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Protein

Proto-oncogene DBL

Gene

MCF2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Guanine-nucleotide releasing factor

Enzyme and pathway databases

ReactomeiR-HSA-193648. NRAGE signals death through JNK.
R-HSA-194840. Rho GTPase cycle.
R-HSA-416482. G alpha (12/13) signalling events.

Chemistry

SwissLipidsiSLP:000001545.

Names & Taxonomyi

Protein namesi
Recommended name:
Proto-oncogene DBL
Alternative name(s):
Proto-oncogene MCF-2
Cleaved into the following 2 chains:
Gene namesi
Name:MCF2
Synonyms:DBL
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

HGNCiHGNC:6940. MCF2.

Subcellular locationi

  • Cytoplasm 1 Publication
Isoform 3 :
  • Membrane

  • Note: Colocalizes with CDC42 to plasma membrane.

GO - Cellular componenti

  • cytoskeleton Source: ProtInc
  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
  • membrane Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Involvement in diseasei

MCF2 and DBL represent two activated versions of the same proto-oncogene.

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi640 – 6467LLLKELL → IIIRDII: Transformation capability reduced; no stimulation of GDP dissociation. 1 Publication

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

PharmGKBiPA30684.

Polymorphism and mutation databases

BioMutaiMCF2.
DMDMi92087039.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 925925Proto-oncogene DBLPRO_0000030432Add
BLAST
Chaini398 – 925528MCF2-transforming proteinPRO_0000030433Add
BLAST
Chaini498 – 925428DBL-transforming proteinPRO_0000030434Add
BLAST

Post-translational modificationi

Phosphorylation by TNK2 enhances guanine nucleotide exchange factor (GEF) activity toward Rho family proteins.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP10911.
PeptideAtlasiP10911.
PRIDEiP10911.

PTM databases

iPTMnetiP10911.
PhosphoSiteiP10911.

Expressioni

Tissue specificityi

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.1 Publication

Gene expression databases

BgeeiENSG00000101977.
CleanExiHS_MCF2.
ExpressionAtlasiP10911. baseline and differential.
GenevisibleiP10911. HS.

Organism-specific databases

HPAiCAB010423.

Interactioni

Subunit structurei

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 CCPG1.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
NME1P155314EBI-1914514,EBI-741141

Protein-protein interaction databases

BioGridi110336. 10 interactions.
IntActiP10911. 1 interaction.
MINTiMINT-1536978.
STRINGi9606.ENSP00000430276.

Structurei

3D structure databases

ProteinModelPortaliP10911.
SMRiP10911. Positions 491-843.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1 – 8888CRAL-TRIOPROSITE-ProRule annotationAdd
BLAST
Repeati221 – 322102SpectrinAdd
BLAST
Domaini495 – 675181DHPROSITE-ProRule annotationAdd
BLAST
Domaini687 – 809123PHPROSITE-ProRule annotationAdd
BLAST

Domaini

The CRAL-TRIO domain is involved in interaction with inositol phospholipids.
The DH domain is essential for transforming activity and directly catalyzes GDP-GTP exchange activity. It may interact with CCPG1.

Sequence similaritiesi

Belongs to the MCF2 family.Curated
Contains 1 CRAL-TRIO domain.PROSITE-ProRule annotation
Contains 1 DH (DBL-homology) domain.PROSITE-ProRule annotation
Contains 1 PH domain.PROSITE-ProRule annotation
Contains 1 spectrin repeat.Curated

Phylogenomic databases

eggNOGiKOG4240. Eukaryota.
ENOG410XPCA. LUCA.
GeneTreeiENSGT00760000119030.
HOGENOMiHOG000231361.
HOVERGENiHBG062385.
InParanoidiP10911.
OMAiERKDDFQ.
OrthoDBiEOG091G04A2.
PhylomeDBiP10911.
TreeFamiTF318080.

Family and domain databases

Gene3Di1.20.900.10. 1 hit.
2.30.29.30. 1 hit.
InterProiIPR001251. CRAL-TRIO_dom.
IPR000219. DH-domain.
IPR001331. GDS_CDC24_CS.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR018159. Spectrin/alpha-actinin.
[Graphical view]
PfamiPF13716. CRAL_TRIO_2. 1 hit.
PF00169. PH. 1 hit.
PF00621. RhoGEF. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
SM00325. RhoGEF. 1 hit.
SM00150. SPEC. 1 hit.
[Graphical view]
SUPFAMiSSF48065. SSF48065. 1 hit.
SSF50729. SSF50729. 1 hit.
PROSITEiPS50191. CRAL_TRIO. 1 hit.
PS00741. DH_1. 1 hit.
PS50010. DH_2. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
[Graphical view]

Sequences (6)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P10911-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MAEANPRRGK MRFRRNAASF PGNLHLVLVL RPTSFLQRTF TDIGFWFSQE
60 70 80 90 100
DFMLKLPVVM LSSVSDLLTY IDDKQLTPEL GGTLQYCHSE WIIFRNAIEN
110 120 130 140 150
FALTVKEMAQ MLQSFGTELA ETELPDDIPS IEEILAIRAE RYHLLKNDIT
160 170 180 190 200
AVTKEGKILL TNLEVPDTEG AVSSRLECHR QISGDWQTIN KLLTQVHDME
210 220 230 240 250
TAFDGFWEKH QLKMEQYLQL WKFEQDFQQL VTEVEFLLNQ QAELADVTGT
260 270 280 290 300
IAQVKQKIKK LENLDENSQE LLSKAQFVIL HGHKLAANHH YALDLICQRC
310 320 330 340 350
NELRYLSDIL VNEIKAKRIQ LSRTFKMHKL LQQARQCCDE GECLLANQEI
360 370 380 390 400
DKFQSKEDAQ KALQDIENFL EMALPFINYE PETLQYEFDV ILSPELKVQM
410 420 430 440 450
KTIQLKLENI RSIFENQQAG FRNLADKHVR PIQFVVPTPE NLVTSGTPFF
460 470 480 490 500
SSKQGKKTWR QNQSNLKIEV VPDCQEKRSS GPSSSLDNGN SLDVLKNHVL
510 520 530 540 550
NELIQTERVY VRELYTVLLG YRAEMDNPEM FDLMPPLLRN KKDILFGNMA
560 570 580 590 600
EIYEFHNDIF LSSLENCAHA PERVGPCFLE RKDDFQMYAK YCQNKPRSET
610 620 630 640 650
IWRKYSECAF FQECQRKLKH RLRLDSYLLK PVQRITKYQL LLKELLKYSK
660 670 680 690 700
DCEGSALLKK ALDAMLDLLK SVNDSMHQIA INGYIGNLNE LGKMIMQGGF
710 720 730 740 750
SVWIGHKKGA TKMKDLARFK PMQRHLFLYE KAIVFCKRRV ESGEGSDRYP
760 770 780 790 800
SYSFKHCWKM DEVGITEYVK GDNRKFEIWY GEKEEVYIVQ ASNVDVKMTW
810 820 830 840 850
LKEIRNILLK QQELLTVKKR KQQDQLTERD KFQISLQQND EKQQGAFIST
860 870 880 890 900
EETELEHTST VVEVCEAIAS VQAEANTVWT EASQSAEISE EPAEWSSNYF
910 920
YPTYDENEEE NRPLMRPVSE MALLY
Length:925
Mass (Da):107,673
Last modified:March 7, 2006 - v3
Checksum:i96233C7AFC85D637
GO
Isoform 2 (identifier: P10911-2) [UniParc]FASTAAdd to basket
Also known as: Var.2

The sequence of this isoform differs from the canonical sequence as follows:
     842-860: KQQGAFISTEETELEHTST → DLCRRWLSYIDEATMSNGK
     861-925: Missing.

Show »
Length:860
Mass (Da):100,409
Checksum:iCCD14CA833425027
GO
Isoform 3 (identifier: P10911-3) [UniParc]FASTAAdd to basket
Also known as: Var.3

The sequence of this isoform differs from the canonical sequence as follows:
     1-17: MAEANPRRGKMRFRRNA → MQDIAFLSGG...SLKISLQKIS

Show »
Length:985
Mass (Da):114,376
Checksum:i8D0C81505593C040
GO
Isoform 4 (identifier: P10911-4) [UniParc]FASTAAdd to basket
Also known as: Var.4

The sequence of this isoform differs from the canonical sequence as follows:
     454-454: Q → QVGVGYSFFQACKLFSK

Show »
Length:941
Mass (Da):109,436
Checksum:iC5B1B4F9F368AC16
GO
Isoform 5 (identifier: P10911-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-17: MAEANPRRGKMRFRRNA → MQDIAFLSGG...SLKISLQKIS
     454-454: Q → QVGVGYSFFQACKLFSK

Show »
Length:1,001
Mass (Da):116,139
Checksum:i8D7277D0703671B3
GO
Isoform 6 (identifier: P10911-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     58-96: Missing.
     842-860: KQQGAFISTEETELEHTST → DLCRRWLSYIDEATMSNGK
     861-925: Missing.

Note: No experimental confirmation available.
Show »
Length:821
Mass (Da):95,940
Checksum:i4FAD1AAA126237A8
GO

Sequence cautioni

The sequence AAA52172 differs from that shown. Reason: Erroneous initiation. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti54 – 541L → P (PubMed:3056717).Curated
Sequence conflicti54 – 541L → P (PubMed:12445822).Curated
Sequence conflicti178 – 1781C → S in BAH12371 (PubMed:14702039).Curated
Sequence conflicti330 – 3301L → F in BAH14787 (PubMed:14702039).Curated
Sequence conflicti358 – 3581D → Y in BAH12371 (PubMed:14702039).Curated
Sequence conflicti634 – 6341R → Q (PubMed:3281159).Curated
Sequence conflicti687 – 6871N → I in BAH14787 (PubMed:14702039).Curated
Sequence conflicti886 – 8861A → V (PubMed:2577874).Curated
Sequence conflicti900 – 9001F → S in BAH13855 (PubMed:14702039).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 1717MAEAN…FRRNA → MQDIAFLSGGRGKDNAWIIT FPENCNFRCIPEEVIAKVLT YLTSIARQNGSDSRFTIILD RRLDTWSSLKISLQKIS in isoform 3 and isoform 5. 3 PublicationsVSP_008150Add
BLAST
Alternative sequencei58 – 9639Missing in isoform 6. 1 PublicationVSP_046118Add
BLAST
Alternative sequencei454 – 4541Q → QVGVGYSFFQACKLFSK in isoform 4 and isoform 5. 2 PublicationsVSP_008153
Alternative sequencei842 – 86019KQQGA…EHTST → DLCRRWLSYIDEATMSNGK in isoform 2 and isoform 6. 2 PublicationsVSP_008151Add
BLAST
Alternative sequencei861 – 92565Missing in isoform 2 and isoform 6. 2 PublicationsVSP_008152Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X12556 mRNA. Translation: CAA31069.1.
AB085901 mRNA. Translation: BAC41200.1.
AB085902 mRNA. Translation: BAC41201.1.
AL117234 mRNA. Translation: CAB55301.1.
AK296488 mRNA. Translation: BAH12371.1.
AK302957 mRNA. Translation: BAH13855.1.
AK316416 mRNA. Translation: BAH14787.1.
AL033403 Genomic DNA. Translation: CAA21955.1.
AL033403 Genomic DNA. Translation: CAI42107.1.
AL033403 Genomic DNA. Translation: CAI42108.1.
AL161777 Genomic DNA. No translation available.
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.
CCDSiCCDS14667.1. [P10911-1]
CCDS48175.1. [P10911-3]
CCDS55514.1. [P10911-6]
CCDS55515.1. [P10911-2]
CCDS55516.1. [P10911-4]
CCDS55517.1. [P10911-5]
PIRiA28051. TVHUBD.
A30040. TVHUDB.
S10138.
RefSeqiNP_001093325.1. NM_001099855.1. [P10911-3]
NP_001165347.1. NM_001171876.1. [P10911-5]
NP_001165348.1. NM_001171877.1. [P10911-6]
NP_001165349.1. NM_001171878.1. [P10911-2]
NP_001165350.1. NM_001171879.1. [P10911-4]
NP_005360.3. NM_005369.4. [P10911-1]
XP_011529641.1. XM_011531339.2. [P10911-5]
UniGeneiHs.387262.

Genome annotation databases

EnsembliENST00000338585; ENSP00000342204; ENSG00000101977. [P10911-4]
ENST00000370573; ENSP00000359605; ENSG00000101977. [P10911-2]
ENST00000370576; ENSP00000359608; ENSG00000101977. [P10911-1]
ENST00000414978; ENSP00000397055; ENSG00000101977. [P10911-3]
ENST00000519895; ENSP00000430276; ENSG00000101977. [P10911-5]
ENST00000520602; ENSP00000427745; ENSG00000101977. [P10911-3]
ENST00000536274; ENSP00000438155; ENSG00000101977. [P10911-6]
GeneIDi4168.
KEGGihsa:4168.
UCSCiuc004fau.4. human. [P10911-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X12556 mRNA. Translation: CAA31069.1.
AB085901 mRNA. Translation: BAC41200.1.
AB085902 mRNA. Translation: BAC41201.1.
AL117234 mRNA. Translation: CAB55301.1.
AK296488 mRNA. Translation: BAH12371.1.
AK302957 mRNA. Translation: BAH13855.1.
AK316416 mRNA. Translation: BAH14787.1.
AL033403 Genomic DNA. Translation: CAA21955.1.
AL033403 Genomic DNA. Translation: CAI42107.1.
AL033403 Genomic DNA. Translation: CAI42108.1.
AL161777 Genomic DNA. No translation available.
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.
CCDSiCCDS14667.1. [P10911-1]
CCDS48175.1. [P10911-3]
CCDS55514.1. [P10911-6]
CCDS55515.1. [P10911-2]
CCDS55516.1. [P10911-4]
CCDS55517.1. [P10911-5]
PIRiA28051. TVHUBD.
A30040. TVHUDB.
S10138.
RefSeqiNP_001093325.1. NM_001099855.1. [P10911-3]
NP_001165347.1. NM_001171876.1. [P10911-5]
NP_001165348.1. NM_001171877.1. [P10911-6]
NP_001165349.1. NM_001171878.1. [P10911-2]
NP_001165350.1. NM_001171879.1. [P10911-4]
NP_005360.3. NM_005369.4. [P10911-1]
XP_011529641.1. XM_011531339.2. [P10911-5]
UniGeneiHs.387262.

3D structure databases

ProteinModelPortaliP10911.
SMRiP10911. Positions 491-843.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110336. 10 interactions.
IntActiP10911. 1 interaction.
MINTiMINT-1536978.
STRINGi9606.ENSP00000430276.

Chemistry

SwissLipidsiSLP:000001545.

PTM databases

iPTMnetiP10911.
PhosphoSiteiP10911.

Polymorphism and mutation databases

BioMutaiMCF2.
DMDMi92087039.

Proteomic databases

PaxDbiP10911.
PeptideAtlasiP10911.
PRIDEiP10911.

Protocols and materials databases

DNASUi4168.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000338585; ENSP00000342204; ENSG00000101977. [P10911-4]
ENST00000370573; ENSP00000359605; ENSG00000101977. [P10911-2]
ENST00000370576; ENSP00000359608; ENSG00000101977. [P10911-1]
ENST00000414978; ENSP00000397055; ENSG00000101977. [P10911-3]
ENST00000519895; ENSP00000430276; ENSG00000101977. [P10911-5]
ENST00000520602; ENSP00000427745; ENSG00000101977. [P10911-3]
ENST00000536274; ENSP00000438155; ENSG00000101977. [P10911-6]
GeneIDi4168.
KEGGihsa:4168.
UCSCiuc004fau.4. human. [P10911-1]

Organism-specific databases

CTDi4168.
GeneCardsiMCF2.
HGNCiHGNC:6940. MCF2.
HPAiCAB010423.
MIMi311030. gene.
neXtProtiNX_P10911.
PharmGKBiPA30684.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4240. Eukaryota.
ENOG410XPCA. LUCA.
GeneTreeiENSGT00760000119030.
HOGENOMiHOG000231361.
HOVERGENiHBG062385.
InParanoidiP10911.
OMAiERKDDFQ.
OrthoDBiEOG091G04A2.
PhylomeDBiP10911.
TreeFamiTF318080.

Enzyme and pathway databases

ReactomeiR-HSA-193648. NRAGE signals death through JNK.
R-HSA-194840. Rho GTPase cycle.
R-HSA-416482. G alpha (12/13) signalling events.

Miscellaneous databases

ChiTaRSiMCF2. human.
GeneWikiiMCF2.
GenomeRNAii4168.
PROiP10911.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000101977.
CleanExiHS_MCF2.
ExpressionAtlasiP10911. baseline and differential.
GenevisibleiP10911. HS.

Family and domain databases

Gene3Di1.20.900.10. 1 hit.
2.30.29.30. 1 hit.
InterProiIPR001251. CRAL-TRIO_dom.
IPR000219. DH-domain.
IPR001331. GDS_CDC24_CS.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR018159. Spectrin/alpha-actinin.
[Graphical view]
PfamiPF13716. CRAL_TRIO_2. 1 hit.
PF00169. PH. 1 hit.
PF00621. RhoGEF. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
SM00325. RhoGEF. 1 hit.
SM00150. SPEC. 1 hit.
[Graphical view]
SUPFAMiSSF48065. SSF48065. 1 hit.
SSF50729. SSF50729. 1 hit.
PROSITEiPS50191. CRAL_TRIO. 1 hit.
PS00741. DH_1. 1 hit.
PS50010. DH_2. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMCF2_HUMAN
AccessioniPrimary (citable) accession number: P10911
Secondary accession number(s): B7Z3Y5
, B7Z869, B7ZAV1, E9PH77, F5H091, P14919, Q5JYJ2, Q5JYJ3, Q5JYJ4, Q8IUF3, Q8IUF4, Q9UJB3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: March 7, 2006
Last modified: September 7, 2016
This is version 176 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.