ID FERM1_MOUSE Reviewed; 677 AA. AC P59113; A2ANX1; Q8BQG6; DT 06-DEC-2002, integrated into UniProtKB/Swiss-Prot. DT 27-JUL-2011, sequence version 4. DT 07-APR-2021, entry version 152. DE RecName: Full=Fermitin family homolog 1; DE AltName: Full=Kindlin-1; DE AltName: Full=Unc-112-related protein 1; GN Name=Fermt1; Synonyms=Kind1, Urp1; 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] OF 1-152 AND 448-677. RC TISSUE=Mammary fibroblast; 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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 41-677. RC STRAIN=C57BL/6J; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [4] RP DISRUPTION PHENOTYPE. RX PubMed=19057668; DOI=10.1371/journal.pgen.1000289; RA Ussar S., Moser M., Widmaier M., Rognoni E., Harrer C., RA Genzel-Boroviczeny O., Fassler R.; RT "Loss of Kindlin-1 causes skin atrophy and lethal neonatal intestinal RT epithelial dysfunction."; RL PLoS Genet. 4:E1000289-E1000289(2008). RN [5] RP STRUCTURE BY NMR OF 1-96, AND DOMAIN FERM. RX PubMed=19804783; DOI=10.1016/j.jmb.2009.09.061; RA Goult B.T., Bouaouina M., Harburger D.S., Bate N., Patel B., Anthis N.J., RA Campbell I.D., Calderwood D.A., Barsukov I.L., Roberts G.C., RA Critchley D.R.; RT "The structure of the N-terminus of kindlin-1: a domain important for RT alphaIIbbeta3 integrin activation."; RL J. Mol. Biol. 394:944-956(2009). CC -!- FUNCTION: Involved in cell adhesion. Contributes to integrin CC activation. When coexpressed with talin, potentiates activation of CC ITGA2B. Required for normal keratinocyte proliferation. Required for CC normal polarization of basal keratinocytes in skin, and for normal cell CC shape. Required for normal adhesion of keratinocytes to fibronectin and CC laminin, and for normal keratinocyte migration to wound sites (By CC similarity). {ECO:0000250}. CC -!- SUBUNIT: Interacts with the cytoplasmic domain of integrins ITGB1 and CC ITGB3. {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton {ECO:0000250}. Cell CC junction, focal adhesion {ECO:0000250}. Cell projection, ruffle CC membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}; CC Cytoplasmic side {ECO:0000250}. Note=Colocalizes with filamentous CC actin. Constituent of focal adhesions (By similarity). Localized at the CC basal aspect of skin keratinocytes, close to the cell membrane (By CC similarity). Upon TGFB1 treatment, it localizes to membrane ruffles (By CC 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. The FERM CC domain contains the subdomains F1, F2 and F3. It is preceded by a F0 CC domain with a ubiquitin-like fold. The F0 domain is required for CC integrin activation and for localization at focal adhesions (By CC similarity). {ECO:0000250}. CC -!- DISRUPTION PHENOTYPE: Mice are born with the expected Mendelian CC distribution and appear normal at birth, but fail to thrive, become CC dehydrated and die after three to five days. They develop skin atrophy CC and die due to a lethal intestinal epithelial dysfunction. The colon is CC shortened and swollen and presents signs of acute inflammation. At the CC time of death, about 80% of the colonic epithelium is detached. CC {ECO:0000269|PubMed:19057668}. CC -!- SIMILARITY: Belongs to the kindlin family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH29093.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={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; AL831763; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC029093; AAH29093.1; ALT_INIT; mRNA. DR EMBL; BC042792; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AK050804; BAC34417.1; -; mRNA. DR CCDS; CCDS38248.1; -. DR RefSeq; NP_932146.2; NM_198029.2. DR RefSeq; XP_017173695.1; XM_017318206.1. DR RefSeq; XP_017173696.1; XM_017318207.1. DR RefSeq; XP_017173699.1; XM_017318210.1. DR PDB; 2KMC; NMR; -; A=1-96. DR PDB; 4BBK; X-ray; 2.10 A; A=364-509. DR PDBsum; 2KMC; -. DR PDBsum; 4BBK; -. DR BMRB; P59113; -. DR SMR; P59113; -. DR BioGRID; 232339; 1. DR IntAct; P59113; 1. DR MINT; P59113; -. DR STRING; 10090.ENSMUSP00000047616; -. DR iPTMnet; P59113; -. DR PhosphoSitePlus; P59113; -. DR MaxQB; P59113; -. DR PaxDb; P59113; -. DR PeptideAtlas; P59113; -. DR PRIDE; P59113; -. DR ProteomicsDB; 271740; -. DR Antibodypedia; 8379; 228 antibodies. DR Ensembl; ENSMUST00000038280; ENSMUSP00000047616; ENSMUSG00000027356. DR GeneID; 241639; -. DR KEGG; mmu:241639; -. DR UCSC; uc008mno.1; mouse. DR CTD; 55612; -. DR MGI; MGI:2443583; Fermt1. DR eggNOG; KOG3727; Eukaryota. DR GeneTree; ENSGT00390000013444; -. DR HOGENOM; CLU_011611_0_0_1; -. DR InParanoid; P59113; -. DR OMA; QMKSLAP; -. DR OrthoDB; 248494at2759; -. DR TreeFam; TF314677; -. DR BioGRID-ORCS; 241639; 0 hits in 52 CRISPR screens. DR EvolutionaryTrace; P59113; -. DR PRO; PR:P59113; -. DR Proteomes; UP000000589; Chromosome 2. DR RNAct; P59113; protein. DR Bgee; ENSMUSG00000027356; Expressed in stomach and 53 other tissues. DR GO; GO:0030054; C:cell junction; ISS:UniProtKB. DR GO; GO:0071944; C:cell periphery; ISO:MGI. DR GO; GO:0030055; C:cell-substrate junction; IBA:GO_Central. DR GO; GO:0005737; C:cytoplasm; ISO:MGI. DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell. DR GO; GO:0005829; C:cytosol; ISS:UniProtKB. DR GO; GO:0005925; C:focal adhesion; IDA:MGI. DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell. DR GO; GO:0051015; F:actin filament binding; IDA:MGI. DR GO; GO:0005178; F:integrin binding; IBA:GO_Central. DR GO; GO:0071711; P:basement membrane organization; IMP:CAFA. DR GO; GO:0007155; P:cell adhesion; ISS:UniProtKB. DR GO; GO:0007160; P:cell-matrix adhesion; IBA:GO_Central. DR GO; GO:0090162; P:establishment of epithelial cell polarity; ISS:UniProtKB. DR GO; GO:0007229; P:integrin-mediated signaling pathway; IEA:InterPro. DR GO; GO:0051546; P:keratinocyte migration; ISS:UniProtKB. DR GO; GO:0043616; P:keratinocyte proliferation; ISS:UniProtKB. DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IMP:CAFA. DR GO; GO:0010629; P:negative regulation of gene expression; IMP:CAFA. DR GO; GO:0042308; P:negative regulation of protein import into nucleus; IMP:CAFA. DR GO; GO:2000647; P:negative regulation of stem cell proliferation; IMP:CAFA. DR GO; GO:0051886; P:negative regulation of timing of anagen; IMP:CAFA. DR GO; GO:0033630; P:positive regulation of cell adhesion mediated by integrin; IMP:CAFA. DR GO; GO:0001954; P:positive regulation of cell-matrix adhesion; IMP:CAFA. DR GO; GO:0033625; P:positive regulation of integrin activation; ISO:MGI. DR GO; GO:0071636; P:positive regulation of transforming growth factor beta production; IMP:CAFA. DR GO; GO:0030511; P:positive regulation of transforming growth factor beta receptor signaling pathway; IMP:CAFA. DR GO; GO:1903691; P:positive regulation of wound healing, spreading of epidermal cells; ISO:MGI. DR CDD; cd14473; FERM_B-lobe; 1. DR CDD; cd01237; PH_fermitin; 1. DR DisProt; DP00655; -. 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; PS00661; FERM_2; 1. DR PROSITE; PS50003; PH_DOMAIN; 1. PE 1: Evidence at protein level; KW 3D-structure; Cell adhesion; Cell junction; Cell membrane; Cell projection; KW Cytoplasm; Cytoskeleton; Membrane; Phosphoprotein; Reference proteome. FT CHAIN 1..677 FT /note="Fermitin family homolog 1" FT /id="PRO_0000219453" FT DOMAIN 96..653 FT /note="FERM" FT DOMAIN 377..473 FT /note="PH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145" FT COMPBIAS 147..154 FT /note="Poly-Lys" FT MOD_RES 170 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9BQL6" FT MOD_RES 179 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9BQL6" FT CONFLICT 522 FT /note="C -> R (in Ref. 2; AAH29093)" FT /evidence="ECO:0000305" FT CONFLICT 586 FT /note="A -> S (in Ref. 2; AAH29093)" FT /evidence="ECO:0000305" FT STRAND 1..5 FT /evidence="ECO:0007744|PDB:2KMC" FT STRAND 12..19 FT /evidence="ECO:0007744|PDB:2KMC" FT STRAND 26..33 FT /evidence="ECO:0007744|PDB:2KMC" FT HELIX 39..50 FT /evidence="ECO:0007744|PDB:2KMC" FT STRAND 57..63 FT /evidence="ECO:0007744|PDB:2KMC" FT TURN 64..67 FT /evidence="ECO:0007744|PDB:2KMC" FT STRAND 68..70 FT /evidence="ECO:0007744|PDB:2KMC" FT HELIX 77..80 FT /evidence="ECO:0007744|PDB:2KMC" FT STRAND 88..92 FT /evidence="ECO:0007744|PDB:2KMC" FT STRAND 372..379 FT /evidence="ECO:0007744|PDB:4BBK" FT STRAND 390..397 FT /evidence="ECO:0007744|PDB:4BBK" FT STRAND 400..406 FT /evidence="ECO:0007744|PDB:4BBK" FT HELIX 407..409 FT /evidence="ECO:0007744|PDB:4BBK" FT STRAND 415..419 FT /evidence="ECO:0007744|PDB:4BBK" FT STRAND 424..430 FT /evidence="ECO:0007744|PDB:4BBK" FT TURN 431..434 FT /evidence="ECO:0007744|PDB:4BBK" FT STRAND 435..444 FT /evidence="ECO:0007744|PDB:4BBK" FT STRAND 447..457 FT /evidence="ECO:0007744|PDB:4BBK" FT HELIX 458..472 FT /evidence="ECO:0007744|PDB:4BBK" FT HELIX 482..496 FT /evidence="ECO:0007744|PDB:4BBK" SQ SEQUENCE 677 AA; 76941 MW; 9B8B1876FA7621EE CRC64; MLSSGDLTSA SWELVVRVDH ANGEQQTEIT LRVSGDLHIG GVMLKLVEQM NIAQDWSDYA LWWEQKRCWL LKTHWTLDKC GVQADANLLF TPQHKMLRLR LPNAKTVRLR VSFSAVVFKA VADICKVLNI RRPEELSLLK PSSDYCKKKK KKEKNSKEPV IEDILNLESS STSSGSPVSP GLYSKTMTPT YDPINGTPAL STMTWFGDSP LTEQNCSVLA FSQPPPSPDV LADMFQPRSL VDKAKMNAGW LDSSRSLMEQ SIQEDEQLQL RFKYYTFFDL NPKYDAVRIN QLYEQARWAV LLEEIDCTEE EMLIFAALQY HISKLSQCAE IQDFATKSEV DEVEAALSSL EVTLEGGKAD NTLEDITDIP KLADYLKLFR PKKLMLKACK QYWFVFKDTS IAYFKNKELE QGEPIEKLNL RGCEIVPDVN VSGRKFGIKL LIPVADGMNE VYLRCDHEDQ YARWMAACIL ASKGKTMADS SYQPEVISIL SFLKMKNRNS SPLVASSLEN MDMNPECLVS PCCAKKHKSK QLAARILEAH HNVAQMPLVE AKLQFIQAWQ SLPEFGLTYY LVRFKGSKKD DILGVAYNRL IRIDAVTGIP VTTWRFANMK QWNVNWEIRQ VAIEFDQNVS IAFTCLSADC KIVHEYIGGY IFLSTRSKDQ NETLDEDLFH KLTGGQD //