ID SMRCD_HUMAN Reviewed; 1026 AA. AC Q9H4L7; B7Z799; Q05D56; Q96SX1; Q9H017; Q9H860; Q9NPU9; Q9ULU7; DT 28-MAR-2003, integrated into UniProtKB/Swiss-Prot. DT 05-OCT-2010, sequence version 2. DT 27-MAR-2024, entry version 198. DE RecName: Full=SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A containing DEAD/H box 1; DE EC=3.6.4.12; DE AltName: Full=ATP-dependent helicase 1; DE Short=hHEL1; GN Name=SMARCAD1; Synonyms=KIAA1122; 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] (ISOFORM 1), TISSUE SPECIFICITY, AND VARIANT RP ALA-301. RC TISSUE=Fetal brain; RX PubMed=11031099; DOI=10.1006/geno.2000.6281; RA Adra C.N., Donato J.-L., Badovinac R., Syed F., Kheraj R., Cai H., RA Moran C., Kolker M.T., Turner H., Weremowicz S., Shirakawa T., Morton C.C., RA Schnipper L.E., Drews R.; RT "SMARCAD1, a novel human helicase family-defining member associated with RT genetic instability: cloning, expression, and mapping to 4q22-q23, a band RT rich in breakpoints and deletion mutants involved in several human RT diseases."; RL Genomics 69:162-173(2000). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain; RX PubMed=10574461; DOI=10.1093/dnares/6.5.329; RA Hirosawa M., Nagase T., Ishikawa K., Kikuno R., Nomura N., Ohara O.; RT "Characterization of cDNA clones selected by the GeneMark analysis from RT size-fractionated cDNA libraries from human brain."; RL DNA Res. 6:329-336(1999). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 1-702 (ISOFORMS 1/2), AND NUCLEOTIDE SEQUENCE [LARGE RP SCALE MRNA] OF 649-1026 (ISOFORM 2). RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANTS ASN-247; RP ALA-301; GLN-351 AND ALA-972. RC TISSUE=Kidney, and Testis; 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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 433-1026 (ISOFORM 1). RC TISSUE=Melanoma, and 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 [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-124; SER-127; SER-239 AND RP SER-242, VARIANT [LARGE SCALE ANALYSIS] ASN-247, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-124; SER-127; SER-132 AND RP SER-302, VARIANT [LARGE SCALE ANALYSIS] ALA-301, AND IDENTIFICATION BY MASS RP 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 [9] RP DNA-BINDING, AND INTERACTION WITH MSH2 AND TRIM28. RX PubMed=18675275; DOI=10.1016/j.jmb.2008.07.031; RA Okazaki N., Ikeda S., Ohara R., Shimada K., Yanagawa T., Nagase T., RA Ohara O., Koga H.; RT "The novel protein complex with SMARCAD1/KIAA1122 binds to the vicinity of RT TSS."; RL J. Mol. Biol. 382:257-265(2008). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-79; SER-124; SER-127; RP SER-132; SER-211 AND SER-214, AND IDENTIFICATION BY MASS SPECTROMETRY RP [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 [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-54; SER-124; SER-127; SER-132 RP AND SER-146, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-124 AND SER-127, 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 [13] RP INVOLVEMENT IN ADERM, TISSUE SPECIFICITY, AND ALTERNATIVE SPLICING (ISOFORM RP 3). RX PubMed=21820097; DOI=10.1016/j.ajhg.2011.07.004; RA Nousbeck J., Burger B., Fuchs-Telem D., Pavlovsky M., Fenig S., Sarig O., RA Itin P., Sprecher E.; RT "A mutation in a skin-specific isoform of SMARCAD1 causes autosomal- RT dominant adermatoglyphia."; RL Am. J. Hum. Genet. 89:302-307(2011). RN [14] 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 [15] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PCNA; TRIM28; HDAC1; RP HDAC2; EHMT2; PARP1 AND CBX3, AND MUTAGENESIS OF LYS-528. RX PubMed=21549307; DOI=10.1016/j.molcel.2011.02.036; RA Rowbotham S.P., Barki L., Neves-Costa A., Santos F., Dean W., Hawkes N., RA Choudhary P., Will W.R., Webster J., Oxley D., Green C.M., Varga-Weisz P., RA Mermoud J.E.; RT "Maintenance of silent chromatin through replication requires SWI/SNF-like RT chromatin remodeler SMARCAD1."; RL Mol. Cell 42:285-296(2011). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-54; SER-57; SER-124; SER-127; RP SER-146; SER-152; SER-239 AND SER-242, AND IDENTIFICATION BY MASS RP 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 [17] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [18] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=22960744; DOI=10.1038/nature11353; RA Costelloe T., Louge R., Tomimatsu N., Mukherjee B., Martini E., RA Khadaroo B., Dubois K., Wiegant W.W., Thierry A., Burma S., van Attikum H., RA Llorente B.; RT "The yeast Fun30 and human SMARCAD1 chromatin remodellers promote DNA end RT resection."; RL Nature 489:581-584(2012). RN [19] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-71; SER-79; SER-146; SER-152; RP SER-211; SER-239 AND SER-302, VARIANT [LARGE SCALE ANALYSIS] ALA-301, 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 [21] RP INVOLVEMENT IN BSNS. RX PubMed=24664640; DOI=10.1002/ajmg.a.36438; RA Marks K.C., Banks W.R. III, Cunningham D., Witman P.M., Herman G.E.; RT "Analysis of two candidate genes for Basan syndrome."; RL Am. J. Med. Genet. A 164A:1188-1191(2014). RN [22] RP INVOLVEMENT IN ADERM. RX PubMed=24909267; DOI=10.1111/bjd.13176; RA Nousbeck J., Sarig O., Magal L., Warshauer E., Burger B., Itin P., RA Sprecher E.; RT "Mutations in SMARCAD1 cause autosomal dominant adermatoglyphia and perturb RT the expression of epidermal differentiation-associated genes."; RL Br. J. Dermatol. 171:1521-1524(2014). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-217, AND IDENTIFICATION BY RP 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 [24] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-77, 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 [25] RP INVOLVEMENT IN BSNS. RX PubMed=26932190; DOI=10.1038/ejhg.2016.15; RA Li M., Wang J., Li Z., Zhang J., Ni C., Cheng R., Yao Z.; RT "Genome-wide linkage analysis and whole-genome sequencing identify a RT recurrent SMARCAD1 variant in a unique Chinese family with Basan RT syndrome."; RL Eur. J. Hum. Genet. 24:1367-1370(2016). RN [26] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-77; LYS-84; LYS-335; LYS-471; RP LYS-724 AND LYS-996, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP 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 [27] RP INVOLVEMENT IN HRZ, AND TISSUE SPECIFICITY. RX PubMed=29409814; DOI=10.1016/j.jid.2018.01.015; RA Guenther C., Lee-Kirsch M.A., Eckhard J., Matanovic A., Kerscher T., RA Rueschendorf F., Klein B., Berndt N., Zimmermann N., Flachmeier C., RA Thuss T., Lucas N., Marenholz I., Esparza-Gordillo J., Huebner N., RA Traupe H., Delaporte E., Lee Y.A.; RT "SMARCAD1 Haploinsufficiency Underlies Huriez Syndrome and Associated Skin RT Cancer Susceptibility."; RL J. Invest. Dermatol. 138:1428-1431(2018). RN [28] RP VARIANT [LARGE SCALE ANALYSIS] ALA-301, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). CC -!- FUNCTION: DNA helicase that possesses intrinsic ATP-dependent CC nucleosome-remodeling activity and is both required for DNA repair and CC heterochromatin organization. Promotes DNA end resection of double- CC strand breaks (DSBs) following DNA damage: probably acts by weakening CC histone DNA interactions in nucleosomes flanking DSBs. Required for the CC restoration of heterochromatin organization after replication. Acts at CC replication sites to facilitate the maintenance of heterochromatin by CC directing H3 and H4 histones deacetylation, H3 'Lys-9' trimethylation CC (H3K9me3) and restoration of silencing. {ECO:0000269|PubMed:21549307, CC ECO:0000269|PubMed:22960744}. 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; EC=3.6.4.12; CC -!- SUBUNIT: Binds to DNA preferentially in the vicinity of transcriptional CC start sites. Interacts with MSH2 and TRIM28. Part of a complex composed CC of TRIM28, HDAC1, HDAC2 and EHMT2. Interacts with PCNA. CC {ECO:0000269|PubMed:18675275, ECO:0000269|PubMed:21549307}. CC -!- SUBCELLULAR LOCATION: Nucleus. Chromosome. Note=Colocalizes with PCNA CC at replication forks during S phase. Recruited to double-strand breaks CC (DSBs) sites of DNA damage. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; Synonyms=Long; CC IsoId=Q9H4L7-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9H4L7-2; Sequence=VSP_007104; CC Name=3; Synonyms=Short; CC IsoId=Q9H4L7-3; Sequence=VSP_043110; CC -!- TISSUE SPECIFICITY: Isoform 1 is expressed ubiquitously. Isoform 3 is CC expressed mainly in skin and esophagus. Expressed in fibroblasts and CC keratinocytes (at protein level) (PubMed:29409814). CC {ECO:0000269|PubMed:11031099, ECO:0000269|PubMed:21820097, CC ECO:0000269|PubMed:29409814}. CC -!- DISEASE: Adermatoglyphia (ADERM) [MIM:136000]: An autosomal dominant CC condition characterized by the lack of epidermal ridges on the palms CC and soles, which results in the absence of fingerprints, and is CC associated with a reduced number of sweat gland openings and reduced CC sweating of palms and soles. {ECO:0000269|PubMed:21820097, CC ECO:0000269|PubMed:24909267}. Note=The disease is caused by variants CC affecting the gene represented in this entry. Splice site mutations CC causing aberrant splicing of skin-specific isoform 3 are likely to CC exert a loss-of-function effect and are involved in ADERM. CC {ECO:0000269|PubMed:21820097, ECO:0000269|PubMed:24909267}. CC -!- DISEASE: Basan syndrome (BSNS) [MIM:129200]: An autosomal dominant form CC of adermatoglyphia associated with congenital facial milia, acral CC blistering, digital contractures, and nail abnormalities. CC Adermatoglyphia is defined by the lack of epidermal ridges on the palms CC and soles, which results in the absence of fingerprints. CC {ECO:0000269|PubMed:24664640, ECO:0000269|PubMed:26932190}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. Splice site mutations causing aberrant splicing of skin-specific CC isoform 3 are likely to exert a loss-of-function effect and are CC involved in BSNS. {ECO:0000269|PubMed:24664640, CC ECO:0000269|PubMed:26932190}. CC -!- DISEASE: Huriez syndrome (HRZ) [MIM:181600]: An autosomal dominant CC syndrome characterized by atrophic fibrosis of the skin of the limbs, CC nail hypoplasia, and palmoplantar keratoderma. Malignant degeneration CC of affected skin resulting in aggressive squamous cell carcinoma and CC early metastasis formation is a distinctive feature of the syndrome. CC {ECO:0000269|PubMed:29409814}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: [Isoform 3]: Skin-specific. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the SNF2/RAD54 helicase family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH17953.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; CC Sequence=BAA86436.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAB14759.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=The ends of our fingers CC - Issue 136 of March 2012; CC URL="https://web.expasy.org/spotlight/back_issues/136"; 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; AY008271; AAG16639.1; -; mRNA. DR EMBL; AB032948; BAA86436.2; ALT_INIT; mRNA. DR EMBL; AK023990; BAB14759.1; ALT_INIT; mRNA. DR EMBL; AK027490; BAB55150.1; -; mRNA. DR EMBL; AK301668; BAH13535.1; -; mRNA. DR EMBL; AC096746; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC017953; AAH17953.1; ALT_SEQ; mRNA. DR EMBL; BC045534; AAH45534.1; -; mRNA. DR EMBL; AL359929; CAB95769.1; -; mRNA. DR EMBL; AL512768; CAC21685.1; -; mRNA. DR CCDS; CCDS3639.1; -. [Q9H4L7-1] DR CCDS; CCDS47101.1; -. [Q9H4L7-2] DR CCDS; CCDS58914.1; -. [Q9H4L7-3] DR RefSeq; NP_001121901.1; NM_001128429.2. [Q9H4L7-2] DR RefSeq; NP_001121902.1; NM_001128430.1. [Q9H4L7-2] DR RefSeq; NP_001241878.1; NM_001254949.1. [Q9H4L7-3] DR RefSeq; NP_064544.2; NM_020159.4. [Q9H4L7-1] DR RefSeq; XP_016863952.1; XM_017008463.1. DR PDB; 6H3A; X-ray; 5.50 A; B/D=95-347. DR PDB; 6QU1; X-ray; 3.70 A; D=151-198. DR PDB; 7Z36; X-ray; 2.80 A; C/S=148-198. DR PDBsum; 6H3A; -. DR PDBsum; 6QU1; -. DR PDBsum; 7Z36; -. DR AlphaFoldDB; Q9H4L7; -. DR SMR; Q9H4L7; -. DR BioGRID; 121244; 189. DR IntAct; Q9H4L7; 23. DR MINT; Q9H4L7; -. DR STRING; 9606.ENSP00000351947; -. DR GlyGen; Q9H4L7; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9H4L7; -. DR MetOSite; Q9H4L7; -. DR PhosphoSitePlus; Q9H4L7; -. DR BioMuta; SMARCAD1; -. DR DMDM; 306526240; -. DR EPD; Q9H4L7; -. DR jPOST; Q9H4L7; -. DR MassIVE; Q9H4L7; -. DR MaxQB; Q9H4L7; -. DR PaxDb; 9606-ENSP00000351947; -. DR PeptideAtlas; Q9H4L7; -. DR ProteomicsDB; 80860; -. [Q9H4L7-1] DR ProteomicsDB; 80861; -. [Q9H4L7-2] DR ProteomicsDB; 80862; -. [Q9H4L7-3] DR Pumba; Q9H4L7; -. DR Antibodypedia; 14709; 159 antibodies from 26 providers. DR DNASU; 56916; -. DR Ensembl; ENST00000354268.9; ENSP00000346217.4; ENSG00000163104.18. [Q9H4L7-1] DR Ensembl; ENST00000359052.8; ENSP00000351947.4; ENSG00000163104.18. [Q9H4L7-2] DR Ensembl; ENST00000457823.6; ENSP00000415576.2; ENSG00000163104.18. [Q9H4L7-2] DR Ensembl; ENST00000509418.1; ENSP00000423286.1; ENSG00000163104.18. [Q9H4L7-3] DR GeneID; 56916; -. DR KEGG; hsa:56916; -. DR MANE-Select; ENST00000354268.9; ENSP00000346217.4; NM_020159.5; NP_064544.2. DR UCSC; uc003htb.5; human. [Q9H4L7-1] DR AGR; HGNC:18398; -. DR CTD; 56916; -. DR DisGeNET; 56916; -. DR GeneCards; SMARCAD1; -. DR HGNC; HGNC:18398; SMARCAD1. DR HPA; ENSG00000163104; Low tissue specificity. DR MalaCards; SMARCAD1; -. DR MIM; 129200; phenotype. DR MIM; 136000; phenotype. DR MIM; 181600; phenotype. DR MIM; 612761; gene. DR neXtProt; NX_Q9H4L7; -. DR OpenTargets; ENSG00000163104; -. DR Orphanet; 1658; Absence of fingerprints-congenital milia syndrome. DR Orphanet; 384; Huriez syndrome. DR Orphanet; 289465; Isolated congenital adermatoglyphia. DR PharmGKB; PA134954731; -. DR VEuPathDB; HostDB:ENSG00000163104; -. DR eggNOG; KOG0389; Eukaryota. DR GeneTree; ENSGT00910000144252; -. DR HOGENOM; CLU_000315_16_3_1; -. DR InParanoid; Q9H4L7; -. DR OMA; MEMRRMA; -. DR OrthoDB; 5482994at2759; -. DR PhylomeDB; Q9H4L7; -. DR TreeFam; TF105768; -. DR PathwayCommons; Q9H4L7; -. DR SignaLink; Q9H4L7; -. DR SIGNOR; Q9H4L7; -. DR BioGRID-ORCS; 56916; 13 hits in 1169 CRISPR screens. DR ChiTaRS; SMARCAD1; human. DR GeneWiki; SMARCAD1; -. DR GenomeRNAi; 56916; -. DR Pharos; Q9H4L7; Tbio. DR PRO; PR:Q9H4L7; -. DR Proteomes; UP000005640; Chromosome 4. DR RNAct; Q9H4L7; Protein. DR Bgee; ENSG00000163104; Expressed in adrenal tissue and 175 other cell types or tissues. DR ExpressionAtlas; Q9H4L7; baseline and differential. DR GO; GO:0000792; C:heterochromatin; ISS:UniProtKB. DR GO; GO:0043596; C:nuclear replication fork; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0035861; C:site of double-strand break; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA. DR GO; GO:0008094; F:ATP-dependent activity, acting on DNA; IBA:GO_Central. DR GO; GO:0140658; F:ATP-dependent chromatin remodeler activity; IMP:GO_Central. DR GO; GO:0003682; F:chromatin binding; IBA:GO_Central. DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB. DR GO; GO:0004386; F:helicase activity; IEA:UniProtKB-KW. DR GO; GO:0043130; F:ubiquitin binding; IEA:InterPro. DR GO; GO:0006338; P:chromatin remodeling; IMP:GO_Central. DR GO; GO:0051304; P:chromosome separation; IMP:UniProtKB. DR GO; GO:0000729; P:DNA double-strand break processing; IMP:UniProtKB. DR GO; GO:0000018; P:regulation of DNA recombination; IEP:UniProtKB. DR CDD; cd17998; DEXHc_SMARCAD1; 1. DR CDD; cd18793; SF2_C_SNF; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR Gene3D; 3.40.50.10810; Tandem AAA-ATPase domain; 1. DR InterPro; IPR003892; CUE. DR InterPro; IPR014001; Helicase_ATP-bd. DR InterPro; IPR001650; Helicase_C. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR038718; SNF2-like_sf. DR InterPro; IPR049730; SNF2/RAD54-like_C. DR InterPro; IPR000330; SNF2_N. DR PANTHER; PTHR10799; SNF2/RAD54 HELICASE FAMILY; 1. DR PANTHER; PTHR10799:SF964; SWI_SNF-RELATED MATRIX-ASSOCIATED ACTIN-DEPENDENT REGULATOR OF CHROMATIN SUBFAMILY A CONTAINING DEAD_H BOX 1; 1. DR Pfam; PF00271; Helicase_C; 1. DR Pfam; PF00176; SNF2-rel_dom; 1. DR SMART; SM00487; DEXDc; 1. DR SMART; SM00490; HELICc; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 2. DR PROSITE; PS51140; CUE; 2. DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1. DR PROSITE; PS51194; HELICASE_CTER; 1. DR Genevisible; Q9H4L7; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; KW Chromatin regulator; Chromosome; DNA damage; DNA repair; DNA-binding; KW Ectodermal dysplasia; Helicase; Hydrolase; Isopeptide bond; KW Nucleotide-binding; Nucleus; Palmoplantar keratoderma; Phosphoprotein; KW Reference proteome; Repeat; Ubl conjugation. FT CHAIN 1..1026 FT /note="SWI/SNF-related matrix-associated actin-dependent FT regulator of chromatin subfamily A containing DEAD/H box 1" FT /id="PRO_0000074356" FT DOMAIN 157..199 FT /note="CUE 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00468" FT DOMAIN 251..294 FT /note="CUE 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00468" FT DOMAIN 509..677 FT /note="Helicase ATP-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541" FT DOMAIN 858..1010 FT /note="Helicase C-terminal" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542" FT REGION 1..82 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 203..251 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 302..328 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 354..373 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 628..631 FT /note="DEGH box" FT MOTIF 721..738 FT /note="Nuclear localization signal" FT /evidence="ECO:0000255" FT MOTIF 1005..1008 FT /note="DEGD box" FT COMPBIAS 44..72 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 223..241 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 521..529 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541" FT BINDING 897..904 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:22223895, FT ECO:0007744|PubMed:22814378" FT MOD_RES 54 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:21406692" FT MOD_RES 57 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 71 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 79 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 124 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:17525332, ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692" FT MOD_RES 127 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:17525332, ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692" FT MOD_RES 132 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17525332, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332" FT MOD_RES 146 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 152 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 211 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 214 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 217 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 239 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 242 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:21406692" FT MOD_RES 302 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17525332, FT ECO:0007744|PubMed:23186163" FT CROSSLNK 77 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 84 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 335 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 471 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 724 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 996 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT VAR_SEQ 1..430 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_043110" FT VAR_SEQ 765 FT /note="L -> LVT (in isoform 2)" FT /evidence="ECO:0000303|PubMed:10574461, FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334" FT /id="VSP_007104" FT VARIANT 66 FT /note="S -> F (in dbSNP:rs11723410)" FT /id="VAR_028037" FT VARIANT 135 FT /note="L -> F (in dbSNP:rs2664891)" FT /id="VAR_028038" FT VARIANT 140 FT /note="R -> C (in dbSNP:rs2632398)" FT /id="VAR_028039" FT VARIANT 245 FT /note="S -> Y (in dbSNP:rs3103117)" FT /id="VAR_028040" FT VARIANT 247 FT /note="S -> N (in dbSNP:rs11722476)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0007744|PubMed:17081983" FT /id="VAR_028041" FT VARIANT 301 FT /note="V -> A (in dbSNP:rs7439869)" FT /evidence="ECO:0000269|PubMed:11031099, FT ECO:0000269|PubMed:15489334, ECO:0007744|PubMed:17525332, FT ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:23186163" FT /id="VAR_028042" FT VARIANT 351 FT /note="P -> Q (in dbSNP:rs17854344)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_028043" FT VARIANT 972 FT /note="V -> A (in dbSNP:rs17857297)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_028044" FT MUTAGEN 528 FT /note="K->R: No effect on subcellular localization and on FT histone deacetylation." FT /evidence="ECO:0000269|PubMed:21549307" FT CONFLICT 215 FT /note="E -> D (in Ref. 5; AAH17953)" FT /evidence="ECO:0000305" FT CONFLICT 937 FT /note="N -> D (in Ref. 3; BAB14759)" FT /evidence="ECO:0000305" FT HELIX 155..168 FT /evidence="ECO:0007829|PDB:7Z36" FT HELIX 174..183 FT /evidence="ECO:0007829|PDB:7Z36" FT HELIX 187..196 FT /evidence="ECO:0007829|PDB:7Z36" SQ SEQUENCE 1026 AA; 117402 MW; 0A5DB5653F478413 CRC64; MNLFNLDRFR FEKRNKIEEA PEATPQPSQP GPSSPISLSA EEENAEGEVS RANTPDSDIT EKTEDSSVPE TPDNERKASI SYFKNQRGIQ YIDLSSDSED VVSPNCSNTV QEKTFNKDTV IIVSEPSEDE ESQGLPTMAR RNDDISELED LSELEDLKDA KLQTLKELFP QRSDNDLLKL IESTSTMDGA IAAALLMFGD AGGGPRKRKL SSSSEPYEED EFNDDQSIKK TRLDHGEESN ESAESSSNWE KQESIVLKLQ KEFPNFDKQE LREVLKEHEW MYTEALESLK VFAEDQDMQY VSQSEVPNGK EVSSRSQNYP KNATKTKLKQ KFSMKAQNGF NKKRKKNVFN PKRVVEDSEY DSGSDVGSSL DEDYSSGEEV MEDGYKGKIL HFLQDASIGE LTLIPQCSQK KAQKITELRP FNSWEALFTK MSKTNGLSED LIWHCKTLIQ ERDVVIRLMN KCEDISNKLT KQVTMLTGNG GGWNIEQPSI LNQSLSLKPY QKVGLNWLAL VHKHGLNGIL ADEMGLGKTI QAIAFLAYLY QEGNNGPHLI VVPASTIDNW LREVNLWCPT LKVLCYYGSQ EERKQIRFNI HSRYEDYNVI VTTYNCAISS SDDRSLFRRL KLNYAIFDEG HMLKNMGSIR YQHLMTINAN NRLLLTGTPV QNNLLELMSL LNFVMPHMFS SSTSEIRRMF SSKTKSADEQ SIYEKERIAH AKQIIKPFIL RRVKEEVLKQ LPPKKDRIEL CAMSEKQEQL YLGLFNRLKK SINNLEKNTE MCNVMMQLRK MANHPLLHRQ YYTAEKLKEM SQLMLKEPTH CEANPDLIFE DMEVMTDFEL HVLCKQYRHI NNFQLDMDLI LDSGKFRVLG CILSELKQKG DRVVLFSQFT MMLDILEVLL KHHQHRYLRL DGKTQISERI HLIDEFNTDM DIFVFLLSTK AGGLGINLTS ANVVILHDID CNPYNDKQAE DRCHRVGQTK EVLVIKLISQ GTIEESMLKI NQQKLKLEQD MTTVDEGDEG SMPADIATLL KTSMGL //