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 Genevisible; Q9Y6D9; HS.
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.
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
//
