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 27-MAR-2024, entry version 205. 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, SCC1 GN {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] {ECO:0007744|PDB:6WG3, ECO:0007744|PDB:6WGE} RP STRUCTURE BY ELECTRON MICROSCOPY (3.90 ANGSTROMS), IDENTIFICATION IN THE RP COHESIN COMPLEX, AND INTERACTION WITH NIPBL. RX PubMed=32409525; DOI=10.1126/science.abb0981; RA Shi Z., Gao H., Bai X.C., Yu H.; RT "Cryo-EM structure of the human cohesin-NIPBL-DNA complex."; RL Science 368:1454-1459(2020). RN [30] 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 [31] 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 [32] 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, PubMed:32409525). Interacts (via C- CC terminus) with SMC1A and (via N-terminus) with SMC3; these interactions CC are direct (PubMed:12198550, PubMed:32409525). 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). NIPBL directly contacts CC all members of the complex, RAD21, SMC1A/B, SMC3 and STAG1 CC (PubMed:32409525). The cohesin complex interacts with DDX11/ChIR1 CC (PubMed:17105772). Directly interacts with WAPL; this interaction is CC stimulated by STAG1/SA1 (PubMed:19696148). Interacts with the ISWI CC chromatin remodeling complex component SMARCA5/SNF2h; the interaction CC is direct (PubMed:12198550). Interacts with the NuRD complex component CC 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 ECO:0000269|PubMed:32409525}. 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 ATPase head of SMC1A, CC while the N-terminal part binds to the ATPase head of SMC3. CC {ECO:0000269|PubMed:32409525}. 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/"; 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; 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 PDB; 7W1M; EM; 6.50 A; C=1-631. DR PDB; 7ZJS; X-ray; 3.24 A; B/D=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 PDBsum; 7W1M; -. DR PDBsum; 7ZJS; -. DR AlphaFoldDB; O60216; -. DR EMDB; EMD-21658; -. DR EMDB; EMD-21663; -. DR EMDB; EMD-32252; -. DR EMDB; EMD-4029; -. DR EMDB; EMD-4030; -. DR EMDB; EMD-4031; -. DR SMR; O60216; -. DR BioGRID; 111822; 395. DR ComplexPortal; CPX-5989; Nuclear mitotic cohesin complex, STAG1 variant. DR ComplexPortal; CPX-5991; Nuclear mitotic cohesin complex, STAG2 variant. DR ComplexPortal; CPX-6082; Nuclear meiotic cohesin complex, RAD21 variant. DR CORUM; O60216; -. DR DIP; DIP-29201N; -. DR ELM; O60216; -. DR IntAct; O60216; 72. DR MINT; O60216; -. DR STRING; 9606.ENSP00000297338; -. DR GlyGen; O60216; 1 site, 1 O-linked glycan (1 site). 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; 9606-ENSP00000297338; -. DR PeptideAtlas; O60216; -. DR ProteomicsDB; 49246; -. DR Pumba; O60216; -. DR Antibodypedia; 13592; 398 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 AGR; HGNC:9811; -. 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 Orphanet; 502; Trichorhinophalangeal syndrome type 2. 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; DDGIDNF; -. DR OrthoDB; 5481351at2759; -. DR PhylomeDB; O60216; -. DR TreeFam; TF101215; -. DR BioCyc; MetaCyc:ENSG00000164754-MONOMER; -. 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; 728 hits in 1136 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 215 other cell types or tissues. DR ExpressionAtlas; O60216; baseline and differential. 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:0000794; C:condensed nuclear chromosome; IEA:Ensembl. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0030893; C:meiotic cohesin complex; NAS:ComplexPortal. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0030496; C:midbody; IDA:HPA. DR GO; GO:0030892; C:mitotic cohesin complex; IPI:ComplexPortal. DR GO; GO:0016363; C:nuclear matrix; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; NAS: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:0140297; F:DNA-binding transcription factor binding; IEA:Ensembl. DR GO; GO:0106222; F:lncRNA binding; IEA:Ensembl. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0140588; P:chromatin looping; IEA:Ensembl. DR GO; GO:0007059; P:chromosome segregation; 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; NAS:ComplexPortal. DR GO; GO:0034087; P:establishment of mitotic sister chromatid cohesion; NAS:ComplexPortal. DR GO; GO:0010972; P:negative regulation of G2/M transition of mitotic cell cycle; IEA:Ensembl. DR GO; GO:0034351; P:negative regulation of glial cell apoptotic process; IEA:Ensembl. DR GO; GO:0032691; P:negative regulation of interleukin-1 beta production; IEA:Ensembl. DR GO; GO:0045841; P:negative regulation of mitotic metaphase/anaphase transition; IEA:Ensembl. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl. DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IEA:Ensembl. DR GO; GO:0032733; P:positive regulation of interleukin-10 production; 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:0001666; P:response to hypoxia; IEA:Ensembl. DR GO; GO:0007062; P:sister chromatid cohesion; IBA:GO_Central. DR CDD; cd21792; Rad21_Rec8_M_NXP1-like; 1. DR Gene3D; 1.10.10.580; Structural maintenance of chromosome 1. Chain E; 1. DR IDEAL; IID00642; -. DR InterPro; IPR049589; NXP1_M-like. 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:SF20; DOUBLE-STRAND-BREAK REPAIR PROTEIN RAD21 HOMOLOG; 1. DR PANTHER; PTHR12585; SCC1 / RAD21 FAMILY MEMBER; 1. DR Pfam; PF04824; Rad21_Rec8; 1. DR Pfam; PF04825; Rad21_Rec8_N; 1. DR SUPFAM; SSF46785; Winged helix' DNA-binding domain; 1. DR Genevisible; O60216; HS. 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 126..282 FT /note="Required for interaction with SMARCA5" FT /evidence="ECO:0000269|PubMed:12198550" FT REGION 154..171 FT /note="Interaction with NIPBL" FT /evidence="ECO:0000269|PubMed:32409525" 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 FT caspase-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 //