P10911 (MCF2_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
January 25, 2012.
Version 130.
History...
Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: Proto-oncogene DBL Alternative name(s): Proto-oncogene MCF-2 Cleaved into the following 2 chains: | ||||
| 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 | 925 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | Guanine nucleotide exchange factor (GEF) that modulates the Rho family of GTPases. Promotes the conversion of some member of the Rho family GTPase from the GDP-bound to the GTP-bound form. Isoform 1 exhibits no activity toward RHOA, RAC1 or CDC42. Isoform 2 exhibits decreased GEF activity toward CDC42. Isoform 3 exhibits a weak but significant activity toward RAC1 and CDC42. Isoform 4 exhibits significant activity toward RHOA and CDC42. The truncated DBL oncogene is active toward RHOA, RAC1 and CDC42. |
| Subunit structure | Interacts with an array of inositol phospholipids such as phosphatidylinositol 3-phosphate (PI3P), phosphatidylinositol 4-phosphate (PI4P) and phosphatidylinositol 5-phosphate (PI5P). May interact with CCPG1. Ref.12 Ref.13 |
| Subcellular location | Isoform 3: Membrane. Note: Colocalizes with CDC42 to plasma membrane. Ref.12 |
| Tissue specificity | Isoform 1 is expressed only in brain. Isoform 3 is expressed in heart, kidney, spleen, liver and testis. Isoform 4 is expressed in brain, heart, kidney, testis, placenta, stomach and peripheral blood. The protein is detectable in brain, heart, kidney, intestine, muscle, lung and testis. Ref.3 |
| Domain | The CRAL-TRIO domain is involved in interaction with inositol phospholipids. Ref.9 Ref.10 Ref.12 The DH domain is essential for transforming activity and directly catalyzes GDP-GTP exchange activity. It may interact with CCPG1. Ref.9 Ref.10 Ref.12 |
| Post-translational modification | Phosphorylation by TNK2 enhances guanine nucleotide exchange factor (GEF) activity toward Rho family proteins. |
| Involvement in disease | Note=MCF2 and DBL represent two activated versions of the same proto-oncogene. |
| Sequence similarities | Belongs to the MCF2 family. Contains 1 CRAL-TRIO domain. Contains 1 DH (DBL-homology) domain. Contains 1 PH domain. Contains 1 spectrin repeat. |
| Sequence caution | The sequence AAA52172.1 differs from that shown. Reason: Erroneous initiation. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| NME1 | P15531 | 13 | EBI-1914514,EBI-741141 |
Alternative products
| This entry describes 4 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: P10911-1) Also known as: Var.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 2 (identifier: P10911-2) Also known as: Var.2; The sequence of this isoform differs from the canonical sequence as follows: 842-860: KQQGAFISTEETELEHTST → DLCRRWLSYIDEATMSNGK 861-925: Missing. | ||||||
| Isoform 3 (identifier: P10911-3) Also known as: Var.3; The sequence of this isoform differs from the canonical sequence as follows: 1-17: MAEANPRRGKMRFRRNA → MQDIAFLSGG...SLKISLQKIS | ||||||
| Isoform 4 (identifier: P10911-4) Also known as: Var.4; The sequence of this isoform differs from the canonical sequence as follows: 454-454: Q → QVGVGYSFFQACKLFSK |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 925 | 925 | Proto-oncogene DBL | PRO_0000030432 | |||||
| Chain | 398 – 925 | 528 | MCF2-transforming protein | PRO_0000030433 | |||||
| Chain | 498 – 925 | 428 | DBL-transforming protein | PRO_0000030434 | |||||
Regions | |||||||||
| Domain | 1 – 88 | 88 | CRAL-TRIO | ||||||
| Repeat | 221 – 322 | 102 | Spectrin | ||||||
| Domain | 495 – 675 | 181 | DH | ||||||
| Domain | 687 – 809 | 123 | PH | ||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 17 | 17 | MAEAN…FRRNA → MQDIAFLSGGRGKDNAWIIT FPENCNFRCIPEEVIAKVLT YLTSIARQNGSDSRFTIILD RRLDTWSSLKISLQKIS in isoform 3. | VSP_008150 | |||||
| Alternative sequence | 454 | 1 | Q → QVGVGYSFFQACKLFSK in isoform 4. | VSP_008153 | |||||
| Alternative sequence | 842 – 860 | 19 | KQQGA…EHTST → DLCRRWLSYIDEATMSNGK in isoform 2. | VSP_008151 | |||||
| Alternative sequence | 861 – 925 | 65 | Missing in isoform 2. | VSP_008152 | |||||
Experimental info | |||||||||
| Mutagenesis | 640 – 646 | 7 | LLLKELL → IIIRDII: Transformation capability reduced; no stimulation of GDP dissociation. | ||||||
| Sequence conflict | 54 | 1 | L → P Ref.1 | ||||||
| Sequence conflict | 54 | 1 | L → P Ref.3 | ||||||
| Sequence conflict | 634 | 1 | R → Q Ref.7 | ||||||
| Sequence conflict | 886 | 1 | A → V Ref.8 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Molecular cloning and characterization of the human dbl proto-oncogene: evidence that its overexpression is sufficient to transform NIH/3T3 cells." Ron D., Tronick S.R., Aaronson S.A., Eva A. EMBO J. 7:2465-2473(1988) [PubMed: 3056717] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Brain. |
| [2] | Ron D. Submitted (JUN-1989) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION. |
| [3] | "Alternative splicing variants of the human DBL (MCF-2) proto-oncogene." Komai K., Okayama R., Kitagawa M., Yagi H., Chihara K., Shiozawa S. Biochem. Biophys. Res. Commun. 299:455-458(2002) [PubMed: 12445822] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 4), TISSUE SPECIFICITY, CHARACTERIZATION. |
| [4] | Rhodes S., Huckle E. Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). |
| [5] | "The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. Bentley D.R.Nature 434:325-337(2005) [PubMed: 15772651] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [6] | 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. Venter J.C.Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [7] | "The predicted DBL oncogene product defines a distinct class of transforming proteins." Eva A., Vecchio G., Rao C.D., Tronick S.R., Aaronson S.A. Proc. Natl. Acad. Sci. U.S.A. 85:2061-2065(1988) [PubMed: 3281159] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 498-925 (ISOFORM 1). |
| [8] | "Activation of a mcf.2 oncogene by deletion of amino-terminal coding sequences." Noguchi T., Galland F., Batoz M., Mattei M.-G., Birnbaum D. Oncogene 3:709-715(1988) [PubMed: 2577874] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 398-925 (ISOFORM 1). |
| [9] | "A region of proto-dbl essential for its transforming activity shows sequence similarity to a yeast cell cycle gene, CDC24, and the human breakpoint cluster gene, bcr." Ron D., Zannini M., Lewis M., Wickner R.B., Hunt L.T., Graziani G., Tronick S.R., Aaronson S.A., Eva A. New Biol. 3:372-379(1991) [PubMed: 2065022] [Abstract] Cited for: DOMAIN DBL-HOMOLOGY, MUTAGENESIS. |
| [10] | "Cellular transformation and guanine nucleotide exchange activity are catalyzed by a common domain on the dbl oncogene product." Hart M.J., Eva A., Zangrilli D., Aaronson S.A., Evans T., Cerione R.A., Zheng Y. J. Biol. Chem. 269:62-65(1994) [PubMed: 8276860] [Abstract] Cited for: CHARACTERIZATION OF DBL DOMAIN. |
| [11] | "Activation of the guanine nucleotide exchange factor Dbl following ACK1-dependent tyrosine phosphorylation." Kato J., Kaziro Y., Satoh T. Biochem. Biophys. Res. Commun. 268:141-147(2000) [PubMed: 10652228] [Abstract] Cited for: PHOSPHORYLATION BY TNK2. |
| [12] | "Role of the Sec14-like domain of Dbl family exchange factors in the regulation of Rho family GTPases in different subcellular sites." Ueda S., Kataoka T., Satoh T. Cell. Signal. 16:899-906(2004) [PubMed: 15157669] [Abstract] Cited for: SUBCELLULAR LOCATION, DOMAIN CRAL-TRIO, INTERACTION WITH INOSITOL PHOSPHOLIPIDS. |
| [13] | "Ccpg1, a novel scaffold protein that regulates the activity of the Rho guanine nucleotide exchange factor Dbs." Kostenko E.V., Olabisi O.O., Sahay S., Rodriguez P.L., Whitehead I.P. Mol. Cell. Biol. 26:8964-8975(2006) [PubMed: 17000758] [Abstract] Cited for: POSSIBLE INTERACTION WITH CCPG1. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | X12556 mRNA. Translation: CAA31069.1. AB085901 mRNA. Translation: BAC41200.1. AB085902 mRNA. Translation: BAC41201.1. AL117234 mRNA. Translation: CAB55301.1. AL033403 Genomic DNA. Translation: CAA21955.1. AL033403 Genomic DNA. Translation: CAI42107.1. AL033403 Genomic DNA. Translation: CAI42108.1. CH471150 Genomic DNA. Translation: EAW88427.1. CH471150 Genomic DNA. Translation: EAW88430.1. J03639 mRNA. Translation: AAA52172.1. Different initiation. X13230 mRNA. Translation: CAA31617.1. Sequence problems. |
| IPI | IPI00339309. IPI00339310. IPI00339312. IPI00641162. |
| PIR | TVHUBD. A28051. TVHUDB. A30040. S10138. |
| RefSeq | NP_001093325.1. NM_001099855.1. NP_001165347.1. NM_001171876.1. NP_001165348.1. NM_001171877.1. NP_001165349.1. NM_001171878.1. NP_001165350.1. NM_001171879.1. NP_005360.3. NM_005369.4. |
| UniGene | Hs.387262. |
3D structure databases | |
| ProteinModelPortal | P10911. |
| SMR | P10911. Positions 216-322, 491-811. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | P10911. 2 interactions. |
| STRING | P10911. |
PTM databases | |
| PhosphoSite | P10911. |
Polymorphism databases | |
| DMDM | 92087039. |
Proteomic databases | |
| PRIDE | P10911. |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000370576; ENSP00000359608; ENSG00000101977. |
| GeneID | 4168. |
| KEGG | hsa:4168. |
| UCSC | uc004fau.2. human. uc004faw.2. human. |
Organism-specific databases | |
| CTD | 4168. |
| GeneCards | GC0XM138663. |
| HGNC | HGNC:6940. MCF2. |
| HPA | CAB010423. |
| MIM | 311030. gene. |
| neXtProt | NX_P10911. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | prNOG10403. |
| HOVERGEN | HBG062385. |
Enzyme and pathway databases | |
| Reactome | REACT_111102. Signal Transduction. |
Gene expression databases | |
| ArrayExpress | P10911. |
| Bgee | P10911. |
| CleanEx | HS_MCF2. |
| Genevestigator | P10911. |
| GermOnline | ENSG00000101977. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR001251. CRAL-TRIO_dom. IPR000219. DH-domain. IPR001331. GDS_CDC24_CS. IPR011993. PH_type. IPR001849. Pleckstrin_homology. IPR018159. Spectrin/alpha-actinin. [Graphical view] |
| Gene3D | G3DSA:2.30.29.30. PH_type. 1 hit. G3DSA:1.20.900.10. RhoGEF. 1 hit. |
| Pfam | PF00621. RhoGEF. 1 hit. [Graphical view] |
| SMART | SM00233. PH. 1 hit. SM00325. RhoGEF. 1 hit. SM00150. SPEC. 1 hit. [Graphical view] |
| SUPFAM | SSF48065. DH-domain. 1 hit. |
| PROSITE | PS50191. CRAL_TRIO. 1 hit. PS00741. DH_1. 1 hit. PS50010. DH_2. 1 hit. PS50003. PH_DOMAIN. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other | |
| NextBio | 16414. |
| SOURCE | Search... |
Entry information
| Entry name | MCF2_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P10911 Secondary accession number(s): P14919 Q9UJB3 | ||||||||
| Entry 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. | ||||||||
Relevant documents
| Human chromosome X Human chromosome X: entries, gene names and cross-references to MIM |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

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