Reviewed,
UniProtKB/Swiss-Prot Q03112 (EVI1_HUMAN)
Last modified
February 9, 2010.
Version 96.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
Third-party data |
Customize display | text xml rdf/xml gff fasta |
Names and origin
| Protein names | Recommended name: MDS1 and EVI1 complex locus protein EVI1 Alternative name(s): Ecotropic virus integration site 1 protein homolog Short name=EVI-1 | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) [Complete proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 1051 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Functions as a transcriptional regulator binding to DNA sequences in the promoter region of target genes and regulating positively or negatively their expression. Oncogene which plays a role in development, cell proliferation and differentiation. May also play a role in apoptosis through regulation of the JNK and TGF-beta signaling. Involved in hematopoiesis. |
| Subunit structure | Homooligomer. Interacts with SUV39H1 (via SET domain); enhances MECOM transcriptional repression activity By similarity. Interacts with CTBP1. Interacts with SMAD3 (via MH2 domain); the interaction is direct. Interacts with SMAD4; through interaction with SMAD3. Interacts with CREBBP, KAT2B and histone deacetylases. Interacts with MAPK8 and MAPK9; inhibits JNK signaling. |
| Subcellular location | |
| Domain | Both zinc finger regions are required for the transcriptional activation of PBX1. |
| Post-translational modification | Phosphorylated By similarity. Phosphorylated upon DNA damage, probably by ATM or ATR. May be acetylated by CREBBP and KAT2B. |
| Involvement in disease | A chromosomal aberration involving EVI1 is a cause of chronic myelogenous leukemia (CML). Translocation t(3;21)(q26;q22) with RUNX1/AML1. |
| Sequence similarities | Contains 10 C2H2-type zinc fingers. |
| Sequence caution | The sequence AAB37456.1 differs from that shown. Reason: Miscellaneous discrepancy. Probable cloning artifact. The sequence BAH14103.1 differs from that shown. Reason: Miscellaneous discrepancy. Aberrant splicing. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| Ctbp2 | P56546 | 3 | EBI-1384862,EBI-1384883 | From a different organism. |
| UXT | Q9UBK9 | 4 | EBI-1384862,EBI-357355 |
Alternative products
| This entry describes 6 isoforms produced by alternative promoter usage and alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q03112-1) Also known as: Long; Evi-1a; 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 2 (identifier: Q03112-3) Also known as: Evi-1c; Mds1/Evi1; The sequence of this isoform differs from the canonical sequence as follows: 1-1: M → MRSKGRARKL...APGEELLLFM | ||||||
| Note: Produced by alternative promoter usage. Contains an additional SET domain at positions 79-194. Unable to form homooligomers, to interact with CTBP1 and SMAD3 and to repress TGF-beta signaling. | ||||||
| Isoform 3 (identifier: Q13465-1) Also known as: Mds1; The sequence of this isoform can be found in the external entry Q13465-1. Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly. | ||||||
| Note: Produced by alternative promoter usage. | ||||||
| Isoform 4 (identifier: Q03112-4) The sequence of this isoform differs from the canonical sequence as follows: 1-1: M → MILDEFYNVKFCIDASQPDVGSWLKYIRFAGCYDQHNLVACQINDQIFYRVVADIAPGEELLLFM 138-138: K → KQ | ||||||
| Isoform 5 (identifier: Q03112-5) The sequence of this isoform differs from the canonical sequence as follows: 672-680: Missing. | ||||||
| Isoform 6 (identifier: Q03112-6) The sequence of this isoform differs from the canonical sequence as follows: 138-138: K → KQ 672-680: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1051 | 1051 | MDS1 and EVI1 complex locus protein EVI1 | PRO_0000047273 | |||||
Regions | |||||||||
| Zinc finger | 21 – 44 | 24 | C2H2-type 1 | ||||||
| Zinc finger | 75 – 97 | 23 | C2H2-type 2 | ||||||
| Zinc finger | 103 – 125 | 23 | C2H2-type 3 | ||||||
| Zinc finger | 131 – 154 | 24 | C2H2-type 4 | ||||||
| Zinc finger | 160 – 182 | 23 | C2H2-type 5 | ||||||
| Zinc finger | 188 – 210 | 23 | C2H2-type 6 | ||||||
| Zinc finger | 217 – 239 | 23 | C2H2-type 7 | ||||||
| Zinc finger | 733 – 755 | 23 | C2H2-type 8 | ||||||
| Zinc finger | 761 – 784 | 24 | C2H2-type 9 | ||||||
| Zinc finger | 790 – 812 | 23 | C2H2-type 10 | ||||||
| Region | 1 – 252 | 252 | Interaction with MAPK9, SMAD3 and probably SUV39H1 | ||||||
| Motif | 421 – 434 | 14 | Nuclear localization signal Potential | ||||||
| Motif | 553 – 557 | 5 | CTBP-binding motif 1 By similarity | ||||||
| Motif | 584 – 588 | 5 | CTBP-binding motif 2 By similarity | ||||||
| Compositional bias | 886 – 937 | 52 | Asp/Glu-rich (acidic) | ||||||
Amino acid modifications | |||||||||
| Modified residue | 854 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 858 | 1 | Phosphoserine Ref.13 | ||||||
| Modified residue | 860 | 1 | Phosphoserine Ref.13 Ref.14 | ||||||
Natural variations | |||||||||
| Alternative sequence | 1 | 1 | M → MRSKGRARKLATNNECVYGN YPEIPLEEMPDADGVASTPS LNIQEPCSPATSSEAFTPKE GSPYKAPIYIPDDIPIPAEF ELRESNMPGAGLGIWTKRKI EVGEKFGPYVGEQRSNLKDP SYGWEILDEFYNVKFCIDAS QPDVGSWLKYIRFAGCYDQH NLVACQINDQIFYRVVADIA PGEELLLFM in isoform 2. | VSP_038733 | |||||
| Alternative sequence | 1 | 1 | M → MILDEFYNVKFCIDASQPDV GSWLKYIRFAGCYDQHNLVA CQINDQIFYRVVADIAPGEE LLLFM in isoform 4. | VSP_038734 | |||||
| Alternative sequence | 138 | 1 | K → KQ in isoform 4 and isoform 6. | VSP_038735 | |||||
| Alternative sequence | 672 – 680 | 9 | Missing in isoform 5 and isoform 6. | VSP_038736 | |||||
| Natural variant | 107 | 1 | Q → R: dbSNP rs34896995. | VAR_061928 | |||||
Experimental info | |||||||||
| Mutagenesis | 555 – 556 | 2 | DL → AS: Partial loss of interaction with CTBP1. Loss of interaction with CTBP1; when associated with 586-A-S-587. | ||||||
| Mutagenesis | 586 – 587 | 2 | DL → AS: Partial loss of interaction with CTBP1. Loss of interaction with CTBP1; when associated with 555-A-S-556. | ||||||
| Sequence conflict | 20 | 1 | Q → R in CAE45952. Ref.4 | ||||||
| Sequence conflict | 175 | 1 | L → P in CAE45952. Ref.4 | ||||||
| Sequence conflict | 301 | 1 | F → S in BAF85554. Ref.3 | ||||||
| Sequence conflict | 303 | 1 | F → V in CAA38735. Ref.1 | ||||||
| Sequence conflict | 443 | 1 | S → P in CAI46086. Ref.4 | ||||||
| Sequence conflict | 543 | 1 | K → R in CAE45952. Ref.4 | ||||||
| Sequence conflict | 730 | 1 | K → R in BAF85554. Ref.3 | ||||||
| Sequence conflict | 741 | 1 | I → V in CAI46086. Ref.4 | ||||||
| Sequence conflict | 796 | 1 | D → Y in CAA38735. Ref.1 | ||||||
| Sequence conflict | 875 | 1 | D → E in CAA38735. Ref.1 | ||||||
| Sequence conflict | 881 | 1 | T → P in CAA38735. Ref.1 | ||||||
| Sequence conflict | 906 | 1 | N → Y in CAA38735. Ref.1 | ||||||
| Sequence conflict | 992 | 1 | V → A in BAF85554. Ref.3 | ||||||
| Sequence conflict | 1013 | 1 | L → P in CAE45952. Ref.4 | ||||||
Sequences
| ||||||||||||||||||||||||||||||||||||||||||||||||
References
| « Hide 'large scale' references | |
| [1] | "Unique expression of the human Evi-1 gene in an endometrial carcinoma cell line: sequence of cDNAs and structure of alternatively spliced transcripts." Morishita K., Parganas E., Douglass E.C., Ihle J.N. Oncogene 5:963-971(1990) [PubMed: 2115646] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ALTERNATIVE SPLICING. |
| [2] | "Generation of the AML1-EVI-1 fusion gene in the t(3;21)(q26;q22) causes blastic crisis in chronic myelocytic leukemia." Mitani K., Ogawa S., Tanaka T., Miyoshi H., Kurokawa M., Mano H., Yazaki Y., Ohki M., Hirai H. EMBO J. 13:504-510(1994) [PubMed: 8313895] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), CHROMOSOMAL TRANSLOCATION WITH RUNX1 IN CHRONIC MYELOCYTIC LEUKEMIA. |
| [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. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-759 (ISOFORM 2). Tissue: Trachea. |
| [4] | "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] (ISOFORM 5). Tissue: Adipose tissue and Fetal kidney. |
| [5] | "The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. Gibbs R.A.Nature 440:1194-1198(2006) [PubMed: 16641997] [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] (ISOFORMS 4 AND 6), NUCLEOTIDE SEQUENCE [MRNA] OF 516-1051 (ISOFORM 5). Tissue: Lung. |
| [7] | "Structurally altered Evi-1 protein generated in the 3q21q26 syndrome." Ogawa S., Kurokawa M., Tanaka T., Mitani K., Inazawa J., Hangaishi A., Tanaka K., Matsuo Y., Minowada J., Tsubota T., Yazaki Y., Hirai H. Oncogene 13:183-191(1996) [PubMed: 8700545] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 970-1007 (ISOFORM 1). |
| [8] | "The oncoprotein Evi-1 represses TGF-beta signalling by inhibiting Smad3." Kurokawa M., Mitani K., Irie K., Matsuyama T., Takahashi T., Chiba S., Yazaki Y., Matsumoto K., Hirai H. Nature 394:92-96(1998) [PubMed: 9665135] [Abstract] Cited for: FUNCTION IN TGF-BETA SIGNALING, INTERACTION WITH SMAD3 AND SMAD4, SUBCELLULAR LOCATION. |
| [9] | "The evi-1 oncoprotein inhibits c-Jun N-terminal kinase and prevents stress-induced cell death." Kurokawa M., Mitani K., Yamagata T., Takahashi T., Izutsu K., Ogawa S., Moriguchi T., Nishida E., Yazaki Y., Hirai H. EMBO J. 19:2958-2968(2000) [PubMed: 10856240] [Abstract] Cited for: FUNCTION, INTERACTION WITH MAPK8 AND MAPK9. |
| [10] | "Interaction of EVI1 with cAMP-responsive element-binding protein-binding protein (CBP) and p300/CBP-associated factor (P/CAF) results in reversible acetylation of EVI1 and in co-localization in nuclear speckles." Chakraborty S., Senyuk V., Sitailo S., Chi Y., Nucifora G. J. Biol. Chem. 276:44936-44943(2001) [PubMed: 11568182] [Abstract] Cited for: FUNCTION, ACETYLATION, INTERACTION WITH CREBBP; CTBP1; KAT2B AND HISTONE DEACETYLASES, SUBCELLULAR LOCATION, MUTAGENESIS OF 555-ASP-LEU-556 AND 586-ASP-LEU-587. |
| [11] | "Oligomerization of Evi-1 regulated by the PR domain contributes to recruitment of corepressor CtBP." Nitta E., Izutsu K., Yamaguchi Y., Imai Y., Ogawa S., Chiba S., Kurokawa M., Hirai H. Oncogene 24:6165-6173(2005) [PubMed: 15897867] [Abstract] Cited for: FUNCTION, ALTERTNATIVE SPLICING (ISOFORMS 1 AND 2), HOMOOLIGOMERIZATION, INTERACTION WITH CTBP1 AND SMAD3, SUBCELLULAR LOCATION. |
| [12] | "Evi1 is a survival factor which conveys resistance to both TGFbeta- and taxol-mediated cell death via PI3K/AKT." Liu Y., Chen L., Ko T.C., Fields A.P., Thompson E.A. Oncogene 25:3565-3575(2006) [PubMed: 16462766] [Abstract] Cited for: FUNCTION IN APOPTOSIS. |
| [13] | "ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-858 AND SER-860, MASS SPECTROMETRY. |
| [14] | "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-860, MASS SPECTROMETRY. |
| [15] | "Pbx1 is a downstream target of Evi-1 in hematopoietic stem/progenitors and leukemic cells." Shimabe M., Goyama S., Watanabe-Okochi N., Yoshimi A., Ichikawa M., Imai Y., Kurokawa M. Oncogene 28:4364-4374(2009) [PubMed: 19767769] [Abstract] Cited for: FUNCTION. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | X54989 mRNA. Translation: CAA38735.1. S69002 mRNA. Translation: AAB29907.1. Different initiation. AK292865 mRNA. Translation: BAF85554.1. AK304098 mRNA. Translation: BAH14103.1. Sequence problems. BX640908 mRNA. Translation: CAE45952.1. BX647613 mRNA. Translation: CAI46086.1. AC007849 Genomic DNA. No translation available. AC024099 Genomic DNA. No translation available. AC069220 Genomic DNA. No translation available. AC074033 Genomic DNA. No translation available. AC078985 Genomic DNA. No translation available. BC031019 mRNA. Translation: AAH31019.1. BC130520 mRNA. Translation: AAI30521.1. Different initiation. BC143951 mRNA. Translation: AAI43952.1. BC143952 mRNA. Translation: AAI43953.1. S82592 mRNA. Translation: AAB37456.1. Sequence problems. |
| IPI | IPI00446866. |
| PIR | A60191. S41705. |
| RefSeq | NP_001098548.2. NP_005232.2. |
| UniGene | Hs.659873 |
3D structure databases | |
| HSSP | HSSP built from PDB template 1SP2 based on UniProtKB P08047. |
| SMR | Q03112. Positions 18-182, 97-212, 727-815. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | Q03112. 2 interactions. |
| STRING | A1L4F3. A8KA00. Q03112. Q5HYI1. Q6MZS6. Q8NEI5. |
PTM databases | |
| PhosphoSite | Q03112. |
Proteomic databases | |
| PRIDE | Q03112. |
Genome annotation databases | |
| Ensembl | ENST00000264674; ENSP00000264674; ENSG00000085276; Homo sapiens. [Genome view] ENST00000392736; ENSP00000376493; ENSG00000085276; Homo sapiens. [Genome view] ENST00000392737; ENSP00000376494; ENSG00000085276; Homo sapiens. [Genome view] ENST00000419148; ENSP00000402701; ENSG00000085276; Homo sapiens. [Genome view] ENST00000433243; ENSP00000394302; ENSG00000085276; Homo sapiens. [Genome view] ENST00000464456; ENSP00000419770; ENSG00000085276; Homo sapiens. [Genome view] ENST00000468789; ENSP00000419995; ENSG00000085276; Homo sapiens. [Genome view] ENST00000472280; ENSP00000420048; ENSG00000085276; Homo sapiens. [Genome view] ENST00000492586; ENSP00000417506; ENSG00000085276; Homo sapiens. [Genome view] ENST00000494292; ENSP00000417899; ENSG00000244102; Homo sapiens. [Genome view] ENST00000498368; ENSP00000418687; ENSG00000244102; Homo sapiens. [Genome view] |
| GeneID | 2122. |
| NMPDR | fig|9606.3.peg.23473. |
| UCSC | uc003ffi.2. human. |
Organism-specific databases | |
| CTD | 2122. |
| GeneCards | GC03M170283. |
| H-InvDB | HIX0003836. |
| HGNC | HGNC:3498. MECOM. |
| MIM | 165215. gene. |
| Orphanet | 52688. Myelodysplastic syndromes. |
| PharmGKB | PA27912. |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOVERGEN | Q03112. |
| InParanoid | Q03112. |
| OMA | EDAYFTE. |
| OrthoDB | EOG9M0HM2. |
| PhylomeDB | Q03112. |
Gene expression databases | |
| ArrayExpress | Q03112. |
| Bgee | Q03112. |
| CleanEx | HS_EVI1. |
| Genevestigator | Q03112. |
| GermOnline | ENSG00000085276. 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. 3 hits. |
| Pfam | PF00096. zf-C2H2. 4 hits. [Graphical view] |
| SMART | SM00355. ZnF_C2H2. 10 hits. [Graphical view] |
| PROSITE | PS50280. SET. 1 hit. PS00028. ZINC_FINGER_C2H2_1. 8 hits. PS50157. ZINC_FINGER_C2H2_2. 10 hits. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 8579. |
| SOURCE | Search... |
Entry information
| Entry name | EVI1_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q03112 Secondary accession number(s): A1L4F3 Q99917 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| 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. | ||||||||
Relevant documents
| Human chromosome 3 Human chromosome 3: 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 |
| SIMILARITY comments Index of protein domains and families |

Clusters with


