GA2L2_HUMAN
ID GA2L2_HUMAN Reviewed; 880 AA.
AC Q8NHY3; Q8NHY4;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=GAS2-like protein 2;
DE AltName: Full=GAS2-related protein on chromosome 17;
DE AltName: Full=Growth arrest-specific protein 2-like 2;
GN Name=GAS2L2; Synonyms=GAR17;
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), FUNCTION, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=12584248; DOI=10.1242/jcs.00272;
RA Goriounov D., Leung C.L., Liem R.K.;
RT "Protein products of human Gas2-related genes on chromosomes 17 and 22
RT (hGAR17 and hGAR22) associate with both microfilaments and microtubules.";
RL J. Cell Sci. 116:1045-1058(2003).
RN [2]
RP INTERACTION WITH GNAS; GNAL; GNAQ AND GNA13.
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 [3]
RP FUNCTION, INTERACTION WITH MAPRE1, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP 369-ILE-PRO-370; 458-LEU-PRO-459; 503-ILE-PRO-504; 590-LEU-PRO-591 AND
RP 795-ILE-PRO-796.
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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND INVOLVEMENT IN CILD41.
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 (PubMed:12584248, PubMed:24706950). Regulates
CC microtubule dynamics and stability by interacting with microtubule
CC plus-end tracking proteins, such as MAPRE1, to regulate microtubule
CC growth along actin stress fibers (PubMed:24706950). Enhances ADORA2-
CC mediated adenylyl cyclase activation by acting as a scaffold to recruit
CC trimeric G-protein complexes to ADORA2A (By similarity). Regulates
CC ciliary orientation and performance in cells located in the airway
CC (PubMed:30665704). {ECO:0000250|UniProtKB:Q5SSG4,
CC ECO:0000269|PubMed:12584248, ECO:0000269|PubMed:24706950,
CC ECO:0000269|PubMed:30665704}.
CC -!- SUBUNIT: Interacts with ADORA2A (via its cytoplasmic C-terminal domain)
CC (By similarity). Interacts with GNAS, GNAL, GNAQ, and GNA13
CC (PubMed:23994616). Interacts with MAPRE1 (PubMed:24706950).
CC {ECO:0000250|UniProtKB:Q5SSG4, ECO:0000269|PubMed:23994616,
CC ECO:0000269|PubMed:24706950}.
CC -!- INTERACTION:
CC Q8NHY3; Q9NYB9-2: ABI2; NbExp=3; IntAct=EBI-7960826, EBI-11096309;
CC Q8NHY3; Q8N9N5-2: BANP; NbExp=3; IntAct=EBI-7960826, EBI-11524452;
CC Q8NHY3; P31415: CASQ1; NbExp=3; IntAct=EBI-7960826, EBI-14017981;
CC Q8NHY3; Q96HB5: CCDC120; NbExp=3; IntAct=EBI-7960826, EBI-744556;
CC Q8NHY3; O95273: CCNDBP1; NbExp=3; IntAct=EBI-7960826, EBI-748961;
CC Q8NHY3; Q9NRI5-2: DISC1; NbExp=3; IntAct=EBI-7960826, EBI-11988027;
CC Q8NHY3; Q9NQM4: DNAAF6; NbExp=4; IntAct=EBI-7960826, EBI-10239299;
CC Q8NHY3; Q5JVL4: EFHC1; NbExp=3; IntAct=EBI-7960826, EBI-743105;
CC Q8NHY3; P51114-2: FXR1; NbExp=3; IntAct=EBI-7960826, EBI-11022345;
CC Q8NHY3; Q08379: GOLGA2; NbExp=3; IntAct=EBI-7960826, EBI-618309;
CC Q8NHY3; A6NEM1: GOLGA6L9; NbExp=3; IntAct=EBI-7960826, EBI-5916454;
CC Q8NHY3; Q6NT76: HMBOX1; NbExp=3; IntAct=EBI-7960826, EBI-2549423;
CC Q8NHY3; Q96ED9-2: HOOK2; NbExp=3; IntAct=EBI-7960826, EBI-10961706;
CC Q8NHY3; O75031: HSF2BP; NbExp=3; IntAct=EBI-7960826, EBI-7116203;
CC Q8NHY3; A0A0C4DFT8: JADE2; NbExp=3; IntAct=EBI-7960826, EBI-12094820;
CC Q8NHY3; Q63ZY3: KANK2; NbExp=3; IntAct=EBI-7960826, EBI-2556193;
CC Q8NHY3; Q96MP8-2: KCTD7; NbExp=3; IntAct=EBI-7960826, EBI-11954971;
CC Q8NHY3; Q9UBR4-2: LHX3; NbExp=5; IntAct=EBI-7960826, EBI-12039345;
CC Q8NHY3; Q9P2M1: LRP2BP; NbExp=3; IntAct=EBI-7960826, EBI-18273118;
CC Q8NHY3; Q96GA3: LTV1; NbExp=3; IntAct=EBI-7960826, EBI-2558389;
CC Q8NHY3; Q15691: MAPRE1; NbExp=3; IntAct=EBI-7960826, EBI-1004115;
CC Q8NHY3; Q15555: MAPRE2; NbExp=3; IntAct=EBI-7960826, EBI-739717;
CC Q8NHY3; Q9UPY8: MAPRE3; NbExp=3; IntAct=EBI-7960826, EBI-726739;
CC Q8NHY3; Q9UJV3-2: MID2; NbExp=3; IntAct=EBI-7960826, EBI-10172526;
CC Q8NHY3; Q5VZ52: MORN5; NbExp=3; IntAct=EBI-7960826, EBI-12835568;
CC Q8NHY3; Q5JR59-3: MTUS2; NbExp=3; IntAct=EBI-7960826, EBI-11522433;
CC Q8NHY3; P55209: NAP1L1; NbExp=3; IntAct=EBI-7960826, EBI-356392;
CC Q8NHY3; P26367: PAX6; NbExp=3; IntAct=EBI-7960826, EBI-747278;
CC Q8NHY3; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-7960826, EBI-79165;
CC Q8NHY3; Q96KQ4: PPP1R13B; NbExp=3; IntAct=EBI-7960826, EBI-1105153;
CC Q8NHY3; P31321: PRKAR1B; NbExp=3; IntAct=EBI-7960826, EBI-2805516;
CC Q8NHY3; Q92753-1: RORB; NbExp=3; IntAct=EBI-7960826, EBI-18560266;
CC Q8NHY3; P21673: SAT1; NbExp=3; IntAct=EBI-7960826, EBI-711613;
CC Q8NHY3; Q13573: SNW1; NbExp=3; IntAct=EBI-7960826, EBI-632715;
CC Q8NHY3; O14512: SOCS7; NbExp=3; IntAct=EBI-7960826, EBI-1539606;
CC Q8NHY3; Q9UBB9: TFIP11; NbExp=3; IntAct=EBI-7960826, EBI-1105213;
CC Q8NHY3; Q12933: TRAF2; NbExp=3; IntAct=EBI-7960826, EBI-355744;
CC Q8NHY3; P14373: TRIM27; NbExp=3; IntAct=EBI-7960826, EBI-719493;
CC Q8NHY3; O00308: WWP2; NbExp=3; IntAct=EBI-7960826, EBI-743923;
CC Q8NHY3; Q9UGI0: ZRANB1; NbExp=3; IntAct=EBI-7960826, EBI-527853;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:12584248, ECO:0000269|PubMed:30665704}. Cell
CC membrane {ECO:0000250|UniProtKB:Q5SSG4}. Cytoplasm, cytoskeleton,
CC stress fiber {ECO:0000269|PubMed:24706950,
CC ECO:0000269|PubMed:30665704}. 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 (PubMed:24706950).
CC {ECO:0000250|UniProtKB:D3ZUE1, ECO:0000269|PubMed:24706950}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Beta;
CC IsoId=Q8NHY3-1; Sequence=Displayed;
CC Name=2; Synonyms=Alpha;
CC IsoId=Q8NHY3-2; Sequence=VSP_015497, VSP_015498;
CC -!- TISSUE SPECIFICITY: Expressed in bronchial and nasal epithelial cells
CC (at protein level) (PubMed:30665704). Expressed in brain, kidney, lung,
CC testis, fallopian tubes, and skeletal muscle (PubMed:12584248,
CC PubMed:30665704). Expressed at low levels in stomach and colon
CC (PubMed:30665704). {ECO:0000269|PubMed:12584248,
CC ECO:0000269|PubMed:30665704}.
CC -!- DISEASE: Ciliary dyskinesia, primary, 41 (CILD41) [MIM:618449]: A form
CC of primary ciliary dyskinesia, a disorder characterized by
CC abnormalities of motile cilia. Respiratory infections leading to
CC chronic inflammation and bronchiectasis are recurrent, due to defects
CC in the respiratory cilia. CILD41 inheritance is autosomal recessive.
CC {ECO:0000269|PubMed:30665704}. Note=The disease is caused by variants
CC affecting the gene represented in this entry. Absence of GAS2L2 results
CC in ciliary orientation defect and affects performance of cilia.
CC {ECO:0000269|PubMed:30665704}.
CC -!- SIMILARITY: Belongs to the GAS2 family. {ECO:0000305}.
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DR EMBL; AF508785; AAM34265.1; -; mRNA.
DR EMBL; AF508784; AAM34264.1; -; mRNA.
DR CCDS; CCDS11298.1; -. [Q8NHY3-1]
DR RefSeq; NP_644814.1; NM_139285.3. [Q8NHY3-1]
DR AlphaFoldDB; Q8NHY3; -.
DR SMR; Q8NHY3; -.
DR BioGRID; 128874; 54.
DR IntAct; Q8NHY3; 42.
DR MINT; Q8NHY3; -.
DR STRING; 9606.ENSP00000474529; -.
DR iPTMnet; Q8NHY3; -.
DR PhosphoSitePlus; Q8NHY3; -.
DR BioMuta; GAS2L2; -.
DR DMDM; 73919614; -.
DR EPD; Q8NHY3; -.
DR MassIVE; Q8NHY3; -.
DR PaxDb; Q8NHY3; -.
DR PeptideAtlas; Q8NHY3; -.
DR PRIDE; Q8NHY3; -.
DR ProteomicsDB; 73788; -. [Q8NHY3-1]
DR ProteomicsDB; 73789; -. [Q8NHY3-2]
DR Antibodypedia; 73370; 73 antibodies from 17 providers.
DR DNASU; 246176; -.
DR Ensembl; ENST00000604641.6; ENSP00000474529.2; ENSG00000270765.7. [Q8NHY3-1]
DR GeneID; 246176; -.
DR KEGG; hsa:246176; -.
DR MANE-Select; ENST00000604641.6; ENSP00000474529.2; NM_139285.4; NP_644814.1.
DR UCSC; uc002hjv.2; human. [Q8NHY3-1]
DR CTD; 246176; -.
DR DisGeNET; 246176; -.
DR GeneCards; GAS2L2; -.
DR HGNC; HGNC:24846; GAS2L2.
DR HPA; ENSG00000270765; Tissue enhanced (choroid plexus, fallopian tube).
DR MalaCards; GAS2L2; -.
DR MIM; 611398; gene.
DR MIM; 618449; phenotype.
DR neXtProt; NX_Q8NHY3; -.
DR OpenTargets; ENSG00000270765; -.
DR Orphanet; 244; Primary ciliary dyskinesia.
DR PharmGKB; PA134986846; -.
DR VEuPathDB; HostDB:ENSG00000270765; -.
DR eggNOG; KOG0516; Eukaryota.
DR GeneTree; ENSGT00940000162866; -.
DR InParanoid; Q8NHY3; -.
DR OMA; QPCHFRN; -.
DR OrthoDB; 1343422at2759; -.
DR PhylomeDB; Q8NHY3; -.
DR TreeFam; TF323754; -.
DR PathwayCommons; Q8NHY3; -.
DR SignaLink; Q8NHY3; -.
DR BioGRID-ORCS; 246176; 33 hits in 1067 CRISPR screens.
DR ChiTaRS; GAS2L2; human.
DR GenomeRNAi; 246176; -.
DR Pharos; Q8NHY3; Tdark.
DR PRO; PR:Q8NHY3; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q8NHY3; protein.
DR Bgee; ENSG00000270765; Expressed in right uterine tube and 72 other tissues.
DR Genevisible; Q8NHY3; HS.
DR GO; GO:0036064; C:ciliary basal body; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0051015; F:actin filament binding; IDA:UniProtKB.
DR GO; GO:0008093; F:cytoskeletal anchor activity; IDA:UniProtKB.
DR GO; GO:0001965; F:G-protein alpha-subunit binding; IEA:Ensembl.
DR GO; GO:0008017; F:microtubule binding; IDA:UniProtKB.
DR GO; GO:0051764; P:actin crosslink formation; IBA:GO_Central.
DR GO; GO:0001578; P:microtubule bundle formation; IMP:UniProtKB.
DR GO; GO:0007026; P:negative regulation of microtubule depolymerization; IMP:UniProtKB.
DR GO; GO:0045745; P:positive regulation of G protein-coupled receptor signaling pathway; IEA:Ensembl.
DR GO; GO:1904825; P:protein localization to microtubule plus-end; IDA:UniProtKB.
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; IMP:UniProtKB.
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 Alternative splicing; Cell membrane; Cell projection; Ciliopathy;
KW Cytoplasm; Cytoskeleton; Membrane; Primary ciliary dyskinesia;
KW Reference proteome.
FT CHAIN 1..880
FT /note="GAS2-like protein 2"
FT /id="PRO_0000190444"
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 180..200
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 283..360
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 372..437
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 438..880
FT /note="Interaction with ADORA2A"
FT /evidence="ECO:0000250|UniProtKB:Q5SSG4"
FT REGION 489..533
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 676..880
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 185..199
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 298..323
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 372..396
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 397..411
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 724..738
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 757..784
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 187..213
FT /note="PPDPSPPAPPRRQPCHFRNLDQMVQSL -> LPQPGPDGAEPCEPLHVPSAV
FT LHGQSV (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12584248"
FT /id="VSP_015497"
FT VAR_SEQ 214..800
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12584248"
FT /id="VSP_015498"
FT VARIANT 164
FT /note="A -> V (in dbSNP:rs11654604)"
FT /id="VAR_059975"
FT VARIANT 540
FT /note="A -> T (in dbSNP:rs12602590)"
FT /id="VAR_053100"
FT VARIANT 654
FT /note="A -> V (in dbSNP:rs3744374)"
FT /id="VAR_053101"
FT VARIANT 829
FT /note="R -> W (in dbSNP:rs56386706)"
FT /id="VAR_062004"
FT MUTAGEN 369..370
FT /note="IP->NN: Loss of microtubule-end localization,
FT microtubule plus-end tracking, and decreases MAPRE1
FT binding; when associated with 458-N--N-459, 503-N-N-504;
FT 590-N-N-591 and 795-N-N-796."
FT /evidence="ECO:0000269|PubMed:24706950"
FT MUTAGEN 458..459
FT /note="LP->NN: Loss of microtubule-end localization,
FT microtubule plus-end tracking, and decreases MAPRE1
FT binding; when associated with 369-N--N-370; 503-N-N-504;
FT 590-N-N-591 and 795-N-N-796."
FT /evidence="ECO:0000269|PubMed:24706950"
FT MUTAGEN 503..504
FT /note="IP->NN: Loss of microtubule-end localization,
FT microtubule plus-end tracking, and decreases MAPRE1
FT binding; when associated with 369-N-N-370; 458-N-N-459;
FT 590-N-N-591 and 795-N-N-796."
FT /evidence="ECO:0000269|PubMed:24706950"
FT MUTAGEN 590..591
FT /note="LP->NN: Loss of microtubule-end localization,
FT microtubule plus-end tracking, and decreases MAPRE1
FT binding; when associated with 369-N-N-370; 458-N-N-459;
FT 503-N-N-504 and 795-N-N-796."
FT /evidence="ECO:0000269|PubMed:24706950"
FT MUTAGEN 795..796
FT /note="IP->NN: Loss of microtubule-end localization,
FT microtubule plus-end tracking, and decreases MAPRE1
FT binding; when associated with 369-N-N-370; 458-N-N-459;
FT 503-N-N-504 and 590-N-N-591."
FT /evidence="ECO:0000269|PubMed:24706950"
SQ SEQUENCE 880 AA; 96520 MW; 2AFCD96EE7F4AB22 CRC64;
MSQPAGGRRK PRTLGPPVCS IRPFKSSEQY LEAMKEDLAE WLRDLYGLDI DAANFLQVLE
TGLVLCQHAN VVTDAALAFL AEAPAQAQKI PMPRVGVSCN GAAQPGTFQA RDNVSNFIQW
CRKEMGIQEV LMFETEDLVL RKNVKNVVLC LLELGRRAWR FGVAAPTLVQ LEEEIEEEVR
RELALPPPDP SPPAPPRRQP CHFRNLDQMV QSLVSHCTCP VQFSMVKVSE GKYRVGDSNT
LIFIRILRNH VMVRVGGGWD TLGHYLDKHD PCRCTSLSHK PGSFLKPPAP PVQHEVRVQD
GPSQTQPTMT ISRSQSPPPP VDWKTYTSSD RRLRPPTPSS PRPRRERGAG TGASREMAPF
LRCQERSLIP SWRQPTAGDS PPSPQSSSTQ KGRDPQCTSS GKREERYPPE LPRGRIPTSW
VHEETDSWGT DAGNPTPQRL RAIEATTKGI SARGPSPLPR SFGPAECLGL RLPLRDEAKG
AFFQFREPES VRSPTPVQGL TKIPIRLPPA RPPTPGRSFP GATSGSPRTE LGRDPIPLRA
VTVDLAGSTH GDCSVEVRQE DQQLDIQVMA EARESWDLGL QEQEGRYTPL PLGGNKEQAI
YCSLEEEILG NMKLLEVRSA CPQGTRSGVI PRSGVYIPRL AGQWPEPGGP YDKAIQELAQ
GSPSLLKVDL EAWKAAPTGS PKPAVTPGPG SLKGKLGARQ SGPRTKASLS AKGTHMRKVP
PQGGQDCSAS TVSASPEAPT PSPLDPNSDK AKACLSKGRR TLRKPKRVPS IYKLKLRPRI
RPRRDHRPEK QPSRIPRPLA YVFLGPARQP PKDRLLRAVL GSKGGEASRV DGASVGEEEE
EGKEEKEPAA PLESSPQPPE GLQPHWLNQA PLPPEEESWV
