STAG2_HUMAN
ID STAG2_HUMAN Reviewed; 1231 AA.
AC Q8N3U4; B1AMT5; D3DTF5; O00540; Q5JTI6; Q68DE9; Q9H1N8;
DT 25-MAR-2003, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2005, sequence version 3.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Cohesin subunit SA-2;
DE AltName: Full=SCC3 homolog 2;
DE AltName: Full=Stromal antigen 2;
GN Name=STAG2; Synonyms=SA2;
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 [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Retina, and Spinal cord;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [3]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Eye;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 48-1231 (ISOFORM 1).
RC TISSUE=Thymus;
RX PubMed=9305759; DOI=10.1016/s0378-1119(97)00121-2;
RA Carramolino L., Lee B.C., Zaballos A., Peled A., Barthelemy I.,
RA Shav-Tal Y., Prieto I., Carmi P., Gothelf Y., Gonzalez de Buitrago G.,
RA Aracil M., Marquez G., Barbero J.L., Zipori D.;
RT "SA-1, a nuclear protein encoded by one member of a novel gene family:
RT molecular cloning and detection in hemopoietic organs.";
RL Gene 195:151-159(1997).
RN [6]
RP ERRATUM OF PUBMED:9305759.
RA Carramolino L., Lee B.C., Zaballos A., Peled A., Barthelemy I.,
RA Shav-Tal Y., Prieto I., Carmi P., Gothelf Y., Gonzalez de Buitrago G.,
RA Aracil M., Marquez G., Barbero J.L., Zipori D.;
RL Gene 206:283-286(1998).
RN [7]
RP IDENTIFICATION IN A COHESIN COMPLEX WITH SMC1A AND SMC3.
RX PubMed=11076961; DOI=10.1083/jcb.151.4.749;
RA Sumara I., Vorlaufer E., Gieffers C., Peters B.H., Peters J.-M.;
RT "Characterization of vertebrate cohesin complexes and their regulation in
RT prophase.";
RL J. Cell Biol. 151:749-762(2000).
RN [8]
RP FUNCTION IN EARLY STEPS OF MEIOSIS.
RX PubMed=12034751; DOI=10.1093/embo-reports/kvf108;
RA Prieto I., Pezzi N., Buesa J.M., Kremer L., Barthelemy I., Carreiro C.,
RA Roncal F., Martinez A., Gomez L., Fernandez R., Martinez-A C.,
RA Barbero J.L.;
RT "STAG2 and Rad21 mammalian mitotic cohesins are implicated in meiosis.";
RL EMBO Rep. 3:543-550(2002).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1061, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1058 AND SER-1061, 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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1058; SER-1061 AND THR-1112,
RP AND 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 [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-607, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-1061; SER-1177 AND SER-1178, AND IDENTIFICATION BY MASS
RP 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 [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1061, AND IDENTIFICATION BY
RP 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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1058 AND SER-1061, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [17]
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 [18]
RP FUNCTION, INVOLVEMENT IN MKMS, VARIANTS MKMS 69-ARG--PHE-1231 DEL AND
RP GLN-604, AND CHARACTERIZATION OF VARIANT MKMS 69-ARG--PHE-1231 DEL.
RX PubMed=28296084; DOI=10.1002/ajmg.a.38207;
RG UCLA Clinical Genomics Center;
RA Mullegama S.V., Klein S.D., Mulatinho M.V., Senaratne T.N., Singh K.,
RA Nguyen D.C., Gallant N.M., Strom S.P., Ghahremani S., Rao N.P.,
RA Martinez-Agosto J.A.;
RT "De novo loss-of-function variants in STAG2 are associated with
RT developmental delay, microcephaly, and congenital anomalies.";
RL Am. J. Med. Genet. A 173:1319-1327(2017).
RN [19]
RP FUNCTION, IDENTIFICATION IN COHESIN COMPLEX, INVOLVEMENT IN MKMS, VARIANT
RP MKMS ASN-327, AND CHARACTERIZATION OF VARIANT MKMS ASN-327.
RX PubMed=29263825; DOI=10.1038/s41525-017-0009-4;
RA Soardi F.C., Machado-Silva A., Linhares N.D., Zheng G., Qu Q., Pena H.B.,
RA Martins T.M.M., Vieira H.G.S., Pereira N.B., Melo-Minardi R.C., Gomes C.C.,
RA Gomez R.S., Gomes D.A., Pires D.E.V., Ascher D.B., Yu H., Pena S.D.J.;
RT "Familial STAG2 germline mutation defines a new human cohesinopathy.";
RL NPJ Genom. Med. 2:7-7(2017).
RN [20]
RP INVOLVEMENT IN HPE13, AND VARIANTS HPE13 69-ARG--PHE-1231 DEL;
RP 146-ARG--PHE-1231 DEL; 259-ARG--PHE-1231 DEL AND 1012-ARG--PHE-1231 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).
RN [21]
RP VARIANTS MKMS 140-GLN--PHE-1231 DEL; CYS-159; 535-CYS--PHE-1231 DEL AND
RP GLN-604.
RX PubMed=30158690; DOI=10.1038/s41436-018-0085-6;
RG DDD Study;
RA Yuan B., Neira J., Pehlivan D., Santiago-Sim T., Song X., Rosenfeld J.,
RA Posey J.E., Patel V., Jin W., Adam M.P., Baple E.L., Dean J., Fong C.T.,
RA Hickey S.E., Hudgins L., Leon E., Madan-Khetarpal S., Rawlins L.,
RA Rustad C.F., Stray-Pedersen A., Tveten K., Wenger O., Diaz J., Jenkins L.,
RA Martin L., McGuire M., Pietryga M., Ramsdell L., Slattery L., Abid F.,
RA Bertuch A.A., Grange D., Immken L., Schaaf C.P., Van Esch H., Bi W.,
RA Cheung S.W., Breman A.M., Smith J.L., Shaw C., Crosby A.H., Eng C.,
RA Yang Y., Lupski J.R., Xiao R., Liu P.;
RT "Clinical exome sequencing reveals locus heterogeneity and phenotypic
RT variability of cohesinopathies.";
RL Genet. Med. 21:663-675(2019).
RN [22]
RP RETRACTED PAPER.
RX PubMed=30765867; DOI=10.1038/s10038-019-0571-y;
RA Aoi H., Lei M., Mizuguchi T., Nishioka N., Goto T., Miyama S., Suzuki T.,
RA Iwama K., Uchiyama Y., Mitsuhashi S., Itakura A., Takeda S., Matsumoto N.;
RT "Nonsense variants in STAG2 result in distinct sex-dependent phenotypes.";
RL J. Hum. Genet. 64:487-492(2019).
RN [23]
RP RETRACTION NOTICE OF PUBMED:30765867.
RX PubMed=32536687; DOI=10.1038/s10038-020-0782-2;
RA Aoi H., Lei M., Mizuguchi T., Nishioka N., Goto T., Miyama S., Suzuki T.,
RA Iwama K., Uchiyama Y., Mitsuhashi S., Itakura A., Takeda S., Matsumoto N.;
RL J. Hum. Genet. 65:811-811(2020).
RN [24]
RP VARIANT MKMS ASN-1009.
RX PubMed=30447054; DOI=10.1002/mgg3.501;
RG UCLA Clinical Genomics Center;
RA Mullegama S.V., Klein S.D., Signer R.H., Vilain E., Martinez-Agosto J.A.;
RT "Mutations in STAG2 cause an X-linked cohesinopathy associated with
RT undergrowth, developmental delay, and dysmorphia: Expanding the phenotype
RT in males.";
RL Mol. Genet. Genomic Med. 7:E00501-E00501(2019).
CC -!- FUNCTION: Component of cohesin complex, a complex required for the
CC cohesion of sister chromatids after DNA replication. The cohesin
CC complex apparently forms a large proteinaceous ring within which sister
CC chromatids can be trapped. At anaphase, the complex is cleaved and
CC dissociates from chromatin, allowing sister chromatids to segregate.
CC The cohesin complex may also play a role in spindle pole assembly
CC during mitosis. {ECO:0000269|PubMed:12034751}.
CC -!- SUBUNIT: Interacts directly with RAD21 in cohesin complex. Cohesin
CC complexes are composed of a heterodimer between a SMC1 protein (SMC1A
CC or SMC1B) and SMC3, which are attached via their hinge domain, and
CC RAD21 which link them at their heads, and one STAG protein (STAG1,
CC STAG2 or STAG3). In cohesin complexes, STAG2 is mutually exclusive with
CC STAG1 and STAG3. {ECO:0000269|PubMed:11076961}.
CC -!- INTERACTION:
CC Q8N3U4; Q29RF7: PDS5A; NbExp=6; IntAct=EBI-1057252, EBI-1175454;
CC Q8N3U4; Q9NTI5: PDS5B; NbExp=4; IntAct=EBI-1057252, EBI-1175604;
CC Q8N3U4; O60216: RAD21; NbExp=19; IntAct=EBI-1057252, EBI-80739;
CC Q8N3U4; Q5FBB7: SGO1; NbExp=7; IntAct=EBI-1057252, EBI-989069;
CC Q8N3U4; Q14683: SMC1A; NbExp=12; IntAct=EBI-1057252, EBI-80690;
CC Q8N3U4; Q9UQE7: SMC3; NbExp=17; IntAct=EBI-1057252, EBI-80718;
CC Q8N3U4; Q9NP77: SSU72; NbExp=4; IntAct=EBI-1057252, EBI-2515416;
CC Q8N3U4; Q8WVM7: STAG1; NbExp=5; IntAct=EBI-1057252, EBI-1175097;
CC Q8N3U4; Q7Z5K2: WAPL; NbExp=13; IntAct=EBI-1057252, EBI-1022242;
CC -!- SUBCELLULAR LOCATION: Nucleus. Chromosome. Chromosome, centromere.
CC Note=Associates with chromatin. Before prophase it is scattered along
CC chromosome arms. During prophase, most of cohesin complexes dissociate
CC from chromatin probably because of phosphorylation by PLK1, except at
CC centromeres, where cohesin complexes remain. At anaphase, the RAD21
CC subunit of cohesin is cleaved, leading to the dissociation of the
CC complex from chromosomes, allowing chromosome separation. In germ
CC cells, cohesin complex dissociates from chromatin at prophase I, and
CC may be replaced by a meiosis-specific cohesin complex.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8N3U4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8N3U4-2; Sequence=VSP_041119;
CC -!- PTM: Phosphorylated by PLK1. The large dissociation of cohesin from
CC chromosome arms during prophase is partly due to its phosphorylation
CC (By similarity). {ECO:0000250}.
CC -!- DISEASE: Mullegama-Klein-Martinez syndrome (MKMS) [MIM:301022]: An X-
CC linked neurodevelopmental disorder with variable features including
CC intellectual deficiency, microcephaly, microtia, hearing loss,
CC developmental delay, dysmorphic features, language delay, congenital
CC heart defect, and clinodactyly of the 5th finger.
CC {ECO:0000269|PubMed:28296084, ECO:0000269|PubMed:29263825,
CC ECO:0000269|PubMed:30158690, ECO:0000269|PubMed:30447054}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Holoprosencephaly 13, X-linked (HPE13) [MIM:301043]: An X-
CC linked form of holoprosencephaly, a structural anomaly of the brain in
CC which the developing forebrain fails to correctly separate into right
CC and left hemispheres. Holoprosencephaly is genetically heterogeneous
CC and associated with several distinct facies and phenotypic variability.
CC HPE13 features range from full alobar holoprosencephaly with cyclopia
CC to semilobar holoprosencephaly or septooptic dysplasia. Dysmorphic
CC features include microcephaly, hypotelorism, low-set ears,
CC micrognathia, and cleft lip/palate. Patients with a more severe
CC phenotype may die in the newborn period, whereas those with a less
CC severe phenotype show global developmental delay.
CC {ECO:0000269|PubMed:31334757}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the SCC3 family. {ECO:0000305}.
CC -!- CAUTION: Variants MKMS 743-TRP--PHE-1231 DEL and HPE13 1033-ARG--PHE-
CC 1231 DEL were previously described; however, the corresponding paper
CC has been retracted as Case 1's sex was incorrectly reported
CC invalidating the conclusions. {ECO:0000269|PubMed:30765867,
CC ECO:0000305|PubMed:32536687}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA99732.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AL831939; CAD38591.1; -; mRNA.
DR EMBL; CR749433; CAH18271.1; -; mRNA.
DR EMBL; AL355476; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471107; EAX11853.1; -; Genomic_DNA.
DR EMBL; CH471107; EAX11854.1; -; Genomic_DNA.
DR EMBL; CH471107; EAX11855.1; -; Genomic_DNA.
DR EMBL; CH471107; EAX11856.1; -; Genomic_DNA.
DR EMBL; CH471107; EAX11857.1; -; Genomic_DNA.
DR EMBL; BC001765; AAH01765.2; -; mRNA.
DR EMBL; Z75331; CAA99732.1; ALT_INIT; mRNA.
DR CCDS; CCDS14607.1; -. [Q8N3U4-1]
DR CCDS; CCDS43990.1; -. [Q8N3U4-2]
DR RefSeq; NP_001036214.1; NM_001042749.2. [Q8N3U4-2]
DR RefSeq; NP_001036215.1; NM_001042750.1. [Q8N3U4-2]
DR RefSeq; NP_001036216.1; NM_001042751.1. [Q8N3U4-1]
DR RefSeq; NP_001269347.1; NM_001282418.1. [Q8N3U4-1]
DR RefSeq; NP_006594.3; NM_006603.4. [Q8N3U4-1]
DR RefSeq; XP_005262414.1; XM_005262357.2. [Q8N3U4-2]
DR RefSeq; XP_005262415.1; XM_005262358.2. [Q8N3U4-2]
DR RefSeq; XP_005262416.1; XM_005262359.3. [Q8N3U4-2]
DR RefSeq; XP_005262417.1; XM_005262360.2. [Q8N3U4-2]
DR RefSeq; XP_005262418.1; XM_005262361.2. [Q8N3U4-1]
DR RefSeq; XP_006724790.1; XM_006724727.1. [Q8N3U4-2]
DR RefSeq; XP_011529555.1; XM_011531253.2. [Q8N3U4-2]
DR RefSeq; XP_016884721.1; XM_017029232.1. [Q8N3U4-1]
DR RefSeq; XP_016884722.1; XM_017029233.1. [Q8N3U4-1]
DR RefSeq; XP_016884723.1; XM_017029234.1.
DR PDB; 4PJU; X-ray; 3.05 A; A=80-1060.
DR PDB; 4PJW; X-ray; 2.85 A; A=80-1060.
DR PDB; 4PK7; X-ray; 2.95 A; A=80-1060.
DR PDB; 6QNX; X-ray; 2.70 A; A=1-1231.
DR PDBsum; 4PJU; -.
DR PDBsum; 4PJW; -.
DR PDBsum; 4PK7; -.
DR PDBsum; 6QNX; -.
DR AlphaFoldDB; Q8N3U4; -.
DR SMR; Q8N3U4; -.
DR BioGRID; 115958; 200.
DR ComplexPortal; CPX-5991; Nuclear meiotic cohesin complex, STAG2 variant.
DR CORUM; Q8N3U4; -.
DR DIP; DIP-35418N; -.
DR IntAct; Q8N3U4; 53.
DR MINT; Q8N3U4; -.
DR STRING; 9606.ENSP00000218089; -.
DR GlyGen; Q8N3U4; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q8N3U4; -.
DR MetOSite; Q8N3U4; -.
DR PhosphoSitePlus; Q8N3U4; -.
DR SwissPalm; Q8N3U4; -.
DR BioMuta; STAG2; -.
DR DMDM; 73621291; -.
DR EPD; Q8N3U4; -.
DR jPOST; Q8N3U4; -.
DR MassIVE; Q8N3U4; -.
DR MaxQB; Q8N3U4; -.
DR PaxDb; Q8N3U4; -.
DR PeptideAtlas; Q8N3U4; -.
DR PRIDE; Q8N3U4; -.
DR ProteomicsDB; 71836; -. [Q8N3U4-1]
DR ProteomicsDB; 71837; -. [Q8N3U4-2]
DR Antibodypedia; 500; 323 antibodies from 37 providers.
DR DNASU; 10735; -.
DR Ensembl; ENST00000218089.13; ENSP00000218089.9; ENSG00000101972.20. [Q8N3U4-2]
DR Ensembl; ENST00000371144.7; ENSP00000360186.3; ENSG00000101972.20. [Q8N3U4-1]
DR Ensembl; ENST00000371145.8; ENSP00000360187.4; ENSG00000101972.20. [Q8N3U4-2]
DR Ensembl; ENST00000371157.7; ENSP00000360199.3; ENSG00000101972.20. [Q8N3U4-1]
DR Ensembl; ENST00000371160.5; ENSP00000360202.1; ENSG00000101972.20. [Q8N3U4-1]
DR Ensembl; ENST00000687852.1; ENSP00000509048.1; ENSG00000101972.20. [Q8N3U4-2]
DR GeneID; 10735; -.
DR KEGG; hsa:10735; -.
DR MANE-Select; ENST00000371145.8; ENSP00000360187.4; NM_001042750.2; NP_001036215.1. [Q8N3U4-2]
DR UCSC; uc004eua.5; human. [Q8N3U4-1]
DR CTD; 10735; -.
DR DisGeNET; 10735; -.
DR GeneCards; STAG2; -.
DR HGNC; HGNC:11355; STAG2.
DR HPA; ENSG00000101972; Low tissue specificity.
DR MalaCards; STAG2; -.
DR MIM; 300826; gene.
DR MIM; 301022; phenotype.
DR MIM; 301043; phenotype.
DR neXtProt; NX_Q8N3U4; -.
DR OpenTargets; ENSG00000101972; -.
DR Orphanet; 93925; Alobar holoprosencephaly.
DR Orphanet; 220386; Semilobar holoprosencephaly.
DR Orphanet; 521258; Xq25 microduplication syndrome.
DR PharmGKB; PA36177; -.
DR VEuPathDB; HostDB:ENSG00000101972; -.
DR eggNOG; KOG2011; Eukaryota.
DR GeneTree; ENSGT00950000182972; -.
DR HOGENOM; CLU_005067_1_0_1; -.
DR InParanoid; Q8N3U4; -.
DR OMA; EAMPEKY; -.
DR PhylomeDB; Q8N3U4; -.
DR TreeFam; TF314604; -.
DR PathwayCommons; Q8N3U4; -.
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; Q8N3U4; -.
DR SIGNOR; Q8N3U4; -.
DR BioGRID-ORCS; 10735; 118 hits in 711 CRISPR screens.
DR ChiTaRS; STAG2; human.
DR GeneWiki; STAG2; -.
DR GenomeRNAi; 10735; -.
DR Pharos; Q8N3U4; Tbio.
DR PRO; PR:Q8N3U4; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q8N3U4; protein.
DR Bgee; ENSG00000101972; Expressed in mucosa of paranasal sinus and 215 other tissues.
DR ExpressionAtlas; Q8N3U4; baseline and differential.
DR Genevisible; Q8N3U4; HS.
DR GO; GO:0000785; C:chromatin; IDA:UniProtKB.
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:0001650; C:fibrillar center; IDA:HPA.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0097431; C:mitotic spindle pole; IDA:UniProtKB.
DR GO; GO:0016363; C:nuclear matrix; IDA:UniProtKB.
DR GO; GO:0034991; C:nuclear meiotic cohesin complex; IPI:ComplexPortal.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0003682; F:chromatin binding; IBA:GO_Central.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0034089; P:establishment of meiotic sister chromatid cohesion; IC:ComplexPortal.
DR GO; GO:0090307; P:mitotic spindle assembly; IMP:UniProtKB.
DR GO; GO:0007062; P:sister chromatid cohesion; IMP:UniProtKB.
DR IDEAL; IID00674; -.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR039662; Cohesin_Scc3/SA.
DR InterPro; IPR020839; SCD.
DR InterPro; IPR013721; STAG.
DR PANTHER; PTHR11199; PTHR11199; 2.
DR Pfam; PF08514; STAG; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR PROSITE; PS51425; SCD; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cell cycle; Cell division;
KW Centromere; Chromosome; Chromosome partition; Disease variant;
KW Holoprosencephaly; Meiosis; Mitosis; Nucleus; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..1231
FT /note="Cohesin subunit SA-2"
FT /id="PRO_0000120185"
FT DOMAIN 293..378
FT /note="SCD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00750"
FT REGION 1..75
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1064..1083
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 21..38
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 607
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 1058
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT MOD_RES 1061
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1064
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35638"
FT MOD_RES 1065
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35638"
FT MOD_RES 1112
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 1177
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 1178
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT VAR_SEQ 1156
FT /note="N -> NTQVTWMLAQRQQEEARQQQERAAMSYVKLRTNLQHAI (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_041119"
FT VARIANT 69..1231
FT /note="Missing (in HPE13 and MKMS; patient cells show
FT decreased protein abundance; increased sister chromatid
FT cohesion)"
FT /evidence="ECO:0000269|PubMed:28296084,
FT ECO:0000269|PubMed:31334757"
FT /id="VAR_083967"
FT VARIANT 140..1231
FT /note="Missing (in MKMS)"
FT /evidence="ECO:0000269|PubMed:30158690"
FT /id="VAR_082294"
FT VARIANT 146..1231
FT /note="Missing (in HPE13)"
FT /evidence="ECO:0000269|PubMed:31334757"
FT /id="VAR_083968"
FT VARIANT 159
FT /note="Y -> C (in MKMS)"
FT /evidence="ECO:0000269|PubMed:30158690"
FT /id="VAR_082295"
FT VARIANT 259..1231
FT /note="Missing (in HPE13)"
FT /evidence="ECO:0000269|PubMed:31334757"
FT /id="VAR_083969"
FT VARIANT 327
FT /note="S -> N (in MKMS; loss of interaction with RAD21;
FT loss of interaction with cohesin complex)"
FT /evidence="ECO:0000269|PubMed:29263825"
FT /id="VAR_082296"
FT VARIANT 535..1231
FT /note="Missing (in MKMS)"
FT /evidence="ECO:0000269|PubMed:30158690"
FT /id="VAR_082297"
FT VARIANT 604
FT /note="R -> Q (in MKMS; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:28296084,
FT ECO:0000269|PubMed:30158690"
FT /id="VAR_082298"
FT VARIANT 699
FT /note="N -> K (in dbSNP:rs6655782)"
FT /id="VAR_060114"
FT VARIANT 1009
FT /note="K -> N (in MKMS)"
FT /evidence="ECO:0000269|PubMed:30447054"
FT /id="VAR_082300"
FT VARIANT 1012..1231
FT /note="Missing (in HPE13)"
FT /evidence="ECO:0000269|PubMed:31334757"
FT /id="VAR_083970"
FT CONFLICT 46
FT /note="G -> D (in Ref. 1; CAD38591)"
FT /evidence="ECO:0000305"
FT CONFLICT 302
FT /note="A -> R (in Ref. 5; CAA99732)"
FT /evidence="ECO:0000305"
FT CONFLICT 327
FT /note="S -> G (in Ref. 1; CAD38591)"
FT /evidence="ECO:0000305"
FT CONFLICT 607..608
FT /note="KH -> ND (in Ref. 5; CAA99732)"
FT /evidence="ECO:0000305"
FT CONFLICT 706
FT /note="W -> R (in Ref. 5; CAA99732)"
FT /evidence="ECO:0000305"
FT CONFLICT 710
FT /note="A -> V (in Ref. 1; CAD38591)"
FT /evidence="ECO:0000305"
FT CONFLICT 835
FT /note="I -> T (in Ref. 1; CAD38591)"
FT /evidence="ECO:0000305"
FT CONFLICT 971
FT /note="A -> T (in Ref. 1; CAH18271)"
FT /evidence="ECO:0000305"
FT CONFLICT 992
FT /note="H -> Y (in Ref. 1; CAD38591)"
FT /evidence="ECO:0000305"
FT CONFLICT 1105
FT /note="S -> T (in Ref. 5; CAA99732)"
FT /evidence="ECO:0000305"
FT CONFLICT 1144
FT /note="M -> K (in Ref. 5; CAA99732)"
FT /evidence="ECO:0000305"
FT HELIX 81..89
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 95..108
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 110..124
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 133..138
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 141..151
FT /evidence="ECO:0007829|PDB:6QNX"
FT STRAND 155..157
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 160..162
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 166..185
FT /evidence="ECO:0007829|PDB:6QNX"
FT TURN 186..189
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 190..192
FT /evidence="ECO:0007829|PDB:6QNX"
FT STRAND 193..195
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 196..207
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 213..252
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 261..291
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 293..296
FT /evidence="ECO:0007829|PDB:6QNX"
FT STRAND 299..301
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 302..318
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 320..323
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 326..335
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 341..356
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 363..377
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 378..380
FT /evidence="ECO:0007829|PDB:6QNX"
FT STRAND 381..383
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 384..400
FT /evidence="ECO:0007829|PDB:6QNX"
FT STRAND 402..404
FT /evidence="ECO:0007829|PDB:4PJW"
FT HELIX 407..415
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 416..418
FT /evidence="ECO:0007829|PDB:6QNX"
FT STRAND 419..421
FT /evidence="ECO:0007829|PDB:4PJW"
FT HELIX 422..436
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 458..470
FT /evidence="ECO:0007829|PDB:6QNX"
FT STRAND 475..477
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 478..483
FT /evidence="ECO:0007829|PDB:6QNX"
FT TURN 485..487
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 489..492
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 495..501
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 515..533
FT /evidence="ECO:0007829|PDB:6QNX"
FT TURN 539..541
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 550..577
FT /evidence="ECO:0007829|PDB:6QNX"
FT TURN 578..580
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 582..588
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 592..594
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 598..602
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 606..621
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 626..639
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 647..672
FT /evidence="ECO:0007829|PDB:6QNX"
FT STRAND 674..676
FT /evidence="ECO:0007829|PDB:4PK7"
FT HELIX 681..700
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 704..706
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 709..722
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 727..747
FT /evidence="ECO:0007829|PDB:6QNX"
FT STRAND 751..753
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 757..775
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 781..797
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 800..802
FT /evidence="ECO:0007829|PDB:6QNX"
FT TURN 804..806
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 808..810
FT /evidence="ECO:0007829|PDB:6QNX"
FT TURN 811..813
FT /evidence="ECO:0007829|PDB:4PK7"
FT HELIX 819..832
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 851..873
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 879..882
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 883..886
FT /evidence="ECO:0007829|PDB:6QNX"
FT TURN 887..892
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 893..910
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 912..933
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 943..957
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 967..981
FT /evidence="ECO:0007829|PDB:6QNX"
FT STRAND 982..984
FT /evidence="ECO:0007829|PDB:6QNX"
FT STRAND 987..989
FT /evidence="ECO:0007829|PDB:4PJW"
FT HELIX 995..998
FT /evidence="ECO:0007829|PDB:4PK7"
FT HELIX 999..1003
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 1004..1009
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 1014..1025
FT /evidence="ECO:0007829|PDB:6QNX"
FT HELIX 1028..1032
FT /evidence="ECO:0007829|PDB:6QNX"
FT STRAND 1035..1037
FT /evidence="ECO:0007829|PDB:4PJU"
FT HELIX 1039..1045
FT /evidence="ECO:0007829|PDB:6QNX"
SQ SEQUENCE 1231 AA; 141326 MW; 692358EFFFF61BB9 CRC64;
MIAAPEIPTD FNLLQESETH FSSDTDFEDI EGKNQKQGKG KTCKKGKKGP AEKGKGGNGG
GKPPSGPNRM NGHHQQNGVE NMMLFEVVKM GKSAMQSVVD DWIESYKHDR DIALLDLINF
FIQCSGCKGV VTAEMFRHMQ NSEIIRKMTE EFDEDSGDYP LTMAGPQWKK FKSSFCEFIG
VLVRQCQYSI IYDEYMMDTV ISLLTGLSDS QVRAFRHTST LAAMKLMTAL VNVALNLSIN
MDNTQRQYEA ERNKMIGKRA NERLELLLQK RKELQENQDE IENMMNAIFK GVFVHRYRDA
IAEIRAICIE EIGIWMKMYS DAFLNDSYLK YVGWTMHDKQ GEVRLKCLTA LQGLYYNKEL
NSKLELFTSR FKDRIVSMTL DKEYDVAVQA IKLLTLVLQS SEEVLTAEDC ENVYHLVYSA
HRPVAVAAGE FLYKKLFSRR DPEEDGMMKR RGRQGPNANL VKTLVFFFLE SELHEHAAYL
VDSMWDCATE LLKDWECMNS LLLEEPLSGE EALTDRQESA LIEIMLCTIR QAAECHPPVG
RGTGKRVLTA KEKKTQLDDR TKITELFAVA LPQLLAKYSV DAEKVTNLLQ LPQYFDLEIY
TTGRLEKHLD ALLRQIRNIV EKHTDTDVLE ACSKTYHALC NEEFTIFNRV DISRSQLIDE
LADKFNRLLE DFLQEGEEPD EDDAYQVLST LKRITAFHNA HDLSKWDLFA CNYKLLKTGI
ENGDMPEQIV IHALQCTHYV ILWQLAKITE SSSTKEDLLR LKKQMRVFCQ ICQHYLTNVN
TTVKEQAFTI LCDILMIFSH QIMSGGRDML EPLVYTPDSS LQSELLSFIL DHVFIEQDDD
NNSADGQQED EASKIEALHK RRNLLAAFCK LIVYTVVEMN TAADIFKQYM KYYNDYGDII
KETMSKTRQI DKIQCAKTLI LSLQQLFNEM IQENGYNFDR SSSTFSGIKE LARRFALTFG
LDQLKTREAI AMLHKDGIEF AFKEPNPQGE SHPPLNLAFL DILSEFSSKL LRQDKRTVYV
YLEKFMTFQM SLRREDVWLP LMSYRNSLLA GGDDDTMSVI SGISSRGSTV RSKKSKPSTG
KRKVVEGMQL SLTEESSSSD SMWLSREQTL HTPVMMQTPQ LTSTIMREPK RLRPEDSFMS
VYPMQTEHHQ TPLDYNRRGT SLMEDDEEPI VEDVMMSSEG RIEDLNEGMD FDTMDIDLPP
SKNRRERTEL KPDFFDPASI MDESVLGVSM F