URP2_MOUSE
ID URP2_MOUSE Reviewed; 665 AA.
AC Q8K1B8;
DT 16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Fermitin family homolog 3;
DE AltName: Full=Kindlin-3;
DE AltName: Full=Unc-112-related protein 2;
GN Name=Fermt3; Synonyms=Kind3, Urp2;
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 MRNA].
RC STRAIN=FVB/N; TISSUE=Salivary gland;
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 [2]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=16876785; DOI=10.1016/j.yexcr.2006.06.030;
RA Ussar S., Wang H.-V., Linder S., Faessler R., Moser M.;
RT "The Kindlins: subcellular localization and expression during murine
RT development.";
RL Exp. Cell Res. 312:3142-3151(2006).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18662549; DOI=10.1016/j.cell.2008.05.033;
RA Krueger M., Moser M., Ussar S., Thievessen I., Luber C.A., Forner F.,
RA Schmidt S., Zanivan S., Faessler R., Mann M.;
RT "SILAC mouse for quantitative proteomics uncovers kindlin-3 as an essential
RT factor for red blood cell function.";
RL Cell 134:353-364(2008).
RN [4]
RP FUNCTION, DISRUPTION PHENOTYPE, INTERACTION WITH ITGB1 AND ITGB3, AND
RP MUTAGENESIS OF GLN-597.
RX PubMed=18278053; DOI=10.1038/nm1722;
RA Moser M., Nieswandt B., Ussar S., Pozgajova M., Faessler R.;
RT "Kindlin-3 is essential for integrin activation and platelet aggregation.";
RL Nat. Med. 14:325-330(2008).
RN [5]
RP FUNCTION, DISRUPTION PHENOTYPE, AND INTERACTION WITH ITGB2.
RX PubMed=19234461; DOI=10.1038/nm.1921;
RA Moser M., Bauer M., Schmid S., Ruppert R., Schmidt S., Sixt M., Wang H.-V.,
RA Sperandio M., Faessler R.;
RT "Kindlin-3 is required for beta2 integrin-mediated leukocyte adhesion to
RT endothelial cells.";
RL Nat. Med. 15:300-305(2009).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Spleen, and
RC Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Plays a central role in cell adhesion in hematopoietic cells
CC (By similarity). Acts by activating the integrin beta-1-3 (ITGB1, ITGB2
CC and ITGB3) (PubMed:18278053). Required for integrin-mediated platelet
CC adhesion and leukocyte adhesion to endothelial cells (PubMed:19234461).
CC Required for activation of integrin beta-2 (ITGB2) in polymorphonuclear
CC granulocytes (PMNs) (PubMed:18278053). {ECO:0000250|UniProtKB:Q86UX7,
CC ECO:0000269|PubMed:18278053, ECO:0000269|PubMed:18662549,
CC ECO:0000269|PubMed:19234461}.
CC -!- SUBUNIT: Interacts with ITGB1, ITGB2 and ITGB3 (via cytoplasmic tails).
CC {ECO:0000269|PubMed:18278053, ECO:0000269|PubMed:19234461}.
CC -!- SUBCELLULAR LOCATION: Cell projection, podosome
CC {ECO:0000269|PubMed:16876785}. Note=Present in the F-actin surrounding
CC ring structure of podosomes, which are specialized adhesion structures
CC of hematopoietic cells.
CC -!- TISSUE SPECIFICITY: Specifically expressed in hematopoietic cells.
CC {ECO:0000269|PubMed:16876785}.
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 -!- DISRUPTION PHENOTYPE: Mice suffer from fatal anemia, caused by severe
CC bleeding and erythrocytopenia. Mice also show markedly reduced size and
CC cellularity. Platelets cannot activate integrins despite normal Talin
CC (Tln1) expression. {ECO:0000269|PubMed:18278053,
CC ECO:0000269|PubMed:18662549, ECO:0000269|PubMed:19234461}.
CC -!- SIMILARITY: Belongs to the kindlin family. {ECO:0000305}.
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DR EMBL; BC025119; AAH25119.1; -; mRNA.
DR EMBL; BC032204; AAH32204.1; -; mRNA.
DR CCDS; CCDS29518.1; -.
DR RefSeq; NP_722490.1; NM_153795.2.
DR RefSeq; XP_006526656.1; XM_006526593.3.
DR PDB; 5L81; X-ray; 2.23 A; A/B=344-478.
DR PDBsum; 5L81; -.
DR AlphaFoldDB; Q8K1B8; -.
DR SMR; Q8K1B8; -.
DR BioGRID; 223834; 11.
DR IntAct; Q8K1B8; 3.
DR MINT; Q8K1B8; -.
DR STRING; 10090.ENSMUSP00000037858; -.
DR iPTMnet; Q8K1B8; -.
DR PhosphoSitePlus; Q8K1B8; -.
DR SwissPalm; Q8K1B8; -.
DR EPD; Q8K1B8; -.
DR jPOST; Q8K1B8; -.
DR MaxQB; Q8K1B8; -.
DR PaxDb; Q8K1B8; -.
DR PRIDE; Q8K1B8; -.
DR ProteomicsDB; 275394; -.
DR Antibodypedia; 29146; 282 antibodies from 37 providers.
DR DNASU; 108101; -.
DR Ensembl; ENSMUST00000040772; ENSMUSP00000037858; ENSMUSG00000024965.
DR GeneID; 108101; -.
DR KEGG; mmu:108101; -.
DR UCSC; uc008gkd.2; mouse.
DR CTD; 83706; -.
DR MGI; MGI:2147790; Fermt3.
DR VEuPathDB; HostDB:ENSMUSG00000024965; -.
DR eggNOG; KOG3727; Eukaryota.
DR GeneTree; ENSGT00390000013444; -.
DR HOGENOM; CLU_011611_0_0_1; -.
DR InParanoid; Q8K1B8; -.
DR OMA; AMAGMKT; -.
DR OrthoDB; 248494at2759; -.
DR PhylomeDB; Q8K1B8; -.
DR TreeFam; TF314677; -.
DR Reactome; R-MMU-114608; Platelet degranulation.
DR BioGRID-ORCS; 108101; 7 hits in 72 CRISPR screens.
DR ChiTaRS; Fermt3; mouse.
DR PRO; PR:Q8K1B8; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q8K1B8; protein.
DR Bgee; ENSMUSG00000024965; Expressed in stroma of bone marrow and 235 other tissues.
DR ExpressionAtlas; Q8K1B8; baseline and differential.
DR Genevisible; Q8K1B8; MM.
DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-KW.
DR GO; GO:0030055; C:cell-substrate junction; IBA:GO_Central.
DR GO; GO:0002102; C:podosome; IDA:UniProtKB.
DR GO; GO:0005178; F:integrin binding; IDA:UniProtKB.
DR GO; GO:0007160; P:cell-matrix adhesion; IBA:GO_Central.
DR GO; GO:0033622; P:integrin activation; IMP:UniProtKB.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0007159; P:leukocyte cell-cell adhesion; IMP:UniProtKB.
DR GO; GO:0070527; P:platelet aggregation; IMP:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; ISS:UniProtKB.
DR GO; GO:0033632; P:regulation of cell-cell adhesion mediated by integrin; IMP:UniProtKB.
DR GO; GO:0034446; P:substrate adhesion-dependent cell spreading; ISS:UniProtKB.
DR CDD; cd14473; FERM_B-lobe; 1.
DR CDD; cd01237; PH_fermitin; 1.
DR Gene3D; 1.20.80.10; -; 1.
DR Gene3D; 2.30.29.30; -; 2.
DR InterPro; IPR019749; Band_41_domain.
DR InterPro; IPR014352; FERM/acyl-CoA-bd_prot_sf.
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 projection;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..665
FT /note="Fermitin family homolog 3"
FT /id="PRO_0000219455"
FT DOMAIN 229..556
FT /note="FERM"
FT DOMAIN 357..453
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT MOD_RES 8
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q86UX7"
FT MOD_RES 11
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q86UX7"
FT MOD_RES 502
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q86UX7"
FT MOD_RES 589
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q86UX7"
FT MUTAGEN 597
FT /note="Q->A: Impairs ability to activate integrins."
FT /evidence="ECO:0000269|PubMed:18278053"
FT STRAND 351..359
FT /evidence="ECO:0007829|PDB:5L81"
FT STRAND 370..377
FT /evidence="ECO:0007829|PDB:5L81"
FT STRAND 380..387
FT /evidence="ECO:0007829|PDB:5L81"
FT TURN 388..392
FT /evidence="ECO:0007829|PDB:5L81"
FT STRAND 395..399
FT /evidence="ECO:0007829|PDB:5L81"
FT STRAND 404..410
FT /evidence="ECO:0007829|PDB:5L81"
FT TURN 411..414
FT /evidence="ECO:0007829|PDB:5L81"
FT STRAND 415..424
FT /evidence="ECO:0007829|PDB:5L81"
FT STRAND 427..434
FT /evidence="ECO:0007829|PDB:5L81"
FT HELIX 438..452
FT /evidence="ECO:0007829|PDB:5L81"
FT HELIX 462..476
FT /evidence="ECO:0007829|PDB:5L81"
SQ SEQUENCE 665 AA; 75635 MW; B0BDC2E6FC3D0894 CRC64;
MAGMKTASGD YIDSSWELRV FVGEEDPEAQ SVTLRVTGES HIGGVLLKIV EEINRKQDWS
DHAIWWEQKR QWLLQTHWTL DKYGILADAR LFFGPQHRPV ILRLPNRRVL RLRASFSKPL
FQTVAAICRL LSIRHPEELS LLRAPEKKEK KKKEKEPEEE VHDLTKVVLA GGVAPTLFRG
MPAHFSDSAQ TEACYHMLSR PQPAPDPLLL QRLPRPSSLP DKTQLHSRWL DSSRCLMQQG
IKAGDVLWLR FKYYSFFDLD PKTDPVRLTQ LYEQARWDLL TEEIDCTEEE MMVFAALQYH
INKLTLSGDV GELASGDLGL DDLDAALNNL EVKLKGSAPS DMLDSLTTIP ELKDHLRIFR
PRKLTLKGYR QYWVVFKDTT LSYYKSQDEA PGDPTQQLNL KGCEVVPDVN VSGQKFCIKL
LVPSPEGMSE IYLRCQDEQQ YAQWMAACRL ASKGRTMADS SYASEVQAIL AFLSLQRAGG
SNGGSGNKPQ GPEAPAEGLN PYGLVAPRFQ RKFKAKQLTP RILEAHQNVA QLSLTEAQLR
FIQAWQSLPD FGISYVMVRF KGSRKDEILG IANNRLIRID LAVGDVVKTW RFSNMRQWNV
NWDIRQVAIE FDEHINVAFS CVSASCRIVH EYIGGYIFLS TRERARGEEL DEDLFLQLTG
GHEAF
