NIPBL_HUMAN
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 03-AUG-2022, entry version 183.
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]
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 [28]
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 [29]
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 [30]
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 [31]
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 [32]
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 [33]
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 [34]
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 SMC1A-SMC3 heterodimer and with the cohesin complex composed
CC of SMC1A, SMC3, RAD21 and STAG1 (PubMed:22628566). Interacts directly
CC (via PxVxL motif) with CBX5 (PubMed:15882967, PubMed:20562864).
CC Interacts with ZNF609 (via N-terminus) (By similarity). Interacts with
CC the multiprotein complex Integrator (By similarity). Interacts (via
CC PxVxL motif) with CBX3 (PubMed:28167679).
CC {ECO:0000250|UniProtKB:Q6KCD5, ECO:0000269|PubMed:15882967,
CC ECO:0000269|PubMed:16682347, ECO:0000269|PubMed:16802858,
CC ECO:0000269|PubMed:20562864, ECO:0000269|PubMed:21934712,
CC ECO:0000269|PubMed:22628566, ECO:0000269|PubMed:28167679}.
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 PDBsum; 6WG3; -.
DR PDBsum; 6WGE; -.
DR SMR; Q6KC79; -.
DR BioGRID; 117363; 160.
DR DIP; DIP-29199N; -.
DR IntAct; Q6KC79; 47.
DR MINT; Q6KC79; -.
DR STRING; 9606.ENSP00000282516; -.
DR GlyGen; Q6KC79; 8 sites, 1 O-linked glycan (8 sites).
DR iPTMnet; Q6KC79; -.
DR PhosphoSitePlus; Q6KC79; -.
DR BioMuta; NIPBL; -.
DR DMDM; 50400865; -.
DR EPD; Q6KC79; -.
DR jPOST; Q6KC79; -.
DR MassIVE; Q6KC79; -.
DR MaxQB; Q6KC79; -.
DR PaxDb; Q6KC79; -.
DR PeptideAtlas; Q6KC79; -.
DR PRIDE; Q6KC79; -.
DR ProteomicsDB; 66538; -. [Q6KC79-1]
DR ProteomicsDB; 66539; -. [Q6KC79-2]
DR ProteomicsDB; 66540; -. [Q6KC79-3]
DR Antibodypedia; 10283; 195 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 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; 7137at2759; -.
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; 259 hits in 1085 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 calcaneal tendon and 194 other tissues.
DR ExpressionAtlas; Q6KC79; baseline and differential.
DR Genevisible; Q6KC79; HS.
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: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:0008022; F:protein C-terminus binding; IPI:UniProtKB.
DR GO; GO:0047485; F:protein N-terminus binding; IPI:UniProtKB.
DR GO; GO:0007420; P:brain development; IMP:BHF-UCL.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IMP:UniProtKB.
DR GO; GO:0071481; P:cellular response to X-ray; IMP:UniProtKB.
DR GO; GO:0050890; P:cognition; IMP:BHF-UCL.
DR GO; GO:0071921; P:cohesin loading; IDA:UniProtKB.
DR GO; GO:0048589; P:developmental growth; IMP:BHF-UCL.
DR GO; GO:0048565; P:digestive tract development; IBA:GO_Central.
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:gall bladder 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; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:BHF-UCL.
DR GO; GO:0003151; P:outflow tract morphogenesis; IMP:BHF-UCL.
DR GO; GO:0031065; P:positive regulation of histone deacetylation; IDA: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; -; 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; PTHR21704; 2.
DR Pfam; PF12765; Cohesin_HEAT; 1.
DR Pfam; PF12830; Nipped-B_C; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
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; unknown pathological
FT 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 variant; no effect on
FT interaction 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
