ID SMHD1_HUMAN Reviewed; 2005 AA. AC A6NHR9; O75141; Q6AHX6; Q6ZTQ8; Q9H6Q2; Q9UG39; DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot. DT 29-APR-2008, sequence version 2. DT 27-MAR-2024, entry version 139. DE RecName: Full=Structural maintenance of chromosomes flexible hinge domain-containing protein 1 {ECO:0000250|UniProtKB:Q6P5D8}; DE Short=SMC hinge domain-containing protein 1 {ECO:0000250|UniProtKB:Q6P5D8}; DE EC=3.6.1.- {ECO:0000269|PubMed:29748383}; GN Name=SMCHD1 {ECO:0000312|HGNC:HGNC:29090}; GN Synonyms=KIAA0650 {ECO:0000303|PubMed:9734811}; 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 [LARGE SCALE MRNA] (ISOFORM 3), AND NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 1674-2005 (ISOFORM 1). RC TISSUE=Trachea; 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 [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16177791; DOI=10.1038/nature03983; RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D., RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J., RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L., RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., RA Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K., RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R., RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.; RT "DNA sequence and analysis of human chromosome 18."; RL Nature 437:551-555(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 530-2005 (ISOFORM 2), AND RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1278-2005 (ISOFORM 1). RC TISSUE=Testis; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1158-2005 (ISOFORM 1). RC TISSUE=Brain; RX PubMed=9734811; DOI=10.1093/dnares/5.3.169; RA Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H., RA Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. X. The RT complete sequences of 100 new cDNA clones from brain which can code for RT large proteins in vitro."; RL DNA Res. 5:169-176(1998). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1699-2005 (ISOFORM 1). RC TISSUE=Eye; 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 2-26; 280-288; 663-671; 826-836; 1208-1220; 1267-1275 RP AND 1495-1506, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Ovarian carcinoma; RA Bienvenut W.V., Lilla S., von Kriegsheim A., Lempens A., Kolch W.; RL Submitted (DEC-2008) to UniProtKB. RN [7] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [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 [8] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-1349, AND IDENTIFICATION BY MASS RP 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 [9] 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 [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-1499 AND SER-1974, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=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 [11] RP FUNCTION, AND INTERACTION WITH LRIF1. RX PubMed=23542155; DOI=10.1038/nsmb.2532; RA Nozawa R.S., Nagao K., Igami K.T., Shibata S., Shirai N., Nozaki N., RA Sado T., Kimura H., Obuse C.; RT "Human inactive X chromosome is compacted through a PRC2-independent RT SMCHD1-HBiX1 pathway."; RL Nat. Struct. Mol. Biol. 20:566-573(2013). RN [12] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=25294876; DOI=10.1074/jbc.m114.601179; RA Tang M., Li Y., Zhang X., Deng T., Zhou Z., Ma W., Songyang Z.; RT "Structural maintenance of chromosomes flexible hinge domain containing 1 RT (SMCHD1) promotes non-homologous end joining and inhibits homologous RT recombination repair upon DNA damage."; RL J. Biol. Chem. 289:34024-34032(2014). RN [13] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=24790221; DOI=10.1242/jcs.140020; RA Coker H., Brockdorff N.; RT "SMCHD1 accumulates at DNA damage sites and facilitates the repair of DNA RT double-strand breaks."; RL J. Cell Sci. 127:1869-1874(2014). RN [14] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-1374, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25218447; DOI=10.1038/nsmb.2890; RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M., RA Vertegaal A.C.; RT "Uncovering global SUMOylation signaling networks in a site-specific RT manner."; RL Nat. Struct. Mol. Biol. 21:927-936(2014). RN [15] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-1374 AND LYS-1496, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [16] RP VARIANTS FSHD2 CYS-353; PRO-479; ARG-492; SER-690; ASN-868 AND SER-1554, RP FUNCTION, AND INVOLVEMENT IN FSHD2. RX PubMed=23143600; DOI=10.1038/ng.2454; RA Lemmers R.J., Tawil R., Petek L.M., Balog J., Block G.J., Santen G.W., RA Amell A.M., van der Vliet P.J., Almomani R., Straasheijm K.R., Krom Y.D., RA Klooster R., Sun Y., den Dunnen J.T., Helmer Q., Donlin-Smith C.M., RA Padberg G.W., van Engelen B.G., de Greef J.C., Aartsma-Rus A.M., RA Frants R.R., de Visser M., Desnuelle C., Sacconi S., Filippova G.N., RA Bakker B., Bamshad M.J., Tapscott S.J., Miller D.G., van der Maarel S.M.; RT "Digenic inheritance of an SMCHD1 mutation and an FSHD-permissive D4Z4 RT allele causes facioscapulohumeral muscular dystrophy type 2."; RL Nat. Genet. 44:1370-1374(2012). RN [17] RP VARIANT FSHD2 MET-527. RX PubMed=24075187; DOI=10.1016/j.ajhg.2013.08.004; RA Sacconi S., Lemmers R.J., Balog J., van der Vliet P.J., Lahaut P., RA van Nieuwenhuizen M.P., Straasheijm K.R., Debipersad R.D., Vos-Versteeg M., RA Salviati L., Casarin A., Pegoraro E., Tawil R., Bakker E., Tapscott S.J., RA Desnuelle C., van der Maarel S.M.; RT "The FSHD2 gene SMCHD1 is a modifier of disease severity in families RT affected by FSHD1."; RL Am. J. Hum. Genet. 93:744-751(2013). RN [18] RP VARIANT FSHD2 LYS-275 DEL. RX PubMed=24128691; DOI=10.1016/j.nmd.2013.08.009; RA Mitsuhashi S., Boyden S.E., Estrella E.A., Jones T.I., Rahimov F., Yu T.W., RA Darras B.T., Amato A.A., Folkerth R.D., Jones P.L., Kunkel L.M., Kang P.B.; RT "Exome sequencing identifies a novel SMCHD1 mutation in facioscapulohumeral RT muscular dystrophy 2."; RL Neuromuscul. Disord. 23:975-980(2013). RN [19] RP VARIANTS FSHD2 THR-110; GLU-478; ASP-615; LYS-1449; PRO-1463; LEU-1485 AND RP 1663-LEU--VAL-2005 DEL. RX PubMed=25370034; DOI=10.1038/ejhg.2014.191; RA Larsen M., Rost S., El Hajj N., Ferbert A., Deschauer M., Walter M.C., RA Schoser B., Tacik P., Kress W., Mueller C.R.; RT "Diagnostic approach for FSHD revisited: SMCHD1 mutations cause FSHD2 and RT act as modifiers of disease severity in FSHD1."; RL Eur. J. Hum. Genet. 23:808-816(2015). RN [20] RP VARIANTS FSHD2 GLU-137; 138-GLN--VAL-2005 DEL; PHE-194; 195-ASN--VAL-2005 RP DEL; ASP-263; 344-ARG--VAL-2005 DEL; CYS-353; ARG-425; 434-TYR--VAL-2005 RP DEL; PRO-479; SER-690; SER-716; 731-GLN--VAL-2005 DEL; PRO-748; RP 780-GLU--VAL-2005 DEL; ASN-849; ASN-868; ILE-1468; SER-1554; RP 1176-THR-ASP-1177 DELINS MET-HIS; 1795-ARG--VAL-2005 DEL AND RP 1868-ARG--VAL-2005 DEL. RX PubMed=25256356; DOI=10.1093/hmg/ddu486; RA Lemmers R.J., Goeman J.J., van der Vliet P.J., van Nieuwenhuizen M.P., RA Balog J., Vos-Versteeg M., Camano P., Ramos Arroyo M.A., Jerico I., RA Rogers M.T., Miller D.G., Upadhyaya M., Verschuuren J.J., RA Lopez de Munain Arregui A., van Engelen B.G., Padberg G.W., Sacconi S., RA Tawil R., Tapscott S.J., Bakker B., van der Maarel S.M.; RT "Inter-individual differences in CpG methylation at D4Z4 correlate with RT clinical variability in FSHD1 and FSHD2."; RL Hum. Mol. Genet. 24:659-669(2015). RN [21] RP VARIANT FSHD2 ARG-425. RX PubMed=27059856; DOI=10.1042/bcj20160189; RA Chen K., Dobson R.C., Lucet I.S., Young S.N., Pearce F.G., Blewitt M.E., RA Murphy J.M.; RT "The epigenetic regulator Smchd1 contains a functional GHKL-type ATPase RT domain."; RL Biochem. J. 473:1733-1744(2016). RN [22] RP INVOLVEMENT IN BAMS, VARIANTS BAMS PRO-107; LYS-129; ASN-135; CYS-135; RP ILE-135; ASP-136; GLU-137; HIS-139; PHE-141; VAL-171; GLY-242; ARG-345; RP ARG-348; LEU-400; VAL-420; GLN-473; LYS-523; SER-524 AND GLN-552, AND RP CHARACTERIZATION OF VARIANTS BAMS PRO-107; LYS-129; ASN-135; CYS-135; RP ILE-135; ASP-136; GLU-137; HIS-139; PHE-141; VAL-171; GLY-242; ARG-345; RP ARG-348; LEU-400; VAL-420; GLN-473; LYS-523; SER-524 AND GLN-552. RX PubMed=28067909; DOI=10.1038/ng.3743; RA Shaw N.D., Brand H., Kupchinsky Z.A., Bengani H., Plummer L., Jones T.I., RA Erdin S., Williamson K.A., Rainger J., Stortchevoi A., Samocha K., RA Currall B.B., Dunican D.S., Collins R.L., Willer J.R., Lek A., Lek M., RA Nassan M., Pereira S., Kammin T., Lucente D., Silva A., Seabra C.M., RA Chiang C., An Y., Ansari M., Rainger J.K., Joss S., Smith J.C., RA Lippincott M.F., Singh S.S., Patel N., Jing J.W., Law J.R., Ferraro N., RA Verloes A., Rauch A., Steindl K., Zweier M., Scheer I., Sato D., RA Okamoto N., Jacobsen C., Tryggestad J., Chernausek S., Schimmenti L.A., RA Brasseur B., Cesaretti C., Garcia-Ortiz J.E., Buitrago T.P., Silva O.P., RA Hoffman J.D., Muehlbauer W., Ruprecht K.W., Loeys B.L., Shino M., RA Kaindl A.M., Cho C.H., Morton C.C., Meehan R.R., van Heyningen V., RA Liao E.C., Balasubramanian R., Hall J.E., Seminara S.B., Macarthur D., RA Moore S.A., Yoshiura K.I., Gusella J.F., Marsh J.A., Graham J.M. Jr., RA Lin A.E., Katsanis N., Jones P.L., Crowley W.F. Jr., Davis E.E., RA FitzPatrick D.R., Talkowski M.E.; RT "SMCHD1 mutations associated with a rare muscular dystrophy can also cause RT isolated arhinia and Bosma arhinia microphthalmia syndrome."; RL Nat. Genet. 49:238-248(2017). RN [23] RP VARIANTS BAMS SER-134; ASN-135; CYS-135; GLY-136; SER-342; ARG-348; RP VAL-420; GLU-518 AND GLN-552, CHARACTERIZATION OF VARIANTS BAMS SER-134; RP CYS-135; GLY-136 AND VAL-420, AND CHARACTERIZATION OF VARIANTS FSHD2 RP CYS-353 AND MET-527. RX PubMed=28067911; DOI=10.1038/ng.3765; RA Gordon C.T., Xue S., Yigit G., Filali H., Chen K., Rosin N., Yoshiura K.I., RA Oufadem M., Beck T.J., McGowan R., Magee A.C., Altmueller J., Dion C., RA Thiele H., Gurzau A.D., Nuernberg P., Meschede D., Muehlbauer W., RA Okamoto N., Varghese V., Irving R., Sigaudy S., Williams D., Ahmed S.F., RA Bonnard C., Kong M.K., Ratbi I., Fejjal N., Fikri M., Elalaoui S.C., RA Reigstad H., Bole-Feysot C., Nitschke P., Ragge N., Levy N., Tuncbilek G., RA Teo A.S., Cunningham M.L., Sefiani A., Kayserili H., Murphy J.M., RA Chatdokmaiprai C., Hillmer A.M., Wattanasirichaigoon D., Lyonnet S., RA Magdinier F., Javed A., Blewitt M.E., Amiel J., Wollnik B., Reversade B.; RT "De novo mutations in SMCHD1 cause Bosma arhinia microphthalmia syndrome RT and abrogate nasal development."; RL Nat. Genet. 49:249-255(2017). RN [24] RP VARIANTS FSHD2 PHE-194; ASP-263; CYS-283; CYS-353; GLU-478; MET-527 AND RP SER-690, VARIANTS BAMS ASN-135; GLU-137; SER-342; ARG-348; VAL-420; RP GLN-473; GLU-518; LYS-523 AND GLN-552, CHARACTERIZATION OF VARIANTS FSHD2 RP PHE-194; ASP-263; CYS-283; CYS-353; GLU-478; MET-527 AND SER-690, RP CHARACTERIZATION OF VARIANTS BAMS ASN-135; GLU-137; SER-342; ARG-348; RP VAL-420; GLN-473; GLU-518; LYS-523 AND GLN-552, FUNCTION, AND CATALYTIC RP ACTIVITY. RX PubMed=29748383; DOI=10.1074/jbc.ra118.003104; RA Gurzau A.D., Chen K., Xue S., Dai W., Lucet I.S., Ly T.T.N., Reversade B., RA Blewitt M.E., Murphy J.M.; RT "FSHD2- and BAMS-associated mutations confer opposing effects on SMCHD1 RT function."; RL J. Biol. Chem. 293:9841-9853(2018). CC -!- FUNCTION: Non-canonical member of the structural maintenance of CC chromosomes (SMC) protein family that plays a key role in epigenetic CC silencing by regulating chromatin architecture (By similarity). CC Promotes heterochromatin formation in both autosomes and chromosome X, CC probably by mediating the merge of chromatin compartments (By CC similarity). Plays a key role in chromosome X inactivation in females CC by promoting the spreading of heterochromatin (PubMed:23542155). CC Recruited to inactivated chromosome X by Xist RNA and acts by mediating CC the merge of chromatin compartments: promotes random chromatin CC interactions that span the boundaries of existing structures, leading CC to create a compartment-less architecture typical of inactivated CC chromosome X (By similarity). Required to facilitate Xist RNA spreading CC (By similarity). Also required for silencing of a subset of clustered CC autosomal loci in somatic cells, such as the DUX4 locus CC (PubMed:23143600). Has ATPase activity; may participate in structural CC manipulation of chromatin in an ATP-dependent manner as part of its CC role in gene expression regulation (PubMed:29748383). Also plays a role CC in DNA repair: localizes to sites of DNA double-strand breaks in CC response to DNA damage to promote the repair of DNA double-strand CC breaks (PubMed:25294876, PubMed:24790221). Acts by promoting non- CC homologous end joining (NHEJ) and inhibiting homologous recombination CC (HR) repair (PubMed:25294876). {ECO:0000250|UniProtKB:Q6P5D8, CC ECO:0000269|PubMed:23143600, ECO:0000269|PubMed:23542155, CC ECO:0000269|PubMed:24790221, ECO:0000269|PubMed:25294876, CC ECO:0000269|PubMed:29748383}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; CC Evidence={ECO:0000269|PubMed:29748383}; CC -!- SUBUNIT: Homodimer; homodimerizes via its SMC hinge domain (By CC similarity). Interacts with LRIF1 (PubMed:23542155). CC {ECO:0000250|UniProtKB:Q6P5D8, ECO:0000269|PubMed:23542155}. CC -!- INTERACTION: CC A6NHR9; Q5T3J3: LRIF1; NbExp=9; IntAct=EBI-2801919, EBI-473196; CC -!- SUBCELLULAR LOCATION: Chromosome {ECO:0000269|PubMed:24790221, CC ECO:0000269|PubMed:25294876}. Note=Recruited to inactivated chromosome CC X in females by Xist RNA (By similarity). Localizes at sites of DNA CC damage at double-strand breaks (DSBs) (PubMed:25294876, CC PubMed:24790221). {ECO:0000250|UniProtKB:Q6P5D8, CC ECO:0000269|PubMed:24790221, ECO:0000269|PubMed:25294876}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=A6NHR9-1; Sequence=Displayed; CC Name=2; CC IsoId=A6NHR9-2; Sequence=VSP_033347, VSP_033348; CC Name=3; CC IsoId=A6NHR9-3; Sequence=VSP_033344, VSP_033345, VSP_033346; CC -!- DOMAIN: Atypical member of the structural maintenance of chromosomes CC (SMC) protein family. Like other members of the SMC family, has ATPase CC activity, which is probably necessary for its engagement with CC chromatin, and a SMC hinge domain. However, the SMC hinge domain adopts CC an unconventional homodimeric arrangement augmented by an CC intermolecular coiled coil formed between the two monomers. This CC suggests that protein may assemble as a head-to-head parallel dimer CC without adopting a hairpin shape at the hinge domain, unlike the CC dimeric arrangement conventionally found in other members of the SMC CC protein family. The SMC hinge domain binds DNA and RNA. CC {ECO:0000250|UniProtKB:Q6P5D8}. CC -!- PTM: Sumoylated with SUMO1. {ECO:0000250|UniProtKB:Q6P5D8}. CC -!- DISEASE: Facioscapulohumeral muscular dystrophy 2, digenic (FSHD2) CC [MIM:158901]: A degenerative muscle disease characterized by slowly CC progressive weakness of the muscles of the face, upper-arm, and CC shoulder girdle. The onset of symptoms usually occurs in the first or CC second decade of life. Affected individuals usually present with CC impairment of upper extremity elevation. This tends to be followed by CC facial weakness, primarily involving the orbicularis oris and CC orbicularis oculi muscles. {ECO:0000269|PubMed:23143600, CC ECO:0000269|PubMed:24075187, ECO:0000269|PubMed:24128691, CC ECO:0000269|PubMed:25256356, ECO:0000269|PubMed:25370034, CC ECO:0000269|PubMed:27059856, ECO:0000269|PubMed:28067911, CC ECO:0000269|PubMed:29748383}. Note=The disease is caused by variants CC affecting the gene represented in this entry. SMCHD1 mutations lead to CC DUX4 expression in somatic tissues, including muscle cells, when an CC haplotype on chromosome 4 is permissive for DUX4 expression CC (PubMed:23143600). Ectopic expression of DUX4 in skeletal muscle CC activates the expression of stem cell and germline genes, and, when CC overexpressed in somatic cells, DUX4 can ultimately lead to cell death CC (PubMed:23143600). FSHD2 and FSHD1 share a common pathophysiological CC pathway in which the FSHD2 gene SMCHD1 can act as a modifier for CC disease severity in families affected by FSHD1 (PubMed:24075187, CC PubMed:25370034). {ECO:0000269|PubMed:23143600, CC ECO:0000269|PubMed:24075187, ECO:0000269|PubMed:25370034}. CC -!- DISEASE: Bosma arhinia microphthalmia syndrome (BAMS) [MIM:603457]: An CC autosomal dominant syndrome characterized by severe hypoplasia of the CC nose, palatal abnormalities, hypoplasia of the eyes, sensory CC abnormalities of taste and smell, hypogonadotropic hypogonadism with CC cryptorchidism, and normal intelligence. {ECO:0000269|PubMed:28067909, CC ECO:0000269|PubMed:28067911, ECO:0000269|PubMed:29748383}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the SMC family. Highly divergent. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAB15202.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BC035774; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=CAH10538.1; Type=Erroneous initiation; Note=Truncated N-terminus.; 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; AK025646; BAB15202.1; ALT_INIT; mRNA. DR EMBL; AK126324; BAC86525.1; -; mRNA. DR EMBL; AP001011; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AP005061; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL080138; CAB45732.1; -; mRNA. DR EMBL; CR627458; CAH10538.1; ALT_INIT; mRNA. DR EMBL; AB014550; BAA31625.1; -; mRNA. DR EMBL; BC035774; -; NOT_ANNOTATED_CDS; mRNA. DR CCDS; CCDS45822.1; -. [A6NHR9-1] DR PIR; T00372; T00372. DR RefSeq; NP_056110.2; NM_015295.2. [A6NHR9-1] DR PDB; 6MW7; X-ray; 2.19 A; A/B/C/D=24-580. DR PDBsum; 6MW7; -. DR AlphaFoldDB; A6NHR9; -. DR SMR; A6NHR9; -. DR BioGRID; 116929; 178. DR IntAct; A6NHR9; 53. DR MINT; A6NHR9; -. DR STRING; 9606.ENSP00000326603; -. DR GlyGen; A6NHR9; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; A6NHR9; -. DR PhosphoSitePlus; A6NHR9; -. DR SwissPalm; A6NHR9; -. DR BioMuta; SMCHD1; -. DR EPD; A6NHR9; -. DR jPOST; A6NHR9; -. DR MassIVE; A6NHR9; -. DR MaxQB; A6NHR9; -. DR PaxDb; 9606-ENSP00000326603; -. DR PeptideAtlas; A6NHR9; -. DR ProteomicsDB; 1220; -. [A6NHR9-1] DR ProteomicsDB; 1221; -. [A6NHR9-2] DR ProteomicsDB; 1222; -. [A6NHR9-3] DR Pumba; A6NHR9; -. DR Antibodypedia; 49899; 108 antibodies from 20 providers. DR DNASU; 23347; -. DR Ensembl; ENST00000320876.11; ENSP00000326603.7; ENSG00000101596.17. [A6NHR9-1] DR GeneID; 23347; -. DR KEGG; hsa:23347; -. DR MANE-Select; ENST00000320876.11; ENSP00000326603.7; NM_015295.3; NP_056110.2. DR UCSC; uc002klm.5; human. [A6NHR9-1] DR AGR; HGNC:29090; -. DR DisGeNET; 23347; -. DR GeneCards; SMCHD1; -. DR GeneReviews; SMCHD1; -. DR HGNC; HGNC:29090; SMCHD1. DR HPA; ENSG00000101596; Low tissue specificity. DR MalaCards; SMCHD1; -. DR MIM; 158901; phenotype. DR MIM; 603457; phenotype. DR MIM; 614982; gene. DR neXtProt; NX_A6NHR9; -. DR OpenTargets; ENSG00000101596; -. DR Orphanet; 269; Facioscapulohumeral dystrophy. DR Orphanet; 2250; Hyposmia-nasal and ocular hypoplasia-hypogonadotropic hypogonadism syndrome. DR PharmGKB; PA128395776; -. DR VEuPathDB; HostDB:ENSG00000101596; -. DR eggNOG; ENOG502QREW; Eukaryota. DR GeneTree; ENSGT00390000006950; -. DR HOGENOM; CLU_002288_1_0_1; -. DR InParanoid; A6NHR9; -. DR OMA; PRGEHIM; -. DR OrthoDB; 5388904at2759; -. DR PhylomeDB; A6NHR9; -. DR TreeFam; TF329426; -. DR PathwayCommons; A6NHR9; -. DR SignaLink; A6NHR9; -. DR BioGRID-ORCS; 23347; 61 hits in 1161 CRISPR screens. DR ChiTaRS; SMCHD1; human. DR GenomeRNAi; 23347; -. DR Pharos; A6NHR9; Tbio. DR PRO; PR:A6NHR9; -. DR Proteomes; UP000005640; Chromosome 18. DR RNAct; A6NHR9; Protein. DR Bgee; ENSG00000101596; Expressed in calcaneal tendon and 202 other cell types or tissues. DR ExpressionAtlas; A6NHR9; baseline and differential. DR GO; GO:0001740; C:Barr body; IDA:UniProtKB. DR GO; GO:0035861; C:site of double-strand break; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:InterPro. DR GO; GO:0016887; F:ATP hydrolysis activity; ISS:UniProtKB. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB. DR GO; GO:0051276; P:chromosome organization; IEA:InterPro. DR GO; GO:0010424; P:DNA methylation on cytosine within a CG sequence; IEA:Ensembl. DR GO; GO:0009048; P:dosage compensation by inactivation of X chromosome; IDA:UniProtKB. DR GO; GO:0006302; P:double-strand break repair; IEA:InterPro. DR GO; GO:2000042; P:negative regulation of double-strand break repair via homologous recombination; IMP:UniProtKB. DR GO; GO:0043584; P:nose development; IMP:UniProtKB. DR GO; GO:0045739; P:positive regulation of DNA repair; IMP:UniProtKB. DR GO; GO:2001034; P:positive regulation of double-strand break repair via nonhomologous end joining; IMP:UniProtKB. DR CDD; cd16937; HATPase_SMCHD1-like; 1. DR Gene3D; 3.30.565.10; Histidine kinase-like ATPase, C-terminal domain; 1. DR InterPro; IPR036890; HATPase_C_sf. DR InterPro; IPR010935; SMC_hinge. DR InterPro; IPR036277; SMC_hinge_sf. DR InterPro; IPR038892; SMCHD1. DR PANTHER; PTHR22640:SF2; STRUCTURAL MAINTENANCE OF CHROMOSOMES FLEXIBLE HINGE DOMAIN-CONTAINING PROTEIN 1; 1. DR PANTHER; PTHR22640; UNCHARACTERIZED; 1. DR Pfam; PF13589; HATPase_c_3; 1. DR Pfam; PF06470; SMC_hinge; 1. DR SMART; SM00968; SMC_hinge; 1. DR SUPFAM; SSF55874; ATPase domain of HSP90 chaperone/DNA topoisomerase II/histidine kinase; 1. DR SUPFAM; SSF75553; Smc hinge domain; 1. DR Genevisible; A6NHR9; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Chromatin regulator; KW Chromosome; Direct protein sequencing; Disease variant; DNA damage; KW DNA repair; DNA-binding; Hydrolase; Hypogonadotropic hypogonadism; KW Isopeptide bond; Kallmann syndrome; Microphthalmia; Phosphoprotein; KW Reference proteome; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|Ref.6, ECO:0007744|PubMed:19413330" FT CHAIN 2..2005 FT /note="Structural maintenance of chromosomes flexible hinge FT domain-containing protein 1" FT /id="PRO_0000332144" FT DOMAIN 1720..1847 FT /note="SMC hinge" FT /evidence="ECO:0000255" FT REGION 1..23 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 111..702 FT /note="ATPase activity domain" FT /evidence="ECO:0000250|UniProtKB:Q6P5D8" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000269|Ref.6, ECO:0007744|PubMed:19413330" FT MOD_RES 1349 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 1499 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1802 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q6P5D8" FT MOD_RES 1974 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT CROSSLNK 1374 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:25218447, FT ECO:0007744|PubMed:28112733" FT CROSSLNK 1496 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT VAR_SEQ 1..1065 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_033344" FT VAR_SEQ 1826..1827 FT /note="VF -> GC (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_033345" FT VAR_SEQ 1828..2005 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_033346" FT VAR_SEQ 1907..1917 FT /note="DLLQQYRSAVC -> VHACVPSYSGG (in isoform 2)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_033347" FT VAR_SEQ 1918..2005 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_033348" FT VARIANT 107 FT /note="L -> P (in BAMS; no change in protein abundance; FT dbSNP:rs1135402737)" FT /evidence="ECO:0000269|PubMed:28067909" FT /id="VAR_078869" FT VARIANT 110 FT /note="A -> T (in FSHD2)" FT /evidence="ECO:0000269|PubMed:25370034" FT /id="VAR_080698" FT VARIANT 129 FT /note="M -> K (in BAMS; no change in protein abundance; FT dbSNP:rs1135402738)" FT /evidence="ECO:0000269|PubMed:28067909" FT /id="VAR_078870" FT VARIANT 134 FT /note="A -> S (in BAMS; has an increased ATPase activity)" FT /evidence="ECO:0000269|PubMed:28067911" FT /id="VAR_078871" FT VARIANT 135 FT /note="S -> C (in BAMS; has an increased ATPase activity; FT no change in protein abundance; dbSNP:rs1057519645)" FT /evidence="ECO:0000269|PubMed:28067909, FT ECO:0000269|PubMed:28067911" FT /id="VAR_078872" FT VARIANT 135 FT /note="S -> I (in BAMS; no change in protein abundance; FT dbSNP:rs1057519646)" FT /evidence="ECO:0000269|PubMed:28067909" FT /id="VAR_078873" FT VARIANT 135 FT /note="S -> N (in BAMS; no change in protein abundance; FT does not affect ATPase activity; dbSNP:rs1057519646)" FT /evidence="ECO:0000269|PubMed:28067909, FT ECO:0000269|PubMed:28067911, ECO:0000269|PubMed:29748383" FT /id="VAR_078874" FT VARIANT 136 FT /note="E -> D (in BAMS; no change in protein abundance; FT dbSNP:rs1057519643)" FT /evidence="ECO:0000269|PubMed:28067909" FT /id="VAR_078875" FT VARIANT 136 FT /note="E -> G (in BAMS; has an increased ATPase activity)" FT /evidence="ECO:0000269|PubMed:28067911" FT /id="VAR_078876" FT VARIANT 137 FT /note="G -> E (in BAMS and FSHD2; no change in protein FT abundance; strongly increased ATPase activity; FT dbSNP:rs1057519644)" FT /evidence="ECO:0000269|PubMed:25256356, FT ECO:0000269|PubMed:28067909, ECO:0000269|PubMed:29748383" FT /id="VAR_078877" FT VARIANT 138..2005 FT /note="Missing (in FSHD2)" FT /evidence="ECO:0000269|PubMed:25256356" FT /id="VAR_078878" FT VARIANT 139 FT /note="N -> H (in BAMS; no change in protein abundance; FT dbSNP:rs1135402739)" FT /evidence="ECO:0000269|PubMed:28067909" FT /id="VAR_078879" FT VARIANT 141 FT /note="L -> F (in BAMS; no change in protein abundance; FT dbSNP:rs1057519641)" FT /evidence="ECO:0000269|PubMed:28067909" FT /id="VAR_078880" FT VARIANT 171 FT /note="F -> V (in BAMS; no change in protein abundance; FT dbSNP:rs1135402740)" FT /evidence="ECO:0000269|PubMed:28067909" FT /id="VAR_078881" FT VARIANT 194 FT /note="L -> F (in FSHD2; decreased ATPase activity)" FT /evidence="ECO:0000269|PubMed:25256356, FT ECO:0000269|PubMed:29748383" FT /id="VAR_078882" FT VARIANT 195..2005 FT /note="Missing (in FSHD2)" FT /evidence="ECO:0000269|PubMed:25256356" FT /id="VAR_078883" FT VARIANT 242 FT /note="A -> G (in BAMS; no change in protein abundance; FT dbSNP:rs1135402741)" FT /evidence="ECO:0000269|PubMed:28067909" FT /id="VAR_078884" FT VARIANT 263 FT /note="H -> D (in FSHD2; decreased ATPase activity)" FT /evidence="ECO:0000269|PubMed:25256356, FT ECO:0000269|PubMed:29748383" FT /id="VAR_078885" FT VARIANT 275 FT /note="Missing (in FSHD2; uncertain significance; FT dbSNP:rs746679988)" FT /evidence="ECO:0000269|PubMed:24128691" FT /id="VAR_080699" FT VARIANT 283 FT /note="Y -> C (in FSHD2; does not affect ATPase activity; FT dbSNP:rs886041921)" FT /evidence="ECO:0000269|PubMed:29748383" FT /id="VAR_080700" FT VARIANT 342 FT /note="W -> S (in BAMS; slightly decreased ATPase FT activity)" FT /evidence="ECO:0000269|PubMed:28067911, FT ECO:0000269|PubMed:29748383" FT /id="VAR_078886" FT VARIANT 344..2005 FT /note="Missing (in FSHD2)" FT /evidence="ECO:0000269|PubMed:25256356" FT /id="VAR_078887" FT VARIANT 345 FT /note="Q -> R (in BAMS; no change in protein abundance; FT dbSNP:rs1057519639)" FT /evidence="ECO:0000269|PubMed:28067909" FT /id="VAR_078888" FT VARIANT 348 FT /note="H -> R (in BAMS; no change in protein abundance; FT does not affect ATPase activity; dbSNP:rs1057519640)" FT /evidence="ECO:0000269|PubMed:28067909, FT ECO:0000269|PubMed:28067911, ECO:0000269|PubMed:29748383" FT /id="VAR_078889" FT VARIANT 353 FT /note="Y -> C (in FSHD2; decreased protein level in FT fibroblasts as compared to wild-type protein; abolished FT ATPase activity)" FT /evidence="ECO:0000269|PubMed:23143600, FT ECO:0000269|PubMed:25256356, ECO:0000269|PubMed:28067911, FT ECO:0000269|PubMed:29748383" FT /id="VAR_069067" FT VARIANT 400 FT /note="Q -> L (in BAMS; no change in protein abundance; FT dbSNP:rs1057519642)" FT /evidence="ECO:0000269|PubMed:28067909" FT /id="VAR_078890" FT VARIANT 420 FT /note="D -> V (in BAMS; no change in protein abundance; FT slightly decreased ATPase activity; dbSNP:rs1135402742)" FT /evidence="ECO:0000269|PubMed:28067909, FT ECO:0000269|PubMed:28067911, ECO:0000269|PubMed:29748383" FT /id="VAR_078891" FT VARIANT 425 FT /note="G -> R (in FSHD2)" FT /evidence="ECO:0000269|PubMed:25256356, FT ECO:0000269|PubMed:27059856" FT /id="VAR_078892" FT VARIANT 434..2005 FT /note="Missing (in FSHD2)" FT /evidence="ECO:0000269|PubMed:25256356" FT /id="VAR_078893" FT VARIANT 473 FT /note="E -> Q (in BAMS; no change in protein abundance; FT slightly decreased ATPase activity; dbSNP:rs1135402743)" FT /evidence="ECO:0000269|PubMed:28067909, FT ECO:0000269|PubMed:29748383" FT /id="VAR_078894" FT VARIANT 478 FT /note="G -> E (in FSHD2; abolished ATPase activity)" FT /evidence="ECO:0000269|PubMed:25370034, FT ECO:0000269|PubMed:29748383" FT /id="VAR_080701" FT VARIANT 479 FT /note="R -> P (in FSHD2; decreased protein level in FT fibroblasts as compared to wild-type protein)" FT /evidence="ECO:0000269|PubMed:23143600, FT ECO:0000269|PubMed:25256356" FT /id="VAR_069068" FT VARIANT 492 FT /note="C -> R (in FSHD2; decreased protein level in FT fibroblasts as compared to wild-type protein)" FT /evidence="ECO:0000269|PubMed:23143600" FT /id="VAR_069069" FT VARIANT 518 FT /note="K -> E (in BAMS; increased ATPase activity)" FT /evidence="ECO:0000269|PubMed:28067911, FT ECO:0000269|PubMed:29748383" FT /id="VAR_078895" FT VARIANT 523 FT /note="T -> K (in BAMS; no change in protein abundance; FT slightly decreased ATPase activity; dbSNP:rs1135402744)" FT /evidence="ECO:0000269|PubMed:28067909, FT ECO:0000269|PubMed:29748383" FT /id="VAR_078896" FT VARIANT 524 FT /note="N -> S (in BAMS; no change in protein abundance; FT dbSNP:rs1135402745)" FT /evidence="ECO:0000269|PubMed:28067909" FT /id="VAR_078897" FT VARIANT 527 FT /note="T -> M (in FSHD2; decreased ATPase activity; FT dbSNP:rs397518422)" FT /evidence="ECO:0000269|PubMed:24075187, FT ECO:0000269|PubMed:28067911, ECO:0000269|PubMed:29748383" FT /id="VAR_078898" FT VARIANT 552 FT /note="R -> Q (in BAMS; no change in protein abundance; FT does not affect ATPase activity; dbSNP:rs886042392)" FT /evidence="ECO:0000269|PubMed:28067909, FT ECO:0000269|PubMed:28067911, ECO:0000269|PubMed:29748383" FT /id="VAR_078899" FT VARIANT 615 FT /note="V -> D (in FSHD2)" FT /evidence="ECO:0000269|PubMed:25370034" FT /id="VAR_080702" FT VARIANT 690 FT /note="P -> S (in FSHD2; decreased protein level in FT fibroblasts as compared to wild-type protein; decreased FT ATPase activity; dbSNP:rs397514623)" FT /evidence="ECO:0000269|PubMed:23143600, FT ECO:0000269|PubMed:25256356, ECO:0000269|PubMed:29748383" FT /id="VAR_069070" FT VARIANT 708 FT /note="V -> I (in dbSNP:rs2276092)" FT /id="VAR_042959" FT VARIANT 716 FT /note="G -> S (in FSHD2)" FT /evidence="ECO:0000269|PubMed:25256356" FT /id="VAR_078900" FT VARIANT 731..2005 FT /note="Missing (in FSHD2)" FT /evidence="ECO:0000269|PubMed:25256356" FT /id="VAR_078901" FT VARIANT 748 FT /note="L -> P (in FSHD2)" FT /evidence="ECO:0000269|PubMed:25256356" FT /id="VAR_078902" FT VARIANT 780..2005 FT /note="Missing (in FSHD2)" FT /evidence="ECO:0000269|PubMed:25256356" FT /id="VAR_078903" FT VARIANT 849 FT /note="D -> N (in FSHD2)" FT /evidence="ECO:0000269|PubMed:25256356" FT /id="VAR_078904" FT VARIANT 868 FT /note="S -> N (in FSHD2; decreased protein level in FT fibroblasts as compared to wild-type protein)" FT /evidence="ECO:0000269|PubMed:23143600, FT ECO:0000269|PubMed:25256356" FT /id="VAR_069071" FT VARIANT 879 FT /note="K -> N (in dbSNP:rs633422)" FT /id="VAR_042960" FT VARIANT 960 FT /note="I -> V (in dbSNP:rs9961682)" FT /id="VAR_051365" FT VARIANT 1176..1177 FT /note="TD -> MH (in FSHD2)" FT /evidence="ECO:0000269|PubMed:25256356" FT /id="VAR_078905" FT VARIANT 1449 FT /note="R -> K (in FSHD2)" FT /evidence="ECO:0000269|PubMed:25370034" FT /id="VAR_080703" FT VARIANT 1463 FT /note="Q -> P (in FSHD2)" FT /evidence="ECO:0000269|PubMed:25370034" FT /id="VAR_080704" FT VARIANT 1468 FT /note="M -> I (in FSHD2)" FT /evidence="ECO:0000269|PubMed:25256356" FT /id="VAR_078906" FT VARIANT 1485 FT /note="P -> L (in FSHD2)" FT /evidence="ECO:0000269|PubMed:25370034" FT /id="VAR_080705" FT VARIANT 1487..1488 FT /note="QP -> HQ (in FSHD2)" FT /evidence="ECO:0000269|PubMed:25256356" FT /id="VAR_078907" FT VARIANT 1554 FT /note="F -> S (in FSHD2; decreased protein level in FT fibroblasts as compared to wild-type protein)" FT /evidence="ECO:0000269|PubMed:23143600, FT ECO:0000269|PubMed:25256356" FT /id="VAR_069072" FT VARIANT 1663..2005 FT /note="Missing (in FSHD2)" FT /evidence="ECO:0000269|PubMed:25370034" FT /id="VAR_080706" FT VARIANT 1795..2005 FT /note="Missing (in FSHD2)" FT /evidence="ECO:0000269|PubMed:25256356" FT /id="VAR_078908" FT VARIANT 1868..2005 FT /note="Missing (in FSHD2)" FT /evidence="ECO:0000269|PubMed:25256356" FT /id="VAR_078909" FT CONFLICT 1278 FT /note="Q -> E (in Ref. 3; CAB45732)" FT /evidence="ECO:0000305" FT CONFLICT 1384 FT /note="G -> E (in Ref. 3; CAH10538)" FT /evidence="ECO:0000305" FT STRAND 26..32 FT /evidence="ECO:0007829|PDB:6MW7" FT STRAND 43..47 FT /evidence="ECO:0007829|PDB:6MW7" FT HELIX 53..64 FT /evidence="ECO:0007829|PDB:6MW7" FT STRAND 73..76 FT /evidence="ECO:0007829|PDB:6MW7" FT TURN 84..86 FT /evidence="ECO:0007829|PDB:6MW7" FT HELIX 87..90 FT /evidence="ECO:0007829|PDB:6MW7" FT STRAND 96..102 FT /evidence="ECO:0007829|PDB:6MW7" FT STRAND 111..116 FT /evidence="ECO:0007829|PDB:6MW7" FT HELIX 122..125 FT /evidence="ECO:0007829|PDB:6MW7" FT TURN 126..131 FT /evidence="ECO:0007829|PDB:6MW7" FT HELIX 141..155 FT /evidence="ECO:0007829|PDB:6MW7" FT TURN 156..158 FT /evidence="ECO:0007829|PDB:6MW7" FT STRAND 163..171 FT /evidence="ECO:0007829|PDB:6MW7" FT HELIX 173..175 FT /evidence="ECO:0007829|PDB:6MW7" FT STRAND 179..184 FT /evidence="ECO:0007829|PDB:6MW7" FT HELIX 191..197 FT /evidence="ECO:0007829|PDB:6MW7" FT TURN 204..206 FT /evidence="ECO:0007829|PDB:6MW7" FT HELIX 225..227 FT /evidence="ECO:0007829|PDB:6MW7" FT HELIX 238..246 FT /evidence="ECO:0007829|PDB:6MW7" FT STRAND 248..255 FT /evidence="ECO:0007829|PDB:6MW7" FT STRAND 260..268 FT /evidence="ECO:0007829|PDB:6MW7" FT HELIX 269..277 FT /evidence="ECO:0007829|PDB:6MW7" FT STRAND 284..290 FT /evidence="ECO:0007829|PDB:6MW7" FT HELIX 301..304 FT /evidence="ECO:0007829|PDB:6MW7" FT HELIX 305..311 FT /evidence="ECO:0007829|PDB:6MW7" FT HELIX 312..315 FT /evidence="ECO:0007829|PDB:6MW7" FT STRAND 317..326 FT /evidence="ECO:0007829|PDB:6MW7" FT HELIX 329..337 FT /evidence="ECO:0007829|PDB:6MW7" FT HELIX 339..349 FT /evidence="ECO:0007829|PDB:6MW7" FT HELIX 351..355 FT /evidence="ECO:0007829|PDB:6MW7" FT STRAND 374..382 FT /evidence="ECO:0007829|PDB:6MW7" FT STRAND 388..391 FT /evidence="ECO:0007829|PDB:6MW7" FT HELIX 392..394 FT /evidence="ECO:0007829|PDB:6MW7" FT HELIX 399..405 FT /evidence="ECO:0007829|PDB:6MW7" FT STRAND 408..416 FT /evidence="ECO:0007829|PDB:6MW7" FT STRAND 422..429 FT /evidence="ECO:0007829|PDB:6MW7" FT STRAND 471..476 FT /evidence="ECO:0007829|PDB:6MW7" FT STRAND 479..486 FT /evidence="ECO:0007829|PDB:6MW7" FT HELIX 490..492 FT /evidence="ECO:0007829|PDB:6MW7" FT HELIX 503..507 FT /evidence="ECO:0007829|PDB:6MW7" FT STRAND 508..515 FT /evidence="ECO:0007829|PDB:6MW7" FT STRAND 525..530 FT /evidence="ECO:0007829|PDB:6MW7" FT HELIX 531..535 FT /evidence="ECO:0007829|PDB:6MW7" FT STRAND 541..546 FT /evidence="ECO:0007829|PDB:6MW7" FT STRAND 549..552 FT /evidence="ECO:0007829|PDB:6MW7" FT HELIX 555..570 FT /evidence="ECO:0007829|PDB:6MW7" SQ SEQUENCE 2005 AA; 226374 MW; B662C681424241B7 CRC64; MAAADGGGPG GASVGTEEDG GGVGHRTVYL FDRREKESEL GDRPLQVGER SDYAGFRACV CQTLGISPEE KFVITTTSRK EITCDNFDET VKDGVTLYLL QSVNQLLLTA TKERIDFLPH YDTLVKSGMY EYYASEGQNP LPFALAELID NSLSATSRNI GVRRIQIKLL FDETQGKPAV AVIDNGRGMT SKQLNNWAVY RLSKFTRQGD FESDHSGYVR PVPVPRSLNS DISYFGVGGK QAVFFVGQSA RMISKPADSQ DVHELVLSKE DFEKKEKNKE AIYSGYIRNR KPSDSVHITN DDERFLHHLI IEEKEKDSFT AVVITGVQPE HIQYLKNYFH LWTRQLAHIY HYYIHGPKGN EIRTSKEVEP FNNIDIEISM FEKGKVPKIV NLREIQDDMQ TLYVNTAADS FEFKAHVEGD GVVEGIIRYH PFLYDRETYP DDPCFPSKLK DEDDEDDCFI LEKAARGKRP IFECFWNGRL IPYTSVEDFD WCTPPKKRGL APIECYNRIS GALFTNDKFQ VSTNKLTFMD LELKLKDKNT LFTRILNGQE QRMKIDREFA LWLKDCHEKY DKQIKFTLFK GVITRPDLPS KKQGPWATYA AIEWDGKIYK AGQLVKTIKT LPLFYGSIVR FFLYGDHDGE VYATGGEVQI AMEPQALYDE VRTVPIAKLD RTVAEKAVKK YVEDEMARLP DRLSVTWPEG DELLPNEVRP AGTPIGALRI EILNKKGEAM QKLPGTSHGG SKKLLVELKV ILHSSSGNKE IISHISQHGG KWPYWFKKME NIQKLGNYTL KLQVVLNESN ADTYAGRPLP SKAIKFSVKE GKPEKFSFGL LDLPFRVGVP FNIPLEFQDE FGHTSQLVTD IQPVLEASGL SLHYEEITKG PNCVIRGVTA KGPVNSCQGK NYNLKVTLPG LKEDSQILKI RLLPGHPRRL KVKPDSEILV IENGTAFPFQ VEVLDESDNI TAQPKLIVHC KFSGAPNLPV YVVDCSSSGT SILTGSAIQV QNIKKDQTLK ARIEIPSCKD VAPVEKTIKL LPSSHVARLQ IFSVEGQKAI QIKHQDEVNW IAGDIMHNLI FQMYDEGERE INITSALAEK IKVNWTPEIN KEHLLQGLLP DVQVPTSVKD MRYCQVSFQD DHVSLESAFT VRPLPDEPKH LKCEMKGGKT VQMGQELQGE VVIIITDQYG NQIQAFSPSS LSSLSIAGVG LDSSNLKTTF QENTQSISVR GIKFIPGPPG NKDLCFTWRE FSDFIRVQLI SGPPAKLLLI DWPELKESIP VINGRDLQNP IIVQLCDQWD NPAPVQHVKI SLTKASNLKL MPSNQQHKTD EKGRANLGVF SVFAPRGEHT LQVKAIYNKS IIEGPIIKLM ILPDPEKPVR LNVKYDKDAS FLAGGLFTDF MISVISEDDS IIKNINPARI SMKMWKLSTS GNRPPANAET FSCNKIKDND KEDGCFYFRD KVIPNKVGTY CIQFGFMMDK TNILNSEQVI VEVLPNQPVK LVPKIKPPTP AVSNVRSVAS RTLVRDLHLS ITDDYDNHTG IDLVGTIIAT IKGSNEEDTD TPLFIGKVRT LEFPFVNGSA EIMSLVLAES SPGRDSTEYF IVFEPRLPLL SRTLEPYILP FMFYNDVKKQ QQMAALTKEK DQLSQSIVMY KSLFEASQQL LNEMKCQVEE ARLKEAQLRN ELKIHNIDIP TTQQVPHIEA LLKRKLSEQE ELKKKPRRSC TLPNYTKGSG DVLGKIAHLA QIEDDRAAMV ISWHLASDMD CVVTLTTDAA RRIYDETQGR QQVLPLDSIY KKTLPDWKRS LPHFRNGKLY FKPIGDPVFA RDLLTFPDNV EHCETVFGML LGDTIILDNL DAANHYRKEV VKITHCPTLL TRDGDRIRSN GKFGGLQNKA PPMDKLRGMV FGAPVPKQCL ILGEQIDLLQ QYRSAVCKLD SVNKDLNSQL EYLRTPDMRK KKQELDEHEK NLKLIEEKLG MTPIRKCNDS LRHSPKVETT DCPVPPKRMR REATRQNRII TKTDV //