FERM2_HUMAN
ID FERM2_HUMAN Reviewed; 680 AA.
AC Q96AC1; B5TJY2; Q14840; Q86TY7;
DT 07-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Fermitin family homolog 2;
DE AltName: Full=Kindlin-2;
DE AltName: Full=Mitogen-inducible gene 2 protein;
DE Short=MIG-2;
DE AltName: Full=Pleckstrin homology domain-containing family C member 1;
DE Short=PH domain-containing family C member 1;
GN Name=FERMT2; Synonyms=KIND2, MIG2, PLEKHC1;
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 INDUCTION.
RC TISSUE=Lung fibroblast;
RX PubMed=8175911; DOI=10.1242/jcs.107.1.227;
RA Wick M., Buerger C., Bruesselbach S., Lucibello F.C., Mueller R.;
RT "Identification of serum-inducible genes: different patterns of gene
RT regulation during G0->S and G1->S progression.";
RL J. Cell Sci. 107:227-239(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND GENOMIC ORGANIZATION.
RC TISSUE=Colon tumor;
RX PubMed=12697302; DOI=10.1016/s0925-4439(03)00035-8;
RA Weinstein E.J., Bourner M., Head R., Zakeri H., Bauer C., Mazzarella R.;
RT "URP1: a member of a novel family of PH and FERM domain-containing
RT membrane-associated proteins is significantly over-expressed in lung and
RT colon carcinomas.";
RL Biochim. Biophys. Acta 1637:207-216(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION
RP WITH FBLIM1.
RC TISSUE=Lung;
RX PubMed=12679033; DOI=10.1016/s0092-8674(03)00163-6;
RA Tu Y., Wu S., Shi X., Chen K., Wu C.;
RT "Migfilin and Mig-2 link focal adhesions to filamin and the actin
RT cytoskeleton and function in cell shape modulation.";
RL Cell 113:37-47(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RA Tan S.-M., Li Y.-F.;
RL Submitted (AUG-2008) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Placenta;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Choriocarcinoma, Lung carcinoma, and 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 [8]
RP FUNCTION, INTERACTION WITH ITGB3, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP 614-GLN-TRP-615.
RX PubMed=18458155; DOI=10.1083/jcb.200710196;
RA Ma Y.Q., Qin J., Wu C., Plow E.F.;
RT "Kindlin-2 (Mig-2): a co-activator of beta3 integrins.";
RL J. Cell Biol. 181:439-446(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-666, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-159; SER-181 AND SER-666, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-159, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-159; SER-339; SER-351 AND
RP SER-666, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [15]
RP INTERACTION WITH ITGB1.
RX PubMed=21768292; DOI=10.1083/jcb.201007108;
RA Brunner M., Millon-Fremillon A., Chevalier G., Nakchbandi I.A., Mosher D.,
RA Block M.R., Albiges-Rizo C., Bouvard D.;
RT "Osteoblast mineralization requires beta1 integrin/ICAP-1-dependent
RT fibronectin deposition.";
RL J. Cell Biol. 194:307-322(2011).
RN [16]
RP FUNCTION, INTERACTION WITH ITGB1 AND ITGB3, LIPID-BINDING, MUTAGENESIS OF
RP LYS-390, AND SUBCELLULAR LOCATION.
RX PubMed=21325030; DOI=10.1242/jcs.076976;
RA Qu H., Tu Y., Shi X., Larjava H., Saleem M.A., Shattil S.J., Fukuda K.,
RA Qin J., Kretzler M., Wu C.;
RT "Kindlin-2 regulates podocyte adhesion and fibronectin matrix deposition
RT through interactions with phosphoinositides and integrins.";
RL J. Cell Sci. 124:879-891(2011).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-159; SER-351 AND SER-666, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [18]
RP FUNCTION, INTERACTION WITH CTNNB1, IDENTIFICATION IN A COMPLEX WITH CTNNB1
RP AND TCF7L2, AND SUBCELLULAR LOCATION.
RX PubMed=22699938; DOI=10.1038/embor.2012.88;
RA Yu Y., Wu J., Wang Y., Zhao T., Ma B., Liu Y., Fang W., Zhu W.G., Zhang H.;
RT "Kindlin 2 forms a transcriptional complex with beta-catenin and TCF4 to
RT enhance Wnt signalling.";
RL EMBO Rep. 13:750-758(2012).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-666, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-159 AND SER-351, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [21]
RP STRUCTURE BY NMR OF 367-500 IN COMPLEX WITH
RP PHOSPHATIDYLINOSITOL-3,4,5-TRISPHOSPHATE, FUNCTION, DOMAIN, MUTAGENESIS OF
RP LYS-383; LYS-385 AND LYS-393, AND LIPID-BINDING.
RX PubMed=22030399; DOI=10.1074/jbc.m111.295352;
RA Liu J., Fukuda K., Xu Z., Ma Y.Q., Hirbawi J., Mao X., Wu C., Plow E.F.,
RA Qin J.;
RT "Structural basis of phosphoinositide binding to kindlin-2 protein
RT pleckstrin homology domain in regulating integrin activation.";
RL J. Biol. Chem. 286:43334-43342(2011).
RN [22]
RP STRUCTURE BY NMR OF 1-105, FUNCTION, DOMAIN, SUBCELLULAR LOCATION,
RP MUTAGENESIS OF HIS-40 AND 74-LYS--LYS-81, AND LIPID-BINDING.
RX PubMed=22078565; DOI=10.1016/j.str.2011.08.012;
RA Perera H.D., Ma Y.Q., Yang J., Hirbawi J., Plow E.F., Qin J.;
RT "Membrane binding of the N-terminal ubiquitin-like domain of kindlin-2 is
RT crucial for its regulation of integrin activation.";
RL Structure 19:1664-1671(2011).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 328-499.
RX PubMed=22653426; DOI=10.1007/s13238-012-2046-1;
RA Liu Y., Zhu Y., Ye S., Zhang R.;
RT "Crystal structure of kindlin-2 PH domain reveals a conformational
RT transition for its membrane anchoring and regulation of integrin
RT activation.";
RL Protein Cell 3:434-440(2012).
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. Recruits FBLIM1 to focal
CC adhesions. Plays a role in the TGFB1 and integrin signaling pathways.
CC Stabilizes active CTNNB1 and plays a role in the regulation of
CC transcription mediated by CTNNB1 and TCF7L2/TCF4 and in Wnt signaling.
CC {ECO:0000269|PubMed:12679033, ECO:0000269|PubMed:18458155,
CC ECO:0000269|PubMed:21325030, ECO:0000269|PubMed:22030399,
CC ECO:0000269|PubMed:22078565, ECO:0000269|PubMed:22699938}.
CC -!- SUBUNIT: Interacts with ILK (By similarity). Interacts with FBLIM1.
CC Interacts with ITGB1 and ITGB3. Interacts with active, unphosphorylated
CC CTNNB1. Identified in a complex with CTNNB1 and TCF7L2/TCF4. Interacts
CC with ITGB1; the interaction is inhibited in presence of ITGB1BP1.
CC {ECO:0000250, ECO:0000269|PubMed:12679033, ECO:0000269|PubMed:18458155,
CC ECO:0000269|PubMed:21325030, ECO:0000269|PubMed:21768292,
CC ECO:0000269|PubMed:22030399, ECO:0000269|PubMed:22699938}.
CC -!- INTERACTION:
CC Q96AC1; P35222: CTNNB1; NbExp=13; IntAct=EBI-4399465, EBI-491549;
CC Q96AC1; P15884: TCF4; NbExp=6; IntAct=EBI-4399465, EBI-533224;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, cell cortex. Cytoplasm,
CC cytoskeleton. Cytoplasm, cytoskeleton, stress fiber. Cell junction,
CC focal adhesion. Membrane; Peripheral membrane protein; Cytoplasmic
CC side. Cell projection, lamellipodium membrane; Peripheral membrane
CC protein; Cytoplasmic side. Nucleus. Cytoplasm, myofibril, sarcomere, I
CC band {ECO:0000250}. Cell surface {ECO:0000250}. Note=Colocalizes with
CC actin stress fibers at cell-ECM focal adhesion sites. Colocalizes with
CC ITGB3 at lamellipodia at the leading edge of spreading cells. Binds to
CC membranes that contain phosphatidylinositides.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q96AC1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96AC1-2; Sequence=VSP_008783, VSP_008784, VSP_008785;
CC Name=3;
CC IsoId=Q96AC1-3; Sequence=VSP_008783;
CC -!- TISSUE SPECIFICITY: Ubiquitous. Found in numerous tumor tissues.
CC -!- INDUCTION: By serum in lung fetal fibroblast cultured cells.
CC {ECO:0000269|PubMed:8175911}.
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 (PubMed:22030399).
CC {ECO:0000269|PubMed:22030399}.
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:0000269|PubMed:22078565}.
CC -!- MISCELLANEOUS: [Isoform 2]: May be due to an exon inclusion and an
CC intron retention. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the kindlin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA80852.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Wikipedia; Note=FERMT2 entry;
CC URL="https://en.wikipedia.org/wiki/FERMT2";
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DR EMBL; Z24725; CAA80852.1; ALT_INIT; mRNA.
DR EMBL; AF443279; AAN75823.1; -; mRNA.
DR EMBL; EU979385; ACH73257.1; -; mRNA.
DR EMBL; BX161467; CAD61925.1; -; mRNA.
DR EMBL; AL139317; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL352979; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC011125; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC017327; AAH17327.1; -; mRNA.
DR CCDS; CCDS45107.1; -. [Q96AC1-3]
DR CCDS; CCDS45108.1; -. [Q96AC1-2]
DR CCDS; CCDS9713.1; -. [Q96AC1-1]
DR PIR; S69890; S69890.
DR RefSeq; NP_001128471.1; NM_001134999.1. [Q96AC1-3]
DR RefSeq; NP_001128472.1; NM_001135000.1. [Q96AC1-2]
DR RefSeq; NP_006823.1; NM_006832.2. [Q96AC1-1]
DR PDB; 2LGX; NMR; -; A=1-105.
DR PDB; 2LKO; NMR; -; A=367-500.
DR PDB; 2MSU; NMR; -; A=339-358.
DR PDB; 4F7H; X-ray; 1.90 A; A=328-499.
DR PDB; 6U4N; NMR; -; A=1-105.
DR PDB; 6XTJ; X-ray; 1.60 A; AAA=8-680.
DR PDBsum; 2LGX; -.
DR PDBsum; 2LKO; -.
DR PDBsum; 2MSU; -.
DR PDBsum; 4F7H; -.
DR PDBsum; 6U4N; -.
DR PDBsum; 6XTJ; -.
DR AlphaFoldDB; Q96AC1; -.
DR BMRB; Q96AC1; -.
DR SMR; Q96AC1; -.
DR BioGRID; 116175; 149.
DR CORUM; Q96AC1; -.
DR IntAct; Q96AC1; 37.
DR MINT; Q96AC1; -.
DR STRING; 9606.ENSP00000342858; -.
DR GlyGen; Q96AC1; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q96AC1; -.
DR MetOSite; Q96AC1; -.
DR PhosphoSitePlus; Q96AC1; -.
DR SwissPalm; Q96AC1; -.
DR BioMuta; FERMT2; -.
DR DMDM; 38258220; -.
DR EPD; Q96AC1; -.
DR jPOST; Q96AC1; -.
DR MassIVE; Q96AC1; -.
DR MaxQB; Q96AC1; -.
DR PaxDb; Q96AC1; -.
DR PeptideAtlas; Q96AC1; -.
DR PRIDE; Q96AC1; -.
DR ProteomicsDB; 75949; -. [Q96AC1-1]
DR ProteomicsDB; 75950; -. [Q96AC1-2]
DR ProteomicsDB; 75951; -. [Q96AC1-3]
DR Antibodypedia; 23904; 326 antibodies from 31 providers.
DR DNASU; 10979; -.
DR Ensembl; ENST00000341590.8; ENSP00000340391.3; ENSG00000073712.15. [Q96AC1-1]
DR Ensembl; ENST00000343279.8; ENSP00000342858.4; ENSG00000073712.15. [Q96AC1-3]
DR Ensembl; ENST00000395631.6; ENSP00000378993.2; ENSG00000073712.15. [Q96AC1-1]
DR Ensembl; ENST00000399304.7; ENSP00000382243.3; ENSG00000073712.15. [Q96AC1-2]
DR Ensembl; ENST00000553373.5; ENSP00000451084.1; ENSG00000073712.15. [Q96AC1-3]
DR GeneID; 10979; -.
DR KEGG; hsa:10979; -.
DR MANE-Select; ENST00000341590.8; ENSP00000340391.3; NM_006832.3; NP_006823.1.
DR UCSC; uc001xac.4; human. [Q96AC1-1]
DR CTD; 10979; -.
DR DisGeNET; 10979; -.
DR GeneCards; FERMT2; -.
DR HGNC; HGNC:15767; FERMT2.
DR HPA; ENSG00000073712; Low tissue specificity.
DR MIM; 607746; gene.
DR neXtProt; NX_Q96AC1; -.
DR OpenTargets; ENSG00000073712; -.
DR PharmGKB; PA162388349; -.
DR VEuPathDB; HostDB:ENSG00000073712; -.
DR eggNOG; KOG3727; Eukaryota.
DR GeneTree; ENSGT00390000013444; -.
DR HOGENOM; CLU_011611_0_0_1; -.
DR InParanoid; Q96AC1; -.
DR OMA; YWVRCEN; -.
DR OrthoDB; 248494at2759; -.
DR PhylomeDB; Q96AC1; -.
DR TreeFam; TF314677; -.
DR PathwayCommons; Q96AC1; -.
DR Reactome; R-HSA-446353; Cell-extracellular matrix interactions.
DR Reactome; R-HSA-9013149; RAC1 GTPase cycle.
DR Reactome; R-HSA-9013423; RAC3 GTPase cycle.
DR SignaLink; Q96AC1; -.
DR SIGNOR; Q96AC1; -.
DR BioGRID-ORCS; 10979; 346 hits in 1097 CRISPR screens.
DR ChiTaRS; FERMT2; human.
DR EvolutionaryTrace; Q96AC1; -.
DR GeneWiki; FERMT2; -.
DR GenomeRNAi; 10979; -.
DR Pharos; Q96AC1; Tbio.
DR PRO; PR:Q96AC1; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q96AC1; protein.
DR Bgee; ENSG00000073712; Expressed in decidua and 205 other tissues.
DR ExpressionAtlas; Q96AC1; baseline and differential.
DR Genevisible; Q96AC1; HS.
DR GO; GO:0005912; C:adherens junction; IDA:ARUK-UCL.
DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
DR GO; GO:0030054; C:cell junction; IDA:ARUK-UCL.
DR GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell.
DR GO; GO:0030055; C:cell-substrate junction; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:ARUK-UCL.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; IDA:UniProtKB.
DR GO; GO:0031674; C:I band; IEA:UniProtKB-SubCell.
DR GO; GO:0031258; C:lamellipodium membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0001725; C:stress fiber; IEA:Ensembl.
DR GO; GO:0003779; F:actin binding; IMP:ARUK-UCL.
DR GO; GO:0051015; F:actin filament binding; IEA:Ensembl.
DR GO; GO:0005178; F:integrin binding; IBA:GO_Central.
DR GO; GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; IDA:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IPI:ARUK-UCL.
DR GO; GO:0046332; F:SMAD binding; IPI:ARUK-UCL.
DR GO; GO:0034713; F:type I transforming growth factor beta receptor binding; IPI:ARUK-UCL.
DR GO; GO:0034334; P:adherens junction maintenance; IMP:ARUK-UCL.
DR GO; GO:0007155; P:cell adhesion; IMP:ARUK-UCL.
DR GO; GO:0007160; P:cell-matrix adhesion; IMP:UniProtKB.
DR GO; GO:0048041; P:focal adhesion assembly; IMP:ARUK-UCL.
DR GO; GO:0033622; P:integrin activation; IMP:UniProtKB.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:0060173; P:limb development; IEA:Ensembl.
DR GO; GO:0060548; P:negative regulation of cell death; IMP:ARUK-UCL.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; IMP:ARUK-UCL.
DR GO; GO:0043116; P:negative regulation of vascular permeability; IMP:ARUK-UCL.
DR GO; GO:0030335; P:positive regulation of cell migration; IMP:ARUK-UCL.
DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; IDA:ARUK-UCL.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:ARUK-UCL.
DR GO; GO:0051894; P:positive regulation of focal adhesion assembly; IMP:ARUK-UCL.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IMP:ARUK-UCL.
DR GO; GO:0033625; P:positive regulation of integrin activation; IGI:ARUK-UCL.
DR GO; GO:1902462; P:positive regulation of mesenchymal stem cell proliferation; IMP:ARUK-UCL.
DR GO; GO:0035505; P:positive regulation of myosin light chain kinase activity; IMP:ARUK-UCL.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; IMP:ARUK-UCL.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IDA:ARUK-UCL.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; IDA:ARUK-UCL.
DR GO; GO:0051496; P:positive regulation of stress fiber assembly; IMP:ARUK-UCL.
DR GO; GO:1900026; P:positive regulation of substrate adhesion-dependent cell spreading; IGI:ARUK-UCL.
DR GO; GO:1903691; P:positive regulation of wound healing, spreading of epidermal cells; IMP:ARUK-UCL.
DR GO; GO:1902414; P:protein localization to cell junction; IMP:ARUK-UCL.
DR GO; GO:0072657; P:protein localization to membrane; ISS:UniProtKB.
DR GO; GO:0022604; P:regulation of cell morphogenesis; IMP:ARUK-UCL.
DR GO; GO:0008360; P:regulation of cell shape; IEA:UniProtKB-KW.
DR GO; GO:0034446; P:substrate adhesion-dependent cell spreading; ISS:UniProtKB.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0016055; P:Wnt signaling pathway; IMP:UniProtKB.
DR CDD; cd14473; FERM_B-lobe; 1.
DR CDD; cd01237; PH_fermitin; 1.
DR DisProt; DP01613; -.
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; 2.
DR PROSITE; PS50003; PH_DOMAIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell adhesion; Cell junction;
KW Cell membrane; Cell projection; Cell shape; Cytoplasm; Cytoskeleton;
KW Lipid-binding; Membrane; Nucleus; Phosphoprotein; Reference proteome;
KW Wnt signaling pathway.
FT CHAIN 1..680
FT /note="Fermitin family homolog 2"
FT /id="PRO_0000219456"
FT DOMAIN 189..661
FT /note="FERM"
FT DOMAIN 380..476
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT REGION 40..81
FT /note="Interaction with membranes containing
FT phosphatidylinositol phosphate"
FT REGION 141..165
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 141..160
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 383
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 MOD_RES 159
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:24275569"
FT MOD_RES 181
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 339
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 351
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:24275569"
FT MOD_RES 666
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT VAR_SEQ 534
FT /note="Q -> QPGYIRDL (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|Ref.4, ECO:0000303|Ref.5"
FT /id="VSP_008783"
FT VAR_SEQ 625..626
FT /note="TV -> NS (in isoform 2)"
FT /evidence="ECO:0000303|Ref.5"
FT /id="VSP_008784"
FT VAR_SEQ 627..680
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.5"
FT /id="VSP_008785"
FT MUTAGEN 40
FT /note="H->A: Abolishes lipid-binding via the N-terminus;
FT when associated with 74-A--A-81."
FT /evidence="ECO:0000269|PubMed:22078565"
FT MUTAGEN 74..81
FT /note="KTHWTLDK->ATAATLDA: Abolishes lipid-binding via the
FT N-terminus; when associated with A-40."
FT /evidence="ECO:0000269|PubMed:22078565"
FT MUTAGEN 383
FT /note="K->A: Reduces phosphatidylinositol phosphate
FT binding. Reduces integrin activation; when associated with
FT A-385."
FT /evidence="ECO:0000269|PubMed:22030399"
FT MUTAGEN 385
FT /note="K->A: Reduces integrin activation; when associated
FT with A-383."
FT /evidence="ECO:0000269|PubMed:22030399"
FT MUTAGEN 390
FT /note="K->A: Abolishes phosphatidylinositol phosphate
FT binding."
FT /evidence="ECO:0000269|PubMed:21325030"
FT MUTAGEN 393
FT /note="K->A: Reduces phosphatidylinositol phosphate
FT binding."
FT /evidence="ECO:0000269|PubMed:22030399"
FT MUTAGEN 614..615
FT /note="QW->AA: Impairs ITGB3 binding. Abolishes enhancement
FT of talin-mediated integrin activation."
FT /evidence="ECO:0000269|PubMed:18458155"
FT CONFLICT 31
FT /note="V -> I (in Ref. 1; CAA80852)"
FT /evidence="ECO:0000305"
FT TURN 9..11
FT /evidence="ECO:0007829|PDB:2LGX"
FT STRAND 12..16
FT /evidence="ECO:0007829|PDB:2LGX"
FT STRAND 18..23
FT /evidence="ECO:0007829|PDB:6U4N"
FT TURN 25..28
FT /evidence="ECO:0007829|PDB:2LGX"
FT STRAND 30..35
FT /evidence="ECO:0007829|PDB:6U4N"
FT HELIX 41..51
FT /evidence="ECO:0007829|PDB:2LGX"
FT STRAND 58..65
FT /evidence="ECO:0007829|PDB:2LGX"
FT TURN 66..68
FT /evidence="ECO:0007829|PDB:2LGX"
FT STRAND 75..77
FT /evidence="ECO:0007829|PDB:6U4N"
FT HELIX 79..82
FT /evidence="ECO:0007829|PDB:2LGX"
FT STRAND 90..92
FT /evidence="ECO:0007829|PDB:6U4N"
FT TURN 347..353
FT /evidence="ECO:0007829|PDB:2MSU"
FT HELIX 354..357
FT /evidence="ECO:0007829|PDB:2MSU"
FT HELIX 369..371
FT /evidence="ECO:0007829|PDB:4F7H"
FT STRAND 375..382
FT /evidence="ECO:0007829|PDB:4F7H"
FT STRAND 393..400
FT /evidence="ECO:0007829|PDB:4F7H"
FT STRAND 403..408
FT /evidence="ECO:0007829|PDB:4F7H"
FT HELIX 410..412
FT /evidence="ECO:0007829|PDB:4F7H"
FT STRAND 418..422
FT /evidence="ECO:0007829|PDB:4F7H"
FT STRAND 427..433
FT /evidence="ECO:0007829|PDB:4F7H"
FT TURN 434..437
FT /evidence="ECO:0007829|PDB:4F7H"
FT STRAND 438..447
FT /evidence="ECO:0007829|PDB:4F7H"
FT STRAND 450..460
FT /evidence="ECO:0007829|PDB:4F7H"
FT HELIX 461..475
FT /evidence="ECO:0007829|PDB:4F7H"
FT HELIX 484..495
FT /evidence="ECO:0007829|PDB:4F7H"
SQ SEQUENCE 680 AA; 77861 MW; BAFF5AF2CD91C43C CRC64;
MALDGIRMPD GCYADGTWEL SVHVTDLNRD VTLRVTGEVH IGGVMLKLVE KLDVKKDWSD
HALWWEKKRT WLLKTHWTLD KYGIQADAKL QFTPQHKLLR LQLPNMKYVK VKVNFSDRVF
KAVSDICKTF NIRHPEELSL LKKPRDPTKK KKKKLDDQSE DEALELEGPL ITPGSGSIYS
SPGLYSKTMT PTYDAHDGSP LSPTSAWFGD SALSEGNPGI LAVSQPITSP EILAKMFKPQ
ALLDKAKINQ GWLDSSRSLM EQDVKENEAL LLRFKYYSFF DLNPKYDAIR INQLYEQAKW
AILLEEIECT EEEMMMFAAL QYHINKLSIM TSENHLNNSD KEVDEVDAAL SDLEITLEGG
KTSTILGDIT SIPELADYIK VFKPKKLTLK GYKQYWCTFK DTSISCYKSK EESSGTPAHQ
MNLRGCEVTP DVNISGQKFN IKLLIPVAEG MNEIWLRCDN EKQYAHWMAA CRLASKGKTM
ADSSYNLEVQ NILSFLKMQH LNPDPQLIPE QITTDITPEC LVSPRYLKKY KNKQITARIL
EAHQNVAQMS LIEAKMRFIQ AWQSLPEFGI THFIARFQGG KKEELIGIAY NRLIRMDAST
GDAIKTWRFS NMKQWNVNWE IKMVTVEFAD EVRLSFICTE VDCKVVHEFI GGYIFLSTRA
KDQNESLDEE MFYKLTSGWV
