ID NIPBL_HUMAN Reviewed; 2804 AA. AC Q6KC79; Q6KCD6; Q6N080; Q6ZT92; Q7Z2E6; Q8N4M5; Q9Y6Y3; Q9Y6Y4; DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot. DT 19-JUL-2004, sequence version 2. DT 27-MAR-2024, entry version 192. DE RecName: Full=Nipped-B-like protein; DE AltName: Full=Delangin; DE AltName: Full=SCC2 homolog; GN Name=NIPBL; Synonyms=IDN3, SCC2 {ECO:0000303|PubMed:22628566}; 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] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, RP DEVELOPMENTAL STAGE, AND VARIANTS CDLS1 ILE-1206 DEL; ARG-1311; ARG-1348 RP AND CYS-2430. RX PubMed=15146185; DOI=10.1038/ng1363; RA Tonkin E.T., Wang T.-J., Lisgo S., Bamshad M.J., Strachan T.; RT "NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion RT proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome."; RL Nat. Genet. 36:636-641(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-1175. RC TISSUE=Endometrium; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 128-2804 (ISOFORM 3). RC TISSUE=Cerebellum; 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 [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 421-2804 (ISOFORMS 1 AND 2). RC TISSUE=Testis; RA Aihara T., Yasuo M., Kumiko K., Sasaki Y., Imaoka S., Monden M., RA Nakamura Y.; RL Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2411-2697 (ISOFORM 2). RC TISSUE=Urinary bladder; 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 [6] RP TISSUE SPECIFICITY, AND INVOLVEMENT IN CDLS1. RX PubMed=15146186; DOI=10.1038/ng1364; RA Krantz I.D., McCallum J., DeScipio C., Kaur M., Gillis L.A., Yaeger D., RA Jukofsky L., Wasserman N., Bottani A., Morris C.A., Nowaczyk M.J.M., RA Toriello H., Bamshad M.J., Carey J.C., Rappaport E., Kawauchi S., RA Lander A.D., Calof A.L., Li H.-H., Devoto M., Jackson L.G.; RT "Cornelia de Lange syndrome is caused by mutations in NIPBL, the human RT homolog of Drosophila melanogaster Nipped-B."; RL Nat. Genet. 36:631-635(2004). RN [7] RP INTERACTION WITH CBX5. RX PubMed=15882967; DOI=10.1016/j.bbrc.2005.04.016; RA Lechner M.S., Schultz D.C., Negorev D., Maul G.G., Rauscher F.J. III; RT "The mammalian heterochromatin protein 1 binds diverse nuclear proteins RT through a common motif that targets the chromoshadow domain."; RL Biochem. Biophys. Res. Commun. 331:929-937(2005). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-318; THR-713; THR-746; RP SER-1096; SER-2658 AND THR-2667, AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [9] RP INTERACTION WITH SCC4. RX PubMed=16682347; DOI=10.1016/j.cub.2006.03.049; RA Watrin E., Schleiffer A., Tanaka K., Eisenhaber F., Nasmyth K., RA Peters J.M.; RT "Human Scc4 is required for cohesin binding to chromatin, sister-chromatid RT cohesion, and mitotic progression."; RL Curr. Biol. 16:863-874(2006). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2658, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=16964243; DOI=10.1038/nbt1240; RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.; RT "A probability-based approach for high-throughput protein phosphorylation RT analysis and site localization."; RL Nat. Biotechnol. 24:1285-1292(2006). RN [11] RP INTERACTION WITH SCC4. RX PubMed=16802858; DOI=10.1371/journal.pbio.0040242; RA Seitan V.C., Banks P., Laval S., Majid N.A., Dorsett D., Rana A., Smith J., RA Bateman A., Krpic S., Hostert A., Rollins R.A., Erdjument-Bromage H., RA Tempst P., Benard C.Y., Hekimi S., Newbury S.F., Strachan T.; RT "Metazoan Scc4 homologs link sister chromatid cohesion to cell and axon RT migration guidance."; RL PLoS Biol. 4:E242-E242(2006). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., RA Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2658, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-150; SER-162; SER-306; RP SER-350; SER-912; SER-1089; SER-1090; SER-1096; SER-1150; SER-1152; RP SER-1154; SER-1160; SER-2509; SER-2511; SER-2513; SER-2515 AND SER-2658, RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-2667 AND SER-2672 (ISOFORM RP 2), AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2658, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1089; SER-1090; SER-1096; RP SER-1150 AND SER-2658, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [19] RP INTERACTION WITH CBX5, AND MUTAGENESIS OF VAL-1003 AND LEU-1005. RX PubMed=20562864; DOI=10.1038/ncb2075; RA Nozawa R.S., Nagao K., Masuda H.T., Iwasaki O., Hirota T., Nozaki N., RA Kimura H., Obuse C.; RT "Human POGZ modulates dissociation of HP1alpha from mitotic chromosome arms RT through Aurora B activation."; RL Nat. Cell Biol. 12:719-727(2010). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-256; SER-318; SER-350; RP SER-2658 AND SER-2672, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [21] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-350; SER-1096; SER-1150; RP SER-1152; SER-1154; SER-1160; SER-2509; SER-2511; SER-2513; SER-2515; RP SER-2658; THR-2667 AND SER-2672, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT RP SER-2672 (ISOFORM 2), AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [23] RP FUNCTION, AND INTERACTION WITH MAU2; HETERODIMER SMC1A-SMC3 AND THE COHESIN RP COMPLEX. RX PubMed=22628566; DOI=10.1073/pnas.1206840109; RA Bermudez V.P., Farina A., Higashi T.L., Du F., Tappin I., Takahashi T.S., RA Hurwitz J.; RT "In vitro loading of human cohesin on DNA by the human Scc2-Scc4 loader RT complex."; RL Proc. Natl. Acad. Sci. U.S.A. 109:9366-9371(2012). RN [24] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-150; SER-243; SER-274; RP SER-280; SER-306; SER-318; SER-350; SER-912; THR-1189; SER-1197; SER-2652; RP SER-2658; THR-2667 AND SER-2672, AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-280; SER-2658 AND SER-2672, RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2672 (ISOFORM 2), AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [26] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=28914604; DOI=10.7554/elife.30000; RA Rhodes J., Mazza D., Nasmyth K., Uphoff S.; RT "Scc2/Nipbl hops between chromosomal cohesin rings after loading."; RL Elife 6:0-0(2017). RN [27] {ECO:0007744|PDB:6WG3, ECO:0007744|PDB:6WGE} RP STRUCTURE BY ELECTRON MICROSCOPY (3.90 ANGSTROMS) OF 1163-2804, AND RP INTERACTION WITH THE COHESIN COMPLEX. RX PubMed=32409525; DOI=10.1126/science.abb0981; RA Shi Z., Gao H., Bai X.C., Yu H.; RT "Cryo-EM structure of the human cohesin-NIPBL-DNA complex."; RL Science 368:1454-1459(2020). RN [28] RP VARIANTS CDLS1 GLY-1246; PRO-1312; LEU-1789; VAL-1803; THR-1856; CYS-2298; RP HIS-2298; ARG-2312; ALA-2381; THR-2390 AND HIS-2440, AND VARIANTS SER-674 RP AND VAL-1206. RX PubMed=15318302; DOI=10.1086/424698; RA Gillis L.A., McCallum J., Kaur M., DeScipio C., Yaeger D., Mariani A., RA Kline A.D., Li H., Devoto M., Jackson L.G., Krantz I.D.; RT "NIPBL mutational analysis in 120 individuals with Cornelia de Lange RT syndrome and evaluation of genotype-phenotype correlations."; RL Am. J. Hum. Genet. 75:610-623(2004). RN [29] RP VARIANT [LARGE SCALE ANALYSIS] LYS-1647. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [30] RP VARIANTS CDLS1 ASN-1897 DEL; ALA-2081; ILE-2090 AND PRO-2150. RX PubMed=20358602; DOI=10.1002/ajmg.a.33348; RA Pie J., Gil-Rodriguez M.C., Ciero M., Lopez-Vinas E., Ribate M.P., RA Arnedo M., Deardorff M.A., Puisac B., Legarreta J., de Karam J.C., RA Rubio E., Bueno I., Baldellou A., Calvo M.T., Casals N., Olivares J.L., RA Losada A., Hegardt F.G., Krantz I.D., Gomez-Puertas P., Ramos F.J.; RT "Mutations and variants in the cohesion factor genes NIPBL, SMC1A, and SMC3 RT in a cohort of 30 unrelated patients with Cornelia de Lange syndrome."; RL Am. J. Med. Genet. A 152:924-929(2010). RN [31] RP VARIANTS CDLS1 LEU-73 AND PRO-1343. RX PubMed=20124326; RA Park H.D., Ki C.S., Kim J.W., Kim W.T., Kim J.K.; RT "Clinical and genetic analysis of Korean patients with Cornelia de Lange RT syndrome: two novel NIPBL mutations."; RL Ann. Clin. Lab. Sci. 40:20-25(2010). RN [32] RP VARIANTS CDLS1 ARG-15; GLN-29; THR-111; SER-179; THR-179; LEU-192; GLY-246 RP AND VAL-254, CHARACTERIZATION OF VARIANTS CDLS1 ARG-15; GLN-29; THR-111; RP SER-179; THR-179; LEU-192; GLY-246 AND VAL-254, AND INTERACTION WITH SCC4. RX PubMed=21934712; DOI=10.1038/ejhg.2011.175; RA Braunholz D., Hullings M., Gil-Rodriguez M.C., Fincher C.T., Mallozzi M.B., RA Loy E., Albrecht M., Kaur M., Limon J., Rampuria A., Clark D., Kline A., RA Dalski A., Eckhold J., Tzschach A., Hennekam R., Gillessen-Kaesbach G., RA Wierzba J., Krantz I.D., Deardorff M.A., Kaiser F.J.; RT "Isolated NIBPL missense mutations that cause Cornelia de Lange syndrome RT alter MAU2 interaction."; RL Eur. J. Hum. Genet. 20:271-276(2012). RN [33] RP VARIANTS CDLS1 ILE-70; SER-179; GLY-246; THR-351; ASN-357; GLN-868; RP LYS-1207; LEU-1441; PHE-1625; LEU-1637; HIS-1722; ASN-2218 DEL; CYS-2298; RP VAL-2312 AND ASN-2433. RX PubMed=23254390; DOI=10.1007/s13353-012-0126-9; RA Kuzniacka A., Wierzba J., Ratajska M., Lipska B.S., Koczkowska M., RA Malinowska M., Limon J.; RT "Spectrum of NIPBL gene mutations in Polish patients with Cornelia de Lange RT syndrome."; RL J. Appl. Genet. 54:27-33(2013). RN [34] RP VARIANT CDLS1 PHE-2091. RX PubMed=25447906; DOI=10.1016/j.gene.2014.11.033; RA Mei L., Liang D., Huang Y., Pan Q., Wu L.; RT "Two novel NIPBL gene mutations in Chinese patients with Cornelia de Lange RT syndrome."; RL Gene 555:476-480(2015). RN [35] RP CHARACTERIZATION OF VARIANT CDLS1 ARG-15, FUNCTION, SUBCELLULAR LOCATION, RP INTERACTION WITH SCC4 AND CBX3, MUTAGENESIS OF VAL-1003 AND LEU-1005, AND RP MOTIF PXVXL. RX PubMed=28167679; DOI=10.1242/jcs.197236; RA Bot C., Pfeiffer A., Giordano F., Manjeera D.E., Dantuma N.P., Stroem L.; RT "Independent mechanisms recruit the cohesin loader protein NIPBL to sites RT of DNA damage."; RL J. Cell Sci. 130:1134-1146(2017). CC -!- FUNCTION: Plays an important role in the loading of the cohesin complex CC on to DNA. Forms a heterodimeric complex (also known as cohesin loading CC complex) with MAU2/SCC4 which mediates the loading of the cohesin CC complex onto chromatin (PubMed:22628566, PubMed:28914604). Plays a role CC in cohesin loading at sites of DNA damage. Its recruitment to double- CC strand breaks (DSBs) sites occurs in a CBX3-, RNF8- and RNF168- CC dependent manner whereas its recruitment to UV irradiation-induced DNA CC damage sites occurs in a ATM-, ATR-, RNF8- and RNF168-dependent manner CC (PubMed:28167679). Along with ZNF609, promotes cortical neuron CC migration during brain development by regulating the transcription of CC crucial genes in this process. Preferentially binds promoters CC containing paused RNA polymerase II. Up-regulates the expression of CC SEMA3A, NRP1, PLXND1 and GABBR2 genes, among others (By similarity). CC {ECO:0000250|UniProtKB:Q6KCD5, ECO:0000269|PubMed:22628566, CC ECO:0000269|PubMed:28167679, ECO:0000269|PubMed:28914604}. CC -!- SUBUNIT: Heterodimerizes with MAU2/SCC4 to form the cohesin loading CC complex (PubMed:16682347, PubMed:16802858, PubMed:21934712, CC PubMed:28167679, PubMed:22628566). The NIPBL-MAU2 heterodimer interacts CC with the cohesin complex composed of SMC1A/B and SMC3 heterodimer, CC RAD21 and STAG1/SA1 (PubMed:22628566). NIPBL directly contacts all CC members of the complex, RAD21, SMC1A/B, SMC3 and STAG1 CC (PubMed:32409525). Interacts directly (via PxVxL motif) with CBX5 CC (PubMed:15882967, PubMed:20562864). Interacts with ZNF609 (via N- CC terminus) (By similarity). Interacts with the multiprotein complex CC Integrator (By similarity). Interacts (via PxVxL motif) with CBX3 CC (PubMed:28167679). {ECO:0000250|UniProtKB:Q6KCD5, CC ECO:0000269|PubMed:15882967, ECO:0000269|PubMed:16682347, CC ECO:0000269|PubMed:16802858, ECO:0000269|PubMed:20562864, CC ECO:0000269|PubMed:21934712, ECO:0000269|PubMed:22628566, CC ECO:0000269|PubMed:28167679, ECO:0000269|PubMed:32409525}. CC -!- INTERACTION: CC Q6KC79; Q9Y6X3: MAU2; NbExp=7; IntAct=EBI-722767, EBI-4395624; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:28167679, CC ECO:0000269|PubMed:28914604}. Chromosome CC {ECO:0000250|UniProtKB:Q6KCD5}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; Synonyms=A, IDN3-A; CC IsoId=Q6KC79-1; Sequence=Displayed; CC Name=2; Synonyms=B, IDN3-B; CC IsoId=Q6KC79-2; Sequence=VSP_011092, VSP_011093; CC Name=3; CC IsoId=Q6KC79-3; Sequence=VSP_011091; CC -!- TISSUE SPECIFICITY: Widely expressed. Highly expressed in heart, CC skeletal muscle, fetal and adult liver, fetal and adult kidney. CC Expressed at intermediates level in thymus, placenta, peripheral CC leukocyte and small intestine. Weakly or not expressed in brain, colon, CC spleen and lung. {ECO:0000269|PubMed:15146185, CC ECO:0000269|PubMed:15146186}. CC -!- DEVELOPMENTAL STAGE: In embryos, it is expressed in developing limbs CC and later in cartilage primordia of the ulna and of various hand bones. CC Sites of craniofacial expression include the cartilage primordium of CC the basioccipital and basisphenoid skull bones and elsewhere in the CC head and face, including a region encompassing the mesenchyme adjacent CC to the cochlear canal. Also expressed in the spinal column, notochord CC and surface ectoderm sclerotome and what seem to be migrating CC myoblasts. Expressed in the developing heart in the atrial and CC ventricular myocardium and in the ventricular tubeculae but absent in CC the endocardial cushions. Also expressed in the developing esophagus, CC trachea and midgut loops, in the bronchi of the lung and in the tubules CC of the metanephros. Expression in organs and tissues not typically CC affected in CDL (e.g. the developing trachea, bronchi, esophagus, heart CC and kidney) may reflect a bias towards underreporting of more subtle CC aspects of the phenotype or problems that typically present later in CC life. Expressed in the mesenchyme surrounding the cochlear canal CC possibly reflecting the hearing impairment commonly found. Weakly or CC not expressed in embryonic brain. {ECO:0000269|PubMed:15146185}. CC -!- DOMAIN: Contains one Pro-Xaa-Val-Xaa-Leu (PxVxL) motif, which is CC required for interaction with chromoshadow domains. This motif requires CC additional residues -7, -6, +4 and +5 of the central Val which contact CC the chromoshadow domain. {ECO:0000269|PubMed:20562864, CC ECO:0000269|PubMed:28167679}. CC -!- DOMAIN: The C-terminal region containing HEAT repeats and Pro-Xaa-Val- CC Xaa-Leu (PxVxL) motif are involved in the recruitment of NIPBL to sites CC of DNA damage. {ECO:0000269|PubMed:28167679}. CC -!- DISEASE: Cornelia de Lange syndrome 1 (CDLS1) [MIM:122470]: A form of CC Cornelia de Lange syndrome, a clinically heterogeneous developmental CC disorder associated with malformations affecting multiple systems. CC Characterized by facial dysmorphisms, abnormal hands and feet, growth CC delay, cognitive retardation, hirsutism, gastroesophageal dysfunction CC and cardiac, ophthalmologic and genitourinary anomalies. CC {ECO:0000269|PubMed:15146185, ECO:0000269|PubMed:15146186, CC ECO:0000269|PubMed:15318302, ECO:0000269|PubMed:20124326, CC ECO:0000269|PubMed:20358602, ECO:0000269|PubMed:21934712, CC ECO:0000269|PubMed:23254390, ECO:0000269|PubMed:25447906, CC ECO:0000269|PubMed:28167679}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the SCC2/Nipped-B family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH33847.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=BAA77335.1; Type=Miscellaneous discrepancy; Note=Chimeric cDNA.; Evidence={ECO:0000305}; CC Sequence=BAA77349.1; Type=Miscellaneous discrepancy; Note=Chimeric cDNA.; Evidence={ECO:0000305}; CC Sequence=BAC86701.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=CAE45790.1; Type=Frameshift; Evidence={ECO:0000305}; 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; AJ627032; CAF25290.1; -; mRNA. DR EMBL; AJ640137; CAG26691.1; -; mRNA. DR EMBL; BX538177; CAD98051.1; -; mRNA. DR EMBL; BX538178; CAD98052.1; -; mRNA. DR EMBL; BX640644; CAE45790.1; ALT_FRAME; mRNA. DR EMBL; AK126804; BAC86701.1; ALT_INIT; mRNA. DR EMBL; AB019494; BAA77335.1; ALT_SEQ; mRNA. DR EMBL; AB019602; BAA77349.1; ALT_SEQ; mRNA. DR EMBL; BC033847; AAH33847.1; ALT_INIT; mRNA. DR CCDS; CCDS3920.1; -. [Q6KC79-1] DR CCDS; CCDS47198.1; -. [Q6KC79-2] DR RefSeq; NP_056199.2; NM_015384.4. [Q6KC79-2] DR RefSeq; NP_597677.2; NM_133433.3. [Q6KC79-1] DR RefSeq; XP_016864819.1; XM_017009330.1. DR PDB; 6WG3; EM; 5.30 A; E=1163-2804. DR PDB; 6WGE; EM; 3.90 A; E=1163-2804. DR PDB; 7W1M; EM; 6.50 A; E=1164-2630. DR PDBsum; 6WG3; -. DR PDBsum; 6WGE; -. DR PDBsum; 7W1M; -. DR EMDB; EMD-21658; -. DR EMDB; EMD-21663; -. DR EMDB; EMD-32252; -. DR SMR; Q6KC79; -. DR BioGRID; 117363; 183. DR ComplexPortal; CPX-8070; SCC2-SCC4 cohesin loader complex. DR DIP; DIP-29199N; -. DR IntAct; Q6KC79; 52. DR MINT; Q6KC79; -. DR STRING; 9606.ENSP00000282516; -. DR GlyCosmos; Q6KC79; 8 sites, 1 glycan. DR GlyGen; Q6KC79; 15 sites, 1 O-linked glycan (15 sites). DR iPTMnet; Q6KC79; -. DR PhosphoSitePlus; Q6KC79; -. DR SwissPalm; Q6KC79; -. DR BioMuta; NIPBL; -. DR DMDM; 50400865; -. DR EPD; Q6KC79; -. DR jPOST; Q6KC79; -. DR MassIVE; Q6KC79; -. DR MaxQB; Q6KC79; -. DR PaxDb; 9606-ENSP00000282516; -. DR PeptideAtlas; Q6KC79; -. DR ProteomicsDB; 66538; -. [Q6KC79-1] DR ProteomicsDB; 66539; -. [Q6KC79-2] DR ProteomicsDB; 66540; -. [Q6KC79-3] DR Pumba; Q6KC79; -. DR Antibodypedia; 10283; 218 antibodies from 34 providers. DR CPTC; Q6KC79; 1 antibody. DR DNASU; 25836; -. DR Ensembl; ENST00000282516.13; ENSP00000282516.8; ENSG00000164190.19. [Q6KC79-1] DR Ensembl; ENST00000448238.2; ENSP00000406266.2; ENSG00000164190.19. [Q6KC79-2] DR GeneID; 25836; -. DR KEGG; hsa:25836; -. DR MANE-Select; ENST00000282516.13; ENSP00000282516.8; NM_133433.4; NP_597677.2. DR UCSC; uc003jkk.5; human. [Q6KC79-1] DR AGR; HGNC:28862; -. DR CTD; 25836; -. DR DisGeNET; 25836; -. DR GeneCards; NIPBL; -. DR GeneReviews; NIPBL; -. DR HGNC; HGNC:28862; NIPBL. DR HPA; ENSG00000164190; Low tissue specificity. DR MalaCards; NIPBL; -. DR MIM; 122470; phenotype. DR MIM; 608667; gene. DR neXtProt; NX_Q6KC79; -. DR OpenTargets; ENSG00000164190; -. DR Orphanet; 329802; 5p13 microduplication syndrome. DR Orphanet; 199; Cornelia de Lange syndrome. DR PharmGKB; PA134962343; -. DR VEuPathDB; HostDB:ENSG00000164190; -. DR eggNOG; KOG1020; Eukaryota. DR GeneTree; ENSGT00390000010427; -. DR HOGENOM; CLU_000763_0_0_1; -. DR InParanoid; Q6KC79; -. DR OMA; KQNENRM; -. DR OrthoDB; 1409889at2759; -. DR PhylomeDB; Q6KC79; -. DR TreeFam; TF313121; -. DR PathwayCommons; Q6KC79; -. DR Reactome; R-HSA-2470946; Cohesin Loading onto Chromatin. DR SignaLink; Q6KC79; -. DR SIGNOR; Q6KC79; -. DR BioGRID-ORCS; 25836; 290 hits in 1165 CRISPR screens. DR ChiTaRS; NIPBL; human. DR GeneWiki; NIPBL; -. DR GenomeRNAi; 25836; -. DR Pharos; Q6KC79; Tbio. DR PRO; PR:Q6KC79; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; Q6KC79; Protein. DR Bgee; ENSG00000164190; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 196 other cell types or tissues. DR ExpressionAtlas; Q6KC79; baseline and differential. DR GO; GO:0000785; C:chromatin; IEA:Ensembl. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0032039; C:integrator complex; ISS:UniProtKB. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0090694; C:Scc2-Scc4 cohesin loading complex; IDA:UniProtKB. DR GO; GO:0032116; C:SMC loading complex; IDA:UniProtKB. DR GO; GO:0003682; F:chromatin binding; IBA:GO_Central. DR GO; GO:0070087; F:chromo shadow domain binding; IPI:BHF-UCL. DR GO; GO:0061775; F:cohesin loader activity; IMP:UniProtKB. DR GO; GO:0042826; F:histone deacetylase binding; IPI:BHF-UCL. DR GO; GO:0036033; F:mediator complex binding; IEA:Ensembl. DR GO; GO:1990841; F:promoter-specific chromatin binding; ISS:ARUK-UCL. DR GO; GO:0003714; F:transcription corepressor activity; IDA:BHF-UCL. DR GO; GO:0007420; P:brain development; IMP:BHF-UCL. DR GO; GO:0071481; P:cellular response to X-ray; IMP:UniProtKB. DR GO; GO:0006338; P:chromatin remodeling; IDA:BHF-UCL. DR GO; GO:0050890; P:cognition; IMP:BHF-UCL. DR GO; GO:0048589; P:developmental growth; IMP:BHF-UCL. DR GO; GO:0048565; P:digestive tract development; IBA:GO_Central. DR GO; GO:0006974; P:DNA damage response; IMP:UniProtKB. DR GO; GO:0042471; P:ear morphogenesis; IMP:BHF-UCL. DR GO; GO:0048557; P:embryonic digestive tract morphogenesis; IMP:BHF-UCL. DR GO; GO:0035115; P:embryonic forelimb morphogenesis; IMP:BHF-UCL. DR GO; GO:0048703; P:embryonic viscerocranium morphogenesis; IBA:GO_Central. DR GO; GO:0034087; P:establishment of mitotic sister chromatid cohesion; IBA:GO_Central. DR GO; GO:0071169; P:establishment of protein localization to chromatin; IBA:GO_Central. DR GO; GO:0035261; P:external genitalia morphogenesis; IMP:BHF-UCL. DR GO; GO:0048592; P:eye morphogenesis; IMP:BHF-UCL. DR GO; GO:0060325; P:face morphogenesis; IMP:BHF-UCL. DR GO; GO:0045444; P:fat cell differentiation; IEA:Ensembl. DR GO; GO:0035136; P:forelimb morphogenesis; IMP:BHF-UCL. DR GO; GO:0061010; P:gallbladder development; IMP:BHF-UCL. DR GO; GO:0003007; P:heart morphogenesis; IMP:BHF-UCL. DR GO; GO:0034088; P:maintenance of mitotic sister chromatid cohesion; IMP:UniProtKB. DR GO; GO:0001656; P:metanephros development; NAS:BHF-UCL. DR GO; GO:0061780; P:mitotic cohesin loading; IEA:InterPro. DR GO; GO:0007064; P:mitotic sister chromatid cohesion; IDA:UniProtKB. DR GO; GO:0000070; P:mitotic sister chromatid segregation; IEA:Ensembl. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL. DR GO; GO:0003151; P:outflow tract morphogenesis; IMP:BHF-UCL. DR GO; GO:0040018; P:positive regulation of multicellular organism growth; IEA:Ensembl. DR GO; GO:2001224; P:positive regulation of neuron migration; ISS:UniProtKB. DR GO; GO:0045778; P:positive regulation of ossification; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl. DR GO; GO:0008104; P:protein localization; IMP:UniProtKB. DR GO; GO:0048638; P:regulation of developmental growth; IMP:BHF-UCL. DR GO; GO:0045995; P:regulation of embryonic development; IMP:BHF-UCL. DR GO; GO:0042634; P:regulation of hair cycle; IMP:BHF-UCL. DR GO; GO:1990414; P:replication-born double-strand break repair via sister chromatid exchange; IBA:GO_Central. DR GO; GO:0007605; P:sensory perception of sound; IMP:BHF-UCL. DR GO; GO:0035019; P:somatic stem cell population maintenance; IEA:Ensembl. DR GO; GO:0061038; P:uterus morphogenesis; IMP:BHF-UCL. DR Gene3D; 1.25.10.10; Leucine-rich Repeat Variant; 2. DR InterPro; IPR011989; ARM-like. DR InterPro; IPR016024; ARM-type_fold. DR InterPro; IPR026003; Cohesin_HEAT. DR InterPro; IPR024986; Nipped-B_C. DR InterPro; IPR033031; Scc2/Nipped-B. DR PANTHER; PTHR21704:SF18; NIPPED-B-LIKE PROTEIN; 1. DR PANTHER; PTHR21704; NIPPED-B-LIKE PROTEIN DELANGIN SCC2-RELATED; 1. DR Pfam; PF12765; Cohesin_HEAT; 1. DR Pfam; PF12830; Nipped-B_C; 1. DR SUPFAM; SSF48371; ARM repeat; 1. DR Genevisible; Q6KC79; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activator; Alternative splicing; Cell cycle; KW Chromosome; Developmental protein; Disease variant; KW Intellectual disability; Nucleus; Phosphoprotein; Reference proteome; KW Repeat; Transcription; Transcription regulation. FT CHAIN 1..2804 FT /note="Nipped-B-like protein" FT /id="PRO_0000218596" FT REPEAT 1767..1805 FT /note="HEAT 1" FT REPEAT 1843..1881 FT /note="HEAT 2" FT REPEAT 1945..1984 FT /note="HEAT 3" FT REPEAT 2227..2267 FT /note="HEAT 4" FT REPEAT 2313..2351 FT /note="HEAT 5" FT REGION 128..340 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 482..946 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1017..1047 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1060..1191 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1691..1710 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2473..2520 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2651..2696 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 996..1009 FT /note="PxVxL motif" FT /evidence="ECO:0000269|PubMed:20562864, FT ECO:0000269|PubMed:28167679" FT COMPBIAS 128..172 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 187..210 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 223..237 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 238..259 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 314..340 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 482..510 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 519..537 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 595..659 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 660..674 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 692..936 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1031..1045 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1067..1090 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1098..1143 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2676..2693 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 150 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 162 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 243 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 256 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 274 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 280 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 284 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6KCD5" FT MOD_RES 301 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6KCD5" FT MOD_RES 306 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 318 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT MOD_RES 350 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 713 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:17081983" FT MOD_RES 746 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:17081983" FT MOD_RES 912 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1082 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q6KCD5" FT MOD_RES 1089 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332" FT MOD_RES 1090 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332" FT MOD_RES 1096 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:21406692" FT MOD_RES 1150 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692" FT MOD_RES 1152 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:21406692" FT MOD_RES 1154 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:21406692" FT MOD_RES 1159 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q6KCD5" FT MOD_RES 1160 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:21406692" FT MOD_RES 1189 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1197 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 2493 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6KCD5" FT MOD_RES 2509 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:21406692" FT MOD_RES 2511 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:21406692" FT MOD_RES 2513 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:21406692" FT MOD_RES 2515 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:21406692" FT MOD_RES 2652 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 2658 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:16964243, FT ECO:0007744|PubMed:17081983, ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 2667 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 2672 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT VAR_SEQ 1102..2804 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_011091" FT VAR_SEQ 2684..2697 FT /note="SLRRSKRNSDSTEL -> VRRRRSQRISQRIT (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15146185, FT ECO:0000303|PubMed:15489334, ECO:0000303|Ref.4" FT /id="VSP_011092" FT VAR_SEQ 2698..2804 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15146185, FT ECO:0000303|PubMed:15489334, ECO:0000303|Ref.4" FT /id="VSP_011093" FT VARIANT 15 FT /note="G -> R (in CDLS1; strongly inhibits interaction with FT SCC4)" FT /evidence="ECO:0000269|PubMed:21934712, FT ECO:0000269|PubMed:28167679" FT /id="VAR_072996" FT VARIANT 29 FT /note="P -> Q (in CDLS1; strongly inhibits interaction with FT SCC4)" FT /evidence="ECO:0000269|PubMed:21934712" FT /id="VAR_072997" FT VARIANT 70 FT /note="N -> I (in CDLS1)" FT /evidence="ECO:0000269|PubMed:23254390" FT /id="VAR_072998" FT VARIANT 73 FT /note="S -> L (in CDLS1; uncertain significance)" FT /evidence="ECO:0000269|PubMed:20124326" FT /id="VAR_072999" FT VARIANT 111 FT /note="S -> T (in CDLS1; no effect on interaction with FT SCC4)" FT /evidence="ECO:0000269|PubMed:21934712" FT /id="VAR_073000" FT VARIANT 135 FT /note="S -> N (in dbSNP:rs1390490298)" FT /id="VAR_019518" FT VARIANT 179 FT /note="A -> S (in CDLS1; no effect on interaction with FT SCC4)" FT /evidence="ECO:0000269|PubMed:21934712, FT ECO:0000269|PubMed:23254390" FT /id="VAR_073001" FT VARIANT 179 FT /note="A -> T (in CDLS1; benign; no effect on interaction FT with SCC4; dbSNP:rs142923613)" FT /evidence="ECO:0000269|PubMed:21934712" FT /id="VAR_073002" FT VARIANT 192 FT /note="P -> L (in CDLS1; no effect on interaction with FT SCC4)" FT /evidence="ECO:0000269|PubMed:21934712" FT /id="VAR_073003" FT VARIANT 246 FT /note="D -> G (in CDLS1; no effect on interaction with FT SCC4; dbSNP:rs587784042)" FT /evidence="ECO:0000269|PubMed:21934712, FT ECO:0000269|PubMed:23254390" FT /id="VAR_073004" FT VARIANT 254 FT /note="L -> V (in CDLS1; no effect on interaction with FT SCC4)" FT /evidence="ECO:0000269|PubMed:21934712" FT /id="VAR_073005" FT VARIANT 261 FT /note="S -> A (in dbSNP:rs16903425)" FT /id="VAR_038411" FT VARIANT 351 FT /note="P -> T (in CDLS1)" FT /evidence="ECO:0000269|PubMed:23254390" FT /id="VAR_073006" FT VARIANT 357 FT /note="K -> N (in CDLS1)" FT /evidence="ECO:0000269|PubMed:23254390" FT /id="VAR_073007" FT VARIANT 384 FT /note="N -> S (in dbSNP:rs2291703)" FT /id="VAR_038412" FT VARIANT 674 FT /note="N -> S (in dbSNP:rs3822471)" FT /evidence="ECO:0000269|PubMed:15318302" FT /id="VAR_021596" FT VARIANT 868 FT /note="R -> Q (in CDLS1; dbSNP:rs149629686)" FT /evidence="ECO:0000269|PubMed:23254390" FT /id="VAR_073008" FT VARIANT 1206 FT /note="I -> V (in dbSNP:rs587783929)" FT /evidence="ECO:0000269|PubMed:15318302" FT /id="VAR_021597" FT VARIANT 1206 FT /note="Missing (in CDLS1; dbSNP:rs121918266)" FT /evidence="ECO:0000269|PubMed:15146185" FT /id="VAR_038413" FT VARIANT 1207 FT /note="E -> K (in CDLS1)" FT /evidence="ECO:0000269|PubMed:23254390" FT /id="VAR_073009" FT VARIANT 1246 FT /note="A -> G (in CDLS1; dbSNP:rs121918268)" FT /evidence="ECO:0000269|PubMed:15318302" FT /id="VAR_021598" FT VARIANT 1311 FT /note="C -> R (in CDLS1)" FT /evidence="ECO:0000269|PubMed:15146185" FT /id="VAR_019519" FT VARIANT 1312 FT /note="L -> P (in CDLS1)" FT /evidence="ECO:0000269|PubMed:15318302" FT /id="VAR_021599" FT VARIANT 1343 FT /note="H -> P (in CDLS1)" FT /evidence="ECO:0000269|PubMed:20124326" FT /id="VAR_073010" FT VARIANT 1348 FT /note="L -> R (in CDLS1)" FT /evidence="ECO:0000269|PubMed:15146185" FT /id="VAR_019520" FT VARIANT 1441 FT /note="V -> L (in CDLS1; dbSNP:rs727503769)" FT /evidence="ECO:0000269|PubMed:23254390" FT /id="VAR_073011" FT VARIANT 1625 FT /note="V -> F (in CDLS1)" FT /evidence="ECO:0000269|PubMed:23254390" FT /id="VAR_073012" FT VARIANT 1637 FT /note="I -> L (in CDLS1)" FT /evidence="ECO:0000269|PubMed:23254390" FT /id="VAR_073013" FT VARIANT 1647 FT /note="E -> K (in a breast cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036164" FT VARIANT 1722 FT /note="N -> H (in CDLS1)" FT /evidence="ECO:0000269|PubMed:23254390" FT /id="VAR_073014" FT VARIANT 1789 FT /note="R -> L (in CDLS1)" FT /evidence="ECO:0000269|PubMed:15318302" FT /id="VAR_021600" FT VARIANT 1803 FT /note="D -> V (in CDLS1)" FT /evidence="ECO:0000269|PubMed:15318302" FT /id="VAR_021601" FT VARIANT 1856 FT /note="R -> T (in CDLS1)" FT /evidence="ECO:0000269|PubMed:15318302" FT /id="VAR_021602" FT VARIANT 1897 FT /note="Missing (in CDLS1)" FT /evidence="ECO:0000269|PubMed:20358602" FT /id="VAR_064544" FT VARIANT 2081 FT /note="G -> A (in CDLS1; dbSNP:rs587784000)" FT /evidence="ECO:0000269|PubMed:20358602" FT /id="VAR_064545" FT VARIANT 2090 FT /note="S -> I (in CDLS1)" FT /evidence="ECO:0000269|PubMed:20358602" FT /id="VAR_064546" FT VARIANT 2091 FT /note="C -> F (in CDLS1)" FT /evidence="ECO:0000269|PubMed:25447906" FT /id="VAR_073015" FT VARIANT 2150 FT /note="L -> P (in CDLS1)" FT /evidence="ECO:0000269|PubMed:20358602" FT /id="VAR_064547" FT VARIANT 2218 FT /note="Missing (in CDLS1)" FT /evidence="ECO:0000269|PubMed:23254390" FT /id="VAR_073016" FT VARIANT 2298 FT /note="R -> C (in CDLS1; dbSNP:rs80358376)" FT /evidence="ECO:0000269|PubMed:15318302, FT ECO:0000269|PubMed:23254390" FT /id="VAR_021603" FT VARIANT 2298 FT /note="R -> H (in CDLS1; dbSNP:rs587784024)" FT /evidence="ECO:0000269|PubMed:15318302" FT /id="VAR_021604" FT VARIANT 2312 FT /note="G -> R (in CDLS1)" FT /evidence="ECO:0000269|PubMed:15318302" FT /id="VAR_021605" FT VARIANT 2312 FT /note="G -> V (in CDLS1; dbSNP:rs587784025)" FT /evidence="ECO:0000269|PubMed:23254390" FT /id="VAR_073017" FT VARIANT 2381 FT /note="G -> A (in CDLS1)" FT /evidence="ECO:0000269|PubMed:15318302" FT /id="VAR_021606" FT VARIANT 2390 FT /note="A -> T (in CDLS1; dbSNP:rs587784036)" FT /evidence="ECO:0000269|PubMed:15318302" FT /id="VAR_021607" FT VARIANT 2430 FT /note="Y -> C (in CDLS1; dbSNP:rs121918265)" FT /evidence="ECO:0000269|PubMed:15146185" FT /id="VAR_019521" FT VARIANT 2433 FT /note="D -> N (in CDLS1)" FT /evidence="ECO:0000269|PubMed:23254390" FT /id="VAR_073018" FT VARIANT 2440 FT /note="Y -> H (in CDLS1)" FT /evidence="ECO:0000269|PubMed:15318302" FT /id="VAR_021608" FT MUTAGEN 1003 FT /note="V->A: Abolishes interaction with CBX3; when FT associated with A-1005." FT /evidence="ECO:0000269|PubMed:20562864, FT ECO:0000269|PubMed:28167679" FT MUTAGEN 1003 FT /note="V->E: Abolishes interaction with CBX5; when FT associated with E-1005." FT /evidence="ECO:0000269|PubMed:20562864" FT MUTAGEN 1005 FT /note="L->A: Abolishes interaction with CBX3; when FT associated with A-1003." FT /evidence="ECO:0000269|PubMed:20562864" FT MUTAGEN 1005 FT /note="L->E: Abolishes interaction with CBX5; when FT associated with E-1003." FT /evidence="ECO:0000269|PubMed:20562864" FT CONFLICT 318 FT /note="S -> F (in Ref. 3)" FT /evidence="ECO:0000305" FT CONFLICT 548 FT /note="A -> T (in Ref. 2; CAD98051/CAD98052)" FT /evidence="ECO:0000305" FT CONFLICT 574 FT /note="N -> S (in Ref. 2; CAD98051/CAD98052)" FT /evidence="ECO:0000305" FT CONFLICT 648 FT /note="T -> I (in Ref. 2; CAD98051/CAD98052)" FT /evidence="ECO:0000305" FT CONFLICT 1172 FT /note="M -> K (in Ref. 2; CAD98051/CAD98052)" FT /evidence="ECO:0000305" FT MOD_RES Q6KC79-2:2667 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES Q6KC79-2:2672 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:24275569" SQ SEQUENCE 2804 AA; 316051 MW; C275425DF53058A3 CRC64; MNGDMPHVPI TTLAGIASLT DLLNQLPLPS PLPATTTKSL LFNARIAEEV NCLLACRDDN LVSQLVHSLN QVSTDHIELK DNLGSDDPEG DIPVLLQAVL ARSPNVFREK SMQNRYVQSG MMMSQYKLSQ NSMHSSPASS NYQQTTISHS PSSRFVPPQT SSGNRFMPQQ NSPVPSPYAP QSPAGYMPYS HPSSYTTHPQ MQQASVSSPI VAGGLRNIHD NKVSGPLSGN SANHHADNPR HGSSEDYLHM VHRLSSDDGD SSTMRNAASF PLRSPQPVCS PAGSEGTPKG SRPPLILQSQ SLPCSSPRDV PPDILLDSPE RKQKKQKKMK LGKDEKEQSE KAAMYDIISS PSKDSTKLTL RLSRVRSSDM DQQEDMISGV ENSNVSENDI PFNVQYPGQT SKTPITPQDI NRPLNAAQCL SQQEQTAFLP ANQVPVLQQN TSVAAKQPQT SVVQNQQQIS QQGPIYDEVE LDALAEIERI ERESAIERER FSKEVQDKDK PLKKRKQDSY PQEAGGATGG NRPASQETGS TGNGSRPALM VSIDLHQAGR VDSQASITQD SDSIKKPEEI KQCNDAPVSV LQEDIVGSLK STPENHPETP KKKSDPELSK SEMKQSESRL AESKPNENRL VETKSSENKL ETKVETQTEE LKQNESRTTE CKQNESTIVE PKQNENRLSD TKPNDNKQNN GRSETTKSRP ETPKQKGESR PETPKQKSDG HPETPKQKGD GRPETPKQKG ESRPETPKQK NEGRPETPKH RHDNRRDSGK PSTEKKPEVS KHKQDTKSDS PRLKSERAEA LKQRPDGRSV SESLRRDHDN KQKSDDRGES ERHRGDQSRV RRPETLRSSS RNEHGIKSDS SKTDKLERKH RHESGDSRER PSSGEQKSRP DSPRVKQGDS NKSRSDKLGF KSPTSKDDKR TEGNKSKVDT NKAHPDNKAE FPSYLLGGRS GALKNFVIPK IKRDKDGNVT QETKKMEMKG EPKDKVEKIG LVEDLNKGAK PVVVLQKLSL DDVQKLIKDR EDKSRSSLKP IKNKPSKSNK GSIDQSVLKE LPPELLAEIE STMPLCERVK MNKRKRSTVN EKPKYAEISS DEDNDSDEAF ESSRKRHKKD DDKAWEYEER DRRSSGDHRR SGHSHEGRRS SGGGRYRNRS PSDSDMEDYS PPPSLSEVAR KMKKKEKQKK RKAYEPKLTP EEMMDSSTFK RFTASIENIL DNLEDMDFTA FGDDDEIPQE LLLGKHQLNE LGSESAKIKA MGIMDKLSTD KTVKVLNILE KNIQDGSKLS TLLNHNNDTE EEERLWRDLI MERVTKSADA CLTTINIMTS PNMPKAVYIE DVIERVIQYT KFHLQNTLYP QYDPVYRLDP HGGGLLSSKA KRAKCSTHKQ RVIVMLYNKV CDIVSSLSEL LEIQLLTDTT ILQVSSMGIT PFFVENVSEL QLCAIKLVTA VFSRYEKHRQ LILEEIFTSL ARLPTSKRSL RNFRLNSSDM DGEPMYIQMV TALVLQLIQC VVHLPSSEKD SNAEEDSNKK IDQDVVITNS YETAMRTAQN FLSIFLKKCG SKQGEEDYRP LFENFVQDLL STVNKPEWPA AELLLSLLGR LLVHQFSNKS TEMALRVASL DYLGTVAARL RKDAVTSKMD QGSIERILKQ VSGGEDEIQQ LQKALLDYLD ENTETDPSLV FSRKFYIAQW FRDTTLETEK AMKSQKDEES SEGTHHAKEI ETTGQIMHRA ENRKKFLRSI IKTTPSQFST LKMNSDTVDY DDACLIVRYL ASMRPFAQSF DIYLTQILRV LGENAIAVRT KAMKCLSEVV AVDPSILARL DMQRGVHGRL MDNSTSVREA AVELLGRFVL CRPQLAEQYY DMLIERILDT GISVRKRVIK ILRDICIEQP TFPKITEMCV KMIRRVNDEE GIKKLVNETF QKLWFTPTPH NDKEAMTRKI LNITDVVAAC RDTGYDWFEQ LLQNLLKSEE DSSYKPVKKA CTQLVDNLVE HILKYEESLA DSDNKGVNSG RLVACITTLF LFSKIRPQLM VKHAMTMQPY LTTKCSTQND FMVICNVAKI LELVVPLMEH PSETFLATIE EDLMKLIIKY GMTVVQHCVS CLGAVVNKVT QNFKFVWACF NRYYGAISKL KSQHQEDPNN TSLLTNKPAL LRSLFTVGAL CRHFDFDLED FKGNSKVNIK DKVLELLMYF TKHSDEEVQT KAIIGLGFAF IQHPSLMFEQ EVKNLYNNIL SDKNSSVNLK IQVLKNLQTY LQEEDTRMQQ ADRDWKKVAK QEDLKEMGDV SSGMSSSIMQ LYLKQVLEAF FHTQSSVRHF ALNVIALTLN QGLIHPVQCV PYLIAMGTDP EPAMRNKADQ QLVEIDKKYA GFIHMKAVAG MKMSYQVQQA INTCLKDPVR GFRQDESSSA LCSHLYSMIR GNRQHRRAFL ISLLNLFDDT AKTDVTMLLY IADNLACFPY QTQEEPLFIM HHIDITLSVS GSNLLQSFKE SMVKDKRKER KSSPSKENES SDSEEEVSRP RKSRKRVDSD SDSDSEDDIN SVMKCLPENS APLIEFANVS QGILLLLMLK QHLKNLCGFS DSKIQKYSPS ESAKVYDKAI NRKTGVHFHP KQTLDFLRSD MANSKITEEV KRSIVKQYLD FKLLMEHLDP DEEEEEGEVS ASTNARNKAI TSLLGGGSPK NNTAAETEDD ESDGEDRGGG TSGSLRRSKR NSDSTELAAQ MNESVDVMDV IAICCPKYKD RPQIARVVQK TSSGFSVQWM AGSYSGSWTE AKRRDGRKLV PWVDTIKESD IIYKKIALTS ANKLTNKVVQ TLRSLYAAKD GTSS //