FERM1_MOUSE
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 03-AUG-2022, entry version 157.
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 AlphaFoldDB; P59113; -.
DR BMRB; P59113; -.
DR SMR; P59113; -.
DR BioGRID; 232339; 1.
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; 238 antibodies from 27 providers.
DR DNASU; 241639; -.
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 VEuPathDB; HostDB:ENSMUSG00000027356; -.
DR eggNOG; KOG3727; Eukaryota.
DR GeneTree; ENSGT00390000013444; -.
DR HOGENOM; CLU_011611_0_0_1; -.
DR InParanoid; P59113; -.
DR OMA; EDQYARW; -.
DR OrthoDB; 248494at2759; -.
DR PhylomeDB; P59113; -.
DR TreeFam; TF314677; -.
DR BioGRID-ORCS; 241639; 2 hits in 74 CRISPR screens.
DR EvolutionaryTrace; P59113; -.
DR PRO; PR:P59113; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; P59113; protein.
DR Bgee; ENSMUSG00000027356; Expressed in right kidney and 66 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 REGION 157..181
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 165..181
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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:0007829|PDB:2KMC"
FT STRAND 12..19
FT /evidence="ECO:0007829|PDB:2KMC"
FT STRAND 26..33
FT /evidence="ECO:0007829|PDB:2KMC"
FT HELIX 39..50
FT /evidence="ECO:0007829|PDB:2KMC"
FT STRAND 57..63
FT /evidence="ECO:0007829|PDB:2KMC"
FT TURN 64..67
FT /evidence="ECO:0007829|PDB:2KMC"
FT STRAND 68..70
FT /evidence="ECO:0007829|PDB:2KMC"
FT HELIX 77..80
FT /evidence="ECO:0007829|PDB:2KMC"
FT STRAND 88..92
FT /evidence="ECO:0007829|PDB:2KMC"
FT STRAND 372..379
FT /evidence="ECO:0007829|PDB:4BBK"
FT STRAND 390..397
FT /evidence="ECO:0007829|PDB:4BBK"
FT STRAND 400..406
FT /evidence="ECO:0007829|PDB:4BBK"
FT HELIX 407..409
FT /evidence="ECO:0007829|PDB:4BBK"
FT STRAND 415..419
FT /evidence="ECO:0007829|PDB:4BBK"
FT STRAND 424..430
FT /evidence="ECO:0007829|PDB:4BBK"
FT TURN 431..434
FT /evidence="ECO:0007829|PDB:4BBK"
FT STRAND 435..444
FT /evidence="ECO:0007829|PDB:4BBK"
FT STRAND 447..457
FT /evidence="ECO:0007829|PDB:4BBK"
FT HELIX 458..472
FT /evidence="ECO:0007829|PDB:4BBK"
FT HELIX 482..496
FT /evidence="ECO:0007829|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
