AGRG1_HUMAN
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 03-AUG-2022, entry version 188.
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}; Synonyms=GPR56, TM7LN4, TM7XN1;
GN 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 BFPP TRP-38; CYS-88; SER-91; SER-346; SER-349;
RP 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 BFPP 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 BPPR.
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 BFPP 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 BFPP 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 BFPP LYS-496, AND CHARACTERIZATION OF VARIANT BFPP 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 BFPP 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: Polymicrogyria, bilateral frontoparietal (BFPP) [MIM:606854]:
CC A malformation of the cortex in which the brain surface is irregular
CC and characterized by an excessive number of small gyri with abnormal
CC lamination, most severe in the frontoparietal regions. BFPP clinical
CC manifestations include developmental and psychomotor delay, cerebellar
CC and pyramidal signs, truncal ataxia, seizures, hyperreflexia.
CC Polymicrogyria is a heterogeneous disorder, considered to be the result
CC of postmigratory abnormal cortical organization.
CC {ECO:0000269|PubMed:15044805, ECO:0000269|PubMed:16240336,
CC ECO:0000269|PubMed:21349848, ECO:0000269|PubMed:21723461,
CC ECO:0000269|PubMed:22238662, ECO:0000269|PubMed:24949629}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Polymicrogyria, bilateral perisylvian, autosomal recessive
CC (BPPR) [MIM:615752]: A form of polymicrogyria, a malformation of the
CC cortex in which the brain surface is irregular and characterized by an
CC excessive number of small gyri with abnormal lamination. BPPR is
CC characterized by strikingly restricted polymicrogyria limited to the
CC cortex surrounding the Sylvian fissure. Affected individuals have
CC intellectual and language difficulty and seizures, but no motor
CC disability. Polymicrogyria is a heterogeneous disorder, considered to
CC be the result of post-migratory abnormal cortical organization.
CC {ECO:0000269|PubMed:24531968}. Note=The disease is caused by variants
CC affecting the gene represented in this entry. Homozygous deletion of 1
CC of 2 tandem 15-bp repeats located 144 bp upstream of the ADGRG1 non-
CC 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}.
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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. [Q9Y653-1]
DR RefSeq; XP_006721408.1; XM_006721345.3. [Q9Y653-1]
DR RefSeq; XP_006721409.1; XM_006721346.2. [Q9Y653-1]
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. [Q9Y653-1]
DR RefSeq; XP_011521767.1; XM_011523465.2. [Q9Y653-1]
DR RefSeq; XP_011521768.1; XM_011523466.2. [Q9Y653-1]
DR RefSeq; XP_011521769.1; XM_011523467.2. [Q9Y653-1]
DR RefSeq; XP_011521770.1; XM_011523468.2. [Q9Y653-1]
DR RefSeq; XP_016879381.1; XM_017023892.1. [Q9Y653-2]
DR AlphaFoldDB; Q9Y653; -.
DR SMR; Q9Y653; -.
DR BioGRID; 114704; 100.
DR CORUM; Q9Y653; -.
DR IntAct; Q9Y653; 8.
DR MINT; Q9Y653; -.
DR STRING; 9606.ENSP00000455215; -.
DR ChEMBL; CHEMBL4523929; -.
DR MEROPS; P02.008; -.
DR GlyConnect; 1288; 5 N-Linked glycans (2 sites).
DR GlyGen; Q9Y653; 7 sites, 5 N-linked glycans (2 sites).
DR iPTMnet; Q9Y653; -.
DR PhosphoSitePlus; Q9Y653; -.
DR BioMuta; ADGRG1; -.
DR DMDM; 45476992; -.
DR EPD; Q9Y653; -.
DR jPOST; Q9Y653; -.
DR MassIVE; Q9Y653; -.
DR MaxQB; Q9Y653; -.
DR PaxDb; Q9Y653; -.
DR PeptideAtlas; Q9Y653; -.
DR PRIDE; Q9Y653; -.
DR ProteomicsDB; 86601; -. [Q9Y653-1]
DR ProteomicsDB; 86602; -. [Q9Y653-2]
DR Antibodypedia; 15123; 331 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 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; NQKWPHV; -.
DR OrthoDB; 501343at2759; -.
DR PhylomeDB; Q9Y653; -.
DR TreeFam; TF321769; -.
DR PathwayCommons; Q9Y653; -.
DR SignaLink; Q9Y653; -.
DR SIGNOR; Q9Y653; -.
DR BioGRID-ORCS; 9289; 25 hits in 1081 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 199 other tissues.
DR ExpressionAtlas; Q9Y653; baseline and differential.
DR Genevisible; Q9Y653; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0097451; C:glial limiting end-foot; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; TAS:GDB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0045121; C:membrane raft; IEA:UniProtKB-SubCell.
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 InterPro; IPR040950; GAIN_A.
DR InterPro; IPR046338; GAIN_dom_sf.
DR InterPro; IPR017981; GPCR_2-like.
DR InterPro; IPR000832; GPCR_2_secretin-like.
DR InterPro; IPR003910; GPR1/GPR3/GPR5.
DR InterPro; IPR000203; GPS.
DR InterPro; IPR040679; PLL.
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.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell adhesion; Cell membrane; Developmental protein;
KW Differentiation; Direct protein sequencing; Disease variant;
KW G-protein coupled receptor; Glycoprotein; Heparin-binding; Membrane;
KW Neurogenesis; Receptor; Reference proteome; Secreted; Signal; Transducer;
KW 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 BFPP; abolishes interaction with COL3A1;
FT 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 BFPP; abolishes interaction with COL3A1;
FT reduces cell surface localization; 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 BFPP; abolishes interaction with COL3A1;
FT reduces cell surface localization; 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 BFPP; abolishes interaction with COL3A1;
FT reduces cell surface localization; 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 BFPP; abolishes autoproteolytic cleavage;
FT reduces cell surface localization; 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 BFPP; abolishes autoproteolytic cleavage;
FT 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 BFPP; reduces cell surface localization;
FT 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 BFPP; reduces cell surface localization;
FT 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 BFPP; 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 heparin-
FT 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"
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
