ID MD2L1_HUMAN Reviewed; 205 AA.
AC Q13257; Q53F56; Q548X9; Q6IRW7; Q8IZX3;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 27-MAR-2024, entry version 219.
DE RecName: Full=Mitotic spindle assembly checkpoint protein MAD2A;
DE Short=HsMAD2;
DE AltName: Full=Mitotic arrest deficient 2-like protein 1;
DE Short=MAD2-like protein 1;
GN Name=MAD2L1; Synonyms=MAD2;
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).
RX PubMed=8824189; DOI=10.1126/science.274.5285.246;
RA Li Y., Benezra R.;
RT "Identification of a human mitotic checkpoint gene: hsMAD2.";
RL Science 274:246-248(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=11390010; DOI=10.1016/s0169-5002(00)00223-3;
RA Gemma A., Hosoya Y., Seike M., Uematsu K., Kurimoto F., Hibino S.,
RA Yoshimura A., Shibuya M., Kudoh S., Emi M.;
RT "Genomic structure of the human MAD2 gene and mutation analysis in human
RT lung and breast cancers.";
RL Lung Cancer 32:289-295(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Jin D.-Y., Jeang K.-T.;
RL Submitted (JUL-1995) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RA Klebert S., Barnikol-Watanabe S., Kratzin H.D., Hilschmann N.;
RL Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Nobori T.;
RT "Complete human MAD2 gene.";
RL Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Yin F., Fan D.M.;
RT "Identifying a new variant of MAD2L1.";
RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Lung;
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Bone marrow, and Muscle;
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 [12]
RP PROTEIN SEQUENCE OF 2-7; 36-45; 123-129 AND 193-205, CLEAVAGE OF INITIATOR
RP METHIONINE, ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Hepatoma;
RA Bienvenut W.V., Dhillon A.S., Kolch W.;
RL Submitted (FEB-2008) to UniProtKB.
RN [13]
RP INTERACTION WITH CDC20.
RX PubMed=9637688; DOI=10.1101/gad.12.12.1871;
RA Fang G., Yu H., Kirschner M.W.;
RT "The checkpoint protein MAD2 and the mitotic regulator CDC20 form a ternary
RT complex with the anaphase-promoting complex to control anaphase
RT initiation.";
RL Genes Dev. 12:1871-1883(1998).
RN [14]
RP INTERACTION WITH ADAM17.
RX PubMed=10527948; DOI=10.1042/bj3430673;
RA Nelson K.K., Schlondorff J., Blobel C.P.;
RT "Evidence for an interaction of the metalloprotease-disintegrin tumour
RT necrosis factor alpha convertase (TACE) with mitotic arrest deficient 2
RT (MAD2), and of the metalloprotease-disintegrin MDC9 with a novel MAD2-
RT related protein, MAD2-beta.";
RL Biochem. J. 343:673-680(1999).
RN [15]
RP INTERACTION WITH MAD2L1BP.
RX PubMed=12456649; DOI=10.1093/emboj/cdf659;
RA Habu T., Kim S.H., Weinstein J., Matsumoto T.;
RT "Identification of a MAD2-binding protein, CMT2, and its role in mitosis.";
RL EMBO J. 21:6419-6428(2002).
RN [16]
RP PHOSPHORYLATION AT SER-170; SER-178 AND SER-195, INTERACTION WITH MAD1L1
RP AND CDC20, AND MUTAGENESIS OF SER-170; SER-178 AND SER-195.
RX PubMed=12574116; DOI=10.1093/emboj/cdg071;
RA Wassmann K., Liberal V., Benezra R.;
RT "Mad2 phosphorylation regulates its association with Mad1 and the APC/C.";
RL EMBO J. 22:797-806(2003).
RN [17]
RP SUBCELLULAR LOCATION.
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 [18]
RP SUBCELLULAR LOCATION.
RX PubMed=15020684; DOI=10.1242/jcs.01006;
RA Johnson V.L., Scott M.I., Holt S.V., Hussein D., Taylor S.S.;
RT "Bub1 is required for kinetochore localization of BubR1, Cenp-E, Cenp-F and
RT Mad2, and chromosome congression.";
RL J. Cell Sci. 117:1577-1589(2004).
RN [19]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH UBD.
RX PubMed=16495226; DOI=10.1074/jbc.m507218200;
RA Ren J., Kan A., Leong S.H., Ooi L.L.P.J., Jeang K.-T., Chong S.S.,
RA Kon O.L., Lee C.G.L.;
RT "FAT10 plays a role in the regulation of chromosomal stability.";
RL J. Biol. Chem. 281:11413-11421(2006).
RN [20]
RP INTERACTION WITH HSF1.
RX PubMed=18794143; DOI=10.1158/0008-5472.can-08-0129;
RA Lee Y.J., Kim E.H., Lee J.S., Jeoung D., Bae S., Kwon S.H., Lee Y.S.;
RT "HSF1 as a mitotic regulator: phosphorylation of HSF1 by Plk1 is essential
RT for mitotic progression.";
RL Cancer Res. 68:7550-7560(2008).
RN [21]
RP INTERACTION WITH MAD1L1, AND SUBCELLULAR LOCATION.
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 [22]
RP INTERACTION WITH TPR; MAD1L1 AND CDC20, AND 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 [23]
RP SUBCELLULAR LOCATION.
RX PubMed=18712773; DOI=10.1002/jcb.21879;
RA Ho C.-Y., Wong C.-H., Li H.-Y.;
RT "Perturbation of the chromosomal binding of RCC1, Mad2 and survivin causes
RT spindle assembly defects and mitotic catastrophe.";
RL J. Cell. Biochem. 105:835-846(2008).
RN [24]
RP REVIEW.
RX PubMed=19029339; DOI=10.1083/jcb.200808122;
RA Skinner J.J., Wood S., Shorter J., Englander S.W., Black B.E.;
RT "The Mad2 partial unfolding model: regulating mitosis through Mad2
RT conformational switching.";
RL J. Cell Biol. 183:761-768(2008).
RN [25]
RP SUBCELLULAR LOCATION, PHOSPHORYLATION, AND INTERACTION WITH NEK2.
RX PubMed=20034488; DOI=10.1016/j.yexmp.2009.12.004;
RA Liu Q., Hirohashi Y., Du X., Greene M.I., Wang Q.;
RT "Nek2 targets the mitotic checkpoint proteins Mad2 and Cdc20: a mechanism
RT for aneuploidy in cancer.";
RL Exp. Mol. Pathol. 88:225-233(2010).
RN [26]
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 [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-6; SER-130; SER-185 AND
RP SER-195, AND 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 [28]
RP INTERACTION WITH UBD.
RX PubMed=25422469; DOI=10.1073/pnas.1403383111;
RA Theng S.S., Wang W., Mah W.C., Chan C., Zhuo J., Gao Y., Qin H., Lim L.,
RA Chong S.S., Song J., Lee C.G.;
RT "Disruption of FAT10-MAD2 binding inhibits tumor progression.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:E5282-E5291(2014).
RN [29]
RP FUNCTION, INTERACTION WITH MAD1L1; CDC20; BUB1B AND TTK, AND MUTAGENESIS OF
RP LEU-13 AND SER-195.
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 [30]
RP STRUCTURE BY NMR OF 11-195, FUNCTION, DOMAIN, AND INTERACTION WITH CDC20.
RX PubMed=10700282; DOI=10.1038/73338;
RA Luo X., Fang G., Coldiron M., Lin Y., Yu H., Kirschner M.W., Wagner G.;
RT "Structure of the Mad2 spindle assembly checkpoint protein and its
RT interaction with Cdc20.";
RL Nat. Struct. Biol. 7:224-229(2000).
RN [31]
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF MUTANT ALA-133 IN COMPLEX WITH
RP MAD1L1, SUBUNIT, DOMAIN, MUTAGENESIS OF ARG-133, AND INTERACTION WITH
RP MAD1L1.
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 [32]
RP STRUCTURE BY NMR OF 11-205 IN COMPLEX WITH PEPTIDE LIGAND, DOMAIN,
RP SUBCELLULAR LOCATION, FUNCTION, AND INTERACTION WITH CDC20 AND MAD1L1.
RX PubMed=11804586; DOI=10.1016/s1097-2765(01)00435-x;
RA Luo X., Tang Z., Rizo J., Yu H.;
RT "The Mad2 spindle checkpoint protein undergoes similar major conformational
RT changes upon binding to either Mad1 or Cdc20.";
RL Mol. Cell 9:59-71(2002).
RN [33]
RP STRUCTURE BY NMR, DOMAIN, SUBUNIT, FUNCTION, INTERACTION WITH MAD1L1, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=15024386; DOI=10.1038/nsmb748;
RA Luo X., Tang Z., Xia G., Wassmann K., Matsumoto T., Rizo J., Yu H.;
RT "The Mad2 spindle checkpoint protein has two distinct natively folded
RT states.";
RL Nat. Struct. Mol. Biol. 11:338-345(2004).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF DIMER CONTAINING BOTH CONFORMERS,
RP AND INTERACTION OF THE TWO MAD2L1 CONFORMERS.
RX PubMed=18022367; DOI=10.1016/j.cell.2007.08.049;
RA Mapelli M., Massimiliano L., Santaguida S., Musacchio A.;
RT "The Mad2 conformational dimer: structure and implications for the spindle
RT assembly checkpoint.";
RL Cell 131:730-743(2007).
RN [35]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF COMPLEXES WITH MAD2L1BP, AND
RP INTERACTION WITH MAD2L1BP.
RX PubMed=18022368; DOI=10.1016/j.cell.2007.08.048;
RA Yang M., Li B., Tomchick D.R., Machius M., Rizo J., Yu H., Luo X.;
RT "p31comet blocks Mad2 activation through structural mimicry.";
RL Cell 131:744-755(2007).
RN [36]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF HOMODIMER OF MUTANT ALA-13 IN THE
RP CLOSED CONFORMATION, DOMAIN, SUBUNIT, AND MUTAGENESIS OF LEU-13; TRP-75;
RP LEU-153; TYR-156; PHE-186; THR-188; HIS-191; VAL-197 AND TYR-199.
RX PubMed=18318601; DOI=10.1371/journal.pbio.0060050;
RA Yang M., Li B., Liu C.-J., Tomchick D.R., Machius M., Rizo J., Yu H.,
RA Luo X.;
RT "Insights into Mad2 regulation in the spindle checkpoint revealed by the
RT crystal structure of the symmetric Mad2 dimer.";
RL PLoS Biol. 6:E50-E50(2008).
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:29162720, PubMed:15024386). In the closed
CC conformation (C-MAD2) forms a heterotetrameric complex with MAD1L1 at
CC unattached kinetochores during prometaphase, the complex recruits open
CC conformation molecules of MAD2L1 (O-MAD2) and then promotes the
CC conversion of O-MAD2 to C-MAD2 (PubMed:29162720). Required for the
CC execution of the mitotic checkpoint which monitors the process of
CC kinetochore-spindle attachment and inhibits the activity of the
CC anaphase promoting complex by sequestering CDC20 until all chromosomes
CC are aligned at the metaphase plate (PubMed:10700282, PubMed:11804586,
CC PubMed:15024386). {ECO:0000269|PubMed:10700282,
CC ECO:0000269|PubMed:11804586, ECO:0000269|PubMed:15024386,
CC ECO:0000269|PubMed:29162720}.
CC -!- SUBUNIT: Monomer and homodimer (PubMed:18022367, PubMed:18318601).
CC Heterodimerizes with MAD2L1 in order to form a tetrameric MAD1L1-MAD2L1
CC core complex (PubMed:12574116, PubMed:18981471, PubMed:12006501,
CC PubMed:15024386). In the closed and open conformation, interacts with
CC MAD1L1 (PubMed:29162720). Formation of a heterotetrameric core complex
CC containing two molecules each of MAD1L1 and of MAD2L1 promotes binding
CC of another molecule of MAD2L1 to each MAD2L1, resulting in a
CC heterohexamer (PubMed:12006501). Interacts with MAD2L1BP
CC (PubMed:12456649, PubMed:18022368). Interacts with ADAM17/TACE
CC (PubMed:10527948). Interacts with CDC20 (PubMed:9637688,
CC PubMed:12574116, PubMed:18981471, PubMed:10700282). Dimeric MAD2L1 in
CC the closed conformation interacts with CDC20 (PubMed:29162720).
CC Monomeric MAD2L1 in the open conformation does not interact with CDC20
CC (PubMed:11804586). CDC20 competes with MAD1L1 for MAD2L1 binding
CC (PubMed:11804586). In the closed conformation, interacts with BUB1B
CC (PubMed:29162720). Interacts with TTK (PubMed:29162720). Interacts with
CC TPR (PubMed:18981471). Binds to UBD (via ubiquitin-like 1 domain)
CC during mitosis (PubMed:16495226, PubMed:25422469). Interacts with
CC isoform 1 and isoform 2 of NEK2 (PubMed:20034488). Interacts with HSF1;
CC this interaction occurs in mitosis (PubMed:18794143). Interacts with
CC isoform 3 of MAD1L1; this interaction leads to the cytoplasmic
CC sequestration of MAD2L1 (PubMed:19010891).
CC {ECO:0000269|PubMed:10527948, ECO:0000269|PubMed:10700282,
CC ECO:0000269|PubMed:11804586, ECO:0000269|PubMed:12006501,
CC ECO:0000269|PubMed:12456649, ECO:0000269|PubMed:12574116,
CC ECO:0000269|PubMed:15024386, ECO:0000269|PubMed:16495226,
CC ECO:0000269|PubMed:18022367, ECO:0000269|PubMed:18022368,
CC ECO:0000269|PubMed:18318601, ECO:0000269|PubMed:18794143,
CC ECO:0000269|PubMed:18981471, ECO:0000269|PubMed:19010891,
CC ECO:0000269|PubMed:20034488, ECO:0000269|PubMed:25422469,
CC ECO:0000269|PubMed:29162720, ECO:0000269|PubMed:9637688}.
CC -!- INTERACTION:
CC Q13257; P78536: ADAM17; NbExp=3; IntAct=EBI-78203, EBI-78188;
CC Q13257; O60566: BUB1B; NbExp=13; IntAct=EBI-78203, EBI-1001438;
CC Q13257; Q12834: CDC20; NbExp=34; IntAct=EBI-78203, EBI-367462;
CC Q13257; P30260: CDC27; NbExp=9; IntAct=EBI-78203, EBI-994813;
CC Q13257; O75140-2: DEPDC5; NbExp=3; IntAct=EBI-78203, EBI-12366971;
CC Q13257; Q7L775: EPM2AIP1; NbExp=3; IntAct=EBI-78203, EBI-6255981;
CC Q13257; P06213-2: INSR; NbExp=3; IntAct=EBI-78203, EBI-9984921;
CC Q13257; Q14145: KEAP1; NbExp=8; IntAct=EBI-78203, EBI-751001;
CC Q13257; Q9Y6D9: MAD1L1; NbExp=39; IntAct=EBI-78203, EBI-742610;
CC Q13257; Q13257: MAD2L1; NbExp=9; IntAct=EBI-78203, EBI-78203;
CC Q13257; Q15013: MAD2L1BP; NbExp=18; IntAct=EBI-78203, EBI-712181;
CC Q13257; O00560: SDCBP; NbExp=3; IntAct=EBI-78203, EBI-727004;
CC Q13257; Q562F6: SGO2; NbExp=10; IntAct=EBI-78203, EBI-989213;
CC Q13257; Q9Y3Q8: TSC22D4; NbExp=5; IntAct=EBI-78203, EBI-739485;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:19010891}.
CC Chromosome, centromere, kinetochore. Cytoplasm
CC {ECO:0000269|PubMed:19010891}. Cytoplasm, cytoskeleton, spindle pole.
CC Note=Recruited by MAD1L1 to unattached kinetochores (Probable).
CC Recruited to the nuclear pore complex by TPR during interphase.
CC Recruited to kinetochores in late prometaphase after BUB1, CENPF, BUB1B
CC and CENPE. Kinetochore association requires the presence of NEK2.
CC Kinetochore association is repressed by UBD. Sequestered to the
CC cytoplasm upon interaction with isoform 3 of MAD1L1 (PubMed:19010891).
CC {ECO:0000269|PubMed:19010891, ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q13257-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13257-2; Sequence=VSP_047644, VSP_047645;
CC -!- DOMAIN: The protein has two highly different native conformations, an
CC inactive open conformation that cannot bind CDC20 and that predominates
CC in cytosolic monomers, and an active closed conformation. The protein
CC in the closed conformation preferentially dimerizes with another
CC molecule in the open conformation, but can also form a dimer with a
CC molecule in the closed conformation. Formation of a heterotetrameric
CC core complex containing two molecules of MAD1L1 and of MAD2L1 in the
CC closed conformation promotes binding of another molecule of MAD2L1 in
CC the open conformation and the conversion of the open to the closed
CC form, and thereby promotes interaction with CDC20.
CC {ECO:0000269|PubMed:10700282, ECO:0000269|PubMed:11804586,
CC ECO:0000269|PubMed:12006501, ECO:0000269|PubMed:15024386,
CC ECO:0000269|PubMed:18318601}.
CC -!- PTM: Phosphorylated on multiple serine residues. The level of
CC phosphorylation varies during the cell cycle and is highest during
CC mitosis. Phosphorylation abolishes interaction with MAD1L1 and reduces
CC interaction with CDC20. Phosphorylated by NEK2.
CC {ECO:0000269|PubMed:12574116, ECO:0000269|PubMed:20034488}.
CC -!- SIMILARITY: Belongs to the MAD2 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="https://atlasgeneticsoncology.org/gene/304/MAD2L1";
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DR EMBL; U65410; AAC50781.1; -; mRNA.
DR EMBL; AF202273; AAK38174.1; -; Genomic_DNA.
DR EMBL; AF202269; AAK38174.1; JOINED; Genomic_DNA.
DR EMBL; AF202270; AAK38174.1; JOINED; Genomic_DNA.
DR EMBL; AF202271; AAK38174.1; JOINED; Genomic_DNA.
DR EMBL; AF202272; AAK38174.1; JOINED; Genomic_DNA.
DR EMBL; U31278; AAC52060.1; -; mRNA.
DR EMBL; AJ000186; CAA03943.1; -; mRNA.
DR EMBL; AB056160; BAB63410.1; -; Genomic_DNA.
DR EMBL; AF394735; AAN74648.1; -; mRNA.
DR EMBL; AK298228; BAG60497.1; -; mRNA.
DR EMBL; AK313827; BAG36562.1; -; mRNA.
DR EMBL; AK223433; BAD97153.1; -; mRNA.
DR EMBL; AC097173; AAY40945.1; -; Genomic_DNA.
DR EMBL; CH471056; EAX05271.1; -; Genomic_DNA.
DR EMBL; CH471056; EAX05273.1; -; Genomic_DNA.
DR EMBL; BC000356; AAH00356.1; -; mRNA.
DR EMBL; BC005945; AAH05945.1; -; mRNA.
DR EMBL; BC070283; AAH70283.1; -; mRNA.
DR CCDS; CCDS3715.1; -. [Q13257-1]
DR PIR; G01942; G01942.
DR RefSeq; NP_002349.1; NM_002358.3. [Q13257-1]
DR PDB; 1DUJ; NMR; -; A=11-195.
DR PDB; 1GO4; X-ray; 2.05 A; A/B/C/D=1-205.
DR PDB; 1KLQ; NMR; -; A=11-205.
DR PDB; 1S2H; NMR; -; A=1-205.
DR PDB; 2QYF; X-ray; 2.30 A; A/C=1-205.
DR PDB; 2V64; X-ray; 2.90 A; A/C/D/E/F/H=2-205.
DR PDB; 2VFX; X-ray; 1.95 A; A/B/C/D/E/F/G/H/I/J/K/L=1-205.
DR PDB; 3GMH; X-ray; 3.95 A; A/B/C/D/E/F/G/H/I/J/K/L=11-205.
DR PDB; 5KHU; EM; 4.80 A; T=1-205.
DR PDB; 5LCW; EM; 4.00 A; Z=1-205.
DR PDB; 6F0X; EM; 4.60 A; Z=1-205.
DR PDB; 6TLJ; EM; 3.80 A; Z=1-205.
DR PDBsum; 1DUJ; -.
DR PDBsum; 1GO4; -.
DR PDBsum; 1KLQ; -.
DR PDBsum; 1S2H; -.
DR PDBsum; 2QYF; -.
DR PDBsum; 2V64; -.
DR PDBsum; 2VFX; -.
DR PDBsum; 3GMH; -.
DR PDBsum; 5KHU; -.
DR PDBsum; 5LCW; -.
DR PDBsum; 6F0X; -.
DR PDBsum; 6TLJ; -.
DR AlphaFoldDB; Q13257; -.
DR BMRB; Q13257; -.
DR EMDB; EMD-10516; -.
DR EMDB; EMD-4037; -.
DR EMDB; EMD-4166; -.
DR SMR; Q13257; -.
DR BioGRID; 110260; 250.
DR ComplexPortal; CPX-3946; Mitotic Checkpoint Complex.
DR ComplexPortal; CPX-85; Mitotic spindle assembly checkpoint MAD1-MAD2 complex.
DR ComplexPortal; CPX-88; Mitotic spindle assembly checkpoint complex MAD2.
DR CORUM; Q13257; -.
DR DIP; DIP-29653N; -.
DR IntAct; Q13257; 81.
DR MINT; Q13257; -.
DR STRING; 9606.ENSP00000296509; -.
DR iPTMnet; Q13257; -.
DR PhosphoSitePlus; Q13257; -.
DR SwissPalm; Q13257; -.
DR BioMuta; MAD2L1; -.
DR DMDM; 12230256; -.
DR EPD; Q13257; -.
DR jPOST; Q13257; -.
DR MassIVE; Q13257; -.
DR MaxQB; Q13257; -.
DR PaxDb; 9606-ENSP00000296509; -.
DR PeptideAtlas; Q13257; -.
DR ProteomicsDB; 59256; -. [Q13257-1]
DR ProteomicsDB; 71439; -.
DR Pumba; Q13257; -.
DR TopDownProteomics; Q13257-1; -. [Q13257-1]
DR ABCD; Q13257; 2 sequenced antibodies.
DR Antibodypedia; 15732; 712 antibodies from 47 providers.
DR DNASU; 4085; -.
DR Ensembl; ENST00000296509.11; ENSP00000296509.5; ENSG00000164109.14. [Q13257-1]
DR Ensembl; ENST00000333047.9; ENSP00000332295.5; ENSG00000164109.14. [Q13257-2]
DR GeneID; 4085; -.
DR KEGG; hsa:4085; -.
DR MANE-Select; ENST00000296509.11; ENSP00000296509.5; NM_002358.4; NP_002349.1.
DR UCSC; uc003idl.3; human. [Q13257-1]
DR AGR; HGNC:6763; -.
DR CTD; 4085; -.
DR DisGeNET; 4085; -.
DR GeneCards; MAD2L1; -.
DR HGNC; HGNC:6763; MAD2L1.
DR HPA; ENSG00000164109; Tissue enhanced (bone marrow, lymphoid tissue).
DR MIM; 601467; gene.
DR neXtProt; NX_Q13257; -.
DR OpenTargets; ENSG00000164109; -.
DR PharmGKB; PA30521; -.
DR VEuPathDB; HostDB:ENSG00000164109; -.
DR eggNOG; KOG3285; Eukaryota.
DR GeneTree; ENSGT00940000153395; -.
DR HOGENOM; CLU_072097_1_0_1; -.
DR InParanoid; Q13257; -.
DR OMA; ETTCAFD; -.
DR OrthoDB; 5474106at2759; -.
DR PhylomeDB; Q13257; -.
DR TreeFam; TF101084; -.
DR PathwayCommons; Q13257; -.
DR Reactome; R-HSA-141405; Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint components.
DR Reactome; R-HSA-141430; Inactivation of APC/C via direct inhibition of the APC/C complex.
DR Reactome; R-HSA-141444; Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal.
DR Reactome; R-HSA-174184; Cdc20:Phospho-APC/C mediated degradation of Cyclin A.
DR Reactome; R-HSA-176409; APC/C:Cdc20 mediated degradation of mitotic proteins.
DR Reactome; R-HSA-179409; APC-Cdc20 mediated degradation of Nek2A.
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; Q13257; -.
DR SIGNOR; Q13257; -.
DR BioGRID-ORCS; 4085; 774 hits in 1142 CRISPR screens.
DR ChiTaRS; MAD2L1; human.
DR EvolutionaryTrace; Q13257; -.
DR GeneWiki; MAD2L1; -.
DR GenomeRNAi; 4085; -.
DR Pharos; Q13257; Tbio.
DR PRO; PR:Q13257; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q13257; Protein.
DR Bgee; ENSG00000164109; Expressed in secondary oocyte and 165 other cell types or tissues.
DR ExpressionAtlas; Q13257; baseline and differential.
DR Genevisible; Q13257; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0000776; C:kinetochore; IDA:UniProtKB.
DR GO; GO:0033597; C:mitotic checkpoint 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:0044615; C:nuclear pore nuclear basket; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0000922; C:spindle pole; IEA:UniProtKB-SubCell.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0051660; P:establishment of centrosome localization; IMP:UniProtKB.
DR GO; GO:0000132; P:establishment of mitotic spindle orientation; IMP:UniProtKB.
DR GO; GO:0000070; P:mitotic sister chromatid segregation; IEA:Ensembl.
DR GO; GO:0007094; P:mitotic spindle assembly checkpoint signaling; IDA:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0045930; P:negative regulation of mitotic cell cycle; IMP:MGI.
DR GO; GO:0042177; P:negative regulation of protein catabolic process; IDA:UniProtKB.
DR GO; GO:1904667; P:negative regulation of ubiquitin protein ligase activity; IDA:UniProtKB.
DR GO; GO:0090267; P:positive regulation of mitotic cell cycle spindle assembly checkpoint; IDA:UniProtKB.
DR Gene3D; 3.30.900.10; HORMA domain; 1.
DR InterPro; IPR003511; HORMA_dom.
DR InterPro; IPR036570; HORMA_dom_sf.
DR InterPro; IPR045091; Mad2-like.
DR PANTHER; PTHR11842; MITOTIC SPINDLE ASSEMBLY CHECKPOINT PROTEIN MAD2; 1.
DR PANTHER; PTHR11842:SF11; MITOTIC SPINDLE ASSEMBLY CHECKPOINT PROTEIN MAD2A; 1.
DR Pfam; PF02301; HORMA; 1.
DR SUPFAM; SSF56019; The spindle assembly checkpoint protein mad2; 1.
DR PROSITE; PS50815; HORMA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cell cycle; Cell division;
KW Centromere; Chromosome; Cytoplasm; Cytoskeleton; Direct protein sequencing;
KW Kinetochore; Mitosis; Nucleus; Phosphoprotein; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.12"
FT CHAIN 2..205
FT /note="Mitotic spindle assembly checkpoint protein MAD2A"
FT /id="PRO_0000126117"
FT DOMAIN 14..197
FT /note="HORMA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00109"
FT REGION 195..205
FT /note="Required for assuming the closed conformation and
FT for interaction with CDC20"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|Ref.12"
FT MOD_RES 6
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 130
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 170
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:12574116"
FT MOD_RES 178
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:12574116"
FT MOD_RES 185
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 195
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:12574116,
FT ECO:0007744|PubMed:23186163"
FT VAR_SEQ 74..90
FT /note="DWLYKCSVQKLVVVISN -> VHPEKSLRKLSRMKSVQ (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.6"
FT /id="VSP_047644"
FT VAR_SEQ 91..205
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.6"
FT /id="VSP_047645"
FT MUTAGEN 13
FT /note="L->A: Leads to formation the closed conformation and
FT homodimerization. Reduces binding to MAD1L1."
FT /evidence="ECO:0000269|PubMed:18318601,
FT ECO:0000269|PubMed:29162720"
FT MUTAGEN 75
FT /note="W->A: Prevents interaction with CDC20 and leads to
FT formation of the closed conformation; when associated with
FT A-133."
FT /evidence="ECO:0000269|PubMed:18318601"
FT MUTAGEN 133
FT /note="R->A: Prevents aggregation and promotes formation of
FT monomeric protein that slowly interconverts between the
FT open and closed conformation."
FT /evidence="ECO:0000269|PubMed:12006501"
FT MUTAGEN 153
FT /note="L->A: Leads to formation of the closed conformation;
FT when associated with A-133."
FT /evidence="ECO:0000269|PubMed:18318601"
FT MUTAGEN 156
FT /note="Y->A: Leads to formation of the closed conformation;
FT when associated with A-133."
FT /evidence="ECO:0000269|PubMed:18318601"
FT MUTAGEN 170
FT /note="S->A: Reduces phosphorylation on serine residues;
FT when associated with A-178. Abolishes phosphorylation on
FT serine residues; when associated with A-178 and A-195."
FT /evidence="ECO:0000269|PubMed:12574116"
FT MUTAGEN 170
FT /note="S->D: Abolishes interaction with MAD1L1 and reduces
FT interaction with CDC20; when associated with D-178 and D-
FT 195."
FT /evidence="ECO:0000269|PubMed:12574116"
FT MUTAGEN 178
FT /note="S->A: Reduces phosphorylation on serine residues;
FT when associated with A-170. Abolishes phosphorylation on
FT serine residues; when associated with A-170 and A-195."
FT /evidence="ECO:0000269|PubMed:12574116"
FT MUTAGEN 178
FT /note="S->D: Abolishes interaction with MAD1L1 and reduces
FT interaction with CDC20; when associated with D-170 and D-
FT 195."
FT /evidence="ECO:0000269|PubMed:12574116"
FT MUTAGEN 186
FT /note="F->A: Prevents formation of the closed conformation
FT and interaction with CDC20; when associated with A-133."
FT /evidence="ECO:0000269|PubMed:18318601"
FT MUTAGEN 188
FT /note="T->A: Prevents formation of the closed conformation
FT and interaction with CDC20; when associated with A-133."
FT /evidence="ECO:0000269|PubMed:18318601"
FT MUTAGEN 191
FT /note="H->A: Prevents formation of the closed conformation
FT and interaction with CDC20; when associated with A-133."
FT /evidence="ECO:0000269|PubMed:18318601"
FT MUTAGEN 195
FT /note="S->A: Abolishes phosphorylation on serine residues;
FT when associated with A-170 and A-178."
FT /evidence="ECO:0000269|PubMed:12574116"
FT MUTAGEN 195
FT /note="S->D: Binds to the N and C-terminus of MAD1L1.
FT Abolishes interaction with MAD1L1 and reduces interaction
FT with CDC20; when associated with D-170 and D-178."
FT /evidence="ECO:0000269|PubMed:12574116,
FT ECO:0000269|PubMed:29162720"
FT MUTAGEN 197
FT /note="V->A: Prevents formation of the closed conformation
FT and interaction with CDC20; when associated with A-133."
FT /evidence="ECO:0000269|PubMed:18318601"
FT MUTAGEN 199
FT /note="Y->A: Prevents formation of the closed conformation
FT and interaction with CDC20; when associated with A-133."
FT /evidence="ECO:0000269|PubMed:18318601"
FT CONFLICT 16
FT /note="S -> C (in Ref. 8; BAD97153)"
FT /evidence="ECO:0000305"
FT CONFLICT 190
FT /note="I -> V (in Ref. 11; AAH70283)"
FT /evidence="ECO:0000305"
FT STRAND 2..5
FT /evidence="ECO:0007829|PDB:2VFX"
FT STRAND 7..9
FT /evidence="ECO:0007829|PDB:1S2H"
FT HELIX 13..34
FT /evidence="ECO:0007829|PDB:2VFX"
FT HELIX 40..42
FT /evidence="ECO:0007829|PDB:2VFX"
FT STRAND 43..48
FT /evidence="ECO:0007829|PDB:2VFX"
FT STRAND 51..56
FT /evidence="ECO:0007829|PDB:2VFX"
FT HELIX 59..77
FT /evidence="ECO:0007829|PDB:2VFX"
FT STRAND 78..80
FT /evidence="ECO:0007829|PDB:1DUJ"
FT STRAND 81..90
FT /evidence="ECO:0007829|PDB:2VFX"
FT TURN 91..93
FT /evidence="ECO:0007829|PDB:2VFX"
FT STRAND 96..106
FT /evidence="ECO:0007829|PDB:2VFX"
FT HELIX 108..111
FT /evidence="ECO:0007829|PDB:1GO4"
FT STRAND 116..118
FT /evidence="ECO:0007829|PDB:1S2H"
FT HELIX 121..139
FT /evidence="ECO:0007829|PDB:2VFX"
FT STRAND 149..157
FT /evidence="ECO:0007829|PDB:2VFX"
FT HELIX 160..162
FT /evidence="ECO:0007829|PDB:2QYF"
FT STRAND 167..169
FT /evidence="ECO:0007829|PDB:1GO4"
FT STRAND 173..175
FT /evidence="ECO:0007829|PDB:2V64"
FT STRAND 177..182
FT /evidence="ECO:0007829|PDB:2VFX"
FT STRAND 189..200
FT /evidence="ECO:0007829|PDB:2VFX"
SQ SEQUENCE 205 AA; 23510 MW; B8DCBF0043836764 CRC64;
MALQLSREQG ITLRGSAEIV AEFFSFGINS ILYQRGIYPS ETFTRVQKYG LTLLVTTDLE
LIKYLNNVVE QLKDWLYKCS VQKLVVVISN IESGEVLERW QFDIECDKTA KDDSAPREKS
QKAIQDEIRS VIRQITATVT FLPLLEVSCS FDLLIYTDKD LVVPEKWEES GPQFITNSEE
VRLRSFTTTI HKVNSMVAYK IPVND
//
