CNOT1_HUMAN
ID CNOT1_HUMAN Reviewed; 2376 AA.
AC A5YKK6; Q68DX7; Q7Z3K2; Q8IWB8; Q8TB53; Q9BVZ6; Q9UFR8; Q9UI27; Q9Y2L0;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 15-JAN-2008, sequence version 2.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=CCR4-NOT transcription complex subunit 1;
DE AltName: Full=CCR4-associated factor 1;
DE AltName: Full=Negative regulator of transcription subunit 1 homolog;
DE Short=NOT1H;
DE Short=hNOT1;
GN Name=CNOT1; Synonyms=CDC39, KIAA1007, NOT1; ORFNames=AD-005;
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 2 AND 3), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 244-2376 (ISOFORM 1).
RC TISSUE=Cervix, Fetal kidney, and Testis;
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=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 757-2376 (ISOFORM 1), AND VARIANT ALA-603.
RC TISSUE=Choriocarcinoma, Leiomyosarcoma, and 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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 537-2376 (ISOFORM 2).
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 [5]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1964-2374 (ISOFORM 1).
RC TISSUE=Adrenal gland;
RX PubMed=10931946; DOI=10.1073/pnas.160270997;
RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X.,
RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W.,
RA Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J., Xu S.-H., Gu J.,
RA Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z.,
RA Chen M.-D., Chen J.-L.;
RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis
RT and full-length cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000).
RN [7]
RP FUNCTION, INTERACTION WITH CNOT2; CNOT4 AND CNOT8, AND TISSUE SPECIFICITY.
RX PubMed=10637334; DOI=10.1093/nar/28.3.809;
RA Albert T.K., Lemaire M., van Berkum N.L., Gentz R., Collart M.A.,
RA Timmers H.T.M.;
RT "Isolation and characterization of human orthologs of yeast CCR4-NOT
RT complex subunits.";
RL Nucleic Acids Res. 28:809-817(2000).
RN [8]
RP FUNCTION, DOMAIN, AND INTERACTION WITH CNOT2; CNOT3; CNOT8; ESR1 AND RXRA.
RX PubMed=16778766; DOI=10.1038/sj.emboj.7601194;
RA Winkler G.S., Mulder K.W., Bardwell V.J., Kalkhoven E., Timmers H.T.;
RT "Human Ccr4-Not complex is a ligand-dependent repressor of nuclear
RT receptor-mediated transcription.";
RL EMBO J. 25:3089-3099(2006).
RN [9]
RP INTERACTION WITH TOB1.
RX PubMed=18377426; DOI=10.1111/j.1349-7006.2008.00746.x;
RA Miyasaka T., Morita M., Ito K., Suzuki T., Fukuda H., Takeda S., Inoue J.,
RA Semba K., Yamamoto T.;
RT "Interaction of antiproliferative protein Tob with the CCR4-NOT deadenylase
RT complex.";
RL Cancer Sci. 99:755-761(2008).
RN [10]
RP IDENTIFICATION IN THE CCR4-NOT COMPLEX, AND COMPOSITION OF THE CCR4-NOT
RP COMPLEX.
RX PubMed=19558367; DOI=10.1042/bj20090500;
RA Lau N.C., Kolkman A., van Schaik F.M., Mulder K.W., Pijnappel W.W.,
RA Heck A.J., Timmers H.T.;
RT "Human Ccr4-Not complexes contain variable deadenylase subunits.";
RL Biochem. J. 422:443-453(2009).
RN [11]
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 [12]
RP INTERACTION WITH TNRC6A; TNRC6B AND TNRC6C.
RX PubMed=21981923; DOI=10.1016/j.molcel.2011.09.007;
RA Braun J.E., Huntzinger E., Fauser M., Izaurralde E.;
RT "GW182 proteins directly recruit cytoplasmic deadenylase complexes to miRNA
RT targets.";
RL Mol. Cell 44:120-133(2011).
RN [13]
RP FUNCTION, AND INTERACTION WITH TNRC6C.
RX PubMed=21984185; DOI=10.1038/nsmb.2149;
RA Fabian M.R., Cieplak M.K., Frank F., Morita M., Green J., Srikumar T.,
RA Nagar B., Yamamoto T., Raught B., Duchaine T.F., Sonenberg N.;
RT "miRNA-mediated deadenylation is orchestrated by GW182 through two
RT conserved motifs that interact with CCR4-NOT.";
RL Nat. Struct. Mol. Biol. 18:1211-1217(2011).
RN [14]
RP FUNCTION, AND INTERACTION WITH ZFP36.
RX PubMed=21278420; DOI=10.1093/nar/gkr011;
RA Sandler H., Kreth J., Timmers H.T., Stoecklin G.;
RT "Not1 mediates recruitment of the deadenylase Caf1 to mRNAs targeted for
RT degradation by tristetraprolin.";
RL Nucleic Acids Res. 39:4373-4386(2011).
RN [15]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=21976065; DOI=10.1007/s13238-011-1092-4;
RA Ito K., Takahashi A., Morita M., Suzuki T., Yamamoto T.;
RT "The role of the CNOT1 subunit of the CCR4-NOT complex in mRNA
RT deadenylation and cell viability.";
RL Protein Cell 2:755-763(2011).
RN [16]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=22367759; DOI=10.1002/stem.1070;
RA Zheng X., Dumitru R., Lackford B.L., Freudenberg J.M., Singh A.P.,
RA Archer T.K., Jothi R., Hu G.;
RT "Cnot1, Cnot2, and Cnot3 maintain mouse and human ESC identity and inhibit
RT extraembryonic differentiation.";
RL Stem Cells 30:910-922(2012).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-318 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 [18]
RP INTERACTION WITH EIF4ENIF1.
RX PubMed=26027925; DOI=10.1016/j.celrep.2015.04.065;
RA Nishimura T., Padamsi Z., Fakim H., Milette S., Dunham W.H., Gingras A.C.,
RA Fabian M.R.;
RT "The eIF4E-Binding protein 4E-T is a component of the mRNA decay machinery
RT that bridges the 5' and 3' termini of target mRNAs.";
RL Cell Rep. 11:1425-1436(2015).
RN [19]
RP FUNCTION, AND INTERACTION WITH YTHDF2.
RX PubMed=27558897; DOI=10.1038/ncomms12626;
RA Du H., Zhao Y., He J., Zhang Y., Xi H., Liu M., Ma J., Wu L.;
RT "YTHDF2 destabilizes m(6)A-containing RNA through direct recruitment of the
RT CCR4-NOT deadenylase complex.";
RL Nat. Commun. 7:12626-12626(2016).
RN [20]
RP INTERACTION WITH EIF4ENIF1.
RX PubMed=27342281; DOI=10.1093/nar/gkw565;
RA Kamenska A., Simpson C., Vindry C., Broomhead H., Benard M.,
RA Ernoult-Lange M., Lee B.P., Harries L.W., Weil D., Standart N.;
RT "The DDX6-4E-T interaction mediates translational repression and P-body
RT assembly.";
RL Nucleic Acids Res. 44:6318-6334(2016).
RN [21]
RP FUNCTION, AND INTERACTION WITH EIF4ENIF1.
RX PubMed=32354837; DOI=10.1101/gad.336073.119;
RA Raesch F., Weber R., Izaurralde E., Igreja C.;
RT "4E-T-bound mRNAs are stored in a silenced and deadenylated form.";
RL Genes Dev. 34:847-860(2020).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 1093-1317 IN COMPLEX WITH CNOT7,
RP INTERACTION WITH CNOT8; CNOT6 AND CNOT6L, AND MUTAGENESIS OF LYS-1208;
RP HIS-1212 AND LYS-1218.
RX PubMed=22977175; DOI=10.1093/nar/gks883;
RA Petit A.P., Wohlbold L., Bawankar P., Huntzinger E., Schmidt S.,
RA Izaurralde E., Weichenrieder O.;
RT "The structural basis for the interaction between the CAF1 nuclease and the
RT NOT1 scaffold of the human CCR4-NOT deadenylase complex.";
RL Nucleic Acids Res. 40:11058-11072(2012).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 800-1004 IN COMPLEX WITH ZFP36,
RP INTERACTION WITH ZFP36, AND FUNCTION.
RX PubMed=23644599; DOI=10.1038/nsmb.2572;
RA Fabian M.R., Frank F., Rouya C., Siddiqui N., Lai W.S., Karetnikov A.,
RA Blackshear P.J., Nagar B., Sonenberg N.;
RT "Structural basis for the recruitment of the human CCR4-NOT deadenylase
RT complex by tristetraprolin.";
RL Nat. Struct. Mol. Biol. 20:735-739(2013).
RN [24] {ECO:0007744|PDB:5ANR}
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 1063-1314 IN COMPLEX WITH
RP EIF4ENIF1 AND DDX6, AND INTERACTION WITH EIF4ENIF1.
RX PubMed=26489469; DOI=10.1016/j.celrep.2015.09.033;
RA Ozgur S., Basquin J., Kamenska A., Filipowicz W., Standart N., Conti E.;
RT "Structure of a human 4E-T/DDX6/CNOT1 complex reveals the different
RT interplay of DDX6-binding proteins with the CCR4-NOT complex.";
RL Cell Rep. 13:703-711(2015).
RN [25]
RP VARIANT HPE12 CYS-535, AND INVOLVEMENT IN HPE12.
RX PubMed=31006513; DOI=10.1016/j.ajhg.2019.03.018;
RA De Franco E., Watson R.A., Weninger W.J., Wong C.C., Flanagan S.E.,
RA Caswell R., Green A., Tudor C., Lelliott C.J., Geyer S.H., Maurer-Gesek B.,
RA Reissig L.F., Lango Allen H., Caliebe A., Siebert R., Holterhus P.M.,
RA Deeb A., Prin F., Hilbrands R., Heimberg H., Ellard S., Hattersley A.T.,
RA Barroso I.;
RT "A specific CNOT1 mutation results in a novel syndrome of pancreatic
RT agenesis and holoprosencephaly through impaired pancreatic and neurological
RT development.";
RL Am. J. Hum. Genet. 104:985-989(2019).
RN [26]
RP VARIANT HPE12 CYS-535, AND INVOLVEMENT IN HPE12.
RX PubMed=31006510; DOI=10.1016/j.ajhg.2019.03.017;
RA Kruszka P., Berger S.I., Weiss K., Everson J.L., Martinez A.F., Hong S.,
RA Anyane-Yeboa K., Lipinski R.J., Muenke M.;
RT "A CCR4-NOT transcription complex, subunit 1, CNOT1, variant associated
RT with holoprosencephaly.";
RL Am. J. Hum. Genet. 104:990-993(2019).
RN [27]
RP VARIANTS VIBOS 26-ARG--SER-2376 DEL; 33-GLN--SER-2376 DEL;
RP 396-TYR--SER-2376 DEL; GLU-642; LYS-897; CYS-900; ILE-1038; LEU-1089;
RP PRO-1148; GLY-1188; ARG-1241; ALA-1419; SER-1428; CYS-1478; HIS-1494;
RP ASP-1572 AND SER-2216, AND INVOLVEMENT IN VIBOS.
RX PubMed=32553196; DOI=10.1016/j.ajhg.2020.05.017;
RG DDD Study;
RA Vissers L.E.L.M., Kalvakuri S., de Boer E., Geuer S., Oud M.,
RA van Outersterp I., Kwint M., Witmond M., Kersten S., Polla D.L.,
RA Weijers D., Begtrup A., McWalter K., Ruiz A., Gabau E., Morton J.E.V.,
RA Griffith C., Weiss K., Gamble C., Bartley J., Vernon H.J., Brunet K.,
RA Ruivenkamp C., Kant S.G., Kruszka P., Larson A., Afenjar A.,
RA Billette de Villemeur T., Nugent K., Raymond F.L., Venselaar H.,
RA Demurger F., Soler-Alfonso C., Li D., Bhoj E., Hayes I., Hamilton N.P.,
RA Ahmad A., Fisher R., van den Born M., Willems M., Sorlin A., Delanne J.,
RA Moutton S., Christophe P., Mau-Them F.T., Vitobello A., Goel H.,
RA Massingham L., Phornphutkul C., Schwab J., Keren B., Charles P.,
RA Vreeburg M., De Simone L., Hoganson G., Iascone M., Milani D.,
RA Evenepoel L., Revencu N., Ward D.I., Burns K., Krantz I., Raible S.E.,
RA Murrell J.R., Wood K., Cho M.T., van Bokhoven H., Muenke M., Kleefstra T.,
RA Bodmer R., de Brouwer A.P.M.;
RT "De Novo Variants in CNOT1, a Central Component of the CCR4-NOT Complex
RT Involved in Gene Expression and RNA and Protein Stability, Cause
RT Neurodevelopmental Delay.";
RL Am. J. Hum. Genet. 107:164-172(2020).
CC -!- FUNCTION: Scaffolding component of the CCR4-NOT complex which is one of
CC the major cellular mRNA deadenylases and is linked to various cellular
CC processes including bulk mRNA degradation, miRNA-mediated repression,
CC translational repression during translational initiation and general
CC transcription regulation. Additional complex functions may be a
CC consequence of its influence on mRNA expression. Its scaffolding
CC function implies its interaction with the catalytic complex module and
CC diverse RNA-binding proteins mediating the complex recruitment to
CC selected mRNA 3'UTRs. Involved in degradation of AU-rich element (ARE)-
CC containing mRNAs probably via association with ZFP36. Mediates the
CC recruitment of the CCR4-NOT complex to miRNA targets and to the RISC
CC complex via association with TNRC6A, TNRC6B or TNRC6C. Acts as a
CC transcriptional repressor. Represses the ligand-dependent
CC transcriptional activation by nuclear receptors. Involved in the
CC maintenance of embryonic stem (ES) cell identity.
CC {ECO:0000269|PubMed:10637334, ECO:0000269|PubMed:16778766,
CC ECO:0000269|PubMed:21278420, ECO:0000269|PubMed:21976065,
CC ECO:0000269|PubMed:21984185, ECO:0000269|PubMed:22367759,
CC ECO:0000269|PubMed:23644599, ECO:0000269|PubMed:27558897,
CC ECO:0000269|PubMed:32354837}.
CC -!- SUBUNIT: Component of the CCR4-NOT complex; distinct complexes seem to
CC exist that differ in the participation of probably mutually exclusive
CC catalytic subunits (PubMed:10637334, PubMed:16778766, PubMed:19558367,
CC PubMed:22977175). In the complex, interacts directly with CNOT6,
CC CNOT6L, CNOT7 or CNOT8 (PubMed:10637334, PubMed:16778766,
CC PubMed:22977175). Interacts in a ligand-dependent fashion with ESR1 and
CC RXRA (PubMed:16778766). Interacts with NANOS2, TOB1 and ZFP36
CC (PubMed:18377426, PubMed:21278420, PubMed:23644599). Interacts with
CC TNRC6A, TNRC6B or TNRC6C; the interactions are direct (PubMed:21981923,
CC PubMed:21984185). Interacts with YTHDF2; the interaction is direct and
CC promotes recruitment of the CCR4-NOT complex to N6-methyladenosine
CC (m6A)-containing mRNAs, leading to their deadenylation and subsequent
CC degradation (PubMed:27558897). Interacts with EIF4ENIF1/4E-T
CC (PubMed:26027925, PubMed:27342281, PubMed:32354837, PubMed:26489469).
CC {ECO:0000269|PubMed:10637334, ECO:0000269|PubMed:16778766,
CC ECO:0000269|PubMed:18377426, ECO:0000269|PubMed:19558367,
CC ECO:0000269|PubMed:21278420, ECO:0000269|PubMed:21981923,
CC ECO:0000269|PubMed:21984185, ECO:0000269|PubMed:22977175,
CC ECO:0000269|PubMed:23644599, ECO:0000269|PubMed:26027925,
CC ECO:0000269|PubMed:26489469, ECO:0000269|PubMed:27342281,
CC ECO:0000269|PubMed:27558897, ECO:0000269|PubMed:32354837}.
CC -!- INTERACTION:
CC A5YKK6; Q3ZCQ2: ANXA2R; NbExp=3; IntAct=EBI-1222758, EBI-21258284;
CC A5YKK6; Q9UKZ1: CNOT11; NbExp=4; IntAct=EBI-1222758, EBI-2562014;
CC A5YKK6; Q9NZN8: CNOT2; NbExp=5; IntAct=EBI-1222758, EBI-743033;
CC A5YKK6; O75175: CNOT3; NbExp=2; IntAct=EBI-1222758, EBI-743073;
CC A5YKK6; Q9ULM6: CNOT6; NbExp=3; IntAct=EBI-1222758, EBI-2104530;
CC A5YKK6; Q96LI5: CNOT6L; NbExp=4; IntAct=EBI-1222758, EBI-1046635;
CC A5YKK6; Q9UIV1: CNOT7; NbExp=7; IntAct=EBI-1222758, EBI-2105113;
CC A5YKK6; Q9UFF9: CNOT8; NbExp=6; IntAct=EBI-1222758, EBI-742299;
CC A5YKK6; Q86TB9: PATL1; NbExp=3; IntAct=EBI-1222758, EBI-2562092;
CC A5YKK6; Q8NDV7: TNRC6A; NbExp=2; IntAct=EBI-1222758, EBI-2269715;
CC A5YKK6; Q9UPQ9: TNRC6B; NbExp=4; IntAct=EBI-1222758, EBI-947158;
CC A5YKK6; Q9HCJ0: TNRC6C; NbExp=16; IntAct=EBI-1222758, EBI-6507625;
CC A5YKK6; P50616: TOB1; NbExp=4; IntAct=EBI-1222758, EBI-723281;
CC A5YKK6; P22893: Zfp36; Xeno; NbExp=5; IntAct=EBI-1222758, EBI-647803;
CC A5YKK6-2; P26651: ZFP36; NbExp=4; IntAct=EBI-16057352, EBI-374248;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, P-body {ECO:0000269|PubMed:21976065}.
CC Nucleus {ECO:0000305|PubMed:21976065}. Note=NANOS2 promotes its
CC localization to P-body. {ECO:0000250|UniProtKB:Q6ZQ08}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=A5YKK6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A5YKK6-2; Sequence=VSP_030559;
CC Name=3;
CC IsoId=A5YKK6-3; Sequence=VSP_030559, VSP_030562, VSP_030563;
CC Name=4;
CC IsoId=A5YKK6-4; Sequence=VSP_030560, VSP_030561;
CC -!- TISSUE SPECIFICITY: Strongly expressed in brain, heart, thymus, spleen,
CC kidney, liver, placenta and lung. Weakly expressed in skeletal muscle
CC and colon. {ECO:0000269|PubMed:10637334}.
CC -!- DEVELOPMENTAL STAGE: Expressed in embryonic stem (ES) cells.
CC {ECO:0000269|PubMed:22367759}.
CC -!- DOMAIN: Contains Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs, a motif known to
CC be important for the association with nuclear receptors.
CC {ECO:0000269|PubMed:16778766}.
CC -!- DISEASE: Holoprosencephaly 12 with or without pancreatic agenesis
CC (HPE12) [MIM:618500]: An autosomal dominant form of holoprosencephaly,
CC a structural anomaly of the brain in which the developing forebrain
CC fails to correctly separate into right and left hemispheres.
CC Holoprosencephaly is genetically heterogeneous and associated with
CC several distinct facies and phenotypic variability. HPE12 clinical
CC features include abnormal forebrain development, dysmorphic features,
CC global developmental delay, learning difficulties, and congenital
CC absence of the pancreas in most patients, resulting in early-onset
CC insulin-dependent diabetes mellitus. Other features may include hearing
CC loss and absence of the gallbladder. {ECO:0000269|PubMed:31006510,
CC ECO:0000269|PubMed:31006513}. Note=The disease may be caused by
CC variants affecting the gene represented in this entry.
CC -!- DISEASE: Vissers-Bodmer syndrome (VIBOS) [MIM:619033]: An autosomal
CC dominant disorder characterized by global developmental delay,
CC intellectual disability of varying degree, speech delay, motor delay,
CC and hypotonia. Abnormal growth, and cerebral, skeletal, muscle and soft
CC tissue abnormalities are frequently observed. Many patients have
CC behavioral problems, including anxiety, obsessive compulsive disorder,
CC autism spectrum disorder and attention-deficit hyperactivity disorder.
CC {ECO:0000269|PubMed:32553196}. Note=The disease may be caused by
CC variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the CNOT1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF14861.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CAH18093.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AL117492; CAB55960.1; -; mRNA.
DR EMBL; BX537840; CAD97851.1; -; mRNA.
DR EMBL; CR749237; CAH18093.1; ALT_INIT; mRNA.
DR EMBL; EF553522; ABQ66268.1; -; mRNA.
DR EMBL; AC009118; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC010287; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC000779; AAH00779.2; -; mRNA.
DR EMBL; BC024317; AAH24317.1; -; mRNA.
DR EMBL; BC040523; AAH40523.1; -; mRNA.
DR EMBL; AB023224; BAA76851.2; -; mRNA.
DR EMBL; AF110778; AAF14861.1; ALT_FRAME; mRNA.
DR CCDS; CCDS10799.1; -. [A5YKK6-1]
DR CCDS; CCDS45501.1; -. [A5YKK6-4]
DR CCDS; CCDS58468.1; -. [A5YKK6-2]
DR PIR; T17270; T17270.
DR RefSeq; NP_001252541.1; NM_001265612.1. [A5YKK6-2]
DR RefSeq; NP_057368.3; NM_016284.4. [A5YKK6-1]
DR RefSeq; NP_996882.1; NM_206999.2. [A5YKK6-4]
DR PDB; 4C0D; X-ray; 3.20 A; A=1565-2371.
DR PDB; 4CQO; X-ray; 2.80 A; A/C=1833-2361.
DR PDB; 4CRU; X-ray; 1.65 A; A=1356-1607.
DR PDB; 4CRV; X-ray; 2.05 A; A=1356-1607.
DR PDB; 4CRW; X-ray; 1.75 A; A=1093-1317.
DR PDB; 4CT4; X-ray; 2.30 A; A/C=1063-1314.
DR PDB; 4CT6; X-ray; 2.10 A; A=1352-1594.
DR PDB; 4CT7; X-ray; 1.90 A; A=1352-1594.
DR PDB; 4GMJ; X-ray; 2.70 A; A/C/E=1093-1317.
DR PDB; 4GML; X-ray; 2.90 A; A/B/C/D/E/F=1093-1317.
DR PDB; 4J8S; X-ray; 1.55 A; A=800-1004.
DR PDB; 5ANR; X-ray; 2.10 A; A=1063-1314.
DR PDB; 5FU6; X-ray; 2.90 A; A/D=1833-2361.
DR PDB; 5FU7; X-ray; 3.10 A; A/E=1833-2361.
DR PDB; 5ONA; X-ray; 2.70 A; A/D=1351-1588.
DR PDBsum; 4C0D; -.
DR PDBsum; 4CQO; -.
DR PDBsum; 4CRU; -.
DR PDBsum; 4CRV; -.
DR PDBsum; 4CRW; -.
DR PDBsum; 4CT4; -.
DR PDBsum; 4CT6; -.
DR PDBsum; 4CT7; -.
DR PDBsum; 4GMJ; -.
DR PDBsum; 4GML; -.
DR PDBsum; 4J8S; -.
DR PDBsum; 5ANR; -.
DR PDBsum; 5FU6; -.
DR PDBsum; 5FU7; -.
DR PDBsum; 5ONA; -.
DR AlphaFoldDB; A5YKK6; -.
DR SMR; A5YKK6; -.
DR BioGRID; 116660; 236.
DR ComplexPortal; CPX-2522; CCR4-NOT mRNA deadenylase complex, CNOT6L-CNOT7 variant.
DR ComplexPortal; CPX-2535; CCR4-NOT mRNA deadenylase complex, CNOT6L-CNOT8 variant.
DR ComplexPortal; CPX-2849; CCR4-NOT mRNA deadenylase complex, CNOT6-CNOT8 variant.
DR ComplexPortal; CPX-707; CCR4-NOT mRNA deadenylase complex, CNOT6-CNOT7 variant.
DR CORUM; A5YKK6; -.
DR DIP; DIP-44954N; -.
DR ELM; A5YKK6; -.
DR IntAct; A5YKK6; 118.
DR MINT; A5YKK6; -.
DR STRING; 9606.ENSP00000320949; -.
DR ChEMBL; CHEMBL4105919; -.
DR CarbonylDB; A5YKK6; -.
DR GlyGen; A5YKK6; 15 sites, 2 O-linked glycans (15 sites).
DR iPTMnet; A5YKK6; -.
DR MetOSite; A5YKK6; -.
DR PhosphoSitePlus; A5YKK6; -.
DR SwissPalm; A5YKK6; -.
DR BioMuta; CNOT1; -.
DR EPD; A5YKK6; -.
DR jPOST; A5YKK6; -.
DR MassIVE; A5YKK6; -.
DR MaxQB; A5YKK6; -.
DR PaxDb; A5YKK6; -.
DR PeptideAtlas; A5YKK6; -.
DR PRIDE; A5YKK6; -.
DR ProteomicsDB; 759; -. [A5YKK6-1]
DR ProteomicsDB; 760; -. [A5YKK6-2]
DR ProteomicsDB; 761; -. [A5YKK6-3]
DR ProteomicsDB; 762; -. [A5YKK6-4]
DR Antibodypedia; 29121; 99 antibodies from 21 providers.
DR DNASU; 23019; -.
DR Ensembl; ENST00000317147.10; ENSP00000320949.5; ENSG00000125107.19. [A5YKK6-1]
DR Ensembl; ENST00000441024.6; ENSP00000413113.2; ENSG00000125107.19. [A5YKK6-4]
DR Ensembl; ENST00000567188.5; ENSP00000456649.1; ENSG00000125107.19. [A5YKK6-3]
DR Ensembl; ENST00000569240.5; ENSP00000455635.1; ENSG00000125107.19. [A5YKK6-2]
DR GeneID; 23019; -.
DR KEGG; hsa:23019; -.
DR MANE-Select; ENST00000317147.10; ENSP00000320949.5; NM_016284.5; NP_057368.3.
DR UCSC; uc002enu.6; human. [A5YKK6-1]
DR CTD; 23019; -.
DR DisGeNET; 23019; -.
DR GeneCards; CNOT1; -.
DR HGNC; HGNC:7877; CNOT1.
DR HPA; ENSG00000125107; Low tissue specificity.
DR MalaCards; CNOT1; -.
DR MIM; 604917; gene.
DR MIM; 618500; phenotype.
DR MIM; 619033; phenotype.
DR neXtProt; NX_A5YKK6; -.
DR OpenTargets; ENSG00000125107; -.
DR Orphanet; 556955; Pancreatic agenesis-holoprosencephaly syndrome.
DR PharmGKB; PA26672; -.
DR VEuPathDB; HostDB:ENSG00000125107; -.
DR eggNOG; KOG1831; Eukaryota.
DR GeneTree; ENSGT00390000014869; -.
DR HOGENOM; CLU_000286_3_0_1; -.
DR InParanoid; A5YKK6; -.
DR OMA; IDEYHCY; -.
DR OrthoDB; 42530at2759; -.
DR PhylomeDB; A5YKK6; -.
DR TreeFam; TF105630; -.
DR PathwayCommons; A5YKK6; -.
DR Reactome; R-HSA-429947; Deadenylation of mRNA.
DR Reactome; R-HSA-6804115; TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain.
DR SignaLink; A5YKK6; -.
DR SIGNOR; A5YKK6; -.
DR BioGRID-ORCS; 23019; 525 hits in 1095 CRISPR screens.
DR ChiTaRS; CNOT1; human.
DR GeneWiki; CNOT1; -.
DR GenomeRNAi; 23019; -.
DR Pharos; A5YKK6; Tbio.
DR PRO; PR:A5YKK6; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; A5YKK6; protein.
DR Bgee; ENSG00000125107; Expressed in left testis and 202 other tissues.
DR ExpressionAtlas; A5YKK6; baseline and differential.
DR Genevisible; A5YKK6; HS.
DR GO; GO:0030014; C:CCR4-NOT complex; IDA:UniProtKB.
DR GO; GO:0030015; C:CCR4-NOT core complex; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0000932; C:P-body; IDA:UniProtKB.
DR GO; GO:0005778; C:peroxisomal membrane; HDA:UniProtKB.
DR GO; GO:0070016; F:armadillo repeat domain binding; IPI:BHF-UCL.
DR GO; GO:0060090; F:molecular adaptor activity; IDA:BHF-UCL.
DR GO; GO:0030331; F:nuclear estrogen receptor binding; IDA:UniProtKB.
DR GO; GO:0042974; F:nuclear retinoic acid receptor binding; IDA:UniProtKB.
DR GO; GO:0019904; F:protein domain specific binding; IPI:BHF-UCL.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0035195; P:miRNA-mediated gene silencing; IDA:BHF-UCL.
DR GO; GO:0033147; P:negative regulation of intracellular estrogen receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0048387; P:negative regulation of retinoic acid receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0017148; P:negative regulation of translation; IDA:BHF-UCL.
DR GO; GO:0000288; P:nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay; IBA:GO_Central.
DR GO; GO:0000289; P:nuclear-transcribed mRNA poly(A) tail shortening; IC:ComplexPortal.
DR GO; GO:0010606; P:positive regulation of cytoplasmic mRNA processing body assembly; IDA:UniProtKB.
DR GO; GO:0061014; P:positive regulation of mRNA catabolic process; IMP:BHF-UCL.
DR GO; GO:1900153; P:positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay; IMP:UniProtKB.
DR GO; GO:0060213; P:positive regulation of nuclear-transcribed mRNA poly(A) tail shortening; IDA:BHF-UCL.
DR GO; GO:2000036; P:regulation of stem cell population maintenance; IMP:UniProtKB.
DR GO; GO:0090503; P:RNA phosphodiester bond hydrolysis, exonucleolytic; IEA:GOC.
DR GO; GO:0001829; P:trophectodermal cell differentiation; IEA:Ensembl.
DR DisProt; DP02524; -.
DR Gene3D; 1.25.40.840; -; 1.
DR IDEAL; IID00423; -.
DR InterPro; IPR007196; CCR4-Not_Not1_C.
DR InterPro; IPR032191; CNOT1_CAF1_bind.
DR InterPro; IPR024557; CNOT1_dom_4.
DR InterPro; IPR032194; CNOT1_HEAT.
DR InterPro; IPR032193; CNOT1_TTP_bind.
DR InterPro; IPR038535; CNOT1_TTP_bind_sf.
DR InterPro; IPR040398; Not1.
DR PANTHER; PTHR13162; PTHR13162; 1.
DR Pfam; PF16415; CNOT1_CAF1_bind; 1.
DR Pfam; PF16418; CNOT1_HEAT; 1.
DR Pfam; PF16417; CNOT1_TTP_bind; 1.
DR Pfam; PF12842; DUF3819; 1.
DR Pfam; PF04054; Not1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Autism spectrum disorder; Cytoplasm;
KW Developmental protein; Disease variant; Holoprosencephaly;
KW Intellectual disability; Nucleus; Phosphoprotein; Reference proteome;
KW Repressor; RNA-mediated gene silencing; Transcription;
KW Transcription regulation; Translation regulation.
FT CHAIN 1..2376
FT /note="CCR4-NOT transcription complex subunit 1"
FT /id="PRO_0000315541"
FT REGION 720..768
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 800..1015
FT /note="Interaction with ZFP36"
FT REGION 1090..1605
FT /note="Interaction with CNOT6, CNOT6L, CNOT7 and CNOT8"
FT /evidence="ECO:0000269|PubMed:22977175"
FT REGION 1315..1352
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 153..157
FT /note="LXXLL"
FT MOTIF 181..185
FT /note="LXXLL"
FT MOTIF 223..227
FT /note="LXXLL"
FT MOTIF 570..574
FT /note="LXXLL"
FT MOTIF 1639..1643
FT /note="LXXLL"
FT MOTIF 1942..1946
FT /note="LXXLL"
FT MOTIF 2096..2100
FT /note="LXXLL"
FT COMPBIAS 723..768
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1329..1352
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 318
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1061
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 822..827
FT /note="SKMKPS -> T (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:10231032,
FT ECO:0000303|PubMed:17974005"
FT /id="VSP_030559"
FT VAR_SEQ 1479..1551
FT /note="TASPQQREMMDQAAAQLAQDNCELACCFIQKTAVEKAGPEMDKRLATEFELR
FT KHARQEGRRYCDPVVLTYQAE -> VSWLFPWYRYKTYYCLSVIIFFFVYIWHWALPLI
FT LNNHHICLMSSIILDCNSVRQSIMSVCFFFFLLYSQHDV (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_030560"
FT VAR_SEQ 1552..2376
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_030561"
FT VAR_SEQ 2152..2155
FT /note="VDML -> SLTL (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_030562"
FT VAR_SEQ 2156..2376
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_030563"
FT VARIANT 26..2376
FT /note="Missing (in VIBOS)"
FT /evidence="ECO:0000269|PubMed:32553196"
FT /id="VAR_084311"
FT VARIANT 33..2376
FT /note="Missing (in VIBOS)"
FT /evidence="ECO:0000269|PubMed:32553196"
FT /id="VAR_084312"
FT VARIANT 396..2376
FT /note="Missing (in VIBOS; dbSNP:rs1567420855)"
FT /evidence="ECO:0000269|PubMed:32553196"
FT /id="VAR_084313"
FT VARIANT 535
FT /note="R -> C (in HPE12; dbSNP:rs1567417422)"
FT /evidence="ECO:0000269|PubMed:31006513"
FT /id="VAR_083066"
FT VARIANT 603
FT /note="D -> A (in dbSNP:rs17854028)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_038254"
FT VARIANT 642
FT /note="Q -> E (in VIBOS; uncertain pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:32553196"
FT /id="VAR_084314"
FT VARIANT 897
FT /note="E -> K (in VIBOS)"
FT /evidence="ECO:0000269|PubMed:32553196"
FT /id="VAR_084315"
FT VARIANT 900
FT /note="R -> C (in VIBOS)"
FT /evidence="ECO:0000269|PubMed:32553196"
FT /id="VAR_084316"
FT VARIANT 1038
FT /note="T -> I (in VIBOS; uncertain pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:32553196"
FT /id="VAR_084317"
FT VARIANT 1089
FT /note="V -> L (in VIBOS; uncertain pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:32553196"
FT /id="VAR_084318"
FT VARIANT 1148
FT /note="L -> P (in VIBOS)"
FT /evidence="ECO:0000269|PubMed:32553196"
FT /id="VAR_084319"
FT VARIANT 1188
FT /note="D -> G (in VIBOS)"
FT /evidence="ECO:0000269|PubMed:32553196"
FT /id="VAR_084320"
FT VARIANT 1241
FT /note="K -> R (in VIBOS)"
FT /evidence="ECO:0000269|PubMed:32553196"
FT /id="VAR_084321"
FT VARIANT 1419
FT /note="T -> A (in VIBOS; dbSNP:rs1038725612)"
FT /evidence="ECO:0000269|PubMed:32553196"
FT /id="VAR_084322"
FT VARIANT 1428
FT /note="F -> S (in VIBOS)"
FT /evidence="ECO:0000269|PubMed:32553196"
FT /id="VAR_084323"
FT VARIANT 1478
FT /note="R -> C (in VIBOS; dbSNP:rs1567396193)"
FT /evidence="ECO:0000269|PubMed:32553196"
FT /id="VAR_084324"
FT VARIANT 1494
FT /note="Q -> H (in VIBOS)"
FT /evidence="ECO:0000269|PubMed:32553196"
FT /id="VAR_084325"
FT VARIANT 1572
FT /note="Y -> D (in VIBOS)"
FT /evidence="ECO:0000269|PubMed:32553196"
FT /id="VAR_084326"
FT VARIANT 2216
FT /note="N -> S (in VIBOS; dbSNP:rs1184460054)"
FT /evidence="ECO:0000269|PubMed:32553196"
FT /id="VAR_084327"
FT MUTAGEN 1208
FT /note="K->E: Impairs interaction with CNOT7; when
FT associated with Y-1212 and E-1218."
FT /evidence="ECO:0000269|PubMed:22977175"
FT MUTAGEN 1209
FT /note="P->Y: Abolishes interaction with CNOT7; when
FT associated with Y-1257."
FT MUTAGEN 1212
FT /note="H->Y: Impairs interaction with CNOT7; when
FT associated with E-1208 and E-1218."
FT /evidence="ECO:0000269|PubMed:22977175"
FT MUTAGEN 1218
FT /note="K->E: Impairs interaction with CNOT7; when
FT associated with E-1208 and Y-1212."
FT /evidence="ECO:0000269|PubMed:22977175"
FT MUTAGEN 1251
FT /note="V->R: Abolishes interaction with CNOT7."
FT MUTAGEN 1257
FT /note="P->Y: Abolishes interaction with CNOT7; when
FT associated with Y-1209."
FT CONFLICT 18
FT /note="D -> G (in Ref. 1; CAD97851)"
FT /evidence="ECO:0000305"
FT CONFLICT 323
FT /note="D -> G (in Ref. 1; CAD97851)"
FT /evidence="ECO:0000305"
FT CONFLICT 922
FT /note="E -> G (in Ref. 1; ABQ66268)"
FT /evidence="ECO:0000305"
FT CONFLICT 1063
FT /note="K -> R (in Ref. 1; CAH18093)"
FT /evidence="ECO:0000305"
FT CONFLICT 1417
FT /note="M -> V (in Ref. 1; CAD97851)"
FT /evidence="ECO:0000305"
FT CONFLICT 1799
FT /note="R -> G (in Ref. 1; CAD97851)"
FT /evidence="ECO:0000305"
FT CONFLICT 1936
FT /note="L -> P (in Ref. 1; CAH18093)"
FT /evidence="ECO:0000305"
FT CONFLICT 2198..2200
FT /note="SNL -> RTV (in Ref. 6; AAF14861)"
FT /evidence="ECO:0000305"
FT CONFLICT 2358
FT /note="Q -> R (in Ref. 1; ABQ66268)"
FT /evidence="ECO:0000305"
FT TURN 830..832
FT /evidence="ECO:0007829|PDB:4J8S"
FT TURN 838..840
FT /evidence="ECO:0007829|PDB:4J8S"
FT HELIX 841..856
FT /evidence="ECO:0007829|PDB:4J8S"
FT HELIX 866..877
FT /evidence="ECO:0007829|PDB:4J8S"
FT HELIX 882..897
FT /evidence="ECO:0007829|PDB:4J8S"
FT HELIX 899..904
FT /evidence="ECO:0007829|PDB:4J8S"
FT HELIX 907..922
FT /evidence="ECO:0007829|PDB:4J8S"
FT HELIX 929..942
FT /evidence="ECO:0007829|PDB:4J8S"
FT HELIX 949..961
FT /evidence="ECO:0007829|PDB:4J8S"
FT HELIX 962..967
FT /evidence="ECO:0007829|PDB:4J8S"
FT HELIX 969..976
FT /evidence="ECO:0007829|PDB:4J8S"
FT HELIX 981..983
FT /evidence="ECO:0007829|PDB:4J8S"
FT HELIX 986..996
FT /evidence="ECO:0007829|PDB:4J8S"
FT HELIX 1076..1082
FT /evidence="ECO:0007829|PDB:5ANR"
FT HELIX 1093..1104
FT /evidence="ECO:0007829|PDB:4CRW"
FT TURN 1108..1110
FT /evidence="ECO:0007829|PDB:4CRW"
FT HELIX 1111..1121
FT /evidence="ECO:0007829|PDB:4CRW"
FT HELIX 1124..1126
FT /evidence="ECO:0007829|PDB:4CRW"
FT HELIX 1127..1137
FT /evidence="ECO:0007829|PDB:4CRW"
FT TURN 1138..1141
FT /evidence="ECO:0007829|PDB:4CRW"
FT HELIX 1143..1145
FT /evidence="ECO:0007829|PDB:4CRW"
FT HELIX 1146..1156
FT /evidence="ECO:0007829|PDB:4CRW"
FT HELIX 1159..1177
FT /evidence="ECO:0007829|PDB:4CRW"
FT HELIX 1181..1183
FT /evidence="ECO:0007829|PDB:5ANR"
FT HELIX 1186..1202
FT /evidence="ECO:0007829|PDB:4CRW"
FT HELIX 1204..1206
FT /evidence="ECO:0007829|PDB:4CRW"
FT TURN 1212..1214
FT /evidence="ECO:0007829|PDB:4CRW"
FT HELIX 1217..1227
FT /evidence="ECO:0007829|PDB:4CRW"
FT HELIX 1229..1243
FT /evidence="ECO:0007829|PDB:4CRW"
FT HELIX 1244..1248
FT /evidence="ECO:0007829|PDB:4CRW"
FT TURN 1250..1252
FT /evidence="ECO:0007829|PDB:4CRW"
FT HELIX 1257..1271
FT /evidence="ECO:0007829|PDB:4CRW"
FT HELIX 1277..1289
FT /evidence="ECO:0007829|PDB:4CRW"
FT HELIX 1294..1296
FT /evidence="ECO:0007829|PDB:4CRW"
FT HELIX 1302..1304
FT /evidence="ECO:0007829|PDB:4CRW"
FT HELIX 1306..1310
FT /evidence="ECO:0007829|PDB:4CRW"
FT HELIX 1359..1361
FT /evidence="ECO:0007829|PDB:4CRU"
FT HELIX 1367..1369
FT /evidence="ECO:0007829|PDB:4CRU"
FT HELIX 1371..1373
FT /evidence="ECO:0007829|PDB:4CRU"
FT HELIX 1381..1385
FT /evidence="ECO:0007829|PDB:4CRU"
FT HELIX 1387..1392
FT /evidence="ECO:0007829|PDB:4CRU"
FT HELIX 1393..1427
FT /evidence="ECO:0007829|PDB:4CRU"
FT TURN 1428..1430
FT /evidence="ECO:0007829|PDB:4CRU"
FT HELIX 1434..1476
FT /evidence="ECO:0007829|PDB:4CRU"
FT HELIX 1482..1522
FT /evidence="ECO:0007829|PDB:4CRU"
FT HELIX 1524..1535
FT /evidence="ECO:0007829|PDB:4CRU"
FT HELIX 1543..1552
FT /evidence="ECO:0007829|PDB:4CRU"
FT HELIX 1555..1557
FT /evidence="ECO:0007829|PDB:4CRU"
FT STRAND 1561..1563
FT /evidence="ECO:0007829|PDB:4CRU"
FT HELIX 1566..1569
FT /evidence="ECO:0007829|PDB:4CRU"
FT HELIX 1570..1577
FT /evidence="ECO:0007829|PDB:4CRU"
FT HELIX 1848..1865
FT /evidence="ECO:0007829|PDB:4CQO"
FT HELIX 1866..1868
FT /evidence="ECO:0007829|PDB:5FU6"
FT HELIX 1870..1885
FT /evidence="ECO:0007829|PDB:4CQO"
FT STRAND 1888..1891
FT /evidence="ECO:0007829|PDB:4CQO"
FT HELIX 1892..1915
FT /evidence="ECO:0007829|PDB:4CQO"
FT HELIX 1926..1948
FT /evidence="ECO:0007829|PDB:4CQO"
FT STRAND 1950..1954
FT /evidence="ECO:0007829|PDB:4CQO"
FT HELIX 1957..1981
FT /evidence="ECO:0007829|PDB:4CQO"
FT HELIX 1982..1984
FT /evidence="ECO:0007829|PDB:4CQO"
FT HELIX 1988..2000
FT /evidence="ECO:0007829|PDB:4CQO"
FT HELIX 2006..2009
FT /evidence="ECO:0007829|PDB:4CQO"
FT HELIX 2012..2025
FT /evidence="ECO:0007829|PDB:4CQO"
FT TURN 2028..2030
FT /evidence="ECO:0007829|PDB:4CQO"
FT HELIX 2032..2034
FT /evidence="ECO:0007829|PDB:4CQO"
FT HELIX 2035..2042
FT /evidence="ECO:0007829|PDB:4CQO"
FT HELIX 2045..2052
FT /evidence="ECO:0007829|PDB:4CQO"
FT HELIX 2056..2058
FT /evidence="ECO:0007829|PDB:4CQO"
FT HELIX 2061..2080
FT /evidence="ECO:0007829|PDB:4CQO"
FT HELIX 2086..2105
FT /evidence="ECO:0007829|PDB:4CQO"
FT HELIX 2107..2112
FT /evidence="ECO:0007829|PDB:4CQO"
FT HELIX 2114..2120
FT /evidence="ECO:0007829|PDB:4CQO"
FT HELIX 2126..2133
FT /evidence="ECO:0007829|PDB:4CQO"
FT STRAND 2145..2147
FT /evidence="ECO:0007829|PDB:4C0D"
FT HELIX 2152..2154
FT /evidence="ECO:0007829|PDB:4CQO"
FT HELIX 2157..2159
FT /evidence="ECO:0007829|PDB:4CQO"
FT HELIX 2168..2171
FT /evidence="ECO:0007829|PDB:4CQO"
FT HELIX 2174..2186
FT /evidence="ECO:0007829|PDB:4CQO"
FT HELIX 2191..2200
FT /evidence="ECO:0007829|PDB:4CQO"
FT STRAND 2204..2207
FT /evidence="ECO:0007829|PDB:5FU6"
FT STRAND 2208..2210
FT /evidence="ECO:0007829|PDB:4CQO"
FT HELIX 2212..2232
FT /evidence="ECO:0007829|PDB:4CQO"
FT TURN 2239..2241
FT /evidence="ECO:0007829|PDB:4CQO"
FT STRAND 2242..2245
FT /evidence="ECO:0007829|PDB:4CQO"
FT HELIX 2246..2257
FT /evidence="ECO:0007829|PDB:4CQO"
FT HELIX 2260..2271
FT /evidence="ECO:0007829|PDB:4CQO"
FT STRAND 2276..2278
FT /evidence="ECO:0007829|PDB:4CQO"
FT HELIX 2279..2293
FT /evidence="ECO:0007829|PDB:4CQO"
FT STRAND 2296..2298
FT /evidence="ECO:0007829|PDB:4CQO"
FT HELIX 2299..2312
FT /evidence="ECO:0007829|PDB:4CQO"
FT STRAND 2313..2316
FT /evidence="ECO:0007829|PDB:4CQO"
FT HELIX 2320..2331
FT /evidence="ECO:0007829|PDB:4CQO"
FT HELIX 2337..2339
FT /evidence="ECO:0007829|PDB:4CQO"
FT TURN 2342..2344
FT /evidence="ECO:0007829|PDB:4CQO"
FT HELIX 2348..2360
FT /evidence="ECO:0007829|PDB:4CQO"
SQ SEQUENCE 2376 AA; 266939 MW; 937A0899537BA615 CRC64;
MNLDSLSLAL SQISYLVDNL TKKNYRASQQ EIQHIVNRHG PEADRHLLRC LFSHVDFSGD
GKSSGKDFHQ TQFLIQECAL LITKPNFIST LSYAIDNPLH YQKSLKPAPH LFAQLSKVLK
LSKVQEVIFG LALLNSSSSD LRGFAAQFIK QKLPDLLRSY IDADVSGNQE GGFQDIAIEV
LHLLLSHLLF GQKGAFGVGQ EQIDAFLKTL RRDFPQERCP VVLAPLLYPE KRDILMDRIL
PDSGGVAKTM MESSLADFMQ EVGYGFCASI EECRNIIVQF GVREVTAAQV ARVLGMMART
HSGLTDGIPL QSISAPGSGI WSDGKDKSDG AQAHTWNVEV LIDVLKELNP SLNFKEVTYE
LDHPGFQIRD SKGLHNVVYG IQRGLGMEVF PVDLIYRPWK HAEGQLSFIQ HSLINPEIFC
FADYPCHTVA TDILKAPPED DNREIATWKS LDLIESLLRL AEVGQYEQVK QLFSFPIKHC
PDMLVLALLQ INTSWHTLRH ELISTLMPIF LGNHPNSAII LHYAWHGQGQ SPSIRQLIMH
AMAEWYMRGE QYDQAKLSRI LDVAQDLKAL SMLLNGTPFA FVIDLAALAS RREYLKLDKW
LTDKIREHGE PFIQACMTFL KRRCPSILGG LAPEKDQPKS AQLPPETLAT MLACLQACAG
SVSQELSETI LTMVANCSNV MNKARQPPPG VMPKGRPPSA SSLDAISPVQ IDPLAGMTSL
SIGGSAAPHT QSMQGFPPNL GSAFSTPQSP AKAFPPLSTP NQTTAFSGIG GLSSQLPVGG
LGTGSLTGIG TGALGLPAVN NDPFVQRKLG TSGLNQPTFQ QSKMKPSDLS QVWPEANQHF
SKEIDDEANS YFQRIYNHPP HPTMSVDEVL EMLQRFKDST IKREREVFNC MLRNLFEEYR
FFPQYPDKEL HITACLFGGI IEKGLVTYMA LGLALRYVLE ALRKPFGSKM YYFGIAALDR
FKNRLKDYPQ YCQHLASISH FMQFPHHLQE YIEYGQQSRD PPVKMQGSIT TPGSIALAQA
QAQAQVPAKA PLAGQVSTMV TTSTTTTVAK TVTVTRPTGV SFKKDVPPSI NTTNIDTLLV
ATDQTERIVE PPENIQEKIA FIFNNLSQSN MTQKVEELKE TVKEEFMPWV SQYLVMKRVS
IEPNFHSLYS NFLDTLKNPE FNKMVLNETY RNIKVLLTSD KAAANFSDRS LLKNLGHWLG
MITLAKNKPI LHTDLDVKSL LLEAYVKGQQ ELLYVVPFVA KVLESSIRSV VFRPPNPWTM
AIMNVLAELH QEHDLKLNLK FEIEVLCKNL ALDINELKPG NLLKDKDRLK NLDEQLSAPK
KDVKQPEELP PITTTTTSTT PATNTTCTAT VPPQPQYSYH DINVYSLAGL APHITLNPTI
PLFQAHPQLK QCVRQAIERA VQELVHPVVD RSIKIAMTTC EQIVRKDFAL DSEESRMRIA
AHHMMRNLTA GMAMITCREP LLMSISTNLK NSFASALRTA SPQQREMMDQ AAAQLAQDNC
ELACCFIQKT AVEKAGPEMD KRLATEFELR KHARQEGRRY CDPVVLTYQA ERMPEQIRLK
VGGVDPKQLA VYEEFARNVP GFLPTNDLSQ PTGFLAQPMK QAWATDDVAQ IYDKCITELE
QHLHAIPPTL AMNPQAQALR SLLEVVVLSR NSRDAIAALG LLQKAVEGLL DATSGADADL
LLRYRECHLL VLKALQDGRA YGSPWCNKQI TRCLIECRDE YKYNVEAVEL LIRNHLVNMQ
QYDLHLAQSM ENGLNYMAVA FAMQLVKILL VDERSVAHVT EADLFHTIET LMRINAHSRG
NAPEGLPQLM EVVRSNYEAM IDRAHGGPNF MMHSGISQAS EYDDPPGLRE KAEYLLREWV
NLYHSAAAGR DSTKAFSAFV GQMHQQGILK TDDLITRFFR LCTEMCVEIS YRAQAEQQHN
PAANPTMIRA KCYHNLDAFV RLIALLVKHS GEATNTVTKI NLLNKVLGIV VGVLLQDHDV
RQSEFQQLPY HRIFIMLLLE LNAPEHVLET INFQTLTAFC NTFHILRPTK APGFVYAWLE
LISHRIFIAR MLAHTPQQKG WPMYAQLLID LFKYLAPFLR NVELTKPMQI LYKGTLRVLL
VLLHDFPEFL CDYHYGFCDV IPPNCIQLRN LILSAFPRNM RLPDPFTPNL KVDMLSEINI
APRILTNFTG VMPPQFKKDL DSYLKTRSPV TFLSDLRSNL QVSNEPGNRY NLQLINALVL
YVGTQAIAHI HNKGSTPSMS TITHSAHMDI FQNLAVDLDT EGRYLFLNAI ANQLRYPNSH
THYFSCTMLY LFAEANTEAI QEQITRVLLE RLIVNRPHPW GLLITFIELI KNPAFKFWNH
EFVHCAPEIE KLFQSVAQCC MGQKQAQQVM EGTGAS
