MINT_HUMAN
ID MINT_HUMAN Reviewed; 3664 AA.
AC Q96T58; Q9H9A8; Q9NWH5; Q9UQ01; Q9Y556;
DT 10-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 201.
DE RecName: Full=Msx2-interacting protein;
DE AltName: Full=SMART/HDAC1-associated repressor protein;
DE AltName: Full=SPEN homolog;
GN Name=SPEN; Synonyms=KIAA0929, MINT, SHARP;
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], FUNCTION, SUBCELLULAR LOCATION, INDUCTION,
RP RNA-BINDING, AND INTERACTION WITH NCOR2; HDAC1; HDAC2; RBBP4; MBD3; RAR AND
RP MTA1L1.
RC TISSUE=Liver, and Pituitary;
RX PubMed=11331609; DOI=10.1101/gad.871201;
RA Shi Y., Downes M., Xie W., Kao H.-Y., Ordentlich P., Tsai C.-C., Hon M.,
RA Evans R.M.;
RT "Sharp, an inducible cofactor that integrates nuclear receptor repression
RT and activation.";
RL Genes Dev. 15:1140-1151(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 294-3664.
RA Rhodes S., Huckle E.;
RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 793-1595, AND VARIANT PRO-1091.
RC TISSUE=Embryo, and Teratocarcinoma;
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 MRNA] OF 2002-3664.
RC TISSUE=Brain;
RX PubMed=10231032; DOI=10.1093/dnares/6.1.63;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:63-70(1999).
RN [6]
RP INTERACTION WITH PPARD.
RX PubMed=11867749; DOI=10.1073/pnas.052707099;
RA Shi Y., Hon M., Evans R.M.;
RT "The peroxisome proliferator-activated receptor delta, an integrator of
RT transcriptional repression and nuclear receptor signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:2613-2618(2002).
RN [7]
RP FUNCTION, AND INTERACTION WITH RBPSUH.
RX PubMed=12374742; DOI=10.1093/emboj/cdf549;
RA Oswald F., Kostezka U., Astrahantseff K., Bourteele S., Dillinger K.,
RA Zechner U., Ludwig L., Wilda M., Hameister H., Knoechel W., Liptay S.,
RA Schmid R.M.;
RT "SHARP is a novel component of the Notch/RBP-Jkappa signalling pathway.";
RL EMBO J. 21:5417-5426(2002).
RN [8]
RP INTERACTION WITH EBV BSFL2/BMLF1 (MICROBIAL INFECTION).
RX PubMed=16129689; DOI=10.1074/jbc.m501725200;
RA Hiriart E., Gruffat H., Buisson M., Mikaelian I., Keppler S., Meresse P.,
RA Mercher T., Bernard O.A., Sergeant A., Manet E.;
RT "Interaction of the Epstein-Barr virus mRNA export factor EB2 with human
RT Spen proteins SHARP, OTT1, and a novel member of the family, OTT3, links
RT Spen proteins with splicing regulation and mRNA export.";
RL J. Biol. Chem. 280:36935-36945(2005).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1268; SER-1278; SER-1283;
RP SER-1380 AND SER-1382, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-736; SER-740; SER-1194;
RP SER-1287; SER-1380; SER-1382; THR-1439; THR-1441; SER-1897; SER-2120;
RP SER-2126; SER-2366; THR-2421; THR-2938; THR-2950 AND SER-3433, 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 [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1222; SER-1268; SER-1278;
RP THR-1947; SER-2452 AND THR-2460, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-309; SER-623; SER-727;
RP SER-1252; SER-1268; SER-1278; SER-1287; SER-1333; THR-1633; SER-1897;
RP SER-2101; SER-2120 AND SER-2159, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-727; SER-1062; SER-1222;
RP SER-1261; SER-1268; SER-1278; SER-1380; SER-1382; SER-2101 AND SER-2120,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-99; SER-188; SER-190;
RP SER-725; SER-727; SER-736; SER-740; SER-770; SER-847; SER-1062; THR-1140;
RP SER-1168; SER-1194; SER-1222; SER-1268; SER-1278; SER-1283; SER-1287;
RP SER-1333; SER-1380; SER-1382; THR-1619; THR-1633; THR-1826; SER-1918;
RP SER-2101; SER-2126; SER-2159; THR-2163; THR-2393; THR-2421; SER-2481 AND
RP SER-2493, 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 [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1062; SER-1268; SER-1278;
RP THR-2393; SER-2456; SER-2481 AND SER-2486, AND IDENTIFICATION BY MASS
RP 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 METHYLATION [LARGE SCALE ANALYSIS] AT ARG-108; ARG-3113 AND ARG-3121, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [19]
RP INVOLVEMENT IN RATARS, AND VARIANTS RATARS 535-ARG--VAL-3664 DEL;
RP 672-ARG--VAL-3664 DEL; 701-GLU--VAL-3664 DEL; 1067-GLN--VAL-3664 DEL;
RP 1170-ARG--VAL-3664 DEL; 1265-ARG--VAL-3664 DEL; 1798-GLN--VAL-3664 DEL;
RP 1936-ARG--VAL-3664 DEL; 2020-GLN--VAL-3664 DEL; 2267-GLU--VAL-3664 DEL;
RP 2342-ARG--VAL-3664 DEL AND 2442-GLU--VAL-3664 DEL.
RX PubMed=33596411; DOI=10.1016/j.ajhg.2021.01.015;
RA Radio F.C., Pang K., Ciolfi A., Levy M.A., Hernandez-Garcia A., Pedace L.,
RA Pantaleoni F., Liu Z., de Boer E., Jackson A., Bruselles A., McConkey H.,
RA Stellacci E., Lo Cicero S., Motta M., Carrozzo R., Dentici M.L.,
RA McWalter K., Desai M., Monaghan K.G., Telegrafi A., Philippe C.,
RA Vitobello A., Au M., Grand K., Sanchez-Lara P.A., Baez J., Lindstrom K.,
RA Kulch P., Sebastian J., Madan-Khetarpal S., Roadhouse C., MacKenzie J.J.,
RA Monteleone B., Saunders C.J., Jean Cuevas J.K., Cross L., Zhou D.,
RA Hartley T., Sawyer S.L., Monteiro F.P., Secches T.V., Kok F.,
RA Schultz-Rogers L.E., Macke E.L., Morava E., Klee E.W., Kemppainen J.,
RA Iascone M., Selicorni A., Tenconi R., Amor D.J., Pais L., Gallacher L.,
RA Turnpenny P.D., Stals K., Ellard S., Cabet S., Lesca G., Pascal J.,
RA Steindl K., Ravid S., Weiss K., Castle A.M.R., Carter M.T., Kalsner L.,
RA de Vries B.B.A., van Bon B.W., Wevers M.R., Pfundt R., Stegmann A.P.A.,
RA Kerr B., Kingston H.M., Chandler K.E., Sheehan W., Elias A.F., Shinde D.N.,
RA Towne M.C., Robin N.H., Goodloe D., Vanderver A., Sherbini O., Bluske K.,
RA Hagelstrom R.T., Zanus C., Faletra F., Musante L., Kurtz-Nelson E.C.,
RA Earl R.K., Anderlid B.M., Morin G., van Slegtenhorst M., Diderich K.E.M.,
RA Brooks A.S., Gribnau J., Boers R.G., Finestra T.R., Carter L.B., Rauch A.,
RA Gasparini P., Boycott K.M., Barakat T.S., Graham J.M. Jr., Faivre L.,
RA Banka S., Wang T., Eichler E.E., Priolo M., Dallapiccola B.,
RA Vissers L.E.L.M., Sadikovic B., Scott D.A., Holder J.L. Jr., Tartaglia M.;
RT "SPEN haploinsufficiency causes a neurodevelopmental disorder overlapping
RT proximal 1p36 deletion syndrome with an episignature of X chromosomes in
RT females.";
RL Am. J. Hum. Genet. 108:502-516(2021).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF SPOC DOMAIN.
RX PubMed=12897056; DOI=10.1101/gad.266203;
RA Ariyoshi M., Schwabe J.W.R.;
RT "A conserved structural motif reveals the essential transcriptional
RT repression function of Spen proteins and their role in developmental
RT signaling.";
RL Genes Dev. 17:1909-1920(2003).
RN [21]
RP VARIANTS [LARGE SCALE ANALYSIS] HIS-990 AND ILE-1488.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: May serve as a nuclear matrix platform that organizes and
CC integrates transcriptional responses. In osteoblasts, supports
CC transcription activation: synergizes with RUNX2 to enhance FGFR2-
CC mediated activation of the osteocalcin FGF-responsive element (OCFRE)
CC (By similarity). Has also been shown to be an essential corepressor
CC protein, which probably regulates different key pathways such as the
CC Notch pathway. Negative regulator of the Notch pathway via its
CC interaction with RBPSUH, which prevents the association between NOTCH1
CC and RBPSUH, and therefore suppresses the transactivation activity of
CC Notch signaling. Blocks the differentiation of precursor B-cells into
CC marginal zone B-cells. Probably represses transcription via the
CC recruitment of large complexes containing histone deacetylase proteins.
CC May bind both to DNA and RNA. {ECO:0000250|UniProtKB:Q62504,
CC ECO:0000269|PubMed:11331609, ECO:0000269|PubMed:12374742}.
CC -!- SUBUNIT: Interacts with MSX2 and HIPK3 (By similarity). Interacts with
CC NCOR2, HDAC1, HDAC2, RBBP4, MBD3 and MTA1L1. Interacts with RBPSUH;
CC this interaction may prevent the interaction between RBPSUH and NOTCH1.
CC Interacts with the nuclear receptors RAR and PPARD. Interacts with RAR
CC in absence of ligand. Binds to the steroid receptor RNA coactivator
CC SRA. {ECO:0000250, ECO:0000269|PubMed:11331609,
CC ECO:0000269|PubMed:11867749, ECO:0000269|PubMed:12374742}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Epstein-Barr virus
CC BSFL2/BMLF1. {ECO:0000269|PubMed:16129689}.
CC -!- INTERACTION:
CC Q96T58; P46108: CRK; NbExp=2; IntAct=EBI-765739, EBI-886;
CC Q96T58; P16333: NCK1; NbExp=3; IntAct=EBI-765739, EBI-389883;
CC Q96T58; Q9Y618: NCOR2; NbExp=5; IntAct=EBI-765739, EBI-80830;
CC Q96T58; Q06330: RBPJ; NbExp=2; IntAct=EBI-765739, EBI-632552;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11331609}.
CC Note=Associates with chromatin.
CC -!- TISSUE SPECIFICITY: Expressed at high level in brain, testis, spleen
CC and thymus. Expressed at intermediate level in kidney, liver, mammary
CC gland and skin.
CC -!- INDUCTION: By 17-beta-estradiol. {ECO:0000269|PubMed:11331609}.
CC -!- DOMAIN: The RID domain mediates the interaction with nuclear receptors.
CC {ECO:0000250}.
CC -!- DOMAIN: The SPOC domain, which mediates the interaction with NCOR2, is
CC essential for the repressive activity.
CC -!- DISEASE: Radio-Tartaglia syndrome (RATARS) [MIM:619312]: An autosomal
CC dominant neurodevelopmental disorder characterized by global
CC developmental delay, hypotonia, mild motor difficulties, impaired
CC intellectual development, speech delay, craniofacial dysmorphism, and
CC variable behavioral abnormalities. {ECO:0000269|PubMed:33596411}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the RRM Spen family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA91405.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB14324.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAB51072.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF356524; AAK52750.1; -; mRNA.
DR EMBL; AL034555; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL450998; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL096858; CAB51072.1; ALT_INIT; mRNA.
DR EMBL; AK000882; BAA91405.1; ALT_INIT; mRNA.
DR EMBL; AK022949; BAB14324.1; ALT_INIT; mRNA.
DR EMBL; AB023146; BAA76773.1; -; mRNA.
DR CCDS; CCDS164.1; -.
DR RefSeq; NP_055816.2; NM_015001.2.
DR PDB; 1OW1; X-ray; 1.80 A; A=3470-3664.
DR PDB; 2RT5; NMR; -; A=3496-3664.
DR PDB; 4P6Q; X-ray; 2.00 A; A=335-620.
DR PDBsum; 1OW1; -.
DR PDBsum; 2RT5; -.
DR PDBsum; 4P6Q; -.
DR BMRB; Q96T58; -.
DR SMR; Q96T58; -.
DR BioGRID; 116655; 102.
DR CORUM; Q96T58; -.
DR DIP; DIP-34569N; -.
DR IntAct; Q96T58; 45.
DR MINT; Q96T58; -.
DR STRING; 9606.ENSP00000364912; -.
DR GlyConnect; 2907; 1 O-Linked glycan (4 sites).
DR GlyGen; Q96T58; 42 sites, 2 O-linked glycans (42 sites).
DR iPTMnet; Q96T58; -.
DR PhosphoSitePlus; Q96T58; -.
DR SwissPalm; Q96T58; -.
DR BioMuta; SPEN; -.
DR DMDM; 41688816; -.
DR EPD; Q96T58; -.
DR jPOST; Q96T58; -.
DR MassIVE; Q96T58; -.
DR MaxQB; Q96T58; -.
DR PaxDb; Q96T58; -.
DR PeptideAtlas; Q96T58; -.
DR PRIDE; Q96T58; -.
DR ProteomicsDB; 78197; -.
DR Antibodypedia; 14431; 55 antibodies from 19 providers.
DR DNASU; 23013; -.
DR Ensembl; ENST00000375759.8; ENSP00000364912.3; ENSG00000065526.12.
DR GeneID; 23013; -.
DR KEGG; hsa:23013; -.
DR MANE-Select; ENST00000375759.8; ENSP00000364912.3; NM_015001.3; NP_055816.2.
DR UCSC; uc001axk.2; human.
DR CTD; 23013; -.
DR DisGeNET; 23013; -.
DR GeneCards; SPEN; -.
DR HGNC; HGNC:17575; SPEN.
DR HPA; ENSG00000065526; Low tissue specificity.
DR MIM; 613484; gene.
DR MIM; 619312; phenotype.
DR neXtProt; NX_Q96T58; -.
DR OpenTargets; ENSG00000065526; -.
DR Orphanet; 1606; 1p36 deletion syndrome.
DR PharmGKB; PA134895302; -.
DR VEuPathDB; HostDB:ENSG00000065526; -.
DR eggNOG; KOG0112; Eukaryota.
DR GeneTree; ENSGT00940000157087; -.
DR HOGENOM; CLU_224781_0_0_1; -.
DR InParanoid; Q96T58; -.
DR OMA; HEARMNT; -.
DR OrthoDB; 367857at2759; -.
DR PhylomeDB; Q96T58; -.
DR TreeFam; TF315637; -.
DR PathwayCommons; Q96T58; -.
DR Reactome; R-HSA-9013422; RHOBTB1 GTPase cycle.
DR SignaLink; Q96T58; -.
DR SIGNOR; Q96T58; -.
DR BioGRID-ORCS; 23013; 44 hits in 1097 CRISPR screens.
DR ChiTaRS; SPEN; human.
DR EvolutionaryTrace; Q96T58; -.
DR GeneWiki; SPEN; -.
DR GenomeRNAi; 23013; -.
DR Pharos; Q96T58; Tbio.
DR PRO; PR:Q96T58; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q96T58; protein.
DR Bgee; ENSG00000065526; Expressed in ventricular zone and 199 other tissues.
DR ExpressionAtlas; Q96T58; baseline and differential.
DR Genevisible; Q96T58; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0017053; C:transcription repressor complex; IDA:BHF-UCL.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003729; F:mRNA binding; IBA:GO_Central.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:BHF-UCL.
DR GO; GO:0003714; F:transcription corepressor activity; IDA:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0050769; P:positive regulation of neurogenesis; IMP:BHF-UCL.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR CDD; cd12348; RRM1_SHARP; 1.
DR CDD; cd12349; RRM2_SHARP; 1.
DR CDD; cd12350; RRM3_SHARP; 1.
DR CDD; cd12351; RRM4_SHARP; 1.
DR DisProt; DP02375; -.
DR Gene3D; 2.40.290.10; -; 1.
DR Gene3D; 3.30.70.330; -; 4.
DR IDEAL; IID00578; -.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf.
DR InterPro; IPR035979; RBD_domain_sf.
DR InterPro; IPR000504; RRM_dom.
DR InterPro; IPR034172; SHARP_RRM1.
DR InterPro; IPR034173; SHARP_RRM2.
DR InterPro; IPR034174; SHARP_RRM3.
DR InterPro; IPR034175; SHARP_RRM4.
DR InterPro; IPR016194; SPOC-like_C_dom_sf.
DR InterPro; IPR012921; SPOC_C.
DR InterPro; IPR010912; SPOC_met.
DR Pfam; PF00076; RRM_1; 4.
DR Pfam; PF07744; SPOC; 1.
DR SMART; SM00360; RRM; 4.
DR SUPFAM; SSF100939; SSF100939; 1.
DR SUPFAM; SSF54928; SSF54928; 2.
DR PROSITE; PS50102; RRM; 4.
DR PROSITE; PS50917; SPOC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Coiled coil; Disease variant; DNA-binding;
KW Host-virus interaction; Intellectual disability; Methylation;
KW Notch signaling pathway; Nucleus; Phosphoprotein; Reference proteome;
KW Repeat; Repressor; RNA-binding; Transcription; Transcription regulation.
FT CHAIN 1..3664
FT /note="Msx2-interacting protein"
FT /id="PRO_0000081627"
FT DOMAIN 6..81
FT /note="RRM 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT DOMAIN 335..415
FT /note="RRM 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT DOMAIN 438..513
FT /note="RRM 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT DOMAIN 517..589
FT /note="RRM 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT DOMAIN 2201..2707
FT /note="RID"
FT DOMAIN 3498..3664
FT /note="SPOC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00249"
FT DNA_BIND 1..573
FT /evidence="ECO:0000250"
FT REGION 70..89
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 103..164
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 183..209
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 225..330
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 678..871
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 918..941
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 957..1020
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1070..1287
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1366..1397
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1497..1524
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1588..2171
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2130..2464
FT /note="Interaction with MSX2"
FT /evidence="ECO:0000250"
FT REGION 2185..2532
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2566..2590
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2709..2870
FT /note="Interaction with RBPSUH"
FT /evidence="ECO:0000250"
FT REGION 2775..2806
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2847..2875
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2978..3010
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3022..3047
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3135..3156
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3208..3265
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3327..3492
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 688..715
FT /evidence="ECO:0000255"
FT COILED 977..1004
FT /evidence="ECO:0000255"
FT COILED 1170..1191
FT /evidence="ECO:0000255"
FT COILED 1408..1428
FT /evidence="ECO:0000255"
FT COILED 1496..1529
FT /evidence="ECO:0000255"
FT COILED 1592..1612
FT /evidence="ECO:0000255"
FT COILED 1928..1944
FT /evidence="ECO:0000255"
FT COMPBIAS 124..164
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 191..205
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 225..241
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 242..325
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 678..727
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 729..746
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 774..827
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 838..870
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 977..1020
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1096..1110
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1120..1253
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1366..1394
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1590..1628
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1639..1656
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1740..1764
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1766..1785
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1839..1876
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1915..1939
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1955..1976
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2028..2052
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2063..2084
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2140..2154
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2196..2210
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2298..2312
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2313..2331
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2356..2380
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2391..2420
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2426..2441
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2492..2532
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2847..2869
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3242..3262
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3346..3377
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3378..3397
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3416..3436
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3443..3469
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 99
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 108
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 188
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 190
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 309
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 623
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 725
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 727
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 736
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 740
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 770
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 830
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62504"
FT MOD_RES 833
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62504"
FT MOD_RES 847
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1062
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 1140
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1168
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1194
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1222
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 1252
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 1261
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 1268
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 1278
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 1283
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1287
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 1333
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1380
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1382
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1439
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1441
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1619
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1633
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1826
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1897
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 1918
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1947
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 2101
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 2120
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692"
FT MOD_RES 2126
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 2159
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 2163
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 2366
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 2393
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 2421
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 2452
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 2456
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 2460
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 2481
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 2486
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 2493
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 2938
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 2950
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 3113
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 3121
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 3433
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT VARIANT 535..3664
FT /note="Missing (in RATARS)"
FT /evidence="ECO:0000269|PubMed:33596411"
FT /id="VAR_085747"
FT VARIANT 672..3664
FT /note="Missing (in RATARS)"
FT /evidence="ECO:0000269|PubMed:33596411"
FT /id="VAR_085748"
FT VARIANT 701..3664
FT /note="Missing (in RATARS)"
FT /evidence="ECO:0000269|PubMed:33596411"
FT /id="VAR_085749"
FT VARIANT 970
FT /note="A -> V (in dbSNP:rs848208)"
FT /id="VAR_017119"
FT VARIANT 990
FT /note="D -> H (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035483"
FT VARIANT 1067..3664
FT /note="Missing (in RATARS)"
FT /evidence="ECO:0000269|PubMed:33596411"
FT /id="VAR_085750"
FT VARIANT 1091
FT /note="L -> P (in dbSNP:rs848209)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_017120"
FT VARIANT 1170..3664
FT /note="Missing (in RATARS)"
FT /evidence="ECO:0000269|PubMed:33596411"
FT /id="VAR_085751"
FT VARIANT 1265..3664
FT /note="Missing (in RATARS)"
FT /evidence="ECO:0000269|PubMed:33596411"
FT /id="VAR_085752"
FT VARIANT 1363
FT /note="D -> E (in dbSNP:rs12095818)"
FT /id="VAR_052208"
FT VARIANT 1488
FT /note="R -> I (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035484"
FT VARIANT 1798..3664
FT /note="Missing (in RATARS; uncertain pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:33596411"
FT /id="VAR_085753"
FT VARIANT 1936..3664
FT /note="Missing (in RATARS; uncertain pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:33596411"
FT /id="VAR_085754"
FT VARIANT 2020..3664
FT /note="Missing (in RATARS)"
FT /evidence="ECO:0000269|PubMed:33596411"
FT /id="VAR_085755"
FT VARIANT 2267..3664
FT /note="Missing (in RATARS; uncertain pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:33596411"
FT /id="VAR_085756"
FT VARIANT 2342..3664
FT /note="Missing (in RATARS)"
FT /evidence="ECO:0000269|PubMed:33596411"
FT /id="VAR_085757"
FT VARIANT 2360
FT /note="N -> D (in dbSNP:rs848210)"
FT /id="VAR_017121"
FT VARIANT 2442..3664
FT /note="Missing (in RATARS)"
FT /evidence="ECO:0000269|PubMed:33596411"
FT /id="VAR_085758"
FT CONFLICT 956
FT /note="G -> D (in Ref. 4)"
FT /evidence="ECO:0000305"
FT STRAND 336..340
FT /evidence="ECO:0007829|PDB:4P6Q"
FT HELIX 348..359
FT /evidence="ECO:0007829|PDB:4P6Q"
FT HELIX 360..362
FT /evidence="ECO:0007829|PDB:4P6Q"
FT STRAND 365..371
FT /evidence="ECO:0007829|PDB:4P6Q"
FT TURN 374..376
FT /evidence="ECO:0007829|PDB:4P6Q"
FT STRAND 378..385
FT /evidence="ECO:0007829|PDB:4P6Q"
FT HELIX 386..395
FT /evidence="ECO:0007829|PDB:4P6Q"
FT TURN 396..398
FT /evidence="ECO:0007829|PDB:4P6Q"
FT STRAND 407..410
FT /evidence="ECO:0007829|PDB:4P6Q"
FT HELIX 414..422
FT /evidence="ECO:0007829|PDB:4P6Q"
FT STRAND 438..444
FT /evidence="ECO:0007829|PDB:4P6Q"
FT HELIX 451..458
FT /evidence="ECO:0007829|PDB:4P6Q"
FT STRAND 464..472
FT /evidence="ECO:0007829|PDB:4P6Q"
FT STRAND 475..485
FT /evidence="ECO:0007829|PDB:4P6Q"
FT HELIX 486..496
FT /evidence="ECO:0007829|PDB:4P6Q"
FT STRAND 507..510
FT /evidence="ECO:0007829|PDB:4P6Q"
FT STRAND 517..522
FT /evidence="ECO:0007829|PDB:4P6Q"
FT HELIX 530..537
FT /evidence="ECO:0007829|PDB:4P6Q"
FT HELIX 538..540
FT /evidence="ECO:0007829|PDB:4P6Q"
FT STRAND 543..549
FT /evidence="ECO:0007829|PDB:4P6Q"
FT TURN 550..553
FT /evidence="ECO:0007829|PDB:4P6Q"
FT STRAND 554..560
FT /evidence="ECO:0007829|PDB:4P6Q"
FT HELIX 562..572
FT /evidence="ECO:0007829|PDB:4P6Q"
FT STRAND 575..577
FT /evidence="ECO:0007829|PDB:4P6Q"
FT STRAND 583..586
FT /evidence="ECO:0007829|PDB:4P6Q"
FT HELIX 589..601
FT /evidence="ECO:0007829|PDB:4P6Q"
FT HELIX 609..618
FT /evidence="ECO:0007829|PDB:4P6Q"
FT HELIX 3501..3504
FT /evidence="ECO:0007829|PDB:1OW1"
FT STRAND 3507..3515
FT /evidence="ECO:0007829|PDB:1OW1"
FT STRAND 3518..3529
FT /evidence="ECO:0007829|PDB:1OW1"
FT HELIX 3531..3537
FT /evidence="ECO:0007829|PDB:1OW1"
FT STRAND 3541..3543
FT /evidence="ECO:0007829|PDB:2RT5"
FT STRAND 3547..3549
FT /evidence="ECO:0007829|PDB:1OW1"
FT STRAND 3551..3554
FT /evidence="ECO:0007829|PDB:1OW1"
FT HELIX 3557..3566
FT /evidence="ECO:0007829|PDB:1OW1"
FT TURN 3570..3572
FT /evidence="ECO:0007829|PDB:1OW1"
FT STRAND 3573..3580
FT /evidence="ECO:0007829|PDB:1OW1"
FT HELIX 3585..3598
FT /evidence="ECO:0007829|PDB:1OW1"
FT HELIX 3600..3606
FT /evidence="ECO:0007829|PDB:1OW1"
FT STRAND 3608..3614
FT /evidence="ECO:0007829|PDB:1OW1"
FT TURN 3617..3619
FT /evidence="ECO:0007829|PDB:2RT5"
FT STRAND 3624..3629
FT /evidence="ECO:0007829|PDB:1OW1"
FT HELIX 3633..3642
FT /evidence="ECO:0007829|PDB:1OW1"
FT HELIX 3644..3650
FT /evidence="ECO:0007829|PDB:1OW1"
FT TURN 3651..3653
FT /evidence="ECO:0007829|PDB:1OW1"
FT STRAND 3657..3663
FT /evidence="ECO:0007829|PDB:1OW1"
SQ SEQUENCE 3664 AA; 402248 MW; 5228C58533E5B27B CRC64;
MVRETRHLWV GNLPENVREE KIIEHFKRYG RVESVKILPK RGSEGGVAAF VDFVDIKSAQ
KAHNSVNKMG DRDLRTDYNE PGTIPSAARG LDDTVSIASR SREVSGFRGG GGGPAYGPPP
SLHAREGRYE RRLDGASDNR ERAYEHSAYG HHERGTGGFD RTRHYDQDYY RDPRERTLQH
GLYYASRSRS PNRFDAHDPR YEPRAREQFT LPSVVHRDIY RDDITREVRG RRPERNYQHS
RSRSPHSSQS RNQSPQRLAS QASRPTRSPS GSGSRSRSSS SDSISSSSST SSDSSDSSSS
SSDDSPARSV QSAAVPAPTS QLLSSLEKDE PRKSFGIKVQ NLPVRSTDTS LKDGLFHEFK
KFGKVTSVQI HGTSEERYGL VFFRQQEDQE KALTASKGKL FFGMQIEVTA WIGPETESEN
EFRPLDERID EFHPKATRTL FIGNLEKTTT YHDLRNIFQR FGEIVDIDIK KVNGVPQYAF
LQYCDIASVC KAIKKMDGEY LGNNRLKLGF GKSMPTNCVW LDGLSSNVSD QYLTRHFCRY
GPVVKVVFDR LKGMALVLYN EIEYAQAAVK ETKGRKIGGN KIKVDFANRE SQLAFYHCME
KSGQDIRDFY EMLAERREER RASYDYNQDR TYYESVRTPG TYPEDSRRDY PARGREFYSE
WETYQGDYYE SRYYDDPREY RDYRNDPYEQ DIREYSYRQR ERERERERFE SDRDRDHERR
PIERSQSPVH LRRPQSPGAS PSQAERLPSD SERRLYSRSS DRSGSCSSLS PPRYEKLDKS
RLERYTKNEK TDKERTFDPE RVERERRLIR KEKVEKDKTD KQKRKGKVHS PSSQSSETDQ
ENEREQSPEK PRSCNKLSRE KADKEGIAKN RLELMPCVVL TRVKEKEGKV IDHTPVEKLK
AKLDNDTVKS SALDQKLQVS QTEPAKSDLS KLESVRMKVP KEKGLSSHVE VVEKEGRLKA
RKHLKPEQPA DGVSAVDLEK LEARKRRFAD SNLKAEKQKP EVKKSSPEME DARVLSKKQP
DVSSREVILL REGEAERKPV RKEILKRESK KIKLDRLNTV ASPKDCQELA SISVGSGSRP
SSDLQARLGE LAGESVENQE VQSKKPIPSK PQLKQLQVLD DQGPEREDVR KNYCSLRDET
PERKSGQEKS HSVNTEEKIG IDIDHTQSYR KQMEQSRRKQ QMEMEIAKSE KFGSPKKDVD
EYERRSLVHE VGKPPQDVTD DSPPSKKKRM DHVDFDICTK RERNYRSSRQ ISEDSERTGG
SPSVRHGSFH EDEDPIGSPR LLSVKGSPKV DEKVLPYSNI TVREESLKFN PYDSSRREQM
ADMAKIKLSV LNSEDELNRW DSQMKQDAGR FDVSFPNSII KRDSLRKRSV RDLEPGEVPS
DSDEDGEHKS HSPRASALYE SSRLSFLLRD REDKLRERDE RLSSSLERNK FYSFALDKTI
TPDTKALLER AKSLSSSREE NWSFLDWDSR FANFRNNKDK EKVDSAPRPI PSWYMKKKKI
RTDSEGKMDD KKEDHKEEEQ ERQELFASRF LHSSIFEQDS KRLQHLERKE EDSDFISGRI
YGKQTSEGAN STTDSIQEPV VLFHSRFMEL TRMQQKEKEK DQKPKEVEKQ EDTENHPKTP
ESAPENKDSE LKTPPSVGPP SVTVVTLESA PSALEKTTGD KTVEAPLVTE EKTVEPATVS
EEAKPASEPA PAPVEQLEQV DLPPGADPDK EAAMMPAGVE EGSSGDQPPY LDAKPPTPGA
SFSQAESNVD PEPDSTQPLS KPAQKSEEAN EPKAEKPDAT ADAEPDANQK AEAAPESQPP
ASEDLEVDPP VAAKDKKPNK SKRSKTPVQA AAVSIVEKPV TRKSERIDRE KLKRSNSPRG
EAQKLLELKM EAEKITRTAS KNSAADLEHP EPSLPLSRTR RRNVRSVYAT MGDHENRSPV
KEPVEQPRVT RKRLERELQE AAAVPTTPRR GRPPKTRRRA DEEEENEAKE PAETLKPPEG
WRSPRSQKTA AGGGPQGKKG KNEPKVDATR PEATTEVGPQ IGVKESSMEP KAAEEEAGSE
QKRDRKDAGT DKNPPETAPV EVVEKKPAPE KNSKSKRGRS RNSRLAVDKS ASLKNVDAAV
SPRGAAAQAG ERESGVVAVS PEKSESPQKE DGLSSQLKSD PVDPDKEPEK EDVSASGPSP
EATQLAKQME LEQAVEHIAK LAEASASAAY KADAPEGLAP EDRDKPAHQA SETELAAAIG
SIINDISGEP ENFPAPPPYP GESQTDLQPP AGAQALQPSE EGMETDEAVS GILETEAATE
SSRPPVNAPD PSAGPTDTKE ARGNSSETSH SVPEAKGSKE VEVTLVRKDK GRQKTTRSRR
KRNTNKKVVA PVESHVPESN QAQGESPAAN EGTTVQHPEA PQEEKQSEKP HSTPPQSCTS
DLSKIPSTEN SSQEISVEER TPTKASVPPD LPPPPQPAPV DEEPQARFRV HSIIESDPVT
PPSDPSIPIP TLPSVTAAKL SPPVASGGIP HQSPPTKVTE WITRQEEPRA QSTPSPALPP
DTKASDVDTS SSTLRKILMD PKYVSATSVT STSVTTAIAE PVSAAPCLHE APPPPVDSKK
PLEEKTAPPV TNNSEIQASE VLVAADKEKV APVIAPKITS VISRMPVSID LENSQKITLA
KPAPQTLTGL VSALTGLVNV SLVPVNALKG PVKGSVTTLK SLVSTPAGPV NVLKGPVNVL
TGPVNVLTTP VNATVGTVNA APGTVNAAAS AVNATASAVT VTAGAVTAAS GGVTATTGTV
TMAGAVIAPS TKCKQRASAN ENSRFHPGSM PVIDDRPADA GSGAGLRVNT SEGVVLLSYS
GQKTEGPQRI SAKISQIPPA SAMDIEFQQS VSKSQVKPDS VTASQPPSKG PQAPAGYANV
ATHSTLVLTA QTYNASPVIS SVKADRPSLE KPEPIHLSVS TPVTQGGTVK VLTQGINTPP
VLVHNQLVLT PSIVTTNKKL ADPVTLKIET KVLQPANLGS TLTPHHPPAL PSKLPTEVNH
VPSGPSIPAD RTVSHLAAAK LDAHSPRPSG PGPSSFPRAS HPSSTASTAL STNATVMLAA
GIPVPQFISS IHPEQSVIMP PHSITQTVSL SHLSQGEVRM NTPTLPSITY SIRPEALHSP
RAPLQPQQIE VRAPQRASTP QPAPAGVPAL ASQHPPEEEV HYHLPVARAT APVQSEVLVM
QSEYRLHPYT VPRDVRIMVH PHVTAVSEQP RAADGVVKVP PASKAPQQPG KEAAKTPDAK
AAPTPTPAPV PVPVPLPAPA PAPHGEARIL TVTPSNQLQG LPLTPPVVVT HGVQIVHSSG
ELFQEYRYGD IRTYHPPAQL THTQFPAASS VGLPSRTKTA AQGPPPEGEP LQPPQPVQST
QPAQPAPPCP PSQLGQPGQP PSSKMPQVSQ EAKGTQTGVE QPRLPAGPAN RPPEPHTQVQ
RAQAETGPTS FPSPVSVSMK PDLPVSLPTQ TAPKQPLFVP TTSGPSTPPG LVLPHTEFQP
APKQDSSPHL TSQRPVDMVQ LLKKYPIVWQ GLLALKNDTA AVQLHFVSGN NVLAHRSLPL
SEGGPPLRIA QRMRLEATQL EGVARRMTVE TDYCLLLALP CGRDQEDVVS QTESLKAAFI
TYLQAKQAAG IINVPNPGSN QPAYVLQIFP PCEFSESHLS RLAPDLLASI SNISPHLMIV
IASV
