SMC1A_HUMAN
ID SMC1A_HUMAN Reviewed; 1233 AA.
AC Q14683; O14995; Q16351; Q2M228;
DT 25-MAR-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 2.
DT 03-AUG-2022, entry version 222.
DE RecName: Full=Structural maintenance of chromosomes protein 1A;
DE Short=SMC protein 1A;
DE Short=SMC-1-alpha;
DE Short=SMC-1A;
DE AltName: Full=Sb1.8;
GN Name=SMC1A; Synonyms=DXS423E, KIAA0178, SB1.8, SMC1, SMC1L1;
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].
RC TISSUE=Fibroblast;
RX PubMed=7757074; DOI=10.1093/hmg/4.2.243;
RA Rocques P.J., Clark J., Ball S., Crew J., Gill S., Christodoulou Z.,
RA Borts R.H., Louis E.J., Davies K.E., Cooper C.S.;
RT "The human SB1.8 gene (DXS423E) encodes a putative chromosome segregation
RT protein conserved in lower eukaryotes and prokaryotes.";
RL Hum. Mol. Genet. 4:243-249(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Bone marrow;
RX PubMed=8724849; DOI=10.1093/dnares/3.1.17;
RA Nagase T., Seki N., Ishikawa K., Tanaka A., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. V. The
RT coding sequences of 40 new genes (KIAA0161-KIAA0200) deduced by analysis of
RT cDNA clones from human cell line KG-1.";
RL DNA Res. 3:17-24(1996).
RN [3]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 PROTEIN SEQUENCE OF 945-984, FUNCTION, INTERACTION WITH BRCA1,
RP PHOSPHORYLATION AT SER-957 AND SER-966, AND MUTAGENESIS OF SER-957 AND
RP SER-966.
RX PubMed=11877377; DOI=10.1101/gad.970702;
RA Yazdi P.T., Wang Y., Zhao S., Patel N., Lee E.Y.-H.P., Qin J.;
RT "SMC1 is a downstream effector in the ATM/NBS1 branch of the human S-phase
RT checkpoint.";
RL Genes Dev. 16:571-582(2002).
RN [7]
RP INTERACTION WITH NDC80.
RX PubMed=9295362; DOI=10.1074/jbc.272.38.24081;
RA Chen Y., Sharp Z.D., Lee W.-H.;
RT "HEC binds to the seventh regulatory subunit of the 26 S proteasome and
RT modulates the proteolysis of mitotic cyclins.";
RL J. Biol. Chem. 272:24081-24087(1997).
RN [8]
RP INTERACTION WITH NDC80.
RX PubMed=10409732; DOI=10.1128/mcb.19.8.5417;
RA Zheng L., Chen Y., Lee W.-H.;
RT "Hec1p, an evolutionarily conserved coiled-coil protein, modulates
RT chromosome segregation through interaction with SMC proteins.";
RL Mol. Cell. Biol. 19:5417-5428(1999).
RN [9]
RP IDENTIFICATION IN A COHESIN COMPLEX WITH SMC3; 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 [10]
RP SUBCELLULAR LOCATION DURING CELL CYCLE.
RX PubMed=12199140; DOI=10.1023/a:1016563523208;
RA Gregson H.C., Van Hooser A.A., Ball A.R. Jr., Brinkley B.R., Yokomori K.;
RT "Localization of human SMC1 protein at kinetochores.";
RL Chromosome Res. 10:267-277(2002).
RN [11]
RP PHOSPHORYLATION AT SER-966, AND MUTAGENESIS OF SER-966.
RX PubMed=14657349; DOI=10.1073/pnas.2536810100;
RA Wang Y., Qin J.;
RT "MSH2 and ATR form a signaling module and regulate two branches of the
RT damage response to DNA methylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:15387-15392(2003).
RN [12]
RP IDENTIFICATION IN A COMPLEX WITH CDCA5; SMC3; 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-358; SER-360 AND SER-966, AND
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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-360; SER-957 AND SER-970, 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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-957, AND IDENTIFICATION BY
RP 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 [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-648 AND LYS-713, AND
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 [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-360; SER-957 AND SER-966, AND
RP 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 [19]
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 [20]
RP INTERACTION WITH BRAT1, AND PHOSPHORYLATION AT SER-966.
RX PubMed=22977523; DOI=10.3892/etm.2011.232;
RA So E.Y., Ouchi T.;
RT "Functional interaction of BRCA1/ATM-associated BAAT1 with the DNA-PK
RT catalytic subunit.";
RL Exp. Ther. Med. 2:443-447(2011).
RN [21]
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 [22]
RP IDENTIFICATION IN A COHESIN COMPLEX WITH SMC3; STAG1 AND RAD21, AND
RP INTERACTION WITH SMC3 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 [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-360; SER-957 AND SER-962, 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 [24]
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 [25]
RP INVOLVEMENT IN DEE85, AND VARIANTS DEE85 171-ARG--GLN-1233 DEL;
RP 531-GLN--GLN-1233 DEL; 733-GLU--GLN-1233 DEL; 975-ARG--GLN-1233 DEL;
RP 1039-GLN--GLN-1233 DEL AND 1049-ARG--GLN-1233 DEL.
RX PubMed=28166369; DOI=10.1111/epi.13669;
RG DDD Study;
RA Symonds J.D., Joss S., Metcalfe K.A., Somarathi S., Cruden J., Devlin A.M.,
RA Donaldson A., DiDonato N., Fitzpatrick D., Kaiser F.J., Lampe A.K.,
RA Lees M.M., McLellan A., Montgomery T., Mundada V., Nairn L., Sarkar A.,
RA Schallner J., Pozojevic J., Parenti I., Tan J., Turnpenny P.,
RA Whitehouse W.P., Zuberi S.M.;
RT "Heterozygous truncation mutations of the SMC1A gene cause a severe early
RT onset epilepsy with cluster seizures in females: Detailed phenotyping of 10
RT new cases.";
RL Epilepsia 58:565-575(2017).
RN [26]
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 [27]
RP VARIANTS CDLS2 ALA-493 AND GLN-832 DEL.
RX PubMed=16604071; DOI=10.1038/ng1779;
RA Musio A., Selicorni A., Focarelli M.L., Gervasini C., Milani D., Russo S.,
RA Vezzoni P., Larizza L.;
RT "X-linked Cornelia de Lange syndrome owing to SMC1L1 mutations.";
RL Nat. Genet. 38:528-530(2006).
RN [28]
RP VARIANTS CDLS2 58-VAL--ARG-62 DEL; VAL-133; HIS-196; CYS-496; HIS-496;
RP TRP-711; GLN-790 AND LEU-1122.
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 [29]
RP VARIANTS CDLS2 HIS-196 AND CYS-1085.
RX PubMed=17221863; DOI=10.1002/humu.9478;
RA Borck G., Zarhrate M., Bonnefont J.-P., Munnich A., Cormier-Daire V.,
RA Colleaux L.;
RT "Incidence and clinical features of X-linked Cornelia de Lange syndrome due
RT to SMC1L1 mutations.";
RL Hum. Mutat. 28:205-206(2007).
RN [30]
RP CHARACTERIZATION OF VARIANTS CDLS2 ALA-493; CYS-496 AND HIS-496, AND
RP GENOMIC INSTABILITY OF 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).
RN [31]
RP VARIANTS CDLS2 58-VAL--ARG-62 DEL; VAL-133; LYS-141; HIS-196; LYS-268 DEL;
RP SER-306 DEL; GLN-398; CYS-496; HIS-496; GLU-683 DEL; GLY-693; TRP-711;
RP PHE-781; GLN-790; GLY-816; GLN-1049; LEU-1122 AND TRP-1123.
RX PubMed=19701948; DOI=10.1002/humu.21095;
RA Liu J., Feldman R., Zhang Z., Deardorff M.A., Haverfield E.V., Kaur M.,
RA Li J.R., Clark D., Kline A.D., Waggoner D.J., Das S., Jackson L.G.,
RA Krantz I.D.;
RT "SMC1A expression and mechanism of pathogenicity in probands with X-Linked
RT Cornelia de Lange syndrome.";
RL Hum. Mutat. 30:1535-1542(2009).
RN [32]
RP VARIANTS CDLS2 HIS-196; LYS-268 DEL AND GLN-711.
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 [33]
RP VARIANT CDLS2 THR-784.
RX PubMed=20635401; DOI=10.1002/ajmg.a.33486;
RA Limongelli G., Russo S., Digilio M.C., Masciadri M., Pacileo G., Fratta F.,
RA Martone F., Maddaloni V., D'Alessandro R., Calabro P., Russo M.G.,
RA Calabro R., Larizza L.;
RT "Hypertrophic cardiomyopathy in a girl with Cornelia de Lange syndrome due
RT to mutation in SMC1A.";
RL Am. J. Med. Genet. A 152:2127-2129(2010).
RN [34]
RP VARIANTS CDLS2 58-VAL--ARG-62 DEL; GLY-398; MET-651; GLN-693; THR-784;
RP GLN-790; THR-1166 AND PHE-1189.
RX PubMed=24124034; DOI=10.1002/ajmg.a.36252;
RA Gervasini C., Russo S., Cereda A., Parenti I., Masciadri M., Azzollini J.,
RA Melis D., Aravena T., Doray B., Ferrarini A., Garavelli L., Selicorni A.,
RA Larizza L.;
RT "Cornelia de Lange individuals with new and recurrent SMC1A mutations
RT enhance delineation of mutation repertoire and phenotypic spectrum.";
RL Am. J. Med. Genet. A 161A:2909-2919(2013).
RN [35]
RP VARIANTS DEE85 499-ARG--GLN-1233 DEL AND GLY-895.
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).
CC -!- FUNCTION: Involved in chromosome cohesion during cell cycle and in DNA
CC repair. Central component of cohesin complex. The cohesin complex is
CC required for the cohesion of sister chromatids after DNA replication.
CC The cohesin complex apparently forms a large proteinaceous ring within
CC which sister chromatids can be trapped. At anaphase, the complex is
CC cleaved and dissociates from chromatin, allowing sister chromatids to
CC segregate. The cohesin complex may also play a role in spindle pole
CC assembly during mitosis. Involved in DNA repair via its interaction
CC with BRCA1 and its related phosphorylation by ATM, or via its
CC phosphorylation by ATR. Works as a downstream effector both in the
CC ATM/NBS1 branch and in the ATR/MSH2 branch of S-phase checkpoint.
CC {ECO:0000269|PubMed:11877377}.
CC -!- SUBUNIT: Forms a heterodimer with SMC3 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 (PubMed:11076961). In germ cell cohesin complexes,
CC SMC1A is mutually exclusive with SMC1B (By similarity). Interacts with
CC BRCA1 (PubMed:11877377). Found in a complex with CDCA5, SMC3 and RAD21,
CC PDS5A/SCC-112 and PDS5B/APRIN (PubMed:15837422). Interacts with NDC80
CC (PubMed:9295362, PubMed:10409732,). Interacts with BRAT1
CC (PubMed:22977523). Found in a complex containing POLE and SMC3.
CC Interacts with RPGR, STAG3 and SYCP2 (By similarity). Found in a
CC cohesin complex with SMC3, STAG1 and RAD21 (PubMed:22628566). The
CC SMC1A-SMC3 heterodimer interacts with the NIPBL-MAU2 heterodimer
CC (PubMed:22628566). {ECO:0000250|UniProtKB:O97593,
CC ECO:0000250|UniProtKB:Q9CU62, ECO:0000250|UniProtKB:Q9Z1M9,
CC ECO:0000269|PubMed:10409732, ECO:0000269|PubMed:11076961,
CC ECO:0000269|PubMed:11877377, ECO:0000269|PubMed:15837422,
CC ECO:0000269|PubMed:22628566, ECO:0000269|PubMed:22977523,
CC ECO:0000269|PubMed:9295362}.
CC -!- INTERACTION:
CC Q14683; Q96FF9: CDCA5; NbExp=6; IntAct=EBI-80690, EBI-718805;
CC Q14683; Q92915-2: FGF14; NbExp=3; IntAct=EBI-80690, EBI-12836320;
CC Q14683; P33993: MCM7; NbExp=8; IntAct=EBI-80690, EBI-355924;
CC Q14683; O60216: RAD21; NbExp=15; IntAct=EBI-80690, EBI-80739;
CC Q14683; P78406: RAE1; NbExp=5; IntAct=EBI-80690, EBI-724495;
CC Q14683; Q5FBB7: SGO1; NbExp=9; IntAct=EBI-80690, EBI-989069;
CC Q14683; Q9UQE7: SMC3; NbExp=14; IntAct=EBI-80690, EBI-80718;
CC Q14683; Q8N3U4: STAG2; NbExp=12; IntAct=EBI-80690, EBI-1057252;
CC Q14683; PRO_0000045603 [Q99IB8]; Xeno; NbExp=3; IntAct=EBI-80690, EBI-6927928;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12199140}. Chromosome
CC {ECO:0000269|PubMed:12199140}. Chromosome, centromere, kinetochore
CC {ECO:0000269|PubMed:12199140}. 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. In germ cells, cohesin complex
CC dissociates from chromatin at prophase I, and may be replaced by a
CC meiosis-specific cohesin complex. The phosphorylated form on Ser-957
CC and Ser-966 associates with chromatin during G1/S/G2 phases but not
CC during M phase, suggesting that phosphorylation does not regulate
CC cohesin function. Integral component of the functional centromere-
CC kinetochore complex at the kinetochore region during mitosis.
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 SMC3, forming a V-shaped heterodimer.
CC The two heads of the heterodimer are then connected by different ends
CC of the cleavable RAD21 protein, forming a ring structure (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Ubiquitinated by the DCX(DCAF15) complex, leading to its
CC degradation. {ECO:0000269|PubMed:31452512}.
CC -!- PTM: Phosphorylated by ATM upon ionizing radiation in a NBS1-dependent
CC manner. Phosphorylated by ATR upon DNA methylation in a MSH2/MSH6-
CC dependent manner. Phosphorylation of Ser-957 and Ser-966 activates it
CC and is required for S-phase checkpoint activation.
CC {ECO:0000269|PubMed:11877377, ECO:0000269|PubMed:14657349}.
CC -!- DISEASE: Cornelia de Lange syndrome 2 (CDLS2) [MIM:300590]: 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:16604071, ECO:0000269|PubMed:17221863,
CC ECO:0000269|PubMed:17273969, ECO:0000269|PubMed:18996922,
CC ECO:0000269|PubMed:19701948, ECO:0000269|PubMed:20358602,
CC ECO:0000269|PubMed:20635401, ECO:0000269|PubMed:24124034}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Developmental and epileptic encephalopathy 85 with or without
CC midline brain defects (DEE85) [MIM:301044]: An X-linked form of
CC epileptic encephalopathy, a heterogeneous group of severe early-onset
CC epilepsies characterized by refractory seizures, neurodevelopmental
CC impairment, and poor prognosis. Development is normal prior to seizure
CC onset, after which cognitive and motor delays become apparent. DEE85 is
CC characterized by onset of severe refractory seizures in the first year
CC of life, global developmental delay with impaired intellectual
CC development and poor or absent speech, and dysmorphic facial features.
CC Many patients have midline brain defects on brain imaging.
CC {ECO:0000269|PubMed:28166369, 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. SMC1 subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
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DR EMBL; S78271; AAB34405.1; -; mRNA.
DR EMBL; D80000; BAA11495.2; -; mRNA.
DR EMBL; AL161779; CAI42089.1; -; Genomic_DNA.
DR EMBL; Z97054; CAI42089.1; JOINED; Genomic_DNA.
DR EMBL; Z97054; CAI42646.1; -; Genomic_DNA.
DR EMBL; AL161779; CAI42646.1; JOINED; Genomic_DNA.
DR EMBL; BC112127; AAI12128.1; -; mRNA.
DR CCDS; CCDS14352.1; -.
DR PIR; I54383; I54383.
DR RefSeq; NP_006297.2; NM_006306.3.
DR PDB; 6WG3; EM; 5.30 A; A=1-1233.
DR PDB; 6WG4; X-ray; 2.31 A; A=499-675.
DR PDB; 6WG6; X-ray; 3.54 A; A/C/E/G/I/K=472-702.
DR PDB; 6WGE; EM; 3.90 A; A=1-1233.
DR PDBsum; 6WG3; -.
DR PDBsum; 6WG4; -.
DR PDBsum; 6WG6; -.
DR PDBsum; 6WGE; -.
DR AlphaFoldDB; Q14683; -.
DR SMR; Q14683; -.
DR BioGRID; 113871; 321.
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; Q14683; -.
DR DIP; DIP-30911N; -.
DR IntAct; Q14683; 140.
DR MINT; Q14683; -.
DR STRING; 9606.ENSP00000323421; -.
DR ChEMBL; CHEMBL4105747; -.
DR GlyGen; Q14683; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q14683; -.
DR MetOSite; Q14683; -.
DR PhosphoSitePlus; Q14683; -.
DR SwissPalm; Q14683; -.
DR BioMuta; SMC1A; -.
DR DMDM; 29336622; -.
DR EPD; Q14683; -.
DR jPOST; Q14683; -.
DR MassIVE; Q14683; -.
DR MaxQB; Q14683; -.
DR PaxDb; Q14683; -.
DR PeptideAtlas; Q14683; -.
DR PRIDE; Q14683; -.
DR ProteomicsDB; 60117; -.
DR Antibodypedia; 491; 1021 antibodies from 43 providers.
DR DNASU; 8243; -.
DR Ensembl; ENST00000322213.9; ENSP00000323421.3; ENSG00000072501.19.
DR GeneID; 8243; -.
DR KEGG; hsa:8243; -.
DR MANE-Select; ENST00000322213.9; ENSP00000323421.3; NM_006306.4; NP_006297.2.
DR UCSC; uc004dsg.4; human.
DR CTD; 8243; -.
DR DisGeNET; 8243; -.
DR GeneCards; SMC1A; -.
DR GeneReviews; SMC1A; -.
DR HGNC; HGNC:11111; SMC1A.
DR HPA; ENSG00000072501; Low tissue specificity.
DR MalaCards; SMC1A; -.
DR MIM; 300040; gene.
DR MIM; 300590; phenotype.
DR MIM; 301044; phenotype.
DR neXtProt; NX_Q14683; -.
DR OpenTargets; ENSG00000072501; -.
DR Orphanet; 3095; Atypical Rett syndrome.
DR Orphanet; 199; Cornelia de Lange syndrome.
DR Orphanet; 220386; Semilobar holoprosencephaly.
DR PharmGKB; PA35961; -.
DR VEuPathDB; HostDB:ENSG00000072501; -.
DR eggNOG; KOG0018; Eukaryota.
DR GeneTree; ENSGT00940000155614; -.
DR HOGENOM; CLU_001042_0_2_1; -.
DR InParanoid; Q14683; -.
DR OMA; YIRDHTT; -.
DR OrthoDB; 326079at2759; -.
DR PhylomeDB; Q14683; -.
DR TreeFam; TF101156; -.
DR PathwayCommons; Q14683; -.
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; Q14683; -.
DR SIGNOR; Q14683; -.
DR BioGRID-ORCS; 8243; 400 hits in 719 CRISPR screens.
DR ChiTaRS; SMC1A; human.
DR GeneWiki; SMC1A; -.
DR GenomeRNAi; 8243; -.
DR Pharos; Q14683; Tchem.
DR PRO; PR:Q14683; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q14683; protein.
DR Bgee; ENSG00000072501; Expressed in sural nerve and 208 other tissues.
DR ExpressionAtlas; Q14683; baseline and differential.
DR Genevisible; Q14683; HS.
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:0000794; C:condensed nuclear chromosome; TAS:ProtInc.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0000776; C:kinetochore; IDA:UniProtKB.
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:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IBA:GO_Central.
DR GO; GO:0036033; F:mediator complex binding; IEA:Ensembl.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0006281; P:DNA repair; TAS:UniProtKB.
DR GO; GO:0034089; P:establishment of meiotic sister chromatid cohesion; IC:ComplexPortal.
DR GO; GO:0051321; P:meiotic cell cycle; ISS:UniProtKB.
DR GO; GO:0007064; P:mitotic sister chromatid cohesion; TAS:UniProtKB.
DR GO; GO:0000070; P:mitotic sister chromatid segregation; TAS:UniProtKB.
DR GO; GO:0090307; P:mitotic spindle assembly; IMP:UniProtKB.
DR GO; GO:0072423; P:response to DNA damage checkpoint signaling; IDA:UniProtKB.
DR GO; GO:0009314; P:response to radiation; IEP:UniProtKB.
DR GO; GO:0007062; P:sister chromatid cohesion; IMP:BHF-UCL.
DR GO; GO:0035019; P:somatic stem cell population maintenance; IEA:Ensembl.
DR CDD; cd03275; ABC_SMC1_euk; 2.
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; IPR028468; Smc1_ABC.
DR InterPro; IPR029683; SMC1A_metazoan.
DR InterPro; IPR010935; SMC_hinge.
DR InterPro; IPR036277; SMC_hinge_sf.
DR PANTHER; PTHR18937:SF170; PTHR18937:SF170; 1.
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; Epilepsy; Intellectual disability;
KW Kinetochore; Meiosis; Mitosis; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Ubl conjugation.
FT CHAIN 1..1233
FT /note="Structural maintenance of chromosomes protein 1A"
FT /id="PRO_0000118989"
FT DOMAIN 515..629
FT /note="SMC hinge"
FT REGION 284..308
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 348..369
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 947..966
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 104..124
FT /evidence="ECO:0000255"
FT COILED 163..503
FT /evidence="ECO:0000255"
FT COILED 660..935
FT /evidence="ECO:0000255"
FT COILED 991..1068
FT /evidence="ECO:0000255"
FT COMPBIAS 949..966
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 358
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17525332"
FT MOD_RES 360
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17525332,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 648
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 713
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 957
FT /note="Phosphoserine; by ATM"
FT /evidence="ECO:0000269|PubMed:11877377,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 962
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 966
FT /note="Phosphoserine; by ATM and ATR"
FT /evidence="ECO:0000269|PubMed:11877377,
FT ECO:0000269|PubMed:14657349, ECO:0000269|PubMed:22977523,
FT ECO:0007744|PubMed:17525332, ECO:0007744|PubMed:20068231"
FT MOD_RES 970
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1037
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9CU62"
FT VARIANT 28
FT /note="T -> P (in dbSNP:rs34530151)"
FT /id="VAR_052438"
FT VARIANT 58..62
FT /note="Missing (in CDLS2)"
FT /evidence="ECO:0000269|PubMed:17273969,
FT ECO:0000269|PubMed:19701948, ECO:0000269|PubMed:24124034"
FT /id="VAR_062785"
FT VARIANT 133
FT /note="F -> V (in CDLS2)"
FT /evidence="ECO:0000269|PubMed:17273969,
FT ECO:0000269|PubMed:19701948"
FT /id="VAR_062786"
FT VARIANT 141
FT /note="E -> K (in CDLS2; dbSNP:rs587784420)"
FT /evidence="ECO:0000269|PubMed:19701948"
FT /id="VAR_062787"
FT VARIANT 171..1233
FT /note="Missing (in DEE85)"
FT /evidence="ECO:0000269|PubMed:28166369"
FT /id="VAR_083971"
FT VARIANT 196
FT /note="R -> H (in CDLS2; dbSNP:rs1556890815)"
FT /evidence="ECO:0000269|PubMed:17221863,
FT ECO:0000269|PubMed:17273969, ECO:0000269|PubMed:19701948,
FT ECO:0000269|PubMed:20358602"
FT /id="VAR_062788"
FT VARIANT 268
FT /note="Missing (in CDLS2; dbSNP:rs727503773)"
FT /evidence="ECO:0000269|PubMed:19701948,
FT ECO:0000269|PubMed:20358602"
FT /id="VAR_062789"
FT VARIANT 306
FT /note="Missing (in CDLS2)"
FT /evidence="ECO:0000269|PubMed:19701948"
FT /id="VAR_062790"
FT VARIANT 398
FT /note="R -> G (in CDLS2)"
FT /evidence="ECO:0000269|PubMed:24124034"
FT /id="VAR_078274"
FT VARIANT 398
FT /note="R -> Q (in CDLS2; dbSNP:rs587784403)"
FT /evidence="ECO:0000269|PubMed:19701948"
FT /id="VAR_062791"
FT VARIANT 493
FT /note="E -> A (in CDLS2; affects the affinity of SMC hinge
FT dimers for DNA; mutated hinge dimers bind DNA with higher
FT affinity than wild-type proteins; dbSNP:rs122454122)"
FT /evidence="ECO:0000269|PubMed:16604071,
FT ECO:0000269|PubMed:18996922"
FT /id="VAR_026529"
FT VARIANT 496
FT /note="R -> C (in CDLS2; 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, ECO:0000269|PubMed:19701948"
FT /id="VAR_062792"
FT VARIANT 496
FT /note="R -> H (in CDLS2; affects the affinity of SMC hinge
FT dimers for DNA; mutated hinge dimers bind DNA with higher
FT affinity than wild-type proteins; dbSNP:rs122454123)"
FT /evidence="ECO:0000269|PubMed:17273969,
FT ECO:0000269|PubMed:18996922, ECO:0000269|PubMed:19701948"
FT /id="VAR_062793"
FT VARIANT 499..1233
FT /note="Missing (in DEE85)"
FT /evidence="ECO:0000269|PubMed:31334757"
FT /id="VAR_083972"
FT VARIANT 531..1233
FT /note="Missing (in DEE85)"
FT /evidence="ECO:0000269|PubMed:28166369"
FT /id="VAR_083973"
FT VARIANT 651
FT /note="V -> M (in CDLS2; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:24124034"
FT /id="VAR_078275"
FT VARIANT 683
FT /note="Missing (in CDLS2)"
FT /evidence="ECO:0000269|PubMed:19701948"
FT /id="VAR_062794"
FT VARIANT 693
FT /note="R -> G (in CDLS2)"
FT /evidence="ECO:0000269|PubMed:19701948"
FT /id="VAR_062795"
FT VARIANT 693
FT /note="R -> Q (in CDLS2; dbSNP:rs587784408)"
FT /evidence="ECO:0000269|PubMed:24124034"
FT /id="VAR_078276"
FT VARIANT 711
FT /note="R -> Q (in CDLS2; dbSNP:rs782176647)"
FT /evidence="ECO:0000269|PubMed:20358602"
FT /id="VAR_064542"
FT VARIANT 711
FT /note="R -> W (in CDLS2; dbSNP:rs587784409)"
FT /evidence="ECO:0000269|PubMed:17273969,
FT ECO:0000269|PubMed:19701948"
FT /id="VAR_062796"
FT VARIANT 733..1233
FT /note="Missing (in DEE85)"
FT /evidence="ECO:0000269|PubMed:28166369"
FT /id="VAR_083974"
FT VARIANT 781
FT /note="C -> F (in CDLS2)"
FT /evidence="ECO:0000269|PubMed:19701948"
FT /id="VAR_062797"
FT VARIANT 784
FT /note="I -> T (in CDLS2; dbSNP:rs387906702)"
FT /evidence="ECO:0000269|PubMed:20635401,
FT ECO:0000269|PubMed:24124034"
FT /id="VAR_064543"
FT VARIANT 790
FT /note="R -> Q (in CDLS2; dbSNP:rs797045993)"
FT /evidence="ECO:0000269|PubMed:17273969,
FT ECO:0000269|PubMed:19701948, ECO:0000269|PubMed:24124034"
FT /id="VAR_062798"
FT VARIANT 816
FT /note="R -> G (in CDLS2)"
FT /evidence="ECO:0000269|PubMed:19701948"
FT /id="VAR_062799"
FT VARIANT 832
FT /note="Missing (in CDLS2)"
FT /evidence="ECO:0000269|PubMed:16604071"
FT /id="VAR_026530"
FT VARIANT 895
FT /note="R -> G (in DEE85)"
FT /evidence="ECO:0000269|PubMed:31334757"
FT /id="VAR_083975"
FT VARIANT 975..1233
FT /note="Missing (in DEE85)"
FT /evidence="ECO:0000269|PubMed:28166369"
FT /id="VAR_083976"
FT VARIANT 1039..1233
FT /note="Missing (in DEE85)"
FT /evidence="ECO:0000269|PubMed:28166369"
FT /id="VAR_083977"
FT VARIANT 1049..1233
FT /note="Missing (in DEE85)"
FT /evidence="ECO:0000269|PubMed:28166369"
FT /id="VAR_083978"
FT VARIANT 1049
FT /note="R -> Q (in CDLS2; dbSNP:rs587784416)"
FT /evidence="ECO:0000269|PubMed:19701948"
FT /id="VAR_062800"
FT VARIANT 1085
FT /note="Y -> C (in CDLS2; dbSNP:rs587784418)"
FT /evidence="ECO:0000269|PubMed:17221863"
FT /id="VAR_062801"
FT VARIANT 1122
FT /note="F -> L (in CDLS2)"
FT /evidence="ECO:0000269|PubMed:17273969,
FT ECO:0000269|PubMed:19701948"
FT /id="VAR_062802"
FT VARIANT 1123
FT /note="R -> W (in CDLS2)"
FT /evidence="ECO:0000269|PubMed:19701948"
FT /id="VAR_062803"
FT VARIANT 1166
FT /note="N -> T (in CDLS2; unknown pathological significance;
FT dbSNP:rs1556885810)"
FT /evidence="ECO:0000269|PubMed:24124034"
FT /id="VAR_078277"
FT VARIANT 1189
FT /note="L -> F (in CDLS2; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:24124034"
FT /id="VAR_078278"
FT MUTAGEN 957
FT /note="S->A: Reduces phosphorylation and the S-phase
FT checkpoint activation. Abolishes S-phase activation; when
FT associated with A-966."
FT /evidence="ECO:0000269|PubMed:11877377"
FT MUTAGEN 966
FT /note="S->A: Reduces phosphorylation and the S-phase
FT checkpoint activation. Increases sensitivity to DNA
FT methylation. Abolishes S-phase activation; when associated
FT with A-957."
FT /evidence="ECO:0000269|PubMed:11877377,
FT ECO:0000269|PubMed:14657349"
FT CONFLICT 163..164
FT /note="EL -> DV (in Ref. 1; AAB34405)"
FT /evidence="ECO:0000305"
FT HELIX 500..510
FT /evidence="ECO:0007829|PDB:6WG4"
FT TURN 512..514
FT /evidence="ECO:0007829|PDB:6WG4"
FT STRAND 515..518
FT /evidence="ECO:0007829|PDB:6WG4"
FT HELIX 519..522
FT /evidence="ECO:0007829|PDB:6WG4"
FT STRAND 523..527
FT /evidence="ECO:0007829|PDB:6WG4"
FT HELIX 528..530
FT /evidence="ECO:0007829|PDB:6WG4"
FT HELIX 531..538
FT /evidence="ECO:0007829|PDB:6WG4"
FT HELIX 539..543
FT /evidence="ECO:0007829|PDB:6WG4"
FT STRAND 545..548
FT /evidence="ECO:0007829|PDB:6WG4"
FT HELIX 550..562
FT /evidence="ECO:0007829|PDB:6WG4"
FT STRAND 570..572
FT /evidence="ECO:0007829|PDB:6WG4"
FT HELIX 583..587
FT /evidence="ECO:0007829|PDB:6WG4"
FT STRAND 591..594
FT /evidence="ECO:0007829|PDB:6WG4"
FT HELIX 595..597
FT /evidence="ECO:0007829|PDB:6WG4"
FT STRAND 598..602
FT /evidence="ECO:0007829|PDB:6WG4"
FT HELIX 603..605
FT /evidence="ECO:0007829|PDB:6WG4"
FT HELIX 606..613
FT /evidence="ECO:0007829|PDB:6WG4"
FT STRAND 617..621
FT /evidence="ECO:0007829|PDB:6WG4"
FT HELIX 622..630
FT /evidence="ECO:0007829|PDB:6WG4"
FT STRAND 631..634
FT /evidence="ECO:0007829|PDB:6WG4"
FT STRAND 652..654
FT /evidence="ECO:0007829|PDB:6WG4"
FT HELIX 656..663
FT /evidence="ECO:0007829|PDB:6WG4"
FT HELIX 665..668
FT /evidence="ECO:0007829|PDB:6WG4"
SQ SEQUENCE 1233 AA; 143233 MW; E0A44CA7476C88A6 CRC64;
MGFLKLIEIE NFKSYKGRQI IGPFQRFTAI IGPNGSGKSN LMDAISFVLG EKTSNLRVKT
LRDLIHGAPV GKPAANRAFV SMVYSEEGAE DRTFARVIVG GSSEYKINNK VVQLHEYSEE
LEKLGILIKA RNFLVFQGAV ESIAMKNPKE RTALFEEISR SGELAQEYDK RKKEMVKAEE
DTQFNYHRKK NIAAERKEAK QEKEEADRYQ RLKDEVVRAQ VQLQLFKLYH NEVEIEKLNK
ELASKNKEIE KDKKRMDKVE DELKEKKKEL GKMMREQQQI EKEIKEKDSE LNQKRPQYIK
AKENTSHKIK KLEAAKKSLQ NAQKHYKKRK GDMDELEKEM LSVEKARQEF EERMEEESQS
QGRDLTLEEN QVKKYHRLKE EASKRAATLA QELEKFNRDQ KADQDRLDLE ERKKVETEAK
IKQKLREIEE NQKRIEKLEE YITTSKQSLE EQKKLEGELT EEVEMAKRRI DEINKELNQV
MEQLGDARID RQESSRQQRK AEIMESIKRL YPGSVYGRLI DLCQPTQKKY QIAVTKVLGK
NMDAIIVDSE KTGRDCIQYI KEQRGEPETF LPLDYLEVKP TDEKLRELKG AKLVIDVIRY
EPPHIKKALQ YACGNALVCD NVEDARRIAF GGHQRHKTVA LDGTLFQKSG VISGGASDLK
AKARRWDEKA VDKLKEKKER LTEELKEQMK AKRKEAELRQ VQSQAHGLQM RLKYSQSDLE
QTKTRHLALN LQEKSKLESE LANFGPRIND IKRIIQSRER EMKDLKEKMN QVEDEVFEEF
CREIGVRNIR EFEEEKVKRQ NEIAKKRLEF ENQKTRLGIQ LDFEKNQLKE DQDKVHMWEQ
TVKKDENEIE KLKKEEQRHM KIIDETMAQL QDLKNQHLAK KSEVNDKNHE MEEIRKKLGG
ANKEMTHLQK EVTAIETKLE QKRSDRHNLL QACKMQDIKL PLSKGTMDDI SQEEGSSQGE
DSVSGSQRIS SIYAREALIE IDYGDLCEDL KDAQAEEEIK QEMNTLQQKL NEQQSVLQRI
AAPNMKAMEK LESVRDKFQE TSDEFEAARK RAKKAKQAFE QIKKERFDRF NACFESVATN
IDEIYKALSR NSSAQAFLGP ENPEEPYLDG INYNCVAPGK RFRPMDNLSG GEKTVAALAL
LFAIHSYKPA PFFVLDEIDA ALDNTNIGKV ANYIKEQSTC NFQAIVISLK EEFYTKAESL
IGVYPEQGDC VISKVLTFDL TKYPDANPNP NEQ
