MD2L2_HUMAN
ID MD2L2_HUMAN Reviewed; 211 AA.
AC Q9UI95; B3KNE3; Q5TGW7; Q9UNA7; Q9Y6I6;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2001, sequence version 2.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Mitotic spindle assembly checkpoint protein MAD2B;
DE AltName: Full=Mitotic arrest deficient 2-like protein 2;
DE Short=MAD2-like protein 2;
DE AltName: Full=REV7 homolog;
DE Short=hREV7;
GN Name=MAD2L2; Synonyms=MAD2B, REV7;
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], AND INTERACTION WITH ADAM9.
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Hirota T., Nakamura H., Tada K., Marumoto T., Saya H.;
RT "Identification of a novel human homolog of the MAD2 protein that interacts
RT with the h-warts protein.";
RL Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA], AND INTERACTION WITH REV3L.
RX PubMed=10660610; DOI=10.1074/jbc.275.6.4391;
RA Murakumo Y., Roth T., Ishii H., Rasio D., Numata S., Croce C.M., Fishel R.;
RT "A human REV7 homolog that interacts with the polymerase zeta catalytic
RT subunit hREV3 and the spindle assembly checkpoint protein hMAD2.";
RL J. Biol. Chem. 275:4391-4397(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cerebellum, and Embryo;
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 [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NIEHS SNPs program;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [8]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
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 [10]
RP FUNCTION, AND INTERACTION WITH FZR1.
RX PubMed=11459825; DOI=10.1101/gad.897901;
RA Pfleger C.M., Salic A., Lee E., Kirschner M.W.;
RT "Inhibition of Cdh1-APC by the MAD2-related protein MAD2L2: a novel
RT mechanism for regulating Cdh1.";
RL Genes Dev. 15:1759-1764(2001).
RN [11]
RP FUNCTION, AND INTERACTION WITH FZR1 AND CDC20.
RX PubMed=11459826; DOI=10.1101/gad.898701;
RA Chen J., Fang G.;
RT "MAD2B is an inhibitor of the anaphase-promoting complex.";
RL Genes Dev. 15:1765-1770(2001).
RN [12]
RP INTERACTION WITH REV1 AND REV3L, AND HOMOOLIGOMERIZATION.
RX PubMed=11485998; DOI=10.1074/jbc.m102051200;
RA Murakumo Y., Ogura Y., Ishii H., Numata S., Ichihara M., Croce C.M.,
RA Fishel R., Takahashi M.;
RT "Interactions in the error-prone postreplication repair proteins hREV1,
RT hREV3, and hREV7.";
RL J. Biol. Chem. 276:35644-35651(2001).
RN [13]
RP INTERACTION WITH PRCC, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=11717438; DOI=10.1073/pnas.241304198;
RA Weterman M.A., van Groningen J.J., Tertoolen L., van Kessel A.G.;
RT "Impairment of MAD2B-PRCC interaction in mitotic checkpoint defective
RT t(X;1)-positive renal cell carcinomas.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:13808-13813(2001).
RN [14]
RP FUNCTION IN APC REGULATION, INTERACTION WITH SHIGELLA FLEXNERI IPAB; FZR1
RP AND CDC20, AND SUBCELLULAR LOCATION.
RX PubMed=17719540; DOI=10.1016/j.cell.2007.06.043;
RA Iwai H., Kim M., Yoshikawa Y., Ashida H., Ogawa M., Fujita Y., Muller D.,
RA Kirikae T., Jackson P.K., Kotani S., Sasakawa C.;
RT "A bacterial effector targets Mad2L2, an APC inhibitor, to modulate host
RT cell cycling.";
RL Cell 130:611-623(2007).
RN [15]
RP INTERACTION WITH YY1AP1, AND SUBCELLULAR LOCATION.
RX PubMed=17541814; DOI=10.1007/s11010-007-9512-8;
RA Li L., Shi Y., Wu H., Wan B., Li P., Zhou L., Shi H., Huo K.;
RT "Hepatocellular carcinoma-associated gene 2 interacts with MAD2L2.";
RL Mol. Cell. Biochem. 304:297-304(2007).
RN [16]
RP FUNCTION, AND INTERACTION WITH ELK1 AND JNK KINASES.
RX PubMed=17296730; DOI=10.1128/mcb.02276-06;
RA Zhang L., Yang S.H., Sharrocks A.D.;
RT "Rev7/MAD2B links c-Jun N-terminal protein kinase pathway signaling to
RT activation of the transcription factor Elk-1.";
RL Mol. Cell. Biol. 27:2861-2869(2007).
RN [17]
RP FUNCTION, AND INTERACTION WITH TCF7L2.
RX PubMed=19443654; DOI=10.1074/jbc.m109.005017;
RA Hong C.F., Chou Y.T., Lin Y.S., Wu C.W.;
RT "MAD2B, a novel TCF4-binding protein, modulates TCF4-mediated epithelial-
RT mesenchymal transdifferentiation.";
RL J. Biol. Chem. 284:19613-19622(2009).
RN [18]
RP INTERACTION WITH RAN, AND SUBCELLULAR LOCATION.
RX PubMed=19753112; DOI=10.1371/journal.pone.0007020;
RA Medendorp K., van Groningen J.J., Vreede L., Hetterschijt L.,
RA van den Hurk W.H., de Bruijn D.R., Brugmans L., van Kessel A.G.;
RT "The mitotic arrest deficient protein MAD2B interacts with the small GTPase
RT RAN throughout the cell cycle.";
RL PLoS ONE 4:E7020-E7020(2009).
RN [19]
RP INTERACTION WITH POGZ.
RX PubMed=20850016; DOI=10.1016/j.cell.2010.08.020;
RA Vermeulen M., Eberl H.C., Matarese F., Marks H., Denissov S., Butter F.,
RA Lee K.K., Olsen J.V., Hyman A.A., Stunnenberg H.G., Mann M.;
RT "Quantitative interaction proteomics and genome-wide profiling of
RT epigenetic histone marks and their readers.";
RL Cell 142:967-980(2010).
RN [20]
RP INTERACTION WITH CHAMP1, AND SUBCELLULAR LOCATION.
RX PubMed=21063390; DOI=10.1038/emboj.2010.276;
RA Itoh G., Kanno S., Uchida K.S., Chiba S., Sugino S., Watanabe K.,
RA Mizuno K., Yasui A., Hirota T., Tanaka K.;
RT "CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-microtubule
RT attachment.";
RL EMBO J. 30:130-144(2011).
RN [21]
RP IDENTIFICATION IN POL-ZETA COMPLEX.
RX PubMed=24449906; DOI=10.1073/pnas.1324001111;
RA Lee Y.S., Gregory M.T., Yang W.;
RT "Human Pol zeta purified with accessory subunits is active in translesion
RT DNA synthesis and complements Pol eta in cisplatin bypass.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:2954-2959(2014).
RN [22]
RP INVOLVEMENT IN FANCV, VARIANT FANCV GLU-85, AND CHARACTERIZATION OF VARIANT
RP FANCV GLU-85.
RX PubMed=27500492; DOI=10.1172/jci88010;
RA Bluteau D., Masliah-Planchon J., Clairmont C., Rousseau A., Ceccaldi R.,
RA Dubois d'Enghien C., Bluteau O., Cuccuini W., Gachet S.,
RA Peffault de Latour R., Leblanc T., Socie G., Baruchel A.,
RA Stoppa-Lyonnet D., D'Andrea A.D., Soulier J.;
RT "Biallelic inactivation of REV7 is associated with Fanconi anemia.";
RL J. Clin. Invest. 126:3580-3584(2016).
RN [23]
RP FUNCTION, IDENTIFICATION IN THE SHIELDIN COMPLEX, INTERACTION WITH SHLD2
RP AND SHLD3, SUBCELLULAR LOCATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=29656893; DOI=10.1016/j.cell.2018.03.050;
RA Gupta R., Somyajit K., Narita T., Maskey E., Stanlie A., Kremer M.,
RA Typas D., Lammers M., Mailand N., Nussenzweig A., Lukas J., Choudhary C.;
RT "DNA repair network analysis reveals shieldin as a key regulator of NHEJ
RT and PARP inhibitor sensitivity.";
RL Cell 0:0-0(2018).
RN [24]
RP INTERACTION WITH SHLD2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=29789392; DOI=10.15252/embj.201899543;
RA Tomida J., Takata K.I., Bhetawal S., Person M.D., Chao H.P., Tang D.G.,
RA Wood R.D.;
RT "FAM35A associates with REV7 and modulates DNA damage responses of normal
RT and BRCA1-defective cells.";
RL EMBO J. 37:0-0(2018).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH REV3L, FUNCTION,
RP MUTAGENESIS OF TYR-63; ARG-124; TRP-171; LEU-186; GLN-200 AND TYR-202, AND
RP INTERACTION WITH REV1.
RX PubMed=20164194; DOI=10.1074/jbc.m109.092403;
RA Hara K., Hashimoto H., Murakumo Y., Kobayashi S., Kogame T., Unzai S.,
RA Akashi S., Takeda S., Shimizu T., Sato M.;
RT "Crystal structure of human REV7 in complex with a human REV3 fragment and
RT structural implication of the interaction between DNA polymerase zeta and
RT REV1.";
RL J. Biol. Chem. 285:12299-12307(2010).
CC -!- FUNCTION: Adapter protein able to interact with different proteins and
CC involved in different biological processes (PubMed:11459825,
CC PubMed:11459826, PubMed:17719540, PubMed:17296730, PubMed:19443654,
CC PubMed:29656893). Mediates the interaction between the error-prone DNA
CC polymerase zeta catalytic subunit REV3L and the inserter polymerase
CC REV1, thereby mediating the second polymerase switching in translesion
CC DNA synthesis (PubMed:20164194). Translesion DNA synthesis releases the
CC replication blockade of replicative polymerases, stalled in presence of
CC DNA lesions (PubMed:20164194). Component of the shieldin complex, which
CC plays an important role in repair of DNA double-stranded breaks (DSBs)
CC (PubMed:29656893). During G1 and S phase of the cell cycle, the complex
CC functions downstream of TP53BP1 to promote non-homologous end joining
CC (NHEJ) and suppress DNA end resection (PubMed:29656893). Mediates
CC various NHEJ-dependent processes including immunoglobulin class-switch
CC recombination, and fusion of unprotected telomeres (PubMed:29656893).
CC May also regulate another aspect of cellular response to DNA damage
CC through regulation of the JNK-mediated phosphorylation and activation
CC of the transcriptional activator ELK1 (PubMed:17296730). Inhibits the
CC FZR1- and probably CDC20-mediated activation of the anaphase promoting
CC complex APC thereby regulating progression through the cell cycle
CC (PubMed:11459825, PubMed:17719540). Regulates TCF7L2-mediated gene
CC transcription and may play a role in epithelial-mesenchymal
CC transdifferentiation (PubMed:19443654). {ECO:0000269|PubMed:11459825,
CC ECO:0000269|PubMed:11459826, ECO:0000269|PubMed:17296730,
CC ECO:0000269|PubMed:17719540, ECO:0000269|PubMed:19443654,
CC ECO:0000269|PubMed:20164194, ECO:0000269|PubMed:29656893}.
CC -!- SUBUNIT: Homooligomer (Probable). Heterodimer with REV3L
CC (PubMed:10660610, PubMed:11485998). This dimer forms the minimal DNA
CC polymerase zeta complex (Pol-zeta2), with REV3L bearing DNA polymerase
CC catalytic activity, although its activity is very low in this context
CC (PubMed:11485998). Component of the tetrameric Pol-zeta complex (Pol-
CC zeta4), which consists of REV3L, MAD2L2, POLD2 and POLD3; Pol-zeta4 is
CC the fully active form of DNA polymerase zeta (PubMed:24449906).
CC Component of the shieldin complex, consisting of SHLD1, SHLD2, SHLD3
CC and MAD2L2/REV7 (PubMed:29656893, PubMed:29789392). Within the complex,
CC SHLD2 forms a scaffold which interacts with a SHLD3-MAD2L2 subcomplex
CC via its N-terminus, and with SHLD1 via its C-terminus
CC (PubMed:29656893). Interacts with REV1 (PubMed:11485998,
CC PubMed:20164194). Interacts with ADAM9 (PubMed:10527948). Interacts
CC with CHAMP1 (PubMed:21063390). Interacts with FZR1 (in complex with the
CC anaphase promoting complex APC) (PubMed:11459825, PubMed:11459826).
CC Interacts with CDC20; PubMed:11459825 could not detect the interaction
CC (PubMed:11459826). Interacts with RAN (PubMed:19753112). Interacts with
CC ELK1; the interaction is direct and recruits MAD2L2 to ELK1-specific
CC promoters (PubMed:17296730). May interact with the JNK kinases MAPK8
CC and/or MAPK9 to stimulate ELK1 phosphorylation and transcriptional
CC activity upon DNA damage (PubMed:17296730). Interacts with TCF7L2;
CC prevents its binding to promoters and negatively modulates its
CC transcriptional activity (PubMed:19443654). Interacts with YY1AP1
CC (PubMed:17541814). Interacts with S.flexneri protein ipaB; prevents the
CC interaction of MAD2L2 with FZR1 and CDC20 resulting in an activation of
CC the anaphase-promoting complex APC and a cell cycle arrest
CC (PubMed:17719540). Interacts with PRCC; the interaction is direct
CC (PubMed:11717438). Interacts with POGZ (PubMed:20850016).
CC {ECO:0000269|PubMed:10527948, ECO:0000269|PubMed:10660610,
CC ECO:0000269|PubMed:11459825, ECO:0000269|PubMed:11459826,
CC ECO:0000269|PubMed:11485998, ECO:0000269|PubMed:11717438,
CC ECO:0000269|PubMed:17296730, ECO:0000269|PubMed:17541814,
CC ECO:0000269|PubMed:17719540, ECO:0000269|PubMed:19443654,
CC ECO:0000269|PubMed:19753112, ECO:0000269|PubMed:20164194,
CC ECO:0000269|PubMed:20850016, ECO:0000269|PubMed:21063390,
CC ECO:0000269|PubMed:24449906, ECO:0000269|PubMed:29656893,
CC ECO:0000269|PubMed:29789392, ECO:0000305}.
CC -!- INTERACTION:
CC Q9UI95; Q13443: ADAM9; NbExp=3; IntAct=EBI-77889, EBI-77903;
CC Q9UI95; Q9H1P6: C20orf85; NbExp=3; IntAct=EBI-77889, EBI-12155483;
CC Q9UI95; Q13554: CAMK2B; NbExp=3; IntAct=EBI-77889, EBI-1058722;
CC Q9UI95; Q12834: CDC20; NbExp=2; IntAct=EBI-77889, EBI-367462;
CC Q9UI95; P30260: CDC27; NbExp=2; IntAct=EBI-77889, EBI-994813;
CC Q9UI95; Q96JM3: CHAMP1; NbExp=6; IntAct=EBI-77889, EBI-2560420;
CC Q9UI95; O75140-2: DEPDC5; NbExp=3; IntAct=EBI-77889, EBI-12366971;
CC Q9UI95; P50570-2: DNM2; NbExp=3; IntAct=EBI-77889, EBI-10968534;
CC Q9UI95; Q9NTX9: FAM217B; NbExp=3; IntAct=EBI-77889, EBI-19153639;
CC Q9UI95; Q9C0B1-2: FTO; NbExp=3; IntAct=EBI-77889, EBI-18138793;
CC Q9UI95; Q9UM11: FZR1; NbExp=2; IntAct=EBI-77889, EBI-724997;
CC Q9UI95; O15499: GSC2; NbExp=3; IntAct=EBI-77889, EBI-19954058;
CC Q9UI95; Q13422: IKZF1; NbExp=3; IntAct=EBI-77889, EBI-745305;
CC Q9UI95; Q9UKT9: IKZF3; NbExp=3; IntAct=EBI-77889, EBI-747204;
CC Q9UI95; Q0VD86: INCA1; NbExp=3; IntAct=EBI-77889, EBI-6509505;
CC Q9UI95; Q7L273: KCTD9; NbExp=3; IntAct=EBI-77889, EBI-4397613;
CC Q9UI95; O76011: KRT34; NbExp=3; IntAct=EBI-77889, EBI-1047093;
CC Q9UI95; Q8WWY6: MBD3L1; NbExp=3; IntAct=EBI-77889, EBI-12516603;
CC Q9UI95; Q9UPG8: PLAGL2; NbExp=3; IntAct=EBI-77889, EBI-2876622;
CC Q9UI95; O75688-3: PPM1B; NbExp=3; IntAct=EBI-77889, EBI-17715099;
CC Q9UI95; Q6MZQ0: PRR5L; NbExp=3; IntAct=EBI-77889, EBI-1567866;
CC Q9UI95; Q86YS3: RAB11FIP4; NbExp=3; IntAct=EBI-77889, EBI-949727;
CC Q9UI95; Q04864: REL; NbExp=3; IntAct=EBI-77889, EBI-307352;
CC Q9UI95; Q04864-2: REL; NbExp=3; IntAct=EBI-77889, EBI-10829018;
CC Q9UI95; O60673: REV3L; NbExp=5; IntAct=EBI-77889, EBI-2871302;
CC Q9UI95; A8K8P3-4: SFI1; NbExp=3; IntAct=EBI-77889, EBI-10321817;
CC Q9UI95; Q6ZNX1: SHLD3; NbExp=7; IntAct=EBI-77889, EBI-20209073;
CC Q9UI95; P15884: TCF4; NbExp=3; IntAct=EBI-77889, EBI-533224;
CC Q9UI95; P15884-3: TCF4; NbExp=3; IntAct=EBI-77889, EBI-13636688;
CC Q9UI95; Q8TBB0: THAP6; NbExp=3; IntAct=EBI-77889, EBI-3925505;
CC Q9UI95; P14373: TRIM27; NbExp=3; IntAct=EBI-77889, EBI-719493;
CC Q9UI95; Q9BYV2: TRIM54; NbExp=3; IntAct=EBI-77889, EBI-2130429;
CC Q9UI95; Q9C029: TRIM7; NbExp=3; IntAct=EBI-77889, EBI-2813981;
CC Q9UI95; O96006: ZBED1; NbExp=3; IntAct=EBI-77889, EBI-740037;
CC Q9UI95; Q9H0C1: ZMYND12; NbExp=3; IntAct=EBI-77889, EBI-12030590;
CC Q9UI95; Q8NB15: ZNF511; NbExp=3; IntAct=EBI-77889, EBI-10269136;
CC Q9UI95; Q96NG5: ZNF558; NbExp=3; IntAct=EBI-77889, EBI-373363;
CC Q9UI95; Q8N720: ZNF655; NbExp=3; IntAct=EBI-77889, EBI-625509;
CC Q9UI95; P18011: ipaB; Xeno; NbExp=7; IntAct=EBI-77889, EBI-490239;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11717438,
CC ECO:0000269|PubMed:17541814, ECO:0000269|PubMed:17719540,
CC ECO:0000269|PubMed:19753112}. Cytoplasm, cytoskeleton, spindle
CC {ECO:0000269|PubMed:19753112, ECO:0000269|PubMed:21063390}. Cytoplasm
CC {ECO:0000269|PubMed:11717438, ECO:0000269|PubMed:17719540}. Chromosome
CC {ECO:0000269|PubMed:29656893}. Note=Recruited to sites of chromosomal
CC double-stranded breaks during G1 and S phase of the cell cycle.
CC {ECO:0000269|PubMed:29656893}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:11717438}.
CC -!- DISEASE: Fanconi anemia, complementation group V (FANCV) [MIM:617243]:
CC A disorder affecting all bone marrow elements and resulting in anemia,
CC leukopenia and thrombopenia. It is associated with cardiac, renal and
CC limb malformations, dermal pigmentary changes, and a predisposition to
CC the development of malignancies. At the cellular level it is associated
CC with hypersensitivity to DNA-damaging agents, chromosomal instability
CC (increased chromosome breakage) and defective DNA repair.
CC {ECO:0000269|PubMed:27500492}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/mad2l2/";
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; AF072933; AAD41647.1; -; mRNA.
DR EMBL; AF080398; AAF20267.1; -; mRNA.
DR EMBL; AF139365; AAD30290.1; -; mRNA.
DR EMBL; AF157482; AAF34357.1; -; mRNA.
DR EMBL; AK027327; BAG51305.1; -; mRNA.
DR EMBL; AK094316; BAG52858.1; -; mRNA.
DR EMBL; DQ017900; AAY26393.1; -; Genomic_DNA.
DR EMBL; AL031731; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471130; EAW71697.1; -; Genomic_DNA.
DR EMBL; BC015244; AAH15244.1; -; mRNA.
DR CCDS; CCDS134.1; -.
DR RefSeq; NP_001120797.1; NM_001127325.1.
DR RefSeq; NP_006332.3; NM_006341.3.
DR RefSeq; XP_011538809.1; XM_011540507.1.
DR PDB; 3ABD; X-ray; 1.90 A; A/B=1-211.
DR PDB; 3ABE; X-ray; 2.60 A; C=1-211.
DR PDB; 3VU7; X-ray; 2.80 A; C=1-211.
DR PDB; 4EXT; X-ray; 1.90 A; C=7-209.
DR PDB; 4GK0; X-ray; 2.70 A; A/B=1-211.
DR PDB; 4GK5; X-ray; 3.21 A; A/B=1-211.
DR PDB; 5XPT; X-ray; 2.10 A; A=1-211.
DR PDB; 5XPU; X-ray; 2.30 A; A=1-211.
DR PDB; 6BC8; X-ray; 1.68 A; A=1-211.
DR PDB; 6BCD; X-ray; 1.43 A; A=1-211.
DR PDB; 6BI7; X-ray; 2.80 A; A/C/E/G=1-211.
DR PDB; 6K07; X-ray; 2.24 A; A=7-211.
DR PDB; 6K08; X-ray; 2.31 A; A=7-211.
DR PDB; 6KEA; X-ray; 2.35 A; A/B/C/D=12-211.
DR PDB; 6KTO; X-ray; 3.45 A; A/B=1-211.
DR PDB; 6M7A; X-ray; 1.90 A; A/B=1-208.
DR PDB; 6M7B; X-ray; 1.77 A; A/B=1-211.
DR PDB; 6NIF; X-ray; 2.00 A; A=2-211.
DR PDB; 6VE5; X-ray; 2.00 A; A=1-211.
DR PDB; 6WS0; X-ray; 2.24 A; CCC=1-211.
DR PDB; 6WS5; X-ray; 2.47 A; CCC=1-211.
DR PDB; 6WW9; X-ray; 2.70 A; A/B=2-211.
DR PDB; 6WWA; X-ray; 3.80 A; A/B/C/D=2-211.
DR PDB; 7L9P; EM; 3.60 A; G/I/J/K=2-211.
DR PDBsum; 3ABD; -.
DR PDBsum; 3ABE; -.
DR PDBsum; 3VU7; -.
DR PDBsum; 4EXT; -.
DR PDBsum; 4GK0; -.
DR PDBsum; 4GK5; -.
DR PDBsum; 5XPT; -.
DR PDBsum; 5XPU; -.
DR PDBsum; 6BC8; -.
DR PDBsum; 6BCD; -.
DR PDBsum; 6BI7; -.
DR PDBsum; 6K07; -.
DR PDBsum; 6K08; -.
DR PDBsum; 6KEA; -.
DR PDBsum; 6KTO; -.
DR PDBsum; 6M7A; -.
DR PDBsum; 6M7B; -.
DR PDBsum; 6NIF; -.
DR PDBsum; 6VE5; -.
DR PDBsum; 6WS0; -.
DR PDBsum; 6WS5; -.
DR PDBsum; 6WW9; -.
DR PDBsum; 6WWA; -.
DR PDBsum; 7L9P; -.
DR AlphaFoldDB; Q9UI95; -.
DR SASBDB; Q9UI95; -.
DR SMR; Q9UI95; -.
DR BioGRID; 115722; 323.
DR ComplexPortal; CPX-3481; Shieldin complex.
DR ComplexPortal; CPX-994; DNA polymerase zeta complex.
DR CORUM; Q9UI95; -.
DR IntAct; Q9UI95; 163.
DR MINT; Q9UI95; -.
DR STRING; 9606.ENSP00000235310; -.
DR ChEMBL; CHEMBL4524021; -.
DR iPTMnet; Q9UI95; -.
DR PhosphoSitePlus; Q9UI95; -.
DR BioMuta; MAD2L2; -.
DR EPD; Q9UI95; -.
DR jPOST; Q9UI95; -.
DR MassIVE; Q9UI95; -.
DR MaxQB; Q9UI95; -.
DR PaxDb; Q9UI95; -.
DR PeptideAtlas; Q9UI95; -.
DR PRIDE; Q9UI95; -.
DR ProteomicsDB; 84481; -.
DR TopDownProteomics; Q9UI95; -.
DR Antibodypedia; 3766; 203 antibodies from 30 providers.
DR DNASU; 10459; -.
DR Ensembl; ENST00000235310.7; ENSP00000235310.2; ENSG00000116670.15.
DR Ensembl; ENST00000376667.7; ENSP00000365855.3; ENSG00000116670.15.
DR Ensembl; ENST00000376692.9; ENSP00000365882.4; ENSG00000116670.15.
DR GeneID; 10459; -.
DR KEGG; hsa:10459; -.
DR MANE-Select; ENST00000376692.9; ENSP00000365882.4; NM_006341.4; NP_006332.3.
DR UCSC; uc001asp.4; human.
DR CTD; 10459; -.
DR DisGeNET; 10459; -.
DR GeneCards; MAD2L2; -.
DR GeneReviews; MAD2L2; -.
DR HGNC; HGNC:6764; MAD2L2.
DR HPA; ENSG00000116670; Low tissue specificity.
DR MalaCards; MAD2L2; -.
DR MIM; 604094; gene.
DR MIM; 617243; phenotype.
DR neXtProt; NX_Q9UI95; -.
DR OpenTargets; ENSG00000116670; -.
DR Orphanet; 84; Fanconi anemia.
DR PharmGKB; PA398; -.
DR VEuPathDB; HostDB:ENSG00000116670; -.
DR eggNOG; KOG3186; Eukaryota.
DR GeneTree; ENSGT00940000153395; -.
DR InParanoid; Q9UI95; -.
DR OMA; CEDFPWI; -.
DR OrthoDB; 1630737at2759; -.
DR PhylomeDB; Q9UI95; -.
DR TreeFam; TF101085; -.
DR PathwayCommons; Q9UI95; -.
DR Reactome; R-HSA-110312; Translesion synthesis by REV1.
DR Reactome; R-HSA-5655862; Translesion synthesis by POLK.
DR Reactome; R-HSA-5656121; Translesion synthesis by POLI.
DR SignaLink; Q9UI95; -.
DR SIGNOR; Q9UI95; -.
DR BioGRID-ORCS; 10459; 684 hits in 1089 CRISPR screens.
DR ChiTaRS; MAD2L2; human.
DR EvolutionaryTrace; Q9UI95; -.
DR GeneWiki; MAD2L2; -.
DR GenomeRNAi; 10459; -.
DR Pharos; Q9UI95; Tbio.
DR PRO; PR:Q9UI95; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9UI95; protein.
DR Bgee; ENSG00000116670; Expressed in ganglionic eminence and 162 other tissues.
DR ExpressionAtlas; Q9UI95; baseline and differential.
DR Genevisible; Q9UI95; HS.
DR GO; GO:0000785; C:chromatin; IC:ComplexPortal.
DR GO; GO:0005694; C:chromosome; IC:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0035861; C:site of double-strand break; IC:UniProtKB.
DR GO; GO:0005819; C:spindle; IDA:UniProtKB.
DR GO; GO:0016035; C:zeta DNA polymerase complex; IDA:UniProtKB.
DR GO; GO:0008432; F:JUN kinase binding; IDA:UniProtKB.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:BHF-UCL.
DR GO; GO:0007015; P:actin filament organization; IMP:BHF-UCL.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0042772; P:DNA damage response, signal transduction resulting in transcription; IDA:UniProtKB.
DR GO; GO:0006302; P:double-strand break repair; IGI:UniProtKB.
DR GO; GO:0042276; P:error-prone translesion synthesis; IDA:ComplexPortal.
DR GO; GO:0007094; P:mitotic spindle assembly checkpoint signaling; TAS:ProtInc.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IMP:BHF-UCL.
DR GO; GO:2000048; P:negative regulation of cell-cell adhesion mediated by cadherin; IMP:BHF-UCL.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IDA:BHF-UCL.
DR GO; GO:2000042; P:negative regulation of double-strand break repair via homologous recombination; IDA:UniProtKB.
DR GO; GO:0010719; P:negative regulation of epithelial to mesenchymal transition; IMP:BHF-UCL.
DR GO; GO:0042177; P:negative regulation of protein catabolic process; IDA:UniProtKB.
DR GO; GO:0010944; P:negative regulation of transcription by competitive promoter binding; IMP:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:2000678; P:negative regulation of transcription regulatory region DNA binding; IMP:BHF-UCL.
DR GO; GO:1904667; P:negative regulation of ubiquitin protein ligase activity; IDA:UniProtKB.
DR GO; GO:2001034; P:positive regulation of double-strand break repair via nonhomologous end joining; IDA:UniProtKB.
DR GO; GO:0045830; P:positive regulation of isotype switching; IDA:UniProtKB.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0001558; P:regulation of cell growth; IGI:UniProtKB.
DR GO; GO:0002208; P:somatic diversification of immunoglobulins involved in immune response; IC:ComplexPortal.
DR GO; GO:0043247; P:telomere maintenance in response to DNA damage; IC:ComplexPortal.
DR Gene3D; 3.30.900.10; -; 1.
DR IDEAL; IID00285; -.
DR InterPro; IPR003511; HORMA_dom.
DR InterPro; IPR036570; HORMA_dom_sf.
DR InterPro; IPR045091; Mad2-like.
DR PANTHER; PTHR11842; PTHR11842; 1.
DR Pfam; PF02301; HORMA; 1.
DR SUPFAM; SSF56019; SSF56019; 1.
DR PROSITE; PS50815; HORMA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell cycle; Cell division; Chromosome; Cytoplasm;
KW Cytoskeleton; Disease variant; DNA damage; DNA repair; Fanconi anemia;
KW Mitosis; Nucleus; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..211
FT /note="Mitotic spindle assembly checkpoint protein MAD2B"
FT /id="PRO_0000126119"
FT DOMAIN 13..203
FT /note="HORMA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00109"
FT REGION 21..155
FT /note="Mediates interaction with REV1 and REV3L and
FT homodimerization"
FT REGION 150..211
FT /note="Mediates interaction with ipaB"
FT VARIANT 85
FT /note="V -> E (in FANCV; drastically reduced protein
FT abundance; dbSNP:rs1057517674)"
FT /evidence="ECO:0000269|PubMed:27500492"
FT /id="VAR_077981"
FT MUTAGEN 63
FT /note="Y->A: Alters interaction with REV3L. Loss of
FT interaction with REV3L; when associated with A-171."
FT /evidence="ECO:0000269|PubMed:20164194"
FT MUTAGEN 124
FT /note="R->A: Induces structural changes that increase
FT affinity for REV3L and REV1. No effect on interaction with
FT REV1; when associated with A-171."
FT /evidence="ECO:0000269|PubMed:20164194"
FT MUTAGEN 171
FT /note="W->A: Alters interaction with REV3L and REV1. Loss
FT of interaction with REV3L; when associated with A-63. No
FT effect on interaction with REV1; when associated with A-
FT 124."
FT /evidence="ECO:0000269|PubMed:20164194"
FT MUTAGEN 186
FT /note="L->A: Significantly prevents interaction with REV1;
FT no effect on interaction with REV3L."
FT /evidence="ECO:0000269|PubMed:20164194"
FT MUTAGEN 200
FT /note="Q->A: Significantly prevents interaction with REV1;
FT no effect on interaction with REV3L."
FT /evidence="ECO:0000269|PubMed:20164194"
FT MUTAGEN 202
FT /note="Y->A: Significantly prevents interaction with REV1;
FT no effect on interaction with REV3L."
FT /evidence="ECO:0000269|PubMed:20164194"
FT CONFLICT 17
FT /note="D -> A (in Ref. 3; AAD30290)"
FT /evidence="ECO:0000305"
FT CONFLICT 96
FT /note="E -> D (in Ref. 2; AAF20267)"
FT /evidence="ECO:0000305"
FT CONFLICT 199
FT /note="M -> V (in Ref. 2; AAF20267)"
FT /evidence="ECO:0000305"
FT HELIX 6..8
FT /evidence="ECO:0007829|PDB:6BCD"
FT HELIX 10..12
FT /evidence="ECO:0007829|PDB:6BCD"
FT HELIX 13..33
FT /evidence="ECO:0007829|PDB:6BCD"
FT HELIX 39..41
FT /evidence="ECO:0007829|PDB:6BCD"
FT STRAND 42..47
FT /evidence="ECO:0007829|PDB:6BCD"
FT STRAND 50..55
FT /evidence="ECO:0007829|PDB:6BCD"
FT HELIX 58..76
FT /evidence="ECO:0007829|PDB:6BCD"
FT STRAND 80..88
FT /evidence="ECO:0007829|PDB:6BCD"
FT STRAND 90..92
FT /evidence="ECO:0007829|PDB:3ABE"
FT STRAND 94..103
FT /evidence="ECO:0007829|PDB:6BCD"
FT TURN 106..111
FT /evidence="ECO:0007829|PDB:5XPT"
FT STRAND 112..114
FT /evidence="ECO:0007829|PDB:6M7B"
FT TURN 115..118
FT /evidence="ECO:0007829|PDB:6BCD"
FT HELIX 119..131
FT /evidence="ECO:0007829|PDB:6BCD"
FT HELIX 133..135
FT /evidence="ECO:0007829|PDB:6BCD"
FT STRAND 145..155
FT /evidence="ECO:0007829|PDB:6BCD"
FT HELIX 156..159
FT /evidence="ECO:0007829|PDB:6M7B"
FT STRAND 162..166
FT /evidence="ECO:0007829|PDB:6BCD"
FT STRAND 169..173
FT /evidence="ECO:0007829|PDB:6BCD"
FT HELIX 176..179
FT /evidence="ECO:0007829|PDB:6BCD"
FT STRAND 185..196
FT /evidence="ECO:0007829|PDB:6BCD"
FT STRAND 198..205
FT /evidence="ECO:0007829|PDB:6BCD"
SQ SEQUENCE 211 AA; 24334 MW; 1DE6353EF7D650B9 CRC64;
MTTLTRQDLN FGQVVADVLC EFLEVAVHLI LYVREVYPVG IFQKRKKYNV PVQMSCHPEL
NQYIQDTLHC VKPLLEKNDV EKVVVVILDK EHRPVEKFVF EITQPPLLSI SSDSLLSHVE
QLLRAFILKI SVCDAVLDHN PPGCTFTVLV HTREAATRNM EKIQVIKDFP WILADEQDVH
MHDPRLIPLK TMTSDILKMQ LYVEERAHKG S
