNGLLQ EELEGLQRKL GRQEKMQETL VGLELENERL LAKLQSWERL DQTMGLSIRT PEDLSRFVVE LQQRELALKD KNSAVTSSAR GLEKARQQLQ EELRQVSGQL LEERKKRETH EALARRLQKR VLLLTKERDG MRAILGSYDS ELTPAEYSPQ LTRRMREAED MVQKVHSHSA EMEAQLSQAL EELGGQKQRA DMLEMELKML KSQSSSAEQS FLFSREEADT LRLKVEELEG ERSRLEEEKR MLEAQLERRA LQGDYDQSRT KVLHMSLNPT SVARQRLRED HSQLQAECER LRGLLRAMER GGTVPADLEA AAASLPSSKE VAELKKQVES AELKNQRLKE VFQTKIQEFR KACYTLTGYQ IDITTENQYR LTSLYAEHPG DCLIFKATSP SGSKMQLLET EFSHTVGELI EVHLRRQDSI PAFLSSLTLE LFSRQTVA //