FER_HUMAN
ID FER_HUMAN Reviewed; 822 AA.
AC P16591; B2RCR4; B4DSQ2; H2FLB8;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 16-MAY-2006, sequence version 2.
DT 03-AUG-2022, entry version 222.
DE RecName: Full=Tyrosine-protein kinase Fer;
DE EC=2.7.10.2;
DE AltName: Full=Feline encephalitis virus-related kinase FER;
DE AltName: Full=Fujinami poultry sarcoma/Feline sarcoma-related protein Fer;
DE AltName: Full=Proto-oncogene c-Fer;
DE AltName: Full=Tyrosine kinase 3;
DE AltName: Full=p94-Fer;
GN Name=FER; Synonyms=TYK3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT VAL-439.
RX PubMed=2725517; DOI=10.1128/mcb.9.4.1587-1593.1989;
RA Hao Q.-L., Heisterkamp N., Groffen J.;
RT "Isolation and sequence analysis of a novel human tyrosine kinase gene.";
RL Mol. Cell. Biol. 9:1587-1593(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), ALTERNATIVE PROMOTER USAGE,
RP FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, AND TISSUE SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=22223638; DOI=10.1074/jbc.m111.327106;
RA Makovski A., Yaffe E., Shpungin S., Nir U.;
RT "Intronic promoter drives the BORIS-regulated expression of FerT in colon
RT carcinoma cells.";
RL J. Biol. Chem. 287:6100-6112(2012).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 686-741.
RX PubMed=8247543;
RA Lee S.-T., Strunk K.M., Spritz R.A.;
RT "A survey of protein tyrosine kinase mRNAs expressed in normal human
RT melanocytes.";
RL Oncogene 8:3403-3410(1993).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=2156206;
RA Krolewski J.J., Lee R., Eddy R., Shows T.B., Dalla-Favera R.;
RT "Identification and chromosomal mapping of new human tyrosine kinase
RT genes.";
RL Oncogene 5:277-282(1990).
RN [8]
RP SUBCELLULAR LOCATION.
RX PubMed=1990274; DOI=10.1128/mcb.11.2.1180-1183.1991;
RA Hao Q.-L., Ferris D.K., White G., Heisterkamp N., Groffen J.;
RT "Nuclear and cytoplasmic location of the FER tyrosine kinase.";
RL Mol. Cell. Biol. 11:1180-1183(1991).
RN [9]
RP FUNCTION IN PHOSPHORYLATION OF CTNND1, AUTOPHOSPHORYLATION, SUBUNIT, AND
RP INTERACTION WITH CTNND1.
RX PubMed=7623846; DOI=10.1128/mcb.15.8.4553;
RA Kim L., Wong T.W.;
RT "The cytoplasmic tyrosine kinase FER is associated with the catenin-like
RT substrate pp120 and is activated by growth factors.";
RL Mol. Cell. Biol. 15:4553-4561(1995).
RN [10]
RP FUNCTION IN PHOSPHORYLATION OF CTTN, INTERACTION WITH CTTN; CTNND1 AND
RP PDGFR, MUTAGENESIS OF LYS-591, AND SUBCELLULAR LOCATION.
RX PubMed=9722593; DOI=10.1074/jbc.273.36.23542;
RA Kim L., Wong T.W.;
RT "Growth factor-dependent phosphorylation of the actin-binding protein
RT cortactin is mediated by the cytoplasmic tyrosine kinase FER.";
RL J. Biol. Chem. 273:23542-23548(1998).
RN [11]
RP FUNCTION IN PHOSPHORYLATION OF PECAM1; PTPN11 AND GAB1, SUBCELLULAR
RP LOCATION, CATALYTIC ACTIVITY, MUTAGENESIS OF ARG-483, AND INTERACTION WITH
RP PECAM1.
RX PubMed=12972546; DOI=10.1091/mbc.e03-02-0080;
RA Kogata N., Masuda M., Kamioka Y., Yamagishi A., Endo A., Okada M.,
RA Mochizuki N.;
RT "Identification of Fer tyrosine kinase localized on microtubules as a
RT platelet endothelial cell adhesion molecule-1 phosphorylating kinase in
RT vascular endothelial cells.";
RL Mol. Biol. Cell 14:3553-3564(2003).
RN [12]
RP FUNCTION IN PHOSPHORYLATION OF JUP AND IN REGULATION OF PROTEIN
RP PHOSPHORYLATION.
RX PubMed=14517306; DOI=10.1128/mcb.23.20.7391-7402.2003;
RA Miravet S., Piedra J., Castano J., Raurell I., Franci C., Dunach M.,
RA Garcia de Herreros A.;
RT "Tyrosine phosphorylation of plakoglobin causes contrary effects on its
RT association with desmosomes and adherens junction components and modulates
RT beta-catenin-mediated transcription.";
RL Mol. Cell. Biol. 23:7391-7402(2003).
RN [13]
RP SUBCELLULAR LOCATION, LIPID-BINDING, AND DOMAIN.
RX PubMed=16418535; DOI=10.1083/jcb.200508091;
RA Tsujita K., Suetsugu S., Sasaki N., Furutani M., Oikawa T., Takenawa T.;
RT "Coordination between the actin cytoskeleton and membrane deformation by a
RT novel membrane tubulation domain of PCH proteins is involved in
RT endocytosis.";
RL J. Cell Biol. 172:269-279(2006).
RN [14]
RP IDENTIFICATION OF ISOFORM 3, AND TISSUE SPECIFICITY.
RX PubMed=18985748; DOI=10.1002/dvdy.21789;
RA Kierszenbaum A.L., Rivkin E., Tres L.L.;
RT "Expression of Fer testis (FerT) tyrosine kinase transcript variants and
RT distribution sites of FerT during the development of the acrosome-
RT acroplaxome-manchette complex in rat spermatids.";
RL Dev. Dyn. 237:3882-3891(2008).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-402 AND SER-434, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [16]
RP FUNCTION IN PHOSPHORYLATION OF PTK2/FAK1, FUNCTION IN REGULATION OF ACTIN
RP CYTOSKELETON, SUBUNIT, AND IDENTIFICATION IN A COMPLEX WITH CTTN AND
RP PTK2/FAK1.
RX PubMed=19339212; DOI=10.1016/j.bbamcr.2009.01.015;
RA Oh M.A., Choi S., Lee M.J., Choi M.C., Lee S.A., Ko W., Cance W.G.,
RA Oh E.S., Buday L., Kim S.H., Lee J.W.;
RT "Specific tyrosine phosphorylation of focal adhesion kinase mediated by Fer
RT tyrosine kinase in suspended hepatocytes.";
RL Biochim. Biophys. Acta 1793:781-791(2009).
RN [17]
RP INTERACTION WITH HSP90.
RX PubMed=19159681; DOI=10.1016/j.cellsig.2008.12.011;
RA Hikri E., Shpungin S., Nir U.;
RT "Hsp90 and a tyrosine embedded in the Hsp90 recognition loop are required
RT for the Fer tyrosine kinase activity.";
RL Cell. Signal. 21:588-596(2009).
RN [18]
RP FUNCTION IN IL6 SIGNALING PATHWAY; CELL PROLIFERATION AND IN
RP PHOSPHORYLATION OF STAT3, AND INTERACTION WITH STAT3.
RX PubMed=19147545; DOI=10.1158/1541-7786.mcr-08-0117;
RA Zoubeidi A., Rocha J., Zouanat F.Z., Hamel L., Scarlata E., Aprikian A.G.,
RA Chevalier S.;
RT "The Fer tyrosine kinase cooperates with interleukin-6 to activate signal
RT transducer and activator of transcription 3 and promote human prostate
RT cancer cell growth.";
RL Mol. Cancer Res. 7:142-155(2009).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-402 AND SER-434, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [20]
RP FUNCTION IN REGULATION OF ACTIN CYTOSKELETON AND CELL MIGRATION, CATALYTIC
RP ACTIVITY, DOMAIN, LIPID-BINDING, AND ACTIVITY REGULATION.
RX PubMed=19738202; DOI=10.1126/scisignal.2000393;
RA Itoh T., Hasegawa J., Tsujita K., Kanaho Y., Takenawa T.;
RT "The tyrosine kinase Fer is a downstream target of the PLD-PA pathway that
RT regulates cell migration.";
RL Sci. Signal. 2:RA52-RA52(2009).
RN [21]
RP FUNCTION IN CELL PROLIFERATION, PHOSPHORYLATION, AND INTERACTION WITH FLT3.
RX PubMed=20111072; DOI=10.1038/leu.2009.301;
RA Voisset E., Lopez S., Chaix A., Georges C., Hanssens K., Prebet T.,
RA Dubreuil P., De Sepulveda P.;
RT "FES kinases are required for oncogenic FLT3 signaling.";
RL Leukemia 24:721-728(2010).
RN [22]
RP FUNCTION IN ACTIVATION OF NF-KAPPA-B DOWNSTREAM OF EGFR AND CELL
RP PROLIFERATION, INTERACTION WITH EGFR, AND PHOSPHORYLATION.
RX PubMed=21518868; DOI=10.1073/pnas.1105369108;
RA Guo C., Stark G.R.;
RT "FER tyrosine kinase (FER) overexpression mediates resistance to quinacrine
RT through EGF-dependent activation of NF-kappaB.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:7968-7973(2011).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-434, AND IDENTIFICATION BY
RP 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 [24]
RP STRUCTURE BY NMR OF 453-557.
RG Northeast structural genomics consortium (NESG);
RT "Solution structure of SH2 domain of proto-oncogene tyrosine-protein kinase
RT FER from Homo sapiens, Northeast structural genomics consortium (NESG)
RT target HR3461D.";
RL Submitted (AUG-2009) to the PDB data bank.
RN [25]
RP REVIEW.
RX PubMed=11994747; DOI=10.1038/nrm783;
RA Greer P.;
RT "Closing in on the biological functions of Fps/Fes and Fer.";
RL Nat. Rev. Mol. Cell Biol. 3:278-289(2002).
RN [26]
RP VARIANT VAL-439.
RX PubMed=1651563; DOI=10.1126/science.1651563;
RA Nishisho I., Nakamura Y., Miyoshi Y., Miki Y., Ando H., Horii A.,
RA Koyama K., Utsunomiya J., Baba S., Hedge P., Markham A., Krush A.J.,
RA Petersen G.M., Hamilton S.R., Nilbert M.C., Levy D.B., Bryan T.M.,
RA Preisinger A.C., Smith K.J., Su L.-K., Kinzler K.W., Vogelstein B.;
RT "Mutations of chromosome 5q21 genes in FAP and colorectal cancer
RT patients.";
RL Science 253:665-669(1991).
RN [27]
RP VARIANTS [LARGE SCALE ANALYSIS] PHE-128; GLN-404; VAL-412; VAL-439;
RP PRO-443; CYS-460 AND GLN-813.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Tyrosine-protein kinase that acts downstream of cell surface
CC receptors for growth factors and plays a role in the regulation of the
CC actin cytoskeleton, microtubule assembly, lamellipodia formation, cell
CC adhesion, cell migration and chemotaxis. Acts downstream of EGFR, KIT,
CC PDGFRA and PDGFRB. Acts downstream of EGFR to promote activation of NF-
CC kappa-B and cell proliferation. May play a role in the regulation of
CC the mitotic cell cycle. Plays a role in the insulin receptor signaling
CC pathway and in activation of phosphatidylinositol 3-kinase. Acts
CC downstream of the activated FCER1 receptor and plays a role in FCER1
CC (high affinity immunoglobulin epsilon receptor)-mediated signaling in
CC mast cells. Plays a role in the regulation of mast cell degranulation.
CC Plays a role in leukocyte recruitment and diapedesis in response to
CC bacterial lipopolysaccharide (LPS). Plays a role in synapse
CC organization, trafficking of synaptic vesicles, the generation of
CC excitatory postsynaptic currents and neuron-neuron synaptic
CC transmission. Plays a role in neuronal cell death after brain damage.
CC Phosphorylates CTTN, CTNND1, PTK2/FAK1, GAB1, PECAM1 and PTPN11. May
CC phosphorylate JUP and PTPN1. Can phosphorylate STAT3, but the
CC biological relevance of this depends on cell type and stimulus.
CC {ECO:0000269|PubMed:12972546, ECO:0000269|PubMed:14517306,
CC ECO:0000269|PubMed:19147545, ECO:0000269|PubMed:19339212,
CC ECO:0000269|PubMed:19738202, ECO:0000269|PubMed:20111072,
CC ECO:0000269|PubMed:21518868, ECO:0000269|PubMed:22223638,
CC ECO:0000269|PubMed:7623846, ECO:0000269|PubMed:9722593}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028,
CC ECO:0000269|PubMed:12972546, ECO:0000269|PubMed:19738202};
CC -!- ACTIVITY REGULATION: Activated by phosphatidic acid binding. Activated
CC by hydrogen peroxide (in vitro). Activated by reactive oxygen species
CC (ROS). {ECO:0000269|PubMed:19738202}.
CC -!- SUBUNIT: Homotrimer. Interacts with ARHGDIA, IRS1, JAK1, NRP1, PIK3R1,
CC PLEC and TMF1. Interacts with PPP1CA and regulates its phosphorylation
CC at 'Thr-320' (By similarity). Interacts with CTNND1, EGFR, FLT3,
CC PECAM1, PDGFR and STAT3. Interacts (via SH2 domain) with CTTN.
CC Interacts with HSP90; this stabilizes phosphorylated FER and protects
CC FER against proteasomal degradation. Component of a complex that
CC contains at least FER, CTTN and PTK2/FAK1. {ECO:0000250,
CC ECO:0000269|PubMed:12972546, ECO:0000269|PubMed:19147545,
CC ECO:0000269|PubMed:19159681, ECO:0000269|PubMed:19339212,
CC ECO:0000269|PubMed:20111072, ECO:0000269|PubMed:21518868,
CC ECO:0000269|PubMed:7623846, ECO:0000269|PubMed:9722593}.
CC -!- INTERACTION:
CC P16591; Q16543: CDC37; NbExp=3; IntAct=EBI-1380661, EBI-295634;
CC P16591; P08238: HSP90AB1; NbExp=2; IntAct=EBI-1380661, EBI-352572;
CC P16591; O42486: Bcat; Xeno; NbExp=2; IntAct=EBI-1380661, EBI-972394;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, cytoskeleton. Cell
CC membrane; Peripheral membrane protein; Cytoplasmic side. Cell
CC projection. Cell junction. Membrane; Peripheral membrane protein;
CC Cytoplasmic side. Nucleus. Cytoplasm, cell cortex. Note=Associated with
CC the chromatin. Detected on microtubules in polarized and motile
CC vascular endothelial cells. Colocalizes with F-actin at the cell
CC cortex. Colocalizes with PECAM1 and CTNND1 at nascent cell-cell
CC contacts.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=p94;
CC IsoId=P16591-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P16591-2; Sequence=VSP_041765;
CC Name=3; Synonyms=FerT, p47;
CC IsoId=P16591-3; Sequence=VSP_043846, VSP_043847;
CC -!- TISSUE SPECIFICITY: Isoform 1 is detected in normal colon and in
CC fibroblasts (at protein level). Isoform 3 is detected in normal testis,
CC in colon carcinoma-derived metastases in lung, liver and ovary, and in
CC colon carcinoma and hepato carcinoma cell lines (at protein level).
CC Isoform 3 is not detected in normal colon or in normal fibroblasts (at
CC protein level). Widely expressed. {ECO:0000269|PubMed:18985748,
CC ECO:0000269|PubMed:2156206, ECO:0000269|PubMed:22223638}.
CC -!- DOMAIN: The coiled coil domains mediate homooligomerization and are
CC required for location at microtubules.
CC -!- DOMAIN: The N-terminal region including the first coiled coil domain
CC mediates interaction with phosphoinositide-containing membranes.
CC -!- PTM: Autophosphorylated. {ECO:0000269|PubMed:20111072,
CC ECO:0000269|PubMed:21518868}.
CC -!- PTM: Polyubiquitinated; this leads to proteasomal degradation.
CC {ECO:0000250}.
CC -!- MISCELLANEOUS: [Isoform 3]: Produced by alternative promoter usage.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. Fes/fps subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
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DR EMBL; J03358; AAA61190.1; -; mRNA.
DR EMBL; JQ412173; AEY69041.1; -; mRNA.
DR EMBL; AK299855; BAG61714.1; -; mRNA.
DR EMBL; AK315234; BAG37661.1; -; mRNA.
DR EMBL; AC034207; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC008871; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC109481; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC008955; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC010228; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC011421; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC116428; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471086; EAW49055.1; -; Genomic_DNA.
DR CCDS; CCDS4098.1; -. [P16591-1]
DR CCDS; CCDS78044.1; -. [P16591-3]
DR PIR; A31943; TVHUFE.
DR RefSeq; NP_001294957.1; NM_001308028.1. [P16591-2]
DR RefSeq; NP_001294960.1; NM_001308031.1. [P16591-3]
DR RefSeq; NP_001294967.1; NM_001308038.1.
DR RefSeq; NP_005237.2; NM_005246.3. [P16591-1]
DR RefSeq; XP_011541573.1; XM_011543271.2. [P16591-1]
DR RefSeq; XP_016864719.1; XM_017009230.1. [P16591-1]
DR RefSeq; XP_016864720.1; XM_017009231.1. [P16591-1]
DR PDB; 2KK6; NMR; -; A=453-557.
DR PDB; 6KC4; X-ray; 1.37 A; A/C/E/G/I/K=453-552.
DR PDBsum; 2KK6; -.
DR PDBsum; 6KC4; -.
DR AlphaFoldDB; P16591; -.
DR BMRB; P16591; -.
DR SMR; P16591; -.
DR BioGRID; 108532; 29.
DR CORUM; P16591; -.
DR IntAct; P16591; 22.
DR MINT; P16591; -.
DR STRING; 9606.ENSP00000281092; -.
DR BindingDB; P16591; -.
DR ChEMBL; CHEMBL3982; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; P16591; -.
DR GuidetoPHARMACOLOGY; 2022; -.
DR iPTMnet; P16591; -.
DR PhosphoSitePlus; P16591; -.
DR BioMuta; FER; -.
DR DMDM; 97536202; -.
DR EPD; P16591; -.
DR jPOST; P16591; -.
DR MassIVE; P16591; -.
DR MaxQB; P16591; -.
DR PaxDb; P16591; -.
DR PeptideAtlas; P16591; -.
DR PRIDE; P16591; -.
DR ProteomicsDB; 53382; -. [P16591-1]
DR ProteomicsDB; 53383; -. [P16591-2]
DR ProteomicsDB; 53384; -. [P16591-3]
DR Antibodypedia; 2083; 600 antibodies from 40 providers.
DR DNASU; 2241; -.
DR Ensembl; ENST00000281092.9; ENSP00000281092.4; ENSG00000151422.14. [P16591-1]
DR Ensembl; ENST00000618353.1; ENSP00000484767.1; ENSG00000151422.14. [P16591-3]
DR GeneID; 2241; -.
DR KEGG; hsa:2241; -.
DR MANE-Select; ENST00000281092.9; ENSP00000281092.4; NM_005246.4; NP_005237.2.
DR UCSC; uc031skp.2; human. [P16591-1]
DR CTD; 2241; -.
DR DisGeNET; 2241; -.
DR GeneCards; FER; -.
DR HGNC; HGNC:3655; FER.
DR HPA; ENSG00000151422; Low tissue specificity.
DR MIM; 176942; gene.
DR neXtProt; NX_P16591; -.
DR OpenTargets; ENSG00000151422; -.
DR PharmGKB; PA28095; -.
DR VEuPathDB; HostDB:ENSG00000151422; -.
DR eggNOG; KOG0194; Eukaryota.
DR GeneTree; ENSGT00940000154997; -.
DR HOGENOM; CLU_005265_0_0_1; -.
DR InParanoid; P16591; -.
DR OMA; NQFQQLT; -.
DR OrthoDB; 556386at2759; -.
DR PhylomeDB; P16591; -.
DR TreeFam; TF315363; -.
DR BRENDA; 2.7.10.2; 2681.
DR PathwayCommons; P16591; -.
DR Reactome; R-HSA-1433557; Signaling by SCF-KIT.
DR SignaLink; P16591; -.
DR SIGNOR; P16591; -.
DR BioGRID-ORCS; 2241; 19 hits in 1113 CRISPR screens.
DR ChiTaRS; FER; human.
DR EvolutionaryTrace; P16591; -.
DR GeneWiki; FER_(gene); -.
DR GenomeRNAi; 2241; -.
DR Pharos; P16591; Tclin.
DR PRO; PR:P16591; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; P16591; protein.
DR Bgee; ENSG00000151422; Expressed in calcaneal tendon and 185 other tissues.
DR ExpressionAtlas; P16591; baseline and differential.
DR Genevisible; P16591; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell.
DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0045098; C:type III intermediate filament; IEA:Ensembl.
DR GO; GO:0003779; F:actin binding; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0045296; F:cadherin binding; IEA:Ensembl.
DR GO; GO:0070097; F:delta-catenin binding; IEA:Ensembl.
DR GO; GO:0005154; F:epidermal growth factor receptor binding; IDA:UniProtKB.
DR GO; GO:0045295; F:gamma-catenin binding; IEA:Ensembl.
DR GO; GO:0008289; F:lipid binding; IDA:UniProtKB.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0008157; F:protein phosphatase 1 binding; IEA:Ensembl.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:1990782; F:protein tyrosine kinase binding; IEA:Ensembl.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0031267; F:small GTPase binding; IEA:Ensembl.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; ISS:UniProtKB.
DR GO; GO:0034333; P:adherens junction assembly; IEA:Ensembl.
DR GO; GO:0120179; P:adherens junction disassembly; IEA:Ensembl.
DR GO; GO:0007155; P:cell adhesion; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0008283; P:cell population proliferation; IEA:InterPro.
DR GO; GO:0044331; P:cell-cell adhesion mediated by cadherin; ISS:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; ISS:UniProtKB.
DR GO; GO:0036006; P:cellular response to macrophage colony-stimulating factor stimulus; IMP:UniProtKB.
DR GO; GO:0034614; P:cellular response to reactive oxygen species; ISS:UniProtKB.
DR GO; GO:0006935; P:chemotaxis; IBA:GO_Central.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:0050904; P:diapedesis; ISS:UniProtKB.
DR GO; GO:0035426; P:extracellular matrix-cell signaling; ISS:UniProtKB.
DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0007281; P:germ cell development; IEA:Ensembl.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0038028; P:insulin receptor signaling pathway via phosphatidylinositol 3-kinase; ISS:UniProtKB.
DR GO; GO:0070102; P:interleukin-6-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; TAS:ProtInc.
DR GO; GO:0038109; P:Kit signaling pathway; ISS:UniProtKB.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IMP:UniProtKB.
DR GO; GO:0033007; P:negative regulation of mast cell activation involved in immune response; ISS:UniProtKB.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
DR GO; GO:0048008; P:platelet-derived growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0030838; P:positive regulation of actin filament polymerization; IMP:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; IMP:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:CACAO.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; TAS:ProtInc.
DR GO; GO:0042058; P:regulation of epidermal growth factor receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0010762; P:regulation of fibroblast migration; IEA:Ensembl.
DR GO; GO:0010591; P:regulation of lamellipodium assembly; IDA:UniProtKB.
DR GO; GO:0043304; P:regulation of mast cell degranulation; IBA:GO_Central.
DR GO; GO:0001932; P:regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0032496; P:response to lipopolysaccharide; ISS:UniProtKB.
DR GO; GO:0036119; P:response to platelet-derived growth factor; ISS:UniProtKB.
DR GO; GO:0060009; P:Sertoli cell development; IEA:Ensembl.
DR GO; GO:0034446; P:substrate adhesion-dependent cell spreading; ISS:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR GO; GO:0007260; P:tyrosine phosphorylation of STAT protein; IDA:UniProtKB.
DR CDD; cd07686; F-BAR_Fer; 1.
DR CDD; cd10361; SH2_Fps_family; 1.
DR Gene3D; 1.20.1270.60; -; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR027267; AH/BAR_dom_sf.
DR InterPro; IPR031160; F_BAR.
DR InterPro; IPR001060; FCH_dom.
DR InterPro; IPR028539; Fer.
DR InterPro; IPR037452; Fer_F-BAR.
DR InterPro; IPR035849; Fes/Fps/Fer_SH2.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR016250; Tyr-prot_kinase_Fes/Fps.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR PANTHER; PTHR24418:SF227; PTHR24418:SF227; 1.
DR Pfam; PF00611; FCH; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF00017; SH2; 1.
DR PIRSF; PIRSF000632; TyrPK_fps; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00055; FCH; 1.
DR SMART; SM00252; SH2; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF103657; SSF103657; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51741; F_BAR; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS50001; SH2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative promoter usage; Alternative splicing;
KW ATP-binding; Cell junction; Cell membrane; Cell projection; Coiled coil;
KW Cytoplasm; Cytoskeleton; Kinase; Lipid-binding; Membrane;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Proto-oncogene;
KW Reference proteome; SH2 domain; Transferase; Tyrosine-protein kinase;
KW Ubl conjugation.
FT CHAIN 1..822
FT /note="Tyrosine-protein kinase Fer"
FT /id="PRO_0000088084"
FT DOMAIN 1..259
FT /note="F-BAR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01077"
FT DOMAIN 460..550
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 563..816
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..300
FT /note="Important for interaction with membranes containing
FT phosphoinositides"
FT COILED 123..185
FT /evidence="ECO:0000255"
FT COILED 301..390
FT /evidence="ECO:0000255"
FT ACT_SITE 684
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 569..577
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 591
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 402
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 434
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:23186163"
FT MOD_RES 615
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P70451"
FT MOD_RES 714
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P70451"
FT VAR_SEQ 1..369
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:22223638"
FT /id="VSP_043846"
FT VAR_SEQ 1..175
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_041765"
FT VAR_SEQ 370..412
FT /note="LRCTEAKFSAQKELLEQKVQENDGKEPPPVVNYEEDARSVTSM -> MEQKM
FT KCPHCKDQLESGFGSQSCKTCALMFSSEPSTSEVHRDQ (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:22223638"
FT /id="VSP_043847"
FT VARIANT 128
FT /note="V -> F (in dbSNP:rs35150210)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041691"
FT VARIANT 404
FT /note="E -> Q (in an ovarian Endometrioid carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041692"
FT VARIANT 412
FT /note="M -> V (in dbSNP:rs33940843)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041693"
FT VARIANT 439
FT /note="L -> V (in dbSNP:rs2229086)"
FT /evidence="ECO:0000269|PubMed:1651563,
FT ECO:0000269|PubMed:17344846, ECO:0000269|PubMed:2725517"
FT /id="VAR_006282"
FT VARIANT 443
FT /note="A -> P (in dbSNP:rs34259824)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041694"
FT VARIANT 460
FT /note="W -> C (in a lung small cell carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041695"
FT VARIANT 507
FT /note="I -> T (in dbSNP:rs34204308)"
FT /id="VAR_051695"
FT VARIANT 813
FT /note="E -> Q (in dbSNP:rs56097357)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041696"
FT MUTAGEN 483
FT /note="R->Q: Abolishes kinase activity. Abolishes location
FT at microtubules."
FT /evidence="ECO:0000269|PubMed:12972546"
FT MUTAGEN 591
FT /note="K->R: Abolishes kinase activity."
FT /evidence="ECO:0000269|PubMed:9722593"
FT CONFLICT 219
FT /note="I -> L (in Ref. 3; BAG61714)"
FT /evidence="ECO:0000305"
FT CONFLICT 234
FT /note="S -> N (in Ref. 3; BAG61714)"
FT /evidence="ECO:0000305"
FT CONFLICT 426
FT /note="H -> Q (in Ref. 3; BAG61714)"
FT /evidence="ECO:0000305"
FT CONFLICT 447
FT /note="M -> L (in Ref. 2; AEY69041)"
FT /evidence="ECO:0000305"
FT CONFLICT 485
FT /note="S -> G (in Ref. 2; AEY69041)"
FT /evidence="ECO:0000305"
FT CONFLICT 492
FT /note="Y -> H (in Ref. 2; AEY69041)"
FT /evidence="ECO:0000305"
FT CONFLICT 505
FT /note="F -> L (in Ref. 3; BAG61714)"
FT /evidence="ECO:0000305"
FT CONFLICT 558
FT /note="L -> F (in Ref. 2; AEY69041)"
FT /evidence="ECO:0000305"
FT CONFLICT 730
FT /note="E -> G (in Ref. 3; BAG61714)"
FT /evidence="ECO:0000305"
FT HELIX 455..457
FT /evidence="ECO:0007829|PDB:6KC4"
FT STRAND 461..464
FT /evidence="ECO:0007829|PDB:2KK6"
FT HELIX 467..473
FT /evidence="ECO:0007829|PDB:6KC4"
FT STRAND 479..484
FT /evidence="ECO:0007829|PDB:6KC4"
FT STRAND 486..488
FT /evidence="ECO:0007829|PDB:6KC4"
FT STRAND 492..498
FT /evidence="ECO:0007829|PDB:6KC4"
FT STRAND 501..510
FT /evidence="ECO:0007829|PDB:6KC4"
FT STRAND 513..518
FT /evidence="ECO:0007829|PDB:6KC4"
FT STRAND 521..523
FT /evidence="ECO:0007829|PDB:6KC4"
FT HELIX 524..534
FT /evidence="ECO:0007829|PDB:6KC4"
FT TURN 540..542
FT /evidence="ECO:0007829|PDB:6KC4"
SQ SEQUENCE 822 AA; 94638 MW; BD42DF6C03419C76 CRC64;
MGFGSDLKNS HEAVLKLQDW ELRLLETVKK FMALRIKSDK EYASTLQNLC NQVDKESTVQ
MNYVSNVSKS WLLMIQQTEQ LSRIMKTHAE DLNSGPLHRL TMMIKDKQQV KKSYIGVHQQ
IEAEMIKVTK TELEKLKCSY RQLIKEMNSA KEKYKEALAK GKETEKAKER YDKATMKLHM
LHNQYVLALK GAQLHQNQYY DITLPLLLDS LQKMQEEMIK ALKGIFDEYS QITSLVTEEI
VNVHKEIQMS VEQIDPSTEY NNFIDVHRTT AAKEQEIEFD TSLLEENENL QANEIMWNNL
TAESLQVMLK TLAEELMQTQ QMLLNKEEAV LELEKRIEES SETCEKKSDI VLLLSQKQAL
EELKQSVQQL RCTEAKFSAQ KELLEQKVQE NDGKEPPPVV NYEEDARSVT SMERKERLSK
FESIRHSIAG IIRSPKSALG SSALSDMISI SEKPLAEQDW YHGAIPRIEA QELLKKQGDF
LVRESHGKPG EYVLSVYSDG QRRHFIIQYV DNMYRFEGTG FSNIPQLIDH HYTTKQVITK
KSGVVLLNPI PKDKKWILSH EDVILGELLG KGNFGEVYKG TLKDKTSVAV KTCKEDLPQE
LKIKFLQEAK ILKQYDHPNI VKLIGVCTQR QPVYIIMELV SGGDFLTFLR RKKDELKLKQ
LVKFSLDAAA GMLYLESKNC IHRDLAARNC LVGENNVLKI SDFGMSRQED GGVYSSSGLK
QIPIKWTAPE ALNYGRYSSE SDVWSFGILL WETFSLGVCP YPGMTNQQAR EQVERGYRMS
APQHCPEDIS KIMMKCWDYK PENRPKFSEL QKELTIIKRK LT
