ERRFI_RAT
ID ERRFI_RAT Reviewed; 459 AA.
AC P05432;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1988, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=ERBB receptor feedback inhibitor 1;
DE AltName: Full=Gene 33 polypeptide;
DE AltName: Full=Mitogen-inducible gene 6 protein homolog;
DE Short=MIG-6;
DE AltName: Full=Receptor-associated late transducer;
DE Short=RALT;
GN Name=Errfi1; Synonyms=33, Mig6;
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 [GENOMIC DNA].
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=3224831; DOI=10.1016/0378-1119(88)90058-3;
RA Tindal M.H., Lee K.-L., Isham K.R., Cadilla C., Kenney F.T.;
RT "Structure of a multihormonally regulated rat gene.";
RL Gene 71:413-420(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=Sprague-Dawley;
RX PubMed=2780291; DOI=10.1093/nar/17.16.6651;
RA Chrapkiewicz N.B., Davis C.M., Chu D.T.W., Granner D.K.;
RT "Rat gene 33: analysis of its structure, messenger RNA and basal promoter
RT activity.";
RL Nucleic Acids Res. 17:6651-6667(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Liver;
RX PubMed=2916834; DOI=10.1016/0003-9861(89)90091-x;
RA Lee K.-L., Makkinje A., Ch'Ang L.-Y., Kenney F.T.;
RT "Molecular cloning and analysis of full-length cDNAs cognate to a rat gene
RT under multihormonal control.";
RL Arch. Biochem. Biophys. 269:106-113(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, PHOSPHORYLATION, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP ERBB2.
RX PubMed=11003669; DOI=10.1128/mcb.20.20.7735-7750.2000;
RA Fiorentino L., Pertica C., Fiorini M., Talora C., Crescenzi M.,
RA Castellani L., Alema S., Benedetti P., Segatto O.;
RT "Inhibition of ErbB-2 mitogenic and transforming activity by RALT, a
RT mitogen-induced signal transducer which binds to the ErbB-2 kinase
RT domain.";
RL Mol. Cell. Biol. 20:7735-7750(2000).
RN [6]
RP FUNCTION, AND INTERACTION WITH EGFR.
RX PubMed=17599051; DOI=10.1038/sj.onc.1210590;
RA Anastasi S., Baietti M.F., Frosi Y., Alema S., Segatto O.;
RT "The evolutionarily conserved EBR module of RALT/MIG6 mediates suppression
RT of the EGFR catalytic activity.";
RL Oncogene 26:7833-7846(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-250, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Negative regulator of EGFR signaling in skin morphogenesis.
CC Acts as a negative regulator for several EGFR family members, including
CC ERBB2, ERBB3 and ERBB4. Inhibits EGFR catalytic activity by interfering
CC with its dimerization. Inhibits autophosphorylation of EGFR, ERBB2 and
CC ERBB4. Important for normal keratinocyte proliferation and
CC differentiation. Plays a role in modulating the response to steroid
CC hormones in the uterus. Required for normal response to progesterone in
CC the uterus and for fertility. Mediates epithelial estrogen responses in
CC the uterus by regulating ESR1 levels and activation. Important for
CC regulation of endometrium cell proliferation. Important for normal
CC prenatal and perinatal lung development (By similarity). {ECO:0000250,
CC ECO:0000269|PubMed:11003669, ECO:0000269|PubMed:17599051}.
CC -!- SUBUNIT: Interacts with EGFR and ERBB2. {ECO:0000269|PubMed:11003669,
CC ECO:0000269|PubMed:17599051}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane
CC {ECO:0000250}; Peripheral membrane protein {ECO:0000250}; Cytoplasmic
CC side {ECO:0000250}. Nucleus {ECO:0000250}. Note=Associated with the
CC plasma membrane of basal skin keratinocytes. Translocates into the
CC nucleus of differentiating suprabasal keratinocytes (By similarity).
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P05432-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P05432-2; Sequence=VSP_011893;
CC -!- INDUCTION: By cAMP, glucocorticoids, phorbol esters and insulin.
CC -!- DOMAIN: The EGFR-binding region prevents binding of a cyclin-like
CC activator to the EGFR kinase domain, and thereby keeps EGFR in an
CC inactive conformation. Also maintains EGFR in an inactive conformation
CC by preventing formation of an asymmetric homodimer (By similarity).
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the MIG6 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M23572; AAB08828.1; -; Genomic_DNA.
DR EMBL; M23570; AAB08828.1; JOINED; Genomic_DNA.
DR EMBL; M23571; AAB08828.1; JOINED; Genomic_DNA.
DR EMBL; X07266; CAA30252.1; -; mRNA.
DR EMBL; BC083845; AAH83845.1; -; mRNA.
DR PIR; S03116; S03116.
DR RefSeq; NP_001014093.1; NM_001014071.1. [P05432-1]
DR RefSeq; XP_008762482.1; XM_008764260.2. [P05432-1]
DR RefSeq; XP_008762483.1; XM_008764261.2. [P05432-1]
DR RefSeq; XP_008762484.1; XM_008764262.2. [P05432-2]
DR AlphaFoldDB; P05432; -.
DR SMR; P05432; -.
DR BioGRID; 260526; 5.
DR iPTMnet; P05432; -.
DR PhosphoSitePlus; P05432; -.
DR PaxDb; P05432; -.
DR GeneID; 313729; -.
DR KEGG; rno:313729; -.
DR UCSC; RGD:1307599; rat. [P05432-1]
DR CTD; 54206; -.
DR RGD; 1307599; Errfi1.
DR VEuPathDB; HostDB:ENSRNOG00000058186; -.
DR eggNOG; ENOG502QPQW; Eukaryota.
DR HOGENOM; CLU_604032_0_0_1; -.
DR InParanoid; P05432; -.
DR OMA; MKTCWGS; -.
DR OrthoDB; 644164at2759; -.
DR PhylomeDB; P05432; -.
DR TreeFam; TF335720; -.
DR PRO; PR:P05432; -.
DR Proteomes; UP000002494; Chromosome 5.
DR Bgee; ENSRNOG00000058186; Expressed in liver and 20 other tissues.
DR Genevisible; P05432; RN.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0019900; F:kinase binding; IPI:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:0017124; F:SH3 domain binding; IDA:RGD.
DR GO; GO:0031267; F:small GTPase binding; IPI:RGD.
DR GO; GO:0071474; P:cellular hyperosmotic response; IEP:RGD.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEP:RGD.
DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; IEP:RGD.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEP:RGD.
DR GO; GO:0036120; P:cellular response to platelet-derived growth factor stimulus; IEP:RGD.
DR GO; GO:0048286; P:lung alveolus development; ISS:UniProtKB.
DR GO; GO:0060428; P:lung epithelium development; ISS:UniProtKB.
DR GO; GO:0060426; P:lung vasculature development; ISS:UniProtKB.
DR GO; GO:1903243; P:negative regulation of cardiac muscle hypertrophy in response to stress; IDA:RGD.
DR GO; GO:0032966; P:negative regulation of collagen biosynthetic process; IMP:RGD.
DR GO; GO:0042059; P:negative regulation of epidermal growth factor receptor signaling pathway; IMP:RGD.
DR GO; GO:0007175; P:negative regulation of epidermal growth factor-activated receptor activity; IDA:UniProtKB.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IDA:RGD.
DR GO; GO:0032691; P:negative regulation of interleukin-1 beta production; IMP:RGD.
DR GO; GO:0050732; P:negative regulation of peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
DR GO; GO:0031953; P:negative regulation of protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IMP:RGD.
DR GO; GO:0045616; P:regulation of keratinocyte differentiation; ISS:UniProtKB.
DR GO; GO:0061469; P:regulation of type B pancreatic cell proliferation; IMP:RGD.
DR GO; GO:0043589; P:skin morphogenesis; ISS:UniProtKB.
DR InterPro; IPR015116; Cdc42-bd-like.
DR InterPro; IPR021619; Mig-6.
DR Pfam; PF09027; GTPase_binding; 1.
DR Pfam; PF11555; Inhibitor_Mig-6; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Cell membrane; Cytoplasm; Membrane;
KW Nucleus; Phosphoprotein; Reference proteome; Tumor suppressor.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q9UJM3"
FT CHAIN 2..459
FT /note="ERBB receptor feedback inhibitor 1"
FT /id="PRO_0000096489"
FT REGION 227..352
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 332..361
FT /note="Interaction with EGFR and ERBB2 and regulation of
FT EGFR activation"
FT /evidence="ECO:0000250"
FT COMPBIAS 323..345
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UJM3"
FT MOD_RES 126
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q99JZ7"
FT MOD_RES 130
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q99JZ7"
FT MOD_RES 250
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 271
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UJM3"
FT MOD_RES 300
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99JZ7"
FT MOD_RES 458
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UJM3"
FT VAR_SEQ 67..142
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:2916834"
FT /id="VSP_011893"
FT CONFLICT 18
FT /note="G -> K (in Ref. 3; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 192
FT /note="Y -> T (in Ref. 3; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 302
FT /note="E -> L (in Ref. 3; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 311
FT /note="E -> L (in Ref. 3; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 396
FT /note="E -> L (in Ref. 3; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 410
FT /note="E -> L (in Ref. 3; no nucleotide entry)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 459 AA; 49941 MW; EBD90F11757AC549 CRC64;
MSTAGVAAQD IRVPLKTGFL HNGQALGNMK TCWGSRNEFE KNFLNIDPIT MAYNLNSPAP
EHLTTLGCAS PSAPGSGHFF AERGPSPKSS LPPLVIPPSE SSGQREEDQV LCGFKKLSVN
GVCASTPPLT PIQSCSSPFP CAAPCDRSSR PLPPLPISED PSLDEADCEV EFLTSADTDF
LLEDCVPSDF KYDVPGRRSF RGCGQINYAY FDSPTVSVAD LSCASDQNRV VPDPNPPPPQ
SHRRLRRSHS GPAGSFNKPA IRISSCTHRA SPSSDEDKPE IPPRVPIPPR PAKPDYRRWS
AEVTSNTYSD EDRPPKVPPR EPLSRSNSRT PSPKSLPSYL NGVMPPTQSF APDPKYVSSK
ALQRQSSEGS AKAPCILPII ENGKKVSSTH YYLLPERPPY LDKYEKYFRE AEEANPSTQI
QPLPAACGMV SATDKLASRM KMDVGGHGKR KHLSYVVSP
