ID FERM1_MOUSE Reviewed; 677 AA. AC P59113; Q8BQG6; DT 06-DEC-2002, integrated into UniProtKB/Swiss-Prot. DT 09-JAN-2007, sequence version 3. DT 20-APR-2010, entry version 72. DE RecName: Full=Fermitin family homolog 1; DE AltName: Full=Unc-112-related protein 1; DE AltName: Full=Kindlin-1; GN Name=Fermt1; Synonyms=Kind1, Urp1; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; Murinae; Mus. OX NCBI_TaxID=10090; RN [1] 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [2] 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., RA Davis M.J., Wilming L.G., Aidinis V., Allen J.E., RA Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., RA Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., RA Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., RA Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., RA di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., RA Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., RA Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., RA Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., RA Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., RA Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., RA Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., RA Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., RA Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., RA Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., RA Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., RA Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., RA Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., RA 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., RA Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., RA Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., RA Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., RA Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., RA Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., RA Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., RA Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., RA Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., RA Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., RA Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., RA Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., RA Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [3] 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 [4] 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., RA Anthis N.J., Campbell I.D., Calderwood D.A., Barsukov I.L., RA Roberts G.C., 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 co-expressed with talin, potentiates activation CC of ITGA2B. Required for normal keratinocyte proliferation. CC Required for normal polarization of basal keratinocytes in skin, CC and for normal cell shape. Required for normal adhesion of CC keratinocytes to fibronectin and laminin, and for normal CC keratinocyte migration to wound sites (By similarity). CC -!- SUBUNIT: Interacts with the cytoplasmic domain of integrins ITGB1 CC and ITGB3 (By similarity). CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton (By similarity). CC Cell junction, focal adhesion (By similarity). Cell projection, CC ruffle membrane; Peripheral membrane protein; Cytoplasmic side (By CC similarity). Note=Colocalizes with filamentous actin. Constituent CC of focal adhesions (By similarity). Localized at the basal aspect CC of skin keratinocytes, close to the cell membrane (By similarity). CC Upon TGFB1 treatment, it localizes to membrane ruffles (By CC similarity). CC -!- DOMAIN: The FERM domain is not correctly detected by PROSITE or CC Pfam techniques because it contains the insertion of a PH domain. CC The FERM domain contains the subdomains F1, F2 and F3. It is CC preceded by a F0 domain with a ubiquitin-like fold. The F0 domain CC is required for integrin activation and for localization at focal CC adhesions (By similarity). CC -!- DISRUPTION PHENOTYPE: Mice are born with the expected Mendelian CC distribution and appear normal at birth, but fail to thrive, CC become dehydrated and die after three to five days. They develop CC skin atrophy and die due to a lethal intestinal epithelial CC dysfunction. The colon is shortened and swollen and presents signs CC of acute inflammation. At the time of death, about 80% of the CC colonic epithelium is detached. CC -!- SIMILARITY: Belongs to the kindlin family. CC -!- SIMILARITY: Contains 1 FERM domain. CC -!- SIMILARITY: Contains 1 PH domain. CC -!- SEQUENCE CAUTION: CC Sequence=AAH29093.1; Type=Erroneous initiation; 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; BC029093; AAH29093.1; ALT_INIT; mRNA. DR EMBL; BC042792; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AK050804; BAC34417.1; -; mRNA. DR IPI; IPI00670967; -. DR RefSeq; NP_932146.2; -. DR UniGene; Mm.209784; -. DR PDB; 2KMC; NMR; -; A=1-96. DR PDBsum; 2KMC; -. DR SMR; P59113; 249-650, 528-651. DR STRING; P59113; -. DR PhosphoSite; P59113; -. DR PRIDE; P59113; -. DR Ensembl; ENSMUST00000038280; ENSMUSP00000047616; ENSMUSG00000027356; Mus musculus. DR GeneID; 241639; -. DR KEGG; mmu:241639; -. DR UCSC; uc008mno.1; mouse. DR CTD; 241639; -. DR MGI; MGI:2443583; Fermt1. DR HOGENOM; HBG315538; -. DR HOVERGEN; HBG020688; -. DR InParanoid; P59113; -. DR NextBio; 385110; -. DR ArrayExpress; P59113; -. DR Bgee; P59113; -. DR Genevestigator; P59113; -. 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:0005515; F:protein binding; IEA:UniProtKB-KW. DR GO; GO:0007155; P:cell adhesion; ISS:UniProtKB. DR GO; GO:0090162; P:establishment of epithelial cell polarity; ISS:UniProtKB. DR GO; GO:0051546; P:keratinocyte migration; ISS:UniProtKB. DR GO; GO:0043616; P:keratinocyte proliferation; ISS:UniProtKB. DR InterPro; IPR019749; Band_41_domain. DR InterPro; IPR019748; FERM_central. DR InterPro; IPR011993; PH_type. DR InterPro; IPR001849; Pleckstrin_homology. DR Gene3D; G3DSA:2.30.29.30; PH_type; 1. DR Pfam; PF00373; FERM_M; 1. DR Pfam; PF00169; PH; 1. DR SMART; SM00295; B41; 1. DR SMART; SM00233; PH; 1. DR SUPFAM; SSF47031; FERM_3-hlx; 1. DR PROSITE; PS00660; FERM_1; FALSE_NEG. DR PROSITE; PS00661; FERM_2; 1. DR PROSITE; PS50057; FERM_3; FALSE_NEG. DR PROSITE; PS50003; PH_DOMAIN; 1. PE 1: Evidence at protein level; KW 3D-structure; Cell adhesion; Cell junction; Cell membrane; KW Cell projection; Cytoplasm; Cytoskeleton; Membrane; Phosphoprotein. FT CHAIN 1 677 Fermitin family homolog 1. FT /FTId=PRO_0000219453. FT DOMAIN 96 653 FERM. FT DOMAIN 377 473 PH. FT COMPBIAS 147 154 Poly-Lys. FT MOD_RES 170 170 Phosphoserine (By similarity). FT MOD_RES 179 179 Phosphoserine (By similarity). FT CONFLICT 522 522 R -> C (in Ref. 2; BAC34417). FT CONFLICT 586 586 S -> A (in Ref. 2; BAC34417). SQ SEQUENCE 677 AA; 77010 MW; 826E62DF73C5A1DD 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 PRCAKKHKSK QLAARILEAH HNVAQMPLVE AKLQFIQAWQ SLPEFGLTYY LVRFKGSKKD DILGVSYNRL IRIDAVTGIP VTTWRFANMK QWNVNWEIRQ VAIEFDQNVS IAFTCLSADC KIVHEYIGGY IFLSTRSKDQ NETLDEDLFH KLTGGQD //