SMC3_HUMAN
ID SMC3_HUMAN Reviewed; 1217 AA.
AC Q9UQE7; A8K156; O60464; Q5T482;
DT 25-MAR-2003, integrated into UniProtKB/Swiss-Prot.
DT 25-MAR-2003, sequence version 2.
DT 03-AUG-2022, entry version 208.
DE RecName: Full=Structural maintenance of chromosomes protein 3;
DE Short=SMC protein 3;
DE Short=SMC-3;
DE AltName: Full=Basement membrane-associated chondroitin proteoglycan;
DE Short=Bamacan;
DE AltName: Full=Chondroitin sulfate proteoglycan 6;
DE AltName: Full=Chromosome-associated polypeptide;
DE Short=hCAP;
GN Name=SMC3; Synonyms=BAM, BMH, CSPG6, SMC3L1;
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], INTERACTION WITH KIFAP3, AND IDENTIFICATION IN
RP A COMPLEX WITH KIFAP3 AND KIF3B.
RC TISSUE=B-cell;
RX PubMed=9506951; DOI=10.1074/jbc.273.12.6591;
RA Shimizu K., Shirataki H., Honda T., Minami S., Takai Y.;
RT "Complex formation of SMAP/KAP3, a KIF3A/B ATPase motor-associated protein,
RT with a human chromosome-associated polypeptide.";
RL J. Biol. Chem. 273:6591-6594(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 410-1217.
RC TISSUE=Umbilical cord blood;
RX PubMed=11042152; DOI=10.1101/gr.140200;
RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT "Cloning and functional analysis of cDNAs with open reading frames for 300
RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor
RT cells.";
RL Genome Res. 10:1546-1560(2000).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 827-1217.
RC TISSUE=Neuron;
RA Stanchi F., Bertocco E., Simionati B., Zimbello R., Lanfranchi G.,
RA Valle G.;
RL Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP PROTEIN SEQUENCE OF 101-113, ACETYLATION AT LYS-105 AND LYS-106, AND
RP MUTAGENESIS OF LYS-105 AND LYS-106.
RX PubMed=18614053; DOI=10.1016/j.molcel.2008.06.006;
RA Zhang J., Shi X., Li Y., Kim B.J., Jia J., Huang Z., Yang T., Fu X.,
RA Jung S.Y., Wang Y., Zhang P., Kim S.T., Pan X., Qin J.;
RT "Acetylation of Smc3 by Eco1 is required for S phase sister chromatid
RT cohesion in both human and yeast.";
RL Mol. Cell 31:143-151(2008).
RN [8]
RP CHARACTERIZATION, FUNCTION, AND IDENTIFICATION IN A COHESIN COMPLEX WITH
RP SMC1A; STAG1 OR STAG2.
RX PubMed=11076961; DOI=10.1083/jcb.151.4.749;
RA Sumara I., Vorlaufer E., Gieffers C., Peters B.H., Peters J.-M.;
RT "Characterization of vertebrate cohesin complexes and their regulation in
RT prophase.";
RL J. Cell Biol. 151:749-762(2000).
RN [9]
RP INTERACTION WITH NUMA1.
RX PubMed=11590136; DOI=10.1074/jbc.m103364200;
RA Gregson H.C., Schmiesing J.A., Kim J.-S., Kobayashi T., Zhou S.,
RA Yokomori K.;
RT "A potential role for human cohesin in mitotic spindle aster assembly.";
RL J. Biol. Chem. 276:47575-47582(2001).
RN [10]
RP INTERACTION WITH HDAC2.
RX PubMed=12198550; DOI=10.1038/nature01024;
RA Hakimi M.-A., Bochar D.A., Schmiesing J.A., Dong Y., Barak O.G.,
RA Speicher D.W., Yokomori K., Shiekhattar R.;
RT "A chromatin remodelling complex that loads cohesin onto human
RT chromosomes.";
RL Nature 418:994-998(2002).
RN [11]
RP INTERACTION WITH KIAA1328.
RX PubMed=15656913; DOI=10.1186/1471-2121-6-3;
RA Patel C.A., Ghiselli G.;
RT "Hinderin, a five-domains protein including coiled-coil motifs that binds
RT to SMC3.";
RL BMC Cell Biol. 6:3-3(2005).
RN [12]
RP IDENTIFICATION IN A COMPLEX WITH CDCA5; SMC1A; RAD21; PDS5A AND PDS5B.
RX PubMed=15837422; DOI=10.1016/j.molcel.2005.03.017;
RA Rankin S., Ayad N.G., Kirschner M.W.;
RT "Sororin, a substrate of the anaphase-promoting complex, is required for
RT sister chromatid cohesion in vertebrates.";
RL Mol. Cell 18:185-200(2005).
RN [13]
RP ERRATUM OF PUBMED:15837422.
RA Rankin S., Ayad N.G., Kirschner M.W.;
RL Mol. Cell 18:609-609(2005).
RN [14]
RP INTERACTION WITH DDX11.
RX PubMed=17105772; DOI=10.1242/jcs.03262;
RA Parish J.L., Rosa J., Wang X., Lahti J.M., Doxsey S.J., Androphy E.J.;
RT "The DNA helicase ChlR1 is required for sister chromatid cohesion in
RT mammalian cells.";
RL J. Cell Sci. 119:4857-4865(2006).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-787; SER-1065 AND SER-1067,
RP AND 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 [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=T-cell;
RX PubMed=19367720; DOI=10.1021/pr800500r;
RA Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J.;
RT "Phosphorylation analysis of primary human T lymphocytes using sequential
RT IMAC and titanium oxide enrichment.";
RL J. Proteome Res. 7:5167-5176(2008).
RN [17]
RP IDENTIFICATION BY 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 [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1065 AND SER-1067, AND
RP 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 [19]
RP FUNCTION, ACETYLATION AT LYS-105 AND LYS-106, INTERACTION WITH PDS5A AND
RP WAPL, AND MUTAGENESIS OF LYS-105 AND LYS-106.
RX PubMed=19907496; DOI=10.1038/nature08550;
RA Terret M.E., Sherwood R., Rahman S., Qin J., Jallepalli P.V.;
RT "Cohesin acetylation speeds the replication fork.";
RL Nature 462:231-234(2009).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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 [21]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-105; LYS-106; LYS-140 AND
RP LYS-1190, AND 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 [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-783; SER-787; SER-1067 AND
RP SER-1083, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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 [23]
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 [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1067 AND SER-1083, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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 [25]
RP ACETYLATION, AND DEACETYLATION BY HDAC8.
RX PubMed=22885700; DOI=10.1038/nature11316;
RA Deardorff M.A., Bando M., Nakato R., Watrin E., Itoh T., Minamino M.,
RA Saitoh K., Komata M., Katou Y., Clark D., Cole K.E., De Baere E.,
RA Decroos C., Di Donato N., Ernst S., Francey L.J., Gyftodimou Y.,
RA Hirashima K., Hullings M., Ishikawa Y., Jaulin C., Kaur M., Kiyono T.,
RA Lombardi P.M., Magnaghi-Jaulin L., Mortier G.R., Nozaki N., Petersen M.B.,
RA Seimiya H., Siu V.M., Suzuki Y., Takagaki K., Wilde J.J., Willems P.J.,
RA Prigent C., Gillessen-Kaesbach G., Christianson D.W., Kaiser F.J.,
RA Jackson L.G., Hirota T., Krantz I.D., Shirahige K.;
RT "HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin
RT acetylation cycle.";
RL Nature 489:313-317(2012).
RN [26]
RP IDENTIFICATION IN A COHESIN COMPLEX WITH SMC1A; STAG1 AND RAD21, AND
RP INTERACTION WITH SMC1A AND HETERODIMER NIPB-MAU2.
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 [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-886 AND SER-1067, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [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 [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1065 AND SER-1067, 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 [29]
RP VARIANT CDLS3 380-GLY--GLN-384 DEL.
RX PubMed=31334757; DOI=10.1093/brain/awz210;
RA Kruszka P., Berger S.I., Casa V., Dekker M.R., Gaesser J., Weiss K.,
RA Martinez A.F., Murdock D.R., Louie R.J., Prijoles E.J., Lichty A.W.,
RA Brouwer O.F., Zonneveld-Huijssoon E., Stephan M.J., Hogue J., Hu P.,
RA Tanima-Nagai M., Everson J.L., Prasad C., Cereda A., Iascone M.,
RA Schreiber A., Zurcher V., Corsten-Janssen N., Escobar L., Clegg N.J.,
RA Delgado M.R., Hajirnis O., Balasubramanian M., Kayserili H., Deardorff M.,
RA Poot R.A., Wendt K.S., Lipinski R.J., Muenke M.;
RT "Cohesin complex-associated holoprosencephaly.";
RL Brain 142:2631-2643(2019).
RN [30]
RP UBIQUITINATION.
RX PubMed=31452512; DOI=10.7554/elife.47362;
RA Pech M.F., Fong L.E., Villalta J.E., Chan L.J., Kharbanda S., O'Brien J.J.,
RA McAllister F.E., Firestone A.J., Jan C.H., Settleman J.;
RT "Systematic identification of cancer cell vulnerabilities to natural killer
RT cell-mediated immune surveillance.";
RL Elife 8:0-0(2019).
RN [31]
RP VARIANT CDLS3 GLU-491 DEL.
RX PubMed=17273969; DOI=10.1086/511888;
RA Deardorff M.A., Kaur M., Yaeger D., Rampuria A., Korolev S., Pie J.,
RA Gil-Rodriguez C., Arnedo M., Loeys B., Kline A.D., Wilson M., Lillquist K.,
RA Siu V., Ramos F.J., Musio A., Jackson L.S., Dorsett D., Krantz I.D.;
RT "Mutations in cohesin complex members SMC3 and SMC1A cause a mild variant
RT of Cornelia de Lange syndrome with predominant mental retardation.";
RL Am. J. Hum. Genet. 80:485-494(2007).
RN [32]
RP CHARACTERIZATION OF VARIANT CDLS3 GLU-491 DEL, AND GENOMIC INSTABILITY OF
RP CDLS CELL LINES TO IONIZING RADIATION.
RX PubMed=18996922; DOI=10.1093/hmg/ddn369;
RA Revenkova E., Focarelli M.L., Susani L., Paulis M., Bassi M.T., Mannini L.,
RA Frattini A., Delia D., Krantz I., Vezzoni P., Jessberger R., Musio A.;
RT "Cornelia de Lange syndrome mutations in SMC1A or SMC3 affect binding to
RT DNA.";
RL Hum. Mol. Genet. 18:418-427(2009).
CC -!- FUNCTION: Central component of cohesin, a complex required for
CC chromosome cohesion during the cell cycle. The cohesin complex may form
CC a large proteinaceous ring within which sister chromatids can be
CC trapped. At anaphase, the complex is cleaved and dissociates from
CC chromatin, allowing sister chromatids to segregate. Cohesion is coupled
CC to DNA replication and is involved in DNA repair. The cohesin complex
CC also plays an important role in spindle pole assembly during mitosis
CC and in chromosomes movement. {ECO:0000269|PubMed:11076961,
CC ECO:0000269|PubMed:19907496}.
CC -!- SUBUNIT: Forms a heterodimer with SMC1A or SMC1B in cohesin complexes
CC (PubMed:22628566). Cohesin complexes are composed of the SMC1 (SMC1A or
CC SMC1B) and SMC3 heterodimer attached via their SMC hinge domain, RAD21
CC which link them, and one STAG protein (STAG1, STAG2 or STAG3), which
CC interacts with RAD21. Also found in meiosis-specific cohesin complexes
CC (PubMed:11076961). Found in a complex with SMC1A, CDCA5 and RAD21,
CC PDS5A/SCC-112 and PDS5B/APRIN (PubMed:15837422). Interacts with NUMA1,
CC and forms a ternary complex with KIF3B and KIFAP3, suggesting a
CC function in tethering the chromosomes to the spindle pole and in
CC chromosome movement (PubMed:9506951, PubMed:11590136). Interacts with
CC PDS5A and WAPL; regulated by SMC3 acetylation (PubMed:19907496).
CC Interacts (via SMC hinge domain) with KIAA1328 (via N- and C-terminal
CC domains) (PubMed:15656913). Interacts with DDX11 (PubMed:17105772).
CC Found in a cohesin complex with SMC1A, STAG1 and RAD21
CC (PubMed:22628566). The SMC1A-SMC3 heterodimer interacts with the NIPBL-
CC MAU2 heterodimer (PubMed:22628566). Interacts with MXI1, MXD3, MXD4,
CC SYCP2, RPGR and STAG3 (By similarity). Interacts with the NuRD complex
CC component HDAC2; the interaction is direct (PubMed:12198550).
CC {ECO:0000250|UniProtKB:O97594, ECO:0000250|UniProtKB:P97690,
CC ECO:0000250|UniProtKB:Q9CW03, ECO:0000269|PubMed:11076961,
CC ECO:0000269|PubMed:11590136, ECO:0000269|PubMed:12198550,
CC ECO:0000269|PubMed:15656913, ECO:0000269|PubMed:15837422,
CC ECO:0000269|PubMed:17105772, ECO:0000269|PubMed:19907496,
CC ECO:0000269|PubMed:22628566, ECO:0000269|PubMed:9506951}.
CC -!- INTERACTION:
CC Q9UQE7; Q9BTE3: MCMBP; NbExp=6; IntAct=EBI-80718, EBI-749378;
CC Q9UQE7; Q29RF7: PDS5A; NbExp=4; IntAct=EBI-80718, EBI-1175454;
CC Q9UQE7; Q9NTI5: PDS5B; NbExp=7; IntAct=EBI-80718, EBI-1175604;
CC Q9UQE7; O60216: RAD21; NbExp=16; IntAct=EBI-80718, EBI-80739;
CC Q9UQE7; Q14683: SMC1A; NbExp=14; IntAct=EBI-80718, EBI-80690;
CC Q9UQE7; Q8WVM7: STAG1; NbExp=13; IntAct=EBI-80718, EBI-1175097;
CC Q9UQE7; Q8N3U4: STAG2; NbExp=17; IntAct=EBI-80718, EBI-1057252;
CC Q9UQE7; P32908: SMC1; Xeno; NbExp=4; IntAct=EBI-80718, EBI-17402;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9CW03}.
CC Chromosome {ECO:0000250|UniProtKB:Q9CW03}. Chromosome, centromere
CC {ECO:0000250|UniProtKB:Q9CW03}. Note=Associates with chromatin. Before
CC prophase it is scattered along chromosome arms. During prophase, most
CC of cohesin complexes dissociate from chromatin probably because of
CC phosphorylation by PLK, except at centromeres, where cohesin complexes
CC remain. At anaphase, the RAD21 subunit of the cohesin complex is
CC cleaved, leading to the dissociation of the complex from chromosomes,
CC allowing chromosome separation. The phosphorylated form at Ser-1083 is
CC preferentially associated with unsynapsed chromosomal regions (By
CC similarity). {ECO:0000250|UniProtKB:Q9CW03}.
CC -!- DOMAIN: The flexible SMC hinge domain, which separates the large
CC intramolecular coiled coil regions, allows the heterotypic interaction
CC with the corresponding domain of SMC1A or SMC1B, forming a V-shaped
CC heterodimer. The two heads of the heterodimer are then connected by
CC different ends of the cleavable RAD21 protein, forming a ring structure
CC (By similarity). {ECO:0000250}.
CC -!- PTM: Ubiquitinated by the DCX(DCAF15) complex, leading to its
CC degradation. {ECO:0000269|PubMed:31452512}.
CC -!- PTM: Phosphorylated at Ser-1083 in a SPO11-dependent manner.
CC {ECO:0000250|UniProtKB:Q9CW03}.
CC -!- PTM: Acetylation at Lys-105 and Lys-106 by ESCO1 is important for
CC genome stability and S phase sister chromatid cohesion. Regulated by
CC DSCC1, it is required for processive DNA synthesis, coupling sister
CC chromatid cohesion establishment during S phase to DNA replication.
CC Deacetylation by HDAC8, regulates release of the cohesin complex from
CC chromatin. {ECO:0000269|PubMed:18614053, ECO:0000269|PubMed:19907496,
CC ECO:0000269|PubMed:22885700}.
CC -!- DISEASE: Cornelia de Lange syndrome 3 with or without midline brain
CC defects (CDLS3) [MIM:610759]: A form of Cornelia de Lange syndrome, a
CC clinically heterogeneous developmental disorder associated with
CC malformations affecting multiple systems. Characterized by facial
CC dysmorphisms, abnormal hands and feet, growth delay, cognitive
CC retardation, hirsutism, gastroesophageal dysfunction and cardiac,
CC ophthalmologic and genitourinary anomalies. Cornelia de Lange syndrome
CC type 3 is a mild form with absence of major structural anomalies. The
CC phenotype in some instances approaches that of apparently non-syndromic
CC intellectual disability. {ECO:0000269|PubMed:17273969,
CC ECO:0000269|PubMed:18996922, ECO:0000269|PubMed:31334757}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- MISCELLANEOUS: Mutated Cornelia de Lange cell lines display genomic
CC instability and sensitivity to ionizing radiation and interstrand
CC cross-linking agents.
CC -!- SIMILARITY: Belongs to the SMC family. SMC3 subfamily. {ECO:0000305}.
CC -!- CAUTION: Was originally isolated as a proteoglycan protein (explaining
CC its name). Although not excluded, such secreted function is not clear.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD32447.1; 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; AF020043; AAC14893.1; -; mRNA.
DR EMBL; AK289771; BAF82460.1; -; mRNA.
DR EMBL; AL359260; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471066; EAW49557.1; -; Genomic_DNA.
DR EMBL; AF067163; AAD32447.1; ALT_FRAME; mRNA.
DR EMBL; AJ005015; CAA06289.1; -; mRNA.
DR CCDS; CCDS31285.1; -.
DR RefSeq; NP_005436.1; NM_005445.3.
DR PDB; 6WG3; EM; 5.30 A; B=1-1217.
DR PDB; 6WG4; X-ray; 2.31 A; B=493-685.
DR PDB; 6WG6; X-ray; 3.54 A; B/D/F/H/J/L=466-713.
DR PDB; 6WGE; EM; 3.90 A; B=1-1217.
DR PDBsum; 6WG3; -.
DR PDBsum; 6WG4; -.
DR PDBsum; 6WG6; -.
DR PDBsum; 6WGE; -.
DR AlphaFoldDB; Q9UQE7; -.
DR SMR; Q9UQE7; -.
DR BioGRID; 114574; 334.
DR ComplexPortal; CPX-5989; Nuclear meiotic cohesin complex, STAG1 variant.
DR ComplexPortal; CPX-5991; Nuclear meiotic cohesin complex, STAG2 variant.
DR ComplexPortal; CPX-6082; Nuclear meiotic cohesin complex, STAG3 variant.
DR CORUM; Q9UQE7; -.
DR DIP; DIP-29200N; -.
DR IntAct; Q9UQE7; 130.
DR MINT; Q9UQE7; -.
DR STRING; 9606.ENSP00000354720; -.
DR MoonDB; Q9UQE7; Curated.
DR GlyGen; Q9UQE7; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; Q9UQE7; -.
DR MetOSite; Q9UQE7; -.
DR PhosphoSitePlus; Q9UQE7; -.
DR SwissPalm; Q9UQE7; -.
DR BioMuta; SMC3; -.
DR DMDM; 29337005; -.
DR CPTAC; CPTAC-1006; -.
DR EPD; Q9UQE7; -.
DR jPOST; Q9UQE7; -.
DR MassIVE; Q9UQE7; -.
DR MaxQB; Q9UQE7; -.
DR PaxDb; Q9UQE7; -.
DR PeptideAtlas; Q9UQE7; -.
DR PRIDE; Q9UQE7; -.
DR ProteomicsDB; 85549; -.
DR Antibodypedia; 18357; 353 antibodies from 39 providers.
DR DNASU; 9126; -.
DR Ensembl; ENST00000361804.5; ENSP00000354720.5; ENSG00000108055.11.
DR GeneID; 9126; -.
DR KEGG; hsa:9126; -.
DR MANE-Select; ENST00000361804.5; ENSP00000354720.5; NM_005445.4; NP_005436.1.
DR UCSC; uc001kze.4; human.
DR CTD; 9126; -.
DR DisGeNET; 9126; -.
DR GeneCards; SMC3; -.
DR GeneReviews; SMC3; -.
DR HGNC; HGNC:2468; SMC3.
DR HPA; ENSG00000108055; Low tissue specificity.
DR MalaCards; SMC3; -.
DR MIM; 606062; gene.
DR MIM; 610759; phenotype.
DR neXtProt; NX_Q9UQE7; -.
DR OpenTargets; ENSG00000108055; -.
DR Orphanet; 199; Cornelia de Lange syndrome.
DR PharmGKB; PA26966; -.
DR VEuPathDB; HostDB:ENSG00000108055; -.
DR eggNOG; KOG0964; Eukaryota.
DR GeneTree; ENSGT00580000081628; -.
DR HOGENOM; CLU_001042_5_0_1; -.
DR InParanoid; Q9UQE7; -.
DR OMA; DQHQSMR; -.
DR OrthoDB; 119789at2759; -.
DR PhylomeDB; Q9UQE7; -.
DR TreeFam; TF105602; -.
DR PathwayCommons; Q9UQE7; -.
DR Reactome; R-HSA-1221632; Meiotic synapsis.
DR Reactome; R-HSA-2467813; Separation of Sister Chromatids.
DR Reactome; R-HSA-2468052; Establishment of Sister Chromatid Cohesion.
DR Reactome; R-HSA-2470946; Cohesin Loading onto Chromatin.
DR Reactome; R-HSA-2500257; Resolution of Sister Chromatid Cohesion.
DR Reactome; R-HSA-3108214; SUMOylation of DNA damage response and repair proteins.
DR Reactome; R-HSA-9018519; Estrogen-dependent gene expression.
DR SignaLink; Q9UQE7; -.
DR SIGNOR; Q9UQE7; -.
DR BioGRID-ORCS; 9126; 710 hits in 1058 CRISPR screens.
DR ChiTaRS; SMC3; human.
DR GeneWiki; SMC3; -.
DR GenomeRNAi; 9126; -.
DR Pharos; Q9UQE7; Tbio.
DR PRO; PR:Q9UQE7; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q9UQE7; protein.
DR Bgee; ENSG00000108055; Expressed in tendon of biceps brachii and 194 other tissues.
DR Genevisible; Q9UQE7; HS.
DR GO; GO:0000785; C:chromatin; IDA:UniProtKB.
DR GO; GO:0005694; C:chromosome; TAS:Reactome.
DR GO; GO:0000775; C:chromosome, centromeric region; TAS:Reactome.
DR GO; GO:0008278; C:cohesin complex; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0000800; C:lateral element; IEA:Ensembl.
DR GO; GO:0030893; C:meiotic cohesin complex; IDA:UniProtKB.
DR GO; GO:0097431; C:mitotic spindle pole; IDA:UniProtKB.
DR GO; GO:0016363; C:nuclear matrix; IDA:UniProtKB.
DR GO; GO:0034991; C:nuclear meiotic cohesin complex; IPI:ComplexPortal.
DR GO; GO:0034990; C:nuclear mitotic cohesin complex; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IC:ComplexPortal.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR GO; GO:0048487; F:beta-tubulin binding; IDA:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
DR GO; GO:0061775; F:cohesin loading activity; IBA:GO_Central.
DR GO; GO:0003690; F:double-stranded DNA binding; IBA:GO_Central.
DR GO; GO:0070840; F:dynein complex binding; IDA:UniProtKB.
DR GO; GO:0036033; F:mediator complex binding; IEA:Ensembl.
DR GO; GO:0003777; F:microtubule motor activity; NAS:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0034089; P:establishment of meiotic sister chromatid cohesion; IC:ComplexPortal.
DR GO; GO:0051321; P:meiotic cell cycle; IDA:UniProtKB.
DR GO; GO:0000278; P:mitotic cell cycle; TAS:ProtInc.
DR GO; GO:0007064; P:mitotic sister chromatid cohesion; IBA:GO_Central.
DR GO; GO:0090307; P:mitotic spindle assembly; IMP:UniProtKB.
DR GO; GO:0006275; P:regulation of DNA replication; IMP:UniProtKB.
DR GO; GO:0007062; P:sister chromatid cohesion; IMP:BHF-UCL.
DR GO; GO:0019827; P:stem cell population maintenance; IEA:Ensembl.
DR CDD; cd03272; ABC_SMC3_euk; 1.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR003395; RecF/RecN/SMC_N.
DR InterPro; IPR024704; SMC.
DR InterPro; IPR041741; SMC3_ABC_euk.
DR InterPro; IPR010935; SMC_hinge.
DR InterPro; IPR036277; SMC_hinge_sf.
DR Pfam; PF06470; SMC_hinge; 1.
DR Pfam; PF02463; SMC_N; 1.
DR PIRSF; PIRSF005719; SMC; 1.
DR SMART; SM00968; SMC_hinge; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF75553; SSF75553; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ATP-binding; Cell cycle; Cell division;
KW Centromere; Chromosome; Coiled coil; Direct protein sequencing;
KW Disease variant; DNA damage; DNA repair; Intellectual disability; Meiosis;
KW Mitosis; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Ubl conjugation.
FT CHAIN 1..1217
FT /note="Structural maintenance of chromosomes protein 3"
FT /id="PRO_0000119001"
FT DOMAIN 530..642
FT /note="SMC hinge"
FT REGION 242..269
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1059..1090
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 179..350
FT /evidence="ECO:0000255"
FT COILED 393..503
FT /evidence="ECO:0000255"
FT COILED 669..916
FT /evidence="ECO:0000255"
FT COILED 958..989
FT /evidence="ECO:0000255"
FT COMPBIAS 1067..1090
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 32..39
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT MOD_RES 105
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:18614053,
FT ECO:0000269|PubMed:19907496, ECO:0007744|PubMed:19608861"
FT MOD_RES 106
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:18614053,
FT ECO:0000269|PubMed:19907496, ECO:0007744|PubMed:19608861"
FT MOD_RES 140
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 783
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 787
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17525332,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 886
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1013
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9CW03"
FT MOD_RES 1065
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17525332,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:24275569"
FT MOD_RES 1067
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17525332,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 1074
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P97690"
FT MOD_RES 1083
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 1190
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT VARIANT 380..384
FT /note="Missing (in CDLS3)"
FT /evidence="ECO:0000269|PubMed:31334757"
FT /id="VAR_083979"
FT VARIANT 491
FT /note="Missing (in CDLS3; affects the affinity of SMC hinge
FT dimers for DNA; mutated hinge dimers bind DNA with higher
FT affinity than wild-type proteins)"
FT /evidence="ECO:0000269|PubMed:17273969,
FT ECO:0000269|PubMed:18996922"
FT /id="VAR_032845"
FT MUTAGEN 105
FT /note="K->A: 20% loss of sister chromatid cohesion, no
FT effect on cohesin complex assembly; when associated with A-
FT 106."
FT /evidence="ECO:0000269|PubMed:18614053,
FT ECO:0000269|PubMed:19907496"
FT MUTAGEN 105
FT /note="K->Q: No effect on sister chromatid cohesion, nor on
FT cohesin complex assembly; when associated with Q-106."
FT /evidence="ECO:0000269|PubMed:18614053"
FT MUTAGEN 105
FT /note="K->R: Stabilizes interaction with PDS5A and WAPL;
FT when associated with R-106."
FT /evidence="ECO:0000269|PubMed:19907496"
FT MUTAGEN 106
FT /note="K->A: 20% loss of sister chromatid cohesion, no
FT effect on cohesin complex assembly; when associated with A-
FT 105."
FT /evidence="ECO:0000269|PubMed:18614053,
FT ECO:0000269|PubMed:19907496"
FT MUTAGEN 106
FT /note="K->Q: No effect on sister chromatid cohesion, nor on
FT cohesin complex assembly; when associated with Q-105."
FT /evidence="ECO:0000269|PubMed:18614053"
FT MUTAGEN 106
FT /note="K->R: Stabilizes interaction with PDS5A and WAPL;
FT when associated with R-105."
FT /evidence="ECO:0000269|PubMed:19907496"
FT CONFLICT 462
FT /note="K -> T (in Ref. 5; AAD32447)"
FT /evidence="ECO:0000305"
FT CONFLICT 509
FT /note="I -> V (in Ref. 5; AAD32447)"
FT /evidence="ECO:0000305"
FT CONFLICT 526
FT /note="Q -> P (in Ref. 5; AAD32447)"
FT /evidence="ECO:0000305"
FT HELIX 501..522
FT /evidence="ECO:0007829|PDB:6WG4"
FT HELIX 526..531
FT /evidence="ECO:0007829|PDB:6WG4"
FT STRAND 532..535
FT /evidence="ECO:0007829|PDB:6WG4"
FT HELIX 536..539
FT /evidence="ECO:0007829|PDB:6WG4"
FT HELIX 544..546
FT /evidence="ECO:0007829|PDB:6WG4"
FT HELIX 547..554
FT /evidence="ECO:0007829|PDB:6WG4"
FT HELIX 555..559
FT /evidence="ECO:0007829|PDB:6WG4"
FT STRAND 561..564
FT /evidence="ECO:0007829|PDB:6WG4"
FT HELIX 566..578
FT /evidence="ECO:0007829|PDB:6WG4"
FT STRAND 585..589
FT /evidence="ECO:0007829|PDB:6WG4"
FT TURN 590..592
FT /evidence="ECO:0007829|PDB:6WG4"
FT STRAND 604..608
FT /evidence="ECO:0007829|PDB:6WG4"
FT HELIX 609..612
FT /evidence="ECO:0007829|PDB:6WG4"
FT HELIX 617..619
FT /evidence="ECO:0007829|PDB:6WG4"
FT HELIX 620..627
FT /evidence="ECO:0007829|PDB:6WG4"
FT STRAND 630..634
FT /evidence="ECO:0007829|PDB:6WG4"
FT HELIX 636..645
FT /evidence="ECO:0007829|PDB:6WG4"
FT STRAND 649..652
FT /evidence="ECO:0007829|PDB:6WG4"
FT STRAND 660..662
FT /evidence="ECO:0007829|PDB:6WG4"
SQ SEQUENCE 1217 AA; 141542 MW; 21EF9A08A5D8096A CRC64;
MYIKQVIIQG FRSYRDQTIV DPFSSKHNVI VGRNGSGKSN FFYAIQFVLS DEFSHLRPEQ
RLALLHEGTG PRVISAFVEI IFDNSDNRLP IDKEEVSLRR VIGAKKDQYF LDKKMVTKND
VMNLLESAGF SRSNPYYIVK QGKINQMATA PDSQRLKLLR EVAGTRVYDE RKEESISLMK
ETEGKREKIN ELLKYIEERL HTLEEEKEEL AQYQKWDKMR RALEYTIYNQ ELNETRAKLD
ELSAKRETSG EKSRQLRDAQ QDARDKMEDI ERQVRELKTK ISAMKEEKEQ LSAERQEQIK
QRTKLELKAK DLQDELAGNS EQRKRLLKER QKLLEKIEEK QKELAETEPK FNSVKEKEER
GIARLAQATQ ERTDLYAKQG RGSQFTSKEE RDKWIKKELK SLDQAINDKK RQIAAIHKDL
EDTEANKEKN LEQYNKLDQD LNEVKARVEE LDRKYYEVKN KKDELQSERN YLWREENAEQ
QALAAKREDL EKKQQLLRAA TGKAILNGID SINKVLDHFR RKGINQHVQN GYHGIVMNNF
ECEPAFYTCV EVTAGNRLFY HIVDSDEVST KILMEFNKMN LPGEVTFLPL NKLDVRDTAY
PETNDAIPMI SKLRYNPRFD KAFKHVFGKT LICRSMEVST QLARAFTMDC ITLEGDQVSH
RGALTGGYYD TRKSRLELQK DVRKAEEELG ELEAKLNENL RRNIERINNE IDQLMNQMQQ
IETQQRKFKA SRDSILSEMK MLKEKRQQSE KTFMPKQRSL QSLEASLHAM ESTRESLKAE
LGTDLLSQLS LEDQKRVDAL NDEIRQLQQE NRQLLNERIK LEGIITRVET YLNENLRKRL
DQVEQELNEL RETEGGTVLT ATTSELEAIN KRVKDTMARS EDLDNSIDKT EAGIKELQKS
MERWKNMEKE HMDAINHDTK ELEKMTNRQG MLLKKKEECM KKIRELGSLP QEAFEKYQTL
SLKQLFRKLE QCNTELKKYS HVNKKALDQF VNFSEQKEKL IKRQEELDRG YKSIMELMNV
LELRKYEAIQ LTFKQVSKNF SEVFQKLVPG GKATLVMKKG DVEGSQSQDE GEGSGESERG
SGSQSSVPSV DQFTGVGIRV SFTGKQGEMR EMQQLSGGQK SLVALALIFA IQKCDPAPFY
LFDEIDQALD AQHRKAVSDM IMELAVHAQF ITTTFRPELL ESADKFYGVK FRNKVSHIDV
ITAEMAKDFV EDDTTHG
