FERM2_DANRE
ID FERM2_DANRE Reviewed; 684 AA.
AC F1Q8X5; Q58EF4;
DT 29-MAY-2013, integrated into UniProtKB/Swiss-Prot.
DT 03-MAY-2011, sequence version 1.
DT 03-AUG-2022, entry version 65.
DE RecName: Full=Fermitin family homolog 2;
DE AltName: Full=Kindlin-2;
GN Name=fermt2;
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 [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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 82-684.
RC TISSUE=Embryo;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=18174465; DOI=10.1161/circresaha.107.161489;
RA Dowling J.J., Gibbs E., Russell M., Goldman D., Minarcik J., Golden J.A.,
RA Feldman E.L.;
RT "Kindlin-2 is an essential component of intercalated discs and is required
RT for vertebrate cardiac structure and function.";
RL Circ. Res. 102:423-431(2008).
RN [4]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=21378273; DOI=10.1182/blood-2010-11-321182;
RA Pluskota E., Dowling J.J., Gordon N., Golden J.A., Szpak D., West X.Z.,
RA Nestor C., Ma Y.Q., Bialkowska K., Byzova T., Plow E.F.;
RT "The integrin coactivator kindlin-2 plays a critical role in angiogenesis
RT in mice and zebrafish.";
RL Blood 117:4978-4987(2011).
CC -!- FUNCTION: Scaffolding protein that enhances integrin activation
CC mediated by TLN1 and/or TLN2, but activates integrins only weakly by
CC itself. Binds to membranes enriched in phosphoinositides. Enhances
CC integrin-mediated cell adhesion onto the extracellular matrix and cell
CC spreading; this requires both its ability to interact with integrins
CC and with phospholipid membranes. Required for the assembly of focal
CC adhesions. Participates in the connection between extracellular matrix
CC adhesion sites and the actin cytoskeleton and also in the orchestration
CC of actin assembly and cell shape modulation. Plays a role in the TGFB1
CC and integrin signaling pathways. Stabilizes active CTNNB1 and plays a
CC role in the regulation of transcription mediated by CTNNB1 and
CC TCF7L2/TCF4 and in Wnt signaling (By similarity). Required for normal
CC embryonic development, including normal heart morphogenesis and normal
CC angiogenesis. {ECO:0000250, ECO:0000269|PubMed:18174465,
CC ECO:0000269|PubMed:21378273}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cytoplasm, cell cortex
CC {ECO:0000250}. Cytoplasm, cytoskeleton {ECO:0000250}. Cytoplasm,
CC cytoskeleton, stress fiber {ECO:0000250}. Cell junction, focal adhesion
CC {ECO:0000250}. Membrane {ECO:0000250}; Peripheral membrane protein
CC {ECO:0000250}; Cytoplasmic side {ECO:0000250}. Cell projection,
CC lamellipodium membrane {ECO:0000250}; Peripheral membrane protein
CC {ECO:0000250}; Cytoplasmic side {ECO:0000250}. Nucleus {ECO:0000250}.
CC Cytoplasm, myofibril, sarcomere, I band {ECO:0000250}. Cell surface
CC {ECO:0000250}. Note=Colocalizes with actin stress fibers at cell-ECM
CC focal adhesion sites. Colocalizes with integrins at lamellipodia at the
CC leading edge of spreading cells. Binds to membranes that contain
CC phosphatidylinositides (By similarity). {ECO:0000250}.
CC -!- DOMAIN: The FERM domain is not correctly detected by PROSITE or Pfam
CC techniques because it contains the insertion of a PH domain.
CC -!- DOMAIN: The PH domain binds phospholipids. Binds preferentially
CC phosphatidylinositol-3,4,5-trisphosphate, and has lower affinity for
CC phosphatidylinositol-4,5-bisphosphate (By similarity). {ECO:0000250}.
CC -!- DOMAIN: The N-terminal region displays a ubiquitin-type fold and
CC mediates interaction with membranes containing negatively charged
CC phosphatidylinositol phosphate via a surface enriched in positively
CC charged residues. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Morpholino knockdown results in severe defects in
CC embryonic development. Nearly all embryos display pericardial edema.
CC Most embryos display abnormal body shape and size, defects in heart
CC morphogenesis, impaired mobility, and die at about 7 dpf. The embryonic
CC cardiac muscle and skeletal muscle show defects in the association of
CC the actin-myosin myofibers with the myocyte membrane (PubMed:18174465).
CC Likewise, morpholino knockdown results in defective angiogenesis, with
CC abnormally short and thin vessels and very little blood flow
CC (PubMed:21378273). {ECO:0000269|PubMed:18174465,
CC ECO:0000269|PubMed:21378273}.
CC -!- SIMILARITY: Belongs to the kindlin family. {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; AL928709; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC091937; AAH91937.1; -; mRNA.
DR RefSeq; NP_001243144.1; NM_001256215.1.
DR AlphaFoldDB; F1Q8X5; -.
DR SMR; F1Q8X5; -.
DR STRING; 7955.ENSDARP00000080431; -.
DR PaxDb; F1Q8X5; -.
DR PRIDE; F1Q8X5; -.
DR Ensembl; ENSDART00000049464; ENSDARP00000049463; ENSDARG00000020242.
DR GeneID; 553051; -.
DR KEGG; dre:553051; -.
DR CTD; 10979; -.
DR ZFIN; ZDB-GENE-050506-132; fermt2.
DR eggNOG; KOG3727; Eukaryota.
DR GeneTree; ENSGT00390000013444; -.
DR HOGENOM; CLU_011611_1_0_1; -.
DR InParanoid; F1Q8X5; -.
DR OMA; MFAALQX; -.
DR OrthoDB; 248494at2759; -.
DR PhylomeDB; F1Q8X5; -.
DR TreeFam; TF314677; -.
DR Reactome; R-DRE-446353; Cell-extracellular matrix interactions.
DR Reactome; R-DRE-9013149; RAC1 GTPase cycle.
DR Reactome; R-DRE-9013423; RAC3 GTPase cycle.
DR PRO; PR:F1Q8X5; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 17.
DR Bgee; ENSDARG00000020242; Expressed in muscle tissue and 25 other tissues.
DR ExpressionAtlas; F1Q8X5; baseline.
DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
DR GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell.
DR GO; GO:0030055; C:cell-substrate junction; IBA:GO_Central.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005925; C:focal adhesion; IBA:GO_Central.
DR GO; GO:0031674; C:I band; IEA:UniProtKB-SubCell.
DR GO; GO:0014704; C:intercalated disc; IMP:ZFIN.
DR GO; GO:0031258; C:lamellipodium membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005178; F:integrin binding; IBA:GO_Central.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0001525; P:angiogenesis; IMP:ZFIN.
DR GO; GO:0055008; P:cardiac muscle tissue morphogenesis; IMP:ZFIN.
DR GO; GO:0016477; P:cell migration; IGI:ZFIN.
DR GO; GO:0007160; P:cell-matrix adhesion; IBA:GO_Central.
DR GO; GO:0007010; P:cytoskeleton organization; IMP:ZFIN.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; IEA:InterPro.
DR GO; GO:0008360; P:regulation of cell shape; IEA:UniProtKB-KW.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR CDD; cd01237; PH_fermitin; 1.
DR Gene3D; 2.30.29.30; -; 2.
DR InterPro; IPR019749; Band_41_domain.
DR InterPro; IPR035963; FERM_2.
DR InterPro; IPR019748; FERM_central.
DR InterPro; IPR037843; Kindlin/fermitin.
DR InterPro; IPR040790; Kindlin_2_N.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR037837; PH_Kindlin/fermitin.
DR PANTHER; PTHR16160; PTHR16160; 1.
DR Pfam; PF00373; FERM_M; 1.
DR Pfam; PF18124; Kindlin_2_N; 1.
DR Pfam; PF00169; PH; 1.
DR SMART; SM00295; B41; 1.
DR SMART; SM00233; PH; 1.
DR SUPFAM; SSF47031; SSF47031; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
PE 2: Evidence at transcript level;
KW Cell adhesion; Cell junction; Cell membrane; Cell projection; Cell shape;
KW Cytoplasm; Cytoskeleton; Lipid-binding; Membrane; Nucleus;
KW Reference proteome; Wnt signaling pathway.
FT CHAIN 1..684
FT /note="Fermitin family homolog 2"
FT /id="PRO_0000422373"
FT DOMAIN 279..577
FT /note="FERM"
FT DOMAIN 378..474
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT REGION 40..81
FT /note="Interaction with membranes containing
FT phosphatidylinositol phosphate"
FT /evidence="ECO:0000250"
FT REGION 141..163
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 141..159
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 381
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-3,4,5-trisphosphate)"
FT /ligand_id="ChEBI:CHEBI:57836"
FT /evidence="ECO:0000250"
FT CONFLICT 82
FT /note="Y -> G (in Ref. 2; AAH91937)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 684 AA; 78476 MW; 925A8C15E65902D8 CRC64;
MALDGIRMPD GCYADGTWEL KMHVTDLNRD VSLRVTGEIH IGGVMLKLVE KLDVKKDWSD
HALWWEKKKT WLLKTHWTLD KYGIQADARL LFTPQHKLLR LQLPNMKHMR VKVNFSDRVF
KAVSDICKTF NIRHPEELSL LRKPRDPKKK KKKLEDAEEE TLELEGPLLT PGSGSIYSSP
GLYSKTMTPT YDSRDGSPLS PTSAWFGDSP LSEGNPSILA VSQPITSPDI LVKMYKPQSL
LDKAKINQGW LDSSRSLMEQ DVKENEVLLL RFKYHSFFDL NPKYDAIRVN QLYEQAKWAI
LLEEIECTEE EMMMFAALQY HINKLSIMSS DNHMNNSEKE VDEVDAALSD LEITLEGGKT
SNTLGDITSI PELADYVKVF KPKKLTLKGY KQYWCTFKDI TISCYKSREE AHGTPAHQMN
LRGCEVTPDV NISGQKFNIK LLIPVADGMN EIWLRCDTEK QYAQWMAACR LASKGKTMAD
SSYNLEVQNI LSFLKMQHMN PDPQIIEPIT TDINPECLVS PRYLKKYKNK QPGFVRDLIS
ARILEAHQNV AQMSLIEAKM RFIQAWQSLP EFGITHFLAK FQGGKKDELI GITYNRLIRM
DAGTGDAIKT WRFSNMKQWN VNWEIKMVTV EFADEPSLAF ICAEVDCKVV HEFIGGYIFL
STRAKDQNES LDEEMFYKLT SGWV
