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Protein

Proto-oncogene DBL

Gene

MCF2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Keywordsi

Molecular functionGuanine-nucleotide releasing factor

Enzyme and pathway databases

ReactomeiR-HSA-193634 Axonal growth inhibition (RHOA activation)
R-HSA-193648 NRAGE signals death through JNK
R-HSA-194840 Rho GTPase cycle
R-HSA-416482 G alpha (12/13) signalling events

Chemistry databases

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

EuPathDBiHostDB:ENSG00000101977.19
HGNCiHGNC:6940 MCF2
MIMi311030 gene
neXtProtiNX_P10911

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Involvement in diseasei

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

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi640 – 646LLLKELL → IIIRDII: Transformation capability reduced; no stimulation of GDP dissociation. 1 Publication7

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

DisGeNETi4168
OpenTargetsiENSG00000101977
PharmGKBiPA30684

Polymorphism and mutation databases

BioMutaiMCF2
DMDMi92087039

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000304321 – 925Proto-oncogene DBLAdd BLAST925
ChainiPRO_0000030433398 – 925MCF2-transforming proteinAdd BLAST528
ChainiPRO_0000030434498 – 925DBL-transforming proteinAdd BLAST428

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
PhosphoSitePlusiP10911

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

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

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi110336, 10 interactors
CORUMiP10911
IntActiP10911, 2 interactors
MINTiP10911
STRINGi9606.ENSP00000430276

Structurei

3D structure databases

ProteinModelPortaliP10911
SMRiP10911
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 88CRAL-TRIOPROSITE-ProRule annotationAdd BLAST88
Repeati221 – 322SpectrinAdd BLAST102
Domaini495 – 675DHPROSITE-ProRule annotationAdd BLAST181
Domaini687 – 809PHPROSITE-ProRule annotationAdd BLAST123

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

Phylogenomic databases

eggNOGiKOG4240 Eukaryota
ENOG410XPCA LUCA
GeneTreeiENSGT00760000119030
HOGENOMiHOG000231361
HOVERGENiHBG062385
InParanoidiP10911
KOiK20685
OMAiWIITFPE
OrthoDBiEOG091G04A2
PhylomeDBiP10911
TreeFamiTF318080

Family and domain databases

CDDicd00160 RhoGEF, 1 hit
Gene3Di1.20.900.10, 1 hit
2.30.29.30, 1 hit
InterProiView protein in InterPro
IPR001251 CRAL-TRIO_dom
IPR035899 DBL_dom_sf
IPR000219 DH-domain
IPR001331 GDS_CDC24_CS
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
IPR018159 Spectrin/alpha-actinin
PfamiView protein in Pfam
PF13716 CRAL_TRIO_2, 1 hit
PF00169 PH, 1 hit
PF00621 RhoGEF, 1 hit
SMARTiView protein in SMART
SM00233 PH, 1 hit
SM00325 RhoGEF, 1 hit
SM00150 SPEC, 1 hit
SUPFAMiSSF48065 SSF48065, 1 hit
PROSITEiView protein in PROSITE
PS50191 CRAL_TRIO, 1 hit
PS00741 DH_1, 1 hit
PS50010 DH_2, 1 hit
PS50003 PH_DOMAIN, 1 hit

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)DescriptionActionsGraphical viewLength
Sequence conflicti54L → P (PubMed:3056717).Curated1
Sequence conflicti54L → P (PubMed:12445822).Curated1
Sequence conflicti178C → S in BAH12371 (PubMed:14702039).Curated1
Sequence conflicti330L → F in BAH14787 (PubMed:14702039).Curated1
Sequence conflicti358D → Y in BAH12371 (PubMed:14702039).Curated1
Sequence conflicti634R → Q (PubMed:3281159).Curated1
Sequence conflicti687N → I in BAH14787 (PubMed:14702039).Curated1
Sequence conflicti886A → V (PubMed:2577874).Curated1
Sequence conflicti900F → S in BAH13855 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0081501 – 17MAEAN…FRRNA → MQDIAFLSGGRGKDNAWIIT FPENCNFRCIPEEVIAKVLT YLTSIARQNGSDSRFTIILD RRLDTWSSLKISLQKIS in isoform 3 and isoform 5. 3 PublicationsAdd BLAST17
Alternative sequenceiVSP_04611858 – 96Missing in isoform 6. 1 PublicationAdd BLAST39
Alternative sequenceiVSP_008153454Q → QVGVGYSFFQACKLFSK in isoform 4 and isoform 5. 2 Publications1
Alternative sequenceiVSP_008151842 – 860KQQGA…EHTST → DLCRRWLSYIDEATMSNGK in isoform 2 and isoform 6. 2 PublicationsAdd BLAST19
Alternative sequenceiVSP_008152861 – 925Missing in isoform 2 and isoform 6. 2 PublicationsAdd BLAST65

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 No translation available.
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]
XP_016885020.1, XM_017029531.1 [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

Similar proteinsi

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 historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: March 7, 2006
Last modified: March 28, 2018
This is version 191 of the entry and version 3 of the sequence. See 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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health