SMHD1_HUMAN
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 03-AUG-2022, entry version 130.
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; 157.
DR IntAct; A6NHR9; 51.
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 BioMuta; SMCHD1; -.
DR EPD; A6NHR9; -.
DR jPOST; A6NHR9; -.
DR MassIVE; A6NHR9; -.
DR MaxQB; A6NHR9; -.
DR PaxDb; A6NHR9; -.
DR PeptideAtlas; A6NHR9; -.
DR PRIDE; A6NHR9; -.
DR ProteomicsDB; 1220; -. [A6NHR9-1]
DR ProteomicsDB; 1221; -. [A6NHR9-2]
DR ProteomicsDB; 1222; -. [A6NHR9-3]
DR Antibodypedia; 49899; 84 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 CTD; 23347; -.
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; SIIMYKS; -.
DR OrthoDB; 390511at2759; -.
DR PhylomeDB; A6NHR9; -.
DR TreeFam; TF329426; -.
DR PathwayCommons; A6NHR9; -.
DR SignaLink; A6NHR9; -.
DR BioGRID-ORCS; 23347; 53 hits in 1083 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 200 other tissues.
DR ExpressionAtlas; A6NHR9; baseline and differential.
DR Genevisible; A6NHR9; HS.
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: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:0060820; P:inactivation of X chromosome by heterochromatin assembly; ISS:UniProtKB.
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 Gene3D; 3.30.565.10; -; 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; PTHR22640; 1.
DR Pfam; PF06470; SMC_hinge; 1.
DR SMART; SM00968; SMC_hinge; 1.
DR SUPFAM; SSF55874; SSF55874; 1.
DR SUPFAM; SSF75553; SSF75553; 1.
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; unknown pathological
FT significance; 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
