ID   ARHGC_HUMAN             Reviewed;        1544 AA.
AC   Q9NZN5; O15086; Q6P526;
DT   29-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2000, sequence version 1.
DT   27-MAR-2024, entry version 198.
DE   RecName: Full=Rho guanine nucleotide exchange factor 12;
DE   AltName: Full=Leukemia-associated RhoGEF;
GN   Name=ARHGEF12; Synonyms=KIAA0382, LARG;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND CHROMOSOMAL
RP   TRANSLOCATION.
RC   TISSUE=Prostate;
RX   PubMed=10681437; DOI=10.1073/pnas.040569197;
RA   Kourlas P.J., Strout M.P., Becknell B., Veronese M.L., Croce C.M.,
RA   Theil K.S., Krahe R., Ruutu T., Knuutila S., Bloomfield C.D.,
RA   Caligiuri M.A.;
RT   "Identification of a gene at 11q23 encoding a guanine nucleotide exchange
RT   factor: evidence for its fusion with MLL in acute myeloid leukemia.";
RL   Proc. Natl. Acad. Sci. U.S.A. 97:2145-2150(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-584 (ISOFORM 2).
RC   TISSUE=Thyroid;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 102-1544, AND VARIANT PHE-973.
RC   TISSUE=Brain;
RX   PubMed=9205841; DOI=10.1093/dnares/4.2.141;
RA   Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N., Miyajima N.,
RA   Tanaka A., Kotani H., Nomura N., Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. VII. The
RT   complete sequences of 100 new cDNA clones from brain which can code for
RT   large proteins in vitro.";
RL   DNA Res. 4:141-150(1997).
RN   [4]
RP   SEQUENCE REVISION.
RA   Ohara O., Nagase T., Kikuno R., Nomura N.;
RL   Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   FUNCTION, AND INTERACTION WITH RHOA; GNA12 AND GNA13.
RX   PubMed=11094164; DOI=10.1016/s0014-5793(00)02224-9;
RA   Fukuhara S., Chikumi H., Gutkind J.S.;
RT   "Leukemia-associated Rho guanine nucleotide exchange factor (LARG) links
RT   heterotrimeric G proteins of the G(12) family to Rho.";
RL   FEBS Lett. 485:183-188(2000).
RN   [6]
RP   INTERACTION WITH IGF1R.
RX   PubMed=11724822; DOI=10.1083/jcb.200106139;
RA   Taya S., Inagaki N., Sengiku H., Makino H., Iwamatsu A., Urakawa I.,
RA   Nagao K., Kataoka S., Kaibuchi K.;
RT   "Direct interaction of insulin-like growth factor-1 receptor with leukemia-
RT   associated RhoGEF.";
RL   J. Cell Biol. 155:809-820(2001).
RN   [7]
RP   INTERACTION WITH PLXNB1 AND PLXNB2.
RX   PubMed=12372594; DOI=10.1016/s0014-5793(02)03323-9;
RA   Driessens M.H.E., Olivo C., Nagata K., Inagaki M., Collard J.G.;
RT   "B plexins activate Rho through PDZ-RhoGEF.";
RL   FEBS Lett. 529:168-172(2002).
RN   [8]
RP   INTERACTION WITH PLXNB1 AND PLXNB2.
RX   PubMed=12183458; DOI=10.1074/jbc.m206005200;
RA   Perrot V., Vazquez-Prado J., Gutkind J.S.;
RT   "Plexin B regulates Rho through the guanine nucleotide exchange factors
RT   leukemia-associated Rho GEF (LARG) and PDZ-RhoGEF.";
RL   J. Biol. Chem. 277:43115-43120(2002).
RN   [9]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Embryonic kidney;
RX   PubMed=17525332; DOI=10.1126/science.1140321;
RA   Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA   Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA   Gygi S.P., Elledge S.J.;
RT   "ATM and ATR substrate analysis reveals extensive protein networks
RT   responsive to DNA damage.";
RL   Science 316:1160-1166(2007).
RN   [10]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-41 (ISOFORM 2), AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18220336; DOI=10.1021/pr0705441;
RA   Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT   "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT   phosphoproteomic analysis.";
RL   J. Proteome Res. 7:1346-1351(2008).
RN   [11]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-736, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Platelet;
RX   PubMed=18088087; DOI=10.1021/pr0704130;
RA   Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA   Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT   "Phosphoproteome of resting human platelets.";
RL   J. Proteome Res. 7:526-534(2008).
RN   [12]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-341, PHOSPHORYLATION [LARGE
RP   SCALE ANALYSIS] AT SER-41 (ISOFORM 2), AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN   [13]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP   METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP   [LARGE SCALE ANALYSIS].
RX   PubMed=19413330; DOI=10.1021/ac9004309;
RA   Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT   "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT   refined SCX-based approach.";
RL   Anal. Chem. 81:4493-4501(2009).
RN   [14]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Leukemic T-cell;
RX   PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA   Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA   Rodionov V., Han D.K.;
RT   "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT   reveals system-wide modulation of protein-protein interactions.";
RL   Sci. Signal. 2:RA46-RA46(2009).
RN   [15]
RP   INTERACTION WITH GCSAM.
RX   PubMed=20844236; DOI=10.1182/blood-2010-04-281568;
RA   Jiang X., Lu X., McNamara G., Liu X., Cubedo E., Sarosiek K.A.,
RA   Sanchez-Garcia I., Helfman D.M., Lossos I.S.;
RT   "HGAL, a germinal center specific protein, decreases lymphoma cell motility
RT   by modulation of the RhoA signaling pathway.";
RL   Blood 116:5217-5227(2010).
RN   [16]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-637, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA   Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA   Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT   "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT   site occupancy during mitosis.";
RL   Sci. Signal. 3:RA3-RA3(2010).
RN   [17]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [18]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-41; SER-309; SER-341;
RP   SER-637; THR-736 AND SER-1288, AND IDENTIFICATION BY MASS SPECTROMETRY
RP   [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma, and Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [19]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-309; SER-637; SER-1327;
RP   SER-1377; SER-1457 AND SER-1541, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT
RP   SER-41 (ISOFORM 2), AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP   ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [20]
RP   X-RAY CRYSTALLOGRAPHY (2.13 ANGSTROMS) OF 766-1138 IN COMPLEX WITH RHOA,
RP   AND SUBUNIT.
RX   PubMed=15331592; DOI=10.1074/jbc.m406056200;
RA   Kristelly R., Gao G., Tesmer J.J.;
RT   "Structural determinants of RhoA binding and nucleotide exchange in
RT   leukemia-associated Rho guanine-nucleotide exchange factor.";
RL   J. Biol. Chem. 279:47352-47362(2004).
RN   [21]
RP   STRUCTURE BY NMR OF 67-151 IN COMPLEX WITH PLXNB1, AND SUBUNIT.
RX   PubMed=18411422; DOI=10.1110/ps.073416508;
RA   Liu J., Zhang J., Yang Y., Huang H., Shen W., Hu Q., Wang X., Wu J.,
RA   Shi Y.;
RT   "Conformational change upon ligand binding and dynamics of the PDZ domain
RT   from leukemia-associated Rho guanine nucleotide exchange factor.";
RL   Protein Sci. 17:1003-1014(2008).
CC   -!- FUNCTION: May play a role in the regulation of RhoA GTPase by guanine
CC       nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13). Acts as
CC       guanine nucleotide exchange factor (GEF) for RhoA GTPase and may act as
CC       GTPase-activating protein (GAP) for GNA12 and GNA13.
CC       {ECO:0000269|PubMed:11094164}.
CC   -!- SUBUNIT: Interacts with GNA12 and GNA13, probably through the RGS-like
CC       domain. Interacts with RHOA, PLXNB1 and PLXNB2. Interacts through its
CC       PDZ domain with IGF1R beta subunit. Interacts with GCSAM.
CC       {ECO:0000269|PubMed:11094164, ECO:0000269|PubMed:11724822,
CC       ECO:0000269|PubMed:12183458, ECO:0000269|PubMed:12372594,
CC       ECO:0000269|PubMed:15331592, ECO:0000269|PubMed:18411422,
CC       ECO:0000269|PubMed:20844236}.
CC   -!- INTERACTION:
CC       Q9NZN5; O14908: GIPC1; NbExp=5; IntAct=EBI-821440, EBI-373132;
CC       Q9NZN5; P08069: IGF1R; NbExp=7; IntAct=EBI-821440, EBI-475981;
CC       Q9NZN5; P61586: RHOA; NbExp=3; IntAct=EBI-821440, EBI-446668;
CC       Q9NZN5; P61793: Lpar1; Xeno; NbExp=3; IntAct=EBI-821440, EBI-7512335;
CC       Q9NZN5-1; Q96PX9: PLEKHG4B; NbExp=3; IntAct=EBI-9640168, EBI-11741362;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}. Membrane {ECO:0000305}.
CC       Note=Translocated to the membrane upon stimulation. {ECO:0000305}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q9NZN5-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q9NZN5-2; Sequence=VSP_008131;
CC   -!- TISSUE SPECIFICITY: Ubiquitously expressed. Isoform 2 is found in
CC       jejunum and testis.
CC   -!- DISEASE: Note=A chromosomal aberration involving ARHGEF12 may be a
CC       cause of acute leukemia. Translocation t(11;11)(q23;23) with
CC       KMT2A/MLL1. {ECO:0000269|PubMed:10681437}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAH63117.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC       Haematology;
CC       URL="https://atlasgeneticsoncology.org/gene/243/LARG";
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DR   EMBL; AF180681; AAF36817.1; -; mRNA.
DR   EMBL; AB002380; BAA20836.2; -; mRNA.
DR   EMBL; BC063117; AAH63117.1; ALT_SEQ; mRNA.
DR   CCDS; CCDS41727.1; -. [Q9NZN5-1]
DR   CCDS; CCDS55794.1; -. [Q9NZN5-2]
DR   RefSeq; NP_001185594.1; NM_001198665.1. [Q9NZN5-2]
DR   RefSeq; NP_001288013.1; NM_001301084.1.
DR   RefSeq; NP_056128.1; NM_015313.2. [Q9NZN5-1]
DR   RefSeq; XP_011541022.1; XM_011542720.2.
DR   RefSeq; XP_016872910.1; XM_017017421.1.
DR   PDB; 1TXD; X-ray; 2.13 A; A=766-1138.
DR   PDB; 1X86; X-ray; 3.22 A; A/C/E/G=766-1138.
DR   PDB; 2OMJ; NMR; -; A=67-151.
DR   PDB; 2OS6; NMR; -; A=67-151.
DR   PDBsum; 1TXD; -.
DR   PDBsum; 1X86; -.
DR   PDBsum; 2OMJ; -.
DR   PDBsum; 2OS6; -.
DR   AlphaFoldDB; Q9NZN5; -.
DR   BMRB; Q9NZN5; -.
DR   SMR; Q9NZN5; -.
DR   BioGRID; 116945; 131.
DR   ComplexPortal; CPX-7724; LIFT actin modulation complex.
DR   DIP; DIP-37887N; -.
DR   IntAct; Q9NZN5; 32.
DR   MINT; Q9NZN5; -.
DR   STRING; 9606.ENSP00000380942; -.
DR   ChEMBL; CHEMBL4523477; -.
DR   GlyCosmos; Q9NZN5; 1 site, 1 glycan.
DR   GlyGen; Q9NZN5; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q9NZN5; -.
DR   PhosphoSitePlus; Q9NZN5; -.
DR   BioMuta; ARHGEF12; -.
DR   DMDM; 34395525; -.
DR   EPD; Q9NZN5; -.
DR   jPOST; Q9NZN5; -.
DR   MassIVE; Q9NZN5; -.
DR   MaxQB; Q9NZN5; -.
DR   PaxDb; 9606-ENSP00000380942; -.
DR   PeptideAtlas; Q9NZN5; -.
DR   ProteomicsDB; 83460; -. [Q9NZN5-1]
DR   ProteomicsDB; 83461; -. [Q9NZN5-2]
DR   Pumba; Q9NZN5; -.
DR   Antibodypedia; 9144; 187 antibodies from 27 providers.
DR   DNASU; 23365; -.
DR   Ensembl; ENST00000356641.7; ENSP00000349056.3; ENSG00000196914.9. [Q9NZN5-2]
DR   Ensembl; ENST00000397843.7; ENSP00000380942.2; ENSG00000196914.9. [Q9NZN5-1]
DR   GeneID; 23365; -.
DR   KEGG; hsa:23365; -.
DR   MANE-Select; ENST00000397843.7; ENSP00000380942.2; NM_015313.3; NP_056128.1.
DR   UCSC; uc001pxl.3; human. [Q9NZN5-1]
DR   AGR; HGNC:14193; -.
DR   CTD; 23365; -.
DR   DisGeNET; 23365; -.
DR   GeneCards; ARHGEF12; -.
DR   HGNC; HGNC:14193; ARHGEF12.
DR   HPA; ENSG00000196914; Low tissue specificity.
DR   MIM; 604763; gene.
DR   neXtProt; NX_Q9NZN5; -.
DR   OpenTargets; ENSG00000196914; -.
DR   PharmGKB; PA24969; -.
DR   VEuPathDB; HostDB:ENSG00000196914; -.
DR   eggNOG; KOG3520; Eukaryota.
DR   GeneTree; ENSGT00940000157662; -.
DR   HOGENOM; CLU_003962_1_0_1; -.
DR   InParanoid; Q9NZN5; -.
DR   OMA; QSEYPMI; -.
DR   OrthoDB; 2875542at2759; -.
DR   PhylomeDB; Q9NZN5; -.
DR   TreeFam; TF106495; -.
DR   PathwayCommons; Q9NZN5; -.
DR   Reactome; R-HSA-193648; NRAGE signals death through JNK.
DR   Reactome; R-HSA-416482; G alpha (12/13) signalling events.
DR   Reactome; R-HSA-416572; Sema4D induced cell migration and growth-cone collapse.
DR   Reactome; R-HSA-8980692; RHOA GTPase cycle.
DR   Reactome; R-HSA-9013026; RHOB GTPase cycle.
DR   Reactome; R-HSA-9013106; RHOC GTPase cycle.
DR   Reactome; R-HSA-9013148; CDC42 GTPase cycle.
DR   SignaLink; Q9NZN5; -.
DR   SIGNOR; Q9NZN5; -.
DR   BioGRID-ORCS; 23365; 25 hits in 1151 CRISPR screens.
DR   ChiTaRS; ARHGEF12; human.
DR   EvolutionaryTrace; Q9NZN5; -.
DR   GeneWiki; ARHGEF12; -.
DR   GenomeRNAi; 23365; -.
DR   Pharos; Q9NZN5; Tchem.
DR   PRO; PR:Q9NZN5; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   RNAct; Q9NZN5; Protein.
DR   Bgee; ENSG00000196914; Expressed in upper leg skin and 205 other cell types or tissues.
DR   ExpressionAtlas; Q9NZN5; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0001664; F:G protein-coupled receptor binding; IDA:MGI.
DR   GO; GO:0005096; F:GTPase activator activity; IEA:UniProtKB-KW.
DR   GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IBA:GO_Central.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:MGI.
DR   GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; TAS:Reactome.
DR   GO; GO:0007266; P:Rho protein signal transduction; IEA:InterPro.
DR   CDD; cd00992; PDZ_signaling; 1.
DR   CDD; cd13390; PH_LARG; 1.
DR   CDD; cd08754; RGS_LARG; 1.
DR   CDD; cd00160; RhoGEF; 1.
DR   Gene3D; 2.30.42.10; -; 1.
DR   Gene3D; 1.20.900.10; Dbl homology (DH) domain; 1.
DR   Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1.
DR   Gene3D; 1.10.167.10; Regulator of G-protein Signalling 4, domain 2; 1.
DR   InterPro; IPR037801; ARHGEF12_PH.
DR   InterPro; IPR035899; DBL_dom_sf.
DR   InterPro; IPR000219; DH-domain.
DR   InterPro; IPR001331; GDS_CDC24_CS.
DR   InterPro; IPR037884; LARG_RGS.
DR   InterPro; IPR001478; PDZ.
DR   InterPro; IPR036034; PDZ_sf.
DR   InterPro; IPR011993; PH-like_dom_sf.
DR   InterPro; IPR041020; PH_16.
DR   InterPro; IPR001849; PH_domain.
DR   InterPro; IPR015212; RGS-like_dom.
DR   InterPro; IPR036305; RGS_sf.
DR   InterPro; IPR044926; RGS_subdomain_2.
DR   PANTHER; PTHR45872:SF3; RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR 12; 1.
DR   PANTHER; PTHR45872; RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR 2, ISOFORM D; 1.
DR   Pfam; PF00595; PDZ; 1.
DR   Pfam; PF17838; PH_16; 1.
DR   Pfam; PF09128; RGS-like; 1.
DR   Pfam; PF00621; RhoGEF; 1.
DR   SMART; SM00228; PDZ; 1.
DR   SMART; SM00233; PH; 1.
DR   SMART; SM00325; RhoGEF; 1.
DR   SUPFAM; SSF48065; DBL homology domain (DH-domain); 1.
DR   SUPFAM; SSF50156; PDZ domain-like; 1.
DR   SUPFAM; SSF50729; PH domain-like; 1.
DR   SUPFAM; SSF48097; Regulator of G-protein signaling, RGS; 1.
DR   PROSITE; PS00741; DH_1; 1.
DR   PROSITE; PS50010; DH_2; 1.
DR   PROSITE; PS50106; PDZ; 1.
DR   PROSITE; PS50003; PH_DOMAIN; 1.
DR   Genevisible; Q9NZN5; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Alternative splicing; Chromosomal rearrangement;
KW   Coiled coil; Cytoplasm; GTPase activation;
KW   Guanine-nucleotide releasing factor; Membrane; Phosphoprotein;
KW   Proto-oncogene; Reference proteome.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0007744|PubMed:19413330"
FT   CHAIN           2..1544
FT                   /note="Rho guanine nucleotide exchange factor 12"
FT                   /id="PRO_0000080930"
FT   DOMAIN          72..151
FT                   /note="PDZ"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT   DOMAIN          367..558
FT                   /note="RGSL"
FT   DOMAIN          787..977
FT                   /note="DH"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT   DOMAIN          1019..1132
FT                   /note="PH"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT   REGION          1..62
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          247..346
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          570..706
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1138..1179
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          194..262
FT                   /evidence="ECO:0000255"
FT   COMPBIAS        13..60
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        250..264
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        310..329
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        570..596
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        628..650
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        660..706
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            308..309
FT                   /note="Breakpoint for translocation to form KMT2A/MLL1-
FT                   ARHGEF12 oncogene"
FT   MOD_RES         2
FT                   /note="N-acetylserine"
FT                   /evidence="ECO:0007744|PubMed:19413330"
FT   MOD_RES         41
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         309
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163,
FT                   ECO:0007744|PubMed:24275569"
FT   MOD_RES         341
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648,
FT                   ECO:0007744|PubMed:23186163"
FT   MOD_RES         637
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:20068231,
FT                   ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT   MOD_RES         736
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:18088087,
FT                   ECO:0007744|PubMed:23186163"
FT   MOD_RES         1288
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         1327
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   MOD_RES         1377
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   MOD_RES         1457
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   MOD_RES         1541
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   VAR_SEQ         48..66
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:10681437,
FT                   ECO:0000303|PubMed:15489334"
FT                   /id="VSP_008131"
FT   VARIANT         973
FT                   /note="Y -> F (in dbSNP:rs2305013)"
FT                   /evidence="ECO:0000269|PubMed:9205841"
FT                   /id="VAR_020191"
FT   STRAND          70..76
FT                   /evidence="ECO:0007829|PDB:2OMJ"
FT   STRAND          85..87
FT                   /evidence="ECO:0007829|PDB:2OMJ"
FT   STRAND          89..91
FT                   /evidence="ECO:0007829|PDB:2OMJ"
FT   STRAND          93..96
FT                   /evidence="ECO:0007829|PDB:2OMJ"
FT   HELIX           102..106
FT                   /evidence="ECO:0007829|PDB:2OMJ"
FT   STRAND          112..119
FT                   /evidence="ECO:0007829|PDB:2OMJ"
FT   TURN            122..124
FT                   /evidence="ECO:0007829|PDB:2OS6"
FT   HELIX           127..135
FT                   /evidence="ECO:0007829|PDB:2OMJ"
FT   STRAND          137..145
FT                   /evidence="ECO:0007829|PDB:2OMJ"
FT   HELIX           769..772
FT                   /evidence="ECO:0007829|PDB:1TXD"
FT   HELIX           775..778
FT                   /evidence="ECO:0007829|PDB:1TXD"
FT   HELIX           783..812
FT                   /evidence="ECO:0007829|PDB:1TXD"
FT   HELIX           814..820
FT                   /evidence="ECO:0007829|PDB:1TXD"
FT   HELIX           825..832
FT                   /evidence="ECO:0007829|PDB:1TXD"
FT   HELIX           835..853
FT                   /evidence="ECO:0007829|PDB:1TXD"
FT   STRAND          857..860
FT                   /evidence="ECO:0007829|PDB:1X86"
FT   HELIX           865..872
FT                   /evidence="ECO:0007829|PDB:1TXD"
FT   HELIX           875..889
FT                   /evidence="ECO:0007829|PDB:1TXD"
FT   HELIX           891..904
FT                   /evidence="ECO:0007829|PDB:1TXD"
FT   HELIX           906..917
FT                   /evidence="ECO:0007829|PDB:1TXD"
FT   HELIX           919..921
FT                   /evidence="ECO:0007829|PDB:1TXD"
FT   HELIX           926..929
FT                   /evidence="ECO:0007829|PDB:1TXD"
FT   HELIX           932..949
FT                   /evidence="ECO:0007829|PDB:1TXD"
FT   HELIX           954..993
FT                   /evidence="ECO:0007829|PDB:1TXD"
FT   STRAND          1001..1003
FT                   /evidence="ECO:0007829|PDB:1X86"
FT   HELIX           1005..1007
FT                   /evidence="ECO:0007829|PDB:1X86"
FT   HELIX           1008..1011
FT                   /evidence="ECO:0007829|PDB:1TXD"
FT   HELIX           1015..1017
FT                   /evidence="ECO:0007829|PDB:1TXD"
FT   STRAND          1020..1033
FT                   /evidence="ECO:0007829|PDB:1TXD"
FT   STRAND          1038..1053
FT                   /evidence="ECO:0007829|PDB:1TXD"
FT   STRAND          1056..1058
FT                   /evidence="ECO:0007829|PDB:1TXD"
FT   STRAND          1078..1081
FT                   /evidence="ECO:0007829|PDB:1TXD"
FT   HELIX           1082..1084
FT                   /evidence="ECO:0007829|PDB:1TXD"
FT   STRAND          1085..1089
FT                   /evidence="ECO:0007829|PDB:1TXD"
FT   STRAND          1091..1093
FT                   /evidence="ECO:0007829|PDB:1X86"
FT   STRAND          1096..1102
FT                   /evidence="ECO:0007829|PDB:1TXD"
FT   STRAND          1107..1113
FT                   /evidence="ECO:0007829|PDB:1TXD"
FT   HELIX           1117..1137
FT                   /evidence="ECO:0007829|PDB:1TXD"
FT   MOD_RES         Q9NZN5-2:41
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18220336,
FT                   ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:24275569"
SQ   SEQUENCE   1544 AA;  173232 MW;  0B7E319CF7C7A224 CRC64;
     MSGTQSTITD RFPLKKPIRH GSILNRESPT DKKQKVERIA SHDFDPTDSS SKKTKSSSEE
     SRSEIYGLVQ RCVIIQKDDN GFGLTVSGDN PVFVQSVKED GAAMRAGVQT GDRIIKVNGT
     LVTHSNHLEV VKLIKSGSYV ALTVQGRPPG SPQIPLADSE VEPSVIGHMS PIMTSPHSPG
     ASGNMERITS PVLMGEENNV VHNQKVEILR KMLQKEQERL QLLQEDYNRT PAQRLLKEIQ
     EAKKHIPQLQ EQLSKATGSA QDGAVVTPSR PLGDTLTVSE AETDPGDVLG RTDCSSGDAS
     RPSSDNADSP KSGPKERIYL EENPEKSETI QDTDTQSLVG SPSTRIAPHI IGAEDDDFGT
     EHEQINGQCS CFQSIELLKS RPAHLAVFLH HVVSQFDPAT LLCYLYSDLY KHTNSKETRR
     IFLEFHQFFL DRSAHLKVSV PDEMSADLEK RRPELIPEDL HRHYIQTMQE RVHPEVQRHL
     EDFRQKRSMG LTLAESELTK LDAERDKDRL TLEKERTCAE QIVAKIEEVL MTAQAVEEDK
     SSTMQYVILM YMKHLGVKVK EPRNLEHKRG RIGFLPKIKQ SMKKDKEGEE KGKRRGFPSI
     LGPPRRPSRH DNSAIGRAME LQKARHPKHL STPSSVSPEP QDSAKLRQSG LANEGTDAGY
     LPANSMSSVA SGASFSQEGG KENDTGSKQV GETSAPGDTL DGTPRTLNTV FDFPPPPLDQ
     VQEEECEVER VTEHGTPKPF RKFDSVAFGE SQSEDEQFEN DLETDPPNWQ QLVSREVLLG
     LKPCEIKRQE VINELFYTER AHVRTLKVLD QVFYQRVSRE GILSPSELRK IFSNLEDILQ
     LHIGLNEQMK AVRKRNETSV IDQIGEDLLT WFSGPGEEKL KHAAATFCSN QPFALEMIKS
     RQKKDSRFQT FVQDAESNPL CRRLQLKDII PTQMQRLTKY PLLLDNIAKY TEWPTEREKV
     KKAADHCRQI LNYVNQAVKE AENKQRLEDY QRRLDTSSLK LSEYPNVEEL RNLDLTKRKM
     IHEGPLVWKV NRDKTIDLYT LLLEDILVLL QKQDDRLVLR CHSKILASTA DSKHTFSPVI
     KLSTVLVRQV ATDNKALFVI SMSDNGAQIY ELVAQTVSEK TVWQDLICRM AASVKEQSTK
     PIPLPQSTPG EGDNDEEDPS KLKEEQHGIS VTGLQSPDRD LGLESTLISS KPQSHSLSTS
     GKSEVRDLFV AERQFAKEQH TDGTLKEVGE DYQIAIPDSH LPVSEERWAL DALRNLGLLK
     QLLVQQLGLT EKSVQEDWQH FPRYRTASQG PQTDSVIQNS ENIKAYHSGE GHMPFRTGTG
     DIATCYSPRT STESFAPRDS VGLAPQDSQA SNILVMDHMI MTPEMPTMEP EGGLDDSGEH
     FFDAREAHSD ENPSEGDGAV NKEEKDVNLR ISGNYLILDG YDPVQESSTD EEVASSLTLQ
     PMTGIPAVES THQQQHSPQN THSDGAISPF TPEFLVQQRW GAMEYSCFEI QSPSSCADSQ
     SQIMEYIHKI EADLEHLKKV EESYTILCQR LAGSALTDKH SDKS
//