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 27-MAR-2024, entry version 189. 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; 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; Q9H1P6: CIMIP1; NbExp=3; IntAct=EBI-77889, EBI-12155483; 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: sctE; 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 EMDB; EMD-23244; -. DR SASBDB; Q9UI95; -. DR SMR; Q9UI95; -. DR BioGRID; 115722; 334. 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; 9606-ENSP00000235310; -. DR PeptideAtlas; Q9UI95; -. DR ProteomicsDB; 84481; -. DR Pumba; Q9UI95; -. DR TopDownProteomics; Q9UI95; -. DR Antibodypedia; 3766; 231 antibodies from 30 providers. DR DNASU; 10459; -. DR Ensembl; ENST00000235310.7; ENSP00000235310.2; ENSG00000116670.16. DR Ensembl; ENST00000376667.7; ENSP00000365855.3; ENSG00000116670.16. DR Ensembl; ENST00000376692.9; ENSP00000365882.4; ENSG00000116670.16. DR Ensembl; ENST00000456915.2; ENSP00000400982.2; ENSG00000116670.16. 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 AGR; HGNC:6764; -. 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; 5384057at2759; -. 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; 716 hits in 1167 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 164 other cell types or tissues. DR ExpressionAtlas; Q9UI95; baseline and differential. DR GO; GO:0000785; C:chromatin; NAS:ComplexPortal. DR GO; GO:0005694; C:chromosome; IC:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0035861; C:site of double-strand break; NAS:ComplexPortal. 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:0045893; P:positive regulation of DNA-templated transcription; IMP:UniProtKB. DR GO; GO:2001034; P:positive regulation of double-strand break repair via nonhomologous end joining; IDA:UniProtKB. DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; IEA:Ensembl. DR GO; GO:1901203; P:positive regulation of extracellular matrix assembly; IEA:Ensembl. 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:0001558; P:regulation of cell growth; IGI:UniProtKB. DR GO; GO:0002208; P:somatic diversification of immunoglobulins involved in immune response; NAS:ComplexPortal. DR GO; GO:0043247; P:telomere maintenance in response to DNA damage; NAS:ComplexPortal. DR Gene3D; 3.30.900.10; HORMA domain; 1. DR IDEAL; IID00285; -. 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:SF10; MITOTIC SPINDLE ASSEMBLY CHECKPOINT PROTEIN MAD2B; 1. DR Pfam; PF02301; HORMA; 1. DR SUPFAM; SSF56019; The spindle assembly checkpoint protein mad2; 1. DR PROSITE; PS50815; HORMA; 1. DR Genevisible; Q9UI95; HS. 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 FT A-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 //