ID   SLF2_HUMAN              Reviewed;        1173 AA.
AC   Q8IX21; A8K950; B1AL17; Q5W0L8; Q6GMU6; Q9NPE8;
DT   16-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT   16-AUG-2005, sequence version 2.
DT   02-SEP-2026, entry version 156.
DE   RecName: Full=SMC5-SMC6 complex localization factor protein 2 {ECO:0000312|HGNC:HGNC:17814};
DE   AltName: Full=Smc5/6 localization factor 1 {ECO:0000303|PubMed:25931565};
GN   Name=SLF2 {ECO:0000303|PubMed:25931565, ECO:0000312|HGNC:HGNC:17814};
GN   Synonyms=C10orf6, FAM178A;
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), VARIANT TYR-541, AND TISSUE
RP   SPECIFICITY.
RC   TISSUE=Lymphoblast;
RX   PubMed=12459258; DOI=10.1016/s0378-1119(02)01019-3;
RA   Nikali K., Saharinen J., Peltonen L.;
RT   "cDNA cloning, expression profile and genomic structure of a novel human
RT   transcript on chromosome 10q24, and its analyses as a candidate gene for
RT   infantile onset spinocerebellar ataxia.";
RL   Gene 299:111-115(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Testis;
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15164054; DOI=10.1038/nature02462;
RA   Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA   Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA   Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA   Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA   Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA   Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA   Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA   Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA   Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA   Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA   Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA   Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA   Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA   Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA   McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA   Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA   Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA   Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA   Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA   Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA   Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA   Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA   Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT   "The DNA sequence and comparative analysis of human chromosome 10.";
RL   Nature 429:375-381(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC   TISSUE=Kidney;
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   [5]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN   [6]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-603; SER-607 AND SER-614, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA   Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA   Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT   "System-wide temporal characterization of the proteome and phosphoproteome
RT   of human embryonic stem cell differentiation.";
RL   Sci. Signal. 4:RS3-RS3(2011).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-481, AND IDENTIFICATION BY
RP   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   [8]
RP   SUBCELLULAR LOCATION, AND MUTAGENESIS OF TYR-142.
RX   PubMed=24561620; DOI=10.1038/ncb2918;
RA   Alabert C., Bukowski-Wills J.C., Lee S.B., Kustatscher G., Nakamura K.,
RA   de Lima Alves F., Menard P., Mejlvang J., Rappsilber J., Groth A.;
RT   "Nascent chromatin capture proteomics determines chromatin dynamics during
RT   DNA replication and identifies unknown fork components.";
RL   Nat. Cell Biol. 16:281-293(2014).
RN   [9]
RP   FUNCTION, INTERACTION WITH RAD18; SLF1; SMC5 AND SMC6, SUBCELLULAR
RP   LOCATION, AND IDENTIFICATION 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   [10]
RP   STRUCTURE BY ELECTRON MICROSCOPY (3.50 ANGSTROMS) OF 635-1173 IN COMPLEX
RP   WITH SIMC1, FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, REGION NSE6-LIKE
RP   DOMAIN, AND INTERACTION WITH SLF1 AND SIMC1.
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   [11]
RP   INVOLVEMENT IN ATELS1, TISSUE SPECIFICITY, INTERACTION WITH SLF1 AND RAD18,
RP   REGION, AND VARIANTS ATELS1 190-ARG--SER-1173 DEL; 815-SER--SER-1173 DEL
RP   AND ILE-861.
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).
RN   [12]
RP   VARIANT CYS-271.
RX   PubMed=33979636; DOI=10.1016/j.ajhg.2021.04.017;
RA   Morava E., Schatz U.A., Torring P.M., Abbott M.A., Baumann M.,
RA   Brasch-Andersen C., Chevalier N., Dunkhase-Heinl U., Fleger M., Haack T.B.,
RA   Nelson S., Potelle S., Radenkovic S., Bommer G.T., Van Schaftingen E.,
RA   Veiga-da-Cunha M.;
RT   "Impaired glucose-1,6-biphosphate production due to bi-allelic PGM2L1
RT   mutations is associated with a neurodevelopmental disorder.";
RL   Am. J. Hum. Genet. 108:1151-1160(2021).
CC   -!- FUNCTION: Plays a role in the DNA damage response (DDR) pathway by
CC       regulating postreplication repair of UV-damaged DNA and genomic
CC       stability maintenance (PubMed:25931565). The SLF1-SLF2 complex acts to
CC       link RAD18 with the SMC5-SMC6 complex at replication-coupled
CC       interstrand cross-links (ICL) and DNA double-strand breaks (DSBs) sites
CC       on chromatin during DNA repair in response to stalled replication forks
CC       (PubMed:25931565). Promotes the recruitment of the SMC5-SMC6 complex to
CC       DNA lesions (PubMed:25931565). Plays a role in SMC5-SMC6 complex
CC       recruitment for viral restriction. Forms a complex with SIMC1 and this
CC       complex is required to recruit SMC5-SMC6 complex to PML nuclear bodies
CC       and sites of viral replication (PubMed:36373674).
CC       {ECO:0000269|PubMed:25931565, ECO:0000269|PubMed:36373674}.
CC   -!- SUBUNIT: Forms a heterodimer with SIMC1 (PubMed:36373674). Interacts
CC       with SLF1 (via N-terminus); this interaction links RAD18 to the SMC5-
CC       SMC6 complex (PubMed:25931565, PubMed:36333305, PubMed:36373674).
CC       Interacts with RAD18; this interaction is increased in a SLF1-dependent
CC       manner (PubMed:25931565, PubMed:36333305). Interacts with SMC5 and SMC6
CC       (PubMed:25931565). {ECO:0000269|PubMed:25931565,
CC       ECO:0000269|PubMed:36333305, ECO:0000269|PubMed:36373674}.
CC   -!- INTERACTION:
CC       Q8IX21; P25786: PSMA1; NbExp=3; IntAct=EBI-2682240, EBI-359352;
CC       Q8IX21; Q5VUG0: SFMBT2; NbExp=3; IntAct=EBI-2682240, EBI-12025260;
CC       Q8IX21; Q8NDZ2: SIMC1; NbExp=8; IntAct=EBI-2682240, EBI-724973;
CC       Q8IX21; Q9BQI6: SLF1; NbExp=9; IntAct=EBI-2682240, EBI-10975834;
CC       Q8IX21; Q8IY18: SMC5; NbExp=4; IntAct=EBI-2682240, EBI-605405;
CC       Q8IX21; Q96SB8: SMC6; NbExp=6; IntAct=EBI-2682240, EBI-605415;
CC       Q8IX21; Q14142: TRIM14; NbExp=3; IntAct=EBI-2682240, EBI-2820256;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:24561620,
CC       ECO:0000269|PubMed:25931565}. Nucleus, PML body
CC       {ECO:0000269|PubMed:36373674}. Note=Mainly localizes in the nucleus
CC       (PubMed:24561620). Colocalizes with PCNA on replication sites
CC       (PubMed:24561620). Associates with chromatin (PubMed:25931565).
CC       Accumulates with RAD18 and the SMC5-SMC6 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:0000269|PubMed:24561620, ECO:0000269|PubMed:25931565}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=Q8IX21-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q8IX21-2; Sequence=VSP_045621;
CC       Name=3;
CC         IsoId=Q8IX21-3; Sequence=VSP_054914, VSP_054915;
CC   -!- TISSUE SPECIFICITY: Widely expressed (PubMed:12459258,
CC       PubMed:36333305). Expressed at higher level in skeletal muscle and at
CC       slightly lower level in brain, liver and heart, than in lung, kidney,
CC       spleen and thymus (PubMed:12459258). {ECO:0000269|PubMed:12459258,
CC       ECO:0000269|PubMed:36333305}.
CC   -!- DISEASE: Atelis syndrome 1 (ATELS1) [MIM:620184]: 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   -!- MISCELLANEOUS: Localized in the locus associated with inherited
CC       infantile onset spinocerebellar ataxia (IOSCA). No mutation were found
CC       associated with IOSCA compared to control subjects. The expression
CC       level in the brain was not different between the 2 populations.
CC   -!- SIMILARITY: Belongs to the FAM178 family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAA91657.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; AF460991; AAN84475.1; -; mRNA.
DR   EMBL; AK001374; BAA91657.1; ALT_INIT; mRNA.
DR   EMBL; AK292565; BAF85254.1; -; mRNA.
DR   EMBL; AL138762; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL133215; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC030565; -; NOT_ANNOTATED_CDS; mRNA.
DR   EMBL; BC073832; AAH73832.1; -; mRNA.
DR   CCDS; CCDS44470.1; -. [Q8IX21-2]
DR   CCDS; CCDS65918.1; -. [Q8IX21-3]
DR   CCDS; CCDS7500.1; -. [Q8IX21-1]
DR   RefSeq; NP_001129595.1; NM_001136123.2. [Q8IX21-2]
DR   RefSeq; NP_001230699.1; NM_001243770.2. [Q8IX21-3]
DR   RefSeq; NP_060591.3; NM_018121.4. [Q8IX21-1]
DR   PDB; 7T5P; EM; 3.40 A; B=635-1173.
DR   AlphaFoldDB; Q8IX21; -.
DR   EMDB; EMD-25706; -.
DR   SMR; Q8IX21; -.
DR   BioGRID; 120841; 42.
DR   ComplexPortal; CPX-5992; SMC5-SMC6 SUMO ligase complex, EID3 variant.
DR   ComplexPortal; CPX-6086; SMC5-SMC6 SUMO ligase complex, NSE4EA variant.
DR   FunCoup; Q8IX21; 1979.
DR   IntAct; Q8IX21; 29.
DR   MINT; Q8IX21; -.
DR   NDEx; IQUERY-CP-SLF2; 1 NDEx IQuery Curated Pathway.
DR   STRING; 9606.ENSP00000359292; -.
DR   GlyGen; Q8IX21; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q8IX21; -.
DR   PhosphoSitePlus; Q8IX21; -.
DR   BioMuta; SLF2; -.
DR   DMDM; 73620064; -.
DR   jPOST; Q8IX21; -.
DR   MassIVE; Q8IX21; -.
DR   PaxDb; 9606-ENSP00000359292; -.
DR   PeptideAtlas; Q8IX21; -.
DR   ProteomicsDB; 3129; -.
DR   ProteomicsDB; 70968; -. [Q8IX21-1]
DR   Pumba; Q8IX21; -.
DR   Antibodypedia; 49598; 19 antibodies from 8 providers.
DR   DNASU; 55719; -.
DR   Ensembl; ENST00000238961.9; ENSP00000238961.3; ENSG00000119906.14. [Q8IX21-1]
DR   Ensembl; ENST00000370269.3; ENSP00000359292.3; ENSG00000119906.14. [Q8IX21-2]
DR   Ensembl; ENST00000609386.1; ENSP00000476379.1; ENSG00000119906.14. [Q8IX21-3]
DR   GeneID; 55719; -.
DR   KEGG; hsa:55719; -.
DR   MANE-Select; ENST00000238961.9; ENSP00000238961.3; NM_018121.4; NP_060591.3.
DR   UCSC; uc001krq.5; human. [Q8IX21-1]
DR   AGR; HGNC:17814; -.
DR   ClinPGx; PA162387411; -.
DR   CTD; 55719; -.
DR   DisGeNET; 55719; -.
DR   GeneCards; SLF2; -.
DR   HGNC; HGNC:17814; SLF2.
DR   HPA; ENSG00000119906; Low tissue specificity.
DR   MalaCards; SLF2; -.
DR   MIM; 610348; gene.
DR   MIM; 620184; phenotype.
DR   OpenTargets; ENSG00000119906; -.
DR   VEuPathDB; HostDB:ENSG00000119906; -.
DR   eggNOG; ENOG502QW1I; Eukaryota.
DR   GeneTree; ENSGT00530000064017; -.
DR   HOGENOM; CLU_008361_0_0_1; -.
DR   InParanoid; Q8IX21; -.
DR   OrthoDB; 6158547at2759; -.
DR   PAN-GO; Q8IX21; 5 GO annotations based on evolutionary models.
DR   PhylomeDB; Q8IX21; -.
DR   PathwayCommons; Q8IX21; -.
DR   SignaLink; Q8IX21; -.
DR   Agora; ENSG00000119906; -.
DR   BioGRID-ORCS; 55719; 57 hits in 1152 CRISPR screens.
DR   ChiTaRS; SLF2; human.
DR   GenomeRNAi; 55719; -.
DR   Pharos; Q8IX21; Tbio.
DR   PRO; PR:Q8IX21; -.
DR   Proteomes; UP000005640; Chromosome 10.
DR   RNAct; Q8IX21; protein.
DR   Bgee; ENSG00000119906; Expressed in adrenal tissue and 198 other cell types or tissues.
DR   ExpressionAtlas; Q8IX21; baseline and differential.
DR   GO; GO:0000785; C:chromatin; IDA:UniProtKB.
DR   GO; GO:0000781; C:chromosome, telomeric region; NAS:ComplexPortal.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0016605; C:PML body; IDA:UniProtKB.
DR   GO; GO:0035861; C:site of double-strand break; IDA:UniProtKB.
DR   GO; GO:0030915; C:Smc5-Smc6 complex; NAS:ComplexPortal.
DR   GO; GO:0044877; F:protein-containing complex binding; IPI:UniProtKB.
DR   GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR   GO; GO:0140588; P:chromatin looping; NAS:ComplexPortal.
DR   GO; GO:0006974; P:DNA damage response; IDA:UniProtKB.
DR   GO; GO:0000724; P:double-strand break repair via homologous recombination; NAS:ComplexPortal.
DR   GO; GO:2000781; P:positive regulation of double-strand break repair; IDA:UniProtKB.
DR   GO; GO:0034184; P:positive regulation of maintenance of mitotic sister chromatid cohesion; IMP:UniProtKB.
DR   GO; GO:0031334; P:positive regulation of protein-containing complex assembly; IMP:UniProtKB.
DR   GO; GO:1990166; P:protein localization to site of double-strand break; IDA:UniProtKB.
DR   GO; GO:0016925; P:protein sumoylation; NAS:ComplexPortal.
DR   GO; GO:0032204; P:regulation of telomere maintenance; NAS:ComplexPortal.
DR   InterPro; IPR044276; CANIN_dom.
DR   InterPro; IPR026161; FAM178.
DR   PANTHER; PTHR16046; SMC5-SMC6 COMPLEX LOCALIZATION FACTOR 2; 1.
DR   PANTHER; PTHR16046:SF10; SMC5-SMC6 COMPLEX LOCALIZATION FACTOR PROTEIN 2; 1.
DR   Pfam; PF14816; CANIN; 1.
DR   PDBsum; 7T5P; -.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Disease variant; DNA damage;
KW   DNA repair; Nucleus; Phosphoprotein; Proteomics identification;
KW   Reference proteome.
FT   CHAIN           1..1173
FT                   /note="SMC5-SMC6 complex localization factor protein 2"
FT                   /id="PRO_0000089778"
FT   REGION          1..109
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          161..230
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          256..275
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          280..373
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          394..620
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          635..1173
FT                   /note="Interaction with SIMC1"
FT                   /evidence="ECO:0000269|PubMed:36373674"
FT   REGION          635..663
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          664..1166
FT                   /note="NSE6-like domain"
FT                   /evidence="ECO:0000269|PubMed:36373674"
FT   REGION          702..1173
FT                   /note="Required for interaction with SLF1 and RAD18"
FT                   /evidence="ECO:0000269|PubMed:36333305"
FT   MOTIF           137..149
FT                   /note="APIM motif"
FT   COMPBIAS        39..50
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        88..106
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        181..199
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        212..221
FT                   /note="Low complexity"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        262..275
FT                   /note="Low complexity"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        280..293
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        317..330
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        339..349
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        355..373
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        409..428
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        499..520
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        571..592
FT                   /note="Low complexity"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        602..619
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         481
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         603
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21406692"
FT   MOD_RES         607
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21406692"
FT   MOD_RES         614
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21406692"
FT   VAR_SEQ         48..63
FT                   /note="KQSIIDFFKPASKQDR -> YRAEGLRRGRVAGARV (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_054914"
FT   VAR_SEQ         64..1173
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_054915"
FT   VAR_SEQ         1163..1173
FT                   /note="GQLHDFWVPDS -> VSFCYTISCILNSFAEWHSSYCLK (in isoform
FT                   2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_045621"
FT   VARIANT         190..1173
FT                   /note="Missing (in ATELS1)"
FT                   /evidence="ECO:0000269|PubMed:36333305"
FT                   /id="VAR_087944"
FT   VARIANT         271
FT                   /note="S -> C (found in a patient with neurodevelopmental
FT                   disorder with hypotonia, dysmorphic facies and skin
FT                   abnormalities; uncertain significance; dbSNP:rs752352367)"
FT                   /evidence="ECO:0000269|PubMed:33979636"
FT                   /id="VAR_087993"
FT   VARIANT         541
FT                   /note="S -> Y (in dbSNP:rs10883563)"
FT                   /evidence="ECO:0000269|PubMed:12459258"
FT                   /id="VAR_023112"
FT   VARIANT         815..1173
FT                   /note="Missing (in ATELS1)"
FT                   /evidence="ECO:0000269|PubMed:36333305"
FT                   /id="VAR_087945"
FT   VARIANT         861
FT                   /note="N -> I (in ATELS1; dbSNP:rs1266675910)"
FT                   /evidence="ECO:0000269|PubMed:36333305"
FT                   /id="VAR_087946"
FT   MUTAGEN         142
FT                   /note="Y->A: In APIMmut; does not affect subcellular
FT                   location."
FT                   /evidence="ECO:0000269|PubMed:24561620"
FT   TURN            756..758
FT                   /evidence="ECO:0007829|PDB:7T5P"
FT   TURN            762..764
FT                   /evidence="ECO:0007829|PDB:7T5P"
FT   HELIX           771..778
FT                   /evidence="ECO:0007829|PDB:7T5P"
FT   HELIX           782..789
FT                   /evidence="ECO:0007829|PDB:7T5P"
FT   HELIX           792..796
FT                   /evidence="ECO:0007829|PDB:7T5P"
FT   STRAND          798..800
FT                   /evidence="ECO:0007829|PDB:7T5P"
FT   HELIX           801..803
FT                   /evidence="ECO:0007829|PDB:7T5P"
FT   HELIX           804..816
FT                   /evidence="ECO:0007829|PDB:7T5P"
FT   HELIX           820..840
FT                   /evidence="ECO:0007829|PDB:7T5P"
FT   STRAND          843..845
FT                   /evidence="ECO:0007829|PDB:7T5P"
FT   HELIX           846..848
FT                   /evidence="ECO:0007829|PDB:7T5P"
FT   HELIX           852..862
FT                   /evidence="ECO:0007829|PDB:7T5P"
FT   HELIX           866..869
FT                   /evidence="ECO:0007829|PDB:7T5P"
FT   HELIX           881..891
FT                   /evidence="ECO:0007829|PDB:7T5P"
FT   HELIX           911..927
FT                   /evidence="ECO:0007829|PDB:7T5P"
FT   HELIX           929..931
FT                   /evidence="ECO:0007829|PDB:7T5P"
FT   HELIX           934..948
FT                   /evidence="ECO:0007829|PDB:7T5P"
FT   TURN            952..955
FT                   /evidence="ECO:0007829|PDB:7T5P"
FT   HELIX           959..971
FT                   /evidence="ECO:0007829|PDB:7T5P"
FT   HELIX           975..988
FT                   /evidence="ECO:0007829|PDB:7T5P"
FT   HELIX           993..1002
FT                   /evidence="ECO:0007829|PDB:7T5P"
FT   HELIX           1008..1025
FT                   /evidence="ECO:0007829|PDB:7T5P"
FT   HELIX           1039..1050
FT                   /evidence="ECO:0007829|PDB:7T5P"
FT   HELIX           1053..1067
FT                   /evidence="ECO:0007829|PDB:7T5P"
FT   STRAND          1068..1070
FT                   /evidence="ECO:0007829|PDB:7T5P"
FT   HELIX           1075..1100
FT                   /evidence="ECO:0007829|PDB:7T5P"
FT   HELIX           1109..1119
FT                   /evidence="ECO:0007829|PDB:7T5P"
FT   HELIX           1120..1125
FT                   /evidence="ECO:0007829|PDB:7T5P"
FT   HELIX           1135..1156
FT                   /evidence="ECO:0007829|PDB:7T5P"
SQ   SEQUENCE   1173 AA;  131873 MW;  0A9FB5662185A633 CRC64;
     MTRRCMPARP GFPSSPAPGS SPPRCHLRPG STAHAAAGKR TESPGDRKQS IIDFFKPASK
     QDRHMLDSPQ KSNIKYGGSR LSITGTEQFE RKLSSPKESK PKRVPPEKSP IIEAFMKGVK
     EHHEDHGIHE SRRPCLSLAS KYLAKGTNIY VPSSYHLPKE MKSLKKKHRS PERRKSLFIH
     ENNEKNDRDR GKTNADSKKQ TTVAEADIFN NSSRSLSSRS SLSRHHPEES PLGAKFQLSL
     ASYCRERELK RLRKEQMEQR INSENSFSEA SSLSLKSSIE RKYKPRQEQR KQNDIIPGKN
     NLSNVENGHL SRKRSSSDSW EPTSAGSKQN KFPEKRKRNS VDSDLKSTRE SMIPKARESF
     LEKRPDGPHQ KEKFIKHIAL KTPGDVLRLE DISKEPSDET DGSSAGLAPS NSGNSGHHST
     RNSDQIQVAG TKETKMQKPH LPLSQEKSAI KKASNLQKNK TASSTTKEKE TKLPLLSRVP
     SAGSSLVPLN AKNCALPVSK KDKERSSSKE CSGHSTESTK HKEHKAKTNK ADSNVSSGKI
     SGGPLRSEYG TPTKSPPAAL EVVPCIPSPA APSDKAPSEG ESSGNSNAGS SALKRKLRGD
     FDSDEESLGY NLDSDEEEET LKSLEEIMAL NFNQTPAATG KPPALSKGLR SQSSDYTGHV
     HPGTYTNTLE RLVKEMEDTQ RLDELQKQLQ EDIRQGRGIK SPIRIGEEDS TDDEDGLLEE
     HKEFLKKFSV TIDAIPDHHP GEEIFNFLNS GKIFNQYTLD LRDSGFIGQS AVEKLILKSG
     KTDQIFLTTQ GFLTSAYHYV QCPVPVLKWL FRMMSVHTDC IVSVQILSTL MEITIRNDTF
     SDSPVWPWIP SLSDVAAVFF NMGIDFRSLF PLENLQPDFN EDYLVSETQT TSRGKESEDS
     SYKPIFSTLP ETNILNVVKF LGLCTSIHPE GYQDREIMLL ILMLFKMSLE KQLKQIPLVD
     FQSLLINLMK NIRDWNTKVP ELCLGINELS SHPHNLLWLV QLVPNWTSRG RQLRQCLSLV
     IISKLLDEKH EDVPNASNLQ VSVLHRYLVQ MKPSDLLKKM VLKKKAEQPD GIIDDSLHLE
     LEKQAYYLTY ILLHLVGEVS CSHSFSSGQR KHFVLLCGAL EKHVKCDIRE DARLFYRTKV
     KDLVARIHGK WQEIIQNCRP TQGQLHDFWV PDS
//