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Q9UJM3 (ERRFI_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 107. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
ERBB receptor feedback inhibitor 1
Alternative name(s):
Mitogen-inducible gene 6 protein
Short name=MIG-6
Gene names
Name:ERRFI1
Synonyms:MIG6
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length462 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

Interacts with ERBB2 By similarity. Interacts with EGFR. Ref.12

Subcellular location

Cytoplasm. Cell membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Nucleus By similarity. Note: Associated with the plasma membrane of basal skin keratinocytes. Translocates into the nucleus of differentiating suprabasal keratinocytes By similarity. Ref.1

Induction

Levels are very low in quiescent cells. Up-regulated by mitogens.

Domain

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. Ref.12

Sequence similarities

Belongs to the MIG6 family.

Ontologies

Keywords
   Cellular componentCell membrane
Cytoplasm
Membrane
Nucleus
   Coding sequence diversityPolymorphism
   DiseaseTumor suppressor
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processlung alveolus development

Inferred from sequence or structural similarity. Source: UniProtKB

lung epithelium development

Inferred from sequence or structural similarity. Source: UniProtKB

lung vasculature development

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of epidermal growth factor-activated receptor activity

Inferred from direct assay Ref.12. Source: UniProtKB

negative regulation of protein autophosphorylation

Inferred from direct assay Ref.12. Source: UniProtKB

positive regulation of Rho GTPase activity

Traceable author statement PubMed 10749885. Source: GOC

regulation of keratinocyte differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

response to stress

Traceable author statement PubMed 10749885. Source: ProtInc

skin morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

extrinsic component of cytoplasmic side of plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionRho GTPase activator activity

Traceable author statement PubMed 10749885. Source: ProtInc

protein binding

Inferred from physical interaction PubMed 15778465PubMed 20936779PubMed 20946980PubMed 21706016PubMed 21988832PubMed 22505024PubMed 24189400. Source: IntAct

protein kinase binding

Inferred from physical interaction Ref.12. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.11
Chain2 – 462461ERBB receptor feedback inhibitor 1
PRO_0000096487

Regions

Region334 – 36330Interaction with EGFR and ERBB2 and regulation of EGFR activation

Amino acid modifications

Modified residue21N-acetylserine Ref.11
Modified residue1311Phosphothreonine By similarity
Modified residue2511Phosphoserine Ref.9 Ref.10
Modified residue2731Phosphoserine By similarity
Modified residue3021Phosphoserine By similarity
Modified residue4611Phosphoserine Ref.8 Ref.9 Ref.10

Natural variations

Natural variant1091D → N.
Corresponds to variant rs34781518 [ dbSNP | Ensembl ].
VAR_063039
Natural variant1581I → L.
Corresponds to variant rs34974993 [ dbSNP | Ensembl ].
VAR_050975

Experimental info

Mutagenesis3461M → A: Abolishes inhibition of EGFR activity. Ref.12
Mutagenesis3521F → A: Abolishes inhibition of EGFR activity. Ref.12
Mutagenesis3581Y → A: Abolishes inhibition of EGFR activity. Ref.12
Sequence conflict71A → T Ref.1
Sequence conflict361S → C Ref.1

Secondary structure

..... 462
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9UJM3 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: 7AFA9F6CEB602912

FASTA46250,560
        10         20         30         40         50         60 
MSIAGVAAQE IRVPLKTGFL HNGRAMGNMR KTYWSSRSEF KNNFLNIDPI TMAYSLNSSA 

        70         80         90        100        110        120 
QERLIPLGHA SKSAPMNGHC FAENGPSQKS SLPPLLIPPS ENLGPHEEDQ VVCGFKKLTV 

       130        140        150        160        170        180 
NGVCASTPPL TPIKNSPSLF PCAPLCERGS RPLPPLPISE ALSLDDTDCE VEFLTSSDTD 

       190        200        210        220        230        240 
FLLEDSTLSD FKYDVPGRRS FRGCGQINYA YFDTPAVSAA DLSYVSDQNG GVPDPNPPPP 

       250        260        270        280        290        300 
QTHRRLRRSH SGPAGSFNKP AIRISNCCIH RASPNSDEDK PEVPPRVPIP PRPVKPDYRR 

       310        320        330        340        350        360 
WSAEVTSSTY SDEDRPPKVP PREPLSPSNS RTPSPKSLPS YLNGVMPPTQ SFAPDPKYVS 

       370        380        390        400        410        420 
SKALQRQNSE GSASKVPCIL PIIENGKKVS STHYYLLPER PPYLDKYEKF FREAEETNGG 

       430        440        450        460 
AQIQPLPADC GISSATEKPD SKTKMDLGGH VKRKHLSYVV SP 

« Hide

References

« Hide 'large scale' references
[1]"Identification of a novel mitogen-inducible gene (mig-6): regulation during G1 progression and differentiation."
Wick M., Buerger C., Funk M., Mueller R.
Exp. Cell Res. 219:527-535(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION.
[2]"The gene for Mig-6 is regulated by methylmethanesulphonate and shows high expression in the liver."
Van Laar T., Schouten T., van der Eb A.J., Terleth C.
Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Testis.
[4]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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].
Tissue: Placenta.
[7]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 302-462.
Tissue: Testis.
[8]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-461, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-251 AND SER-461, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-251 AND SER-461, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[12]"Inhibition of the EGF receptor by binding of MIG6 to an activating kinase domain interface."
Zhang X., Pickin K.A., Bose R., Jura N., Cole P.A., Kuriyan J.
Nature 450:741-744(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 325-364 IN COMPLEX WITH EGFR, SUBUNIT, MUTAGENESIS OF MET-346; PHE-352 AND TYR-358, DOMAIN.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ276373 mRNA. Translation: CAC20426.1.
AL034417 Genomic DNA. Translation: CAB52551.1.
AK315718 mRNA. Translation: BAG38076.1.
CH471130 Genomic DNA. Translation: EAW71593.1.
BC025337 mRNA. Translation: AAH25337.1.
AL137274 mRNA. Translation: CAB70672.1.
CCDSCCDS94.1.
PIRT46346.
RefSeqNP_061821.1. NM_018948.3.
XP_006710760.1. XM_006710697.1.
UniGeneHs.605445.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2RF9X-ray3.50C/D315-374[»]
2RFDX-ray3.60C/D340-364[»]
2RFEX-ray2.90E/F325-364[»]
4I21X-ray3.37C/D315-374[»]
ProteinModelPortalQ9UJM3.
SMRQ9UJM3. Positions 335-364.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid119923. 11 interactions.
DIPDIP-42379N.
IntActQ9UJM3. 18 interactions.
MINTMINT-1591605.
STRING9606.ENSP00000366702.

PTM databases

PhosphoSiteQ9UJM3.

Polymorphism databases

DMDM27923810.

Proteomic databases

MaxQBQ9UJM3.
PaxDbQ9UJM3.
PRIDEQ9UJM3.

Protocols and materials databases

DNASU54206.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000377482; ENSP00000366702; ENSG00000116285.
GeneID54206.
KEGGhsa:54206.
UCSCuc001aoz.3. human.

Organism-specific databases

CTD54206.
GeneCardsGC01M008064.
HGNCHGNC:18185. ERRFI1.
HPAHPA027206.
MIM608069. gene.
neXtProtNX_Q9UJM3.
PharmGKBPA142671904.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG147618.
HOGENOMHOG000234207.
HOVERGENHBG031710.
InParanoidQ9UJM3.
OMAKPAIRIS.
PhylomeDBQ9UJM3.
TreeFamTF335720.

Enzyme and pathway databases

SignaLinkQ9UJM3.

Gene expression databases

ArrayExpressQ9UJM3.
BgeeQ9UJM3.
CleanExHS_ERRFI1.
GenevestigatorQ9UJM3.

Family and domain databases

InterProIPR015116. Cdc42_binding_dom_like.
IPR021619. Inhibitor_Mig-6.
[Graphical view]
PfamPF09027. GTPase_binding. 1 hit.
PF11555. Inhibitor_Mig-6. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSERRFI1. human.
EvolutionaryTraceQ9UJM3.
GeneWikiERRFI1.
GenomeRNAi54206.
NextBio56530.
PROQ9UJM3.
SOURCESearch...

Entry information

Entry nameERRFI_HUMAN
AccessionPrimary (citable) accession number: Q9UJM3
Secondary accession number(s): B2RDX9, Q9NTG9, Q9UD05
Entry history
Integrated into UniProtKB/Swiss-Prot: January 27, 2003
Last sequence update: May 1, 2000
Last modified: July 9, 2014
This is version 107 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM