MCF2L_MOUSE
ID MCF2L_MOUSE Reviewed; 1149 AA.
AC Q64096; E9PV70;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 25-MAY-2022, entry version 167.
DE RecName: Full=Guanine nucleotide exchange factor DBS;
DE AltName: Full=DBL's big sister;
DE AltName: Full=MCF2-transforming sequence-like protein;
GN Name=Mcf2l; Synonyms=Dbs;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Hematopoietic;
RX PubMed=7862449;
RA Whitehead I., Kirk H., Kay R.;
RT "Retroviral transduction and oncogenic selection of a cDNA encoding Dbs, a
RT homolog of the Dbl guanine nucleotide exchange factor.";
RL Oncogene 10:713-721(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic brain;
RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200;
RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.;
RT "Phosphoproteomic analysis of the developing mouse brain.";
RL Mol. Cell. Proteomics 3:1093-1101(2004).
RN [4]
RP FUNCTION, INTERACTION WITH CCPG1, AND SUBCELLULAR LOCATION.
RX PubMed=17000758; DOI=10.1128/mcb.00670-06;
RA Kostenko E.V., Olabisi O.O., Sahay S., Rodriguez P.L., Whitehead I.P.;
RT "Ccpg1, a novel scaffold protein that regulates the activity of the Rho
RT guanine nucleotide exchange factor Dbs.";
RL Mol. Cell. Biol. 26:8964-8975(2006).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-621; THR-622; SER-1033;
RP SER-1034; SER-1041 AND SER-1042, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, and Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 623-967 IN COMPLEX WITH CDC42, AND
RP FUNCTION.
RX PubMed=11889037; DOI=10.1093/emboj/21.6.1315;
RA Rossman K.L., Worthylake D.K., Snyder J.T., Siderovski D.P., Campbell S.L.,
RA Sondek J.;
RT "A crystallographic view of interactions between Dbs and Cdc42: PH domain-
RT assisted guanine nucleotide exchange.";
RL EMBO J. 21:1315-1326(2002).
RN [7] {ECO:0007744|PDB:1LB1}
RP X-RAY CRYSTALLOGRAPHY (2.81 ANGSTROMS) OF 623-967 IN COMPLEX WITH RHOA, AND
RP FUNCTION.
RX PubMed=12006984; DOI=10.1038/nsb796;
RA Snyder J.T., Worthylake D.K., Rossman K.L., Betts L., Pruitt W.M.,
RA Siderovski D.P., Der C.J., Sondek J.;
RT "Structural basis for the selective activation of Rho GTPases by Dbl
RT exchange factors.";
RL Nat. Struct. Biol. 9:468-475(2002).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 498-843.
RX PubMed=15274927; DOI=10.1016/j.str.2004.03.021;
RA Worthylake D.K., Rossman K.L., Sondek J.;
RT "Crystal structure of the DH/PH fragment of Dbs without bound GTPase.";
RL Structure 12:1078-1086(2004).
CC -!- FUNCTION: Guanine nucleotide exchange factor that catalyzes guanine
CC nucleotide exchange on RHOA and CDC42, and thereby contributes to the
CC regulation of RHOA and CDC42 signaling pathways (PubMed:17000758,
CC PubMed:11889037, PubMed:12006984). Seems to lack activity with RAC1.
CC Becomes activated and highly tumorigenic by truncation of the N-
CC terminus (By similarity). {ECO:0000250|UniProtKB:Q63406,
CC ECO:0000269|PubMed:11889037, ECO:0000269|PubMed:12006984}.
CC -!- SUBUNIT: Interacts with GTP-bound RAC1 (By similarity). Interacts with
CC CDC42 (PubMed:11889037). Interacts with RHOA (PubMed:12006984).
CC Interacts with CCPG1, which results in specific inhibition of its
CC exchange activity toward RHOA, but does not affect its activity on
CC CDC42 (PubMed:17000758). {ECO:0000250|UniProtKB:Q63406,
CC ECO:0000269|PubMed:17000758}.
CC -!- INTERACTION:
CC Q64096; P60953-2: CDC42; Xeno; NbExp=4; IntAct=EBI-602123, EBI-287394;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17000758}. Cell
CC membrane {ECO:0000269|PubMed:17000758}; Peripheral membrane protein
CC {ECO:0000269|PubMed:17000758}; Cytoplasmic side
CC {ECO:0000269|PubMed:17000758}.
CC -!- TISSUE SPECIFICITY: Expressed at low levels in several hemopoietic cell
CC lines and in thymus and spleen, and at higher levels in other tissues,
CC particularly in brain. {ECO:0000269|PubMed:7862449}.
CC -!- DOMAIN: The DH domain is involved in interaction with CCPG1.
CC {ECO:0000269|PubMed:17000758}.
CC -!- DOMAIN: The CRAL-TRIO domain mediates interaction with various inositol
CC phospholipids, such as phosphatidylinositol 3-phosphate (PI3P),
CC phosphatidylinositol 4-phosphate (PI4P) and phosphatidylinositol 5-
CC phosphate (PI5P). {ECO:0000250|UniProtKB:O15068}.
CC -!- SIMILARITY: Belongs to the MCF2 family. {ECO:0000305}.
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DR EMBL; S76838; AAB33461.2; -; mRNA.
DR EMBL; AC127308; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC134581; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS90372.1; -.
DR PDB; 1KZ7; X-ray; 2.40 A; A/C=623-967.
DR PDB; 1KZG; X-ray; 2.60 A; A/C=623-967.
DR PDB; 1LB1; X-ray; 2.81 A; A/C/E/G=623-967.
DR PDB; 1RJ2; X-ray; 3.00 A; A/D/G/J=623-968.
DR PDBsum; 1KZ7; -.
DR PDBsum; 1KZG; -.
DR PDBsum; 1LB1; -.
DR PDBsum; 1RJ2; -.
DR AlphaFoldDB; Q64096; -.
DR SMR; Q64096; -.
DR DIP; DIP-34544N; -.
DR IntAct; Q64096; 4.
DR MINT; Q64096; -.
DR STRING; 10090.ENSMUSP00000106500; -.
DR iPTMnet; Q64096; -.
DR PhosphoSitePlus; Q64096; -.
DR EPD; Q64096; -.
DR MaxQB; Q64096; -.
DR PRIDE; Q64096; -.
DR ProteomicsDB; 295979; -.
DR MGI; MGI:103263; Mcf2l.
DR eggNOG; KOG4240; Eukaryota.
DR InParanoid; Q64096; -.
DR Reactome; R-MMU-193648; NRAGE signals death through JNK.
DR Reactome; R-MMU-416482; G alpha (12/13) signalling events.
DR Reactome; R-MMU-8980692; RHOA GTPase cycle.
DR Reactome; R-MMU-9013026; RHOB GTPase cycle.
DR Reactome; R-MMU-9013106; RHOC GTPase cycle.
DR Reactome; R-MMU-9013148; CDC42 GTPase cycle.
DR Reactome; R-MMU-9013149; RAC1 GTPase cycle.
DR Reactome; R-MMU-9013408; RHOG GTPase cycle.
DR ChiTaRS; Mcf2l; mouse.
DR EvolutionaryTrace; Q64096; -.
DR PRO; PR:Q64096; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q64096; protein.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0012505; C:endomembrane system; ISO:MGI.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; ISO:MGI.
DR GO; GO:0019898; C:extrinsic component of membrane; ISS:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; IDA:MGI.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0005545; F:1-phosphatidylinositol binding; IDA:MGI.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:MGI.
DR GO; GO:0035091; F:phosphatidylinositol binding; ISO:MGI.
DR GO; GO:0035025; P:positive regulation of Rho protein signal transduction; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IGI:MGI.
DR GO; GO:0007266; P:Rho protein signal transduction; IDA:MGI.
DR CDD; cd01227; PH_Dbs; 1.
DR CDD; cd00160; RhoGEF; 1.
DR CDD; cd00170; SEC14; 1.
DR CDD; cd11857; SH3_DBS; 1.
DR CDD; cd00176; SPEC; 1.
DR Gene3D; 1.20.900.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR001251; CRAL-TRIO_dom.
DR InterPro; IPR036865; CRAL-TRIO_dom_sf.
DR InterPro; IPR035899; DBL_dom_sf.
DR InterPro; IPR035534; DBS_PH.
DR InterPro; IPR035532; DBS_SH3.
DR InterPro; IPR000219; DH-domain.
DR InterPro; IPR001331; GDS_CDC24_CS.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR InterPro; IPR018159; Spectrin/alpha-actinin.
DR InterPro; IPR002017; Spectrin_repeat.
DR Pfam; PF13716; CRAL_TRIO_2; 1.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF00621; RhoGEF; 1.
DR Pfam; PF00435; Spectrin; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00325; RhoGEF; 1.
DR SMART; SM00516; SEC14; 1.
DR SMART; SM00326; SH3; 1.
DR SMART; SM00150; SPEC; 1.
DR SUPFAM; SSF48065; SSF48065; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF52087; SSF52087; 1.
DR PROSITE; PS50191; CRAL_TRIO; 1.
DR PROSITE; PS00741; DH_1; 1.
DR PROSITE; PS50010; DH_2; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Coiled coil; Cytoplasm;
KW Guanine-nucleotide releasing factor; Lipid-binding; Membrane;
KW Phosphoprotein; Proto-oncogene; Reference proteome; SH3 domain.
FT CHAIN 1..1149
FT /note="Guanine nucleotide exchange factor DBS"
FT /id="PRO_0000080936"
FT DOMAIN 52..224
FT /note="CRAL-TRIO"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00056"
FT REPEAT 351..456
FT /note="Spectrin"
FT DOMAIN 632..812
FT /note="DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT DOMAIN 841..950
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 1055..1116
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT REGION 555..627
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 956..1033
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 503..529
FT /evidence="ECO:0000255"
FT COMPBIAS 578..598
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 601..627
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 961..982
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 457
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63406"
FT MOD_RES 462
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63406"
FT MOD_RES 471
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63406"
FT MOD_RES 480
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63406"
FT MOD_RES 621
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 622
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1033
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1034
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1041
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1042
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CONFLICT 495..496
FT /note="AL -> SF (in Ref. 1; AAB33461)"
FT /evidence="ECO:0000305"
FT CONFLICT 701
FT /note="L -> V (in Ref. 1; AAB33461)"
FT /evidence="ECO:0000305"
FT HELIX 625..657
FT /evidence="ECO:0007829|PDB:1KZ7"
FT HELIX 660..663
FT /evidence="ECO:0007829|PDB:1KZ7"
FT TURN 665..670
FT /evidence="ECO:0007829|PDB:1KZ7"
FT HELIX 673..677
FT /evidence="ECO:0007829|PDB:1KZ7"
FT HELIX 679..683
FT /evidence="ECO:0007829|PDB:1KZ7"
FT HELIX 686..695
FT /evidence="ECO:0007829|PDB:1KZ7"
FT HELIX 697..702
FT /evidence="ECO:0007829|PDB:1KZ7"
FT TURN 703..706
FT /evidence="ECO:0007829|PDB:1KZ7"
FT HELIX 708..710
FT /evidence="ECO:0007829|PDB:1KZ7"
FT HELIX 711..716
FT /evidence="ECO:0007829|PDB:1KZ7"
FT TURN 717..720
FT /evidence="ECO:0007829|PDB:1KZ7"
FT HELIX 721..723
FT /evidence="ECO:0007829|PDB:1KZ7"
FT HELIX 724..742
FT /evidence="ECO:0007829|PDB:1KZ7"
FT HELIX 746..755
FT /evidence="ECO:0007829|PDB:1KZ7"
FT HELIX 761..765
FT /evidence="ECO:0007829|PDB:1KZ7"
FT HELIX 767..784
FT /evidence="ECO:0007829|PDB:1KZ7"
FT TURN 785..788
FT /evidence="ECO:0007829|PDB:1RJ2"
FT HELIX 792..815
FT /evidence="ECO:0007829|PDB:1KZ7"
FT STRAND 818..820
FT /evidence="ECO:0007829|PDB:1KZ7"
FT HELIX 825..828
FT /evidence="ECO:0007829|PDB:1KZ7"
FT STRAND 831..841
FT /evidence="ECO:0007829|PDB:1KZ7"
FT STRAND 848..851
FT /evidence="ECO:0007829|PDB:1RJ2"
FT STRAND 855..857
FT /evidence="ECO:0007829|PDB:1KZ7"
FT STRAND 859..876
FT /evidence="ECO:0007829|PDB:1KZ7"
FT TURN 880..883
FT /evidence="ECO:0007829|PDB:1KZG"
FT STRAND 888..896
FT /evidence="ECO:0007829|PDB:1KZ7"
FT HELIX 897..899
FT /evidence="ECO:0007829|PDB:1KZ7"
FT STRAND 900..903
FT /evidence="ECO:0007829|PDB:1KZ7"
FT STRAND 912..917
FT /evidence="ECO:0007829|PDB:1KZ7"
FT TURN 918..921
FT /evidence="ECO:0007829|PDB:1KZ7"
FT STRAND 922..927
FT /evidence="ECO:0007829|PDB:1KZ7"
FT HELIX 931..958
FT /evidence="ECO:0007829|PDB:1KZ7"
FT TURN 959..964
FT /evidence="ECO:0007829|PDB:1KZ7"
SQ SEQUENCE 1149 AA; 129113 MW; 0A325FB42E49BA6D CRC64;
MSDCWCFIFC KEHVRSNPLS PQHDGASREE ADHQVDVSDG IRLVPDKAEA TAATASDEIM
HQDIVPLCAA DIQEQLKKRF AYLSGGRGQD GSPVITFPDY PAFSEIPDKE FQNVMTYLTS
IPSLQDAGIG FILVIDRRQD KWTSVKASVL RIAASFPANL QLVLVLRPTG FFQRTLSDIA
FKFNRDEFKM KVPVMMLSSV PELHGYIDKS QLTEDLGGTL DYCHSRWLCH RTAIESFALM
VKQTAQMLQA FGTELAETEL PNDVQSTSLV LSAHTEKKAK VKEDLQLALK EGNSILESLR
EPLAESAAHS VNQDQLDNQA TVQRLLAQLN ETEAAFDEFW AKHQQKLEQC LQLRHFEQGF
REVKTTLDSM SQKIAAFTDV GNSLAHVQHL LKDLTAFEEK SSVAVDKARA LSLEGQQLIE
NRHYAVDSIH PKCEELQHLC DHFASEVTRR RGLLSKSLEL HSLLETSMKW SDEGIFLLAS
QPVDKCQSQD GAEAALQEIE KFLETGAENK IQELNEIYKE YECILNQDLL EHVQKVFQKQ
ESTEEMFHRR QASLKKLAAK QTRPVQPVAP RPEALTKSPS PSPGSWRSSE NSSSEGNALR
RGPYRRAKSE MSEPRQGRTS STGEEEESLA ILRRHVMNEL LDTERAYVEE LLCVLEGYAA
EMDNPLMAHL ISTGLQNKKN ILFGNMEEIY HFHNRNIPAG LESCIDCPEL VGRCFLERME
EFQIYEKYCQ NKPRSESLWR QCSDCPFFQE CQKKLDHKLS LDSYLLKPVQ RITKYQLLLK
EMLKYSKHCE GAEDLQEALS SILGILKAVN DSMHLIAITG YDGNLGDLGK LLMQGSFSVW
TDHKKGHTKV KELARFKPMQ RHLFLHEKAV LFCKKREENG EGYEKAPSYS YKQSLNMTAV
GITENVKGDT KKFEIWYNAR EEVYIIQAPT PEIKAAWVNE IRKVLTSQLQ ACREASQHRA
LEQSHSLPLP TPSSTSPTKG NTRNVKKLED RKTDPLSLEG YVSSSLPKPP EKGKGWSKTS
HSLEAPEEDG GWSSAEELIN SSDAEEDGGV GPKKLVPGKY TVVMDDEKGG PDTLAMRSGD
MVEVVEEGAE GLWYVRDLTS SKEGWVPASS LSTLLGKSSS AQCLSSSGKI HCARQLCPEP
AEILSPEPV
