ID   MD2L1_MOUSE             Reviewed;         205 AA.
AC   Q9Z1B5; Q9JI53;
DT   11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT   11-JAN-2001, sequence version 2.
DT   27-MAR-2024, entry version 181.
DE   RecName: Full=Mitotic spindle assembly checkpoint protein MAD2A;
DE   AltName: Full=Mitotic arrest deficient 2-like protein 1;
DE            Short=MAD2-like protein 1;
GN   Name=Mad2l1; Synonyms=Mad2a;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Embryo;
RA   Jin D.-Y., Jeang K.-T.;
RT   "Identification of a novel component of the spindle assembly checkpoint in
RT   mammalian cells.";
RL   Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=129;
RX   PubMed=10892650; DOI=10.1016/s0092-8674(00)80875-2;
RA   Dobles M., Liberal V., Scott M.L., Benezra R., Sorger P.K.;
RT   "Chromosome missegregation and apoptosis in mice lacking the mitotic
RT   checkpoint protein Mad2.";
RL   Cell 101:635-645(2000).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [4]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver, Lung, Pancreas, Spleen, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
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 (By similarity). In the closed conformation (C-MAD2)
CC       forms a heterotetrameric complex with MAD1L1 at unattached kinetochores
CC       during prometaphase, and recruits an open conformation of MAD2L1 (O-
CC       MAD2) which then promotes the conversion of O-MAD2 to C-MAD2 (By
CC       similarity). Required for the execution of the mitotic checkpoint which
CC       monitors the process of kinetochore-spindle attachment and inhibits the
CC       activity of the anaphase promoting complex by sequestering CDC20 until
CC       all chromosomes are aligned at the metaphase plate (By similarity).
CC       {ECO:0000250|UniProtKB:Q13257}.
CC   -!- SUBUNIT: Monomer and homodimer (By similarity). Heterodimerizes with
CC       MAD2L1 in order to form a tetrameric MAD1L1-MAD2L1 core complex (By
CC       similarity). In the closed and open conformation, interacts with MAD1L1
CC       (By similarity). 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 (By similarity). Interacts with MAD2L1BP (By similarity).
CC       Interacts with ADAM17/TACE (By similarity). Interacts with CDC20 (By
CC       similarity). Dimeric MAD2L1 in the closed conformation interacts with
CC       CDC20 (By similarity). Monomeric MAD2L1 in the open conformation does
CC       not interact with CDC20 (By similarity). CDC20 competes with MAD1L1 for
CC       MAD2L1 binding (By similarity). In the closed conformation, interacts
CC       with BUB1B (By similarity). Interacts with TTK (By similarity).
CC       Interacts with TPR (By similarity). Binds to UBD (via ubiquitin-like 1
CC       domain) during mitosis (By similarity). Interacts with isoform 1 and
CC       isoform 2 of NEK2 (By similarity). Interacts with HSF1; this
CC       interaction occurs in mitosis (By similarity).
CC       {ECO:0000250|UniProtKB:Q13257}.
CC   -!- INTERACTION:
CC       Q9Z1B5; Q7TSY8: Sgo2; NbExp=3; IntAct=EBI-2552918, EBI-2552468;
CC       Q9Z1B5; Q9NRI5: DISC1; Xeno; NbExp=2; IntAct=EBI-2552918, EBI-529989;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q13257}.
CC       Chromosome, centromere, kinetochore {ECO:0000250}. Cytoplasm
CC       {ECO:0000250|UniProtKB:Q13257}. Cytoplasm, cytoskeleton, spindle pole
CC       {ECO:0000250}. Note=Recruited by MAD1L1 to unattached kinetochores (By
CC       similarity). Recruited to the nuclear pore complex by TPR during
CC       interphase (By similarity). Recruited to kinetochores in late
CC       prometaphase after BUB1, CENPF, BUB1B and CENPE. Kinetochore
CC       association requires the presence of NEK2 (By similarity).
CC       {ECO:0000250}.
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 (By similarity).
CC       {ECO:0000250}.
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 (By similarity).
CC       {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the MAD2 family. {ECO:0000305}.
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DR   EMBL; U83902; AAD09238.1; -; mRNA.
DR   EMBL; AF261919; AAF69525.1; -; Genomic_DNA.
DR   EMBL; AK082934; BAC38700.1; -; mRNA.
DR   CCDS; CCDS20210.1; -.
DR   RefSeq; NP_062372.2; NM_019499.4.
DR   RefSeq; XP_006506469.1; XM_006506406.3.
DR   AlphaFoldDB; Q9Z1B5; -.
DR   SMR; Q9Z1B5; -.
DR   BioGRID; 207818; 108.
DR   ComplexPortal; CPX-3968; Mitotic Checkpoint Complex.
DR   ComplexPortal; CPX-87; Mitotic spindle assembly checkpoint Mad1-Mad2 complex.
DR   ComplexPortal; CPX-90; Mitotic spindle assembly checkpoint complex MAD2.
DR   IntAct; Q9Z1B5; 107.
DR   MINT; Q9Z1B5; -.
DR   STRING; 10090.ENSMUSP00000112304; -.
DR   GlyGen; Q9Z1B5; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q9Z1B5; -.
DR   PhosphoSitePlus; Q9Z1B5; -.
DR   EPD; Q9Z1B5; -.
DR   MaxQB; Q9Z1B5; -.
DR   PaxDb; 10090-ENSMUSP00000098897; -.
DR   ProteomicsDB; 295982; -.
DR   Pumba; Q9Z1B5; -.
DR   TopDownProteomics; Q9Z1B5; -.
DR   Antibodypedia; 15732; 712 antibodies from 47 providers.
DR   DNASU; 56150; -.
DR   Ensembl; ENSMUST00000101343.2; ENSMUSP00000098897.2; ENSMUSG00000029910.15.
DR   Ensembl; ENSMUST00000116605.8; ENSMUSP00000112304.2; ENSMUSG00000029910.15.
DR   GeneID; 56150; -.
DR   KEGG; mmu:56150; -.
DR   UCSC; uc009cen.1; mouse.
DR   AGR; MGI:1860374; -.
DR   CTD; 4085; -.
DR   MGI; MGI:1860374; Mad2l1.
DR   VEuPathDB; HostDB:ENSMUSG00000029910; -.
DR   eggNOG; KOG3285; Eukaryota.
DR   GeneTree; ENSGT00940000153395; -.
DR   HOGENOM; CLU_072097_1_0_1; -.
DR   InParanoid; Q9Z1B5; -.
DR   OMA; ETTCAFD; -.
DR   OrthoDB; 5474106at2759; -.
DR   PhylomeDB; Q9Z1B5; -.
DR   TreeFam; TF101084; -.
DR   Reactome; R-MMU-141405; Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint components.
DR   Reactome; R-MMU-141430; Inactivation of APC/C via direct inhibition of the APC/C complex.
DR   Reactome; R-MMU-141444; Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal.
DR   Reactome; R-MMU-174184; Cdc20:Phospho-APC/C mediated degradation of Cyclin A.
DR   Reactome; R-MMU-176409; APC/C:Cdc20 mediated degradation of mitotic proteins.
DR   Reactome; R-MMU-179409; APC-Cdc20 mediated degradation of Nek2A.
DR   Reactome; R-MMU-2467813; Separation of Sister Chromatids.
DR   Reactome; R-MMU-2500257; Resolution of Sister Chromatid Cohesion.
DR   Reactome; R-MMU-5663220; RHO GTPases Activate Formins.
DR   Reactome; R-MMU-68877; Mitotic Prometaphase.
DR   Reactome; R-MMU-9648025; EML4 and NUDC in mitotic spindle formation.
DR   BioGRID-ORCS; 56150; 21 hits in 72 CRISPR screens.
DR   ChiTaRS; Mad2l1; mouse.
DR   PRO; PR:Q9Z1B5; -.
DR   Proteomes; UP000000589; Chromosome 6.
DR   RNAct; Q9Z1B5; Protein.
DR   Bgee; ENSMUSG00000029910; Expressed in animal zygote and 264 other cell types or tissues.
DR   ExpressionAtlas; Q9Z1B5; baseline and differential.
DR   GO; GO:0005694; C:chromosome; IDA:MGI.
DR   GO; GO:0000775; C:chromosome, centromeric region; IDA:MGI.
DR   GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR   GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR   GO; GO:0000776; C:kinetochore; IDA:MGI.
DR   GO; GO:0033597; C:mitotic checkpoint complex; ISO:MGI.
DR   GO; GO:0072686; C:mitotic spindle; ISS:UniProtKB.
DR   GO; GO:1990728; C:mitotic spindle assembly checkpoint MAD1-MAD2 complex; IPI:ComplexPortal.
DR   GO; GO:0044615; C:nuclear pore nuclear basket; ISO:MGI.
DR   GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR   GO; GO:0005634; C:nucleus; IDA:MGI.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR   GO; GO:0000922; C:spindle pole; IDA:MGI.
DR   GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR   GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR   GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR   GO; GO:0051660; P:establishment of centrosome localization; ISO:MGI.
DR   GO; GO:0000132; P:establishment of mitotic spindle orientation; ISO:MGI.
DR   GO; GO:0000070; P:mitotic sister chromatid segregation; IMP:MGI.
DR   GO; GO:0007094; P:mitotic spindle assembly checkpoint signaling; IMP:MGI.
DR   GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR   GO; GO:0045930; P:negative regulation of mitotic cell cycle; ISO:MGI.
DR   GO; GO:0045841; P:negative regulation of mitotic metaphase/anaphase transition; TAS:MGI.
DR   GO; GO:0042177; P:negative regulation of protein catabolic process; ISS:UniProtKB.
DR   GO; GO:0090267; P:positive regulation of mitotic cell cycle spindle assembly checkpoint; IMP: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.
DR   Genevisible; Q9Z1B5; MM.
PE   1: Evidence at protein level;
KW   Acetylation; Cell cycle; Cell division; Centromere; Chromosome; Cytoplasm;
KW   Cytoskeleton; Kinetochore; Mitosis; Nucleus; Phosphoprotein;
KW   Reference proteome.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000250|UniProtKB:Q13257"
FT   CHAIN           2..205
FT                   /note="Mitotic spindle assembly checkpoint protein MAD2A"
FT                   /id="PRO_0000126118"
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                   /evidence="ECO:0000250"
FT   MOD_RES         2
FT                   /note="N-acetylalanine"
FT                   /evidence="ECO:0000250|UniProtKB:Q13257"
FT   MOD_RES         130
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q13257"
FT   MOD_RES         170
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q13257"
FT   MOD_RES         185
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q13257"
FT   MOD_RES         195
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q13257"
FT   CONFLICT        157
FT                   /note="T -> A (in Ref. 1; AAD09238)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        178
FT                   /note="C -> S (in Ref. 1; AAD09238)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        201
FT                   /note="T -> I (in Ref. 1; AAD09238)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   205 AA;  23598 MW;  A9F3F28BC4C9738E CRC64;
     MAQQLAREQG ITLRGSAEIV AEFFSFGINS ILYQRGIYPS ETFTRVQKYG LTLLTTTDPE
     LIKYLNNVVE QLKEWLYKCS VQKLVVVISN IESGEVLERW QFDIECDKTA KEEGVRREKS
     QKAIQDEIRS VIRQITATVT FLPLLEVSCS FDLLIYTDKD LVVPEKWEES GPQFITNCEE
     VRLRSFTTTI HKVNSMVAYK TPVND
//