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

625-720 (F3 subdomain)

Relief mechanism

PTM

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

0 structures for Q18685

Entry ID Method Resolution Chain Position Source
No available structures

No variants for Q18685

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for Q18685

No associated diseases with Q18685

3 regional properties for Q18685

Type Name Position InterPro Accession
domain Peptidase S3, togavirin 108 - 268 IPR000930
domain Alphavirus E3 spike glycoprotein 274 - 326 IPR002533
domain Alphavirus E1 glycoprotein 749 - 1238 IPR002548

Functions

Description
EC Number
Subcellular Localization
  • Cell membrane ; Peripheral membrane protein
  • Cytoplasm, myofibril, sarcomere, M line
  • Colocalizes with pat-3/beta-integrin in body wall muscles
  • Requires unc-52/perlecan and pat-3 to be localized to the muscle cell membrane (PubMed:10893272)
  • Colocalizes with cpna-1 in M line and dense bodies (PubMed:23283987)
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

5 GO annotations of cellular component

Name Definition
cell-substrate junction A cell junction that forms a connection between a cell and the extracellular matrix.
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
M band The midline of aligned thick filaments in a sarcomere; location of specific proteins that link thick filaments. Depending on muscle type the M band consists of different numbers of M lines.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
striated muscle dense body A vinculin-containing myofibril attachment structure of striated muscle that connects sarcomeres to the extracellular matrix. In nematode body wall muscle, the dense body performs the dual role of Z-disk and costamere.

4 GO annotations of molecular function

Name Definition
cell adhesion molecule binding Binding to a cell adhesion molecule.
integrin binding Binding to an integrin.
protein self-association Binding to a domain within the same polypeptide.
protein-macromolecule adaptor activity The binding activity of a protein that brings together two or more macromolecules in contact, permitting those molecules to function in a coordinated way. The adaptor can bring together two proteins, or a protein and another macromolecule such as a lipid or a nucleic acid.

11 GO annotations of biological process

Name Definition
cell-matrix adhesion The binding of a cell to the extracellular matrix via adhesion molecules.
establishment of protein localization to organelle The directed movement of a protein to a specific location on or in an organelle. Encompasses establishment of localization in the membrane or lumen of a membrane-bounded organelle.
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.
locomotion Self-propelled movement of a cell or organism from one location to another.
mitochondrion organization A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of a mitochondrion; includes mitochondrial morphogenesis and distribution, and replication of the mitochondrial genome as well as synthesis of new mitochondrial components.
muscle cell cellular homeostasis The cellular homeostatic process that preserves a muscle cell in a stable functional or structural state.
muscle organ development The process whose specific outcome is the progression of the muscle over time, from its formation to the mature structure. The muscle is an organ consisting of a tissue made up of various elongated cells that are specialized to contract and thus to produce movement and mechanical work.
positive regulation of locomotion Any process that activates or increases the frequency, rate or extent of locomotion of a cell or organism.
positive regulation of myosin II filament organization Any process that activates or increases the frequency, rate or extent of myosin II filament organization.
positive regulation of sarcomere organization Any process that increases the rate, frequency or extent of myofibril assembly by organization of muscle actomyosin into sarcomeres. The sarcomere is the repeating unit of a myofibril in a muscle cell, composed of an array of overlapping thick and thin filaments between two adjacent Z discs.
regulation of engulfment of apoptotic cell Any process that modulates the frequency, rate or extent of engulfment of apoptotic cell.

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
Q9BQL6 FERMT1 Fermitin family homolog 1 Homo sapiens (Human) SS
Q96AC1 FERMT2 Fermitin family homolog 2 Homo sapiens (Human) SS
Q9Y4G6 TLN2 Talin-2 Homo sapiens (Human) SS
Q9Y490 TLN1 Talin-1 Homo sapiens (Human) EV
P59113 Fermt1 Fermitin family homolog 1 Mus musculus (Mouse) SS
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
F1Q8X5 fermt2 Fermitin family homolog 2 Danio rerio (Zebrafish) (Brachydanio rerio) SS
10 20 30 40 50 60
MAHLVEGTSI IDGKWQLPIL VTDLNIQRSI SVLGNLNVGG LMLELVSECD VERDWSDHAL
70 80 90 100 110 120
WWPEKRRWLQ HTRSTLDQNG ITAETQLEFT PMHKEARIQL PDMQMIDARV DFSVNSFKAT
130 140 150 160 170 180
KKLCRDLGIR YSEELSLKRY IPPEDLRRGT SDADNMNGPL SMRPGEESVG PMTLRKAAPI
190 200 210 220 230 240
FASQSNLDMR RRGQSPALSQ SGHIFNAHEM GTLPRHGTLP RGVSPSPGAY NDTMRRTPIM
250 260 270 280 290 300
PSISFSEGLE NEQFDDALIH SPRLAPSRDT PVFRPQNYVE KAAINRGWLD SSRSLMEQGI
310 320 330 340 350 360
FEGDIILLRF KFMNFFDLNP KYDPVRINQL YEQAKWSILL DEFDHTEEEA TLFAALQLQA
370 380 390 400 410 420
TLQRDSPEPE ENNKDDVDIL LDELEQNLDA AALNRRSDLT QVPELADYLK YMKPKKLAAF
430 440 450 460 470 480
KGFKRAFFSF RDLYLSYHQS SSDVNSAPLG HFSLKGCEVS QDVSVGQQKY HIKLLLPTAE
490 500 510 520 530 540
GMIDFILKCD SEHQYARWMA ACRLASRGKS MADSSYQQEV ESIKNLLKMQ SGNGNENGNS
550 560 570 580 590 600
NTASRKAAAV KLPNDFNVDE YISSKYVRRA RSKQQIQQRV SDAHGNVRQL TATEAKLQYI
610 620 630 640 650 660
RAWQALPEHG IHYFIVRFRN ARKAELVAVA VNRLAKLNMD NGESLKTWRF ANMKKWHVNW
670 680 690 700 710
EIRHLKIQFE DEDIEFKPLS ADCKVVHEFI GGYIFLSMRS KEHSQNLDEE LFHKLTGGWA