RAD21_HUMAN
ID RAD21_HUMAN Reviewed; 631 AA.
AC O60216; A8K0E0; Q15001; Q99568;
DT 15-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 15-NOV-2002, sequence version 2.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=Double-strand-break repair protein rad21 homolog;
DE Short=hHR21 {ECO:0000303|PubMed:8812457};
DE AltName: Full=Nuclear matrix protein 1 {ECO:0000303|PubMed:10623634};
DE Short=NXP-1 {ECO:0000303|PubMed:10623634};
DE AltName: Full=SCC1 homolog;
DE Contains:
DE RecName: Full=64-kDa C-terminal product {ECO:0000303|PubMed:12417729};
DE AltName: Full=64-kDa carboxy-terminal product {ECO:0000303|PubMed:12417729};
DE AltName: Full=65-kDa carboxy-terminal product {ECO:0000303|PubMed:11875078};
GN Name=RAD21;
GN Synonyms=HR21 {ECO:0000303|PubMed:11483345}, KIAA0078, NXP1,
GN SCC1 {ECO:0000303|PubMed:11509732};
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], AND DEVELOPMENTAL STAGE.
RC TISSUE=Testis;
RX PubMed=8812457; DOI=10.1006/geno.1996.0466;
RA McKay M.J., Troelstra C., van der Spek P., Kanaar R., Smit B.,
RA Hagemeijer A., Bootsma D., Hoeijmakers J.H.J.;
RT "Sequence conservation of the rad21 Schizosaccharomyces pombe DNA double-
RT strand break repair gene in human and mouse.";
RL Genomics 36:305-315(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Bone marrow;
RX PubMed=7584044; DOI=10.1093/dnares/1.5.223;
RA Nomura N., Nagase T., Miyajima N., Sazuka T., Tanaka A., Sato S., Seki N.,
RA Kawarabayasi Y., Ishikawa K., Tabata S.;
RT "Prediction of the coding sequences of unidentified human genes. II. The
RT coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of
RT cDNA clones from human cell line KG-1.";
RL DNA Res. 1:223-229(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NIEHS SNPs program;
RL Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cerebellum;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=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 [7]
RP IDENTIFICATION IN THE COHESIN COMPLEX.
RX PubMed=10931856; DOI=10.1083/jcb.150.3.405;
RA Losada A., Yokochi T., Kobayashi R., Hirano T.;
RT "Identification and characterization of SA/Scc3p subunits in the Xenopus
RT and human cohesin complexes.";
RL J. Cell Biol. 150:405-416(2000).
RN [8]
RP PROTEIN SEQUENCE OF 406-418, IDENTIFICATION IN THE COHESIN COMPLEX,
RP INTERACTION WITH NUMA1, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=11590136; DOI=10.1074/jbc.m103364200;
RA Gregson H.C., Schmiesing J.A., Kim J.-S., Kobayashi T., Zhou S.,
RA Yokomori K.;
RT "A potential role for human cohesin in mitotic spindle aster assembly.";
RL J. Biol. Chem. 276:47575-47582(2001).
RN [9]
RP PHOSPHORYLATION BY PLK1.
RX PubMed=11931760; DOI=10.1016/s1097-2765(02)00473-2;
RA Sumara I., Vorlaufer E., Stukenberg P.T., Kelm O., Redemann N., Nigg E.A.,
RA Peters J.-M.;
RT "The dissociation of cohesin from chromosomes in prophase is regulated by
RT Polo-like kinase.";
RL Mol. Cell 9:515-525(2002).
RN [10]
RP PROTEIN SEQUENCE OF 280-286 (64-KDA C-TERMINAL PRODUCT), CLEAVAGE BY
RP CASPASE-3 OR CASPASE-7, FUNCTION, MUTAGENESIS OF 276-ASP--SER-280 AND
RP ASP-279, AND SUBCELLULAR LOCATION.
RX PubMed=12417729; DOI=10.1128/mcb.22.23.8267-8277.2002;
RA Pati D., Zhang N., Plon S.E.;
RT "Linking sister chromatid cohesion and apoptosis: role of rad21.";
RL Mol. Cell. Biol. 22:8267-8277(2002).
RN [11]
RP SUBCELLULAR LOCATION.
RX PubMed=10623634; DOI=10.1006/bbrc.1999.1969;
RA Sadano H., Sugimoto H., Sakai F., Nomura N., Osumi T.;
RT "NXP-1, a human protein related to Rad21/Scc1/Mcd1, is a component of the
RT nuclear matrix.";
RL Biochem. Biophys. Res. Commun. 267:418-422(2000).
RN [12]
RP SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND PHOSPHORYLATION.
RX PubMed=11073952; DOI=10.1074/jbc.m007809200;
RA Hoque M.T., Ishikawa F.;
RT "Human chromatid cohesin component hRad21 is phosphorylated in M phase and
RT associated with metaphase centromeres.";
RL J. Biol. Chem. 276:5059-5067(2001).
RN [13]
RP FUNCTION, CLEAVAGE BY ESPL1, MUTAGENESIS OF ARG-172 AND ARG-450, AND
RP SUBCELLULAR LOCATION.
RX PubMed=11509732; DOI=10.1126/science.1061376;
RA Hauf S., Waizenegger I.C., Peters J.-M.;
RT "Cohesin cleavage by separase required for anaphase and cytokinesis in
RT human cells.";
RL Science 293:1320-1323(2001).
RN [14]
RP FUNCTION, CLEAVAGE BY CASPASE-3 OR CASPASE-7, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF ASP-279 AND ASP-282.
RX PubMed=11875078; DOI=10.1074/jbc.m201322200;
RA Chen F., Kamradt M., Mulcahy M., Byun Y., Xu H., McKay M.J., Cryns V.L.;
RT "Caspase proteolysis of the cohesin component RAD21 promotes apoptosis.";
RL J. Biol. Chem. 277:16775-16781(2002).
RN [15]
RP INTERACTION WITH SMARCA5; SMC1A AND CHD4, AND MUTAGENESIS OF 1-MET--ASP-126
RP AND 126-ASP--ASP-282.
RX PubMed=12198550; DOI=10.1038/nature01024;
RA Hakimi M.-A., Bochar D.A., Schmiesing J.A., Dong Y., Barak O.G.,
RA Speicher D.W., Yokomori K., Shiekhattar R.;
RT "A chromatin remodelling complex that loads cohesin onto human
RT chromosomes.";
RL Nature 418:994-998(2002).
RN [16]
RP INTERACTION WITH CDCA5; PDS5A AND PDS5B.
RX PubMed=15837422; DOI=10.1016/j.molcel.2005.03.017;
RA Rankin S., Ayad N.G., Kirschner M.W.;
RT "Sororin, a substrate of the anaphase-promoting complex, is required for
RT sister chromatid cohesion in vertebrates.";
RL Mol. Cell 18:185-200(2005).
RN [17]
RP ERRATUM OF PUBMED:15837422.
RA Rankin S., Ayad N.G., Kirschner M.W.;
RL Mol. Cell 18:609-609(2005).
RN [18]
RP INTERACTION WITH DDX11.
RX PubMed=17105772; DOI=10.1242/jcs.03262;
RA Parish J.L., Rosa J., Wang X., Lahti J.M., Doxsey S.J., Androphy E.J.;
RT "The DNA helicase ChlR1 is required for sister chromatid cohesion in
RT mammalian cells.";
RL J. Cell Sci. 119:4857-4865(2006).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-46 AND SER-175, AND
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 [20]
RP INTERACTION WITH PDS5B; STAG1 AND WAPL.
RX PubMed=19696148; DOI=10.1101/gad.1844309;
RA Shintomi K., Hirano T.;
RT "Releasing cohesin from chromosome arms in early mitosis: opposing actions
RT of Wapl-Pds5 and Sgo1.";
RL Genes Dev. 23:2224-2236(2009).
RN [21]
RP VARIANT ARG-481.
RX PubMed=11483345; DOI=10.1016/s0360-3016(01)01608-x;
RA Severin D.M., Leong T., Cassidy B., Elsaleh H., Peters L., Venter D.,
RA Southey M., McKay M.;
RT "Novel DNA sequence variants in the hHR21 DNA repair gene in radiosensitive
RT cancer patients.";
RL Int. J. Radiat. Oncol. Biol. Phys. 50:1323-1331(2001).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-153 AND SER-175, AND
RP IDENTIFICATION BY 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 [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-46 AND SER-153, 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 [24]
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 [25]
RP IDENTIFICATION IN THE COHESIN COMPLEX, AND INTERACTION WITH NIPBL AND MAU2.
RX PubMed=22628566; DOI=10.1073/pnas.1206840109;
RA Bermudez V.P., Farina A., Higashi T.L., Du F., Tappin I., Takahashi T.S.,
RA Hurwitz J.;
RT "In vitro loading of human cohesin on DNA by the human Scc2-Scc4 loader
RT complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:9366-9371(2012).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-394; SER-454; SER-545 AND
RP THR-623, AND 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 [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-153 AND SER-249, AND
RP IDENTIFICATION BY 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 [28]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-48; LYS-216 AND LYS-418, 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 [29]
RP INVOLVEMENT IN CDLS4, AND VARIANTS CDLS4 ARG-376 AND ARG-585.
RX PubMed=22633399; DOI=10.1016/j.ajhg.2012.04.019;
RA Deardorff M.A., Wilde J.J., Albrecht M., Dickinson E., Tennstedt S.,
RA Braunholz D., Monnich M., Yan Y., Xu W., Gil-Rodriguez M.C., Clark D.,
RA Hakonarson H., Halbach S., Michelis L.D., Rampuria A., Rossier E.,
RA Spranger S., Van Maldergem L., Lynch S.A., Gillessen-Kaesbach G.,
RA Ludecke H.J., Ramsay R.G., McKay M.J., Krantz I.D., Xu H., Horsfield J.A.,
RA Kaiser F.J.;
RT "RAD21 mutations cause a human cohesinopathy.";
RL Am. J. Hum. Genet. 90:1014-1027(2012).
RN [30]
RP INVOLVEMENT IN MGS, VARIANT MGS THR-622, CHARACTERIZATION OF VARIANT MGS
RP THR-622, FUNCTION, INTERACTION WITH SMC1, AND TISSUE SPECIFICITY.
RX PubMed=25575569; DOI=10.1053/j.gastro.2014.12.034;
RA Bonora E., Bianco F., Cordeddu L., Bamshad M., Francescatto L., Dowless D.,
RA Stanghellini V., Cogliandro R.F., Lindberg G., Mungan Z., Cefle K.,
RA Ozcelik T., Palanduz S., Ozturk S., Gedikbasi A., Gori A., Pippucci T.,
RA Graziano C., Volta U., Caio G., Barbara G., D'Amato M., Seri M.,
RA Katsanis N., Romeo G., De Giorgio R.;
RT "Mutations in RAD21 disrupt regulation of APOB in patients with chronic
RT intestinal pseudo-obstruction.";
RL Gastroenterology 148:771-782(2015).
RN [31]
RP VARIANT CDLS4 197-GLN--ILE-631 DEL.
RX PubMed=31334757; DOI=10.1093/brain/awz210;
RA Kruszka P., Berger S.I., Casa V., Dekker M.R., Gaesser J., Weiss K.,
RA Martinez A.F., Murdock D.R., Louie R.J., Prijoles E.J., Lichty A.W.,
RA Brouwer O.F., Zonneveld-Huijssoon E., Stephan M.J., Hogue J., Hu P.,
RA Tanima-Nagai M., Everson J.L., Prasad C., Cereda A., Iascone M.,
RA Schreiber A., Zurcher V., Corsten-Janssen N., Escobar L., Clegg N.J.,
RA Delgado M.R., Hajirnis O., Balasubramanian M., Kayserili H., Deardorff M.,
RA Poot R.A., Wendt K.S., Lipinski R.J., Muenke M.;
RT "Cohesin complex-associated holoprosencephaly.";
RL Brain 142:2631-2643(2019).
CC -!- FUNCTION: [Double-strand-break repair protein rad21 homolog]: As a
CC member of the cohesin complex, involved in sister chromatid cohesion
CC from the time of DNA replication in S phase to their segregation in
CC mitosis, a function that is essential for proper chromosome
CC segregation, post-replicative DNA repair, and the prevention of
CC inappropriate recombination between repetitive regions
CC (PubMed:11509732). The cohesin complex may also play a role in spindle
CC pole assembly during mitosis (PubMed:11590136). In interphase, cohesins
CC may function in the control of gene expression by binding to numerous
CC sites within the genome (By similarity). May control RUNX1 gene
CC expression (Probable). Binds to and represses APOB gene promoter
CC (PubMed:25575569). May play a role in embryonic gut development,
CC possibly through the regulation of enteric neuron development (By
CC similarity). {ECO:0000250|UniProtKB:Q61550,
CC ECO:0000250|UniProtKB:Q6TEL1, ECO:0000269|PubMed:11509732,
CC ECO:0000269|PubMed:11590136, ECO:0000269|PubMed:25575569,
CC ECO:0000305|PubMed:25575569}.
CC -!- FUNCTION: [64-kDa C-terminal product]: May promote apoptosis.
CC {ECO:0000269|PubMed:11875078, ECO:0000269|PubMed:12417729}.
CC -!- SUBUNIT: Component of the cohesin complex, which consists of an SMC1A/B
CC and SMC3 heterodimer core and 2 non-Smc subunits RAD21 and STAG1/SA1,
CC STAG2/SA2 or STAG3/SA3 (PubMed:10931856, PubMed:11590136,
CC PubMed:22628566, PubMed:25575569). Interacts (via N-terminus) with
CC SMC1A; the interaction is direct (PubMed:12198550). The cohesin complex
CC interacts with NUMA1 (PubMed:11590136). The cohesin complex also
CC interacts with CDCA5, PDS5A and PDS5B; this interaction might regulate
CC the ability of the cohesin complex to mediate sister chromatid cohesion
CC (PubMed:15837422). The interaction with PDS5B is direct and is
CC stimulated by STAG1/SA1 (PubMed:19696148). The cohesin complex
CC interacts with the cohesin loading complex subunits NIPBL/Scc2 (via
CC HEAT repeats) and MAU2/Scc4 (PubMed:22628566). The cohesin complex
CC interacts with DDX11/ChIR1 (PubMed:17105772). Directly interacts with
CC WAPL; this interaction is stimulated by STAG1/SA1 (PubMed:19696148).
CC Interacts with the ISWI chromatin remodeling complex component SMARCA5;
CC the interaction is direct (PubMed:12198550). Interacts with the NuRD
CC complex component CHD4; the interaction is direct (PubMed:12198550).
CC {ECO:0000269|PubMed:10931856, ECO:0000269|PubMed:11590136,
CC ECO:0000269|PubMed:12198550, ECO:0000269|PubMed:15837422,
CC ECO:0000269|PubMed:17105772, ECO:0000269|PubMed:19696148,
CC ECO:0000269|PubMed:22628566, ECO:0000269|PubMed:25575569}.
CC -!- INTERACTION:
CC O60216; Q13643: FHL3; NbExp=4; IntAct=EBI-80739, EBI-741101;
CC O60216; Q29RF7: PDS5A; NbExp=5; IntAct=EBI-80739, EBI-1175454;
CC O60216; Q9NTI5: PDS5B; NbExp=4; IntAct=EBI-80739, EBI-1175604;
CC O60216; Q14683: SMC1A; NbExp=15; IntAct=EBI-80739, EBI-80690;
CC O60216; Q9UQE7: SMC3; NbExp=16; IntAct=EBI-80739, EBI-80718;
CC O60216; Q9NP77: SSU72; NbExp=9; IntAct=EBI-80739, EBI-2515416;
CC O60216; Q8N3U4: STAG2; NbExp=19; IntAct=EBI-80739, EBI-1057252;
CC O60216; Q7Z5K2: WAPL; NbExp=15; IntAct=EBI-80739, EBI-1022242;
CC -!- SUBCELLULAR LOCATION: [Double-strand-break repair protein rad21
CC homolog]: Nucleus {ECO:0000269|PubMed:11073952,
CC ECO:0000269|PubMed:11509732, ECO:0000269|PubMed:12417729}. Nucleus
CC matrix {ECO:0000269|PubMed:10623634, ECO:0000269|PubMed:11590136}.
CC Chromosome {ECO:0000269|PubMed:11073952, ECO:0000269|PubMed:11590136}.
CC Chromosome, centromere {ECO:0000269|PubMed:11073952}. Cytoplasm,
CC cytoskeleton, spindle pole {ECO:0000269|PubMed:11073952,
CC ECO:0000269|PubMed:11590136}. Note=Associates with chromatin
CC (PubMed:11590136, PubMed:11073952). Before prophase, scattered along
CC chromosome arms (PubMed:11073952). During prophase and prometaphase,
CC most cohesins dissociate from the arms of condensing chromosome,
CC possibly through PLK1-mediated phosphorylation (PubMed:11931760). A
CC small amount of cohesin remains in centromeric regions and is removed
CC from chromosomes only at the onset of anaphase. At anaphase, cleavage
CC by separase/ESPL1 leads to the dissociation of cohesin from chromosomes
CC and chromosome separation (PubMed:11073952, PubMed:11509732).
CC {ECO:0000269|PubMed:11073952, ECO:0000269|PubMed:11509732,
CC ECO:0000269|PubMed:11590136, ECO:0000269|PubMed:11931760}.
CC -!- SUBCELLULAR LOCATION: [64-kDa C-terminal product]: Cytoplasm, cytosol
CC {ECO:0000269|PubMed:11875078, ECO:0000269|PubMed:12417729}. Nucleus
CC {ECO:0000269|PubMed:11875078, ECO:0000269|PubMed:12417729}.
CC -!- TISSUE SPECIFICITY: Expressed in the gut (at protein level).
CC {ECO:0000269|PubMed:25575569}.
CC -!- DEVELOPMENTAL STAGE: Regulated in a cell cycle-dependent manner:
CC expression increases in late S phase and reaches maximum in G2 at the
CC nucleotide level (PubMed:8812457). Not regulated during the cell cycle
CC (at protein level) (PubMed:11073952). {ECO:0000269|PubMed:11073952,
CC ECO:0000269|PubMed:8812457}.
CC -!- DOMAIN: The C-terminal part associates with the head of SMC1A, while
CC the N-terminal part binds to the head of SMC3. {ECO:0000250}.
CC -!- PTM: Cleaved by separase/ESPL1 at the onset of anaphase; this cleavage
CC is required for sister chromatid separation and cytokinesis
CC (PubMed:11509732). Cleaved by caspase-3/CASP3 or caspase-7/CASP7 at the
CC beginning of apoptosis (PubMed:12417729, PubMed:11875078).
CC {ECO:0000269|PubMed:11509732, ECO:0000269|PubMed:11875078,
CC ECO:0000269|PubMed:12417729}.
CC -!- PTM: Phosphorylated; becomes hyperphosphorylated in M phase of cell
CC cycle. The large dissociation of cohesin from chromosome arms during
CC prophase may be partly due to its phosphorylation by PLK1.
CC {ECO:0000269|PubMed:11073952}.
CC -!- DISEASE: Cornelia de Lange syndrome 4 with or without midline brain
CC defects (CDLS4) [MIM:614701]: A form of Cornelia de Lange syndrome, a
CC clinically heterogeneous developmental disorder associated with
CC malformations affecting multiple systems. It is characterized by facial
CC dysmorphisms, abnormal hands and feet, growth delay, cognitive
CC retardation, hirsutism, gastroesophageal dysfunction and cardiac,
CC ophthalmologic and genitourinary anomalies.
CC {ECO:0000269|PubMed:22633399, ECO:0000269|PubMed:31334757}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Mungan syndrome (MGS) [MIM:611376]: An autosomal recessive
CC disease characterized by visceral neuromyopathy, intestinal dysmotility
CC and chronic intestinal pseudoobstruction, megaduodenum, long-segment
CC Barrett esophagus, and a variety of cardiac valve or septal defects
CC such as membranous ventricular septal defect, pulmonary and tricuspid
CC valve regurgitation. {ECO:0000269|PubMed:25575569}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the rad21 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA07554.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/rad21/";
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DR EMBL; X98294; CAA66940.1; -; mRNA.
DR EMBL; D38551; BAA07554.2; ALT_INIT; mRNA.
DR EMBL; AY675320; AAT70725.1; -; Genomic_DNA.
DR EMBL; AK289505; BAF82194.1; -; mRNA.
DR EMBL; CH471060; EAW91963.1; -; Genomic_DNA.
DR EMBL; BC050381; AAH50381.1; -; mRNA.
DR CCDS; CCDS6321.1; -.
DR RefSeq; NP_006256.1; NM_006265.2.
DR PDB; 4PJU; X-ray; 3.05 A; B=281-420.
DR PDB; 4PJW; X-ray; 2.85 A; B=281-420.
DR PDB; 4PK7; X-ray; 2.95 A; B=281-420.
DR PDB; 6QNX; X-ray; 2.70 A; B=1-631.
DR PDB; 6RRC; X-ray; 2.37 A; B/D=321-345.
DR PDB; 6RRK; X-ray; 3.17 A; C/D=356-395.
DR PDB; 6WG3; EM; 5.30 A; C=1-631.
DR PDB; 6WGE; EM; 3.90 A; C=1-631.
DR PDBsum; 4PJU; -.
DR PDBsum; 4PJW; -.
DR PDBsum; 4PK7; -.
DR PDBsum; 6QNX; -.
DR PDBsum; 6RRC; -.
DR PDBsum; 6RRK; -.
DR PDBsum; 6WG3; -.
DR PDBsum; 6WGE; -.
DR AlphaFoldDB; O60216; -.
DR SMR; O60216; -.
DR BioGRID; 111822; 361.
DR ComplexPortal; CPX-5989; Nuclear meiotic cohesin complex, STAG1 variant.
DR ComplexPortal; CPX-5991; Nuclear meiotic cohesin complex, STAG2 variant.
DR ComplexPortal; CPX-6082; Nuclear meiotic cohesin complex, STAG3 variant.
DR CORUM; O60216; -.
DR DIP; DIP-29201N; -.
DR ELM; O60216; -.
DR IntAct; O60216; 66.
DR MINT; O60216; -.
DR STRING; 9606.ENSP00000297338; -.
DR iPTMnet; O60216; -.
DR MetOSite; O60216; -.
DR PhosphoSitePlus; O60216; -.
DR SwissPalm; O60216; -.
DR BioMuta; RAD21; -.
DR EPD; O60216; -.
DR jPOST; O60216; -.
DR MassIVE; O60216; -.
DR MaxQB; O60216; -.
DR PaxDb; O60216; -.
DR PeptideAtlas; O60216; -.
DR PRIDE; O60216; -.
DR ProteomicsDB; 49246; -.
DR Antibodypedia; 13592; 328 antibodies from 35 providers.
DR DNASU; 5885; -.
DR Ensembl; ENST00000297338.7; ENSP00000297338.2; ENSG00000164754.16.
DR Ensembl; ENST00000517485.6; ENSP00000427923.2; ENSG00000164754.16.
DR Ensembl; ENST00000517749.2; ENSP00000430273.2; ENSG00000164754.16.
DR Ensembl; ENST00000519837.6; ENSP00000430524.2; ENSG00000164754.16.
DR Ensembl; ENST00000520992.6; ENSP00000429342.2; ENSG00000164754.16.
DR Ensembl; ENST00000522699.2; ENSP00000428158.2; ENSG00000164754.16.
DR Ensembl; ENST00000687358.1; ENSP00000509687.1; ENSG00000164754.16.
DR GeneID; 5885; -.
DR KEGG; hsa:5885; -.
DR MANE-Select; ENST00000297338.7; ENSP00000297338.2; NM_006265.3; NP_006256.1.
DR UCSC; uc003yod.4; human.
DR CTD; 5885; -.
DR DisGeNET; 5885; -.
DR GeneCards; RAD21; -.
DR GeneReviews; RAD21; -.
DR HGNC; HGNC:9811; RAD21.
DR HPA; ENSG00000164754; Low tissue specificity.
DR MalaCards; RAD21; -.
DR MIM; 606462; gene.
DR MIM; 611376; phenotype.
DR MIM; 614701; phenotype.
DR neXtProt; NX_O60216; -.
DR OpenTargets; ENSG00000164754; -.
DR Orphanet; 199; Cornelia de Lange syndrome.
DR PharmGKB; PA34170; -.
DR VEuPathDB; HostDB:ENSG00000164754; -.
DR eggNOG; KOG1213; Eukaryota.
DR GeneTree; ENSGT00940000154655; -.
DR HOGENOM; CLU_015775_1_1_1; -.
DR InParanoid; O60216; -.
DR OMA; LKQEEPY; -.
DR OrthoDB; 1253899at2759; -.
DR PhylomeDB; O60216; -.
DR TreeFam; TF101215; -.
DR BioCyc; MetaCyc:ENSG00000164754-MON; -.
DR PathwayCommons; O60216; -.
DR Reactome; R-HSA-1221632; Meiotic synapsis.
DR Reactome; R-HSA-2467813; Separation of Sister Chromatids.
DR Reactome; R-HSA-2468052; Establishment of Sister Chromatid Cohesion.
DR Reactome; R-HSA-2470946; Cohesin Loading onto Chromatin.
DR Reactome; R-HSA-2500257; Resolution of Sister Chromatid Cohesion.
DR Reactome; R-HSA-3108214; SUMOylation of DNA damage response and repair proteins.
DR Reactome; R-HSA-9018519; Estrogen-dependent gene expression.
DR SignaLink; O60216; -.
DR SIGNOR; O60216; -.
DR BioGRID-ORCS; 5885; 698 hits in 1054 CRISPR screens.
DR ChiTaRS; RAD21; human.
DR GeneWiki; RAD21; -.
DR GenomeRNAi; 5885; -.
DR Pharos; O60216; Tbio.
DR PRO; PR:O60216; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; O60216; protein.
DR Bgee; ENSG00000164754; Expressed in ventricular zone and 213 other tissues.
DR ExpressionAtlas; O60216; baseline and differential.
DR Genevisible; O60216; HS.
DR GO; GO:0000785; C:chromatin; IEA:Ensembl.
DR GO; GO:0005694; C:chromosome; TAS:Reactome.
DR GO; GO:0000775; C:chromosome, centromeric region; TAS:Reactome.
DR GO; GO:0008278; C:cohesin complex; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0030496; C:midbody; IDA:HPA.
DR GO; GO:0016363; C:nuclear matrix; IDA:UniProtKB.
DR GO; GO:0034991; C:nuclear meiotic cohesin complex; IPI:ComplexPortal.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IC:ComplexPortal.
DR GO; GO:0000922; C:spindle pole; IEA:UniProtKB-SubCell.
DR GO; GO:0003682; F:chromatin binding; IBA:GO_Central.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0006310; P:DNA recombination; TAS:ProtInc.
DR GO; GO:0006302; P:double-strand break repair; TAS:ProtInc.
DR GO; GO:0034089; P:establishment of meiotic sister chromatid cohesion; IC:ComplexPortal.
DR GO; GO:0010972; P:negative regulation of G2/M transition of mitotic cell cycle; IEA:Ensembl.
DR GO; GO:0045841; P:negative regulation of mitotic metaphase/anaphase transition; IEA:Ensembl.
DR GO; GO:0045876; P:positive regulation of sister chromatid cohesion; IMP:UniProtKB.
DR GO; GO:0071168; P:protein localization to chromatin; IMP:UniProtKB.
DR GO; GO:0007131; P:reciprocal meiotic recombination; TAS:ProtInc.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:1990414; P:replication-born double-strand break repair via sister chromatid exchange; IBA:GO_Central.
DR GO; GO:0007062; P:sister chromatid cohesion; IBA:GO_Central.
DR Gene3D; 1.10.10.580; -; 1.
DR IDEAL; IID00642; -.
DR InterPro; IPR039781; Rad21/Rec8-like.
DR InterPro; IPR006909; Rad21/Rec8_C_eu.
DR InterPro; IPR006910; Rad21_Rec8_N.
DR InterPro; IPR023093; ScpA-like_C.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR PANTHER; PTHR12585; PTHR12585; 1.
DR Pfam; PF04824; Rad21_Rec8; 1.
DR Pfam; PF04825; Rad21_Rec8_N; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Apoptosis; Cell cycle; Cell division; Centromere;
KW Chromosome; Chromosome partition; Cytoplasm; Cytoskeleton;
KW Developmental protein; Direct protein sequencing; Disease variant;
KW DNA damage; DNA repair; DNA-binding; Intellectual disability;
KW Isopeptide bond; Mitosis; Nucleus; Phosphoprotein; Reference proteome;
KW Repressor; Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1..631
FT /note="Double-strand-break repair protein rad21 homolog"
FT /id="PRO_0000097872"
FT CHAIN 280..631
FT /note="64-kDa C-terminal product"
FT /evidence="ECO:0000269|PubMed:12417729"
FT /id="PRO_0000446317"
FT REGION 1..126
FT /note="Required for interaction with SMCA1"
FT /evidence="ECO:0000269|PubMed:12198550"
FT REGION 126..282
FT /note="Required for interaction with SMARCA5"
FT /evidence="ECO:0000269|PubMed:12198550"
FT REGION 258..285
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 287..403
FT /note="Interaction with WAPL and PDS5B"
FT /evidence="ECO:0000269|PubMed:19696148"
FT REGION 362..403
FT /note="Interaction with STAG1"
FT /evidence="ECO:0000269|PubMed:19696148"
FT REGION 423..489
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 517..558
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 423..448
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 533..547
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 172..173
FT /note="Cleavage; by ESPL1"
FT /evidence="ECO:0000269|PubMed:11509732"
FT SITE 279..280
FT /note="Cleavage; by caspase-3 or caspase-7"
FT /evidence="ECO:0000269|PubMed:12417729"
FT SITE 450..451
FT /note="Cleavage; by ESPL1"
FT /evidence="ECO:0000269|PubMed:11509732"
FT MOD_RES 46
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 153
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:24275569"
FT MOD_RES 175
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 249
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 394
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 454
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 545
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 623
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CROSSLNK 48
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 216
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 418
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VARIANT 197..631
FT /note="Missing (in CDLS4)"
FT /evidence="ECO:0000269|PubMed:31334757"
FT /id="VAR_083980"
FT VARIANT 376
FT /note="P -> R (in CDLS4; dbSNP:rs387907212)"
FT /evidence="ECO:0000269|PubMed:22633399"
FT /id="VAR_068691"
FT VARIANT 481
FT /note="G -> R (found in a radiation-sensitive cancer
FT patient; dbSNP:rs755168088)"
FT /evidence="ECO:0000269|PubMed:11483345"
FT /id="VAR_014281"
FT VARIANT 585
FT /note="C -> R (in CDLS4; dbSNP:rs387907213)"
FT /evidence="ECO:0000269|PubMed:22633399"
FT /id="VAR_068692"
FT VARIANT 622
FT /note="A -> T (in MGS; causes delayed food transit along
FT the gut, when tested in zebrafish; may affect RUNX1 and
FT APOB expression; dbSNP:rs775266057)"
FT /evidence="ECO:0000269|PubMed:25575569"
FT /id="VAR_081285"
FT MUTAGEN 1..126
FT /note="Missing: Abolishes interaction with SMC1."
FT /evidence="ECO:0000269|PubMed:12198550"
FT MUTAGEN 126..282
FT /note="Missing: Abolishes binding to SMARCA5."
FT /evidence="ECO:0000269|PubMed:12198550"
FT MUTAGEN 172
FT /note="R->A: Abolishes first cleavage by ESPL1, no effect
FT on nuclear localization."
FT /evidence="ECO:0000269|PubMed:11509732"
FT MUTAGEN 276..280
FT /note="DSPDS->AAPAA: Loss of cleavage by caspase-3 or
FT caspase-7."
FT /evidence="ECO:0000269|PubMed:12417729"
FT MUTAGEN 279
FT /note="D->A,E: Loss of cleavage by caspase-3 or caspase-7."
FT /evidence="ECO:0000269|PubMed:11875078,
FT ECO:0000269|PubMed:12417729"
FT MUTAGEN 282
FT /note="D->E: No effect on cleavage by caspase-3 or caspase-
FT 7."
FT /evidence="ECO:0000269|PubMed:11875078"
FT MUTAGEN 450
FT /note="R->A: Abolishes second cleavage by ESPL1, no effect
FT on nuclear localization."
FT /evidence="ECO:0000269|PubMed:11509732"
FT CONFLICT 136
FT /note="N -> I (in Ref. 1; CAA66940)"
FT /evidence="ECO:0000305"
FT HELIX 334..336
FT /evidence="ECO:0007829|PDB:6RRC"
FT HELIX 345..347
FT /evidence="ECO:0007829|PDB:4PK7"
FT HELIX 358..365
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 369..372
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 383..390
FT /evidence="ECO:0007829|PDB:6QNX"
FT TURN 391..393
FT /evidence="ECO:0007829|PDB:4PK7"
SQ SEQUENCE 631 AA; 71690 MW; 7D4A6EA6392BE73D CRC64;
MFYAHFVLSK RGPLAKIWLA AHWDKKLTKA HVFECNLESS VESIISPKVK MALRTSGHLL
LGVVRIYHRK AKYLLADCNE AFIKIKMAFR PGVVDLPEEN REAAYNAITL PEEFHDFDQP
LPDLDDIDVA QQFSLNQSRV EEITMREEVG NISILQENDF GDFGMDDREI MREGSAFEDD
DMLVSTTTSN LLLESEQSTS NLNEKINHLE YEDQYKDDNF GEGNDGGILD DKLISNNDGG
IFDDPPALSE AGVMLPEQPA HDDMDEDDNV SMGGPDSPDS VDPVEPMPTM TDQTTLVPNE
EEAFALEPID ITVKETKAKR KRKLIVDSVK ELDSKTIRAQ LSDYSDIVTT LDLAPPTKKL
MMWKETGGVE KLFSLPAQPL WNNRLLKLFT RCLTPLVPED LRKRRKGGEA DNLDEFLKEF
ENPEVPREDQ QQQHQQRDVI DEPIIEEPSR LQESVMEASR TNIDESAMPP PPPQGVKRKA
GQIDPEPVMP PQQVEQMEIP PVELPPEEPP NICQLIPELE LLPEKEKEKE KEKEDDEEEE
DEDASGGDQD QEERRWNKRT QQMLHGLQRA LAKTGAESIS LLELCRNTNR KQAAAKFYSF
LVLKKQQAIE LTQEEPYSDI IATPGPRFHI I
