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   27-MAR-2024, entry version 176.
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.ENSRNOP00000075379; -.
DR   BindingDB; P07522; -.
DR   GlyCosmos; P07522; 6 sites, No reported glycans.
DR   GlyGen; P07522; 6 sites.
DR   iPTMnet; P07522; -.
DR   PhosphoSitePlus; P07522; -.
DR   PaxDb; 10116-ENSRNOP00000066558; -.
DR   GeneID; 25313; -.
DR   KEGG; rno:25313; -.
DR   UCSC; RGD:2542; rat.
DR   AGR; RGD:2542; -.
DR   CTD; 1950; -.
DR   RGD; 2542; Egf.
DR   eggNOG; KOG1215; Eukaryota.
DR   InParanoid; P07522; -.
DR   OrthoDB; 5351433at2759; -.
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: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:0008283; P:cell population proliferation; ISO:RGD.
DR   GO; GO:0021930; P:cerebellar granule cell precursor proliferation; ISO:RGD.
DR   GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IDA:RGD.
DR   GO; GO:0050673; P:epithelial cell proliferation; ISO:RGD.
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: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; ISS:UniProtKB.
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:0045893; P:positive regulation of DNA-templated transcription; ISO:RGD.
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:0050679; P:positive regulation of epithelial cell proliferation; 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:0043410; P:positive regulation of MAPK cascade; ISS:UniProtKB.
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:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISO:RGD.
DR   GO; GO:0042327; P:positive regulation of phosphorylation; ISO:RGD.
DR   GO; GO:1902966; P:positive regulation of protein localization to early endosome; ISO:RGD.
DR   GO; GO:0002092; P:positive regulation of receptor internalization; 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:0051223; P:regulation of protein transport; IDA:MGI.
DR   GO; GO:0046425; P:regulation of receptor signaling pathway via JAK-STAT; ISS:UniProtKB.
DR   CDD; cd00054; EGF_CA; 3.
DR   Gene3D; 2.10.25.10; Laminin; 7.
DR   Gene3D; 2.120.10.30; TolB, C-terminal domain; 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   PANTHER; PTHR46513:SF5; PRO-EPIDERMAL GROWTH FACTOR; 1.
DR   PANTHER; PTHR46513; VITELLOGENIN RECEPTOR-LIKE PROTEIN-RELATED-RELATED; 1.
DR   Pfam; PF00008; EGF; 1.
DR   Pfam; PF07645; EGF_CA; 2.
DR   Pfam; PF14670; FXa_inhibition; 2.
DR   Pfam; PF00058; Ldl_recept_b; 3.
DR   PIRSF; PIRSF001778; Pro-epidermal_growth_factor; 1.
DR   PRINTS; PR00009; EGFTGF.
DR   SMART; SM00181; EGF; 8.
DR   SMART; SM00179; EGF_CA; 5.
DR   SMART; SM00135; LY; 8.
DR   SUPFAM; SSF57196; EGF/Laminin; 2.
DR   SUPFAM; SSF57184; Growth factor receptor domain; 2.
DR   SUPFAM; SSF63825; YWTD domain; 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
//