EGF_RAT
ID EGF_RAT Reviewed; 1133 AA.
AC P07522; Q63183;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 2.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Pro-epidermal growth factor;
DE Short=EGF;
DE Contains:
DE RecName: Full=Epidermal growth factor;
DE Flags: Precursor;
GN Name=Egf;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Kidney;
RX PubMed=1524680; DOI=10.1089/dna.1992.11.481;
RA Price P.M., Saggi S.J., Safirstein R.;
RT "Cloning and sequencing of the rat preproepidermal growth factor cDNA:
RT comparison with mouse and human sequences.";
RL DNA Cell Biol. 11:481-487(1992).
RN [2]
RP SEQUENCE REVISION.
RC TISSUE=Kidney;
RA Price P.M.;
RL Submitted (JAN-1994) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP PROTEIN SEQUENCE OF 974-1021.
RX PubMed=3000782; DOI=10.1111/j.1432-1033.1985.tb09346.x;
RA Simpson R.J., Smith J.A., Moritz R.L., O'Hare M.J., Rudland P.S.,
RA Morrison J.R., Lloyd C.J., Grego B., Burgess A.W., Nice E.C.;
RT "Rat epidermal growth factor: complete amino acid sequence. Homology with
RT the corresponding murine and human proteins; isolation of a form truncated
RT at both ends with full in vitro biological activity.";
RL Eur. J. Biochem. 153:629-637(1985).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 994-1133.
RC STRAIN=Sprague-Dawley; TISSUE=Kidney;
RX PubMed=3262867; DOI=10.1093/nar/16.19.9338;
RA Dorow D.S., Simpson R.J.;
RT "Cloning and sequence analysis of a cDNA for rat epidermal growth factor.";
RL Nucleic Acids Res. 16:9338-9338(1988).
CC -!- FUNCTION: EGF stimulates the growth of various epidermal and epithelial
CC tissues in vivo and in vitro and of some fibroblasts in cell culture.
CC Magnesiotropic hormone that stimulates magnesium reabsorption in the
CC renal distal convoluted tubule via engagement of EGFR and activation of
CC the magnesium channel TRPM6 (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. Interacts
CC with RHBDF1; may retain EGF in the endoplasmic reticulum and regulates
CC its degradation through the endoplasmic reticulum-associated
CC degradation (ERAD) (By similarity). Interacts with RHBDF2 (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
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DR EMBL; U04842; AAB60436.1; -; mRNA.
DR EMBL; X12748; CAA31241.1; -; mRNA.
DR PIR; I52995; EGRT.
DR RefSeq; NP_036974.1; NM_012842.1.
DR AlphaFoldDB; P07522; -.
DR SMR; P07522; -.
DR STRING; 10116.ENSRNOP00000066558; -.
DR BindingDB; P07522; -.
DR GlyGen; P07522; 6 sites.
DR iPTMnet; P07522; -.
DR PhosphoSitePlus; P07522; -.
DR PaxDb; P07522; -.
DR PRIDE; P07522; -.
DR GeneID; 25313; -.
DR KEGG; rno:25313; -.
DR UCSC; RGD:2542; rat.
DR CTD; 1950; -.
DR RGD; 2542; Egf.
DR eggNOG; KOG1215; Eukaryota.
DR InParanoid; P07522; -.
DR OrthoDB; 828765at2759; -.
DR PhylomeDB; P07522; -.
DR Reactome; R-RNO-114608; Platelet degranulation.
DR Reactome; R-RNO-1227986; Signaling by ERBB2.
DR Reactome; R-RNO-1236394; Signaling by ERBB4.
DR Reactome; R-RNO-1250196; SHC1 events in ERBB2 signaling.
DR Reactome; R-RNO-1257604; PIP3 activates AKT signaling.
DR Reactome; R-RNO-177929; Signaling by EGFR.
DR Reactome; R-RNO-179812; GRB2 events in EGFR signaling.
DR Reactome; R-RNO-180292; GAB1 signalosome.
DR Reactome; R-RNO-180336; SHC1 events in EGFR signaling.
DR Reactome; R-RNO-182971; EGFR downregulation.
DR Reactome; R-RNO-1963642; PI3K events in ERBB2 signaling.
DR Reactome; R-RNO-212718; EGFR interacts with phospholipase C-gamma.
DR Reactome; R-RNO-5673001; RAF/MAP kinase cascade.
DR Reactome; R-RNO-6785631; ERBB2 Regulates Cell Motility.
DR Reactome; R-RNO-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-RNO-8847993; ERBB2 Activates PTK6 Signaling.
DR Reactome; R-RNO-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-RNO-8856828; Clathrin-mediated endocytosis.
DR Reactome; R-RNO-8863795; Downregulation of ERBB2 signaling.
DR Reactome; R-RNO-9009391; Extra-nuclear estrogen signaling.
DR Reactome; R-RNO-9013507; NOTCH3 Activation and Transmission of Signal to the Nucleus.
DR PRO; PR:P07522; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0070062; C:extracellular exosome; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0005154; F:epidermal growth factor receptor binding; IDA:RGD.
DR GO; GO:0008083; F:growth factor activity; ISO:RGD.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; ISO:RGD.
DR GO; GO:0048018; F:receptor ligand activity; ISO:RGD.
DR GO; GO:0030297; F:transmembrane receptor protein tyrosine kinase activator activity; ISO:RGD.
DR GO; GO:0001525; P:angiogenesis; ISO:RGD.
DR GO; GO:0048754; P:branching morphogenesis of an epithelial tube; ISO:RGD.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IDA:RGD.
DR GO; GO:0038029; P:epidermal growth factor receptor signaling pathway via MAPK cascade; ISS:UniProtKB.
DR GO; GO:0038134; P:ERBB2-EGFR signaling pathway; ISO:RGD.
DR GO; GO:0070371; P:ERK1 and ERK2 cascade; ISO:RGD.
DR GO; GO:0035556; P:intracellular signal transduction; TAS:RGD.
DR GO; GO:0001822; P:kidney development; IEP:RGD.
DR GO; GO:0060749; P:mammary gland alveolus development; ISO:RGD.
DR GO; GO:0090370; P:negative regulation of cholesterol efflux; ISO:RGD.
DR GO; GO:0051048; P:negative regulation of secretion; ISO:RGD.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISO:RGD.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; ISO:RGD.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0021940; P:positive regulation of cerebellar granule cell precursor proliferation; ISO:RGD.
DR GO; GO:0043388; P:positive regulation of DNA binding; ISS:UniProtKB.
DR GO; GO:2000573; P:positive regulation of DNA biosynthetic process; IDA:RGD.
DR GO; GO:0045740; P:positive regulation of DNA replication; ISS:UniProtKB.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; ISO:RGD.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; ISO:RGD.
DR GO; GO:0045741; P:positive regulation of epidermal growth factor-activated receptor activity; ISO:RGD.
DR GO; GO:1905278; P:positive regulation of epithelial tube formation; ISO:RGD.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:RGD.
DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; IDA:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:1900127; P:positive regulation of hyaluronan biosynthetic process; ISO:RGD.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; ISO:RGD.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:RGD.
DR GO; GO:0045840; P:positive regulation of mitotic nuclear division; ISO:RGD.
DR GO; GO:0010800; P:positive regulation of peptidyl-threonine phosphorylation; ISO:RGD.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:RGD.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISO:RGD.
DR GO; GO:0042327; P:positive regulation of phosphorylation; ISO:RGD.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISO:RGD.
DR GO; GO:1902966; P:positive regulation of protein localization to early endosome; ISO:RGD.
DR GO; GO:0061098; P:positive regulation of protein tyrosine kinase activity; ISO:RGD.
DR GO; GO:0002092; P:positive regulation of receptor internalization; ISO:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:2000060; P:positive regulation of ubiquitin-dependent protein catabolic process; ISO:RGD.
DR GO; GO:0090279; P:regulation of calcium ion import; ISO:RGD.
DR GO; GO:0050730; P:regulation of peptidyl-tyrosine phosphorylation; ISO:RGD.
DR GO; GO:2000008; P:regulation of protein localization to cell surface; ISO:RGD.
DR GO; GO:0050708; P:regulation of protein secretion; IMP:RGD.
DR GO; GO:0051223; P:regulation of protein transport; IDA:MGI.
DR GO; GO:0046425; P:regulation of receptor signaling pathway via JAK-STAT; ISS:UniProtKB.
DR Gene3D; 2.120.10.30; -; 2.
DR InterPro; IPR011042; 6-blade_b-propeller_TolB-like.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
DR InterPro; IPR018097; EGF_Ca-bd_CS.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR000033; LDLR_classB_rpt.
DR InterPro; IPR016317; Pro-epidermal_GF.
DR Pfam; PF00008; EGF; 1.
DR Pfam; PF07645; EGF_CA; 3.
DR Pfam; PF00058; Ldl_recept_b; 3.
DR PIRSF; PIRSF001778; Pro-epidermal_growth_factor; 1.
DR SMART; SM00181; EGF; 8.
DR SMART; SM00179; EGF_CA; 5.
DR SMART; SM00135; LY; 8.
DR SUPFAM; SSF57184; SSF57184; 2.
DR PROSITE; PS00010; ASX_HYDROXYL; 3.
DR PROSITE; PS00022; EGF_1; 1.
DR PROSITE; PS01186; EGF_2; 6.
DR PROSITE; PS50026; EGF_3; 5.
DR PROSITE; PS01187; EGF_CA; 3.
DR PROSITE; PS51120; LDLRB; 9.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Disulfide bond; EGF-like domain; Glycoprotein;
KW Growth factor; Membrane; Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..1133
FT /note="Pro-epidermal growth factor"
FT /id="PRO_0000007546"
FT CHAIN 974..1026
FT /note="Epidermal growth factor"
FT /id="PRO_0000007547"
FT TOPO_DOM 22..1035
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1036..1057
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1058..1133
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 87..128
FT /note="LDL-receptor class B 1"
FT REPEAT 129..170
FT /note="LDL-receptor class B 2"
FT REPEAT 171..212
FT /note="LDL-receptor class B 3"
FT REPEAT 213..259
FT /note="LDL-receptor class B 4"
FT DOMAIN 322..356
FT /note="EGF-like 1; incomplete"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 357..397
FT /note="EGF-like 2; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 398..438
FT /note="EGF-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 436..478
FT /note="EGF-like 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REPEAT 485..525
FT /note="LDL-receptor class B 5"
FT REPEAT 526..568
FT /note="LDL-receptor class B 6"
FT REPEAT 569..611
FT /note="LDL-receptor class B 7"
FT REPEAT 612..655
FT /note="LDL-receptor class B 8"
FT REPEAT 656..698
FT /note="LDL-receptor class B 9"
FT DOMAIN 743..783
FT /note="EGF-like 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 835..873
FT /note="EGF-like 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 874..915
FT /note="EGF-like 7; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 916..956
FT /note="EGF-like 8; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 975..1016
FT /note="EGF-like 9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REGION 1069..1097
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1072..1095
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 105
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 118
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 149
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 405
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 930
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 941
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 361..372
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 368..381
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 383..396
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 402..413
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 409..422
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 424..437
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 440..452
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 448..462
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 464..477
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 747..758
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 754..767
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 769..782
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 839..850
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 844..859
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 861..872
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 878..892
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 885..901
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 903..914
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 920..933
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 927..942
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 944..955
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 979..993
FT DISULFID 987..1004
FT DISULFID 1006..1015
FT VARIANT 955
FT /note="C -> V"
FT CONFLICT 1024..1025
FT /note="KL -> NW (in Ref. 4; CAA31241)"
FT /evidence="ECO:0000305"
FT CONFLICT 1109..1133
FT /note="QPKNGRLPAAGTNGAVVEAGLSSSL -> SGAGVSSGPQPWFVVLEEHQ
FT (in Ref. 4; CAA31241)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1133 AA; 124126 MW; C224A302E9578031 CRC64;
MLFSLTFLSV FLKITVLSVT AQQTRNCQSG PLERSGTTTY AAAGPPRFLI FLQGNSIFRI
NTDGTNHQQL VVDAGVSVVM DFHYKEERLY WVDLERQLLQ RVFFNGSGQE TVCKVDKNVS
GLAINWIDGE ILRTDRWKGV ITVTDMNGNN SRVLLSSLKR PANILVDPTE RLIFWSSVVT
GNLHRADLGG MDVKTLLEAP ERISVLILDI LDKRLFWAQD GREGSHGYIH SCDYNGGSIH
HIRHQARHDL LTMAIFGDKI LYSALKEKAI WIADKHTGKN VVRVNLDPAS VPPRELRVVH
LHAQPGTENR AQASDSERCK QRRGQCLYSL SERDPNSDSS ACAEGYTLSR DRKYCEDVNE
CALQNHGCTL GCENIPGSYY CTCPTGFVLL PDGKRCHELV ACPGNRSECS HDCILTSDGP
LCICPAGSVL GKDGKTCTGC SFSDNGGCSQ ICLPLSLASW ECDCFPGYDL QLDRKSCAAS
MGPQPFLLFA NSQDIRHMHF DGTDYKTLLS RQMGMVFALD YDPVESKIYF AQTALKWIER
ANLDGSQRER RITEGVDTPE GLAVDWIGRR IYWTDSGKSV IEGSDLSGKH HQIIIKESIS
RPRGIAVHPK ARRLFWTDTG MSPRIESSSL QGSDRTLIAS SNLLEPSGIA IDYLTDTLYW
CDTKLSVIEM ADLDGSKRRR LTQNDVGHPF SLAVFEDHVW FSDWAIPSVI RVNKRTGQNR
VRLRGSMLKP SSLVVVHPLA KPGADPCLHR NGGCEHICQE SLGTAQCLCR EGFVKAPDGK
MCLTRKDDQI LAGDNADLSK EVASLDNSPK AYVPDDDRTE SSTLVAEIMV SGLNYEDDCG
PGGCGSHAHC ISEGEAAVCQ CLKGFAGDGN LCSDIDECEL GSSDCPPTSS RCINTEGGYV
CQCSEGYEGD GIYCLDVDEC QQGSHGCSEN ATCTNTEGGY NCTCAGCPSA PGLPCPDSTS
PSLLGKDGCH WVRNSNTGCP PSYDGYCLNG GVCMYVESVD RYVCNCVIGY IGERCQHRDL
RWWKLRHADY GQRHDITVVS VCVVALALLL LLGMWGTYYY RTRKQLSESS KKPSEESSSN
VSSNGPDSSG AGVSSGPQPW FVVLEEHQQP KNGRLPAAGT NGAVVEAGLS SSL
