ID AGRG1_HUMAN Reviewed; 693 AA. AC Q9Y653; A6NIT7; A6NJV9; B0M0K4; B4DR54; O95966; Q6ZMP1; Q8NGB3; Q96HB4; DT 15-MAR-2004, integrated into UniProtKB/Swiss-Prot. DT 15-MAR-2004, sequence version 2. DT 27-MAR-2024, entry version 197. DE RecName: Full=Adhesion G-protein coupled receptor G1; DE AltName: Full=G-protein coupled receptor 56; DE AltName: Full=Protein TM7XN1; DE Contains: DE RecName: Full=ADGRG1 N-terminal fragment; DE Short=ADGRG1 NT; DE AltName: Full=GPR56 N-terminal fragment; DE Short=GPR56 NT; DE Short=GPR56(N); DE AltName: Full=GPR56 extracellular subunit; DE AltName: Full=GPR56 subunit alpha; DE Contains: DE RecName: Full=ADGRG1 C-terminal fragment; DE Short=ADGRG1 CT; DE AltName: Full=GPR56 C-terminal fragment; DE Short=GPR56 CT; DE Short=GPR56(C); DE AltName: Full=GPR56 seven-transmembrane subunit; DE Short=GPR56 7TM; DE AltName: Full=GPR56 subunit beta; DE Flags: Precursor; GN Name=ADGRG1 {ECO:0000312|HGNC:HGNC:4512}; GN Synonyms=GPR56, TM7LN4, TM7XN1; ORFNames=UNQ540/PRO1083; 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] (ISOFORM 1), AND VARIANTS ARG-281 AND HIS-306. RX PubMed=10049584; DOI=10.1006/geno.1998.5644; RA Liu M., Parker R.M.C., Darby K., Eyre H.J., Copeland N.G., Crawford J., RA Gilbert D.J., Sutherland G.R., Jenkins N.A., Herzog H.; RT "GPR56, a novel secretin-like human G-protein-coupled receptor gene."; RL Genomics 55:296-305(1999). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANTS ARG-281 AND HIS-306. RX PubMed=10100861; DOI=10.1016/s0014-5793(99)00230-6; RA Zendman A.J.W., Cornelissen I.M.H.A., Weidle U.H., Ruiter D.J., RA van Muijen G.N.P.; RT "TM7XN1, a novel human EGF-TM7 like protein, detected with mRNA RT differential display using human melanoma cell lines with different RT metastatic potential."; RL FEBS Lett. 446:292-298(1999). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Brain; RA Kaighin V.A., Martin A.L., Aronstam R.S.; RL Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A., RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale effort to RT identify novel human secreted and transmembrane proteins: a bioinformatics RT assessment."; RL Genome Res. 13:2265-2270(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4), AND VARIANTS RP ARG-281 AND HIS-306. RC TISSUE=Prostate; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Suwa M., Sato T., Okouchi I., Arita M., Futami K., Matsumoto S., RA Tsutsumi S., Aburatani H., Asai K., Akiyama Y.; RT "Genome-wide discovery and analysis of human seven transmembrane helix RT receptor genes."; RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT HIS-306. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5), AND VARIANT HIS-306. RC TISSUE=Colon carcinoma; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15616553; DOI=10.1038/nature03187; RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M., RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., RA Myers R.M., Rubin E.M., Pennacchio L.A.; RT "The sequence and analysis of duplication-rich human chromosome 16."; RL Nature 432:988-994(2004). RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT HIS-306. RC TISSUE=Placenta; 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 [12] RP PROTEIN SEQUENCE OF 26-40. RX PubMed=15340161; DOI=10.1110/ps.04682504; RA Zhang Z., Henzel W.J.; RT "Signal peptide prediction based on analysis of experimentally verified RT cleavage sites."; RL Protein Sci. 13:2819-2824(2004). RN [13] RP INTERACTION WITH CD81; CD9 AND GNA11. RX PubMed=15004227; DOI=10.1091/mbc.e03-12-0886; RA Little K.D., Hemler M.E., Stipp C.S.; RT "Dynamic regulation of a GPCR-tetraspanin-G protein complex on intact RT cells: central role of CD81 in facilitating GPR56-Galpha q/11 RT association."; RL Mol. Biol. Cell 15:2375-2387(2004). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [15] RP FUNCTION, TISSUE SPECIFICITY, AND INTERACTION WITH TGM2. RX PubMed=16757564; DOI=10.1073/pnas.0602681103; RA Xu L., Begum S., Hearn J.D., Hynes R.O.; RT "GPR56, an atypical G protein-coupled receptor, binds tissue RT transglutaminase, TG2, and inhibits melanoma tumor growth and metastasis."; RL Proc. Natl. Acad. Sci. U.S.A. 103:9023-9028(2006). RN [16] RP FUNCTION, AND ALTERNATIVE SPLICING (ISOFORMS 3; 4 AND 5). RX PubMed=19572147; DOI=10.1007/s00432-009-0635-z; RA Kim J.E., Han J.M., Park C.R., Shin K.J., Ahn C., Seong J.Y., Hwang J.I.; RT "Splicing variants of the orphan G-protein-coupled receptor GPR56 regulate RT the activity of transcription factors associated with tumorigenesis."; RL J. Cancer Res. Clin. Oncol. 136:47-53(2010). RN [17] RP FUNCTION (ADGRG1 N-TERMINAL FRAGMENT AND ADGRG1 C-TERMINAL FRAGMENT), AND RP INTERACTION WITH TGM2. RX PubMed=21724588; DOI=10.1158/0008-5472.can-10-4543; RA Yang L., Chen G., Mohanty S., Scott G., Fazal F., Rahman A., Begum S., RA Hynes R.O., Xu L.; RT "GPR56 Regulates VEGF production and angiogenesis during melanoma RT progression."; RL Cancer Res. 71:5558-5568(2011). RN [18] RP SUBUNIT, SUBCELLULAR LOCATION (ADGRG1 N-TERMINAL FRAGMENT), GLYCOSYLATION, RP CHARACTERIZATION OF VARIANTS CDCBM14A TRP-38; CYS-88; SER-91; SER-346; RP SER-349; TRP-565 AND ARG-640, AND MUTAGENESIS OF THR-383. RX PubMed=21349848; DOI=10.1074/jbc.m110.183830; RA Chiang N.Y., Hsiao C.C., Huang Y.S., Chen H.Y., Hsieh I.J., Chang G.W., RA Lin H.H.; RT "Disease-associated GPR56 mutations cause bilateral frontoparietal RT polymicrogyria via multiple mechanisms."; RL J. Biol. Chem. 286:14215-14225(2011). RN [19] RP FUNCTION, SUBUNIT, ACTIVITY REGULATION, AND UBIQUITINATION. RX PubMed=21708946; DOI=10.1074/jbc.m111.247973; RA Paavola K.J., Stephenson J.R., Ritter S.L., Alter S.P., Hall R.A.; RT "The N terminus of the adhesion G protein-coupled receptor GPR56 controls RT receptor signaling activity."; RL J. Biol. Chem. 286:28914-28921(2011). RN [20] RP PROTEOLYTIC PROCESSING, AND MUTAGENESIS OF HIS-381 AND THR-383. RX PubMed=22333914; DOI=10.1038/emboj.2012.26; RA Arac D., Boucard A.A., Bolliger M.F., Nguyen J., Soltis S.M., Sudhof T.C., RA Brunger A.T.; RT "A novel evolutionarily conserved domain of cell-adhesion GPCRs mediates RT autoproteolysis."; RL EMBO J. 31:1364-1378(2012). RN [21] RP LIGAND-BINDING, AND CHARACTERIZATION OF VARIANTS CDCBM14A GLN-38; TRP-38; RP CYS-88 AND SER-91. RX PubMed=22238662; DOI=10.1371/journal.pone.0029818; RA Luo R., Jin Z., Deng Y., Strokes N., Piao X.; RT "Disease-associated mutations prevent GPR56-collagen III interaction."; RL PLoS ONE 7:E29818-E29818(2012). RN [22] RP FUNCTION, AND INVOLVEMENT IN CDCBM14B. RX PubMed=24531968; DOI=10.1126/science.1244392; RA Bae B.I., Tietjen I., Atabay K.D., Evrony G.D., Johnson M.B., Asare E., RA Wang P.P., Murayama A.Y., Im K., Lisgo S.N., Overman L., Sestan N., RA Chang B.S., Barkovich A.J., Grant P.E., Topcu M., Politsky J., Okano H., RA Piao X., Walsh C.A.; RT "Evolutionarily dynamic alternative splicing of GPR56 regulates regional RT cerebral cortical patterning."; RL Science 343:764-768(2014). RN [23] RP ACTIVITY REGULATION. RX PubMed=25918380; DOI=10.1073/pnas.1421785112; RA Stoveken H.M., Hajduczok A.G., Xu L., Tall G.G.; RT "Adhesion G protein-coupled receptors are activated by exposure of a RT cryptic tethered agonist."; RL Proc. Natl. Acad. Sci. U.S.A. 112:6194-6199(2015). RN [24] RP ACTIVITY REGULATION, AND MUTAGENESIS OF THR-383. RX PubMed=26710850; DOI=10.1074/jbc.m115.689349; RA Kishore A., Purcell R.H., Nassiri-Toosi Z., Hall R.A.; RT "Stalk-dependent and stalk-independent signaling by the adhesion G protein- RT coupled receptors GPR56 (ADGRG1) and BAI1 (ADGRB1)."; RL J. Biol. Chem. 291:3385-3394(2016). RN [25] RP HEPARIN-BINDING DOMAINS, AND MUTAGENESIS OF HIS-28; ARG-29 AND ARG-33. RX PubMed=27068534; DOI=10.1242/jcs.174458; RA Chiang N.Y., Chang G.W., Huang Y.S., Peng Y.M., Hsiao C.C., Kuo M.L., RA Lin H.H.; RT "Heparin interacts with adhesion-GPCR GPR56/ADGRG1, reduces receptor RT shedding, and promotes cell adhesion and motility."; RL J. Cell Sci. 129:2156-2169(2016). RN [26] RP INTERACTION WITH COL3A1. RX PubMed=28258187; DOI=10.1136/jmedgenet-2016-104421; RA Vandervore L., Stouffs K., Tanyalcin I., Vanderhasselt T., Roelens F., RA Holder-Espinasse M., Joergensen A., Pepin M.G., Petit F., Khau Van Kien P., RA Bahi-Buisson N., Lissens W., Gheldof A., Byers P.H., Jansen A.C.; RT "Bi-allelic variants in COL3A1 encoding the ligand to GPR56 are associated RT with cobblestone-like cortical malformation, white matter changes and RT cerebellar cysts."; RL J. Med. Genet. 54:432-440(2017). RN [27] RP VARIANTS CDCBM14A TRP-38; CYS-88; SER-91; SER-346 AND TRP-565. RX PubMed=15044805; DOI=10.1126/science.1092780; RA Piao X., Hill R.S., Bodell A., Chang B.S., Basel-Vanagaite L., RA Straussberg R., Dobyns W.B., Qasrawi B., Winter R.M., Innes A.M., Voit T., RA Ross M.E., Michaud J.L., Descarie J.-C., Barkovich A.J., Walsh C.A.; RT "G protein-coupled receptor-dependent development of human frontal RT cortex."; RL Science 303:2033-2036(2004). RN [28] RP VARIANTS CDCBM14A GLN-38; TRP-38; SER-349; TRP-565 AND ARG-640. RX PubMed=16240336; DOI=10.1002/ana.20616; RA Piao X., Chang B.S., Bodell A., Woods K., Benzeev B., Topcu M., RA Guerrini R., Goldberg-Stern H., Sztriha L., Dobyns W.B., Barkovich A.J., RA Walsh C.A.; RT "Genotype-phenotype analysis of human frontoparietal polymicrogyria RT syndromes."; RL Ann. Neurol. 58:680-687(2005). RN [29] RP VARIANT CDCBM14A LYS-496, AND CHARACTERIZATION OF VARIANT CDCBM14A LYS-496. RX PubMed=21723461; DOI=10.1016/j.pediatrneurol.2011.02.004; RA Luo R., Yang H.M., Jin Z., Halley D.J., Chang B.S., MacPherson L., RA Brueton L., Piao X.; RT "A novel GPR56 mutation causes bilateral frontoparietal polymicrogyria."; RL Pediatr. Neurol. 45:49-53(2011). RN [30] RP CHARACTERIZATION OF VARIANT CDCBM14A ARG-640, LIGAND-BINDING, SUBCELLULAR RP LOCATION, AND ACTIVITY REGULATION. RX PubMed=24949629; DOI=10.1371/journal.pone.0100043; RA Luo R., Jeong S.J., Yang A., Wen M., Saslowsky D.E., Lencer W.I., Arac D., RA Piao X.; RT "Mechanism for adhesion G protein-coupled receptor GPR56-mediated RhoA RT activation induced by collagen III stimulation."; RL PLoS ONE 9:E100043-E100043(2014). CC -!- FUNCTION: Receptor involved in cell adhesion and probably in cell-cell CC interactions. Mediates cell matrix adhesion in developing neurons and CC hematopoietic stem cells. Receptor for collagen III/COL3A1 in the CC developing brain and involved in regulation of cortical development, CC specifically in maintenance of the pial basement membrane integrity and CC in cortical lamination (By similarity). Binding to the COL3A1 ligand CC inhibits neuronal migration and activates the RhoA pathway by coupling CC to GNA13 and possibly GNA12 (PubMed:22238662). Plays a role in the CC maintenance of hematopoietic stem cells and/or leukemia stem cells in CC bone marrow niche (By similarity). Plays a critical role in cancer CC progression by inhibiting VEGFA production threreby inhibiting CC angiogenesis through a signaling pathway mediated by PRKCA CC (PubMed:16757564, PubMed:21724588). Plays an essential role in testis CC development (By similarity). {ECO:0000250|UniProtKB:Q8K209, CC ECO:0000269|PubMed:16757564, ECO:0000269|PubMed:19572147, CC ECO:0000269|PubMed:21708946, ECO:0000269|PubMed:21724588, CC ECO:0000269|PubMed:22238662, ECO:0000269|PubMed:24531968}. CC -!- FUNCTION: [ADGRG1 N-terminal fragment]: Plays a critical role in cancer CC progression by activating VEGFA production and angiogenesis through a CC signaling pathway mediated by PRKCA (PubMed:21724588). CC {ECO:0000269|PubMed:21724588}. CC -!- ACTIVITY REGULATION: ADGRG1 NT is proposed to inhibit receptor CC signaling; its interactions with extracellular ligands and /or CC homophilic ADGRG1NT interactions may relieve the inhibition CC (PubMed:21708946, PubMed:24949629, PubMed:25918380). Following ligand CC binding to the N-terminal fragment, the N-terminal fragment is released CC from the seven-transmembrane C-terminal fragment to unveil a new N- CC terminal stalk, which then stimulates G-protein-dependent signaling CC activity (PubMed:25918380). The N-terminal stalk has also been shown to CC be dispensable for at least some G-protein-dependent signaling CC (PubMed:26710850). {ECO:0000269|PubMed:21708946, CC ECO:0000269|PubMed:24949629, ECO:0000269|PubMed:25918380, CC ECO:0000269|PubMed:26710850}. CC -!- SUBUNIT: Heterodimer of 2 chains generated by proteolytic processing; CC the large extracellular N-terminal fragment (ADGRG1 NT) and the CC membrane-bound C-terminal fragment (ADGRG1-CT) predominantly remain CC associated and non-covalently linked. ADGRG1 NT self-associates in a CC trans-trans manner; the homophilic interaction enhances receptor CC signaling. ADGRG1-CT interacts with ARRB2; the interaction is impaired CC by ADGRG1 NT. Interacts with TGM2; TGM2 probably is not a ADGRG1 ligand CC and the interaction is reported controversial (PubMed:16757564, CC PubMed:21349848). Part of a GPCR-tetraspanin complex at least CC consisting of ADGRG1, CD81, eventually CD9, and GNA11 in which CD81 is CC enhancing the association of ADGRG1 with GNA11. Interacts with heparin; CC leading to the reduction of ADGRG1 shedding (PubMed:27068534). CC Interacts with COL3A1 (PubMed:28258187). {ECO:0000269|PubMed:15004227, CC ECO:0000269|PubMed:16757564, ECO:0000269|PubMed:21349848, CC ECO:0000269|PubMed:21708946, ECO:0000269|PubMed:21724588, CC ECO:0000269|PubMed:27068534, ECO:0000269|PubMed:28258187}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21349848, CC ECO:0000269|PubMed:24949629}; Multi-pass membrane protein CC {ECO:0000255}. CC -!- SUBCELLULAR LOCATION: [ADGRG1 N-terminal fragment]: Secreted CC {ECO:0000269|PubMed:21349848}. CC -!- SUBCELLULAR LOCATION: [ADGRG1 C-terminal fragment]: Membrane raft CC {ECO:0000269|PubMed:24949629}. Note=Interaction with its ligand COL3A1 CC leads to the release of ADGRG1 NT from the membrane and triggers the CC association of ADGRG1 CT with lipid rafts. CC {ECO:0000269|PubMed:24949629}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1; CC IsoId=Q9Y653-1; Sequence=Displayed; CC Name=2; Synonyms=S1; CC IsoId=Q9Y653-2; Sequence=VSP_035068; CC Name=3; Synonyms=S2; CC IsoId=Q9Y653-3; Sequence=VSP_047555, VSP_035068; CC Name=4; Synonyms=S3; CC IsoId=Q9Y653-4; Sequence=VSP_047556; CC Name=5; Synonyms=S4; CC IsoId=Q9Y653-5; Sequence=VSP_047554; CC -!- TISSUE SPECIFICITY: Widely distributed with highest levels found in CC thyroid gland, brain and heart. Expressed in a great number of tumor CC cells. Expression is down-regulated in different tumors from highly CC metastatic cells. {ECO:0000269|PubMed:16757564}. CC -!- PTM: Autoproteolytically cleaved into 2 fragments; the large CC extracellular N-terminal fragment (ADGRG1 NT) and the membrane-bound C- CC terminal fragment (ADGRG1 CT) predominantly remain associated and non- CC covalently linked. Shedding to yield the secreted ADGRG1 N-terminal CC fragment seems to involve metalloprotease(s) (PubMed:22333914). CC {ECO:0000269|PubMed:22333914}. CC -!- PTM: N-glycosylated. Contains sialic acid residues. CC {ECO:0000269|PubMed:21349848}. CC -!- PTM: Ubiquitinated. Undergoes polyubiquitination upon activation. CC {ECO:0000269|PubMed:21708946}. CC -!- DISEASE: Cortical dysplasia, complex, with other brain malformations CC 14A (bilateral frontoparietal) (CDCBM14A) [MIM:606854]: An autosomal CC recessive disorder characterized by global developmental delay with CC impaired intellectual development, motor delay, poor speech, cerebellar CC and pyramidal signs, truncal ataxia, and early-onset seizures. Brain CC imaging shows bilateral frontoparietal polymicrogyria, a malformation CC of the cortex in which the brain surface is irregular and characterized CC by an excessive number of small gyri with abnormal lamination. CC Polymicrogyria is considered to be the result of postmigratory abnormal CC cortical organization. {ECO:0000269|PubMed:15044805, CC ECO:0000269|PubMed:16240336, ECO:0000269|PubMed:21349848, CC ECO:0000269|PubMed:21723461, ECO:0000269|PubMed:22238662, CC ECO:0000269|PubMed:24949629}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Cortical dysplasia, complex, with other brain malformations CC 14B (bilateral perisylvian) (CDCBM14B) [MIM:615752]: An autosomal CC recessive disorder characterized by strikingly restricted CC polymicrogyria limited to the cortex surrounding the Sylvian fissure. CC Affected individuals have intellectual and language difficulty and CC seizures, but no motor disability. Polymicrogyria is a malformation of CC the cortex in which the brain surface is irregular and characterized by CC an excessive number of small gyri with abnormal lamination. It is CC considered to be the result of postmigratory abnormal cortical CC organization. {ECO:0000269|PubMed:24531968}. Note=The disease is caused CC by variants affecting the gene represented in this entry. Homozygous CC deletion of 1 of 2 tandem 15-bp repeats located 144 bp upstream of the CC ADGRG1 non-coding exon 1m transcription start site, results in impaired CC perisylvian ADGRG1 expression and disruption of perisylvian gyri CC (PubMed:24531968). {ECO:0000269|PubMed:24531968}. CC -!- MISCELLANEOUS: [Isoform 5]: Has no predictable signal peptide. CC {ECO:0000305}. CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 2 family. LN-TM7 CC subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF106858; AAD30545.1; -; mRNA. DR EMBL; AJ011001; CAB37294.1; -; mRNA. DR EMBL; EU432119; ABY87918.1; -; mRNA. DR EMBL; AY358400; AAQ88766.1; -; mRNA. DR EMBL; AK131550; BAD18684.1; -; mRNA. DR EMBL; AK299110; BAG61166.1; -; mRNA. DR EMBL; AB065909; BAC06124.1; -; Genomic_DNA. DR EMBL; BT007311; AAP35975.1; -; mRNA. DR EMBL; CR936747; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AC018552; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471092; EAW82939.1; -; Genomic_DNA. DR EMBL; CH471092; EAW82940.1; -; Genomic_DNA. DR EMBL; BC008770; AAH08770.1; -; mRNA. DR CCDS; CCDS32460.1; -. [Q9Y653-1] DR CCDS; CCDS32461.1; -. [Q9Y653-2] DR CCDS; CCDS73893.1; -. [Q9Y653-3] DR RefSeq; NP_001139242.1; NM_001145770.2. [Q9Y653-2] DR RefSeq; NP_001139243.1; NM_001145771.2. [Q9Y653-1] DR RefSeq; NP_001139244.1; NM_001145772.2. [Q9Y653-2] DR RefSeq; NP_001139245.1; NM_001145773.2. [Q9Y653-3] DR RefSeq; NP_001139246.1; NM_001145774.2. [Q9Y653-2] DR RefSeq; NP_001277071.1; NM_001290142.1. [Q9Y653-4] DR RefSeq; NP_001277072.1; NM_001290143.1. [Q9Y653-5] DR RefSeq; NP_005673.3; NM_005682.6. [Q9Y653-1] DR RefSeq; NP_958932.1; NM_201524.3. [Q9Y653-2] DR RefSeq; NP_958933.1; NM_201525.3. [Q9Y653-2] DR RefSeq; XP_005256303.1; XM_005256246.2. [Q9Y653-1] DR RefSeq; XP_005256304.1; XM_005256247.2. DR RefSeq; XP_005256305.1; XM_005256248.2. [Q9Y653-1] DR RefSeq; XP_005256306.1; XM_005256249.3. DR RefSeq; XP_005256308.1; XM_005256251.4. DR RefSeq; XP_005256309.1; XM_005256252.2. [Q9Y653-1] DR RefSeq; XP_005256311.1; XM_005256254.2. [Q9Y653-1] DR RefSeq; XP_005256312.1; XM_005256255.2. [Q9Y653-2] DR RefSeq; XP_006721405.1; XM_006721342.2. [Q9Y653-1] DR RefSeq; XP_006721406.1; XM_006721343.3. DR RefSeq; XP_006721407.1; XM_006721344.2. DR RefSeq; XP_006721408.1; XM_006721345.3. DR RefSeq; XP_006721409.1; XM_006721346.2. DR RefSeq; XP_006721410.1; XM_006721347.2. [Q9Y653-3] DR RefSeq; XP_011521765.1; XM_011523463.2. DR RefSeq; XP_011521766.1; XM_011523464.2. DR RefSeq; XP_011521767.1; XM_011523465.2. DR RefSeq; XP_011521768.1; XM_011523466.2. [Q9Y653-1] DR RefSeq; XP_011521769.1; XM_011523467.2. DR RefSeq; XP_011521770.1; XM_011523468.2. [Q9Y653-1] DR RefSeq; XP_016879381.1; XM_017023892.1. [Q9Y653-2] DR PDB; 7SF8; EM; 2.70 A; A=383-693. DR PDBsum; 7SF8; -. DR AlphaFoldDB; Q9Y653; -. DR EMDB; EMD-25077; -. DR SMR; Q9Y653; -. DR BioGRID; 114704; 102. DR CORUM; Q9Y653; -. DR IntAct; Q9Y653; 9. DR MINT; Q9Y653; -. DR STRING; 9606.ENSP00000455215; -. DR ChEMBL; CHEMBL4523929; -. DR MEROPS; P02.008; -. DR GlyConnect; 1288; 5 N-Linked glycans (2 sites). DR GlyCosmos; Q9Y653; 7 sites, 5 glycans. DR GlyGen; Q9Y653; 9 sites, 5 N-linked glycans (2 sites), 1 O-linked glycan (2 sites). DR iPTMnet; Q9Y653; -. DR PhosphoSitePlus; Q9Y653; -. DR SwissPalm; Q9Y653; -. DR BioMuta; ADGRG1; -. DR DMDM; 45476992; -. DR EPD; Q9Y653; -. DR jPOST; Q9Y653; -. DR MassIVE; Q9Y653; -. DR MaxQB; Q9Y653; -. DR PaxDb; 9606-ENSP00000455215; -. DR PeptideAtlas; Q9Y653; -. DR ProteomicsDB; 86601; -. [Q9Y653-1] DR ProteomicsDB; 86602; -. [Q9Y653-2] DR Pumba; Q9Y653; -. DR Antibodypedia; 15123; 365 antibodies from 34 providers. DR DNASU; 9289; -. DR Ensembl; ENST00000388813.9; ENSP00000373465.5; ENSG00000205336.14. [Q9Y653-2] DR Ensembl; ENST00000456916.5; ENSP00000398034.2; ENSG00000205336.14. [Q9Y653-3] DR Ensembl; ENST00000540164.6; ENSP00000444911.2; ENSG00000205336.14. [Q9Y653-2] DR Ensembl; ENST00000562558.6; ENSP00000456620.1; ENSG00000205336.14. [Q9Y653-2] DR Ensembl; ENST00000562631.7; ENSP00000455351.2; ENSG00000205336.14. [Q9Y653-2] DR Ensembl; ENST00000565976.6; ENSP00000454933.2; ENSG00000205336.14. [Q9Y653-1] DR Ensembl; ENST00000567835.5; ENSP00000456794.1; ENSG00000205336.14. [Q9Y653-1] DR Ensembl; ENST00000568908.5; ENSP00000457456.1; ENSG00000205336.14. [Q9Y653-2] DR Ensembl; ENST00000568909.5; ENSP00000455215.1; ENSG00000205336.14. [Q9Y653-1] DR Ensembl; ENST00000673126.2; ENSP00000500185.2; ENSG00000205336.14. [Q9Y653-1] DR GeneID; 9289; -. DR KEGG; hsa:9289; -. DR MANE-Select; ENST00000562631.7; ENSP00000455351.2; NM_201525.4; NP_958933.1. [Q9Y653-2] DR UCSC; uc002emb.3; human. [Q9Y653-1] DR AGR; HGNC:4512; -. DR CTD; 9289; -. DR DisGeNET; 9289; -. DR GeneCards; ADGRG1; -. DR HGNC; HGNC:4512; ADGRG1. DR HPA; ENSG00000205336; Tissue enhanced (thyroid). DR MalaCards; ADGRG1; -. DR MIM; 604110; gene. DR MIM; 606854; phenotype. DR MIM; 615752; phenotype. DR neXtProt; NX_Q9Y653; -. DR OpenTargets; ENSG00000205336; -. DR Orphanet; 101070; Bilateral frontoparietal polymicrogyria. DR Orphanet; 98889; Bilateral perisylvian polymicrogyria. DR PharmGKB; PA28901; -. DR VEuPathDB; HostDB:ENSG00000205336; -. DR eggNOG; KOG4193; Eukaryota. DR GeneTree; ENSGT00940000160843; -. DR HOGENOM; CLU_002753_3_9_1; -. DR InParanoid; Q9Y653; -. DR OMA; NLLWAIF; -. DR OrthoDB; 5477252at2759; -. DR PhylomeDB; Q9Y653; -. DR TreeFam; TF321769; -. DR PathwayCommons; Q9Y653; -. DR SignaLink; Q9Y653; -. DR SIGNOR; Q9Y653; -. DR BioGRID-ORCS; 9289; 26 hits in 1159 CRISPR screens. DR ChiTaRS; ADGRG1; human. DR GenomeRNAi; 9289; -. DR Pharos; Q9Y653; Tbio. DR PRO; PR:Q9Y653; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; Q9Y653; Protein. DR Bgee; ENSG00000205336; Expressed in granulocyte and 201 other cell types or tissues. DR ExpressionAtlas; Q9Y653; baseline and differential. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0097451; C:glial limiting end-foot; ISS:UniProtKB. DR GO; GO:0016020; C:membrane; TAS:GDB. DR GO; GO:0045121; C:membrane raft; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; TAS:ProtInc. DR GO; GO:0005518; F:collagen binding; ISS:UniProtKB. DR GO; GO:0050840; F:extracellular matrix binding; ISS:UniProtKB. DR GO; GO:0004930; F:G protein-coupled receptor activity; ISS:UniProtKB. DR GO; GO:0008201; F:heparin binding; IDA:UniProtKB. DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IBA:GO_Central. DR GO; GO:0001525; P:angiogenesis; IDA:UniProtKB. DR GO; GO:0007420; P:brain development; IMP:GDB. DR GO; GO:0007155; P:cell adhesion; IDA:UniProtKB. DR GO; GO:0016477; P:cell migration; IDA:UniProtKB. DR GO; GO:0007166; P:cell surface receptor signaling pathway; IEA:InterPro. DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc. DR GO; GO:0021801; P:cerebral cortex radial glia-guided migration; ISS:UniProtKB. DR GO; GO:0021796; P:cerebral cortex regionalization; IEA:Ensembl. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:ProtInc. DR GO; GO:0061484; P:hematopoietic stem cell homeostasis; IEA:Ensembl. DR GO; GO:0021819; P:layer formation in cerebral cortex; ISS:UniProtKB. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB. DR GO; GO:2001223; P:negative regulation of neuron migration; ISS:UniProtKB. DR GO; GO:0061351; P:neural precursor cell proliferation; IEA:Ensembl. DR GO; GO:0045785; P:positive regulation of cell adhesion; IDA:UniProtKB. DR GO; GO:2000179; P:positive regulation of neural precursor cell proliferation; IEA:Ensembl. DR GO; GO:0035025; P:positive regulation of Rho protein signal transduction; ISS:UniProtKB. DR GO; GO:0070528; P:protein kinase C signaling; IDA:UniProtKB. DR GO; GO:0007266; P:Rho protein signal transduction; IDA:UniProtKB. DR GO; GO:0072520; P:seminiferous tubule development; IEA:Ensembl. DR GO; GO:0010573; P:vascular endothelial growth factor production; IDA:UniProtKB. DR Gene3D; 2.60.220.50; -; 1. DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1. DR InterPro; IPR040950; ADGRG1_GAIN_A. DR InterPro; IPR046338; GAIN_dom_sf. DR InterPro; IPR017981; GPCR_2-like_7TM. DR InterPro; IPR000832; GPCR_2_secretin-like. DR InterPro; IPR003910; GPR1/GPR3/GPR5. DR InterPro; IPR000203; GPS. DR InterPro; IPR040679; PLL. DR PANTHER; PTHR12011; ADHESION G-PROTEIN COUPLED RECEPTOR; 1. DR PANTHER; PTHR12011:SF318; ADHESION G-PROTEIN COUPLED RECEPTOR G1; 1. DR Pfam; PF00002; 7tm_2; 1. DR Pfam; PF18619; GAIN_A; 1. DR Pfam; PF01825; GPS; 1. DR Pfam; PF18587; PLL; 1. DR PRINTS; PR00249; GPCRSECRETIN. DR PRINTS; PR01422; GPR56ORPHANR. DR SMART; SM00303; GPS; 1. DR PROSITE; PS50261; G_PROTEIN_RECEP_F2_4; 1. DR PROSITE; PS50221; GPS; 1. DR Genevisible; Q9Y653; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell adhesion; Cell membrane; KW Developmental protein; Differentiation; Direct protein sequencing; KW Disease variant; G-protein coupled receptor; Glycoprotein; Heparin-binding; KW Membrane; Neurogenesis; Receptor; Reference proteome; Secreted; Signal; KW Transducer; Transmembrane; Transmembrane helix; Ubl conjugation. FT SIGNAL 1..25 FT /evidence="ECO:0000269|PubMed:15340161" FT CHAIN 26..693 FT /note="Adhesion G-protein coupled receptor G1" FT /id="PRO_0000012880" FT CHAIN 26..?382 FT /note="ADGRG1 N-terminal fragment" FT /evidence="ECO:0000305|PubMed:22333914" FT /id="PRO_0000423086" FT CHAIN ?383..693 FT /note="ADGRG1 C-terminal fragment" FT /evidence="ECO:0000305|PubMed:22333914" FT /id="PRO_0000423087" FT TOPO_DOM 26..402 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 403..423 FT /note="Helical; Name=1" FT /evidence="ECO:0000255" FT TOPO_DOM 424..448 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 449..469 FT /note="Helical; Name=2" FT /evidence="ECO:0000255" FT TOPO_DOM 470..476 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 477..497 FT /note="Helical; Name=3" FT /evidence="ECO:0000255" FT TOPO_DOM 498..518 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 519..539 FT /note="Helical; Name=4" FT /evidence="ECO:0000255" FT TOPO_DOM 540..576 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 577..597 FT /note="Helical; Name=5" FT /evidence="ECO:0000255" FT TOPO_DOM 598..609 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 610..630 FT /note="Helical; Name=6" FT /evidence="ECO:0000255" FT TOPO_DOM 631..636 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 637..657 FT /note="Helical; Name=7" FT /evidence="ECO:0000255" FT TOPO_DOM 658..693 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 343..394 FT /note="GPS" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00098" FT REGION 670..693 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 26..33 FT /ligand="heparin" FT /ligand_id="ChEBI:CHEBI:28304" FT /evidence="ECO:0000269|PubMed:27068534" FT BINDING 190..200 FT /ligand="heparin" FT /ligand_id="ChEBI:CHEBI:28304" FT /evidence="ECO:0000269|PubMed:27068534" FT SITE 382..383 FT /note="Cleavage; by autolysis" FT /evidence="ECO:0000305|PubMed:22333914" FT CARBOHYD 39 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 148 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 171 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 234 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 303 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 324 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 341 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VAR_SEQ 1..175 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_047554" FT VAR_SEQ 21 FT /note="Q -> QASASS (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_047555" FT VAR_SEQ 38..207 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_047556" FT VAR_SEQ 429..434 FT /note="Missing (in isoform 2 and isoform 3)" FT /evidence="ECO:0000303|PubMed:10100861, FT ECO:0000303|PubMed:14702039" FT /id="VSP_035068" FT VARIANT 38 FT /note="R -> Q (in CDCBM14A; abolishes interaction with FT COL3A1; dbSNP:rs764367185)" FT /evidence="ECO:0000269|PubMed:16240336, FT ECO:0000269|PubMed:22238662" FT /id="VAR_069581" FT VARIANT 38 FT /note="R -> W (in CDCBM14A; abolishes interaction with FT COL3A1; reduces cell surface localization; FT dbSNP:rs121908462)" FT /evidence="ECO:0000269|PubMed:15044805, FT ECO:0000269|PubMed:16240336, ECO:0000269|PubMed:21349848, FT ECO:0000269|PubMed:22238662" FT /id="VAR_026242" FT VARIANT 88 FT /note="Y -> C (in CDCBM14A; abolishes interaction with FT COL3A1; reduces cell surface localization; FT dbSNP:rs121908466)" FT /evidence="ECO:0000269|PubMed:15044805, FT ECO:0000269|PubMed:21349848, ECO:0000269|PubMed:22238662" FT /id="VAR_026243" FT VARIANT 91 FT /note="C -> S (in CDCBM14A; abolishes interaction with FT COL3A1; reduces cell surface localization; FT dbSNP:rs121908465)" FT /evidence="ECO:0000269|PubMed:15044805, FT ECO:0000269|PubMed:21349848, ECO:0000269|PubMed:22238662" FT /id="VAR_026244" FT VARIANT 281 FT /note="S -> R (in dbSNP:rs1801257)" FT /evidence="ECO:0000269|PubMed:10049584, FT ECO:0000269|PubMed:10100861, ECO:0000269|PubMed:14702039" FT /id="VAR_017910" FT VARIANT 306 FT /note="Q -> H (in dbSNP:rs1801255)" FT /evidence="ECO:0000269|PubMed:10049584, FT ECO:0000269|PubMed:10100861, ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:17974005, FT ECO:0000269|Ref.7" FT /id="VAR_017911" FT VARIANT 346 FT /note="C -> S (in CDCBM14A; abolishes autoproteolytic FT cleavage; reduces cell surface localization; FT dbSNP:rs121908463)" FT /evidence="ECO:0000269|PubMed:15044805, FT ECO:0000269|PubMed:21349848" FT /id="VAR_026245" FT VARIANT 349 FT /note="W -> S (in CDCBM14A; abolishes autoproteolytic FT cleavage; reduces cell surface localization)" FT /evidence="ECO:0000269|PubMed:16240336, FT ECO:0000269|PubMed:21349848" FT /id="VAR_069582" FT VARIANT 493 FT /note="M -> T (in dbSNP:rs17379472)" FT /id="VAR_049457" FT VARIANT 496 FT /note="E -> K (in CDCBM14A; reduces cell surface FT localization; dbSNP:rs556518689)" FT /evidence="ECO:0000269|PubMed:21723461" FT /id="VAR_069583" FT VARIANT 527 FT /note="P -> L (in dbSNP:rs16958679)" FT /id="VAR_049458" FT VARIANT 565 FT /note="R -> W (in CDCBM14A; reduces cell surface FT localization; dbSNP:rs121908464)" FT /evidence="ECO:0000269|PubMed:15044805, FT ECO:0000269|PubMed:16240336, ECO:0000269|PubMed:21349848" FT /id="VAR_026246" FT VARIANT 640 FT /note="L -> R (in CDCBM14A; unclear effects on cell surface FT localization; blocks downstream RhoA activation)" FT /evidence="ECO:0000269|PubMed:16240336, FT ECO:0000269|PubMed:21349848, ECO:0000269|PubMed:24949629" FT /id="VAR_069584" FT MUTAGEN 28 FT /note="H->A: Abolishes heparin-binding; when associated FT with A-29 and A-33." FT /evidence="ECO:0000269|PubMed:27068534" FT MUTAGEN 29 FT /note="R->A: Abolishes heparin-binding; when associated FT with A-28 and A-33." FT /evidence="ECO:0000269|PubMed:27068534" FT MUTAGEN 33 FT /note="R->A: Reduces heparin-binding. Abolishes FT heparin-binding; when associated with A-28 and A-29." FT /evidence="ECO:0000269|PubMed:27068534" FT MUTAGEN 381 FT /note="H->S: Abolishes cleavage." FT /evidence="ECO:0000269|PubMed:22333914" FT MUTAGEN 383 FT /note="T->G: Abolishes cleavage but does not affect cell FT membrane localization or signaling activity." FT /evidence="ECO:0000269|PubMed:21349848, FT ECO:0000269|PubMed:22333914, ECO:0000269|PubMed:26710850" FT CONFLICT 329 FT /note="V -> A (in Ref. 8)" FT /evidence="ECO:0000305" FT CONFLICT 561 FT /note="M -> R (in Ref. 5; BAD18684)" FT /evidence="ECO:0000305" FT CONFLICT 678 FT /note="S -> C (in Ref. 1; AAD30545)" FT /evidence="ECO:0000305" FT HELIX 385..387 FT /evidence="ECO:0007829|PDB:7SF8" FT HELIX 397..426 FT /evidence="ECO:0007829|PDB:7SF8" FT STRAND 427..429 FT /evidence="ECO:0007829|PDB:7SF8" FT HELIX 441..469 FT /evidence="ECO:0007829|PDB:7SF8" FT HELIX 474..504 FT /evidence="ECO:0007829|PDB:7SF8" FT HELIX 515..534 FT /evidence="ECO:0007829|PDB:7SF8" FT TURN 535..537 FT /evidence="ECO:0007829|PDB:7SF8" FT HELIX 539..541 FT /evidence="ECO:0007829|PDB:7SF8" FT STRAND 563..565 FT /evidence="ECO:0007829|PDB:7SF8" FT HELIX 567..573 FT /evidence="ECO:0007829|PDB:7SF8" FT HELIX 575..596 FT /evidence="ECO:0007829|PDB:7SF8" FT HELIX 609..619 FT /evidence="ECO:0007829|PDB:7SF8" FT HELIX 621..630 FT /evidence="ECO:0007829|PDB:7SF8" FT TURN 633..635 FT /evidence="ECO:0007829|PDB:7SF8" FT HELIX 636..648 FT /evidence="ECO:0007829|PDB:7SF8" FT HELIX 650..661 FT /evidence="ECO:0007829|PDB:7SF8" SQ SEQUENCE 693 AA; 77738 MW; 801C8E62666A5155 CRC64; MTPQSLLQTT LFLLSLLFLV QGAHGRGHRE DFRFCSQRNQ THRSSLHYKP TPDLRISIEN SEEALTVHAP FPAAHPASRS FPDPRGLYHF CLYWNRHAGR LHLLYGKRDF LLSDKASSLL CFQHQEESLA QGPPLLATSV TSWWSPQNIS LPSAASFTFS FHSPPHTAAH NASVDMCELK RDLQLLSQFL KHPQKASRRP SAAPASQQLQ SLESKLTSVR FMGDMVSFEE DRINATVWKL QPTAGLQDLH IHSRQEEEQS EIMEYSVLLP RTLFQRTKGR SGEAEKRLLL VDFSSQALFQ DKNSSQVLGE KVLGIVVQNT KVANLTEPVV LTFQHQLQPK NVTLQCVFWV EDPTLSSPGH WSSAGCETVR RETQTSCFCN HLTYFAVLMV SSVEVDAVHK HYLSLLSYVG CVVSALACLV TIAAYLCSRV PLPCRRKPRD YTIKVHMNLL LAVFLLDTSF LLSEPVALTG SEAGCRASAI FLHFSLLTCL SWMGLEGYNL YRLVVEVFGT YVPGYLLKLS AMGWGFPIFL VTLVALVDVD NYGPIILAVH RTPEGVIYPS MCWIRDSLVS YITNLGLFSL VFLFNMAMLA TMVVQILRLR PHTQKWSHVL TLLGLSLVLG LPWALIFFSF ASGTFQLVVL YLFSIITSFQ GFLIFIWYWS MRLQARGGPS PLKSNSDSAR LPISSGSTSS SRI //