P59113
SS
Gene name |
Fermt1 (Kind1, Urp1) |
Protein name |
Fermitin family homolog 1 |
Names |
Kindlin-1 , Unc-112-related protein 1 |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:241639 |
EC number |
|
Protein Class |
|
Descriptions
Kindlin-3 is a member of the kindlin family of focal adhesion proteins which bind to integrin beta-chain cytoplasmic domains to regulate integrin function. kindlin-3 is maintained in a homotrimer state, which is different from the monomer that binds integrin β cytoplasmic tails. The trimer formation of kindlin-3 results in an autoinhibited state, as the integrin-binding pocket is blocked by the pleckstrin homology (PH) domain of another protomer. Mutations disrupting the trimer interface (Q471A, A475F, S478A) lead to increased integrin-mediated cell adhesion and spreading, indicating relief from autoinhibition. This autoinhibition regulates kindlin-3’s role in integrin activation and signaling, with implications for diseases like leukocyte adhesion deficiency (LAD) III and cancer.
Autoinhibitory domains (AIDs)
Target domain |
581-677 (F3 subdomain) |
Relief mechanism |
PTM |
Assay |
|
Accessory elements
No accessory elements
Autoinhibited structure
Activated structure
3 structures for P59113
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| 2KMC | NMR | - | A | 1-96 | PDB |
| 4BBK | X-ray | 210 A | A | 364-509 | PDB |
| AF-P59113-F1 | Predicted | AlphaFoldDB |
36 variants for P59113
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs3392229057 | 58 | D>V | No | EVA | |
| rs3392297217 | 79 | K>N | No | EVA | |
| rs3392087833 | 79 | K>T | No | EVA | |
| rs225455452 | 80 | C>Y | No | EVA | |
| rs3392297228 | 81 | G>R | No | EVA | |
| rs3388596198 | 100 | R>G | No | EVA | |
| rs3388594408 | 103 | N>H | No | EVA | |
| rs3388597983 | 121 | V>F | No | EVA | |
| rs52427777 | 175 | G>C | No | EVA | |
| rs3392098220 | 234 | M>L | No | EVA | |
| rs27245590 | 269 | Q>L | No | EVA | |
| rs3388581122 | 292 | L>H | No | EVA | |
| rs3388596868 | 318 | L>M | No | EVA | |
| rs3388594755 | 319 | Q>H | No | EVA | |
| rs3392256276 | 324 | K>T | No | EVA | |
| rs222479848 | 327 | Q>L | No | EVA | |
| rs3388595988 | 341 | D>N | No | EVA | |
| rs229311036 | 388 | A>P | No | EVA | |
| rs3392098265 | 400 | S>P | No | EVA | |
| rs27245651 | 409 | L>F | No | EVA | |
| rs256443850 | 420 | L>I | No | EVA | |
| rs3388595162 | 430 | N>G* | No | EVA | |
| rs27245656 | 456 | D>N | No | EVA | |
| rs3388591581 | 478 | A>T | No | EVA | |
| rs260174379 | 487 | I>V | No | EVA | |
| rs3388595155 | 489 | I>V | No | EVA | |
| rs27245668 | 522 | C>R | No | EVA | |
| rs3388586885 | 526 | K>M | No | EVA | |
| rs3388586885 | 526 | K>R | No | EVA | |
| rs3388594329 | 543 | V>L | No | EVA | |
| rs3392229097 | 546 | M>R | No | EVA | |
| rs3392098262 | 547 | P>H | No | EVA | |
| rs3388586900 | 571 | L>R | No | EVA | |
| rs27245702 | 586 | A>S | No | EVA | |
| rs3388596237 | 646 | Y>F | No | EVA | |
| rs3388592965 | 657 | S>P | No | EVA |
No associated diseases with P59113
5 regional properties for P59113
Functions
5 GO annotations of cellular component
| Name | Definition |
|---|---|
| cell junction | A cellular component that forms a specialized region of connection between two or more cells, or between a cell and the extracellular matrix, or between two membrane-bound components of a cell, such as flagella. |
| cytoskeleton | A cellular structure that forms the internal framework of eukaryotic and prokaryotic cells. The cytoskeleton includes intermediate filaments, microfilaments, microtubules, the microtrabecular lattice, and other structures characterized by a polymeric filamentous nature and long-range order within the cell. The various elements of the cytoskeleton not only serve in the maintenance of cellular shape but also have roles in other cellular functions, including cellular movement, cell division, endocytosis, and movement of organelles. |
| cytosol | The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. |
| focal adhesion | A cell-substrate junction that anchors the cell to the extracellular matrix and that forms a point of termination of actin filaments. In insects focal adhesion has also been referred to as hemi-adherens junction (HAJ). |
| ruffle membrane | The portion of the plasma membrane surrounding a ruffle. |
2 GO annotations of molecular function
| Name | Definition |
|---|---|
| actin filament binding | Binding to an actin filament, also known as F-actin, a helical filamentous polymer of globular G-actin subunits. |
| integrin binding | Binding to an integrin. |
18 GO annotations of biological process
| Name | Definition |
|---|---|
| basement membrane organization | A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of the basement membrane. |
| cell adhesion | The attachment of a cell, either to another cell or to an underlying substrate such as the extracellular matrix, via cell adhesion molecules. |
| cell-matrix adhesion | The binding of a cell to the extracellular matrix via adhesion molecules. |
| establishment of epithelial cell polarity | The specification and formation of anisotropic intracellular organization of an epithelial cell. |
| integrin-mediated signaling pathway | The series of molecular signals initiated by an extracellular ligand binding to an integrin on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. |
| keratinocyte migration | The directed movement of a keratinocyte, epidermal cells which synthesize keratin, from one site to another. |
| keratinocyte proliferation | The multiplication or reproduction of keratinocytes, resulting in the expansion of a cell population. Keratinocytes are epidermal cells which synthesize keratin and undergo a characteristic change as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. |
| negative regulation of canonical Wnt signaling pathway | Any process that decreases the rate, frequency, or extent of the Wnt signaling pathway through beta-catenin, the series of molecular signals initiated by binding of a Wnt protein to a frizzled family receptor on the surface of the target cell, followed by propagation of the signal via beta-catenin, and ending with a change in transcription of target genes. |
| negative regulation of gene expression | Any process that decreases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA). |
| negative regulation of protein import into nucleus | Any process that stops, prevents, or reduces the frequency, rate or extent of the movement of proteins from the cytoplasm into the nucleus. |
| negative regulation of stem cell proliferation | Any process that stops, prevents or reduces the frequency, rate or extent of stem cell proliferation. |
| negative regulation of timing of anagen | Any process that stops, prevents, or reduces the frequency, rate or extent of timing of anagen, the growth phase of the hair cycle. |
| positive regulation of cell adhesion mediated by integrin | Any process that activates or increases the frequency, rate, or extent of cell adhesion mediated by integrin. |
| positive regulation of cell-matrix adhesion | Any process that activates or increases the rate or extent of cell adhesion to an extracellular matrix. |
| positive regulation of integrin activation | Any process that activates or increases the frequency, rate, or extent of integrin activation. |
| positive regulation of transforming growth factor beta production | Any process that activates or increases the frequency, rate, or extent of production of transforming growth factor-beta. |
| positive regulation of transforming growth factor beta receptor signaling pathway | Any process that activates or increases the frequency, rate or extent of TGF-beta receptor signaling pathway activity. |
| positive regulation of wound healing, spreading of epidermal cells | Any process that activates or increases the frequency, rate or extent of wound healing, spreading of epidermal cells. |
12 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| Q32LP0 | FERMT3 | Fermitin family homolog 3 | Bos taurus (Bovine) | SS |
| Q9VZI3 | Fit1 | Unc-112-related protein | Drosophila melanogaster (Fruit fly) | SS |
| Q86UX7 | FERMT3 | Fermitin family homolog 3 | Homo sapiens (Human) | EV |
| Q96AC1 | FERMT2 | Fermitin family homolog 2 | Homo sapiens (Human) | SS |
| Q9BQL6 | FERMT1 | Fermitin family homolog 1 | Homo sapiens (Human) | SS |
| Q9Y4G6 | TLN2 | Talin-2 | Homo sapiens (Human) | SS |
| Q9Y490 | TLN1 | Talin-1 | Homo sapiens (Human) | EV |
| Q8CIB5 | Fermt2 | Fermitin family homolog 2 | Mus musculus (Mouse) | SS |
| Q8K1B8 | Fermt3 | Fermitin family homolog 3 | Mus musculus (Mouse) | SS |
| P26039 | Tln1 | Talin-1 | Mus musculus (Mouse) | EV |
| Q18685 | unc-112 | Protein unc-112 | Caenorhabditis elegans | SS |
| F1Q8X5 | fermt2 | Fermitin family homolog 2 | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MLSSGDLTSA | SWELVVRVDH | ANGEQQTEIT | LRVSGDLHIG | GVMLKLVEQM | NIAQDWSDYA |
| 70 | 80 | 90 | 100 | 110 | 120 |
| LWWEQKRCWL | LKTHWTLDKC | GVQADANLLF | TPQHKMLRLR | LPNAKTVRLR | VSFSAVVFKA |
| 130 | 140 | 150 | 160 | 170 | 180 |
| VADICKVLNI | RRPEELSLLK | PSSDYCKKKK | KKEKNSKEPV | IEDILNLESS | STSSGSPVSP |
| 190 | 200 | 210 | 220 | 230 | 240 |
| GLYSKTMTPT | YDPINGTPAL | STMTWFGDSP | LTEQNCSVLA | FSQPPPSPDV | LADMFQPRSL |
| 250 | 260 | 270 | 280 | 290 | 300 |
| VDKAKMNAGW | LDSSRSLMEQ | SIQEDEQLQL | RFKYYTFFDL | NPKYDAVRIN | QLYEQARWAV |
| 310 | 320 | 330 | 340 | 350 | 360 |
| LLEEIDCTEE | EMLIFAALQY | HISKLSQCAE | IQDFATKSEV | DEVEAALSSL | EVTLEGGKAD |
| 370 | 380 | 390 | 400 | 410 | 420 |
| NTLEDITDIP | KLADYLKLFR | PKKLMLKACK | QYWFVFKDTS | IAYFKNKELE | QGEPIEKLNL |
| 430 | 440 | 450 | 460 | 470 | 480 |
| RGCEIVPDVN | VSGRKFGIKL | LIPVADGMNE | VYLRCDHEDQ | YARWMAACIL | ASKGKTMADS |
| 490 | 500 | 510 | 520 | 530 | 540 |
| SYQPEVISIL | SFLKMKNRNS | SPLVASSLEN | MDMNPECLVS | PCCAKKHKSK | QLAARILEAH |
| 550 | 560 | 570 | 580 | 590 | 600 |
| HNVAQMPLVE | AKLQFIQAWQ | SLPEFGLTYY | LVRFKGSKKD | DILGVAYNRL | IRIDAVTGIP |
| 610 | 620 | 630 | 640 | 650 | 660 |
| VTTWRFANMK | QWNVNWEIRQ | VAIEFDQNVS | IAFTCLSADC | KIVHEYIGGY | IFLSTRSKDQ |
| 670 | |||||
| NETLDEDLFH | KLTGGQD |