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Q61527 (ERBB4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 131. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Receptor tyrosine-protein kinase erbB-4

EC=2.7.10.1
Alternative name(s):
Proto-oncogene-like protein c-ErbB-4

Cleaved into the following chain:

  1. ERBB4 intracellular domain
    Short name=4ICD
    Short name=E4ICD
    Alternative name(s):
    s80HER4
Gene names
Name:Erbb4
Synonyms:Mer4
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1308 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins and EGF family members and regulates development of the heart, the central nervous system and the mammary gland, gene transcription, cell proliferation, differentiation, migration and apoptosis. Required for normal cardiac muscle differentiation during embryonic development, and for postnatal cardiomyocyte proliferation. Required for normal development of the embryonic central nervous system, especially for normal neural crest cell migration and normal axon guidance. Required for mammary gland differentiation, induction of milk proteins and lactation. Acts as cell-surface receptor for the neuregulins NRG1, NRG2, NRG3 and NRG4 and the EGF family members BTC, EREG and HBEGF. Ligand binding triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. Ligand specificity and signaling is modulated by alternative splicing, proteolytic processing, and by the formation of heterodimers with other ERBB family members, thereby creating multiple combinations of intracellular phosphotyrosines that trigger ligand- and context-specific cellular responses. Mediates phosphorylation of SHC1 and activation of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Isoform JM-ACYT-1 and isoform JM-BCYT-1 phosphorylate PIK3R1, leading to the activation of phosphatidylinositol 3-kinase and AKT1 and protect cells against apoptosis. Isoform JM-ACYT-1 and isoform JM-BCYT-1 mediate reorganization of the actin cytoskeleton and promote cell migration in response to NRG1. Isoform JM-ACYT-2 and isoform JM-BCYT-2 lack the phosphotyrosine that mediates interaction with PIK3R1, and hence do not phosphorylate PIK3R1, do not protect cells against apoptosis, and do not promote reorganization of the actin cytoskeleton and cell migration. Proteolytic processing of isoform JM-ACYT-1 and isoform JM-ACYT-2 gives rise to the corresponding soluble intracellular domains (4ICD) that translocate to the nucleus, promote nuclear import of STAT5A, activation of STAT5A, mammary epithelium differentiation, cell proliferation and activation of gene expression. The ERBB4 soluble intracellular domains (4ICD) colocalize with STAT5A at the CSN2 promoter to regulate transcription of milk proteins during lactation. The ERBB4 soluble intracellular domains can also translocate to mitochondria and promote apoptosis. Ref.6 Ref.7 Ref.9 Ref.12 Ref.13 Ref.15 Ref.16 Ref.17

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

Enzyme regulation

Binding of a cognate ligand leads to dimerization and activation by autophosphorylation on tyrosine residues. In vitro kinase activity is increased by Mg2+ By similarity.

Subunit structure

Monomer in the absence of bound ligand. Homodimer or heterodimer with another ERBB family member upon ligand binding, thus forming heterotetramers. Interacts with EGFR and ERBB2. Interacts with DLG2 (via its PDZ domain), DLG3 (via its PDZ domain), DLG4 (via its PDZ domain) and SNTB2 (via its PDZ domain). Interacts with MUC1. Interacts (via its PPxy motifs) with WWOX. Interacts (via the PPxY motif 3 of isoform JM-ACYT-2) with YAP1 (via the WW domain 1 of isoform 1) Interacts (isoform JM-ACYT-1 and isoform JM-BCYT-1) with WWP1. Interacts (via its intracellular domain) with TRIM28. Interacts (via the intracellular domains of both CYT-1 and CYT-2 isoforms) with KAP1; the interaction does not phosphorylate KAP1 but represses ERBB4-mediated transcriptional activity. Interacts with PRPU, DDX23, MATR3, RBM15, ILF3, KAP1, U5S1, U2SURP, ITCH, HNRPU, AP2A1, NULC, LEO1, WWP2, IGHG1, HXK1, GRB7 AND ARS2. Interacts (phosphorylated isoform JM-ACYT-1 and isoform JM-BCYT-1) with PIK3R1. Interacts with SHC1. Interacts with GRB2. Interacts (soluble intracellular domain) with BCL2. Interacts (phosphorylated) with STAT1 By similarity. Interacts with CBFA2T3. Interacts (soluble intracellular domain) with STAT5A. Ref.7 Ref.14

Subcellular location

Cell membrane; Single-pass type I membrane protein. Note: In response to NRG1 treatment, the activated receptor is internalized. Ref.15

ERBB4 intracellular domain: Nucleus. Mitochondrion By similarity. Note: Following proteolytical processing E4ICD (E4ICD1 or E4ICD2 generated from the respective isoforms) is translocated to the nucleus. Significantly more E4ICD2 than E4ICD1 is found in the nucleus. E4ICD2 colocalizes with YAP1 in the nucleus By similarity. Ref.15

Tissue specificity

Isoform JM-ACYT-2 and isoform JM-BCYT-2 are expressed in cerebellum, cerebral cortex, spinal cord, medulla oblongata and eye, but the kidney expresses solely isoform JM-ACYT-2 and the heart solely isoform JM-BCYT-2. Ref.8

Post-translational modification

Isoform JM-ACYT-1 and isoform JM-ACYT-2 are processed by ADAM17. Proteolytic processing in response to ligand or 12-O-tetradecanoylphorbol-13-acetate stimulation results in the production of 120 kDa soluble receptor forms and intermediate membrane-anchored 80 kDa fragments (m80HER4), which are further processed by a presenilin-dependent gamma-secretase to release a cytoplasmic intracellular domain (E4ICD; E4ICD1/s80Cyt1 or E4ICD2/s80Cyt2, depending on the isoform). Membrane-anchored 80 kDa fragments of the processed isoform JM-ACYT-1 are more readily degraded by the proteasome than fragments of isoform JM-ACYT-2, suggesting a prevalence of E4ICD2 over E4ICD1. Isoform JM-BCYT-1 and isoform JM-BCYT-2 lack the ADAM17 cleavage site and are not processed by ADAM17, precluding further processing by gamma-secretase By similarity.

Autophosphorylated on tyrosine residues in response to ligand binding. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Ligands trigger phosphorylation at specific tyrosine residues, thereby creating binding sites for scaffold proteins and effectors. Constitutively phosphorylated at a basal level when overexpressed in heterologous systems; ligand binding leads to increased phosphorylation. Phosphorylation at Tyr-1035 is important for interaction with STAT1. Phosphorylation at Tyr-1056 is important for interaction with PIK3R1. Phosphorylation at Tyr-1242 is important for interaction with SHC1. Phosphorylation at Tyr-1188 may also contribute to the interaction with SHC1. Isoform JM-ACYT-2 is constitutively phosphorylated on tyrosine residues in a ligand-independent manner. E4ICD2 but not E4ICD1 is phosphorylated on tyrosine residues By similarity.

Ubiquitinated. During mitosis, the ERBB4 intracellular domain is ubiquitinated by the APC/C complex and targeted to proteasomal degradation. Isoform JM-ACYT-1 and isoform JM-BCYT-1 are ubiquitinated by WWP1. The ERBB4 intracellular domain (E4ICD1) is ubiquitinated, and this involves NEDD4 By similarity.

Disruption phenotype

Embryonically lethal. Embryos die at about 10 dpc, due to defects in the development of myocardial trabeculae in the heart ventricle that lead to severely reduced embryonic blood flow. Mice also display aberrant innervation from and to the hindbrain, especially concerning the trigeminal, facial and acoustic ganglia. This is due to aberrant migration of a subpopulation of cranial neural crest cells. Ref.6 Ref.9 Ref.10 Ref.11

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processApoptosis
Lactation
Transcription
Transcription regulation
   Cellular componentCell membrane
Membrane
Mitochondrion
Nucleus
   Coding sequence diversityAlternative splicing
   DiseaseTumor suppressor
   DomainRepeat
Signal
Transmembrane
Transmembrane helix
   LigandATP-binding
Nucleotide-binding
   Molecular functionActivator
Developmental protein
Kinase
Receptor
Transferase
Tyrosine-protein kinase
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcardiac muscle tissue regeneration

Inferred from mutant phenotype Ref.17. Source: UniProtKB

cell fate commitment

Inferred from direct assay PubMed 12399441. Source: MGI

cell migration

Inferred from sequence or structural similarity. Source: UniProtKB

central nervous system morphogenesis

Inferred from mutant phenotype Ref.9. Source: UniProtKB

embryonic pattern specification

Inferred from mutant phenotype Ref.9. Source: UniProtKB

heart development

Inferred from mutant phenotype Ref.6. Source: MGI

lactation

Inferred from mutant phenotype Ref.7. Source: UniProtKB

mammary gland alveolus development

Inferred from mutant phenotype Ref.7. Source: UniProtKB

mammary gland epithelial cell differentiation

Inferred from mutant phenotype Ref.15. Source: UniProtKB

mitochondrial fragmentation involved in apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

nervous system development

Inferred from mutant phenotype Ref.6. Source: MGI

neural crest cell migration

Inferred from mutant phenotype Ref.9. Source: UniProtKB

olfactory bulb interneuron differentiation

Inferred from mutant phenotype Ref.12. Source: UniProtKB

peptidyl-tyrosine phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of ERK1 and ERK2 cascade

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of STAT protein import into nucleus

Inferred from mutant phenotype Ref.15. Source: UniProtKB

positive regulation of cardiac muscle cell proliferation

Inferred from mutant phenotype Ref.17. Source: UniProtKB

positive regulation of cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of phosphatidylinositol 3-kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transcription, DNA-templated

Inferred from mutant phenotype Ref.15. Source: UniProtKB

positive regulation of tyrosine phosphorylation of Stat5 protein

Inferred from mutant phenotype Ref.7Ref.15. Source: UniProtKB

protein autophosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of cell migration

Inferred from mutant phenotype Ref.12. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

transmembrane receptor protein tyrosine kinase signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentbasolateral plasma membrane

Inferred from electronic annotation. Source: Ensembl

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

mitochondrion

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

receptor complex

Inferred from sequence orthology PubMed 23382219. Source: MGI

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

receptor signaling protein tyrosine kinase activity

Inferred from electronic annotation. Source: InterPro

transcription regulatory region DNA binding

Inferred from electronic annotation. Source: Ensembl

transmembrane receptor protein tyrosine kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

WWOXQ9NZC73EBI-4398741,EBI-4320739From a different organism.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform JM-A CYT-1 (identifier: Q61527-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Note: Proteolytical processing generates E4ICD1 (s80Cyt1).
Isoform JM-B CYT-2 (identifier: Q61527-2)

The sequence of this isoform differs from the canonical sequence as follows:
     626-648: NGPTSHDCIYYPWTGHSTLPQHA → IGSSIEDCIGLTD
Isoform JM-A CYT-2 (identifier: Q61527-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1046-1061: Missing.
Note: Proteolytical processing generates E4ICD2 (s80Cyt2).

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2525 Potential
Chain26 – 13081283Receptor tyrosine-protein kinase erbB-4
PRO_0000270146
Chain676 – 1308633ERBB4 intracellular domain
PRO_0000396798

Regions

Topological domain26 – 652627Extracellular Potential
Transmembrane653 – 67321 Potential
Topological domain674 – 1308635Cytoplasmic Potential
Domain718 – 985268Protein kinase
Nucleotide binding724 – 7329ATP By similarity
Nucleotide binding797 – 7993ATP By similarity
Nucleotide binding843 – 8486ATP By similarity
Motif676 – 6849Nuclear localization signal By similarity
Motif1032 – 10354PPxy motif 1 By similarity
Motif1282 – 12854PPxY motif 2 By similarity
Motif1290 – 12923PDZ-binding By similarity
Compositional bias186 – 26277Cys-rich
Compositional bias496 – 59398Cys-rich
Compositional bias1281 – 12844Poly-Pro

Sites

Active site8431Proton acceptor By similarity
Binding site7511ATP By similarity

Amino acid modifications

Modified residue8751Phosphotyrosine; by autocatalysis By similarity
Modified residue10351Phosphotyrosine; by autocatalysis By similarity
Modified residue10561Phosphotyrosine; by autocatalysis By similarity
Modified residue11501Phosphotyrosine; by autocatalysis By similarity
Modified residue11621Phosphotyrosine; by autocatalysis By similarity
Modified residue11881Phosphotyrosine; by autocatalysis By similarity
Modified residue12021Phosphotyrosine; by autocatalysis By similarity
Modified residue12421Phosphotyrosine; by autocatalysis By similarity
Modified residue12581Phosphotyrosine; by autocatalysis By similarity
Modified residue12841Phosphotyrosine; by autocatalysis By similarity
Glycosylation1381N-linked (GlcNAc...) Potential
Glycosylation1741N-linked (GlcNAc...) Potential
Glycosylation1811N-linked (GlcNAc...) Potential
Glycosylation2531N-linked (GlcNAc...) Potential
Glycosylation4101N-linked (GlcNAc...) Potential
Glycosylation4731N-linked (GlcNAc...) Potential
Glycosylation4951N-linked (GlcNAc...) Potential
Glycosylation5481N-linked (GlcNAc...) Potential
Glycosylation5761N-linked (GlcNAc...) Potential
Glycosylation6201N-linked (GlcNAc...) Potential
Disulfide bond29 ↔ 56 By similarity
Disulfide bond156 ↔ 186 By similarity
Disulfide bond189 ↔ 197 By similarity
Disulfide bond193 ↔ 205 By similarity
Disulfide bond213 ↔ 221 By similarity
Disulfide bond217 ↔ 229 By similarity
Disulfide bond230 ↔ 238 By similarity
Disulfide bond234 ↔ 246 By similarity
Disulfide bond249 ↔ 258 By similarity
Disulfide bond262 ↔ 289 By similarity
Disulfide bond293 ↔ 304 By similarity
Disulfide bond308 ↔ 323 By similarity
Disulfide bond326 ↔ 330 By similarity
Disulfide bond503 ↔ 512 By similarity
Disulfide bond507 ↔ 520 By similarity
Disulfide bond523 ↔ 532 By similarity
Disulfide bond536 ↔ 552 By similarity
Disulfide bond555 ↔ 569 By similarity
Disulfide bond559 ↔ 577 By similarity
Disulfide bond580 ↔ 589 By similarity
Disulfide bond593 ↔ 614 By similarity
Disulfide bond617 ↔ 625 By similarity
Disulfide bond621 ↔ 633 By similarity

Natural variations

Alternative sequence626 – 64823NGPTS…LPQHA → IGSSIEDCIGLTD in isoform JM-B CYT-2.
VSP_002896
Alternative sequence1046 – 106116Missing in isoform JM-A CYT-2.
VSP_042131

Experimental info

Sequence conflict10191A → V in AAC28334. Ref.5

Sequences

Sequence LengthMass (Da)Tools
Isoform JM-A CYT-1 [UniParc].

Last modified January 25, 2012. Version 5.
Checksum: 65943278A7E7F2F6

FASTA1,308146,855
        10         20         30         40         50         60 
MKLATGLWVW GSLLMAAGTV QPSASQSVCA GTENKLSSLS DLEQQYRALR KYYENCEVVM 

        70         80         90        100        110        120 
GNLEITSIEH NRDLSFLRSI REVTGYVLVA LNQFRYLPLE NLRIIRGTKL YEDRYALAIF 

       130        140        150        160        170        180 
LNYRKDGNFG LQELGLKNLT EILNGGVYVD QNKFLCYADT IHWQDIVRNP WPSNMTLVST 

       190        200        210        220        230        240 
NGSSGCGRCH KSCTGRCWGP TENHCQTLTR TVCAEQCDGR CYGPYVSDCC HRECAGGCSG 

       250        260        270        280        290        300 
PKDTDCFACM NFNDSGACVT QCPQTFVYNP TTFQLEHNFN AKYTYGAFCV KKCPHNFVVD 

       310        320        330        340        350        360 
SSSCVRACPS SKMEVEENGI KMCKPCTDIC PKACDGIGTG SLMSAQTVDS SNIDKFINCT 

       370        380        390        400        410        420 
KINGNLIFLV TGIHGDPYNA IDAIDPEKLN VFRTVREITG FLNIQSWPPN MTDFSVFSNL 

       430        440        450        460        470        480 
VTIGGRVLYS GLSLLILKQQ GITSLQFQSL KEISAGNIYI TDNSNLCYYH TINWTTLFST 

       490        500        510        520        530        540 
INQRIVIRDN RRAENCTAEG MVCNHLCSND GCWGPGPDQC LSCRRFSRGK ICIESCNLYD 

       550        560        570        580        590        600 
GEFREFENGS ICVECDSQCE KMEDGLLTCH GPGPDNCTKC SHFKDGPNCV EKCPDGLQGA 

       610        620        630        640        650        660 
NSFIFKYADQ DRECHPCHPN CTQGCNGPTS HDCIYYPWTG HSTLPQHART PLIAAGVIGG 

       670        680        690        700        710        720 
LFILVIMALT FAVYVRRKSI KKKRALRRFL ETELVEPLTP SGTAPNQAQL RILKETELKR 

       730        740        750        760        770        780 
VKVLGSGAFG TVYKGIWVPE GETVKIPVAI KILNETTGPK ANVEFMDEAL IMASMDHPHL 

       790        800        810        820        830        840 
VRLLGVCLSP TIQLVTQLMP HGCLLDYVHE HKDNIGSQLL LNWCVQIAKG MMYLEERRLV 

       850        860        870        880        890        900 
HRDLAARNVL VKSPNHVKIT DFGLARLLEG DEKEYNADGG KMPIKWMALE CIHYRKFTHQ 

       910        920        930        940        950        960 
SDVWSYGVTI WELMTFGGKP YDGIPTREIP DLLEKGERLP QPPICTIDVY MVMVKCWMID 

       970        980        990       1000       1010       1020 
ADSRPKFKEL AAEFSRMARD PQRYLVIQGD DRMKLPSPND SKFFQNLLDE EDLEDMMDAE 

      1030       1040       1050       1060       1070       1080 
EYLVPQAFNI PPPIYTSRTR IDSNRSEIGH SPPPAYTPMS GNQFVYQDGG FATQQGMPMP 

      1090       1100       1110       1120       1130       1140 
YRATTSTIPE APVAQGATAE MFDDSCCNGT LRKPVAPHVQ EDSSTQRYSA DPTVFAPERN 

      1150       1160       1170       1180       1190       1200 
PRGELDEEGY MTPMHDKPKQ EYLNPVEENP FVSRRKNGDL QALDNPEYHS ASSGPPKAED 

      1210       1220       1230       1240       1250       1260 
EYVNEPLYLN TFANALGSAE YMKNSVLSVP EKAKKAFDNP DYWNHSLPPR STLQHPDYLQ 

      1270       1280       1290       1300 
EYSTKYFYKQ NGRIRPIVAE NPEYLSEFSL KPGTMLPPPP YRHRNTVV 

« Hide

Isoform JM-B CYT-2 [UniParc].

Checksum: 22EF9A9BE932C0F7
Show »

FASTA1,298145,595
Isoform JM-A CYT-2 [UniParc].

Checksum: 46FBDC6AE4D69E08
Show »

FASTA1,292145,245

References

« Hide 'large scale' references
[1]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-1263 (JM-A CYT-2).
Strain: C57BL/6J.
Tissue: Kidney.
[3]"A novel juxtamembrane domain isoform of HER4/ErbB4. Isoform-specific tissue distribution and differential processing in response to phorbol ester."
Elenius K., Corfas G., Paul S., Choi C.J., Rio C., Plowman G.D., Klagsbrun M.
J. Biol. Chem. 272:26761-26768(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 624-650 (ISOFORMS JM-A CYT-2 AND JM-B CYT-2).
Tissue: Heart and Kidney.
[4]"Synapse-associated expression of an acetylcholine receptor-inducing protein, ARIA/heregulin, and its putative receptors, ErbB2 and ErbB3, in developing mammalian muscle."
Moscoso L.M., Chu G.C., Gautam M., Noakes P.G., Merlie J.P., Sanes J.R.
Dev. Biol. 172:158-169(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1019-1102 (ISOFORM JM-A CYT-1).
Strain: C57BL/6.
Tissue: Brain.
[5]"Potential signaling network by EGF-like growth factors in the mouse uterus during early pregnancy."
Lim H., Das S.K., Dey S.K.
Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1019-1093 (ISOFORM JM-A CYT-1).
Strain: CD-1.
Tissue: Uterus.
[6]"Aberrant neural and cardiac development in mice lacking the ErbB4 neuregulin receptor."
Gassmann M., Casagranda F., Orioli D., Simon H., Lai C., Klein R., Lemke G.
Nature 378:390-394(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION.
[7]"ErbB4 signaling in the mammary gland is required for lobuloalveolar development and Stat5 activation during lactation."
Jones F.E., Welte T., Fu X.Y., Stern D.F.
J. Cell Biol. 147:77-88(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN MAMMARY GLAND DEVELOPMENT AND ACTIVATION OF STAT5A, INTERACTION WITH STAT5A.
[8]"Characterization of a naturally occurring ErbB4 isoform that does not bind or activate phosphatidyl inositol 3-kinase."
Elenius K., Choi C.J., Paul S., Santiestevan E., Nishi E., Klagsbrun M.
Oncogene 18:2607-2615(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING, TISSUE SPECIFICITY.
[9]"Defects in pathfinding by cranial neural crest cells in mice lacking the neuregulin receptor ErbB4."
Golding J.P., Trainor P., Krumlauf R., Gassmann M.
Nat. Cell Biol. 2:103-109(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION.
[10]"Impaired differentiation and lactational failure of Erbb4-deficient mammary glands identify ERBB4 as an obligate mediator of STAT5."
Long W., Wagner K.U., Lloyd K.C., Binart N., Shillingford J.M., Hennighausen L., Jones F.E.
Development 130:5257-5268(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
[11]"Neural and mammary gland defects in ErbB4 knockout mice genetically rescued from embryonic lethality."
Tidcombe H., Jackson-Fisher A., Mathers K., Stern D.F., Gassmann M., Golding J.P.
Proc. Natl. Acad. Sci. U.S.A. 100:8281-8286(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
[12]"Receptor tyrosine kinase ErbB4 modulates neuroblast migration and placement in the adult forebrain."
Anton E.S., Ghashghaei H.T., Weber J.L., McCann C., Fischer T.M., Cheung I.D., Gassmann M., Messing A., Klein R., Schwab M.H., Lloyd K.C., Lai C.
Nat. Neurosci. 7:1319-1328(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN NEUROBLAST MIGRATION.
[13]"ERBB4/HER4 potentiates STAT5A transcriptional activity by regulating novel STAT5A serine phosphorylation events."
Clark D.E., Williams C.C., Duplessis T.T., Moring K.L., Notwick A.R., Long W., Lane W.S., Beuvink I., Hynes N.E., Jones F.E.
J. Biol. Chem. 280:24175-24180(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[14]"ErbB-4 s80 intracellular domain abrogates ETO2-dependent transcriptional repression."
Linggi B., Carpenter G.
J. Biol. Chem. 281:25373-25380(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CBFA2T3.
[15]"The intracellular domain of ErbB4 induces differentiation of mammary epithelial cells."
Muraoka-Cook R.S., Sandahl M., Husted C., Hunter D., Miraglia L., Feng S.M., Elenius K., Earp H.S. III
Mol. Biol. Cell 17:4118-4129(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PROTEOLYTIC PROCESSING, SUBCELLULAR LOCATION.
[16]"ErbB4 splice variants Cyt1 and Cyt2 differ by 16 amino acids and exert opposing effects on the mammary epithelium in vivo."
Muraoka-Cook R.S., Sandahl M.A., Strunk K.E., Miraglia L.C., Husted C., Hunter D.M., Elenius K., Chodosh L.A., Earp H.S. III
Mol. Cell. Biol. 29:4935-4948(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION OF E4ICD.
[17]"Neuregulin1/ErbB4 signaling induces cardiomyocyte proliferation and repair of heart injury."
Bersell K., Arab S., Haring B., Kuhn B.
Cell 138:257-270(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS NRG1 RECEPTOR IN POSTNATAL CARDIOMYOCYTE PROLIFERATION.
[18]"ErbB4 signaling during breast and neural development: novel genetic models reveal unique ErbB4 activities."
Jones F.E., Golding J.P., Gassmann M.
Cell Cycle 2:555-559(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[19]"Neuregulin signaling, cortical circuitry development and schizophrenia."
Rico B., Marin O.
Curr. Opin. Genet. Dev. 21:262-270(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON ROLE AS NEUREGULIN RECEPTOR.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
CU368746 expand/collapse EMBL AC list , CU372923, CU392849, CU405881, CU407006, CU459008, CU459207 Genomic DNA. Translation: CAQ51554.1.
CU368746 expand/collapse EMBL AC list , CU372923, CU392849, CU405881, CU407006, CU459008, CU459207 Genomic DNA. Translation: CAQ51555.1.
CU392849 expand/collapse EMBL AC list , CU368746, CU372923, CU405881, CU407006, CU459008, CU459207 Genomic DNA. Translation: CAQ51831.1.
CU459207 expand/collapse EMBL AC list , CU368746, CU372923, CU392849, CU405881, CU407006, CU459008 Genomic DNA. Translation: CAQ51899.1.
CU392849 expand/collapse EMBL AC list , CU368746, CU372923, CU405881, CU407006, CU459008, CU459207 Genomic DNA. Translation: CAQ51832.1.
CU459207 expand/collapse EMBL AC list , CU368746, CU372923, CU392849, CU405881, CU407006, CU459008 Genomic DNA. Translation: CAQ51900.1.
CU405881 expand/collapse EMBL AC list , CU368746, CU372923, CU392849, CU407006, CU459008, CU459207 Genomic DNA. Translation: CAQ52134.1.
CU405881 expand/collapse EMBL AC list , CU368746, CU372923, CU392849, CU407006, CU459008, CU459207 Genomic DNA. Translation: CAQ52135.1.
CU459008 expand/collapse EMBL AC list , CU368746, CU372923, CU392849, CU405881, CU407006, CU459207 Genomic DNA. Translation: CAQ52171.1.
CU459008 expand/collapse EMBL AC list , CU368746, CU372923, CU392849, CU405881, CU407006, CU459207 Genomic DNA. Translation: CAQ52172.1.
CU407006 expand/collapse EMBL AC list , CU368746, CU372923, CU392849, CU405881, CU459008, CU459207 Genomic DNA. Translation: CAQ52191.1.
CU407006 expand/collapse EMBL AC list , CU368746, CU372923, CU392849, CU405881, CU459008, CU459207 Genomic DNA. Translation: CAQ52192.1.
CU372923 expand/collapse EMBL AC list , CU368746, CU392849, CU405881, CU407006, CU459008, CU459207 Genomic DNA. Translation: CAQ52287.1.
CU372923 expand/collapse EMBL AC list , CU368746, CU392849, CU405881, CU407006, CU459008, CU459207 Genomic DNA. Translation: CAQ52288.1.
AK144050 mRNA. Translation: BAE25671.1.
L47241 mRNA. Translation: AAA93534.1.
AF059177 mRNA. Translation: AAC28334.1.
RefSeqNP_034284.1. NM_010154.1.
XP_006495755.1. XM_006495692.1.
XP_006495756.1. XM_006495693.1.
XP_006536970.1. XM_006536907.1.
UniGeneMm.442420.

3D structure databases

ProteinModelPortalQ61527.
SMRQ61527. Positions 26-639, 642-1026.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-29887N.
IntActQ61527. 2 interactions.
STRING10090.ENSMUSP00000112713.

Proteomic databases

PaxDbQ61527.
PRIDEQ61527.

Protocols and materials databases

DNASU13869.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000119142; ENSMUSP00000112713; ENSMUSG00000062209. [Q61527-1]
ENSMUST00000121473; ENSMUSP00000114123; ENSMUSG00000062209. [Q61527-3]
GeneID13869.
KEGGmmu:13869.
UCSCuc007bjb.1. mouse. [Q61527-3]

Organism-specific databases

CTD2066.
MGIMGI:104771. Erbb4.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00600000084253.
HOGENOMHOG000230982.
HOVERGENHBG000490.
InParanoidB2KGF6.
KOK05085.
OMAQGVPVPY.
OrthoDBEOG7V49XM.
PhylomeDBQ61527.
TreeFamTF106002.

Gene expression databases

BgeeQ61527.
GenevestigatorQ61527.

Family and domain databases

Gene3D3.80.20.20. 2 hits.
InterProIPR000494. EGF_rcpt_L.
IPR006211. Furin-like_Cys-rich_dom.
IPR006212. Furin_repeat.
IPR009030. Growth_fac_rcpt_N_dom.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR016245. Tyr_kinase_EGF/ERB/XmrK_rcpt.
[Graphical view]
PfamPF00757. Furin-like. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF01030. Recep_L_domain. 2 hits.
[Graphical view]
PIRSFPIRSF000619. TyrPK_EGF-R. 1 hit.
PRINTSPR00109. TYRKINASE.
SMARTSM00261. FU. 5 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
SSF57184. SSF57184. 2 hits.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio284772.
PROQ61527.
SOURCESearch...

Entry information

Entry nameERBB4_MOUSE
AccessionPrimary (citable) accession number: Q61527
Secondary accession number(s): B2KGF5 expand/collapse secondary AC list , B2KGF6, O88460, Q3UNS6
Entry history
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: January 25, 2012
Last modified: April 16, 2014
This is version 131 of the entry and version 5 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot