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AMOL2_DANRE
ID   AMOL2_DANRE             Reviewed;         721 AA.
AC   A1YB07; B3DIZ1; F1QMD1;
DT   05-SEP-2012, integrated into UniProtKB/Swiss-Prot.
DT   05-SEP-2012, sequence version 2.
DT   03-AUG-2022, entry version 82.
DE   RecName: Full=Angiomotin-like 2a;
GN   Name=amotl2a; Synonyms=amotl2;
OS   Danio rerio (Zebrafish) (Brachydanio rerio).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC   Danionidae; Danioninae; Danio.
OX   NCBI_TaxID=7955;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH SRC, DEVELOPMENTAL
RP   STAGE, AND INDUCTION.
RX   PubMed=17293535; DOI=10.1242/dev.02782;
RA   Huang H., Lu F.I., Jia S., Meng S., Cao Y., Wang Y., Ma W., Yin K., Wen Z.,
RA   Peng J., Thisse C., Thisse B., Meng A.;
RT   "Amotl2 is essential for cell movements in zebrafish embryo and regulates
RT   c-Src translocation.";
RL   Development 134:979-988(2007).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Tuebingen;
RX   PubMed=23594743; DOI=10.1038/nature12111;
RA   Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA   Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA   Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA   White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA   Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA   Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA   Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA   Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA   Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA   Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA   Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA   Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA   Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA   Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA   Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA   McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA   Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA   Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA   Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA   Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA   Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA   Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA   Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA   Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA   Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA   Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA   Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA   Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA   de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA   Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT   "The zebrafish reference genome sequence and its relationship to the human
RT   genome.";
RL   Nature 496:498-503(2013).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RG   NIH - Zebrafish Gene Collection (ZGC) project;
RL   Submitted (APR-2008) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   FUNCTION, PHOSPHORYLATION AT TYR-103, AND MUTAGENESIS OF TYR-103.
RX   PubMed=21937427; DOI=10.1074/jbc.m111.296806;
RA   Wang Y., Li Z., Xu P., Huang L., Tong J., Huang H., Meng A.;
RT   "Angiomotin-like2 gene (amotl2) is required for migration and proliferation
RT   of endothelial cells during angiogenesis.";
RL   J. Biol. Chem. 286:41095-41104(2011).
RN   [5]
RP   FUNCTION, INTERACTION WITH SRC, AND SUBCELLULAR LOCATION.
RX   PubMed=22362771; DOI=10.1074/jbc.m112.347419;
RA   Li Z., Wang Y., Zhang M., Xu P., Huang H., Wu D., Meng A.;
RT   "The Amotl2 gene inhibits Wnt/beta-catenin signaling and regulates
RT   embryonic development in zebrafish.";
RL   J. Biol. Chem. 287:13005-13015(2012).
CC   -!- FUNCTION: Regulates the translocation of phosphorylated SRC to
CC       peripheral cell-matrix adhesion sites. Required for proper architecture
CC       of actin filaments and for cell movements during embryogenesis.
CC       Inhibits the Wnt/beta-catenin signaling pathway, probably by recruiting
CC       CTNNB1 to recycling endosomes and hence preventing its translocation to
CC       the nucleus. Participates in angiogenesis. May play a role in the
CC       polarity, proliferation and migration of endothelial cells. Selectively
CC       promotes FGF-induced MAPK activation through SRC.
CC       {ECO:0000269|PubMed:17293535, ECO:0000269|PubMed:21937427,
CC       ECO:0000269|PubMed:22362771}.
CC   -!- SUBUNIT: Interacts with SRC. {ECO:0000269|PubMed:17293535,
CC       ECO:0000269|PubMed:22362771}.
CC   -!- SUBCELLULAR LOCATION: Recycling endosome {ECO:0000269|PubMed:22362771}.
CC   -!- DEVELOPMENTAL STAGE: Detected before the 1k-cell stage, suggesting that
CC       it is maternally supplied. At the sphere stage, stronger expression in
CC       the dorsal blastomeres. In the gastrula, expressed in the whole embryo,
CC       except in the evacuation zone. During segmentation and pharyngula
CC       period, expressed in many distinct domains, including the polster,
CC       telencephalon, trigeminal placodes, rhombomeres, trunk neurons, somites
CC       and axial vasculature. During the pharyngula period, additional
CC       expression observed in lateral line primordia and in intersegmental
CC       vessels. {ECO:0000269|PubMed:17293535}.
CC   -!- INDUCTION: Up-regulated by fgf17 and fgf8.
CC       {ECO:0000269|PubMed:17293535}.
CC   -!- PTM: Phosphorylation at Tyr-103 is necessary for efficient binding to
CC       SRC and synergistically functioning with SRC to activate the downstream
CC       MAPK pathway. {ECO:0000269|PubMed:21937427}.
CC   -!- SIMILARITY: Belongs to the angiomotin family. {ECO:0000305}.
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DR   EMBL; DQ887096; ABI74626.1; -; mRNA.
DR   EMBL; CR626940; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC163299; AAI63299.1; -; mRNA.
DR   RefSeq; NP_001073646.1; NM_001080177.1.
DR   AlphaFoldDB; A1YB07; -.
DR   SMR; A1YB07; -.
DR   STRING; 7955.ENSDARP00000083347; -.
DR   iPTMnet; A1YB07; -.
DR   PaxDb; A1YB07; -.
DR   PeptideAtlas; A1YB07; -.
DR   PRIDE; A1YB07; -.
DR   Ensembl; ENSDART00000088914; ENSDARP00000083347; ENSDARG00000061923.
DR   Ensembl; ENSDART00000160354; ENSDARP00000134595; ENSDARG00000061923.
DR   GeneID; 558920; -.
DR   KEGG; dre:558920; -.
DR   CTD; 558920; -.
DR   ZFIN; ZDB-GENE-030131-9770; amotl2a.
DR   eggNOG; ENOG502QR7W; Eukaryota.
DR   GeneTree; ENSGT00940000156577; -.
DR   HOGENOM; CLU_009937_2_0_1; -.
DR   InParanoid; A1YB07; -.
DR   OMA; YRFYQPQ; -.
DR   OrthoDB; 369983at2759; -.
DR   PhylomeDB; A1YB07; -.
DR   TreeFam; TF333368; -.
DR   Reactome; R-DRE-2028269; Signaling by Hippo.
DR   PRO; PR:A1YB07; -.
DR   Proteomes; UP000000437; Genome assembly.
DR   Proteomes; UP000814640; Chromosome 6.
DR   Bgee; ENSDARG00000061923; Expressed in somite and 56 other tissues.
DR   ExpressionAtlas; A1YB07; baseline and differential.
DR   GO; GO:0005923; C:bicellular tight junction; IBA:GO_Central.
DR   GO; GO:0005938; C:cell cortex; IDA:ZFIN.
DR   GO; GO:0030054; C:cell junction; IDA:ZFIN.
DR   GO; GO:0005911; C:cell-cell junction; IDA:ZFIN.
DR   GO; GO:0031410; C:cytoplasmic vesicle; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0099513; C:polymeric cytoskeletal fiber; IDA:ZFIN.
DR   GO; GO:0055037; C:recycling endosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0030036; P:actin cytoskeleton organization; IGI:ZFIN.
DR   GO; GO:0001525; P:angiogenesis; IMP:ZFIN.
DR   GO; GO:0016477; P:cell migration; IMP:ZFIN.
DR   GO; GO:0060026; P:convergent extension; IMP:ZFIN.
DR   GO; GO:0030866; P:cortical actin cytoskeleton organization; IMP:ZFIN.
DR   GO; GO:0035907; P:dorsal aorta development; IGI:ZFIN.
DR   GO; GO:0035912; P:dorsal aorta morphogenesis; IMP:ZFIN.
DR   GO; GO:0009880; P:embryonic pattern specification; IMP:ZFIN.
DR   GO; GO:0001935; P:endothelial cell proliferation; IMP:ZFIN.
DR   GO; GO:0003365; P:establishment of cell polarity involved in ameboidal cell migration; IBA:GO_Central.
DR   GO; GO:0051649; P:establishment of localization in cell; IGI:ZFIN.
DR   GO; GO:0046847; P:filopodium assembly; IMP:ZFIN.
DR   GO; GO:0030334; P:regulation of cell migration; IBA:GO_Central.
DR   GO; GO:0008360; P:regulation of cell shape; IGI:ZFIN.
DR   GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR   InterPro; IPR009114; Angiomotin.
DR   InterPro; IPR024646; Angiomotin_C.
DR   Pfam; PF12240; Angiomotin_C; 1.
DR   PRINTS; PR01807; ANGIOMOTIN.
PE   1: Evidence at protein level;
KW   Coiled coil; Endosome; Phosphoprotein; Reference proteome;
KW   Wnt signaling pathway.
FT   CHAIN           1..721
FT                   /note="Angiomotin-like 2a"
FT                   /id="PRO_0000418839"
FT   REGION          35..84
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          169..214
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          554..575
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          666..709
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          275..531
FT                   /evidence="ECO:0000255"
FT   MOTIF           718..721
FT                   /note="PDZ-binding"
FT   COMPBIAS        35..83
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        169..199
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        554..571
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        690..709
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         103
FT                   /note="Phosphotyrosine; by FGFR1"
FT                   /evidence="ECO:0000269|PubMed:21937427"
FT   MUTAGEN         103
FT                   /note="Y->F: Loss of phosphorylation. Drastic reduction in
FT                   SRC-binding and in activation of MAPK."
FT                   /evidence="ECO:0000269|PubMed:21937427"
FT   CONFLICT        124
FT                   /note="Q -> H (in Ref. 1; ABI74626 and 3; AAI63299)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        167
FT                   /note="A -> G (in Ref. 3; AAI63299)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        189
FT                   /note="T -> S (in Ref. 3; AAI63299)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        194
FT                   /note="Q -> K (in Ref. 3; AAI63299)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        683
FT                   /note="A -> V (in Ref. 3; AAI63299)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   721 AA;  81711 MW;  650F7F103BC4D6C9 CRC64;
     MRTAEESSGT VLHRLIQEQL RYGNPTDPTL LAIQQQALRG GSSGGGAGSP RSSLESLTQE
     ESLSPQLSAR QEPQGQEHQG DFQHSESPVC HLYQLHTEEL PTYEEAKAHS QYLAYQRGQI
     GLHQGSLESP GGVGGAEQDD SMWDAKREHA RSLSERLLQL SLERNCAHDN IPMSSSHSYP
     QLSNNHSDTV VNEQSVHQPD QRGPPPEYPF MVRSPGYMLS HSQEHGHYYN EPPPAFHSQH
     YRLFPTQPQA PRHNGLPTLT PAGQDVNVGG YSIPANNFQM EQLIKENERL KREVDSYSEK
     AARLQKLEQE IQRISEAYET LMKGSAKREA LEKTMRNKLE SEIKRLHDFN RDLRDRLETA
     NKQRAAIEVE DKSRHAFAKL VEQNEDHLRE RERLEKETQH LRASGEEWKR RREALEQALI
     TAQTRNRQLE EELRRKRAYV EKVERMQSAL AQLQAACEKR EALELRLRTR LEQELKSLRA
     QQWQAQTQHA SPGSYLDLNV SSLQQQLRER EEQVLALEAD ITRWEQKYLE ESTMRQFAMD
     AAATAAAQRD TTIINHSPRN SPNSSFNEDL PSPNHRHQEM ENRIRALYAQ LLEKDAIIKV
     MQQRSRREQG RPELQGLRPA RSVPSINTVA TASTTRAKGK SLSDDQTAVA SLPPLPHLLA
     KIQCRDSSTQ CDSEEPSCKA EPADVAVSAP EPSTASSSES TSLKTTQISS AVENDMVEIL
     I
 
 
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