FERMT2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesFERMT2, KIND2, MIG2, PLEKHC1, UNC112, UNC112B, mig-2, fermitin family member 2, URP2SF, FERM domain containing kindlin 2
External IDsOMIM: 607746 MGI: 2385001 HomoloGene: 4976 GeneCards: FERMT2
Orthologs
SpeciesHumanMouse
Entrez

10979

218952

Ensembl

ENSG00000073712

ENSMUSG00000037712

UniProt

Q96AC1

Q8CIB5

RefSeq (mRNA)

NM_001134999
NM_001135000
NM_006832

NM_146054
NM_001360525
NM_001360526

RefSeq (protein)

NP_001128471
NP_001128472
NP_006823

NP_666166
NP_001347454
NP_001347455

Location (UCSC)Chr 14: 52.86 – 52.95 MbChr 14: 45.7 – 45.77 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Fermitin family homolog 2 (FERMT2) also known as pleckstrin homology domain-containing family C member 1 (PLEKHC1) or kindlin-2 is a protein that in humans is encoded by the FERMT2 gene.[5][6][7]

Kindlin-2 is the first of the kindlin protein to be discovered in 1994. It was detected in a screen for epidermal growth factor (EGF)-induced mRNAs and initially named mitogen-inducible gene 2 (Mig-2) protein.[5]

Function

FERMT2 is a component of extracellular matrix structures in mammalian cells and is required for proper control of cell shape change.[8]

A major task of kindlins is to regulate the activation of integrins.[9]

Interactions

FERMT2 has been shown to interact with FBLIM1.[8]

Role in health and diseases

  • Loss of kindlin-2 in mice leads to peri-implantation lethality.[10]
  • Kindlin-2 is highly expressed in activated myofibroblasts for regulation of focal adhesion formation.[11]
  • Deletion of Kindlin-2 retards insulin secretion and reduces β-cell mass in mice.[12]
  • Elevated kindlin-2 expression was observed in tubular intestinal fibrosis of the kidney, a condition is characterized by massive expansion of the cortical interstitium, conversion of fibroblasts into myofibroblasts and progressive EMT of tubular epithelial cells.[13]
  • Kindlin-2 is required for angiogenesis and blood vessel homeostasis.[14]
  • Kindlin-2 can exert tumor-promoting or tumor-inhibiting functions based on tumor-type-dependent.[15]
  • FERMT2 modulates the Alzheimer's Disease risk by regulating APP metabolism and Aβ peptide production.[16]


References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000073712 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000037712 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 Wick M, Bürger C, Brüsselbach S, Lucibello FC, Müller R (January 1994). "Identification of serum-inducible genes: different patterns of gene regulation during G0-->S and G1-->S progression". Journal of Cell Science. 107 ( Pt 1) (1): 227–39. doi:10.1242/jcs.107.1.227. PMID 8175911.
  6. ↑ Weinstein EJ, Bourner M, Head R, Zakeri H, Bauer C, Mazzarella R (April 2003). "URP1: a member of a novel family of PH and FERM domain-containing membrane-associated proteins is significantly over-expressed in lung and colon carcinomas". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1637 (3): 207–16. doi:10.1016/S0925-4439(03)00035-8. PMID 12697302.
  7. ↑ "Entrez Gene: FERMT2".
  8. 1 2 Tu Y, Wu S, Shi X, Chen K, Wu C (April 2003). "Migfilin and Mig-2 link focal adhesions to filamin and the actin cytoskeleton and function in cell shape modulation". Cell. 113 (1): 37–47. doi:10.1016/S0092-8674(03)00163-6. PMID 12679033.
  9. ↑ Rognoni E, Ruppert R, Fässler R (January 2016). "The kindlin family: functions, signaling properties and implications for human disease". Journal of Cell Science. 129 (1): 17–27. doi:10.1242/jcs.161190. PMID 26729028.
  10. ↑ Montanez E, Ussar S, Schifferer M, Bösl M, Zent R, Moser M, Fässler R (May 2008). "Kindlin-2 controls bidirectional signaling of integrins". Genes & Development. 22 (10): 1325–30. doi:10.1101/gad.469408. PMC 2377186. PMID 18483218.
  11. ↑ He Y, Esser P, Schacht V, Bruckner-Tuderman L, Has C (January 2011). "Role of kindlin-2 in fibroblast functions: implications for wound healing". The Journal of Investigative Dermatology. 131 (1): 245–56. doi:10.1038/jid.2010.273. PMID 20861856.
  12. ↑ Zhu K, Lai Y, Cao H, Bai X, Liu C, Yan Q, et al. (January 2020). "Kindlin-2 modulates MafA and β-catenin expression to regulate β-cell function and mass in mice". Nature Communications. 11 (1): 484. Bibcode:2020NatCo..11..484Z. doi:10.1038/s41467-019-14186-y. PMC 6981167. PMID 31980627.
  13. ↑ Bielesz B, Sirin Y, Si H, Niranjan T, Gruenwald A, Ahn S, Kato H, Pullman J, Gessler M, Haase VH, Susztak K (November 2010). "Epithelial Notch signaling regulates interstitial fibrosis development in the kidneys of mice and humans". The Journal of Clinical Investigation. 120 (11): 4040–54. doi:10.1172/JCI43025. PMC 2964979. PMID 20978353.
  14. ↑ Pluskota E, Dowling JJ, Gordon N, Golden JA, Szpak D, West XZ, Nestor C, Ma YQ, Bialkowska K, Byzova T, Plow EF (May 2011). "The integrin coactivator kindlin-2 plays a critical role in angiogenesis in mice and zebrafish". Blood. 117 (18): 4978–87. doi:10.1182/blood-2010-11-321182. PMC 3100704. PMID 21378273.
  15. ↑ Zhan J, Zhang H (May 2018). "Kindlins: Roles in development and cancer progression". The International Journal of Biochemistry & Cell Biology. 98: 93–103. doi:10.1016/j.biocel.2018.03.008. PMID 29544897.
  16. ↑ DOI = 10.1007/s00401-016-1652-z

Further reading

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