CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-014347
UniProt Accession
Genbank Protein ID
 CU368746; CU372923; CU392849; CU405881; CU407006; CU459008; CU459207; CU368746; CU372923; CU392849; CU405881; CU407006; CU459008; CU459207; CU392849; CU368746; CU372923; CU405881; CU407006; CU459008; CU459207; CU459207; CU368746; CU372923; CU392849; CU405881; CU407006; CU459008; CU392849; CU368746; CU372923; CU405881; CU407006; CU459008; CU459207; CU459207; CU368746; CU372923; CU392849; CU405881; CU407006; CU459008; CU405881; CU368746; CU372923; CU392849; CU407006; CU459008; CU459207; CU405881; CU368746; CU372923; CU392849; CU407006; CU459008; CU459207; CU459008; CU368746; CU372923; CU392849; CU405881; CU407006; CU459207; CU459008; CU368746; CU372923; CU392849; CU405881; CU407006; CU459207; CU407006; CU368746; CU372923; CU392849; CU405881; CU459008; CU459207; CU407006; CU368746; CU372923; CU392849; CU405881; CU459008; CU459207; CU372923; CU368746; CU392849; CU405881; CU407006; CU459008; CU459207; CU372923; CU368746; CU392849; CU405881; CU407006; CU459008; CU459207; AK144050; L47241; AF059177 
Genbank Nucleotide ID
 CAQ51554.1; CAQ51554.1; CAQ51554.1; CAQ51554.1; CAQ51554.1; CAQ51554.1; CAQ51554.1; CAQ51555.1; CAQ51555.1; CAQ51555.1; CAQ51555.1; CAQ51555.1; CAQ51555.1; CAQ51555.1; CAQ51831.1; CAQ51831.1; CAQ51831.1; CAQ51831.1; CAQ51831.1; CAQ51831.1; CAQ51831.1; CAQ51899.1; CAQ51899.1; CAQ51899.1; CAQ51899.1; CAQ51899.1; CAQ51899.1; CAQ51899.1; CAQ51832.1; CAQ51832.1; CAQ51832.1; CAQ51832.1; CAQ51832.1; CAQ51832.1; CAQ51832.1; CAQ51900.1; CAQ51900.1; CAQ51900.1; CAQ51900.1; CAQ51900.1; CAQ51900.1; CAQ51900.1; CAQ52134.1; CAQ52134.1; CAQ52134.1; CAQ52134.1; CAQ52134.1; CAQ52134.1; CAQ52134.1; CAQ52135.1; CAQ52135.1; CAQ52135.1; CAQ52135.1; CAQ52135.1; CAQ52135.1; CAQ52135.1; CAQ52171.1; CAQ52171.1; CAQ52171.1; CAQ52171.1; CAQ52171.1; CAQ52171.1; CAQ52171.1; CAQ52172.1; CAQ52172.1; CAQ52172.1; CAQ52172.1; CAQ52172.1; CAQ52172.1; CAQ52172.1; CAQ52191.1; CAQ52191.1; CAQ52191.1; CAQ52191.1; CAQ52191.1; CAQ52191.1; CAQ52191.1; CAQ52192.1; CAQ52192.1; CAQ52192.1; CAQ52192.1; CAQ52192.1; CAQ52192.1; CAQ52192.1; CAQ52287.1; CAQ52287.1; CAQ52287.1; CAQ52287.1; CAQ52287.1; CAQ52287.1; CAQ52287.1; CAQ52288.1; CAQ52288.1; CAQ52288.1; CAQ52288.1; CAQ52288.1; CAQ52288.1; CAQ52288.1; BAE25671.1; AAA93534.1; AAC28334.1 
Protein Name
 Receptor tyrosine-protein kinase erbB-4 
Protein Synonyms/Alias
 Proto-oncogene-like protein c-ErbB-4; ERBB4 intracellular domain; 4ICD; E4ICD; s80HER4 
Gene Name
 Erbb4 
Gene Synonyms/Alias
 Mer4 
Created Date
 July 27, 2013 
Organism
 Mus musculus (Mouse) 
NCBI Taxa ID
 10090 
Lysine Modification
Position
Peptide
Type
References
745VPEGETVKIPVAIKIubiquitination[1]
Reference
 [1] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023] 
Functional Description
 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. 
Sequence Annotation
 DOMAIN 718 985 Protein kinase.
 NP_BIND 724 732 ATP (By similarity).
 NP_BIND 797 799 ATP (By similarity).
 NP_BIND 843 848 ATP (By similarity).
 MOTIF 676 684 Nuclear localization signal (By
 MOTIF 1032 1035 PPxy motif 1 (By similarity).
 MOTIF 1282 1285 PPxY motif 2 (By similarity).
 MOTIF 1290 1292 PDZ-binding (By similarity).
 ACT_SITE 843 843 Proton acceptor (By similarity).
 BINDING 751 751 ATP (By similarity).
 MOD_RES 875 875 Phosphotyrosine; by autocatalysis (By
 MOD_RES 1035 1035 Phosphotyrosine; by autocatalysis (By
 MOD_RES 1056 1056 Phosphotyrosine; by autocatalysis (By
 MOD_RES 1150 1150 Phosphotyrosine; by autocatalysis (By
 MOD_RES 1162 1162 Phosphotyrosine; by autocatalysis (By
 MOD_RES 1188 1188 Phosphotyrosine; by autocatalysis (By
 MOD_RES 1202 1202 Phosphotyrosine; by autocatalysis (By
 MOD_RES 1242 1242 Phosphotyrosine; by autocatalysis (By
 MOD_RES 1258 1258 Phosphotyrosine; by autocatalysis (By
 MOD_RES 1284 1284 Phosphotyrosine; by autocatalysis (By
 CARBOHYD 138 138 N-linked (GlcNAc...) (Potential).
 CARBOHYD 174 174 N-linked (GlcNAc...) (Potential).
 CARBOHYD 181 181 N-linked (GlcNAc...) (Potential).
 CARBOHYD 253 253 N-linked (GlcNAc...) (Potential).
 CARBOHYD 410 410 N-linked (GlcNAc...) (Potential).
 CARBOHYD 473 473 N-linked (GlcNAc...) (Potential).
 CARBOHYD 495 495 N-linked (GlcNAc...) (Potential).
 CARBOHYD 548 548 N-linked (GlcNAc...) (Potential).
 CARBOHYD 576 576 N-linked (GlcNAc...) (Potential).
 CARBOHYD 620 620 N-linked (GlcNAc...) (Potential).
 DISULFID 29 56 By similarity.
 DISULFID 156 186 By similarity.
 DISULFID 189 197 By similarity.
 DISULFID 193 205 By similarity.
 DISULFID 213 221 By similarity.
 DISULFID 217 229 By similarity.
 DISULFID 230 238 By similarity.
 DISULFID 234 246 By similarity.
 DISULFID 249 258 By similarity.
 DISULFID 262 289 By similarity.
 DISULFID 293 304 By similarity.
 DISULFID 308 323 By similarity.
 DISULFID 326 330 By similarity.
 DISULFID 503 512 By similarity.
 DISULFID 507 520 By similarity.
 DISULFID 523 532 By similarity.
 DISULFID 536 552 By similarity.
 DISULFID 555 569 By similarity.
 DISULFID 559 577 By similarity.
 DISULFID 580 589 By similarity.
 DISULFID 593 614 By similarity.
 DISULFID 617 625 By similarity.
 DISULFID 621 633 By similarity.  
Keyword
 Activator; Alternative splicing; Apoptosis; ATP-binding; Cell membrane; Complete proteome; Developmental protein; Disulfide bond; Glycoprotein; Kinase; Lactation; Membrane; Mitochondrion; Nucleotide-binding; Nucleus; Phosphoprotein; Receptor; Reference proteome; Repeat; Signal; Transcription; Transcription regulation; Transferase; Transmembrane; Transmembrane helix; Tumor suppressor; Tyrosine-protein kinase; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1308 AA 
Protein Sequence
MKLATGLWVW GSLLMAAGTV QPSASQSVCA GTENKLSSLS DLEQQYRALR KYYENCEVVM 60
GNLEITSIEH NRDLSFLRSI REVTGYVLVA LNQFRYLPLE NLRIIRGTKL YEDRYALAIF 120
LNYRKDGNFG LQELGLKNLT EILNGGVYVD QNKFLCYADT IHWQDIVRNP WPSNMTLVST 180
NGSSGCGRCH KSCTGRCWGP TENHCQTLTR TVCAEQCDGR CYGPYVSDCC HRECAGGCSG 240
PKDTDCFACM NFNDSGACVT QCPQTFVYNP TTFQLEHNFN AKYTYGAFCV KKCPHNFVVD 300
SSSCVRACPS SKMEVEENGI KMCKPCTDIC PKACDGIGTG SLMSAQTVDS SNIDKFINCT 360
KINGNLIFLV TGIHGDPYNA IDAIDPEKLN VFRTVREITG FLNIQSWPPN MTDFSVFSNL 420
VTIGGRVLYS GLSLLILKQQ GITSLQFQSL KEISAGNIYI TDNSNLCYYH TINWTTLFST 480
INQRIVIRDN RRAENCTAEG MVCNHLCSND GCWGPGPDQC LSCRRFSRGK ICIESCNLYD 540
GEFREFENGS ICVECDSQCE KMEDGLLTCH GPGPDNCTKC SHFKDGPNCV EKCPDGLQGA 600
NSFIFKYADQ DRECHPCHPN CTQGCNGPTS HDCIYYPWTG HSTLPQHART PLIAAGVIGG 660
LFILVIMALT FAVYVRRKSI KKKRALRRFL ETELVEPLTP SGTAPNQAQL RILKETELKR 720
VKVLGSGAFG TVYKGIWVPE GETVKIPVAI KILNETTGPK ANVEFMDEAL IMASMDHPHL 780
VRLLGVCLSP TIQLVTQLMP HGCLLDYVHE HKDNIGSQLL LNWCVQIAKG MMYLEERRLV 840
HRDLAARNVL VKSPNHVKIT DFGLARLLEG DEKEYNADGG KMPIKWMALE CIHYRKFTHQ 900
SDVWSYGVTI WELMTFGGKP YDGIPTREIP DLLEKGERLP QPPICTIDVY MVMVKCWMID 960
ADSRPKFKEL AAEFSRMARD PQRYLVIQGD DRMKLPSPND SKFFQNLLDE EDLEDMMDAE 1020
EYLVPQAFNI PPPIYTSRTR IDSNRSEIGH SPPPAYTPMS GNQFVYQDGG FATQQGMPMP 1080
YRATTSTIPE APVAQGATAE MFDDSCCNGT LRKPVAPHVQ EDSSTQRYSA DPTVFAPERN 1140
PRGELDEEGY MTPMHDKPKQ EYLNPVEENP FVSRRKNGDL QALDNPEYHS ASSGPPKAED 1200
EYVNEPLYLN TFANALGSAE YMKNSVLSVP EKAKKAFDNP DYWNHSLPPR STLQHPDYLQ 1260
EYSTKYFYKQ NGRIRPIVAE NPEYLSEFSL KPGTMLPPPP YRHRNTVV 1308 
Gene Ontology
 GO:0016323; C:basolateral plasma membrane; IEA:Compara.
 GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
 GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
 GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004716; F:receptor signaling protein tyrosine kinase activity; IEA:InterPro.
 GO:0044212; F:transcription regulatory region DNA binding; IEA:Compara.
 GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; ISS:UniProtKB.
 GO:0061026; P:cardiac muscle tissue regeneration; IMP:UniProtKB.
 GO:0045165; P:cell fate commitment; IDA:MGI.
 GO:0021551; P:central nervous system morphogenesis; IMP:UniProtKB.
 GO:0009880; P:embryonic pattern specification; IMP:UniProtKB.
 GO:0007507; P:heart development; IMP:MGI.
 GO:0007595; P:lactation; IMP:UniProtKB.
 GO:0060749; P:mammary gland alveolus development; IMP:UniProtKB.
 GO:0060644; P:mammary gland epithelial cell differentiation; IMP:UniProtKB.
 GO:0043653; P:mitochondrial fragmentation involved in apoptotic process; ISS:UniProtKB.
 GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
 GO:0008285; P:negative regulation of cell proliferation; ISS:UniProtKB.
 GO:0001755; P:neural crest cell migration; IMP:UniProtKB.
 GO:0021889; P:olfactory bulb interneuron differentiation; IMP:UniProtKB.
 GO:0018108; P:peptidyl-tyrosine phosphorylation; ISS:UniProtKB.
 GO:0060045; P:positive regulation of cardiac muscle cell proliferation; IMP:UniProtKB.
 GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
 GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; ISS:UniProtKB.
 GO:2000366; P:positive regulation of STAT protein import into nucleus; IMP:UniProtKB.
 GO:0045893; P:positive regulation of transcription, DNA-dependent; IMP:UniProtKB.
 GO:0042523; P:positive regulation of tyrosine phosphorylation of Stat5 protein; IMP:UniProtKB.
 GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
 GO:0030334; P:regulation of cell migration; IMP:UniProtKB.
 GO:0023014; P:signal transduction by phosphorylation; IEA:GOC.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
 GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; ISS:UniProtKB. 
Interpro
 IPR000494; 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_cat_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. 
Pfam
 PF00757; Furin-like
 PF07714; Pkinase_Tyr
 PF01030; Recep_L_domain 
SMART
 SM00261; FU
 SM00219; TyrKc 
PROSITE
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00109; PROTEIN_KINASE_TYR 
PRINTS
 PR00109; TYRKINASE.