ID SMC5_HUMAN Reviewed; 1101 AA. AC Q8IY18; A6NM81; O60335; Q05D92; Q5VZ60; Q96SB9; DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot. DT 09-JAN-2007, sequence version 2. DT 27-MAR-2024, entry version 160. DE RecName: Full=Structural maintenance of chromosomes protein 5; DE Short=SMC protein 5; DE Short=SMC-5; DE Short=hSMC5; GN Name=SMC5; Synonyms=KIAA0594, SMC5L1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH SMC6, SUBCELLULAR LOCATION, RP TISSUE SPECIFICITY, AND VARIANTS ILE-306 AND ARG-308. RX PubMed=11408570; DOI=10.1091/mbc.12.6.1583; RA Taylor E.M., Moghraby J.S., Lees J.H., Smit B., Moens P.B., Lehmann A.R.; RT "Characterization of a novel human SMC heterodimer homologous to the RT Schizosaccharomyces pombe Rad18/Spr18 complex."; RL Mol. Biol. Cell 12:1583-1594(2001). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ILE-306. RC TISSUE=Brain; RX PubMed=9628581; DOI=10.1093/dnares/5.1.31; RA Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N., RA Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. IX. The RT complete sequences of 100 new cDNA clones from brain which can code for RT large proteins in vitro."; RL DNA Res. 5:31-39(1998). RN [3] RP SEQUENCE REVISION. RX PubMed=12168954; DOI=10.1093/dnares/9.3.99; RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.; RT "Construction of expression-ready cDNA clones for KIAA genes: manual RT curation of 330 KIAA cDNA clones."; RL DNA Res. 9:99-106(2002). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., RA Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ILE-306 AND ARG-308. RC TISSUE=Mammary gland, and Uterus; 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 INTERACTION WITH NSMCE2. RX PubMed=16055714; DOI=10.1128/mcb.25.16.7021-7032.2005; RA Potts P.R., Yu H.; RT "Human MMS21/NSE2 is a SUMO ligase required for DNA repair."; RL Mol. Cell. Biol. 25:7021-7032(2005). RN [7] RP FUNCTION. RX PubMed=16810316; DOI=10.1038/sj.emboj.7601218; RA Potts P.R., Porteus M.H., Yu H.; RT "Human SMC5/6 complex promotes sister chromatid homologous recombination by RT recruiting the SMC1/3 cohesin complex to double-strand breaks."; RL EMBO J. 25:3377-3388(2006). RN [8] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=17589526; DOI=10.1038/nsmb1259; RA Potts P.R., Yu H.; RT "The SMC5/6 complex maintains telomere length in ALT cancer cells through RT SUMOylation of telomere-binding proteins."; RL Nat. Struct. Mol. Biol. 14:581-590(2007). RN [9] RP SUMOYLATION, UBIQUITINATION, AND IDENTIFICATION IN THE SMC5-SMC6 COMPLEX. RX PubMed=18086888; DOI=10.1128/mcb.00767-07; RA Taylor E.M., Copsey A.C., Hudson J.J., Vidot S., Lehmann A.R.; RT "Identification of the proteins, including MAGEG1, that make up the human RT SMC5-6 protein complex."; RL Mol. Cell. Biol. 28:1197-1206(2008). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-35, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [11] RP FUNCTION. RX PubMed=19502785; DOI=10.4161/cc.8.14.8979; RA Behlke-Steinert S., Touat-Todeschini L., Skoufias D.A., Margolis R.L.; RT "SMC5 and MMS21 are required for chromosome cohesion and mitotic RT progression."; RL Cell Cycle 8:2211-2218(2009). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-35, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [13] 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 [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-25 AND SER-35, 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 [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-35, 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 [16] RP INTERACTION WITH RAD18 AND SLF2, SUBCELLULAR LOCATION, AND IDENTIFICATION RP BY MASS SPECTROMETRY. RX PubMed=25931565; DOI=10.1126/science.1253671; RA Raeschle M., Smeenk G., Hansen R.K., Temu T., Oka Y., Hein M.Y., RA Nagaraj N., Long D.T., Walter J.C., Hofmann K., Storchova Z., Cox J., RA Bekker-Jensen S., Mailand N., Mann M.; RT "DNA repair. Proteomics reveals dynamic assembly of repair complexes during RT bypass of DNA cross-links."; RL Science 348:1253671-1253671(2015). RN [17] RP FUNCTION, DEGRADATION (MICROBIAL INFECTION), AND SUBUNIT (MICROBIAL RP INFECTION). RX PubMed=26983541; DOI=10.1038/nature17170; RA Decorsiere A., Mueller H., van Breugel P.C., Abdul F., Gerossier L., RA Beran R.K., Livingston C.M., Niu C., Fletcher S.P., Hantz O., Strubin M.; RT "Hepatitis B virus X protein identifies the Smc5/6 complex as a host RT restriction factor."; RL Nature 531:386-389(2016). RN [18] RP SUBCELLULAR LOCATION. RX PubMed=36373674; DOI=10.7554/elife.79676; RA Oravcova M., Nie M., Zilio N., Maeda S., Jami-Alahmadi Y., RA Lazzerini-Denchi E., Wohlschlegel J.A., Ulrich H.D., Otomo T., Boddy M.N.; RT "The Nse5/6-like SIMC1-SLF2 complex localizes SMC5/6 to viral replication RT centers."; RL Elife 11:0-0(2022). RN [19] RP INTERACTION WITH HUMAN HERPESVIRUS 8 PROTEIN RTA/ORF50 (MICROBIAL RP INFECTION), AND SUBCELLULAR LOCATION. RX PubMed=35914008; DOI=10.1371/journal.ppat.1010744; RA Han C., Zhang D., Gui C., Huang L., Chang S., Dong L., Bai L., Wu S., RA Lan K.; RT "KSHV RTA antagonizes SMC5/6 complex-induced viral chromatin compaction by RT hijacking the ubiquitin-proteasome system."; RL PLoS Pathog. 18:e1010744-e1010744(2022). RN [20] RP VARIANTS ATELS2 ARG-372 DEL; 425-ARG--SER-1101 DEL AND ASP-990, INVOLVEMENT RP IN ATELS2, CHARACTERIZATION OF VARIANTS ATELS2 ARG-372 DEL; RP 425-ARG--SER-1101 DEL AND ASP-990, AND INTERACTION WITH SMC6; SLF2 AND RP NSMCE2. RX PubMed=36333305; DOI=10.1038/s41467-022-34349-8; RA Grange L.J., Reynolds J.J., Ullah F., Isidor B., Shearer R.F., Latypova X., RA Baxley R.M., Oliver A.W., Ganesh A., Cooke S.L., Jhujh S.S., McNee G.S., RA Hollingworth R., Higgs M.R., Natsume T., Khan T., Martos-Moreno G.A., RA Chupp S., Mathew C.G., Parry D., Simpson M.A., Nahavandi N., Yueksel Z., RA Drasdo M., Kron A., Vogt P., Jonasson A., Seth S.A., Gonzaga-Jauregui C., RA Brigatti K.W., Stegmann A.P.A., Kanemaki M., Josifova D., Uchiyama Y., RA Oh Y., Morimoto A., Osaka H., Ammous Z., Argente J., Matsumoto N., RA Stumpel C.T.R.M., Taylor A.M.R., Jackson A.P., Bielinsky A.K., Mailand N., RA Le Caignec C., Davis E.E., Stewart G.S.; RT "Pathogenic variants in SLF2 and SMC5 cause segmented chromosomes and RT mosaic variegated hyperploidy."; RL Nat. Commun. 13:6664-6664(2022). CC -!- FUNCTION: Core component of the SMC5-SMC6 complex, a complex involved CC in repair of DNA double-strand breaks by homologous recombination. The CC complex may promote sister chromatid homologous recombination by CC recruiting the SMC1-SMC3 cohesin complex to double-strand breaks. The CC complex is required for telomere maintenance via recombination in ALT CC (alternative lengthening of telomeres) cell lines and mediates CC sumoylation of shelterin complex (telosome) components which is CC proposed to lead to shelterin complex disassembly in ALT-associated PML CC bodies (APBs). Required for recruitment of telomeres to PML nuclear CC bodies. Required for sister chromatid cohesion during prometaphase and CC mitotic progression; the function seems to be independent of SMC6. CC SMC5-SMC6 complex may prevent transcription of episomal DNA, such as CC circular viral DNA genome (PubMed:26983541). CC {ECO:0000269|PubMed:16810316, ECO:0000269|PubMed:17589526, CC ECO:0000269|PubMed:19502785, ECO:0000269|PubMed:26983541}. CC -!- SUBUNIT: Forms a heterodimer with SMC6 (PubMed:11408570). Component of CC the SMC5-SMC6 complex which consists at least of SMC5, SMC6, NSMCE2, CC NSMCE1, NSMCE4A or EID3 and NSMCE3 (PubMed:18086888). Interacts with CC NSMCE2 (PubMed:16055714, PubMed:36333305). Interacts with SLF2; this CC interaction induces an association of the SLF1-SLF2 complex with the CC SMC5-SMC6 complex (PubMed:25931565, PubMed:36333305). Interacts with CC RAD18; this interaction is increased in a SLF1 or SLF2-dependent manner CC (PubMed:25931565). {ECO:0000269|PubMed:11408570, CC ECO:0000269|PubMed:16055714, ECO:0000269|PubMed:18086888, CC ECO:0000269|PubMed:25931565, ECO:0000269|PubMed:36333305}. CC -!- SUBUNIT: (Microbial infection) SMC5-SMC6 complex interacts with CC Hepatitis B X protein. {ECO:0000269|PubMed:26983541}. CC -!- SUBUNIT: (Microbial infection) Interacts with human herpesvirus 8 CC (KSHV) protein RTA/ORF50; this interaction targets the SMC5-SMC6 CC complex for proteasomal degradation. {ECO:0000269|PubMed:35914008}. CC -!- INTERACTION: CC Q8IY18; Q9NRI5-2: DISC1; NbExp=3; IntAct=EBI-605405, EBI-11988027; CC Q8IY18; Q8N140: EID3; NbExp=4; IntAct=EBI-605405, EBI-744483; CC Q8IY18; Q8IX21: SLF2; NbExp=3; IntAct=EBI-605405, EBI-2682240; CC Q8IY18; Q96SB8: SMC6; NbExp=6; IntAct=EBI-605405, EBI-605415; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11408570, CC ECO:0000269|PubMed:25931565, ECO:0000269|PubMed:35914008}. Chromosome CC {ECO:0000250|UniProtKB:Q8CG46}. Nucleus, PML body CC {ECO:0000269|PubMed:17589526, ECO:0000269|PubMed:36373674}. Chromosome, CC telomere {ECO:0000269|PubMed:17589526}. Note=Associates with chromatin CC (PubMed:25931565). Colocalizes with SMC6 on the X-Y chromosome pair CC within the sex vesicle during late pachytene/diplotene (By similarity). CC Localizes to PML nuclear bodies in ALT cell lines (PubMed:17589526). CC Accumulates with RAD18 and the SLF1-SLF2 complex at replication-coupled CC DNA interstrand repair and DNA double-strand breaks (DSBs) sites on CC chromatin in a ubiquitin-dependent manner (PubMed:25931565). CC {ECO:0000250|UniProtKB:Q8CG46, ECO:0000269|PubMed:25931565}. CC -!- TISSUE SPECIFICITY: Widely expressed (PubMed:11408570). Strongly CC expressed in testis (PubMed:11408570). {ECO:0000269|PubMed:11408570}. CC -!- DOMAIN: The flexible hinge domain, which separates the large CC intramolecular coiled coil regions, allows the heterotypic interaction CC with the corresponding domain of SMC6, forming a V-shaped heterodimer. CC {ECO:0000250}. CC -!- PTM: Sumoylated. {ECO:0000269|PubMed:18086888}. CC -!- PTM: Ubiquitinated. {ECO:0000269|PubMed:18086888}. CC -!- PTM: (Microbial infection) SMC5-SMC6 complex is degraded by the CC activity of Hepatitis B X protein. {ECO:0000269|PubMed:26983541}. CC -!- DISEASE: Atelis syndrome 2 (ATELS2) [MIM:620185]: A form of Atelis CC syndrome, an autosomal recessive neurodevelopmental disorder CC characterized by mild to severe developmental delay, learning CC difficulties, microcephaly, and growth restriction with short stature. CC Additional features include anemia, skin hyperpigmentation, ocular CC anomalies, congenital heart defects, and mild skeletal abnormalities. CC Death in childhood may occur. Patient cells show spontaneous chromosome CC breakage and chromosomal anomalies, hallmarked by segmented and CC dicentric chromosomes and mosaic variegated hyperploidy. CC {ECO:0000269|PubMed:36333305}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the SMC family. SMC5 subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH17666.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; 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; AJ310550; CAC39247.1; -; mRNA. DR EMBL; AB011166; BAA25520.2; -; mRNA. DR EMBL; AL162390; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC017666; AAH17666.1; ALT_SEQ; mRNA. DR EMBL; BC038225; AAH38225.1; -; mRNA. DR CCDS; CCDS6632.1; -. DR RefSeq; NP_055925.2; NM_015110.3. DR AlphaFoldDB; Q8IY18; -. DR SMR; Q8IY18; -. DR BioGRID; 116754; 55. DR ComplexPortal; CPX-5992; SMC5-SMC6 SUMO ligase complex, EID3 variant. DR ComplexPortal; CPX-6086; SMC5-SMC6 SUMO ligase complex, NSE4EA variant. DR IntAct; Q8IY18; 112. DR MINT; Q8IY18; -. DR STRING; 9606.ENSP00000354957; -. DR GlyGen; Q8IY18; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q8IY18; -. DR MetOSite; Q8IY18; -. DR PhosphoSitePlus; Q8IY18; -. DR BioMuta; SMC5; -. DR DMDM; 122070387; -. DR EPD; Q8IY18; -. DR jPOST; Q8IY18; -. DR MassIVE; Q8IY18; -. DR MaxQB; Q8IY18; -. DR PaxDb; 9606-ENSP00000354957; -. DR PeptideAtlas; Q8IY18; -. DR ProteomicsDB; 71087; -. DR Pumba; Q8IY18; -. DR Antibodypedia; 26866; 222 antibodies from 27 providers. DR DNASU; 23137; -. DR Ensembl; ENST00000361138.7; ENSP00000354957.5; ENSG00000198887.9. DR GeneID; 23137; -. DR KEGG; hsa:23137; -. DR MANE-Select; ENST00000361138.7; ENSP00000354957.5; NM_015110.4; NP_055925.2. DR UCSC; uc004ahr.3; human. DR AGR; HGNC:20465; -. DR CTD; 23137; -. DR DisGeNET; 23137; -. DR GeneCards; SMC5; -. DR HGNC; HGNC:20465; SMC5. DR HPA; ENSG00000198887; Low tissue specificity. DR MalaCards; SMC5; -. DR MIM; 609386; gene. DR MIM; 620185; phenotype. DR neXtProt; NX_Q8IY18; -. DR OpenTargets; ENSG00000198887; -. DR PharmGKB; PA134993662; -. DR VEuPathDB; HostDB:ENSG00000198887; -. DR eggNOG; KOG0979; Eukaryota. DR GeneTree; ENSGT00550000074816; -. DR HOGENOM; CLU_004969_1_0_1; -. DR InParanoid; Q8IY18; -. DR OMA; RFWTSQP; -. DR OrthoDB; 232016at2759; -. DR PhylomeDB; Q8IY18; -. DR TreeFam; TF105708; -. DR PathwayCommons; Q8IY18; -. DR Reactome; R-HSA-3108214; SUMOylation of DNA damage response and repair proteins. DR SignaLink; Q8IY18; -. DR SIGNOR; Q8IY18; -. DR BioGRID-ORCS; 23137; 599 hits in 1168 CRISPR screens. DR ChiTaRS; SMC5; human. DR GeneWiki; SMC5; -. DR GenomeRNAi; 23137; -. DR Pharos; Q8IY18; Tbio. DR PRO; PR:Q8IY18; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; Q8IY18; Protein. DR Bgee; ENSG00000198887; Expressed in sural nerve and 196 other cell types or tissues. DR GO; GO:0030054; C:cell junction; IDA:HPA. DR GO; GO:0000775; C:chromosome, centromeric region; IEA:Ensembl. DR GO; GO:0000781; C:chromosome, telomeric region; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl. DR GO; GO:0035061; C:interchromatin granule; IDA:UniProtKB. DR GO; GO:0016607; C:nuclear speck; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0016605; C:PML body; IDA:UniProtKB. DR GO; GO:0000803; C:sex chromosome; ISS:UniProtKB. DR GO; GO:0035861; C:site of double-strand break; IDA:UniProtKB. DR GO; GO:0030915; C:Smc5-Smc6 complex; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro. DR GO; GO:0000217; F:DNA secondary structure binding; IDA:UniProt. DR GO; GO:0003697; F:single-stranded DNA binding; IBA:GO_Central. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0090398; P:cellular senescence; IMP:UniProtKB. DR GO; GO:0140588; P:chromatin looping; NAS:ComplexPortal. DR GO; GO:0030261; P:chromosome condensation; IEA:Ensembl. DR GO; GO:0007059; P:chromosome segregation; IEA:Ensembl. DR GO; GO:0006974; P:DNA damage response; IDA:UniProtKB. DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IMP:UniProtKB. DR GO; GO:0044772; P:mitotic cell cycle phase transition; IEA:Ensembl. DR GO; GO:0044828; P:negative regulation by host of viral genome replication; IDA:UniProt. DR GO; GO:0051984; P:positive regulation of chromosome segregation; IMP:UniProtKB. DR GO; GO:0034184; P:positive regulation of maintenance of mitotic sister chromatid cohesion; IMP:UniProtKB. DR GO; GO:0071459; P:protein localization to chromosome, centromeric region; IEA:Ensembl. DR GO; GO:0016925; P:protein sumoylation; NAS:ComplexPortal. DR GO; GO:0032204; P:regulation of telomere maintenance; NAS:ComplexPortal. DR GO; GO:0019827; P:stem cell population maintenance; IEA:Ensembl. DR GO; GO:0000722; P:telomere maintenance via recombination; IMP:UniProtKB. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 2. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR003395; RecF/RecN/SMC_N. DR InterPro; IPR027131; SMC5. DR PANTHER; PTHR45916; STRUCTURAL MAINTENANCE OF CHROMOSOMES PROTEIN 5; 1. DR PANTHER; PTHR45916:SF1; STRUCTURAL MAINTENANCE OF CHROMOSOMES PROTEIN 5; 1. DR Pfam; PF02463; SMC_N; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR Genevisible; Q8IY18; HS. PE 1: Evidence at protein level; KW ATP-binding; Cell cycle; Cell division; Chromosome; Coiled coil; KW Disease variant; DNA damage; DNA recombination; DNA repair; Mitosis; KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Telomere; KW Ubl conjugation. FT CHAIN 1..1101 FT /note="Structural maintenance of chromosomes protein 5" FT /id="PRO_0000270951" FT REGION 1..43 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 446..646 FT /note="Flexible hinge" FT COILED 207..445 FT /evidence="ECO:0000255" FT COILED 647..828 FT /evidence="ECO:0000255" FT COILED 888..927 FT /evidence="ECO:0000255" FT COMPBIAS 1..16 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 80..87 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255" FT MOD_RES 25 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 35 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT VARIANT 306 FT /note="V -> I (in dbSNP:rs1180116)" FT /evidence="ECO:0000269|PubMed:11408570, FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9628581" FT /id="VAR_029824" FT VARIANT 308 FT /note="C -> R (in dbSNP:rs1180117)" FT /evidence="ECO:0000269|PubMed:11408570, FT ECO:0000269|PubMed:15489334" FT /id="VAR_029825" FT VARIANT 372 FT /note="Missing (in ATELS2; loss-of-function variant; unable FT to rescue microcephaly and aberrant craniofacial patterning FT in zebrafish lacking SMC5; does not relocalize efficiently FT to sites of laser irradiation-induced DNA damage; loss of FT interaction with SLF2 and NSMCE2; severely decreased FT interaction with SMC6)" FT /evidence="ECO:0000269|PubMed:36333305" FT /id="VAR_087971" FT VARIANT 425..1101 FT /note="Missing (in ATELS2; loss-of-function variant; unable FT to rescue microcephaly and aberrant craniofacial patterning FT in zebrafish lacking SMC5; loss of interaction with SLF2, FT SMC6 and NSMCE2)" FT /evidence="ECO:0000269|PubMed:36333305" FT /id="VAR_087972" FT VARIANT 682 FT /note="H -> R (in dbSNP:rs11142365)" FT /id="VAR_061869" FT VARIANT 990 FT /note="H -> D (in ATELS2; loss-of-function variant; unable FT to rescue microcephaly and aberrant craniofacial patterning FT in zebrafish lacking SMC5; does not relocalize efficiently FT to sites of laser irradiation-induced DNA damage; no effect FT on interaction with SLF2, SMC6 and NSMCE2)" FT /evidence="ECO:0000269|PubMed:36333305" FT /id="VAR_087973" SQ SEQUENCE 1101 AA; 128806 MW; 54393D50688A914A CRC64; MATPSKKTST PSPQPSKRAL PRDPSSEVPS KRKNSAPQLP LLQSSGPFVE GSIVRISMEN FLTYDICEVS PGPHLNMIVG ANGTGKSSIV CAICLGLAGK PAFMGRADKV GFFVKRGCSR GMVEIELFRA SGNLVITREI DVAKNQSFWF INKKSTTQKI VEEKVAALNI QVGNLCQFLP QDKVGEFAKL SKIELLEATE KSIGPPEMHK YHCELKNLRE KEKQLETSCK EKTEYLQKMV QRNERYKQDV ERFYERKRHL DLIEMLEAKR PWVEYENVRQ EYEEVKLVRD RVKEEVRKLK EGQIPVTCRI EEMENERHNL EARIKEKATD IKEASQKCKQ KQDVIERKDK HIEELQQALI VKQNEELDRQ RRIGNTRKMI EDLQNELKTT ENCENLQPQI DAITNDLRRI QDEKALCEGE IIDKRRERET LEKEKKSVDD HIVRFDNLMN QKEDKLRQRF RDTYDAVLWL RNNRDKFKQR VCEPIMLTIN MKDNKNAKYI ENHIPSNDLR AFVFESQEDM EVFLKEVRDN KKLRVNAVIA PKSSYADKAP SRSLNELKQY GFFSYLRELF DAPDPVMSYL CCQYHIHEVP VGTEKTRERI ERVIQETRLK QIYTAEEKYV VKTSFYSNKV ISSNTSLKVA QFLTVTVDLE QRRHLEEQLK EIHRKLQAVD SGLIALRETS KHLEHKDNEL RQKKKELLER KTKKRQLEQK ISSKLGSLKL MEQDTCNLEE EERKASTKIK EINVQKAKLV TELTNLIKIC TSLHIQKVDL ILQNTTVISE KNKLESDYMA ASSQLRLTEQ HFIELDENRQ RLLQKCKELM KRARQVCNLG AEQTLPQEYQ TQVPTIPNGH NSSLPMVFQD LPNTLDEIDA LLTEERSRAS CFTGLNPTIV QEYTKREEEI EQLTEELKGK KVELDQYREN ISQVKERWLN PLKELVEKIN EKFSNFFSSM QCAGEVDLHT ENEEDYDKYG IRIRVKFRSS TQLHELTPHH QSGGERSVST MLYLMALQEL NRCPFRVVDE INQGMDPINE RRVFEMVVNT ACKENTSQYF FITPKLLQNL PYSEKMTVLF VYNGPHMLEP NTWNLKAFQR RRRRITFTQP S //