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Protein

Receptor tyrosine-protein kinase erbB-4

Gene

Erbb4

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 lactation. The ERBB4 soluble intracellular domains can also translocate to mitochondria and promote apoptosis.5 Publications

Catalytic activityi

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

Enzyme regulationi

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).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei751 – 7511ATPPROSITE-ProRule annotation
Active sitei843 – 8431Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi724 – 7329ATPPROSITE-ProRule annotation
Nucleotide bindingi797 – 7993ATPPROSITE-ProRule annotation
Nucleotide bindingi843 – 8486ATPPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator, Developmental protein, Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Apoptosis, Lactation, Transcription, Transcription regulation

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1. 5301.

Names & Taxonomyi

Protein namesi
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:
ERBB4 intracellular domain
Short name:
4ICD
Short name:
E4ICD
Alternative name(s):
s80HER4
Gene namesi
Name:Erbb4
Synonyms:Tyro-2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi620486. Erbb4.

Subcellular locationi

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).By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini26 – 651626ExtracellularSequence analysisAdd
BLAST
Transmembranei652 – 67524Sequence analysisAdd
BLAST
Topological domaini676 – 1308633CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • caveola Source: RGD
  • cytoplasm Source: RGD
  • integral component of membrane Source: UniProtKB-KW
  • membrane raft Source: RGD
  • mitochondrion Source: UniProtKB-SubCell
  • nucleus Source: RGD
  • plasma membrane Source: RGD
  • postsynaptic density Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Mitochondrion, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2525Sequence analysisAdd
BLAST
Chaini26 – 13081283Receptor tyrosine-protein kinase erbB-4PRO_0000016675Add
BLAST
Chaini676 – 1308633ERBB4 intracellular domainBy similarityPRO_0000396799Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi29 ↔ 56By similarity
Glycosylationi138 – 1381N-linked (GlcNAc...)Sequence analysis
Disulfide bondi156 ↔ 186By similarity
Glycosylationi174 – 1741N-linked (GlcNAc...)Sequence analysis
Disulfide bondi189 ↔ 197By similarity
Disulfide bondi193 ↔ 205By similarity
Disulfide bondi213 ↔ 221By similarity
Disulfide bondi217 ↔ 229By similarity
Disulfide bondi230 ↔ 238By similarity
Disulfide bondi234 ↔ 246By similarity
Disulfide bondi249 ↔ 258By similarity
Glycosylationi253 – 2531N-linked (GlcNAc...)Sequence analysis
Disulfide bondi262 ↔ 289By similarity
Disulfide bondi293 ↔ 304By similarity
Disulfide bondi308 ↔ 323By similarity
Disulfide bondi326 ↔ 330By similarity
Glycosylationi358 – 3581N-linked (GlcNAc...)Sequence analysis
Glycosylationi410 – 4101N-linked (GlcNAc...)Sequence analysis
Glycosylationi473 – 4731N-linked (GlcNAc...)Sequence analysis
Glycosylationi495 – 4951N-linked (GlcNAc...)Sequence analysis
Disulfide bondi503 ↔ 512By similarity
Disulfide bondi507 ↔ 520By similarity
Disulfide bondi523 ↔ 532By similarity
Disulfide bondi536 ↔ 552By similarity
Glycosylationi548 – 5481N-linked (GlcNAc...)Sequence analysis
Disulfide bondi555 ↔ 569By similarity
Disulfide bondi559 ↔ 577By similarity
Glycosylationi576 – 5761N-linked (GlcNAc...)Sequence analysis
Disulfide bondi580 ↔ 589By similarity
Disulfide bondi593 ↔ 614By similarity
Disulfide bondi617 ↔ 625By similarity
Glycosylationi620 – 6201N-linked (GlcNAc...)Sequence analysis
Disulfide bondi621 ↔ 633By similarity
Modified residuei875 – 8751Phosphotyrosine; by autocatalysisBy similarity
Modified residuei1035 – 10351Phosphotyrosine; by autocatalysisBy similarity
Modified residuei1056 – 10561Phosphotyrosine; by autocatalysisBy similarity
Modified residuei1150 – 11501Phosphotyrosine; by autocatalysisBy similarity
Modified residuei1162 – 11621Phosphotyrosine; by autocatalysisBy similarity
Modified residuei1188 – 11881Phosphotyrosine; by autocatalysisBy similarity
Modified residuei1202 – 12021Phosphotyrosine; by autocatalysisBy similarity
Modified residuei1242 – 12421Phosphotyrosine; by autocatalysisBy similarity
Modified residuei1258 – 12581Phosphotyrosine; by autocatalysisBy similarity
Modified residuei1284 – 12841Phosphotyrosine; by autocatalysisBy similarity

Post-translational modificationi

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).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).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).By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ62956.
PRIDEiQ62956.

PTM databases

PhosphoSiteiQ62956.
SwissPalmiQ62956.

Expressioni

Tissue specificityi

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 thalamus. Very low levels in kidney, and heart.

Interactioni

Subunit structurei

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).By similarity

Protein-protein interaction databases

MINTiMINT-125039.
STRINGi10116.ENSRNOP00000019283.

Structurei

3D structure databases

ProteinModelPortaliQ62956.
SMRiQ62956. Positions 26-639, 694-1025.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini718 – 985268Protein kinasePROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi676 – 6849Nuclear localization signalBy similarity
Motifi1032 – 10354PPxy motif 1
Motifi1298 – 13014PPxY motif 2
Motifi1306 – 13083PDZ-binding

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi186 – 334149Cys-richAdd
BLAST
Compositional biasi496 – 633138Cys-richAdd
BLAST

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1025. Eukaryota.
ENOG410XNSR. LUCA.
HOGENOMiHOG000230982.
HOVERGENiHBG000490.
InParanoidiQ62956.
KOiK05085.
PhylomeDBiQ62956.

Family and domain databases

Gene3Di3.80.20.20. 2 hits.
InterProiIPR006211. Furin-like_Cys-rich_dom.
IPR006212. Furin_repeat.
IPR032778. GF_recep_IV.
IPR009030. Growth_fac_rcpt_.
IPR011009. Kinase-like_dom.
IPR032675. L_dom-like.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR000494. Rcpt_L-dom.
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]
PfamiPF00757. Furin-like. 1 hit.
PF14843. GF_recep_IV. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF01030. Recep_L_domain. 2 hits.
[Graphical view]
PIRSFiPIRSF000619. TyrPK_EGF-R. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiSM00261. FU. 5 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF52058. SSF52058. 2 hits.
SSF56112. SSF56112. 1 hit.
SSF57184. SSF57184. 2 hits.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.

Isoform JM-A CYT1 (identifier: Q62956-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MKLATGLWVW GSLLVAARTV QPSASQSVCA GTENKLSSLS DLEQQYRALR
60 70 80 90 100
KYYENCEVVM GNLEITSIEH NRDLSFLRSI REVTGYVLVA LNQFRYLPLE
110 120 130 140 150
NLRIIRGTKL YEDRYALAIF LNYRKDGNFG LQELGLKNLT EILNGGVYVD
160 170 180 190 200
QNKFLCYADT IHWQDIVRNP WPSNMTLVST IGSSGCGRCH KSCTGRCWGP
210 220 230 240 250
TENHCQTLTR TVCAEQCDGR CYGPYVSDCC HRECAGGCSG PKDTDCFACM
260 270 280 290 300
NFNDSGACVT QCPQTFVYNP TTFQLEHNFN AKYTYGAFCV KKCPHNFVVD
310 320 330 340 350
SSSCVRACPS SKMEVEENGI KMCKPCTDIC PKACDGIGTG SLMSAQTVDS
360 370 380 390 400
SNIDKFINCT KINGNLIFLV TGIHGDPYNA IDAIDPEKLN VFRTVREITG
410 420 430 440 450
FLNIQTWPPN MTDFSVFSNL VTIGGRVLYS GLSLLILKQQ GITSLQFQSL
460 470 480 490 500
KEISAGNIYI TDNSNLCYYH TINWTTLFST VNQRIVIRDN RRAENCTAEG
510 520 530 540 550
MVCNHLCSND GCWGPGPDQC LSCRRFSRGK ICIESCNLYD GEFREFENGS
560 570 580 590 600
ICVECDSQCE KMEDGLLTCH GPGPDNCTKC SHFKDGPNCV EKCPDVLQGA
610 620 630 640 650
NSFIFKYADQ DRECHPCHPN CTQGCNGPTS HDCIYYPWTG HSTLPQHART
660 670 680 690 700
PLIAAGVIGG LFILVIMALT FAVYVRRKSI KKKRALRRFL ETELVEPLTP
710 720 730 740 750
SGTAPNQAQL RILKETELKR VKVLGSGAFG TVYKGIWVPE GETVKIPVAI
760 770 780 790 800
KILNETTGPK ANVEFMDEAL IMASVDHPHL VRLLGVCLSP TIQLVTQLMP
810 820 830 840 850
HGCLLEYVHE HKDNIGSQLL LNWCVQIAKG MMYLEERRLV HRDLAARNVL
860 870 880 890 900
VKSPNHVKIT DFGLARLLEG DEKEYNADGG KMPIKWMALE CIHYRKFTHQ
910 920 930 940 950
SDVWSYGVTI WELMTFGGKP YDGIPTREIP DLLEKGERLP QPPICTIDVY
960 970 980 990 1000
IVMVKCWMID ADSRPKFKEL AAEFSRMARD PQRYLVIQGD DRMKLPSPND
1010 1020 1030 1040 1050
SKFFQNLLDE EDLEDMMDAE EYLVPQAFNI PPPIYTSRTR IDSNRSEIGH
1060 1070 1080 1090 1100
SPPPAYTPMS GSQFVYQDGG FATQQGMPMP YTATTSTIPE APVAQGATAE
1110 1120 1130 1140 1150
MFDDSCCNGT LRKPVVPHVQ EDSSTQRYSA DPTVFAPERN PRAELDEEGY
1160 1170 1180 1190 1200
MTPMHDKPKQ EYLNPVEENP FVSRRKNGDL QALDNPEYHS ASSGPPKAED
1210 1220 1230 1240 1250
EYVNEPLYLN TFTNALGNAE YMKNSLLSVP EKAKKAFDNP DYWNHSLPPR
1260 1270 1280 1290 1300
STLQHPDYLQ EYSTKYFYKQ NGRIRPIVAE NPEYLSEFSL KPGTMLPPPP

YRHRNTVV
Length:1,308
Mass (Da):146,958
Last modified:June 6, 2002 - v3
Checksum:iD944BB0996A08B41
GO
Isoform JM-A CYT2 (identifier: Q62956-2) [UniParc]FASTAAdd to basket

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.
Show »
Length:1,292
Mass (Da):145,376
Checksum:i4249D5FD4B5A9272
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti406 – 4061T → S in AAQ77348 (PubMed:15355992).Curated
Sequence conflicti406 – 4061T → S in AAQ77349 (PubMed:15355992).Curated
Sequence conflicti596 – 5961V → G in AAQ77348 (PubMed:15355992).Curated
Sequence conflicti596 – 5961V → G in AAQ77349 (PubMed:15355992).Curated
Sequence conflicti951 – 9511I → M in AAQ77348 (PubMed:15355992).Curated
Sequence conflicti951 – 9511I → M in AAQ77349 (PubMed:15355992).Curated
Sequence conflicti1062 – 10621S → N in AAQ77348 (PubMed:15355992).Curated
Sequence conflicti1062 – 10621S → N in AAC53051 (PubMed:9030624).Curated
Sequence conflicti1080 – 10823PYT → SYR in AAC53051 (PubMed:9030624).Curated
Sequence conflicti1082 – 10821T → R in AAQ77348 (PubMed:15355992).Curated
Sequence conflicti1082 – 10821T → R in AAQ77349 (PubMed:15355992).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1046 – 106217SEIGH…PMSGS → N in isoform JM-A CYT2. 1 PublicationVSP_022150Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF041838 mRNA. Translation: AAD08899.1.
AY375306 mRNA. Translation: AAQ77348.1.
AY375307 mRNA. Translation: AAQ77349.1.
U52531 mRNA. Translation: AAC53051.1.
PIRiPT0184.
RefSeqiNP_067719.1. NM_021687.1. [Q62956-1]
UniGeneiRn.163078.

Genome annotation databases

GeneIDi59323.
KEGGirno:59323.
UCSCiRGD:620486. rat. [Q62956-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF041838 mRNA. Translation: AAD08899.1.
AY375306 mRNA. Translation: AAQ77348.1.
AY375307 mRNA. Translation: AAQ77349.1.
U52531 mRNA. Translation: AAC53051.1.
PIRiPT0184.
RefSeqiNP_067719.1. NM_021687.1. [Q62956-1]
UniGeneiRn.163078.

3D structure databases

ProteinModelPortaliQ62956.
SMRiQ62956. Positions 26-639, 694-1025.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

MINTiMINT-125039.
STRINGi10116.ENSRNOP00000019283.

PTM databases

PhosphoSiteiQ62956.
SwissPalmiQ62956.

Proteomic databases

PaxDbiQ62956.
PRIDEiQ62956.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi59323.
KEGGirno:59323.
UCSCiRGD:620486. rat. [Q62956-1]

Organism-specific databases

CTDi2066.
RGDi620486. Erbb4.

Phylogenomic databases

eggNOGiKOG1025. Eukaryota.
ENOG410XNSR. LUCA.
HOGENOMiHOG000230982.
HOVERGENiHBG000490.
InParanoidiQ62956.
KOiK05085.
PhylomeDBiQ62956.

Enzyme and pathway databases

BRENDAi2.7.10.1. 5301.

Miscellaneous databases

NextBioi611909.
PROiQ62956.

Family and domain databases

Gene3Di3.80.20.20. 2 hits.
InterProiIPR006211. Furin-like_Cys-rich_dom.
IPR006212. Furin_repeat.
IPR032778. GF_recep_IV.
IPR009030. Growth_fac_rcpt_.
IPR011009. Kinase-like_dom.
IPR032675. L_dom-like.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR000494. Rcpt_L-dom.
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]
PfamiPF00757. Furin-like. 1 hit.
PF14843. GF_recep_IV. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF01030. Recep_L_domain. 2 hits.
[Graphical view]
PIRSFiPIRSF000619. TyrPK_EGF-R. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiSM00261. FU. 5 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF52058. SSF52058. 2 hits.
SSF56112. SSF56112. 1 hit.
SSF57184. SSF57184. 2 hits.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiERBB4_RAT
AccessioniPrimary (citable) accession number: Q62956
Secondary accession number(s): Q6UA28, Q6UA29, Q9Z2N7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: June 6, 2002
Last modified: February 17, 2016
This is version 154 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.