Reviewed, UniProtKB/Swiss-Prot P11161 (EGR2_HUMAN)

Names and origin

Protein names

Recommended name:
    Early growth response protein 2
      Short name=EGR-2
Alternative name(s):
    Protein Krox-20
    AT591

Gene names

Name:	EGR2
Synonyms:	KROX20

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	476 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Sequence-specific DNA-binding transcription factor. Binds to two specific DNA sites located in the promoter region of HOXA4.
Subunit structure	Interacts with HCFC1.
Subcellular location	Nucleus.
Involvement in disease	Defects in EGR2 are a cause of congenital hypomyelination neuropathy (CHN) [MIM:605253]. Inheritance can be autosomal dominant or recessive. Recessive CHN is also known as Charcot-Marie-Tooth disease type 4E (CMT4E). CHN is characterized clinically by early onset of hypotonia, areflexia, distal muscle weakness, and very slow nerve conduction velocities. Defects in EGR2 are a cause of Charcot-Marie-Tooth disease type 1D (CMT1D) [MIM:607678]. CMT1D is a form of Charcot-Marie-Tooth disease, the most common inherited disorder of the peripheral nervous system. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathy or CMT1, and primary peripheral axonal neuropathy or CMT2. Neuropathies of the CMT1 group are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. Defects in EGR2 are a cause of Dejerine-Sottas syndrome (DSS) [MIM:145900]; also known as Dejerine-Sottas neuropathy (DSN) or hereditary motor and sensory neuropathy III (HMSN3). DSS is a severe degenerating neuropathy of the demyelinating Charcot-Marie-Tooth disease category, with onset by age 2 years. DSS is characterized by motor and sensory neuropathy with very slow nerve conduction velocities, increased cerebrospinal fluid protein concentrations, hypertrophic nerve changes, delayed age of walking as well as areflexia. There are both autosomal dominant and autosomal recessive forms of Dejerine-Sottas syndrome.
Sequence similarities	Belongs to the EGR C2H2-type zinc-finger protein family. Contains 3 C2H2-type zinc fingers.
Sequence caution	The sequence AAA52372.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence AAA52372.1 differs from that shown. Reason: Frameshift at position 449.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Disease	Charcot-Marie-Tooth disease Dejerine-Sottas syndrome Disease mutation
Domain	Repeat Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Activator
Gene Ontology (GO)
Biological process	brain development Ref.3 Traceable author statement. Source: ProtInc mechanosensory behavior Inferred from electronic annotation. Source: UniProtKB-KW peripheral nervous system development Ref.3 Traceable author statement. Source: ProtInc regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	protein binding Ref.8 Inferred from physical interaction. Source: UniProtKB transcription factor activity Ref.8 Inferred from direct assay. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Long (identifier: P11161-1)

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.

Isoform Short (identifier: P11161-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-50: Missing.

Notes: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 476	476	Early growth response protein 2		PRO_0000047119
Regions
	Zinc finger	340 – 364	25	C2H2-type 1
	Zinc finger	370 – 392	23	C2H2-type 2
	Zinc finger	398 – 420	23	C2H2-type 3
	Motif	162 – 165	4	HCFC1-binding-motif (HBM)
	Compositional bias	300 – 309	10	Poly-Ala
Natural variations
	Alternative sequence	1 – 50	50	Missing in isoform Short.		VSP_006863
	Natural variant	268	1	I → N in CHN.		VAR_007735
	Natural variant	355	1	D → V in CMT1D.		VAR_007736
	Natural variant	359	1	R → W in DSS and CMT1D; associated with A-136 in the GJB1 gene in a DSS Korean girl.		VAR_009874
	Natural variant	381	1	R → C in CMT1D.		VAR_029958
	Natural variant	381	1	R → H in CMT1D.		VAR_009875
	Natural variant	382 – 383	2	SD → RY in CHN.		VAR_007737
	Natural variant	383	1	D → Y in CMT1D.		VAR_029959
	Natural variant	409	1	R → W in CMT1D.		VAR_007738
Experimental info
	Mutagenesis	162 – 165	4	DHLY → AAAA: Inhibits association with HCFC1
	Sequence conflict	68	1	K → R in CAH18435. Ref.4
	Sequence conflict	247	1	K → KPFPCPLDTLRVPPPLTPLS TIRK in AAH35625. Ref.6
	Sequence conflict	280	1	V → M in AAA52372. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified July 19, 2003. Version 3. Checksum: 7810D1B1B418DF1F	FASTA	476	50,302
	10 20 30 40 50 60 MMTAKAVDKI PVTLSGFVHQ LSDNIYPVED LAATSVTIFP NAELGGPFDQ MNGVAGDGMI 70 80 90 100 110 120 NIDMTGEKRS LDLPYPSSFA PVSAPRNQTF TYMGKFSIDP QYPGASCYPE GIINIVSAGI 130 140 150 160 170 180 LQGVTSPAST TASSSVTSAS PNPLATGPLG VCTMSQTQPD LDHLYSPPPP PPPYSGCAGD 190 200 210 220 230 240 LYQDPSAFLS AATTSTSSSL AYPPPPSYPS PKPATDPGLF PMIPDYPGFF PSQCQRDLHG 250 260 270 280 290 300 TAGPDRKPFP CPLDTLRVPP PLTPLSTIRN FTLGGPSAGV TGPGASGGSE GPRLPGSSSA 310 320 330 340 350 360 AAAAAAAAAY NPHHLPLRPI LRPRKYPNRP SKTPVHERPY PCPAEGCDRR FSRSDELTRH 370 380 390 400 410 420 IRIHTGHKPF QCRICMRNFS RSDHLTTHIR THTGEKPFAC DYCGRKFARS DERKRHTKIH 430 440 450 460 470 LRQKERKSSA PSASVPAPST ASCSGGVQPG GTLCSSNSSS LGGGPLAPCS SRTRTP
	Isoform Short [UniParc]. Checksum: DD358E32D00B4353		426	44,970
	10 20 30 40 50 60 MNGVAGDGMI NIDMTGEKRS LDLPYPSSFA PVSAPRNQTF TYMGKFSIDP QYPGASCYPE 70 80 90 100 110 120 GIINIVSAGI LQGVTSPAST TASSSVTSAS PNPLATGPLG VCTMSQTQPD LDHLYSPPPP 130 140 150 160 170 180 PPPYSGCAGD LYQDPSAFLS AATTSTSSSL AYPPPPSYPS PKPATDPGLF PMIPDYPGFF 190 200 210 220 230 240 PSQCQRDLHG TAGPDRKPFP CPLDTLRVPP PLTPLSTIRN FTLGGPSAGV TGPGASGGSE 250 260 270 280 290 300 GPRLPGSSSA AAAAAAAAAY NPHHLPLRPI LRPRKYPNRP SKTPVHERPY PCPAEGCDRR 310 320 330 340 350 360 FSRSDELTRH IRIHTGHKPF QCRICMRNFS RSDHLTTHIR THTGEKPFAC DYCGRKFARS 370 380 390 400 410 420 DERKRHTKIH LRQKERKSSA PSASVPAPST ASCSGGVQPG GTLCSSNSSS LGGGPLAPCS SRTRTP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning, sequencing, and mapping of EGR2, a human early growth response gene encoding a protein with 'zinc-binding finger' structure." Joseph L.J., le Beau M.M., Jamieson G.A. Jr., Acharya S., Shows T.B., Rowley J.D., Sukhatme V.P. Proc. Natl. Acad. Sci. U.S.A. 85:7164-7168(1988) [PubMed: 3140236] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
[2]	Erratum Joseph L.J., le Beau M.M., Jamieson G.A. Jr., Acharya S., Shows T.B., Rowley J.D., Sukhatme V.P. Proc. Natl. Acad. Sci. U.S.A. 86:515-515(1989) Cited for: SEQUENCE REVISION TO C-TERMINUS.
[3]	"Mutations in the early growth response 2 (EGR2) gene are associated with hereditary myelinopathies." Warner L.E., Mancias P., Butler I.J., McDonald C.M., Keppen L., Koob K.G., Lupski J.R. Nat. Genet. 18:382-384(1998) [PubMed: 9537424] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), VARIANTS CHN ASN-268 AND 382-ARG-TYR-383, VARIANT CMT1D TRP-409.
[4]	The German cDNA consortium Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Endometrium.
[5]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed: 15164054] [Abstract] 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].
[7]	"The serum and TPA responsive promoter and intron-exon structure of EGR2, a human early growth response gene encoding a zinc finger protein." Rangnekar V.M., Aplin A.C., Sukhatme V.P. Nucleic Acids Res. 18:2749-2757(1990) [PubMed: 2111009] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-21.
[8]	"HCF-1 functions as a coactivator for the zinc finger protein Krox20." Luciano R.L., Wilson A.C. J. Biol. Chem. 278:51116-51124(2003) [PubMed: 14532282] [Abstract] Cited for: INTERACTION WITH HCFC1, MUTAGENESIS OF 162-ASP--TYR-165.
[9]	"EGR2 gene mutation in a patient affected with Charcot-Marie-Tooth type 1." Di Maria E., Bellone E., Soriani S., Varese A., Lamba Doria L., Grandis M., Schenone A., Levi G., Ajmar F., Mandich P. Eur. J. Hum. Genet. Suppl. 7:99-99(1999) Cited for: VARIANT CMT1D VAL-355.
[10]	"A novel mutation (D305V) in the early growth response 2 gene is associated with severe Charcot-Marie-Tooth type 1 disease." Bellone E., Di Maria E., Soriani S., Varese A., Lamba Doria L., Ajmar F., Mandich P. Hum. Mutat. 14:353-354(1999) [PubMed: 10502832] [Abstract] Cited for: VARIANT CMT1D VAL-355.
[11]	"Novel missense mutation in the early growth response 2 gene associated with Dejerine-Sottas syndrome phenotype." Timmerman V., De Jonghe P., Ceuterick C., De Vriendt E., Lofgren A., Nelis E., Warner L.E., Lupski J.R., Martin J.-J., Van Broeckhoven C. Neurology 52:1827-1832(1999) [PubMed: 10371530] [Abstract] Cited for: VARIANT DSS TRP-359.
[12]	"Cranial nerve involvement in CMT disease type 1 due to early growth response 2 gene mutation." Pareyson D., Taroni F., Botti S., Morbin M., Baratta S., Lauria G., Ciano C., Sghirlanzoni A. Neurology 54:1696-1698(2000) [PubMed: 10762521] [Abstract] Cited for: VARIANT CMT1D HIS-381.
[13]	"A novel missense mutation in the early growth response 2 gene associated with late-onset Charcot-Marie-Tooth disease type 1." Yoshihara T., Kanda F., Yamamoto M., Ishihara H., Misu K., Hattori N., Chihara K., Sobue G. J. Neurol. Sci. 184:149-153(2001) [PubMed: 11239949] [Abstract] Cited for: VARIANT CMT1D CYS-381.
[14]	"Screening of the early growth response 2 gene in Japanese patients with Charcot-Marie-Tooth disease type 1." Numakura C., Shirahata E., Yamashita S., Kanai M., Kijima K., Matsuki T., Hayasaka K. J. Neurol. Sci. 210:61-64(2003) [PubMed: 12736090] [Abstract] Cited for: VARIANT CMT1D TYR-383.
[15]	"Mutational analysis of PMP22, MPZ, GJB1, EGR2 and NEFL in Korean Charcot-Marie-Tooth neuropathy patients." Choi B.-O., Lee M.S., Shin S.H., Hwang J.H., Choi K.-G., Kim W.-K., Sunwoo I.N., Kim N.K., Chung K.W. Hum. Mutat. 24:185-186(2004) [PubMed: 15241803] [Abstract] Cited for: VARIANT CMT1D TRP-359.
[16]	"Two missense mutations of EGR2 R359W and GJB1 V136A in a Charcot-Marie-Tooth disease family." Chung K.W., Sunwoo I.N., Kim S.M., Park K.D., Kim W.-K., Kim T.S., Koo H., Cho M., Lee J., Choi B.O. Neurogenetics 6:159-163(2005) [PubMed: 15947997] [Abstract] Cited for: VARIANT CMT1D TRP-359.
+	Additional computationally mapped references.

Web resources

Inherited peripheral neuropathies mutation db

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	J04076 mRNA. Translation: AAA52372.1. Sequence problems. AF139463 mRNA. Translation: AAD24588.1. CR749641 mRNA. Translation: CAH18435.1. AL133417 Genomic DNA. Translation: CAH73827.2. BC035625 mRNA. Translation: AAH35625.1. X53700 Genomic DNA. No translation available.
RefSeq	NP_000390.2.
UniGene	Hs.1395
3D structure databases
HSSP	HSSP built from PDB template 1P47 based on UniProtKB P08046.
SMR	P11161. Positions 337-423.
ModBase	Search...
Protein-protein interaction databases
IntAct	P11161.
Genome annotation databases
Ensembl	ENSG00000122877. Homo sapiens. [Contig view]
GeneID	1959.
KEGG	hsa:1959.
Organism-specific databases
H-InvDB	HIX0008861.
HGNC	HGNC:3239. EGR2.
MIM	129010. gene. 145900. phenotype. 605253. phenotype. 607678. phenotype.
Orphanet	65753. Charcot-Marie-Tooth disease, type 1. 101084. Charcot-Marie-Tooth disease, type 1D. 64749. Charcot-Marie-Tooth disease, type 4. 99951. Charcot-Marie-Tooth disease, type 4E. 99952. Charcot-Marie-Tooth disease, type 4F. 64748. Dejerine-Sottas syndrome.
PharmGKB	PA27674.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	P11161.
HOVERGEN	P11161.
Gene expression databases
ArrayExpress	P11161.
CleanEx	HS_EGR2.
GermOnline	ENSG00000122877. Homo sapiens.
Family and domain databases
InterPro	IPR007087. Znf_C2H2. IPR015880. Znf_C2H2-like. IPR013087. Znf_C2H2/integrase_DNA-bd. [Graphical view]
Gene3D	G3DSA:3.30.160.60. Znf_C2H2/integrase_DNA-bd. 2 hits.
Pfam	PF00096. zf-C2H2. 3 hits. [Graphical view]
ProDom	PD000003. Znf_C2H2. 2 hits. [Graphical view] [Entries sharing at least one domain]
SMART	SM00355. ZnF_C2H2. 3 hits. [Graphical view]
PROSITE	PS00028. ZINC_FINGER_C2H2_1. 3 hits. PS50157. ZINC_FINGER_C2H2_2. 3 hits. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	7947.
SOURCE	Search...

Entry information

Entry name

EGR2_HUMAN

Accession

Primary (citable) accession number: P11161
Secondary accession number(s): Q68CZ5, Q8IV26, Q9UNA6

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	July 19, 2003
Last modified:	November 25, 2008
This is version 100 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)