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Protein

ERBB receptor feedback inhibitor 1

Gene

Errfi1

Organism
Rattus norvegicus (Rat)
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 (By similarity).By similarity2 Publications

GO - Molecular functioni

  • kinase binding Source: UniProtKB
  • SH3 domain binding Source: RGD
  • small GTPase binding Source: RGD

GO - Biological processi

  • cellular hyperosmotic response Source: RGD
  • cellular response to dexamethasone stimulus Source: RGD
  • cellular response to epidermal growth factor stimulus Source: RGD
  • cellular response to insulin stimulus Source: RGD
  • cellular response to platelet-derived growth factor stimulus Source: RGD
  • lung alveolus development Source: UniProtKB
  • lung epithelium development Source: UniProtKB
  • lung vasculature development Source: UniProtKB
  • negative regulation of cardiac muscle hypertrophy in response to stress Source: RGD
  • negative regulation of collagen biosynthetic process Source: RGD
  • negative regulation of epidermal growth factor-activated receptor activity Source: UniProtKB
  • negative regulation of epidermal growth factor receptor signaling pathway Source: RGD
  • negative regulation of ERK1 and ERK2 cascade Source: RGD
  • negative regulation of interleukin-1 beta production Source: RGD
  • negative regulation of peptidyl-tyrosine phosphorylation Source: UniProtKB
  • negative regulation of protein autophosphorylation Source: UniProtKB
  • negative regulation of tumor necrosis factor biosynthetic process Source: RGD
  • regulation of keratinocyte differentiation Source: UniProtKB
  • regulation of type B pancreatic cell proliferation Source: RGD
  • skin morphogenesis Source: UniProtKB
Complete GO annotation...

Names & Taxonomyi

Protein namesi
Recommended name:
ERBB receptor feedback inhibitor 1
Alternative name(s):
Gene 33 polypeptide
Mitogen-inducible gene 6 protein homolog
Short name:
MIG-6
Receptor-associated late transducer
Short name:
RALT
Gene namesi
Name:Errfi1
Synonyms:33, Mig6
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 5

Organism-specific databases

RGDi1307599. Errfi1.

Subcellular locationi

GO - Cellular componenti

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

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Keywords - Diseasei

Tumor suppressor

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 459458ERBB receptor feedback inhibitor 1PRO_0000096489Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserineBy similarity
Modified residuei126 – 1261PhosphothreonineBy similarity
Modified residuei130 – 1301PhosphothreonineBy similarity
Modified residuei250 – 2501PhosphoserineCombined sources
Modified residuei271 – 2711PhosphoserineBy similarity
Modified residuei300 – 3001PhosphoserineBy similarity
Modified residuei458 – 4581PhosphoserineBy similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiP05432.
PRIDEiP05432.

PTM databases

PhosphoSiteiP05432.

Expressioni

Inductioni

By cAMP, glucocorticoids, phorbol esters and insulin.

Gene expression databases

GenevisibleiP05432. RN.

Interactioni

Subunit structurei

Interacts with EGFR and ERBB2.2 Publications

GO - Molecular functioni

  • kinase binding Source: UniProtKB
  • SH3 domain binding Source: RGD
  • small GTPase binding Source: RGD

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000065431.

Structurei

3D structure databases

ProteinModelPortaliP05432.
SMRiP05432. Positions 334-360.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni332 – 36130Interaction 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

GeneTreeiENSGT00440000033870.
HOGENOMiHOG000234207.
HOVERGENiHBG031710.
InParanoidiP05432.
OMAiNYAYFDA.
OrthoDBiEOG7HB59W.
PhylomeDBiP05432.
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]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P05432-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSTAGVAAQD IRVPLKTGFL HNGQALGNMK TCWGSRNEFE KNFLNIDPIT
60 70 80 90 100
MAYNLNSPAP EHLTTLGCAS PSAPGSGHFF AERGPSPKSS LPPLVIPPSE
110 120 130 140 150
SSGQREEDQV LCGFKKLSVN GVCASTPPLT PIQSCSSPFP CAAPCDRSSR
160 170 180 190 200
PLPPLPISED PSLDEADCEV EFLTSADTDF LLEDCVPSDF KYDVPGRRSF
210 220 230 240 250
RGCGQINYAY FDSPTVSVAD LSCASDQNRV VPDPNPPPPQ SHRRLRRSHS
260 270 280 290 300
GPAGSFNKPA IRISSCTHRA SPSSDEDKPE IPPRVPIPPR PAKPDYRRWS
310 320 330 340 350
AEVTSNTYSD EDRPPKVPPR EPLSRSNSRT PSPKSLPSYL NGVMPPTQSF
360 370 380 390 400
APDPKYVSSK ALQRQSSEGS AKAPCILPII ENGKKVSSTH YYLLPERPPY
410 420 430 440 450
LDKYEKYFRE AEEANPSTQI QPLPAACGMV SATDKLASRM KMDVGGHGKR

KHLSYVVSP
Length:459
Mass (Da):49,941
Last modified:November 1, 1988 - v1
Checksum:iEBD90F11757AC549
GO
Isoform 2 (identifier: P05432-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     67-142: Missing.

Show »
Length:383
Mass (Da):42,246
Checksum:i8C3EBCDBFC6277AD
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti18 – 181G → K no nucleotide entry (PubMed:2916834).Curated
Sequence conflicti192 – 1921Y → T no nucleotide entry (PubMed:2916834).Curated
Sequence conflicti302 – 3021E → L no nucleotide entry (PubMed:2916834).Curated
Sequence conflicti311 – 3111E → L no nucleotide entry (PubMed:2916834).Curated
Sequence conflicti396 – 3961E → L no nucleotide entry (PubMed:2916834).Curated
Sequence conflicti410 – 4101E → L no nucleotide entry (PubMed:2916834).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei67 – 14276Missing in isoform 2. 1 PublicationVSP_011893Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M23572, M23570, M23571 Genomic DNA. Translation: AAB08828.1.
X07266 mRNA. Translation: CAA30252.1.
BC083845 mRNA. Translation: AAH83845.1.
PIRiS03116.
RefSeqiNP_001014093.1. NM_001014071.1. [P05432-1]
XP_008762482.1. XM_008764260.1. [P05432-1]
XP_008762483.1. XM_008764261.1. [P05432-1]
XP_008762484.1. XM_008764262.1. [P05432-2]
UniGeneiRn.100336.

Genome annotation databases

EnsembliENSRNOT00000085315; ENSRNOP00000072811; ENSRNOG00000058186. [P05432-1]
GeneIDi313729.
KEGGirno:313729.
UCSCiRGD:1307599. rat. [P05432-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M23572, M23570, M23571 Genomic DNA. Translation: AAB08828.1.
X07266 mRNA. Translation: CAA30252.1.
BC083845 mRNA. Translation: AAH83845.1.
PIRiS03116.
RefSeqiNP_001014093.1. NM_001014071.1. [P05432-1]
XP_008762482.1. XM_008764260.1. [P05432-1]
XP_008762483.1. XM_008764261.1. [P05432-1]
XP_008762484.1. XM_008764262.1. [P05432-2]
UniGeneiRn.100336.

3D structure databases

ProteinModelPortaliP05432.
SMRiP05432. Positions 334-360.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000065431.

PTM databases

PhosphoSiteiP05432.

Proteomic databases

PaxDbiP05432.
PRIDEiP05432.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000085315; ENSRNOP00000072811; ENSRNOG00000058186. [P05432-1]
GeneIDi313729.
KEGGirno:313729.
UCSCiRGD:1307599. rat. [P05432-1]

Organism-specific databases

CTDi54206.
RGDi1307599. Errfi1.

Phylogenomic databases

GeneTreeiENSGT00440000033870.
HOGENOMiHOG000234207.
HOVERGENiHBG031710.
InParanoidiP05432.
OMAiNYAYFDA.
OrthoDBiEOG7HB59W.
PhylomeDBiP05432.
TreeFamiTF335720.

Miscellaneous databases

NextBioi666720.
PROiP05432.

Gene expression databases

GenevisibleiP05432. RN.

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...

Publicationsi

« Hide 'large scale' publications
  1. "Structure of a multihormonally regulated rat gene."
    Tindal M.H., Lee K.-L., Isham K.R., Cadilla C., Kenney F.T.
    Gene 71:413-420(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: Sprague-Dawley.
    Tissue: Liver.
  2. "Rat gene 33: analysis of its structure, messenger RNA and basal promoter activity."
    Chrapkiewicz N.B., Davis C.M., Chu D.T.W., Granner D.K.
    Nucleic Acids Res. 17:6651-6667(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Strain: Sprague-Dawley.
  3. "Molecular cloning and analysis of full-length cDNAs cognate to a rat gene under multihormonal control."
    Lee K.-L., Makkinje A., Ch'Ang L.-Y., Kenney F.T.
    Arch. Biochem. Biophys. 269:106-113(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
    Tissue: Liver.
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Lung.
  5. "Inhibition of ErbB-2 mitogenic and transforming activity by RALT, a mitogen-induced signal transducer which binds to the ErbB-2 kinase domain."
    Fiorentino L., Pertica C., Fiorini M., Talora C., Crescenzi M., Castellani L., Alema S., Benedetti P., Segatto O.
    Mol. Cell. Biol. 20:7735-7750(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, PHOSPHORYLATION, SUBCELLULAR LOCATION, INTERACTION WITH ERBB2.
  6. "The evolutionarily conserved EBR module of RALT/MIG6 mediates suppression of the EGFR catalytic activity."
    Anastasi S., Baietti M.F., Frosi Y., Alema S., Segatto O.
    Oncogene 26:7833-7846(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH EGFR.
  7. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
    Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
    Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-250, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiERRFI_RAT
AccessioniPrimary (citable) accession number: P05432
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: November 1, 1988
Last modified: December 9, 2015
This is version 115 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. 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.