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 27-MAR-2024, entry version 147. 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}; 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; 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 PDB; 7VOI; X-ray; 4.38 A; A=1093-1317. DR PDB; 8BFI; X-ray; 3.00 A; A=1-687. DR PDB; 8FY3; EM; 2.88 A; A=1-1000. 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 PDBsum; 7VOI; -. DR PDBsum; 8BFI; -. DR PDBsum; 8FY3; -. DR AlphaFoldDB; A5YKK6; -. DR EMDB; EMD-29551; -. DR SMR; A5YKK6; -. DR BioGRID; 116660; 293. 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; 121. DR MINT; A5YKK6; -. DR STRING; 9606.ENSP00000320949; -. DR ChEMBL; CHEMBL4105919; -. DR CarbonylDB; A5YKK6; -. DR GlyCosmos; A5YKK6; 15 sites, 2 glycans. DR GlyGen; A5YKK6; 19 sites, 2 O-linked glycans (19 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; 9606-ENSP00000320949; -. DR PeptideAtlas; A5YKK6; -. DR ProteomicsDB; 759; -. [A5YKK6-1] DR ProteomicsDB; 760; -. [A5YKK6-2] DR ProteomicsDB; 761; -. [A5YKK6-3] DR ProteomicsDB; 762; -. [A5YKK6-4] DR Pumba; A5YKK6; -. DR Antibodypedia; 29121; 107 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 AGR; HGNC:7877; -. 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; 1329322at2759; -. 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 Reactome; R-HSA-9820841; M-decay: degradation of maternal mRNAs by maternally stored factors. DR SignaLink; A5YKK6; -. DR SIGNOR; A5YKK6; -. DR BioGRID-ORCS; 23019; 542 hits in 1182 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 primordial germ cell in gonad and 204 other cell types or tissues. DR ExpressionAtlas; A5YKK6; baseline and differential. 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 post-transcriptional 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; NAS: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:0001829; P:trophectodermal cell differentiation; IEA:Ensembl. DR CDD; cd20710; NOT1_connector; 1. DR DisProt; DP02524; -. DR Gene3D; 1.25.40.180; -; 1. DR Gene3D; 1.25.40.790; -; 1. DR Gene3D; 1.25.40.800; -; 1. DR Gene3D; 1.25.40.840; CCR4-NOT transcription complex subunit 1 TTP binding domain; 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; CCR4-NOT TRANSCRIPTION COMPLEX; 1. DR PANTHER; PTHR13162:SF8; CCR4-NOT TRANSCRIPTION COMPLEX SUBUNIT 1; 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. DR Genevisible; A5YKK6; HS. 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 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 significance)" FT /evidence="ECO:0000269|PubMed:32553196" FT /id="VAR_084317" FT VARIANT 1089 FT /note="V -> L (in VIBOS; uncertain significance; FT dbSNP:rs2040438229)" 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 HELIX 7..18 FT /evidence="ECO:0007829|PDB:8FY3" FT TURN 22..24 FT /evidence="ECO:0007829|PDB:8BFI" FT HELIX 25..39 FT /evidence="ECO:0007829|PDB:8FY3" FT HELIX 43..54 FT /evidence="ECO:0007829|PDB:8FY3" FT HELIX 69..81 FT /evidence="ECO:0007829|PDB:8FY3" FT HELIX 87..96 FT /evidence="ECO:0007829|PDB:8FY3" FT STRAND 104..106 FT /evidence="ECO:0007829|PDB:8FY3" FT HELIX 111..118 FT /evidence="ECO:0007829|PDB:8FY3" FT HELIX 124..133 FT /evidence="ECO:0007829|PDB:8FY3" FT HELIX 139..162 FT /evidence="ECO:0007829|PDB:8FY3" FT HELIX 178..189 FT /evidence="ECO:0007829|PDB:8FY3" FT STRAND 193..196 FT /evidence="ECO:0007829|PDB:8FY3" FT HELIX 200..213 FT /evidence="ECO:0007829|PDB:8FY3" FT TURN 216..218 FT /evidence="ECO:0007829|PDB:8FY3" FT TURN 221..223 FT /evidence="ECO:0007829|PDB:8FY3" FT HELIX 224..227 FT /evidence="ECO:0007829|PDB:8FY3" FT STRAND 236..240 FT /evidence="ECO:0007829|PDB:8BFI" FT HELIX 255..262 FT /evidence="ECO:0007829|PDB:8FY3" FT TURN 264..267 FT /evidence="ECO:0007829|PDB:8FY3" FT HELIX 270..280 FT /evidence="ECO:0007829|PDB:8FY3" FT TURN 282..284 FT /evidence="ECO:0007829|PDB:8BFI" FT HELIX 287..299 FT /evidence="ECO:0007829|PDB:8FY3" FT STRAND 300..302 FT /evidence="ECO:0007829|PDB:8BFI" FT HELIX 338..348 FT /evidence="ECO:0007829|PDB:8FY3" FT HELIX 354..359 FT /evidence="ECO:0007829|PDB:8FY3" FT HELIX 371..385 FT /evidence="ECO:0007829|PDB:8FY3" FT STRAND 386..388 FT /evidence="ECO:0007829|PDB:8BFI" FT HELIX 393..396 FT /evidence="ECO:0007829|PDB:8FY3" FT HELIX 402..413 FT /evidence="ECO:0007829|PDB:8FY3" FT TURN 416..418 FT /evidence="ECO:0007829|PDB:8BFI" FT TURN 421..423 FT /evidence="ECO:0007829|PDB:8BFI" FT HELIX 443..447 FT /evidence="ECO:0007829|PDB:8FY3" FT HELIX 451..463 FT /evidence="ECO:0007829|PDB:8FY3" FT HELIX 467..478 FT /evidence="ECO:0007829|PDB:8FY3" FT HELIX 483..489 FT /evidence="ECO:0007829|PDB:8FY3" FT HELIX 497..510 FT /evidence="ECO:0007829|PDB:8FY3" FT HELIX 517..525 FT /evidence="ECO:0007829|PDB:8FY3" FT HELIX 532..541 FT /evidence="ECO:0007829|PDB:8FY3" FT HELIX 542..544 FT /evidence="ECO:0007829|PDB:8FY3" FT HELIX 558..566 FT /evidence="ECO:0007829|PDB:8FY3" FT HELIX 570..574 FT /evidence="ECO:0007829|PDB:8BFI" FT HELIX 579..591 FT /evidence="ECO:0007829|PDB:8FY3" FT HELIX 597..607 FT /evidence="ECO:0007829|PDB:8FY3" FT HELIX 610..613 FT /evidence="ECO:0007829|PDB:8FY3" FT TURN 616..621 FT /evidence="ECO:0007829|PDB:8FY3" FT HELIX 645..657 FT /evidence="ECO:0007829|PDB:8BFI" FT TURN 658..660 FT /evidence="ECO:0007829|PDB:8BFI" 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 //