GA2L2_MOUSE
ID GA2L2_MOUSE Reviewed; 860 AA.
AC Q5SSG4; B9EJR3;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 116.
DE RecName: Full=GAS2-like protein 2;
DE AltName: Full=Growth arrest-specific protein 2-like 2;
GN Name=Gas2l2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Testis;
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 FUNCTION, INTERACTION WITH ADORA2A; GNAS; GNAL; GNAQ AND GNA13, AND
RP SUBCELLULAR LOCATION.
RX PubMed=23994616; DOI=10.1016/j.bbamcr.2013.08.009;
RA Wu Y.C., Lai H.L., Chang W.C., Lin J.T., Liu Y.J., Chern Y.;
RT "A novel Galphas-binding protein, Gas-2 like 2, facilitates the signaling
RT of the A2A adenosine receptor.";
RL Biochim. Biophys. Acta 1833:3145-3154(2013).
RN [4]
RP INTERACTION WITH MAPRE1.
RX PubMed=24706950; DOI=10.1242/jcs.140558;
RA Stroud M.J., Nazgiewicz A., McKenzie E.A., Wang Y., Kammerer R.A.,
RA Ballestrem C.;
RT "GAS2-like proteins mediate communication between microtubules and actin
RT through interactions with end-binding proteins.";
RL J. Cell Sci. 127:2672-2682(2014).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE,
RP AND CONDITIONAL KNOCKOUT IN TRACHEAL CELLS.
RX PubMed=30665704; DOI=10.1016/j.ajhg.2018.12.009;
RA Bustamante-Marin X.M., Yin W.N., Sears P.R., Werner M.E., Brotslaw E.J.,
RA Mitchell B.J., Jania C.M., Zeman K.L., Rogers T.D., Herring L.E.,
RA Refabert L., Thomas L., Amselem S., Escudier E., Legendre M., Grubb B.R.,
RA Knowles M.R., Zariwala M.A., Ostrowski L.E.;
RT "Lack of GAS2L2 Causes PCD by Impairing Cilia Orientation and Mucociliary
RT Clearance.";
RL Am. J. Hum. Genet. 104:229-245(2019).
CC -!- FUNCTION: Involved in the cross-linking of microtubules and
CC microfilaments (By similarity). Regulates microtubule dynamics and
CC stability by interacting with microtubule plus-end tracking proteins,
CC such as MAPRE1, to regulate microtubule growth along actin stress
CC fibers (By similarity). Enhances ADORA2-mediated adenylyl cyclase
CC activation by acting as a scaffold to recruit trimeric G-protein
CC complexes to ADORA2A (PubMed:23994616). Regulates ciliary orientation
CC and performance in cells located in the airway (PubMed:30665704).
CC {ECO:0000250|UniProtKB:Q8NHY3, ECO:0000269|PubMed:23994616,
CC ECO:0000269|PubMed:30665704}.
CC -!- SUBUNIT: Interacts with ADORA2A (via its cytoplasmic C-terminal domain)
CC (PubMed:23994616). Interacts with GNAS, GNAL, GNAQ, and GNA13
CC (PubMed:23994616). Interacts with MAPRE1 (PubMed:24706950).
CC {ECO:0000269|PubMed:23994616, ECO:0000269|PubMed:24706950}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:23994616}. Cell membrane
CC {ECO:0000269|PubMed:23994616}. Cytoplasm, cytoskeleton, stress fiber
CC {ECO:0000250|UniProtKB:Q8NHY3}. Cytoplasm, cytoskeleton, cilium basal
CC body {ECO:0000269|PubMed:30665704}. Note=Colocalizes with ADORA2A at
CC neuronal processes (By similarity). Colocalizes with and tracks the
CC tips of microtubule plus ends (By similarity).
CC {ECO:0000250|UniProtKB:D3ZUE1, ECO:0000250|UniProtKB:Q8NHY3}.
CC -!- TISSUE SPECIFICITY: Expressed in tracheal epithelial cells (at protein
CC level). {ECO:0000269|PubMed:30665704}.
CC -!- DISRUPTION PHENOTYPE: Knockout mice exhibit a high rate of neonatal
CC death (PubMed:30665704). Mice that survive show signs of hydrocephalus
CC at postnatal days 14 and 21, along with mucus accumulation in multiple
CC sinuses, and remodeling of the nasal cavity (PubMed:30665704).
CC Conditional knockout in tracheal cells lead to isolated cases of
CC hydrocephalus, as well as chronic rhinosinusitis and accumulation of
CC mucus in the nasal cavity, which is caused by impaired mucociliary
CC clearance (PubMed:30665704). {ECO:0000269|PubMed:30665704}.
CC -!- SIMILARITY: Belongs to the GAS2 family. {ECO:0000305}.
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DR EMBL; AL663096; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC147480; AAI47481.1; -; mRNA.
DR EMBL; BC150847; AAI50848.1; -; mRNA.
DR CCDS; CCDS25164.1; -.
DR RefSeq; NP_001013781.1; NM_001013759.2.
DR AlphaFoldDB; Q5SSG4; -.
DR SMR; Q5SSG4; -.
DR STRING; 10090.ENSMUSP00000051907; -.
DR iPTMnet; Q5SSG4; -.
DR PhosphoSitePlus; Q5SSG4; -.
DR PaxDb; Q5SSG4; -.
DR PRIDE; Q5SSG4; -.
DR ProteomicsDB; 265724; -.
DR Antibodypedia; 73370; 73 antibodies from 17 providers.
DR DNASU; 237891; -.
DR Ensembl; ENSMUST00000052521; ENSMUSP00000051907; ENSMUSG00000020686.
DR GeneID; 237891; -.
DR KEGG; mmu:237891; -.
DR UCSC; uc007koy.2; mouse.
DR CTD; 246176; -.
DR MGI; MGI:3652048; Gas2l2.
DR VEuPathDB; HostDB:ENSMUSG00000020686; -.
DR eggNOG; KOG0516; Eukaryota.
DR GeneTree; ENSGT00940000162866; -.
DR HOGENOM; CLU_015447_1_0_1; -.
DR InParanoid; Q5SSG4; -.
DR OMA; QPCHFRN; -.
DR OrthoDB; 1343422at2759; -.
DR PhylomeDB; Q5SSG4; -.
DR TreeFam; TF323754; -.
DR BioGRID-ORCS; 237891; 4 hits in 72 CRISPR screens.
DR PRO; PR:Q5SSG4; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q5SSG4; protein.
DR Bgee; ENSMUSG00000020686; Expressed in dentate gyrus of hippocampal formation granule cell and 11 other tissues.
DR ExpressionAtlas; Q5SSG4; baseline and differential.
DR Genevisible; Q5SSG4; MM.
DR GO; GO:0005884; C:actin filament; ISO:MGI.
DR GO; GO:0036064; C:ciliary basal body; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005874; C:microtubule; ISO:MGI.
DR GO; GO:0035371; C:microtubule plus-end; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0001725; C:stress fiber; ISO:MGI.
DR GO; GO:0051015; F:actin filament binding; ISS:UniProtKB.
DR GO; GO:0008093; F:cytoskeletal anchor activity; ISS:UniProtKB.
DR GO; GO:0001965; F:G-protein alpha-subunit binding; IPI:UniProtKB.
DR GO; GO:0008017; F:microtubule binding; ISS:UniProtKB.
DR GO; GO:0051764; P:actin crosslink formation; IBA:GO_Central.
DR GO; GO:0001578; P:microtubule bundle formation; ISS:UniProtKB.
DR GO; GO:0007026; P:negative regulation of microtubule depolymerization; ISS:UniProtKB.
DR GO; GO:0045745; P:positive regulation of G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:1904825; P:protein localization to microtubule plus-end; ISO:MGI.
DR GO; GO:0060296; P:regulation of cilium beat frequency involved in ciliary motility; IMP:UniProtKB.
DR GO; GO:0031110; P:regulation of microtubule polymerization or depolymerization; ISO:MGI.
DR CDD; cd00014; CH; 1.
DR Gene3D; 1.10.418.10; -; 1.
DR Gene3D; 3.30.920.20; -; 1.
DR InterPro; IPR001715; CH-domain.
DR InterPro; IPR036872; CH_dom_sf.
DR InterPro; IPR003108; GAR_dom.
DR InterPro; IPR036534; GAR_dom_sf.
DR Pfam; PF00307; CH; 1.
DR Pfam; PF02187; GAS2; 1.
DR SMART; SM00033; CH; 1.
DR SMART; SM00243; GAS2; 1.
DR SUPFAM; SSF143575; SSF143575; 1.
DR SUPFAM; SSF47576; SSF47576; 1.
DR PROSITE; PS50021; CH; 1.
DR PROSITE; PS51460; GAR; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cell projection; Cytoplasm; Cytoskeleton; Membrane;
KW Reference proteome.
FT CHAIN 1..860
FT /note="GAS2-like protein 2"
FT /id="PRO_0000190445"
FT DOMAIN 32..159
FT /note="Calponin-homology (CH)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00044"
FT DOMAIN 201..273
FT /note="GAR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00792"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 281..459
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 431..860
FT /note="Interaction with ADORA2A and GNAS"
FT /evidence="ECO:0000269|PubMed:23994616"
FT REGION 473..574
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 697..743
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 758..781
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 801..860
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 299..336
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 363..396
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 424..452
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 509..530
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 531..545
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 546..561
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 697..732
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 860 AA; 94318 MW; FDAC3DEFC5D213A1 CRC64;
MSQHVGHGRR PRTPGPPVRS IRPFKSSEQY LEAMKEDLAE WLRDLYGLDI DADNFLRVLE
TGLVLCRHAN TVTEAALAFL AEAPERAQKI PMPQAGVFCN GAAQPGTFQA RDNISNFIQW
CRKEMGIQEV LMFETEDLVL RKNVKSVVLC LLELGRRAWR FGVAAPALVH LEEEIDEELR
RDLALPSPDP PPPIPPARRP CHFHNLDQMV QSLVSHCTCP VQFSMVKISE GKYRVGDSNT
LIFIRILRSH VMVRVGGGWD TLGHYLDKHD PCRCTSLSHK PGSFLKPPGP PVQHEVKVQD
GPSQPQPTMT ISRSQSPLPP VDWKTYTSSS RKLRPPTPSS PGLRSEPPVR ARTLREDPLP
RSQEKPTPSQ RMSSPGPQFS STCRGPDLQS TLSGKRANRC PGEPPRGRTP TLWVHKEAGS
RGTHTKAPTP QRLQIPEATS KRTSARGPSP PPRSSSLASP HMIWVLHQGA SPQLSEPMTV
HSSSPGKGLT KIPIRLSPAR PPTPGRSSLG TEGEYSTGRG SISSRALEGN LDRSTHGHHS
VEASGDHQTD IQTTSETEDP RSLGTQKWKE RHTSLALGRR REQALYDNLK EEVVANMKLL
EVGTAYTQGT RSQAIPRSGV YVPSLGGRWP EPGGPYDKVI RELVQGPPPL LKVDLKAWKV
GSECLPRPIV DPGSPKEKLG SRETGTRIKA SLNAEDTTVR TVSPARGQGC STPPVSANLE
APTRSCSDPS SDKASVCLGK GKRTLRKPQK IPSIYKLKLR PRIRPRRDHR PEKRPSRIPK
PLPYSCLVLA RTAPGSRLLK ATLGGKGGVP CQVNGTGKKE EEKKKGGSNI SLESSIQPAE
SQEPLKLGGT PLSPEEESWV
