Q9UJM3 (ERRFI_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
ERBB receptor feedback inhibitor 1

Alternative name(s):
Mitogen-inducible gene 6 protein
Short name=MIG-6

Gene names

Name:	ERRFI1
Synonyms:	MIG6

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	462 AA.
Sequence status	Complete.
Protein existence	Evidence 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.13
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.13
Sequence similarities	Belongs to the MIG6 family.

Ontologies

Keywords
Cellular component	Cell membrane Cytoplasm Membrane Nucleus
Coding sequence diversity	Polymorphism
Disease	Tumor suppressor
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	lung 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.13. Source: UniProtKB negative regulation of protein autophosphorylation Inferred from direct assay Ref.13. Source: UniProtKB regulation of keratinocyte differentiation Inferred from sequence or structural similarity. Source: UniProtKB response to stress Traceable author statement. Source: ProtInc skin morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB extrinsic to internal side of plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	Rho GTPase activator activity Traceable author statement. Source: ProtInc protein kinase binding Inferred from physical interaction Ref.13. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EGFR	P00533	2	EBI-2941912,EBI-297353
GRB2	P62993	4	EBI-2941912,EBI-401755

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 462

462

ERBB receptor feedback inhibitor 1

PRO_0000096487

Regions

Region

334 – 363

30

Interaction with EGFR and ERBB2 and regulation of EGFR activation

Amino acid modifications

Modified residue

127

1

Phosphothreonine By similarity

Modified residue

131

1

Phosphothreonine By similarity

Modified residue

251

1

Phosphoserine Ref.12

Modified residue

273

1

Phosphoserine By similarity

Modified residue

394

1

Phosphotyrosine Ref.8 Ref.11

Modified residue

395

1

Phosphotyrosine Ref.8 Ref.11

Modified residue

461

1

Phosphoserine Ref.9 Ref.10

Natural variations

Natural variant

109

1

D → N.
Corresponds to variant rs34781518 [ dbSNP | Ensembl ].

VAR_063039

Natural variant

158

1

I → L.
Corresponds to variant rs34974993 [ dbSNP | Ensembl ].

VAR_050975

Experimental info

Mutagenesis

346

1

M → A: Abolishes inhibition of EGFR activity. Ref.13

Mutagenesis

352

1

F → A: Abolishes inhibition of EGFR activity. Ref.13

Mutagenesis

358

1

Y → A: Abolishes inhibition of EGFR activity. Ref.13

Sequence conflict

7

1

A → T Ref.1

Sequence conflict

36

1

S → C Ref.1

Secondary structure

1

.

.

.

462

Helix Strand Turn

Details...

Turn

356 – 358

3

Sequences

	Sequence		Length	Mass (Da)
	Q9UJM3 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 7AFA9F6CEB602912	FASTA	462	50,560
	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

References

	« Hide 'large scale' referencesShow '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: 7641805] [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. , 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: 14702039] [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. , 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: 16710414] [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. , 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: 15489334] [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: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 302-462. Tissue: Testis.
[8]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-394 AND TYR-395, MASS SPECTROMETRY. Tissue: Lung 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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-461, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"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: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-461, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"An extensive survey of tyrosine phosphorylation revealing new sites in human mammary epithelial cells." Heibeck T.H., Ding S.-J., Opresko L.K., Zhao R., Schepmoes A.A., Yang F., Tolmachev A.V., Monroe M.E., Camp D.G. II, Smith R.D., Wiley H.S., Qian W.-J. J. Proteome Res. 8:3852-3861(2009) [PubMed: 19534553] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-394 AND TYR-395, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[12]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-251, MASS SPECTROMETRY.
[13]	"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: 18046415] [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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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.

IPI

IPI00004399.

PIR

T46346.

RefSeq

NP_061821.1. NM_018948.3.

UniGene

Hs.605445.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2RF9	X-ray	3.50	C/D	315-374	[»]
2RFD	X-ray	3.60	C/D	340-364	[»]
2RFE	X-ray	2.90	E/F	325-364	[»]

ProteinModelPortal

Q9UJM3.

SMR

Q9UJM3. Positions 4-46, 336-362.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-42379N.

IntAct

Q9UJM3. 2 interactions.

MINT

MINT-1591605.

STRING

Q9UJM3.

PTM databases

PhosphoSite

Q9UJM3.

Polymorphism databases

DMDM

27923810.

Proteomic databases

PRIDE

Q9UJM3.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000377482; ENSP00000366702; ENSG00000116285.

GeneID

54206.

KEGG

hsa:54206.

UCSC

uc001aoz.1. human.

Organism-specific databases

CTD

54206.

GeneCards

GC01M008064.

H-InvDB

HIX0000098.

HGNC

HGNC:18185. ERRFI1.

HPA

HPA027206.

MIM

608069. gene.

neXtProt

NX_Q9UJM3.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG15552.

GeneTree

ENSGT00440000033870.

HOGENOM

HBG716106.

HOVERGEN

HBG031710.

InParanoid

Q9UJM3.

OMA

DPITMAY.

OrthoDB

EOG4CVG6X.

PhylomeDB

Q9UJM3.

Gene expression databases

ArrayExpress

Q9UJM3.

Bgee

Q9UJM3.

CleanEx

HS_ERRFI1.

Genevestigator

Q9UJM3.

GermOnline

ENSG00000116285. Homo sapiens.

Family and domain databases

InterPro

IPR015116. GTPase_binding.
IPR021619. Inhibitor_Mig-6.
[Graphical view]

Pfam

PF09027. GTPase_binding. 1 hit.
PF11555. Inhibitor_Mig-6. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

56530.

SOURCE

Search...

Entry information

Entry name

ERRFI_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 82 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.