MCF2L_RAT
ID MCF2L_RAT Reviewed; 1149 AA.
AC Q63406;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 3.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Guanine nucleotide exchange factor DBS;
DE AltName: Full=DBL's big sister;
DE AltName: Full=MCF2-transforming sequence-like protein;
DE AltName: Full=OST oncogene {ECO:0000303|PubMed:7957046};
GN Name=Mcf2l; Synonyms=Ost {ECO:0000303|PubMed:7957046};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 124-1058, FUNCTION, SUBCELLULAR LOCATION,
RP INTERACTION WITH RAC1, PHOSPHORYLATION, AND TISSUE SPECIFICITY.
RC TISSUE=Osteosarcoma;
RX PubMed=7957046; DOI=10.1002/j.1460-2075.1994.tb06803.x;
RA Horii Y., Beeler J.F., Sakaguchi K., Tachibana M., Miki T.;
RT "A novel oncogene, ost, encodes a guanine nucleotide exchange factor that
RT potentially links Rho and Rac signaling pathways.";
RL EMBO J. 13:4776-4786(1994).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-457; SER-462; SER-471 AND
RP SER-480, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=16641100; DOI=10.1073/pnas.0600895103;
RA Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.;
RT "Quantitative phosphoproteomics of vasopressin-sensitive renal cells:
RT regulation of aquaporin-2 phosphorylation at two sites.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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. Seems to lack activity
CC with RAC1. Becomes activated and highly tumorigenic by truncation of
CC the N-terminus. {ECO:0000269|PubMed:7957046}.
CC -!- SUBUNIT: Interacts with GTP-bound RAC1 (PubMed:7957046). Interacts with
CC CDC42. Interacts with RHOA. Interacts with CCPG1, which results in
CC specific inhibition of its exchange activity toward RHOA, but does not
CC affect its activity on CDC42 (By similarity).
CC {ECO:0000250|UniProtKB:Q64096, ECO:0000269|PubMed:7957046}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:7957046}. Cell
CC membrane {ECO:0000250|UniProtKB:Q64096}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q64096}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q64096}.
CC -!- TISSUE SPECIFICITY: Highest expression in the brain, where it is found
CC in neurons and alpha-tanycytes (at protein level). Detected in brain,
CC and at lower levels in the heart. {ECO:0000269|PubMed:7957046}.
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 -!- DOMAIN: The DH domain is involved in interaction with CCPG1.
CC {ECO:0000250|UniProtKB:Q64096}.
CC -!- PTM: Mainly phosphorylated on serine. {ECO:0000269|PubMed:7957046}.
CC -!- SIMILARITY: Belongs to the MCF2 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA84713.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
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DR EMBL; AC117058; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z35654; CAA84713.1; ALT_SEQ; mRNA.
DR PIR; S51620; S51620.
DR AlphaFoldDB; Q63406; -.
DR SMR; Q63406; -.
DR CORUM; Q63406; -.
DR STRING; 10116.ENSRNOP00000023352; -.
DR iPTMnet; Q63406; -.
DR PhosphoSitePlus; Q63406; -.
DR PaxDb; Q63406; -.
DR PRIDE; Q63406; -.
DR Ensembl; ENSRNOT00000079096; ENSRNOP00000068993; ENSRNOG00000028426.
DR UCSC; RGD:619782; rat.
DR RGD; 619782; Mcf2l.
DR eggNOG; KOG4240; Eukaryota.
DR GeneTree; ENSGT00940000157874; -.
DR InParanoid; Q63406; -.
DR Reactome; R-RNO-193648; NRAGE signals death through JNK.
DR Reactome; R-RNO-416482; G alpha (12/13) signalling events.
DR Reactome; R-RNO-8980692; RHOA GTPase cycle.
DR Reactome; R-RNO-9013026; RHOB GTPase cycle.
DR Reactome; R-RNO-9013106; RHOC GTPase cycle.
DR Reactome; R-RNO-9013148; CDC42 GTPase cycle.
DR Reactome; R-RNO-9013149; RAC1 GTPase cycle.
DR Reactome; R-RNO-9013408; RHOG GTPase cycle.
DR PRO; PR:Q63406; -.
DR Proteomes; UP000002494; Chromosome 16.
DR Bgee; ENSRNOG00000028426; Expressed in frontal cortex and 19 other tissues.
DR ExpressionAtlas; Q63406; baseline and differential.
DR Genevisible; Q63406; RN.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0019898; C:extrinsic component of membrane; IDA:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; ISO:RGD.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005545; F:1-phosphatidylinositol binding; ISO:RGD.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB.
DR GO; GO:0035091; F:phosphatidylinositol binding; ISO:RGD.
DR GO; GO:0035025; P:positive regulation of Rho protein signal transduction; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0007266; P:Rho protein signal transduction; ISO:RGD.
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 Cell membrane; Coiled coil; Cytoplasm; Guanine-nucleotide releasing factor;
KW Lipid-binding; Membrane; Phosphoprotein; Proto-oncogene;
KW Reference proteome; SH3 domain.
FT CHAIN 1..1149
FT /note="Guanine nucleotide exchange factor DBS"
FT /id="PRO_0000080937"
FT DOMAIN 52..224
FT /note="CRAL-TRIO"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00056"
FT REPEAT 355..454
FT /note="Spectrin"
FT DOMAIN 632..812
FT /note="DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT DOMAIN 830..946
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..528
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:0007744|PubMed:16641100"
FT MOD_RES 462
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT MOD_RES 471
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT MOD_RES 480
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT MOD_RES 621
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64096"
FT MOD_RES 622
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q64096"
FT MOD_RES 1033
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64096"
FT MOD_RES 1034
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64096"
FT MOD_RES 1041
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64096"
FT MOD_RES 1042
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64096"
SQ SEQUENCE 1149 AA; 129410 MW; 1735D8565A965963 CRC64;
MSNCWCFIFC KERVRSNSSS PQHDGTSREE ADHQVDVSDG IRLVPDKAEA TMATASDEIM
HQDIVPLCAA DIQEQLKKRF AYLSGGRGQD GSPVITFPDY PAFSEIPDKE FQNVMTYLTS
IPSLQDAGIG FILVIDRRQD KWTSVKASVL RIAASFPANL QLVLVLRPTG FFQRTLSDIA
FKFNRDEFKM KVPVMMLSSV PELHGYIDKS QLTEDLGGTL DYCHSRWLCH RTAIESFALM
VKQTAQMLQA FGTELAETEL PNDVQSTSLV LSAHTEKKAK VKEDLQLALT EGNSILESLR
EPLAESIVHS VNQDQLDNQA TVKRLLTQLN ETEAAFDEFW AKHQQKLEQC LQLRHFEQGF
REVKTALDSM SQKIAAFTDV GNSLAHVQHL LKDLTTFEEK SSVAVDKARA LSLEGQQLIE
NRHYAVDSIH PKCEELQHLC DHFASEVTRR RDLLSKSLEL HSLLETSMKW SDEGIFLLAS
QPVDKCQSQD GAEAALQEIE KFLETGAENK IQELNKIYKE YECILNQDLL EHVQKVFQKQ
ESTEEMFHRR QASLKKLAAK QTRPVQPVAP RPEALTKSPS PSPGSWRSSE NSSSEGNALR
RGPYRRAKSE MSEPRQGRTS STGEEEESLA ILRRHVMNEL LDTERAYVEE LLCVLEGYAA
EMDNPLMAHL ISTGLQNKKN ILFGNMEEIY HFHNRIFLRE 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 TPASTSPTKG STRNVKKLED RKTDPLCLEG CVSSSLPKPP EKGKGWSKTS
HSLEAPEEDG GWSSAEELIN SSDAEEDGGV GPRKLVPGKY TVLMDGEKGG SDTLAMRSGD
MVEVVEEGTE GLWYVRDLTS SKEGWVPASS LATLLGKSSS AQCLSSSGKT HCARQLCPEP
AKILSPEPV
