Reviewed,
UniProtKB/Swiss-Prot P11161 (EGR2_HUMAN)
Last modified
November 25, 2008.
Version 100.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
Third-party data |
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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 |
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| 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 | |
| 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
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
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References
| « Hide '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. 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. |
Cross-references
Sequence databases | |
|---|---|
| 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 |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 10 Human chromosome 10: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| UniProtKB secondary accession numbers Index of UniProtKB secondary accession numbers |
| SIMILARITY comments Index of protein domains and families |

Clusters with


