ERRFI_MOUSE
ID ERRFI_MOUSE Reviewed; 461 AA.
AC Q99JZ7;
DT 27-JAN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=ERBB receptor feedback inhibitor 1;
DE AltName: Full=Mitogen-inducible gene 6 protein homolog;
DE Short=MIG-6;
GN Name=Errfi1; Synonyms=Mig6;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary gland;
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 [2]
RP DISRUPTION PHENOTYPE, FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=16648858; DOI=10.1038/nm1401;
RA Ferby I., Reschke M., Kudlacek O., Knyazev P., Pante G., Amann K.,
RA Sommergruber W., Kraut N., Ullrich A., Fassler R., Klein R.;
RT "Mig6 is a negative regulator of EGF receptor-mediated skin morphogenesis
RT and tumor formation.";
RL Nat. Med. 12:568-573(2006).
RN [3]
RP ERRATUM OF PUBMED:16648858.
RX DOI=10.1038/nm0706-862b;
RA Ferby I., Reschke M., Kudlacek O., Knyazev P., Pante G., Amann K.,
RA Sommergruber W., Kraut N., Ullrich A., Fassler R., Klein R.;
RL Nat. Med. 12:862-862(2006).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-130; SER-251; SER-272 AND
RP SER-301, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [5]
RP DISRUPTION PHENOTYPE, FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=19710174; DOI=10.1242/dev.032979;
RA Jin N., Cho S.N., Raso M.G., Wistuba I., Smith Y., Yang Y., Kurie J.M.,
RA Yen R., Evans C.M., Ludwig T., Jeong J.W., DeMayo F.J.;
RT "Mig-6 is required for appropriate lung development and to ensure normal
RT adult lung homeostasis.";
RL Development 136:3347-3356(2009).
RN [6]
RP INDUCTION, AND FUNCTION.
RX PubMed=19683494; DOI=10.1016/j.molcel.2009.07.015;
RA Descot A., Hoffmann R., Shaposhnikov D., Reschke M., Ullrich A., Posern G.;
RT "Negative regulation of the EGFR-MAPK cascade by actin-MAL-mediated
RT Mig6/Errfi-1 induction.";
RL Mol. Cell 35:291-304(2009).
RN [7]
RP DISRUPTION PHENOTYPE, FUNCTION, AND INDUCTION.
RX PubMed=19439667; DOI=10.1073/pnas.0903632106;
RA Jeong J.W., Lee H.S., Lee K.Y., White L.D., Broaddus R.R., Zhang Y.W.,
RA Vande Woude G.F., Giudice L.C., Young S.L., Lessey B.A., Tsai S.Y.,
RA Lydon J.P., DeMayo F.J.;
RT "Mig-6 modulates uterine steroid hormone responsiveness and exhibits
RT altered expression in endometrial disease.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:8677-8682(2009).
RN [8]
RP DISRUPTION PHENOTYPE, FUNCTION, AND INDUCTION.
RX PubMed=20018910; DOI=10.1095/biolreprod.109.081307;
RA Kim T.H., Lee D.K., Franco H.L., Lydon J.P., Jeong J.W.;
RT "ERBB receptor feedback inhibitor 1 regulation of estrogen receptor
RT activity is critical for uterine implantation in mice.";
RL Biol. Reprod. 82:706-713(2010).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-126 AND THR-130, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, and Kidney;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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. {ECO:0000269|PubMed:16648858,
CC ECO:0000269|PubMed:19439667, ECO:0000269|PubMed:19683494,
CC ECO:0000269|PubMed:19710174, ECO:0000269|PubMed:20018910}.
CC -!- SUBUNIT: Interacts with EGFR (By similarity). Interacts with ERBB2.
CC {ECO:0000250}.
CC -!- INTERACTION:
CC Q99JZ7; Q60631: Grb2; NbExp=3; IntAct=EBI-643375, EBI-1688;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16648858}. Cell
CC membrane {ECO:0000269|PubMed:16648858}; Peripheral membrane protein
CC {ECO:0000269|PubMed:16648858}; Cytoplasmic side
CC {ECO:0000269|PubMed:16648858}. Nucleus {ECO:0000305|PubMed:16648858}.
CC Note=Associated with the plasma membrane of basal skin keratinocytes.
CC Translocates into the nucleus of differentiating suprabasal
CC keratinocytes.
CC -!- TISSUE SPECIFICITY: Detected in lung, in airway epithelial cells and
CC alveolar type 2 cells (at protein level). Detected in uterus stroma,
CC luminal epithelium and glandular epithelium.
CC {ECO:0000269|PubMed:16648858, ECO:0000269|PubMed:19710174}.
CC -!- DEVELOPMENTAL STAGE: Detected at low levels during embryogenesis.
CC Strongly up-regulated during the first days after birth. Levels are
CC increased on the first day after birth, and culminate three days after
CC birth. Detected at low levels four days after birth, and throughout the
CC remaining life span. {ECO:0000269|PubMed:19710174}.
CC -!- INDUCTION: Up-regulated by lysophosphatidic acid (LPA) and sphingosine
CC 1-phosphate. Up-regulated by globular actin monomers, via MKL1
CC signaling. Up-regulated in uterus in response to progesterone. Up-
CC regulated in uterus in response to estrogen. Up-regulated in pregnant
CC uterus. {ECO:0000269|PubMed:19439667, ECO:0000269|PubMed:19683494,
CC ECO:0000269|PubMed:20018910}.
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 -!- DISRUPTION PHENOTYPE: Embryos are present at the expected Mendelian
CC ratio, but half of the mice die before adolescence, due to defects in
CC prenatal and perinatal lung development. In the 15.5 dpc embryo, lungs
CC are smaller, have a less complex structure than normal, and present
CC fewer blood vessels. Lungs in newborns present abnormal patterns of
CC cell proliferation and apoptosis. Adults develop chronic obstructive
CC pulmonary disease (COPD). Mice present epidermal hyperplasia with
CC thickening and flaking skin and ulcerations on tail and footpads.
CC Papillomas develop at sites of wounding. Mice are highly susceptible to
CC chemical carcinogens and develop melanomas and/or papillomas after
CC application of a carcinogen. They have a high incidence of spontaneous
CC hyperplastic and neoplastic lesions, such as adenocarcinomas or
CC squamous cell carcinomas. They present bone and cartilage hyperplasia,
CC leading to fixed joints. Mice have altered response to progesterone in
CC the uterus, resulting in endometrial epithelial hyperplasia and
CC complete loss of fertility. Mice have a shortened life span and die
CC prematurely at an age of five to seven months.
CC {ECO:0000269|PubMed:16648858, ECO:0000269|PubMed:19439667,
CC ECO:0000269|PubMed:19710174, ECO:0000269|PubMed:20018910}.
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; BC005546; AAH05546.1; -; mRNA.
DR EMBL; BC057646; AAH57646.1; -; mRNA.
DR CCDS; CCDS18974.1; -.
DR RefSeq; NP_598514.1; NM_133753.1.
DR RefSeq; XP_006539273.1; XM_006539210.1.
DR AlphaFoldDB; Q99JZ7; -.
DR BioGRID; 216532; 1.
DR IntAct; Q99JZ7; 2.
DR STRING; 10090.ENSMUSP00000030811; -.
DR iPTMnet; Q99JZ7; -.
DR PhosphoSitePlus; Q99JZ7; -.
DR jPOST; Q99JZ7; -.
DR MaxQB; Q99JZ7; -.
DR PaxDb; Q99JZ7; -.
DR PRIDE; Q99JZ7; -.
DR ProteomicsDB; 275889; -.
DR Antibodypedia; 27548; 214 antibodies from 29 providers.
DR DNASU; 74155; -.
DR Ensembl; ENSMUST00000030811; ENSMUSP00000030811; ENSMUSG00000028967.
DR Ensembl; ENSMUST00000073600; ENSMUSP00000073285; ENSMUSG00000028967.
DR GeneID; 74155; -.
DR KEGG; mmu:74155; -.
DR UCSC; uc008vxw.1; mouse.
DR CTD; 54206; -.
DR MGI; MGI:1921405; Errfi1.
DR VEuPathDB; HostDB:ENSMUSG00000028967; -.
DR eggNOG; ENOG502QPQW; Eukaryota.
DR GeneTree; ENSGT00440000033870; -.
DR HOGENOM; CLU_604032_0_0_1; -.
DR InParanoid; Q99JZ7; -.
DR OMA; MKTCWGS; -.
DR OrthoDB; 644164at2759; -.
DR PhylomeDB; Q99JZ7; -.
DR TreeFam; TF335720; -.
DR BioGRID-ORCS; 74155; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Errfi1; mouse.
DR PRO; PR:Q99JZ7; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q99JZ7; protein.
DR Bgee; ENSMUSG00000028967; Expressed in left lobe of liver and 259 other tissues.
DR ExpressionAtlas; Q99JZ7; baseline and differential.
DR Genevisible; Q99JZ7; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0019900; F:kinase binding; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0017124; F:SH3 domain binding; ISO:MGI.
DR GO; GO:0031267; F:small GTPase binding; ISO:MGI.
DR GO; GO:0071474; P:cellular hyperosmotic response; IEA:Ensembl.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEA:Ensembl.
DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; IEA:Ensembl.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEA:Ensembl.
DR GO; GO:0036120; P:cellular response to platelet-derived growth factor stimulus; IEA:Ensembl.
DR GO; GO:0048286; P:lung alveolus development; IMP:UniProtKB.
DR GO; GO:0060428; P:lung epithelium development; IMP:UniProtKB.
DR GO; GO:0060426; P:lung vasculature development; IMP:UniProtKB.
DR GO; GO:1903243; P:negative regulation of cardiac muscle hypertrophy in response to stress; ISO:MGI.
DR GO; GO:0032966; P:negative regulation of collagen biosynthetic process; ISO:MGI.
DR GO; GO:0042059; P:negative regulation of epidermal growth factor receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0007175; P:negative regulation of epidermal growth factor-activated receptor activity; IMP:UniProtKB.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; ISO:MGI.
DR GO; GO:0032691; P:negative regulation of interleukin-1 beta production; ISO:MGI.
DR GO; GO:0050732; P:negative regulation of peptidyl-tyrosine phosphorylation; ISS: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; ISO:MGI.
DR GO; GO:0045616; P:regulation of keratinocyte differentiation; IMP:UniProtKB.
DR GO; GO:0061469; P:regulation of type B pancreatic cell proliferation; ISO:MGI.
DR GO; GO:0043589; P:skin morphogenesis; IMP:UniProtKB.
DR GO; GO:0031098; P:stress-activated protein kinase signaling cascade; ISO:MGI.
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; Cell membrane; Cytoplasm; Membrane; Nucleus; Phosphoprotein;
KW Reference proteome; Tumor suppressor.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q9UJM3"
FT CHAIN 2..461
FT /note="ERBB receptor feedback inhibitor 1"
FT /id="PRO_0000096488"
FT REGION 228..353
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 333..362
FT /note="Interaction with EGFR and ERBB2 and regulation of
FT EGFR activation"
FT /evidence="ECO:0000250"
FT COMPBIAS 324..346
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:0007744|PubMed:21183079"
FT MOD_RES 130
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 251
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355"
FT MOD_RES 272
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355"
FT MOD_RES 301
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355"
FT MOD_RES 460
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UJM3"
SQ SEQUENCE 461 AA; 50075 MW; 0CA414516FAE27A6 CRC64;
MSTAGVAAQD IRVPLKTGFL HNGQALGNMK SCWGSHSEFE NNFLNIDPIT MAYNLNSPAQ
EHLTTVGCAA RSAPGSGHFF AECGPSPRSS LPPLVISPSE SSGQREEDQV MCGFKKLSVN
GVCTSTPPLT PIKSCPSPFP CAALCDRGSR PLPPLPISED LCVDEADSEV ELLTTSSDTD
LLLEDSAPSD FKYDAPGRRS FRGCGQINYA YFDSPTVSVA DLSCASDQNR VVPDPNPPPP
QSHRRLRRSH SGPAGSFNKP AIRISSCTHR ASPSSDEDKP EVPPRVPIPP RPAKPDYRRW
SAEVTSNTYS DEDRPPKVPP REPLSRSNSR TPSPKSLPSY LNGVMPPTQS FAPDPKYVSS
KALQRQSSEG SANKVPCILP IIENGKKVSS THYYLLPERP PYLDKYEKYF KEAEETNPST
QIQPLPAACG MASATEKLAS RMKIDMGSHG KRKHLSYVVS P
