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Protein

ERBB receptor feedback inhibitor 1

Gene

Errfi1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Negative regulator of EGFR signaling in skin morphogenesis. Acts as a negative regulator for several EGFR family members, including ERBB2, ERBB3 and ERBB4. Inhibits EGFR catalytic activity by interfering with its dimerization. Inhibits autophosphorylation of EGFR, ERBB2 and ERBB4. Important for normal keratinocyte proliferation and differentiation. Plays a role in modulating the response to steroid hormones in the uterus. Required for normal response to progesterone in the uterus and for fertility. Mediates epithelial estrogen responses in the uterus by regulating ESR1 levels and activation. Important for regulation of endometrium cell proliferation. Important for normal prenatal and perinatal lung development.5 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Names & Taxonomyi

Protein namesi
Recommended name:
ERBB receptor feedback inhibitor 1
Alternative name(s):
Mitogen-inducible gene 6 protein homolog
Short name:
MIG-6
Gene namesi
Name:Errfi1
Synonyms:Mig6
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:1921405. Errfi1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: MGI
  • extrinsic component of cytoplasmic side of plasma membrane Source: UniProtKB
  • nucleus Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Disruption phenotypei

Embryos are present at the expected Mendelian ratio, but half of the mice die before adolescence, due to defects in prenatal and perinatal lung development. In the E15.5 embryo, lungs are smaller, have a less complex structure than normal, and present fewer blood vessels. Lungs in newborns present abnormal patterns of cell proliferation and apoptosis. Adults develop chronic obstructive pulmonary disease (COPD). Mice present epidermal hyperplasia with thickening and flaking skin and ulcerations on tail and footpads. Papillomas develop at sites of wounding. Mice are highly susceptible to chemical carcinogens and develop melanomas and/or papillomas after application of a carcinogen. They have a high incidence of spontaneous hyperplastic and neoplastic lesions, such as adenocarcinomas or squamous cell carcinomas. They present bone and cartilage hyperplasia, leading to fixed joints. Mice have altered response to progesterone in the uterus, resulting in endometrial epithelial hyperplasia and complete loss of fertility. Mice have a shortened life span and die prematurely at an age of five to seven months.4 Publications

Keywords - Diseasei

Tumor suppressor

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 461460ERBB receptor feedback inhibitor 1PRO_0000096488Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserineBy similarity
Modified residuei126 – 1261PhosphothreonineCombined sources
Modified residuei130 – 1301PhosphothreonineCombined sources
Modified residuei251 – 2511PhosphoserineCombined sources
Modified residuei272 – 2721PhosphoserineCombined sources
Modified residuei301 – 3011PhosphoserineCombined sources
Modified residuei460 – 4601PhosphoserineBy similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiQ99JZ7.
PaxDbiQ99JZ7.
PRIDEiQ99JZ7.

PTM databases

iPTMnetiQ99JZ7.
PhosphoSiteiQ99JZ7.

Expressioni

Tissue specificityi

Detected in lung, in airway epithelial cells and alveolar type 2 cells (at protein level). Detected in uterus stroma, luminal epithelium and glandular epithelium.2 Publications

Developmental stagei

Detected at low levels during embryogenesis. Strongly up-regulated during the first days after birth. Levels are increased on the first day after birth, and culminate three days after birth. Detected at low levels four days after birth, and throughout the remaining life span.1 Publication

Inductioni

Up-regulated by lysophosphatidic acid (LPA) and sphingosine 1-phosphate. Up-regulated by globular actin monomers, via MKL1 signaling. Up-regulated in uterus in response to progesterone. Up-regulated in uterus in response to estrogen. Up-regulated in pregnant uterus.3 Publications

Gene expression databases

BgeeiENSMUSG00000028967.
CleanExiMM_ERRFI1.
ExpressionAtlasiQ99JZ7. baseline and differential.
GenevisibleiQ99JZ7. MM.

Interactioni

Subunit structurei

Interacts with EGFR (By similarity). Interacts with ERBB2.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Grb2Q606313EBI-643375,EBI-1688

GO - Molecular functioni

Protein-protein interaction databases

BioGridi216532. 1 interaction.
IntActiQ99JZ7. 2 interactions.
MINTiMINT-1758229.
STRINGi10090.ENSMUSP00000030811.

Structurei

3D structure databases

ProteinModelPortaliQ99JZ7.
SMRiQ99JZ7. Positions 334-397.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni333 – 36230Interaction with EGFR and ERBB2 and regulation of EGFR activationBy similarityAdd
BLAST

Domaini

The EGFR-binding region prevents binding of a cyclin-like activator to the EGFR kinase domain, and thereby keeps EGFR in an inactive conformation. Also maintains EGFR in an inactive conformation by preventing formation of an asymmetric homodimer (By similarity).By similarity

Sequence similaritiesi

Belongs to the MIG6 family.Curated

Phylogenomic databases

eggNOGiENOG410IEVS. Eukaryota.
ENOG4111HB5. LUCA.
GeneTreeiENSGT00440000033870.
HOGENOMiHOG000234207.
HOVERGENiHBG031710.
InParanoidiQ99JZ7.
OMAiNYAYFDA.
OrthoDBiEOG091G0BER.
PhylomeDBiQ99JZ7.
TreeFamiTF335720.

Family and domain databases

InterProiIPR015116. Cdc42_binding_dom-like.
IPR021619. Mig-6.
[Graphical view]
PfamiPF09027. GTPase_binding. 1 hit.
PF11555. Inhibitor_Mig-6. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q99JZ7-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSTAGVAAQD IRVPLKTGFL HNGQALGNMK SCWGSHSEFE NNFLNIDPIT
60 70 80 90 100
MAYNLNSPAQ EHLTTVGCAA RSAPGSGHFF AECGPSPRSS LPPLVISPSE
110 120 130 140 150
SSGQREEDQV MCGFKKLSVN GVCTSTPPLT PIKSCPSPFP CAALCDRGSR
160 170 180 190 200
PLPPLPISED LCVDEADSEV ELLTTSSDTD LLLEDSAPSD FKYDAPGRRS
210 220 230 240 250
FRGCGQINYA YFDSPTVSVA DLSCASDQNR VVPDPNPPPP QSHRRLRRSH
260 270 280 290 300
SGPAGSFNKP AIRISSCTHR ASPSSDEDKP EVPPRVPIPP RPAKPDYRRW
310 320 330 340 350
SAEVTSNTYS DEDRPPKVPP REPLSRSNSR TPSPKSLPSY LNGVMPPTQS
360 370 380 390 400
FAPDPKYVSS KALQRQSSEG SANKVPCILP IIENGKKVSS THYYLLPERP
410 420 430 440 450
PYLDKYEKYF KEAEETNPST QIQPLPAACG MASATEKLAS RMKIDMGSHG
460
KRKHLSYVVS P
Length:461
Mass (Da):50,075
Last modified:June 1, 2001 - v1
Checksum:i0CA414516FAE27A6
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC005546 mRNA. Translation: AAH05546.1.
BC057646 mRNA. Translation: AAH57646.1.
CCDSiCCDS18974.1.
RefSeqiNP_598514.1. NM_133753.1.
XP_006537151.1. XM_006537088.1.
XP_006539273.1. XM_006539210.1.
UniGeneiMm.318841.

Genome annotation databases

EnsembliENSMUST00000030811; ENSMUSP00000030811; ENSMUSG00000028967.
ENSMUST00000073600; ENSMUSP00000073285; ENSMUSG00000028967.
GeneIDi74155.
KEGGimmu:74155.
UCSCiuc008vxw.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC005546 mRNA. Translation: AAH05546.1.
BC057646 mRNA. Translation: AAH57646.1.
CCDSiCCDS18974.1.
RefSeqiNP_598514.1. NM_133753.1.
XP_006537151.1. XM_006537088.1.
XP_006539273.1. XM_006539210.1.
UniGeneiMm.318841.

3D structure databases

ProteinModelPortaliQ99JZ7.
SMRiQ99JZ7. Positions 334-397.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi216532. 1 interaction.
IntActiQ99JZ7. 2 interactions.
MINTiMINT-1758229.
STRINGi10090.ENSMUSP00000030811.

PTM databases

iPTMnetiQ99JZ7.
PhosphoSiteiQ99JZ7.

Proteomic databases

MaxQBiQ99JZ7.
PaxDbiQ99JZ7.
PRIDEiQ99JZ7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000030811; ENSMUSP00000030811; ENSMUSG00000028967.
ENSMUST00000073600; ENSMUSP00000073285; ENSMUSG00000028967.
GeneIDi74155.
KEGGimmu:74155.
UCSCiuc008vxw.1. mouse.

Organism-specific databases

CTDi54206.
MGIiMGI:1921405. Errfi1.

Phylogenomic databases

eggNOGiENOG410IEVS. Eukaryota.
ENOG4111HB5. LUCA.
GeneTreeiENSGT00440000033870.
HOGENOMiHOG000234207.
HOVERGENiHBG031710.
InParanoidiQ99JZ7.
OMAiNYAYFDA.
OrthoDBiEOG091G0BER.
PhylomeDBiQ99JZ7.
TreeFamiTF335720.

Miscellaneous databases

PROiQ99JZ7.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000028967.
CleanExiMM_ERRFI1.
ExpressionAtlasiQ99JZ7. baseline and differential.
GenevisibleiQ99JZ7. MM.

Family and domain databases

InterProiIPR015116. Cdc42_binding_dom-like.
IPR021619. Mig-6.
[Graphical view]
PfamiPF09027. GTPase_binding. 1 hit.
PF11555. Inhibitor_Mig-6. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiERRFI_MOUSE
AccessioniPrimary (citable) accession number: Q99JZ7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 27, 2003
Last sequence update: June 1, 2001
Last modified: September 7, 2016
This is version 107 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.