FERMT2

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]

FERMT2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2LGX, 2LKO, 2MSU, 4F7H
Identifiers
Aliases	FERMT2, KIND2, MIG2, PLEKHC1, UNC112, UNC112B, mig-2, fermitin family member 2, URP2SF, FERM domain containing kindlin 2
External IDs	OMIM: 607746; MGI: 2385001; HomoloGene: 4976; GeneCards: FERMT2; OMA:FERMT2 - orthologs
Gene location (Human) Chr. Chromosome 14 (human)[1] Band 14q22.1 Start 52,857,268 bp[1] End 52,952,435 bp[1]
Gene location (Mouse) Chr. Chromosome 14 (mouse)[2] Band 14|14 C1 Start 45,696,252 bp[2] End 45,767,575 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in decidua tail of epididymis metanephric glomerulus saphenous vein cartilage tissue parietal pleura seminal vesicula visceral pleura tibia secondary oocyte Top expressed in left lung left lung lobe ankle right lung lobe vastus lateralis muscle triceps brachii muscle sternocleidomastoid muscle tail of embryo temporal muscle digastric muscle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding phosphatidylinositol-3,4,5-trisphosphate binding lipid binding actin filament binding Cellular component cytoplasm filamentous actin cytosol cell projection membrane I band focal adhesion extrinsic component of cytoplasmic side of plasma membrane plasma membrane stress fiber nucleoplasm cell surface cell junction cell cortex cytoskeleton lamellipodium membrane nucleus Biological process protein localization to membrane Wnt signaling pathway focal adhesion assembly cell adhesion regulation of cell shape integrin-mediated signaling pathway substrate adhesion-dependent cell spreading integrin activation cell-matrix adhesion transforming growth factor beta receptor signaling pathway cell junction assembly Sources:Amigo / QuickGO
Orthologs Species Human Mouse 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 Mb Chr 14: 45.7 – 45.77 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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. GRCh38: Ensembl release 89: ENSG00000073712 – Ensembl, May 2017
2. 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. 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. 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

• Kato K, Shiozawa T, Mitsushita J, Toda A, Horiuchi A, Nikaido T, Fujii S, Konishi I (January 2004). "Expression of the mitogen-inducible gene-2 (mig-2) is elevated in human uterine leiomyomas but not in leiomyosarcomas". Human Pathology. 35 (1): 55–60. doi:10.1016/j.humpath.2003.08.019. PMID 14745725.
• Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (November 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983.
• Wang L, Deng W, Shi T, Ma D (April 2008). "URP2SF, a FERM and PH domain containing protein, regulates NF-kappaB and apoptosis". Biochemical and Biophysical Research Communications. 368 (4): 899–906. doi:10.1016/j.bbrc.2008.02.024. PMID 18280249.

External links

• FERMT2 Info with links in the Cell Migration Gateway Archived 2014-12-11 at the Wayback Machine