ARG28_RAT
ID ARG28_RAT Reviewed; 1700 AA.
AC P0C6P5;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 18-MAR-2008, sequence version 1.
DT 03-AUG-2022, entry version 94.
DE RecName: Full=Rho guanine nucleotide exchange factor 28;
DE AltName: Full=190 kDa guanine nucleotide exchange factor;
DE Short=p190-RhoGEF;
DE Short=p190RhoGEF;
DE AltName: Full=Rho guanine nucleotide exchange factor;
GN Name=Arhgef28; Synonyms=Rgnef;
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 FUNCTION IN NEFL EXPRESSION, AND RNA-BINDING.
RX PubMed=11435431; DOI=10.1074/jbc.m104104200;
RA Canete-Soler R., Wu J., Zhai J., Shamim M., Schlaepfer W.W.;
RT "p190RhoGEF Binds to a destabilizing element in the 3' untranslated region
RT of light neurofilament subunit mRNA and alters the stability of the
RT transcript.";
RL J. Biol. Chem. 276:32046-32050(2001).
RN [3]
RP FUNCTION, AND RNA-BINDING.
RX PubMed=12215442; DOI=10.1074/jbc.m206635200;
RA Ge W.-W., Wu J., Zhai J., Nie Z., Lin H., Schlaepfer W.W., Canete-Soler R.;
RT "Binding of p190RhoGEF to a destabilizing element on the light
RT neurofilament mRNA is competed by BC1 RNA.";
RL J. Biol. Chem. 277:42701-42705(2002).
RN [4]
RP OLIGOMERIZATION, AND IDENTIFICATION IN A COMPLEX WITH MAPK8 AND MAPK8IP1.
RX PubMed=14499478; DOI=10.1016/s0169-328x(03)00263-8;
RA Wu J., Zhai J., Lin H., Nie Z., Ge W.-W., Garcia-Bermejo L., Muschel R.J.,
RA Schlaepfer W.W., Canete-Soler R.;
RT "Cytoplasmic retention sites in p190RhoGEF confer anti-apoptotic activity
RT to an EGFP-tagged protein.";
RL Brain Res. Mol. Brain Res. 117:27-38(2003).
RN [5]
RP INTERACTION WITH PTK2/FAK1.
RX PubMed=12702722; DOI=10.1074/jbc.m302381200;
RA Zhai J., Lin H., Nie Z., Wu J., Canete-Soler R., Schlaepfer W.W.,
RA Schlaepfer D.D.;
RT "Direct interaction of focal adhesion kinase with p190RhoGEF.";
RL J. Biol. Chem. 278:24865-24873(2003).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-312; SER-314 AND SER-478, AND
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: Functions as a RHOA-specific guanine nucleotide exchange
CC factor regulating signaling pathways downstream of integrins and growth
CC factor receptors. Functions in axonal branching, synapse formation and
CC dendritic morphogenesis. Functions also in focal adhesion formation,
CC cell motility and B-lymphocytes activation. May regulate NEFL
CC expression and aggregation and play a role in apoptosis.
CC {ECO:0000269|PubMed:11435431, ECO:0000269|PubMed:12215442}.
CC -!- SUBUNIT: Homooligomer; forms cytoplasmic aggregates. Forms a complex
CC with MAPK8 and MAPK8IP1. Interacts with RHOA. Interacts with
CC microtubules. Interacts with YWHAE and YWHAH. Interacts with PTK2/FAK1.
CC Interacts with NEFL. Interacts with CTNND2; prevents interaction with
CC RHOA (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane
CC {ECO:0000250}. Note=Colocalizes with the microtubule radial and
CC cortical systems. {ECO:0000250}.
CC -!- PTM: Phosphorylated on tyrosine upon stimulation of cells by laminin.
CC {ECO:0000250}.
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DR EMBL; AABR03012977; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03013324; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03013680; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03015604; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03016111; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03017173; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03017199; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03018551; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03019008; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03021286; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03022481; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_008758898.1; XM_008760676.1.
DR AlphaFoldDB; P0C6P5; -.
DR SMR; P0C6P5; -.
DR STRING; 10116.ENSRNOP00000059196; -.
DR iPTMnet; P0C6P5; -.
DR PhosphoSitePlus; P0C6P5; -.
DR jPOST; P0C6P5; -.
DR PaxDb; P0C6P5; -.
DR GeneID; 361882; -.
DR UCSC; RGD:1307061; rat.
DR CTD; 64283; -.
DR RGD; 1307061; Arhgef28.
DR VEuPathDB; HostDB:ENSRNOG00000016544; -.
DR eggNOG; KOG3519; Eukaryota.
DR eggNOG; KOG3520; Eukaryota.
DR HOGENOM; CLU_002466_2_1_1; -.
DR InParanoid; P0C6P5; -.
DR OMA; EQECQSQ; -.
DR OrthoDB; 69816at2759; -.
DR PhylomeDB; P0C6P5; -.
DR TreeFam; TF334740; -.
DR Reactome; R-RNO-3928662; EPHB-mediated forward signaling.
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 PRO; PR:P0C6P5; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Bgee; ENSRNOG00000016544; Expressed in kidney and 18 other tissues.
DR Genevisible; P0C6P5; RN.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0000902; P:cell morphogenesis; IBA:GO_Central.
DR GO; GO:0021955; P:central nervous system neuron axonogenesis; ISO:RGD.
DR GO; GO:0060052; P:neurofilament cytoskeleton organization; ISO:RGD.
DR GO; GO:0035023; P:regulation of Rho protein signal transduction; IBA:GO_Central.
DR CDD; cd00029; C1; 1.
DR CDD; cd14680; PH_p190RhoGEF; 1.
DR CDD; cd00160; RhoGEF; 1.
DR Gene3D; 1.20.900.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR037819; ARHGEF28_PH.
DR InterPro; IPR046349; C1-like_sf.
DR InterPro; IPR035899; DBL_dom_sf.
DR InterPro; IPR000219; DH-domain.
DR InterPro; IPR002219; PE/DAG-bd.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR041020; PH_16.
DR InterPro; IPR001849; PH_domain.
DR Pfam; PF00130; C1_1; 1.
DR Pfam; PF17838; PH_16; 1.
DR Pfam; PF00621; RhoGEF; 1.
DR SMART; SM00109; C1; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00325; RhoGEF; 1.
DR SUPFAM; SSF48065; SSF48065; 1.
DR SUPFAM; SSF57889; SSF57889; 1.
DR PROSITE; PS50010; DH_2; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS00479; ZF_DAG_PE_1; 1.
DR PROSITE; PS50081; ZF_DAG_PE_2; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Coiled coil; Cytoplasm; Differentiation;
KW Guanine-nucleotide releasing factor; Membrane; Metal-binding;
KW Phosphoprotein; Reference proteome; RNA-binding; Zinc; Zinc-finger.
FT CHAIN 1..1700
FT /note="Rho guanine nucleotide exchange factor 28"
FT /id="PRO_0000324120"
FT DOMAIN 848..1043
FT /note="DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT DOMAIN 1085..1187
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT ZN_FING 651..698
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 288..335
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 483..525
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 709..761
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 774..799
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1186..1207
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1294..1303
FT /note="Interaction with PTK2/FAK1; required for regulation
FT of axonal branching and synapse formation"
FT /evidence="ECO:0000250"
FT REGION 1369..1380
FT /note="Mediates cytoplasmic retention and interaction with
FT YWHAH"
FT /evidence="ECO:0000250"
FT REGION 1421..1700
FT /note="Interaction with microtubules"
FT /evidence="ECO:0000250"
FT REGION 1493..1524
FT /note="RNA-binding"
FT REGION 1563..1576
FT /note="Mediates cytoplasmic retention and interaction with
FT MAPK8IP1"
FT /evidence="ECO:0000250"
FT REGION 1574..1598
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1611..1700
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 1473..1522
FT /evidence="ECO:0000255"
FT COMPBIAS 301..323
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1192..1207
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1611..1626
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1642..1674
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 312
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 314
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 478
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 623
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8N1W1"
FT MOD_RES 1535
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8N1W1"
FT MOD_RES 1604
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P97433"
SQ SEQUENCE 1700 AA; 190757 MW; 0D21C8E6600728F1 CRC64;
MELSCSEVPL YGQRTVYAKF GKNVYLPEDA EFYFIYDGSH QRHVVIADRV EDNVLQSIIP
GHWLQETVMV SVCLCSEGYS PVTMGSGSVT YVDNMACRLA RLLVTQADRL TPCSHQTLLT
PFALTAEALP ALDEELVLAL TQLELPLGWT VLGNSSLEVC LHRESLLHLA VRWALPKLFH
FLLCLPGGVK ALELPNEEAT TPLDLALHGG HSMLVEDISN FQGRRSPGFS RLRLNEDATL
QFDRSSETLT LTVNHTAEHL LEADIKLFRK YFWDRAFLVK ALDQEAKTER ATMPSGAAET
EEEVRNLESG RSPSEEEEDG QLVKSQADGP SEQEDQDRLV LDHSFDGLKK SKHAPASLAA
GQLSDVPNGG DEVYANCMVI DQVGDLDINY INIEGLSTHT SPESMRSTLG PQACKHILPP
DTSPCGHLLC EDSDRTLDAA ASQSCMSPPS SHTSNLNLSF GLHGFVKEQS HLKKRSSSLD
ALVADSEEEG RSEPPICYAV GSQSSPRTGL PGGDELDSFD ANTEPDCNIS RTESLSLSST
LHSKESLLSG IRSRSYSCSS PKISSGKSRL VRDFTVCSSS EEQRSYSFQE PPGEKRIQEE
EWDDYIIPAK AESEKHKVSR TFSFLMNRMT SPRNKSKMKN KDTKDKEKLN RHQFVPGTFS
GVLQCSGCDK TLLGKESLQC ANCKANTHKG CKDTVPPCTK KFQDKYNKNK PQTILGSSSV
RDVPPPGLSL HPSPSMPIGL PAGRKETAGQ AHPLSRSVPG TTLESFRRAV TSLESEGDSN
SWRSRSHSDE LFQSMGSSPS TESFMMEDVV DSSLWSELSS DAQEFEAESW SLVVDPSFCS
RQEKDVIKRQ DVIFELMQTE VHHIQTLLIM SEVFRKGMKE ELQLDHSTVD RIFPCLDELL
ETHKHFFFSM KERRQESCTG NDRNFVINQI GDILVQQFSE ENASKMKRIY GDFCSHHKEA
MSLFKELQQN KKFQNFIKIR NSNLLARRRG IPECILLVTQ RITKYPVLVE RILQYTKERT
EEHRDLCRAL GLIKDMIAAV DLKVSEYEKN QKWLEILNKI ENKTYTKLKN GHVFRKQALM
SQERALLHDG LVYWKTATGR FKDILALLLT DVLLFLQEKD QKYIFAAVDQ KPSVISLQKL
IAREVANEER GMFLISASSA GPEMYEIHTS SKEERNNWMR RIQQAVESCP EEEGGRTSES
DEERRKADAR VAKIQQCQEI LSNQDQQICT YLEEKLHIYA ELGELSGFED VHLEPHLLIK
PDPGEPPQAA SLLAAALREA ESLQVAVKAS KLADVSQPSE EGPGGAVLAD TLSAQDAPAS
PTAFTEGTEG RGCWDVDPRL QGVVTDLAVS DAGEKVEYRS FSGSSQSEII QAIQNLTRLL
YSLQAALTIQ DSHIEIHKLV LQQQESLAPS HSFRGGPLQD QEKSRYLEKH REELANIHKL
QYQFQQEQRR WHRTCDQQQR EQEAQESWLQ ARERECQSQE ELLLRHRSEL DHQLQEYQQN
LERLREGQRM VERERQRMRD QQGLLGHCKH SRQRSLPAVF SPGSKEVTEL NRAESLCHEK
SFFLNDAFTH MSLNTSNKPN PSGAPWDAHP PGGSHLDLAR TSDSQIEVKM DVSQPSDVNS
ELWTTGLGPQ RPARQESIKD SCKNVADLNS FQTESPDPQD SNQRGPQPQT LITEAKLTPP
MAAGHGGDAG DGAEENIVYL
