ID SOCS3_MOUSE Reviewed; 225 AA. AC O35718; P97803; Q3U7X5; DT 16-APR-2002, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1998, sequence version 1. DT 14-OCT-2015, entry version 143. DE RecName: Full=Suppressor of cytokine signaling 3; DE Short=SOCS-3; DE AltName: Full=Cytokine-inducible SH2 protein 3; DE Short=CIS-3; DE AltName: Full=Protein EF-10; GN Name=Socs3; Synonyms=Cis3, Cish3; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Lung, and Thymus; RX PubMed=9202125; DOI=10.1038/43206; RA Starr R., Willson T.A., Viney E.M., Murray L.J.L., Rayner J.R., RA Jenkins B.J., Gonda T.J., Alexander W.S., Metcalf D., Nicola N.A., RA Hilton D.J.; RT "A family of cytokine-inducible inhibitors of signaling."; RL Nature 387:917-921(1997). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Le Provost F., Henninghausen L.; RT "Murine SOCS3 gene structure."; RL Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J, and NOD; TISSUE=Bone marrow, Cerebellum, and Spleen; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., RA Davis M.J., Wilming L.G., Aidinis V., Allen J.E., RA Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., RA Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., RA Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., RA Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., RA di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., RA Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., RA Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., RA Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., RA Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., RA Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., RA Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., RA Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., RA Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., RA Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., RA Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., RA Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., RA Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., RA Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., RA Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., RA Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., RA Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., RA Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., RA Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., RA Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., RA Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., RA Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., RA Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., RA Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., RA Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., RA Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6; TISSUE=Brain; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-30. RC STRAIN=ICR X Swiss Webster; RX PubMed=10359822; DOI=10.1073/pnas.96.12.6964; RA Auernhammer C.J., Bousquet C., Melmed S.; RT "Autoregulation of pituitary corticotroph SOCS-3 expression: RT characterization of the murine SOCS-3 promoter."; RL Proc. Natl. Acad. Sci. U.S.A. 96:6964-6969(1999). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 221-225. RC STRAIN=BALB/c; RX PubMed=9032278; RA Fu X., Kamps M.P.; RT "E2a-Pbx1 induces aberrant expression of tissue-specific and RT developmentally regulated genes when expressed in NIH 3T3 RT fibroblasts."; RL Mol. Cell. Biol. 17:1503-1512(1997). RN [7] RP FUNCTION IN LIF AND IL6 SIGNALING. RX PubMed=9889194; DOI=10.1093/emboj/18.2.375; RA Nicholson S.E., Willson T.A., Farley A., Starr R., Zhang J.-G., RA Baca M., Alexander W.S., Metcalf D., Hilton D.J., Nicola N.A.; RT "Mutational analyses of the SOCS proteins suggest a dual domain RT requirement but distinct mechanisms for inhibition of LIF and IL-6 RT signal transduction."; RL EMBO J. 18:375-385(1999). RN [8] RP FUNCTION IN INHIBITION OF INSR KINASE ACTIVITY, AND INTERACTION WITH RP INSR. RX PubMed=10821852; DOI=10.1074/jbc.275.21.15985; RA Emanuelli B., Peraldi P., Filloux C., Sawka-Verhelle D., Hilton D., RA Van Obberghen E.; RT "SOCS-3 is an insulin-induced negative regulator of insulin RT signaling."; RL J. Biol. Chem. 275:15985-15991(2000). RN [9] RP INTERACTION WITH EPOR AND JAK2, AND MUTAGENESIS OF LEU-22; PHE-25; RP GLY-45 AND ARG-71. RX PubMed=10882725; DOI=10.1074/jbc.M003456200; RA Sasaki A., Yasukawa H., Shouda T., Kitamura T., Dikic I., RA Yoshimura A.; RT "CIS3/SOCS-3 suppresses erythropoietin (EPO) signaling by binding the RT EPO receptor and JAK2."; RL J. Biol. Chem. 275:29338-29347(2000). RN [10] RP TISSUE SPECIFICITY. RX PubMed=12242343; DOI=10.1073/pnas.202477099; RA Seki Y., Hayashi K., Matsumoto A., Seki N., Tsukada J., Ransom J., RA Naka T., Kishimoto T., Yoshimura A., Kubo M.; RT "Expression of the suppressor of cytokine signaling-5 (SOCS5) RT negatively regulates IL-4-dependent STAT6 activation and Th2 RT differentiation."; RL Proc. Natl. Acad. Sci. U.S.A. 99:13003-13008(2002). RN [11] RP FUNCTION IN ERYTHROPOIESIS. RX PubMed=10490101; DOI=10.1016/S0092-8674(00)80049-5; RA Marine J.-C., McKay C., Wang D., Topham D.J., Parganas E., RA Nakajima H., Pendeville H., Yasukawa H., Sasaki A., Yoshimura A., RA Ihle J.N.; RT "SOCS3 is essential in the regulation of fetal liver erythropoiesis."; RL Cell 98:617-627(1999). RN [12] RP ROLE IN IL-6 SIGNALING. RX PubMed=12754505; DOI=10.1038/ni931; RA Croker B.A., Krebs D.L., Zhang J.-G., Wormald S., Willson T.A., RA Stanley E.G., Robb L., Greenhalgh C.J., Foerster I., Clausen B.E., RA Nicola N.A., Metcalf D., Hilton D.J., Roberts A.W., Alexander W.S.; RT "SOCS3 negatively regulates IL-6 signaling in vivo."; RL Nat. Immunol. 4:540-545(2003). RN [13] RP ROLE IN ALLERGIC RESPONSE, AND INDUCTION BY IL-4. RX PubMed=12847520; DOI=10.1038/nm896; RA Seki Y., Inoue H., Nagata N., Hayashi K., Fukuyama S., Matsumoto K., RA Komine O., Hamano S., Himeno K., Inagaki-Ohara K., Cacalano N., RA O'Garra A., Oshida T., Saito H., Johnston J.A., Yoshimura A., Kubo M.; RT "SOCS-3 regulates onset and maintenance of T(H)2-mediated allergic RT responses."; RL Nat. Med. 9:1047-1054(2003). RN [14] RP INTERACTION WITH BCL10. RX PubMed=15213237; DOI=10.1074/jbc.M400241200; RA Liu Y., Dong W., Chen L., Xiang R., Xiao H., De G., Wang Z., Qi Y.; RT "BCL10 mediates lipopolysaccharide/toll-like receptor-4 signaling RT through interaction with Pellino2."; RL J. Biol. Chem. 279:37436-37444(2004). RN [15] RP INTERACTION WITH NOD2. RX PubMed=23019338; DOI=10.1074/jbc.M112.410027; RA Lee K.H., Biswas A., Liu Y.J., Kobayashi K.S.; RT "Proteasomal degradation of Nod2 protein mediates tolerance to RT bacterial cell wall components."; RL J. Biol. Chem. 287:39800-39811(2012). RN [16] RP STRUCTURE BY NMR OF 22-185. RX PubMed=16630890; DOI=10.1016/j.molcel.2006.03.024; RA Babon J.J., McManus E.J., Yao S., DeSouza D.P., Mielke L.A., RA Sprigg N.S., Willson T.A., Hilton D.J., Nicola N.A., Baca M., RA Nicholson S.E., Norton R.S.; RT "The structure of SOCS3 reveals the basis of the extended SH2 domain RT function and identifies an unstructured insertion that regulates RT stability."; RL Mol. Cell 22:205-216(2006). RN [17] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 15-185 IN COMPLEX WITH RP PHOSPHORYLATED IL6ST. RX PubMed=16905102; DOI=10.1016/j.str.2006.06.011; RA Bergamin E., Wu J., Hubbard S.R.; RT "Structural basis for phosphotyrosine recognition by suppressor of RT cytokine signaling-3."; RL Structure 14:1285-1292(2006). CC -!- FUNCTION: SOCS family proteins form part of a classical negative CC feedback system that regulates cytokine signal transduction. SOCS3 CC is involved in negative regulation of cytokines that signal CC through the JAK/STAT pathway. Inhibits cytokine signal CC transduction by binding to tyrosine kinase receptors including CC gp130, LIF, erythropoietin, insulin, IL12, GCSF and leptin CC receptors. Binding to JAK2 inhibits its kinase activity. CC Suppresses fetal liver erythropoiesis. Regulates onset and CC maintenance of allergic responses mediated by T-helper type 2 CC cells. Regulates IL-6 signaling in vivo. Probable substrate- CC recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS- CC box protein) E3 ubiquitin-protein ligase complex which mediates CC the ubiquitination and subsequent proteasomal degradation of CC target proteins (By similarity). Seems to recognize IL6ST. CC {ECO:0000250, ECO:0000269|PubMed:10490101, CC ECO:0000269|PubMed:10821852, ECO:0000269|PubMed:12754505, CC ECO:0000269|PubMed:12847520, ECO:0000269|PubMed:9889194}. CC -!- PATHWAY: Protein modification; protein ubiquitination. CC -!- SUBUNIT: Interacts with multiple activated proteins of the CC tyrosine kinase signaling pathway including IGF1 receptor, insulin CC receptor and JAK2. Binding to JAK2 is mediated through the KIR and CC SH2 domains to a phosphorylated tyrosine residue within the JAK2 CC JH1 domain (By similarity). Binds specific activated tyrosine CC residues of the leptin, EPO, IL12, GSCF and gp130 receptors CC (PubMed:10882725). Interaction with CSNK1E stabilizes SOCS3 CC protein (By similarity). Component of the probable ECS(SOCS3) E3 CC ubiquitin-protein ligase complex which contains CUL5, RNF7/RBX2, CC elongin BC complex and SOCS3 (By similarity). Interacts with CUL5, CC RNF7, TCEB1 and TCEB2 (By similarity). Interacts with FGFR3 (By CC similarity). Interacts with INSR (PubMed:10821852). Interacts with CC BCL10; this interaction may interfere with BCL10-binding with CC PELI2 (PubMed:15213237). Interacts with NOD2 (via CARD domain); CC the interaction promotes NOD2 degradation (PubMed:23019338). CC {ECO:0000250|UniProtKB:O14543, ECO:0000269|PubMed:10821852, CC ECO:0000269|PubMed:10882725, ECO:0000269|PubMed:15213237, CC ECO:0000269|PubMed:16905102, ECO:0000269|PubMed:23019338}. CC -!- INTERACTION: CC Q00560:Il6st; NbExp=3; IntAct=EBI-2659360, EBI-3862992; CC -!- TISSUE SPECIFICITY: Low expression in lung, spleen and thymus. CC Expressed in Th2 but not TH1 cells. {ECO:0000269|PubMed:12242343}. CC -!- DEVELOPMENTAL STAGE: In the developing brain, expressed at low CC levels from E10 stages to young adulthood (P25) with peak levels CC from E14 to P8. In the cortex, first expressed uniformly in all CC cells at E14. Not expressed in the retina. Highly expressed in CC fetal liver progenitors at E12.5. CC -!- INDUCTION: By a subset of cytokines including EPO, leptin, LIF, CC IL-2, IL-3, IL-4, IGF1, growth hormone and prolactin. CC {ECO:0000269|PubMed:12847520}. CC -!- DOMAIN: The ESS and SH2 domains are required for JAK CC phosphotyrosine binding. Further interaction with the KIR domain CC is necessary for signal and kinase inhibition. CC -!- DOMAIN: The SOCS box domain mediates the interaction with the CC Elongin BC complex, an adapter module in different E3 ubiquitin CC ligase complexes. {ECO:0000250}. CC -!- PTM: Phosphorylated on tyrosine residues after stimulation by the CC cytokines, IL-2, EPO or IGF1. {ECO:0000250}. CC -!- SIMILARITY: Contains 1 SH2 domain. {ECO:0000255|PROSITE- CC ProRule:PRU00191}. CC -!- SIMILARITY: Contains 1 SOCS box domain. {ECO:0000255|PROSITE- CC ProRule:PRU00194}. 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; U88328; AAB62403.1; -; mRNA. DR EMBL; AF314501; AAK60601.1; -; Genomic_DNA. DR EMBL; AK047165; BAC32977.1; -; mRNA. DR EMBL; AK139241; BAE23929.1; -; mRNA. DR EMBL; AK152468; BAE31244.1; -; mRNA. DR EMBL; AK152514; BAE31277.1; -; mRNA. DR EMBL; AK157708; BAE34161.1; -; mRNA. DR EMBL; AK159395; BAE35049.1; -; mRNA. DR EMBL; AK170406; BAE41773.1; -; mRNA. DR EMBL; AK172399; BAE42985.1; -; mRNA. DR EMBL; BC052031; AAH52031.1; -; mRNA. DR EMBL; AF117732; AAD18024.1; -; Genomic_DNA. DR EMBL; U72673; AAB51035.1; ALT_SEQ; mRNA. DR CCDS; CCDS25697.1; -. DR RefSeq; NP_031733.1; NM_007707.3. DR RefSeq; XP_011247009.1; XM_011248707.1. DR UniGene; Mm.3468; -. DR PDB; 2BBU; NMR; -; A=22-185. DR PDB; 2HMH; X-ray; 2.00 A; A=15-185. DR PDB; 2JZ3; NMR; -; A=186-225. DR PDB; 4GL9; X-ray; 3.90 A; E/F/G/H=22-128, E/F/G/H=179-185. DR PDBsum; 2BBU; -. DR PDBsum; 2HMH; -. DR PDBsum; 2JZ3; -. DR PDBsum; 4GL9; -. DR DisProt; DP00446; -. DR ProteinModelPortal; O35718; -. DR SMR; O35718; 30-185. DR BioGrid; 198718; 13. DR DIP; DIP-29137N; -. DR IntAct; O35718; 9. DR MINT; MINT-2569503; -. DR STRING; 10090.ENSMUSP00000059129; -. DR PhosphoSite; O35718; -. DR PRIDE; O35718; -. DR DNASU; 12702; -. DR Ensembl; ENSMUST00000054002; ENSMUSP00000059129; ENSMUSG00000053113. DR GeneID; 12702; -. DR KEGG; mmu:12702; -. DR UCSC; uc007moi.2; mouse. DR CTD; 9021; -. DR MGI; MGI:1201791; Socs3. DR eggNOG; NOG281730; -. DR GeneTree; ENSGT00760000119136; -. DR HOGENOM; HOG000236320; -. DR HOVERGEN; HBG105645; -. DR InParanoid; O35718; -. DR KO; K04696; -. DR OMA; KRTYYIY; -. DR OrthoDB; EOG7TXKHR; -. DR PhylomeDB; O35718; -. DR TreeFam; TF321368; -. DR Reactome; R-MMU-1059683; Interleukin-6 signaling. DR Reactome; R-MMU-2586551; Signaling by Leptin. DR Reactome; R-MMU-2586552; Signaling by Leptin. DR Reactome; R-MMU-877300; Interferon gamma signaling. DR Reactome; R-MMU-877312; Regulation of IFNG signaling. DR Reactome; R-MMU-909733; Interferon alpha/beta signaling. DR Reactome; R-MMU-982772; Growth hormone receptor signaling. DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR UniPathway; UPA00143; -. DR EvolutionaryTrace; O35718; -. DR NextBio; 281958; -. DR PRO; PR:O35718; -. DR Proteomes; UP000000589; Chromosome 11. DR Bgee; O35718; -. DR CleanEx; MM_SOCS3; -. DR Genevisible; O35718; MM. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0004860; F:protein kinase inhibitor activity; IBA:GO_Central. DR GO; GO:0007568; P:aging; IEA:Ensembl. DR GO; GO:0060670; P:branching involved in labyrinthine layer morphogenesis; IMP:MGI. DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IBA:GO_Central. DR GO; GO:0007259; P:JAK-STAT cascade; IEA:InterPro. DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:InterPro. DR GO; GO:1904030; P:negative regulation of cyclin-dependent protein kinase activity; IBA:GOC. DR GO; GO:0050728; P:negative regulation of inflammatory response; IGI:MGI. DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IDA:MGI. DR GO; GO:0046426; P:negative regulation of JAK-STAT cascade; IBA:GO_Central. DR GO; GO:0006469; P:negative regulation of protein kinase activity; IBA:GO_Central. DR GO; GO:0009968; P:negative regulation of signal transduction; IGI:MGI. DR GO; GO:0031100; P:organ regeneration; IEA:Ensembl. DR GO; GO:0060674; P:placenta blood vessel development; IMP:MGI. DR GO; GO:0045597; P:positive regulation of cell differentiation; IDA:MGI. DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway. DR GO; GO:0045595; P:regulation of cell differentiation; IMP:MGI. DR GO; GO:0040008; P:regulation of growth; IEA:UniProtKB-KW. DR GO; GO:0001932; P:regulation of protein phosphorylation; IDA:MGI. DR GO; GO:0042493; P:response to drug; IEA:Ensembl. DR GO; GO:0032355; P:response to estradiol; IEA:Ensembl. DR GO; GO:0032094; P:response to food; IEA:Ensembl. DR GO; GO:0010332; P:response to gamma radiation; IEA:Ensembl. DR GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl. DR GO; GO:0009408; P:response to heat; IEA:Ensembl. DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl. DR GO; GO:0032868; P:response to insulin; IEA:Ensembl. DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:0032570; P:response to progesterone; IEA:Ensembl. DR GO; GO:0060708; P:spongiotrophoblast differentiation; IMP:MGI. DR GO; GO:0060707; P:trophoblast giant cell differentiation; IMP:MGI. DR Gene3D; 3.30.505.10; -; 2. DR InterPro; IPR000980; SH2. DR InterPro; IPR028413; SOCS. DR InterPro; IPR028414; SOCS3. DR InterPro; IPR001496; SOCS_box. DR PANTHER; PTHR10385; PTHR10385; 1. DR PANTHER; PTHR10385:SF4; PTHR10385:SF4; 1. DR Pfam; PF00017; SH2; 1. DR Pfam; PF07525; SOCS_box; 1. DR SMART; SM00252; SH2; 1. DR SMART; SM00253; SOCS; 1. DR SMART; SM00969; SOCS_box; 1. DR SUPFAM; SSF55550; SSF55550; 1. DR PROSITE; PS50001; SH2; 1. DR PROSITE; PS50225; SOCS; 1. PE 1: Evidence at protein level; KW 3D-structure; Complete proteome; Growth regulation; Phosphoprotein; KW Reference proteome; SH2 domain; Signal transduction inhibitor; KW Ubl conjugation pathway. FT CHAIN 1 225 Suppressor of cytokine signaling 3. FT /FTId=PRO_0000181244. FT DOMAIN 46 142 SH2. {ECO:0000255|PROSITE- FT ProRule:PRU00191}. FT DOMAIN 177 224 SOCS box. {ECO:0000255|PROSITE- FT ProRule:PRU00194}. FT REGION 22 33 Kinase inhibitory region (KIR). FT REGION 34 45 Extended SH2 subdomain (ESS). FT MUTAGEN 22 22 L->A: No effect on LIF-induced signal FT transduction suppression. FT {ECO:0000269|PubMed:10882725}. FT MUTAGEN 22 22 L->D: Abolishes binding to JAK2. No FT effect on binding to EPOR. FT {ECO:0000269|PubMed:10882725}. FT MUTAGEN 25 25 F->A: Loss of LIF/EPO-induced signal FT transduction suppression. Abolishes FT binding to JAK2 and to EPOR. FT {ECO:0000269|PubMed:10882725}. FT MUTAGEN 30 30 E->R: No effect on LIF-induced signal FT transduction suppression. FT MUTAGEN 45 45 G->A: Abolishes binding to EPOR. No FT effect on binding to JAK2. FT {ECO:0000269|PubMed:10882725}. FT MUTAGEN 71 71 R->K: Little effect on LIF-induced signal FT transduction suppression. Loss of EPO- FT induced signal transduction suppression. FT Abolishes binding to JAK2 and EPOR. FT {ECO:0000269|PubMed:10882725}. FT HELIX 32 43 {ECO:0000244|PDB:2HMH}. FT STRAND 45 48 {ECO:0000244|PDB:2HMH}. FT HELIX 53 61 {ECO:0000244|PDB:2HMH}. FT STRAND 67 72 {ECO:0000244|PDB:2HMH}. FT STRAND 79 86 {ECO:0000244|PDB:2HMH}. FT STRAND 89 96 {ECO:0000244|PDB:2HMH}. FT HELIX 98 100 {ECO:0000244|PDB:2HMH}. FT STRAND 102 104 {ECO:0000244|PDB:2HMH}. FT STRAND 117 119 {ECO:0000244|PDB:2HMH}. FT HELIX 120 126 {ECO:0000244|PDB:2HMH}. FT STRAND 137 139 {ECO:0000244|PDB:2BBU}. FT STRAND 165 167 {ECO:0000244|PDB:2HMH}. FT STRAND 174 176 {ECO:0000244|PDB:2HMH}. FT HELIX 189 199 {ECO:0000244|PDB:2JZ3}. SQ SEQUENCE 225 AA; 24776 MW; CD3859561D4CCDED CRC64; MVTHSKFPAA GMSRPLDTSL RLKTFSSKSE YQLVVNAVRK LQESGFYWSA VTGGEANLLL SAEPAGTFLI RDSSDQRHFF TLSVKTQSGT KNLRIQCEGG SFSLQSDPRS TQPVPRFDCV LKLVHHYMPP PGTPSFSLPP TEPSSEVPEQ PPAQALPGST PKRAYYIYSG GEKIPLVLSR PLSSNVATLQ HLCRKTVNGH LDSYEKVTQL PGPIREFLDQ YDAPL //