ID   MD1L1_MOUSE             Reviewed;         717 AA.
AC   Q9WTX8; Q9WTX9;
DT   27-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1999, sequence version 1.
DT   27-MAR-2024, entry version 152.
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;
GN   Name=Mad1l1; Synonyms=Mad1;
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] (ISOFORMS 1 AND 2).
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   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   STRAIN=FVB/N; TISSUE=Mammary tumor;
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   [3]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Spleen;
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). Forms a heterotetrameric complex with
CC       the closed conformation form of MAD2L1 (C-MAD2) at unattached
CC       kinetochores during prometaphase, recruits an open conformation of
CC       MAD2L1 (O-MAD2) and promotes the conversion of O-MAD2 to C-MAD2, which
CC       ensures mitotic checkpoint signaling (By similarity).
CC       {ECO:0000250|UniProtKB:Q9Y6D9}.
CC   -!- SUBUNIT: Homodimer (By similarity). Dimerizes via its N- and
CC       C- terminal regions (By similarity). Heterodimerizes with MAD2L1 in
CC       order to form a tetrameric MAD1L1-MAD2L1 core complex (By similarity).
CC       Interacts with the closed conformation form of MAD2L1 (C-MAD2) and open
CC       conformation form of MAD2L1 (O-MAD2) (By similarity). It is unclear
CC       whether MAD1L1 dimerization promotes the conversion of closed to open
CC       conformation of MAD2L1 (By similarity). Formation of a heterotetrameric
CC       core complex containing two molecules each of MAD1L1 and of MAD2L1
CC       promotes binding of another molecule of MAD2L1 to each MAD2L1,
CC       resulting in a heterohexamer (By similarity). Perturbation of the
CC       original MAD1L1-MAD2L1 structure by the spindle checkpoint may decrease
CC       MAD2L1 affinity for MAD1L1 (By similarity). CDC20 can compete with
CC       MAD1L1 for MAD2L1 binding, until the attachment and/or tension dampen
CC       the checkpoint signal, preventing further release of MAD2L1 on to CDC20
CC       (By similarity). Also able to interact with the BUB1/BUB3 complex (By
CC       similarity). Interacts with NEK2 (By similarity). Interacts with TTK
CC       (By similarity). Interacts with TPR; the interactions occurs in a
CC       microtubule-independent manner (By similarity). Interacts with IK (By
CC       similarity). Interacts with the viral Tax protein (By similarity).
CC       Interacts with PRAP1 (By similarity). {ECO:0000250|UniProtKB:Q9Y6D9}.
CC   -!- INTERACTION:
CC       Q9WTX8; O35231: Kifc3; NbExp=3; IntAct=EBI-4285225, EBI-11097964;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9Y6D9}.
CC       Chromosome, centromere, kinetochore {ECO:0000250|UniProtKB:Q9Y6D9}.
CC       Nucleus envelope {ECO:0000250|UniProtKB:Q9Y6D9}. Cytoplasm,
CC       cytoskeleton, microtubule organizing center, centrosome {ECO:0000250}.
CC       Cytoplasm, cytoskeleton, spindle {ECO:0000250}. Cytoplasm,
CC       cytoskeleton, spindle pole {ECO:0000250|UniProtKB:Q9Y6D9}.
CC       Note=Detected at the nucleus envelope during interphase. 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. Detected at kinetochores during prometaphase.
CC       Colocalizes with NEK2 at the kinetochore. Colocalizes with IK at
CC       spindle poles during metaphase and anaphase.
CC       {ECO:0000250|UniProtKB:Q9Y6D9}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1; Synonyms=MAD1a;
CC         IsoId=Q9WTX8-1; Sequence=Displayed;
CC       Name=2; Synonyms=MAD1b;
CC         IsoId=Q9WTX8-2; Sequence=VSP_011638;
CC   -!- PTM: Phosphorylated; by BUB1. Become hyperphosphorylated in late S
CC       through M phases or after mitotic spindle damage.
CC       {ECO:0000250|UniProtKB:Q9Y6D9}.
CC   -!- SIMILARITY: Belongs to the MAD1 family. {ECO:0000305}.
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DR   EMBL; AF083812; AAD24499.1; -; mRNA.
DR   EMBL; AF083813; AAD24500.1; -; mRNA.
DR   EMBL; BC010702; AAH10702.1; -; mRNA.
DR   CCDS; CCDS19817.1; -. [Q9WTX8-1]
DR   RefSeq; NP_034882.2; NM_010752.3. [Q9WTX8-1]
DR   RefSeq; XP_006504714.1; XM_006504651.2.
DR   AlphaFoldDB; Q9WTX8; -.
DR   SMR; Q9WTX8; -.
DR   BioGRID; 201270; 14.
DR   ComplexPortal; CPX-84; Mitotic spindle assembly checkpoint Mad1 complex.
DR   ComplexPortal; CPX-87; Mitotic spindle assembly checkpoint Mad1-Mad2 complex.
DR   IntAct; Q9WTX8; 5.
DR   MINT; Q9WTX8; -.
DR   STRING; 10090.ENSMUSP00000031534; -.
DR   iPTMnet; Q9WTX8; -.
DR   PhosphoSitePlus; Q9WTX8; -.
DR   EPD; Q9WTX8; -.
DR   MaxQB; Q9WTX8; -.
DR   PaxDb; 10090-ENSMUSP00000031534; -.
DR   PeptideAtlas; Q9WTX8; -.
DR   ProteomicsDB; 295720; -. [Q9WTX8-1]
DR   ProteomicsDB; 295721; -. [Q9WTX8-2]
DR   Pumba; Q9WTX8; -.
DR   Antibodypedia; 1135; 449 antibodies from 38 providers.
DR   DNASU; 17120; -.
DR   Ensembl; ENSMUST00000031534.9; ENSMUSP00000031534.7; ENSMUSG00000029554.16. [Q9WTX8-1]
DR   Ensembl; ENSMUST00000110829.7; ENSMUSP00000106453.3; ENSMUSG00000029554.16. [Q9WTX8-2]
DR   GeneID; 17120; -.
DR   KEGG; mmu:17120; -.
DR   UCSC; uc009ahj.1; mouse. [Q9WTX8-1]
DR   AGR; MGI:1341857; -.
DR   CTD; 8379; -.
DR   MGI; MGI:1341857; Mad1l1.
DR   VEuPathDB; HostDB:ENSMUSG00000029554; -.
DR   eggNOG; KOG4593; Eukaryota.
DR   GeneTree; ENSGT00390000001316; -.
DR   HOGENOM; CLU_023576_0_0_1; -.
DR   InParanoid; Q9WTX8; -.
DR   OMA; YKLDFMP; -.
DR   OrthoDB; 8224at2759; -.
DR   PhylomeDB; Q9WTX8; -.
DR   TreeFam; TF101083; -.
DR   Reactome; R-MMU-141444; Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal.
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; 17120; 6 hits in 80 CRISPR screens.
DR   ChiTaRS; Mad1l1; mouse.
DR   PRO; PR:Q9WTX8; -.
DR   Proteomes; UP000000589; Chromosome 5.
DR   RNAct; Q9WTX8; Protein.
DR   Bgee; ENSMUSG00000029554; Expressed in secondary oocyte and 119 other cell types or tissues.
DR   GO; GO:0005813; C:centrosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR   GO; GO:0000776; C:kinetochore; IDA:UniProtKB.
DR   GO; GO:1990706; C:MAD1 complex; IDA:ComplexPortal.
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:0097431; C:mitotic spindle pole; IEA:Ensembl.
DR   GO; GO:0005635; C:nuclear envelope; ISO:MGI.
DR   GO; GO:0044615; C:nuclear pore nuclear basket; ISS:UniProtKB.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0000922; C:spindle pole; IDA:MGI.
DR   GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR   GO; GO:0043515; F:kinetochore binding; ISS: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; ISO:MGI.
DR   GO; GO:1902426; P:deactivation of mitotic spindle assembly checkpoint; ISO:MGI.
DR   GO; GO:0007094; P:mitotic spindle assembly checkpoint signaling; ISS:UniProtKB.
DR   GO; GO:0042130; P:negative regulation of T cell proliferation; IDA:MGI.
DR   GO; GO:0090267; P:positive regulation of mitotic cell cycle spindle assembly checkpoint; ISS:UniProtKB.
DR   GO; GO:0090235; P:regulation of metaphase plate congression; ISS:UniProtKB.
DR   GO; GO:1901990; P:regulation of mitotic cell cycle phase transition; IDA:MGI.
DR   GO; GO:0048538; P:thymus development; IDA:MGI.
DR   Gene3D; 1.20.5.170; -; 1.
DR   Gene3D; 3.30.457.60; -; 1.
DR   Gene3D; 6.10.250.90; -; 1.
DR   InterPro; IPR008672; Mad1.
DR   PANTHER; PTHR23168:SF0; MITOTIC SPINDLE ASSEMBLY CHECKPOINT PROTEIN MAD1; 1.
DR   PANTHER; PTHR23168; MITOTIC SPINDLE ASSEMBLY CHECKPOINT PROTEIN MAD1 MITOTIC ARREST DEFICIENT-LIKE PROTEIN 1; 1.
DR   Pfam; PF05557; MAD; 1.
DR   SUPFAM; SSF75704; Mitotic arrest deficient-like 1, Mad1; 1.
DR   Genevisible; Q9WTX8; MM.
PE   1: Evidence at protein level;
KW   Acetylation; Alternative splicing; Cell cycle; Cell division; Centromere;
KW   Chromosome; Coiled coil; Cytoplasm; Cytoskeleton; Isopeptide bond;
KW   Kinetochore; Mitosis; Nucleus; Phosphoprotein; Reference proteome;
KW   Ubl conjugation.
FT   CHAIN           1..717
FT                   /note="Mitotic spindle assembly checkpoint protein MAD1"
FT                   /id="PRO_0000213801"
FT   REGION          380..532
FT                   /note="Necessary for interaction with NEK2"
FT                   /evidence="ECO:0000250"
FT   REGION          540..551
FT                   /note="Necessary for interaction with MAD2L1"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6D9"
FT   COILED          48..631
FT                   /evidence="ECO:0000255"
FT   MOTIF           79..82
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6D9"
FT   MOD_RES         1
FT                   /note="N-acetylmethionine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6D9"
FT   MOD_RES         16
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6D9"
FT   MOD_RES         61
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6D9"
FT   MOD_RES         214
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6D9"
FT   MOD_RES         428
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6D9"
FT   CROSSLNK        61
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2); alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6D9"
FT   VAR_SEQ         503..717
FT                   /note="LKVEELEGERSRLEQEKQVLEMQMEKLTLQGDYNQSRTKVLHMSLNPISMAR
FT                   QRQHEDHDRLQEECERLRGLVHALERGGPIPADLEAASSLPSSKEVAELRKQVESAELK
FT                   NQRLKEVFQTKIQEFRKVCYTLTGYQIDVTTESQYRLTSRYAEHQTDCLIFKATGPSGS
FT                   KMQLLETEFSRSVPELIELHLLQQDSIPAFLSALTIELFSRQTSI -> VTTTRVEPKC
FT                   YT (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:10049595"
FT                   /id="VSP_011638"
SQ   SEQUENCE   717 AA;  83541 MW;  4EEB880AE7D80838 CRC64;
     MEDLGENTTV LSSLRSLNNF ISQRMEGTSG LDVSTSASGS LQKQYEYHMQ LEERAEQIRS
     KSYLIQVERE KMQMELSHKR ARVELERAAS TNARNYEREV DRNQELLARI RQLQECEATA
     EEKMREQLER HRLCKQNLDA VSQQLREQED SLASAREMIS SLKGRVSELQ LSAMDQKVQV
     KRLESEKQEL KEQLELQQRK WQEANQKIQE LQASQDERAE HEQKIKDLEQ KLCLQEQDAA
     VVKSMKSELM RMPRMERELK RLHEENTHLR EMKETNGLLT EELEGLQRKL SRQEKMQEAL
     VDLELEKEKL LAKLQSWENL DQTMGLNLRT PEDLSRFVVE LQQRELTLKE KNNSITSSAR
     GLEKVQQQLQ DEVRQANAQL LEERKKRETH EALARRLQKR NALLTKERDG MRAILGSYDS
     ELTQTEYSTQ LTQRLWEAED MVQKVHAHSS EMEAQLSQAL EELGVQKQRA DTLEMELKML
     KAQTSSAESS FSFCKEEVDA LRLKVEELEG ERSRLEQEKQ VLEMQMEKLT LQGDYNQSRT
     KVLHMSLNPI SMARQRQHED HDRLQEECER LRGLVHALER GGPIPADLEA ASSLPSSKEV
     AELRKQVESA ELKNQRLKEV FQTKIQEFRK VCYTLTGYQI DVTTESQYRL TSRYAEHQTD
     CLIFKATGPS GSKMQLLETE FSRSVPELIE LHLLQQDSIP AFLSALTIEL FSRQTSI
//