ERBB4_MOUSE
ID ERBB4_MOUSE Reviewed; 1308 AA.
AC Q61527; B2KGF5; B2KGF6; O88460; Q3UNS6;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 25-JAN-2012, sequence version 5.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=Receptor tyrosine-protein kinase erbB-4;
DE EC=2.7.10.1;
DE AltName: Full=Proto-oncogene-like protein c-ErbB-4;
DE Contains:
DE RecName: Full=ERBB4 intracellular domain;
DE Short=4ICD;
DE Short=E4ICD;
DE AltName: Full=s80HER4;
DE Flags: Precursor;
GN Name=Erbb4; Synonyms=Mer4;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-1263 (JM-A CYT-2).
RC STRAIN=C57BL/6J; TISSUE=Kidney;
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., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., 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., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 624-650 (ISOFORMS JM-A CYT-2 AND JM-B CYT-2).
RC TISSUE=Heart, and Kidney;
RX PubMed=9334263; DOI=10.1074/jbc.272.42.26761;
RA Elenius K., Corfas G., Paul S., Choi C.J., Rio C., Plowman G.D.,
RA Klagsbrun M.;
RT "A novel juxtamembrane domain isoform of HER4/ErbB4. Isoform-specific
RT tissue distribution and differential processing in response to phorbol
RT ester.";
RL J. Biol. Chem. 272:26761-26768(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1019-1102 (ISOFORM JM-A CYT-1).
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=7589796; DOI=10.1006/dbio.1995.0012;
RA Moscoso L.M., Chu G.C., Gautam M., Noakes P.G., Merlie J.P., Sanes J.R.;
RT "Synapse-associated expression of an acetylcholine receptor-inducing
RT protein, ARIA/heregulin, and its putative receptors, ErbB2 and ErbB3, in
RT developing mammalian muscle.";
RL Dev. Biol. 172:158-169(1995).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1019-1093 (ISOFORM JM-A CYT-1).
RC STRAIN=CD-1; TISSUE=Uterus;
RA Lim H., Das S.K., Dey S.K.;
RT "Potential signaling network by EGF-like growth factors in the mouse uterus
RT during early pregnancy.";
RL Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=7477376; DOI=10.1038/378390a0;
RA Gassmann M., Casagranda F., Orioli D., Simon H., Lai C., Klein R.,
RA Lemke G.;
RT "Aberrant neural and cardiac development in mice lacking the ErbB4
RT neuregulin receptor.";
RL Nature 378:390-394(1995).
RN [7]
RP FUNCTION IN MAMMARY GLAND DEVELOPMENT AND ACTIVATION OF STAT5A, AND
RP INTERACTION WITH STAT5A.
RX PubMed=10508857; DOI=10.1083/jcb.147.1.77;
RA Jones F.E., Welte T., Fu X.Y., Stern D.F.;
RT "ErbB4 signaling in the mammary gland is required for lobuloalveolar
RT development and Stat5 activation during lactation.";
RL J. Cell Biol. 147:77-88(1999).
RN [8]
RP ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY.
RX PubMed=10353604; DOI=10.1038/sj.onc.1202612;
RA Elenius K., Choi C.J., Paul S., Santiestevan E., Nishi E., Klagsbrun M.;
RT "Characterization of a naturally occurring ErbB4 isoform that does not bind
RT or activate phosphatidyl inositol 3-kinase.";
RL Oncogene 18:2607-2615(1999).
RN [9]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=10655590; DOI=10.1038/35000058;
RA Golding J.P., Trainor P., Krumlauf R., Gassmann M.;
RT "Defects in pathfinding by cranial neural crest cells in mice lacking the
RT neuregulin receptor ErbB4.";
RL Nat. Cell Biol. 2:103-109(2000).
RN [10]
RP DISRUPTION PHENOTYPE.
RX PubMed=12954715; DOI=10.1242/dev.00715;
RA Long W., Wagner K.U., Lloyd K.C., Binart N., Shillingford J.M.,
RA Hennighausen L., Jones F.E.;
RT "Impaired differentiation and lactational failure of Erbb4-deficient
RT mammary glands identify ERBB4 as an obligate mediator of STAT5.";
RL Development 130:5257-5268(2003).
RN [11]
RP DISRUPTION PHENOTYPE.
RX PubMed=12824469; DOI=10.1073/pnas.1436402100;
RA Tidcombe H., Jackson-Fisher A., Mathers K., Stern D.F., Gassmann M.,
RA Golding J.P.;
RT "Neural and mammary gland defects in ErbB4 knockout mice genetically
RT rescued from embryonic lethality.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:8281-8286(2003).
RN [12]
RP FUNCTION IN NEUROBLAST MIGRATION.
RX PubMed=15543145; DOI=10.1038/nn1345;
RA Anton E.S., Ghashghaei H.T., Weber J.L., McCann C., Fischer T.M.,
RA Cheung I.D., Gassmann M., Messing A., Klein R., Schwab M.H., Lloyd K.C.,
RA Lai C.;
RT "Receptor tyrosine kinase ErbB4 modulates neuroblast migration and
RT placement in the adult forebrain.";
RL Nat. Neurosci. 7:1319-1328(2004).
RN [13]
RP FUNCTION.
RX PubMed=15863494; DOI=10.1074/jbc.m414044200;
RA Clark D.E., Williams C.C., Duplessis T.T., Moring K.L., Notwick A.R.,
RA Long W., Lane W.S., Beuvink I., Hynes N.E., Jones F.E.;
RT "ERBB4/HER4 potentiates STAT5A transcriptional activity by regulating novel
RT STAT5A serine phosphorylation events.";
RL J. Biol. Chem. 280:24175-24180(2005).
RN [14]
RP INTERACTION WITH CBFA2T3.
RX PubMed=16815842; DOI=10.1074/jbc.m603998200;
RA Linggi B., Carpenter G.;
RT "ErbB-4 s80 intracellular domain abrogates ETO2-dependent transcriptional
RT repression.";
RL J. Biol. Chem. 281:25373-25380(2006).
RN [15]
RP FUNCTION, PROTEOLYTIC PROCESSING, AND SUBCELLULAR LOCATION.
RX PubMed=16837552; DOI=10.1091/mbc.e06-02-0101;
RA Muraoka-Cook R.S., Sandahl M., Husted C., Hunter D., Miraglia L.,
RA Feng S.M., Elenius K., Earp H.S. III;
RT "The intracellular domain of ErbB4 induces differentiation of mammary
RT epithelial cells.";
RL Mol. Biol. Cell 17:4118-4129(2006).
RN [16]
RP FUNCTION OF E4ICD.
RX PubMed=19596786; DOI=10.1128/mcb.01705-08;
RA Muraoka-Cook R.S., Sandahl M.A., Strunk K.E., Miraglia L.C., Husted C.,
RA Hunter D.M., Elenius K., Chodosh L.A., Earp H.S. III;
RT "ErbB4 splice variants Cyt1 and Cyt2 differ by 16 amino acids and exert
RT opposing effects on the mammary epithelium in vivo.";
RL Mol. Cell. Biol. 29:4935-4948(2009).
RN [17]
RP FUNCTION AS NRG1 RECEPTOR IN POSTNATAL CARDIOMYOCYTE PROLIFERATION.
RX PubMed=19632177; DOI=10.1016/j.cell.2009.04.060;
RA Bersell K., Arab S., Haring B., Kuhn B.;
RT "Neuregulin1/ErbB4 signaling induces cardiomyocyte proliferation and repair
RT of heart injury.";
RL Cell 138:257-270(2009).
RN [18]
RP REVIEW.
RX PubMed=14504474;
RA Jones F.E., Golding J.P., Gassmann M.;
RT "ErbB4 signaling during breast and neural development: novel genetic models
RT reveal unique ErbB4 activities.";
RL Cell Cycle 2:555-559(2003).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [20]
RP REVIEW ON ROLE AS NEUREGULIN RECEPTOR.
RX PubMed=21295966; DOI=10.1016/j.gde.2010.12.010;
RA Rico B., Marin O.;
RT "Neuregulin signaling, cortical circuitry development and schizophrenia.";
RL Curr. Opin. Genet. Dev. 21:262-270(2011).
CC -!- FUNCTION: Tyrosine-protein kinase that plays an essential role as cell
CC surface receptor for neuregulins and EGF family members and regulates
CC development of the heart, the central nervous system and the mammary
CC gland, gene transcription, cell proliferation, differentiation,
CC migration and apoptosis. Required for normal cardiac muscle
CC differentiation during embryonic development, and for postnatal
CC cardiomyocyte proliferation. Required for normal development of the
CC embryonic central nervous system, especially for normal neural crest
CC cell migration and normal axon guidance. Required for mammary gland
CC differentiation, induction of milk proteins and lactation. Acts as
CC cell-surface receptor for the neuregulins NRG1, NRG2, NRG3 and NRG4 and
CC the EGF family members BTC, EREG and HBEGF. Ligand binding triggers
CC receptor dimerization and autophosphorylation at specific tyrosine
CC residues that then serve as binding sites for scaffold proteins and
CC effectors. Ligand specificity and signaling is modulated by alternative
CC splicing, proteolytic processing, and by the formation of heterodimers
CC with other ERBB family members, thereby creating multiple combinations
CC of intracellular phosphotyrosines that trigger ligand- and context-
CC specific cellular responses. Mediates phosphorylation of SHC1 and
CC activation of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Isoform JM-A
CC CYT-1 and isoform JM-B CYT-1 phosphorylate PIK3R1, leading to the
CC activation of phosphatidylinositol 3-kinase and AKT1 and protect cells
CC against apoptosis. Isoform JM-A CYT-1 and isoform JM-B CYT-1 mediate
CC reorganization of the actin cytoskeleton and promote cell migration in
CC response to NRG1. Isoform JM-A CYT-2 and isoform JM-B CYT-2 lack the
CC phosphotyrosine that mediates interaction with PIK3R1, and hence do not
CC phosphorylate PIK3R1, do not protect cells against apoptosis, and do
CC not promote reorganization of the actin cytoskeleton and cell
CC migration. Proteolytic processing of isoform JM-A CYT-1 and isoform JM-
CC A CYT-2 gives rise to the corresponding soluble intracellular domains
CC (4ICD) that translocate to the nucleus, promote nuclear import of
CC STAT5A, activation of STAT5A, mammary epithelium differentiation, cell
CC proliferation and activation of gene expression. The ERBB4 soluble
CC intracellular domains (4ICD) colocalize with STAT5A at the CSN2
CC promoter to regulate transcription of milk proteins during lactation.
CC The ERBB4 soluble intracellular domains can also translocate to
CC mitochondria and promote apoptosis. {ECO:0000269|PubMed:10508857,
CC ECO:0000269|PubMed:10655590, ECO:0000269|PubMed:15543145,
CC ECO:0000269|PubMed:15863494, ECO:0000269|PubMed:16837552,
CC ECO:0000269|PubMed:19596786, ECO:0000269|PubMed:19632177,
CC ECO:0000269|PubMed:7477376}.
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=2.7.10.1;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
CC -!- ACTIVITY REGULATION: Binding of a cognate ligand leads to dimerization
CC and activation by autophosphorylation on tyrosine residues. In vitro
CC kinase activity is increased by Mg(2+) (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Monomer in the absence of bound ligand. Homodimer or
CC heterodimer with another ERBB family member upon ligand binding, thus
CC forming heterotetramers. Interacts with EGFR and ERBB2. Interacts with
CC DLG2 (via its PDZ domain), DLG3 (via its PDZ domain), DLG4 (via its PDZ
CC domain) and SNTB2 (via its PDZ domain). Interacts with MUC1. Interacts
CC (via its PPxy motifs) with WWOX. Interacts (via the PPxY motif 3 of
CC isoform JM-A CYT-2) with YAP1 (via the WW domain 1 of isoform 1).
CC Interacts (isoform JM-A CYT-1 and isoform JM-B CYT-1) with WWP1.
CC Interacts (via its intracellular domain) with TRIM28. Interacts (via
CC the intracellular domains of both CYT-1 and CYT-2 isoforms) with KAP1;
CC the interaction does not phosphorylate KAP1 but represses ERBB4-
CC mediated transcriptional activity. Interacts with PRPU, DDX23, MATR3,
CC RBM15, ILF3, KAP1, U5S1, U2SURP, ITCH, HNRNPU, AP2A1, NULC, LEO1, WWP2,
CC IGHG1, HXK1, GRB7 AND SRRT. Interacts (phosphorylated isoform JM-A CYT-
CC 1 and isoform JM-B CYT-1) with PIK3R1. Interacts with SHC1. Interacts
CC with GRB2. Interacts (soluble intracellular domain) with BCL2.
CC Interacts (phosphorylated) with STAT1 (By similarity). Interacts with
CC CBFA2T3. Interacts (soluble intracellular domain) with STAT5A.
CC {ECO:0000250, ECO:0000269|PubMed:10508857,
CC ECO:0000269|PubMed:16815842}.
CC -!- INTERACTION:
CC Q61527; Q9NZC7: WWOX; Xeno; NbExp=3; IntAct=EBI-4398741, EBI-4320739;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16837552};
CC Single-pass type I membrane protein {ECO:0000269|PubMed:16837552}.
CC Note=In response to NRG1 treatment, the activated receptor is
CC internalized.
CC -!- SUBCELLULAR LOCATION: [ERBB4 intracellular domain]: Nucleus.
CC Mitochondrion {ECO:0000250}. Note=Following proteolytical processing
CC E4ICD (E4ICD1 or E4ICD2 generated from the respective isoforms) is
CC translocated to the nucleus. Significantly more E4ICD2 than E4ICD1 is
CC found in the nucleus. E4ICD2 colocalizes with YAP1 in the nucleus (By
CC similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Comment=Additional isoforms seem to exist.;
CC Name=JM-A CYT-1;
CC IsoId=Q61527-1; Sequence=Displayed;
CC Name=JM-B CYT-2;
CC IsoId=Q61527-2; Sequence=VSP_002896;
CC Name=JM-A CYT-2;
CC IsoId=Q61527-3; Sequence=VSP_042131;
CC -!- TISSUE SPECIFICITY: Isoform JM-A CYT-2 and isoform JM-B CYT-2 are
CC expressed in cerebellum, cerebral cortex, spinal cord, medulla
CC oblongata and eye, but the kidney expresses solely isoform JM-A CYT-2
CC and the heart solely isoform JM-B CYT-2. {ECO:0000269|PubMed:10353604}.
CC -!- PTM: Isoform JM-A CYT-1 and isoform JM-A CYT-2 are processed by ADAM17.
CC Proteolytic processing in response to ligand or 12-O-
CC tetradecanoylphorbol-13-acetate stimulation results in the production
CC of 120 kDa soluble receptor forms and intermediate membrane-anchored 80
CC kDa fragments (m80HER4), which are further processed by a presenilin-
CC dependent gamma-secretase to release a cytoplasmic intracellular domain
CC (E4ICD; E4ICD1/s80Cyt1 or E4ICD2/s80Cyt2, depending on the isoform).
CC Membrane-anchored 80 kDa fragments of the processed isoform JM-A CYT-1
CC are more readily degraded by the proteasome than fragments of isoform
CC JM-A CYT-2, suggesting a prevalence of E4ICD2 over E4ICD1. Isoform JM-B
CC CYT-1 and isoform JM-B CYT-2 lack the ADAM17 cleavage site and are not
CC processed by ADAM17, precluding further processing by gamma-secretase
CC (By similarity). {ECO:0000250}.
CC -!- PTM: Autophosphorylated on tyrosine residues in response to ligand
CC binding. Autophosphorylation occurs in trans, i.e. one subunit of the
CC dimeric receptor phosphorylates tyrosine residues on the other subunit.
CC Ligands trigger phosphorylation at specific tyrosine residues, thereby
CC creating binding sites for scaffold proteins and effectors.
CC Constitutively phosphorylated at a basal level when overexpressed in
CC heterologous systems; ligand binding leads to increased
CC phosphorylation. Phosphorylation at Tyr-1035 is important for
CC interaction with STAT1. Phosphorylation at Tyr-1056 is important for
CC interaction with PIK3R1. Phosphorylation at Tyr-1242 is important for
CC interaction with SHC1. Phosphorylation at Tyr-1188 may also contribute
CC to the interaction with SHC1. Isoform JM-A CYT-2 is constitutively
CC phosphorylated on tyrosine residues in a ligand-independent manner.
CC E4ICD2 but not E4ICD1 is phosphorylated on tyrosine residues (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Ubiquitinated. During mitosis, the ERBB4 intracellular domain is
CC ubiquitinated by the APC/C complex and targeted to proteasomal
CC degradation. Isoform JM-A CYT-1 and isoform JM-B CYT-1 are
CC ubiquitinated by WWP1. The ERBB4 intracellular domain (E4ICD1) is
CC ubiquitinated, and this involves NEDD4 (By similarity). {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Embryonically lethal. Embryos die at about 10
CC dpc, due to defects in the development of myocardial trabeculae in the
CC heart ventricle that lead to severely reduced embryonic blood flow.
CC Mice also display aberrant innervation from and to the hindbrain,
CC especially concerning the trigeminal, facial and acoustic ganglia. This
CC is due to aberrant migration of a subpopulation of cranial neural crest
CC cells. {ECO:0000269|PubMed:10655590, ECO:0000269|PubMed:12824469,
CC ECO:0000269|PubMed:12954715, ECO:0000269|PubMed:7477376}.
CC -!- MISCELLANEOUS: [Isoform JM-A CYT-1]: Proteolytical processing generates
CC E4ICD1 (s80Cyt1).
CC -!- MISCELLANEOUS: [Isoform JM-A CYT-2]: Proteolytical processing generates
CC E4ICD2 (s80Cyt2). {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. EGF receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
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; CU368746; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CU372923; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CU392849; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CU405881; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CU407006; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CU459008; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CU459207; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK144050; BAE25671.1; -; mRNA.
DR EMBL; L47241; AAA93534.1; -; mRNA.
DR EMBL; AF059177; AAC28334.1; -; mRNA.
DR CCDS; CCDS48285.1; -. [Q61527-3]
DR RefSeq; NP_034284.1; NM_010154.2. [Q61527-3]
DR RefSeq; XP_006495755.1; XM_006495692.3. [Q61527-1]
DR RefSeq; XP_006495756.1; XM_006495693.3. [Q61527-2]
DR AlphaFoldDB; Q61527; -.
DR SMR; Q61527; -.
DR BioGRID; 199498; 5.
DR DIP; DIP-29887N; -.
DR IntAct; Q61527; 3.
DR STRING; 10090.ENSMUSP00000114123; -.
DR GlyConnect; 2677; 1 N-Linked glycan (1 site).
DR GlyGen; Q61527; 11 sites, 1 N-linked glycan (1 site).
DR iPTMnet; Q61527; -.
DR PhosphoSitePlus; Q61527; -.
DR jPOST; Q61527; -.
DR MaxQB; Q61527; -.
DR PaxDb; Q61527; -.
DR PeptideAtlas; Q61527; -.
DR PRIDE; Q61527; -.
DR ProteomicsDB; 275879; -. [Q61527-1]
DR ProteomicsDB; 275880; -. [Q61527-2]
DR ProteomicsDB; 275881; -. [Q61527-3]
DR Antibodypedia; 1602; 1470 antibodies from 46 providers.
DR DNASU; 13869; -.
DR Ensembl; ENSMUST00000119142; ENSMUSP00000112713; ENSMUSG00000062209. [Q61527-1]
DR Ensembl; ENSMUST00000121473; ENSMUSP00000114123; ENSMUSG00000062209. [Q61527-3]
DR GeneID; 13869; -.
DR KEGG; mmu:13869; -.
DR UCSC; uc007bjb.1; mouse. [Q61527-3]
DR CTD; 2066; -.
DR MGI; MGI:104771; Erbb4.
DR VEuPathDB; HostDB:ENSMUSG00000062209; -.
DR eggNOG; KOG1025; Eukaryota.
DR GeneTree; ENSGT00940000154695; -.
DR HOGENOM; CLU_003384_1_1_1; -.
DR InParanoid; Q61527; -.
DR OMA; XEALIMA; -.
DR OrthoDB; 81952at2759; -.
DR PhylomeDB; Q61527; -.
DR TreeFam; TF106002; -.
DR Reactome; R-MMU-1227986; Signaling by ERBB2.
DR Reactome; R-MMU-1236394; Signaling by ERBB4.
DR Reactome; R-MMU-1250196; SHC1 events in ERBB2 signaling.
DR Reactome; R-MMU-1250342; PI3K events in ERBB4 signaling.
DR Reactome; R-MMU-1250347; SHC1 events in ERBB4 signaling.
DR Reactome; R-MMU-1251985; Nuclear signaling by ERBB4.
DR Reactome; R-MMU-1253288; Downregulation of ERBB4 signaling.
DR Reactome; R-MMU-1257604; PIP3 activates AKT signaling.
DR Reactome; R-MMU-1963640; GRB2 events in ERBB2 signaling.
DR Reactome; R-MMU-1963642; PI3K events in ERBB2 signaling.
DR Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
DR Reactome; R-MMU-6785631; ERBB2 Regulates Cell Motility.
DR Reactome; R-MMU-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-MMU-8847993; ERBB2 Activates PTK6 Signaling.
DR Reactome; R-MMU-8863795; Downregulation of ERBB2 signaling.
DR Reactome; R-MMU-9018519; Estrogen-dependent gene expression.
DR BioGRID-ORCS; 13869; 1 hit in 76 CRISPR screens.
DR ChiTaRS; Erbb4; mouse.
DR PRO; PR:Q61527; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q61527; protein.
DR Bgee; ENSMUSG00000062209; Expressed in neural tube mantle layer and 155 other tissues.
DR ExpressionAtlas; Q61527; baseline and differential.
DR Genevisible; Q61527; MM.
DR GO; GO:0009925; C:basal plasma membrane; IBA:GO_Central.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:MGI.
DR GO; GO:0005901; C:caveola; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0098982; C:GABA-ergic synapse; IDA:SynGO.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0060077; C:inhibitory synapse; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0099061; C:integral component of postsynaptic density membrane; IDA:MGI.
DR GO; GO:0099056; C:integral component of presynaptic membrane; IDA:SynGO.
DR GO; GO:0045121; C:membrane raft; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0014069; C:postsynaptic density; ISO:MGI.
DR GO; GO:0098839; C:postsynaptic density membrane; IDA:MGI.
DR GO; GO:0045211; C:postsynaptic membrane; ISS:UniProtKB.
DR GO; GO:0043235; C:receptor complex; ISO:MGI.
DR GO; GO:0044214; C:spanning component of plasma membrane; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005006; F:epidermal growth factor receptor activity; IGI:MGI.
DR GO; GO:0005154; F:epidermal growth factor receptor binding; ISO:MGI.
DR GO; GO:0050811; F:GABA receptor binding; IDA:MGI.
DR GO; GO:0038132; F:neuregulin binding; ISO:MGI.
DR GO; GO:0038131; F:neuregulin receptor activity; IDA:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0030296; F:protein tyrosine kinase activator activity; IDA:MGI.
DR GO; GO:0004713; F:protein tyrosine kinase activity; ISO:MGI.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:MGI.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IDA:MGI.
DR GO; GO:0061026; P:cardiac muscle tissue regeneration; IMP:UniProtKB.
DR GO; GO:0045165; P:cell fate commitment; IDA:MGI.
DR GO; GO:0016477; P:cell migration; ISS:UniProtKB.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IDA:MGI.
DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; IDA:MGI.
DR GO; GO:0021551; P:central nervous system morphogenesis; IMP:UniProtKB.
DR GO; GO:0009880; P:embryonic pattern specification; IMP:UniProtKB.
DR GO; GO:0038135; P:ERBB2-ERBB4 signaling pathway; IDA:MGI.
DR GO; GO:0038130; P:ERBB4 signaling pathway; IMP:MGI.
DR GO; GO:0038138; P:ERBB4-ERBB4 signaling pathway; IDA:MGI.
DR GO; GO:0072046; P:establishment of planar polarity involved in nephron morphogenesis; IMP:MGI.
DR GO; GO:0007507; P:heart development; IMP:MGI.
DR GO; GO:0007595; P:lactation; IMP:UniProtKB.
DR GO; GO:0060749; P:mammary gland alveolus development; IMP:UniProtKB.
DR GO; GO:0060644; P:mammary gland epithelial cell differentiation; IMP:UniProtKB.
DR GO; GO:0043653; P:mitochondrial fragmentation involved in apoptotic process; ISS:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0010656; P:negative regulation of muscle cell apoptotic process; ISO:MGI.
DR GO; GO:0007399; P:nervous system development; IMP:MGI.
DR GO; GO:0001755; P:neural crest cell migration; IMP:UniProtKB.
DR GO; GO:0021889; P:olfactory bulb interneuron differentiation; IMP:UniProtKB.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISS:UniProtKB.
DR GO; GO:0060045; P:positive regulation of cardiac muscle cell proliferation; IMP:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; ISO:MGI.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0046326; P:positive regulation of glucose import; ISO:MGI.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; ISS:UniProtKB.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IGI:MGI.
DR GO; GO:0071073; P:positive regulation of phospholipid biosynthetic process; ISO:MGI.
DR GO; GO:2000010; P:positive regulation of protein localization to cell surface; IGI:MGI.
DR GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; IMP:UniProtKB.
DR GO; GO:0032230; P:positive regulation of synaptic transmission, GABAergic; ISO:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IMP:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0030334; P:regulation of cell migration; IMP:UniProtKB.
DR GO; GO:0007165; P:signal transduction; ISO:MGI.
DR GO; GO:0043129; P:surfactant homeostasis; ISO:MGI.
DR GO; GO:0007416; P:synapse assembly; IDA:SynGO.
DR GO; GO:0060074; P:synapse maturation; ISO:MGI.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; ISS:UniProtKB.
DR CDD; cd00064; FU; 3.
DR Gene3D; 3.80.20.20; -; 2.
DR InterPro; IPR006211; Furin-like_Cys-rich_dom.
DR InterPro; IPR006212; Furin_repeat.
DR InterPro; IPR032778; GF_recep_IV.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR000494; Rcpt_L-dom.
DR InterPro; IPR036941; Rcpt_L-dom_sf.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR InterPro; IPR016245; Tyr_kinase_EGF/ERB/XmrK_rcpt.
DR Pfam; PF00757; Furin-like; 1.
DR Pfam; PF14843; GF_recep_IV; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF01030; Recep_L_domain; 2.
DR PIRSF; PIRSF000619; TyrPK_EGF-R; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00261; FU; 5.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57184; SSF57184; 2.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
PE 1: Evidence at protein level;
KW Activator; Alternative splicing; Apoptosis; ATP-binding; Cell membrane;
KW Developmental protein; Disulfide bond; Glycoprotein; Kinase; Lactation;
KW Membrane; Mitochondrion; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Receptor; Reference proteome; Repeat; Signal; Transcription;
KW Transcription regulation; Transferase; Transmembrane; Transmembrane helix;
KW Tyrosine-protein kinase; Ubl conjugation.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..1308
FT /note="Receptor tyrosine-protein kinase erbB-4"
FT /id="PRO_0000270146"
FT CHAIN 676..1308
FT /note="ERBB4 intracellular domain"
FT /id="PRO_0000396798"
FT TOPO_DOM 26..652
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 653..673
FT /evidence="ECO:0000255"
FT TOPO_DOM 674..1308
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 718..985
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1117..1149
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 676..684
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT MOTIF 1032..1035
FT /note="PPxy motif 1"
FT /evidence="ECO:0000250"
FT MOTIF 1282..1285
FT /note="PPxY motif 2"
FT /evidence="ECO:0000250"
FT MOTIF 1290..1292
FT /note="PDZ-binding"
FT /evidence="ECO:0000250"
FT ACT_SITE 843
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 724..732
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 751
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 797..799
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 843..848
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 875
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q15303"
FT MOD_RES 1035
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q15303"
FT MOD_RES 1056
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q15303"
FT MOD_RES 1150
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q15303"
FT MOD_RES 1162
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q15303"
FT MOD_RES 1188
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q15303"
FT MOD_RES 1202
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q15303"
FT MOD_RES 1242
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q15303"
FT MOD_RES 1258
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q15303"
FT MOD_RES 1284
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q15303"
FT CARBOHYD 138
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 174
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 181
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 253
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 410
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 473
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 495
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 548
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 576
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 620
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 29..56
FT /evidence="ECO:0000250"
FT DISULFID 156..186
FT /evidence="ECO:0000250"
FT DISULFID 189..197
FT /evidence="ECO:0000250"
FT DISULFID 193..205
FT /evidence="ECO:0000250"
FT DISULFID 213..221
FT /evidence="ECO:0000250"
FT DISULFID 217..229
FT /evidence="ECO:0000250"
FT DISULFID 230..238
FT /evidence="ECO:0000250"
FT DISULFID 234..246
FT /evidence="ECO:0000250"
FT DISULFID 249..258
FT /evidence="ECO:0000250"
FT DISULFID 262..289
FT /evidence="ECO:0000250"
FT DISULFID 293..304
FT /evidence="ECO:0000250"
FT DISULFID 308..323
FT /evidence="ECO:0000250"
FT DISULFID 326..330
FT /evidence="ECO:0000250"
FT DISULFID 503..512
FT /evidence="ECO:0000250"
FT DISULFID 507..520
FT /evidence="ECO:0000250"
FT DISULFID 523..532
FT /evidence="ECO:0000250"
FT DISULFID 536..552
FT /evidence="ECO:0000250"
FT DISULFID 555..569
FT /evidence="ECO:0000250"
FT DISULFID 559..577
FT /evidence="ECO:0000250"
FT DISULFID 580..589
FT /evidence="ECO:0000250"
FT DISULFID 593..614
FT /evidence="ECO:0000250"
FT DISULFID 617..625
FT /evidence="ECO:0000250"
FT DISULFID 621..633
FT /evidence="ECO:0000250"
FT VAR_SEQ 626..648
FT /note="NGPTSHDCIYYPWTGHSTLPQHA -> IGSSIEDCIGLTD (in isoform
FT JM-B CYT-2)"
FT /evidence="ECO:0000303|PubMed:9334263"
FT /id="VSP_002896"
FT VAR_SEQ 1046..1061
FT /note="Missing (in isoform JM-A CYT-2)"
FT /evidence="ECO:0000303|PubMed:9334263"
FT /id="VSP_042131"
FT CONFLICT 1019
FT /note="A -> V (in Ref. 5; AAC28334)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1308 AA; 146855 MW; 65943278A7E7F2F6 CRC64;
MKLATGLWVW GSLLMAAGTV QPSASQSVCA GTENKLSSLS DLEQQYRALR KYYENCEVVM
GNLEITSIEH NRDLSFLRSI REVTGYVLVA LNQFRYLPLE NLRIIRGTKL YEDRYALAIF
LNYRKDGNFG LQELGLKNLT EILNGGVYVD QNKFLCYADT IHWQDIVRNP WPSNMTLVST
NGSSGCGRCH KSCTGRCWGP TENHCQTLTR TVCAEQCDGR CYGPYVSDCC HRECAGGCSG
PKDTDCFACM NFNDSGACVT QCPQTFVYNP TTFQLEHNFN AKYTYGAFCV KKCPHNFVVD
SSSCVRACPS SKMEVEENGI KMCKPCTDIC PKACDGIGTG SLMSAQTVDS SNIDKFINCT
KINGNLIFLV TGIHGDPYNA IDAIDPEKLN VFRTVREITG FLNIQSWPPN MTDFSVFSNL
VTIGGRVLYS GLSLLILKQQ GITSLQFQSL KEISAGNIYI TDNSNLCYYH TINWTTLFST
INQRIVIRDN RRAENCTAEG MVCNHLCSND GCWGPGPDQC LSCRRFSRGK ICIESCNLYD
GEFREFENGS ICVECDSQCE KMEDGLLTCH GPGPDNCTKC SHFKDGPNCV EKCPDGLQGA
NSFIFKYADQ DRECHPCHPN CTQGCNGPTS HDCIYYPWTG HSTLPQHART PLIAAGVIGG
LFILVIMALT FAVYVRRKSI KKKRALRRFL ETELVEPLTP SGTAPNQAQL RILKETELKR
VKVLGSGAFG TVYKGIWVPE GETVKIPVAI KILNETTGPK ANVEFMDEAL IMASMDHPHL
VRLLGVCLSP TIQLVTQLMP HGCLLDYVHE HKDNIGSQLL LNWCVQIAKG MMYLEERRLV
HRDLAARNVL VKSPNHVKIT DFGLARLLEG DEKEYNADGG KMPIKWMALE CIHYRKFTHQ
SDVWSYGVTI WELMTFGGKP YDGIPTREIP DLLEKGERLP QPPICTIDVY MVMVKCWMID
ADSRPKFKEL AAEFSRMARD PQRYLVIQGD DRMKLPSPND SKFFQNLLDE EDLEDMMDAE
EYLVPQAFNI PPPIYTSRTR IDSNRSEIGH SPPPAYTPMS GNQFVYQDGG FATQQGMPMP
YRATTSTIPE APVAQGATAE MFDDSCCNGT LRKPVAPHVQ EDSSTQRYSA DPTVFAPERN
PRGELDEEGY MTPMHDKPKQ EYLNPVEENP FVSRRKNGDL QALDNPEYHS ASSGPPKAED
EYVNEPLYLN TFANALGSAE YMKNSVLSVP EKAKKAFDNP DYWNHSLPPR STLQHPDYLQ
EYSTKYFYKQ NGRIRPIVAE NPEYLSEFSL KPGTMLPPPP YRHRNTVV
