Q62956 (ERBB4_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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:	Tyro-2

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	1308 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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-A CYT-1 and isoform JM-B CYT-1 phosphorylate PIK3R1, leading to the activation of phosphatidylinositol 3-kinase and AKT1 and protect cells against apoptosis. Isoform JM-A CYT-1 and isoform JM-B CYT-1 mediate reorganization of the actin cytoskeleton and promote cell migration in response to NRG1. Isoform JM-A CYT-2 and isoform JM-B CYT-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-A CYT-1 and isoform JM-A CYT-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 lactaction. The ERBB4 soluble intracellular domains can also translocate to mitochondria and promote apoptosis. Ref.5 Ref.6 Ref.7 Ref.8 Ref.9
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. Ref.6
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-A CYT-2) with YAP1 (via the WW domain 1 of isoform 1). Interacts (isoform JM-A CYT-1 and isoform JM-B CYT-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-A CYT-1 and isoform JM-B CYT-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 By similarity.
Subcellular location	Cell membrane; Single-pass type I membrane protein. Note: In response to NRG1 treatment, the activated receptor is internalized. Ref.7 Ref.8 ERBB4 intracellular domain: Nucleus By similarity. 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 derived from processing of isoform JM-A CYT-2 colocalizes with YAP1 in the nucleus By similarity. Ref.7 Ref.8
Tissue specificity	Preferentially expressed in the developing nervous system. Exhibits distinct and highly regionalized patterns of expression in the adult brain, where it is mainly found in the reticular nucleus of the thallamus. Very low levels in kidney, and heart.
Post-translational modification	Isoform JM-A CYT-2 and isoform JM-A CYT-1 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, which are further processed by a presenilin-dependent gamma-secretase to release the respective cytoplasmic intracellular domain E4ICD (either E4ICD1/s80Cyt1 or E4ICD2/s80Cyt2) 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-A CYT-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-A CYT-1 and isoform JM-B CYT-1 are ubiquitinated by WWP1. The ERBB4 intracellular domain (E4ICD1) is ubiquitinated, and this involves NEDD4 By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Apoptosis Lactation Transcription Transcription regulation
Cellular component	Cell membrane Membrane Mitochondrion Nucleus
Coding sequence diversity	Alternative splicing
Disease	Tumor suppressor
Domain	Repeat Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Activator Developmental protein Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Disulfide bond Glycoprotein Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB cardiac muscle tissue regeneration Inferred from sequence or structural similarity. Source: UniProtKB central nervous system morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB embryonic pattern specification Inferred from sequence or structural similarity. Source: UniProtKB heart development Inferred from sequence or structural similarity. Source: UniProtKB lactation Inferred from sequence or structural similarity. Source: UniProtKB mammary gland alveolus development Inferred from sequence or structural similarity. Source: UniProtKB mammary gland epithelial cell differentiation 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 neural crest cell migration Inferred from sequence or structural similarity. Source: UniProtKB odontogenesis Inferred from expression pattern. Source: RGD olfactory bulb interneuron differentiation Inferred from sequence or structural similarity. 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 sequence or structural similarity. Source: UniProtKB positive regulation of anti-apoptosis Inferred from mutant phenotype Ref.6. Source: RGD positive regulation of cardiac muscle cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of cell migration Inferred from mutant phenotype Ref.2. Source: RGD positive regulation of epithelial cell proliferation Inferred from mutant phenotype. Source: RGD positive regulation of glucose import Inferred from mutant phenotype. Source: RGD positive regulation of phosphatidylinositol 3-kinase activity Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of synaptic transmission, GABAergic Inferred from mutant phenotype. Source: RGD positive regulation of transcription, DNA-dependent Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of tyrosine phosphorylation of Stat5 protein Inferred from sequence or structural similarity. Source: UniProtKB protein autophosphorylation Inferred from sequence or structural similarity. Source: UniProtKB response to drug Inferred from expression pattern. Source: RGD response to hydrogen peroxide Inferred from expression pattern. Source: RGD response to progesterone stimulus Inferred from expression pattern. Source: RGD surfactant homeostasis Inferred from mutant phenotype. Source: RGD synapse maturation Inferred from mutant phenotype Ref.9. Source: RGD transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transmembrane receptor protein tyrosine kinase signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	caveola Inferred from direct assay. Source: RGD cytoplasm Inferred from direct assay. Source: RGD integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW nucleus Inferred from direct assay. Source: RGD postsynaptic density Inferred from direct assay Ref.7. Source: RGD
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW receptor signaling protein tyrosine kinase activity Inferred from electronic annotation. Source: InterPro transmembrane receptor protein tyrosine kinase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.

Isoform JM-A CYT1 (identifier: Q62956-1)

Also known as: JMa cyt1;

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.

Isoform JM-A CYT2 (identifier: Q62956-2)

Also known as: JMa cyt2;

The sequence of this isoform differs from the canonical sequence as follows:
     1046-1062: SEIGHSPPPAYTPMSGS → N

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 25	25	Potential
	Chain	26 – 1308	1283	Receptor tyrosine-protein kinase erbB-4		PRO_0000016675
	Chain	676 – 1308	633	ERBB4 intracellular domain By similarity		PRO_0000396799
Regions
	Topological domain	26 – 651	626	Extracellular Potential
	Transmembrane	652 – 675	24	Potential
	Topological domain	676 – 1308	633	Cytoplasmic Potential
	Domain	718 – 985	268	Protein kinase
	Nucleotide binding	724 – 732	9	ATP By similarity
	Nucleotide binding	797 – 799	3	ATP By similarity
	Nucleotide binding	843 – 848	6	ATP By similarity
	Motif	676 – 684	9	Nuclear localization signal By similarity
	Motif	1032 – 1035	4	PPxy motif 1
	Motif	1298 – 1301	4	PPxY motif 2
	Motif	1306 – 1308	3	PDZ-binding
	Compositional bias	186 – 334	149	Cys-rich
	Compositional bias	496 – 633	138	Cys-rich
Sites
	Active site	843	1	Proton acceptor By similarity
	Binding site	751	1	ATP By similarity
Amino acid modifications
	Modified residue	733	1	Phosphotyrosine By similarity
	Modified residue	875	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	1035	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	1056	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	1150	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	1162	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	1188	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	1202	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	1242	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	1258	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	1284	1	Phosphotyrosine; by autocatalysis By similarity
	Glycosylation	138	1	N-linked (GlcNAc...) Potential
	Glycosylation	174	1	N-linked (GlcNAc...) Potential
	Glycosylation	253	1	N-linked (GlcNAc...) Potential
	Glycosylation	358	1	N-linked (GlcNAc...) Potential
	Glycosylation	410	1	N-linked (GlcNAc...) Potential
	Glycosylation	473	1	N-linked (GlcNAc...) Potential
	Glycosylation	495	1	N-linked (GlcNAc...) Potential
	Glycosylation	548	1	N-linked (GlcNAc...) Potential
	Glycosylation	576	1	N-linked (GlcNAc...) Potential
	Glycosylation	620	1	N-linked (GlcNAc...) Potential
	Disulfide bond	29 ↔ 56		By similarity
	Disulfide bond	156 ↔ 186		By similarity
	Disulfide bond	189 ↔ 197		By similarity
	Disulfide bond	193 ↔ 205		By similarity
	Disulfide bond	213 ↔ 221		By similarity
	Disulfide bond	217 ↔ 229		By similarity
	Disulfide bond	230 ↔ 238		By similarity
	Disulfide bond	234 ↔ 246		By similarity
	Disulfide bond	249 ↔ 258		By similarity
	Disulfide bond	262 ↔ 289		By similarity
	Disulfide bond	293 ↔ 304		By similarity
	Disulfide bond	308 ↔ 323		By similarity
	Disulfide bond	326 ↔ 330		By similarity
	Disulfide bond	503 ↔ 512		By similarity
	Disulfide bond	507 ↔ 520		By similarity
	Disulfide bond	523 ↔ 532		By similarity
	Disulfide bond	536 ↔ 552		By similarity
	Disulfide bond	555 ↔ 569		By similarity
	Disulfide bond	559 ↔ 577		By similarity
	Disulfide bond	580 ↔ 589		By similarity
	Disulfide bond	593 ↔ 614		By similarity
	Disulfide bond	617 ↔ 625		By similarity
	Disulfide bond	621 ↔ 633		By similarity
Natural variations
	Alternative sequence	1046 – 1062	17	SEIGH…PMSGS → N in isoform JM-A CYT2.		VSP_022150
Experimental info
	Sequence conflict	406	1	T → S in AAQ77348. Ref.2
	Sequence conflict	406	1	T → S in AAQ77349. Ref.2
	Sequence conflict	596	1	V → G in AAQ77348. Ref.2
	Sequence conflict	596	1	V → G in AAQ77349. Ref.2
	Sequence conflict	951	1	I → M in AAQ77348. Ref.2
	Sequence conflict	951	1	I → M in AAQ77349. Ref.2
	Sequence conflict	1062	1	S → N in AAQ77348. Ref.2
	Sequence conflict	1062	1	S → N in AAC53051. Ref.4
	Sequence conflict	1080 – 1082	3	PYT → SYR in AAC53051. Ref.4
	Sequence conflict	1082	1	T → R in AAQ77348. Ref.2
	Sequence conflict	1082	1	T → R in AAQ77349. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform JM-A CYT1 (JMa cyt1) [UniParc]. Last modified June 6, 2002. Version 3. Checksum: D944BB0996A08B41	FASTA	1,308	146,958
	10 20 30 40 50 60 MKLATGLWVW GSLLVAARTV 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 IGSSGCGRCH 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 FLNIQTWPPN MTDFSVFSNL 430 440 450 460 470 480 VTIGGRVLYS GLSLLILKQQ GITSLQFQSL KEISAGNIYI TDNSNLCYYH TINWTTLFST 490 500 510 520 530 540 VNQRIVIRDN RRAENCTAEG MVCNHLCSND GCWGPGPDQC LSCRRFSRGK ICIESCNLYD 550 560 570 580 590 600 GEFREFENGS ICVECDSQCE KMEDGLLTCH GPGPDNCTKC SHFKDGPNCV EKCPDVLQGA 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 IMASVDHPHL 790 800 810 820 830 840 VRLLGVCLSP TIQLVTQLMP HGCLLEYVHE 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 IVMVKCWMID 970 980 990 1000 1010 1020 ADSRPKFKEL AAEFSRMARD PQRYLVIQGD DRMKLPSPND SKFFQNLLDE EDLEDMMDAE 1030 1040 1050 1060 1070 1080 EYLVPQAFNI PPPIYTSRTR IDSNRSEIGH SPPPAYTPMS GSQFVYQDGG FATQQGMPMP 1090 1100 1110 1120 1130 1140 YTATTSTIPE APVAQGATAE MFDDSCCNGT LRKPVVPHVQ EDSSTQRYSA DPTVFAPERN 1150 1160 1170 1180 1190 1200 PRAELDEEGY MTPMHDKPKQ EYLNPVEENP FVSRRKNGDL QALDNPEYHS ASSGPPKAED 1210 1220 1230 1240 1250 1260 EYVNEPLYLN TFTNALGNAE YMKNSLLSVP EKAKKAFDNP DYWNHSLPPR STLQHPDYLQ 1270 1280 1290 1300 EYSTKYFYKQ NGRIRPIVAE NPEYLSEFSL KPGTMLPPPP YRHRNTVV
	Isoform JM-A CYT2 (JMa cyt2) [UniParc]. Checksum: 4249D5FD4B5A9272	FASTA	1,292	145,376
	10 20 30 40 50 60 MKLATGLWVW GSLLVAARTV 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 IGSSGCGRCH 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 FLNIQTWPPN MTDFSVFSNL 430 440 450 460 470 480 VTIGGRVLYS GLSLLILKQQ GITSLQFQSL KEISAGNIYI TDNSNLCYYH TINWTTLFST 490 500 510 520 530 540 VNQRIVIRDN RRAENCTAEG MVCNHLCSND GCWGPGPDQC LSCRRFSRGK ICIESCNLYD 550 560 570 580 590 600 GEFREFENGS ICVECDSQCE KMEDGLLTCH GPGPDNCTKC SHFKDGPNCV EKCPDVLQGA 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 IMASVDHPHL 790 800 810 820 830 840 VRLLGVCLSP TIQLVTQLMP HGCLLEYVHE 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 IVMVKCWMID 970 980 990 1000 1010 1020 ADSRPKFKEL AAEFSRMARD PQRYLVIQGD DRMKLPSPND SKFFQNLLDE EDLEDMMDAE 1030 1040 1050 1060 1070 1080 EYLVPQAFNI PPPIYTSRTR IDSNRNQFVY QDGGFATQQG MPMPYTATTS TIPEAPVAQG 1090 1100 1110 1120 1130 1140 ATAEMFDDSC CNGTLRKPVV PHVQEDSSTQ RYSADPTVFA PERNPRAELD EEGYMTPMHD 1150 1160 1170 1180 1190 1200 KPKQEYLNPV EENPFVSRRK NGDLQALDNP EYHSASSGPP KAEDEYVNEP LYLNTFTNAL 1210 1220 1230 1240 1250 1260 GNAEYMKNSL LSVPEKAKKA FDNPDYWNHS LPPRSTLQHP DYLQEYSTKY FYKQNGRIRP 1270 1280 1290 IVAENPEYLS EFSLKPGTML PPPPYRHRNT VV

References

[1]	"Neuregulins promote survival and growth of cardiac myocytes. Persistence of ErbB2 and ErbB4 expression in neonatal and adult ventricular myocytes." Zhao Y.-Y., Sawyer D.R., Baliga R.R., Opel D.J., Han X., Marchionni M.A., Kelly R.A. J. Biol. Chem. 273:10261-10269(1998) [PubMed: 9553078] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM JM-A CYT1). Tissue: Heart.
[2]	"ErbB4 expression in neural progenitor cells (ST14A) is necessary to mediate neuregulin-1-beta1-induced migration." Gambarotta G., Garzotto D., Destro E., Mautino B., Giampietro C., Cutrupi S., Dati C., Cattaneo E., Fasolo A., Perroteau I. J. Biol. Chem. 279:48808-48816(2004) [PubMed: 15355992] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS JM-A CYT1 AND JM-A CYT2). Strain: Wistar. Tissue: Olfactory bulb.
[3]	"An extended family of protein-tyrosine kinase genes differentially expressed in the vertebrate nervous system." Lai C., Lemke G. Neuron 6:691-704(1991) [PubMed: 2025425] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 848-901. Tissue: Sciatic nerve.
[4]	"Expression of neuregulins and their putative receptors, ErbB2 and ErbB3, is induced during Wallerian degeneration." Carroll S.L., Miller M.L., Frohnert P.W., Kim S.S., Corbett J.A. J. Neurosci. 17:1642-1659(1997) [PubMed: 9030624] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1031-1198. Strain: Sprague-Dawley. Tissue: Spinal cord.
[5]	"Regulation of neuregulin signaling by PSD-95 interacting with ErbB4 at CNS synapses." Huang Y.Z., Won S., Ali D.W., Wang Q., Tanowitz M., Du Q.S., Pelkey K.A., Yang D.J., Xiong W.C., Salter M.W., Mei L. Neuron 26:443-455(2000) [PubMed: 10839362] [Abstract] Cited for: FUNCTION.
[6]	"Neuregulin-1 protects ventricular myocytes from anthracycline-induced apoptosis via erbB4-dependent activation of PI3-kinase/Akt." Fukazawa R., Miller T.A., Kuramochi Y., Frantz S., Kim Y.D., Marchionni M.A., Kelly R.A., Sawyer D.B. J. Mol. Cell. Cardiol. 35:1473-1479(2003) [PubMed: 14654373] [Abstract] Cited for: FUNCTION, ENZYME REGULATION.
[7]	"Ligand-dependent recruitment of the ErbB4 signaling complex into neuronal lipid rafts." Ma L., Huang Y.Z., Pitcher G.M., Valtschanoff J.G., Ma Y.H., Feng L.Y., Lu B., Xiong W.C., Salter M.W., Weinberg R.J., Mei L. J. Neurosci. 23:3164-3175(2003) [PubMed: 12716924] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[8]	"Stimulated ErbB4 internalization is necessary for neuregulin signaling in neurons." Liu Y., Tao Y.M., Woo R.S., Xiong W.C., Mei L. Biochem. Biophys. Res. Commun. 354:505-510(2007) [PubMed: 17250808] [Abstract] Cited for: FUNCTION AS NRG1 RECEPTOR IN ACTIVATION OF AKT1 AND THE MAP KINASES MAPK1/ERK2 AND/OR MAPK3/ERK1, SUBCELLULAR LOCATION.
[9]	"The neuregulin-1 receptor erbB4 controls glutamatergic synapse maturation and plasticity." Li B., Woo R.S., Mei L., Malinow R. Neuron 54:583-597(2007) [PubMed: 17521571] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF041838 mRNA. Translation: AAD08899.1. AY375306 mRNA. Translation: AAQ77348.1. AY375307 mRNA. Translation: AAQ77349.1. U52531 mRNA. Translation: AAC53051.1.
IPI	IPI00210292. IPI00778194.
PIR	PT0184.
RefSeq	NP_067719.1. NM_021687.1.
UniGene	Rn.163078.
3D structure databases
ProteinModelPortal	Q62956.
SMR	Q62956. Positions 26-639, 694-1025.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-125039.
STRING	Q62956.
PTM databases
PhosphoSite	Q62956.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	59323.
KEGG	rno:59323.
UCSC	NM_021687. rat.
Organism-specific databases
CTD	2066.
RGD	620486. Erbb4.
Phylogenomic databases
eggNOG	roNOG05099.
HOVERGEN	HBG000490.
InParanoid	Q62956.
Enzyme and pathway databases
BRENDA	2.7.10.1. 5301.
Gene expression databases
ArrayExpress	Q62956.
Genevestigator	Q62956.
GermOnline	ENSRNOG00000014248. Rattus norvegicus.
Family and domain databases
InterPro	IPR000494. EGF_rcpt_L. IPR006211. Furin-like_Cys-rich_dom. IPR006212. Furin_repeat. IPR009030. Growth_fac_rcpt. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR001245. Ser-Thr/Tyr_kinase. IPR008266. Tyr_kinase_AS. IPR020635. Tyr_kinase_cat_dom. IPR016245. Tyr_kinase_EGF/ERB/XmrK_rcpt. [Graphical view]
KO	K05085.
Pfam	PF00757. Furin-like. 1 hit. PF07714. Pkinase_Tyr. 1 hit. PF01030. Recep_L_domain. 2 hits. [Graphical view]
PIRSF	PIRSF000619. TyrPK_EGF-R. 1 hit.
PRINTS	PR00109. TYRKINASE.
SMART	SM00261. FU. 5 hits. SM00219. TyrKc. 1 hit. [Graphical view]
SUPFAM	SSF57184. Grow_fac_recept. 2 hits. SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00109. PROTEIN_KINASE_TYR. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	611909.

Entry information

Entry name

ERBB4_RAT

Accession

Primary (citable) accession number: Q62956
Secondary accession number(s): Q6UA28, Q6UA29, Q9Z2N7

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 15, 1998
Last sequence update:	June 6, 2002
Last modified:	January 25, 2012
This is version 122 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program