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Protein

Fermitin family homolog 2

Gene

Fermt2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Scaffolding protein that enhances integrin activation mediated by TLN1 and/or TLN2, but activates integrins only weakly by itself. Binds to membranes enriched in phosphoinositides. Enhances integrin-mediated cell adhesion onto the extracellular matrix and cell spreading; this requires both its ability to interact with integrins and with phospholipid membranes. Required for the assembly of focal adhesions. Participates in the connection between extracellular matrix adhesion sites and the actin cytoskeleton and also in the orchestration of actin assembly and cell shape modulation. Recruits FBLIM1 to focal adhesions. Plays a role in the TGFB1 and integrin signaling pathways. Stabilizes active CTNNB1 and plays a role in the regulation of transcription mediated by CTNNB1 and TCF7L2/TCF4 and in Wnt signaling.3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei383Phosphatidylinositol phosphateBy similarity1

GO - Molecular functioni

  • actin filament binding Source: MGI
  • phosphatidylinositol-3,4,5-trisphosphate binding Source: UniProtKB

GO - Biological processi

Keywordsi

Biological processCell adhesion, Cell shape, Wnt signaling pathway
LigandLipid-binding

Enzyme and pathway databases

ReactomeiR-MMU-446353 Cell-extracellular matrix interactions

Names & Taxonomyi

Protein namesi
Recommended name:
Fermitin family homolog 2
Alternative name(s):
Kindlin-2
Pleckstrin homology domain-containing family C member 1
Gene namesi
Name:Fermt2
Synonyms:Plekhc1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 14

Organism-specific databases

MGIiMGI:2385001 Fermt2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Cytoplasm, Cytoskeleton, Membrane, Nucleus

Pathology & Biotechi

Disruption phenotypei

Complete embryonic lethality at peri-implantation stage, due to severe detachment of the endoderm and epiblast from the basement membrane. Heterozygous mice lacking one copy of Fermt2 show no visible phenotype, but show decreased tumor angiogenesis upon transplantation of tumor cells, and their blood vessels are abnormally leaky.3 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi614 – 615QW → AA: Abolishes interaction with integrins ITGB1 and ITGB3. 1 Publication2

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002194571 – 680Fermitin family homolog 2Add BLAST680

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei159PhosphoserineCombined sources1
Modified residuei181PhosphoserineBy similarity1
Modified residuei339PhosphoserineBy similarity1
Modified residuei351PhosphoserineBy similarity1
Modified residuei666PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ8CIB5
MaxQBiQ8CIB5
PaxDbiQ8CIB5
PRIDEiQ8CIB5

PTM databases

iPTMnetiQ8CIB5
PhosphoSitePlusiQ8CIB5
SwissPalmiQ8CIB5

Expressioni

Tissue specificityi

Detected in adult heart muscle (at protein level). Detected in heart, skeletal muscle and testis.1 Publication

Gene expression databases

BgeeiENSMUSG00000037712 Expressed in 294 organ(s), highest expression level in ureter smooth muscle
CleanExiMM_FERMT2
ExpressionAtlasiQ8CIB5 baseline and differential
GenevisibleiQ8CIB5 MM

Interactioni

Subunit structurei

Interacts with ITGB1; the interaction is inhibited in presence of ITGB1BP1. Interacts with FBLIM1. Interacts with active, unphosphorylated CTNNB1. Identified in a complex with CTNNB1 and TCF7L2/TCF4 (By similarity). Interacts with ILK, ITGB1 and ITGB3.By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi230085, 4 interactors
IntActiQ8CIB5, 4 interactors
MINTiQ8CIB5
STRINGi10090.ENSMUSP00000044554

Structurei

Secondary structure

1680
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ8CIB5
SMRiQ8CIB5
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini189 – 661FERMAdd BLAST473
Domaini380 – 476PHPROSITE-ProRule annotationAdd BLAST97

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni40 – 81Interaction with membranes containing phosphatidylinositol phosphateBy similarityAdd BLAST42

Domaini

The FERM domain is not correctly detected by PROSITE or Pfam techniques because it contains the insertion of a PH domain.
The PH domain binds phospholipids. Binds preferentially phosphatidylinositol-3,4,5-trisphosphate, and has lower affinity for phosphatidylinositol-4,5-bisphosphate (By similarity).By similarity
The N-terminal region displays a ubiquitin-type fold and mediates interaction with membranes containing negatively charged phosphatidylinositol phosphate via a surface enriched in positively charged residues.By similarity

Sequence similaritiesi

Belongs to the kindlin family.Curated

Phylogenomic databases

eggNOGiKOG3727 Eukaryota
ENOG410XS1B LUCA
GeneTreeiENSGT00390000013444
HOGENOMiHOG000231715
HOVERGENiHBG020688
InParanoidiQ8CIB5
KOiK17083
OMAiVNWEVKH
OrthoDBiEOG091G03SD
PhylomeDBiQ8CIB5
TreeFamiTF314677

Family and domain databases

CDDicd14473 FERM_B-lobe, 1 hit
cd01237 PH_fermitin, 1 hit
Gene3Di2.30.29.30, 2 hits
InterProiView protein in InterPro
IPR019749 Band_41_domain
IPR035963 FERM_2
IPR019748 FERM_central
IPR037843 Kindlin/fermitin
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
IPR037837 PH_Kindlin/fermitin
PANTHERiPTHR16160 PTHR16160, 1 hit
PfamiView protein in Pfam
PF00373 FERM_M, 1 hit
PF00169 PH, 1 hit
SMARTiView protein in SMART
SM00295 B41, 1 hit
SM00233 PH, 1 hit
SUPFAMiSSF47031 SSF47031, 2 hits
PROSITEiView protein in PROSITE
PS50003 PH_DOMAIN, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All

Q8CIB5-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MALDGIRMPD GCYADGTWEL SVHVTDLNRD VTLRVTGEVH IGGVMLKLVE
60 70 80 90 100
KLDVKKDWSD HALWWEKKRT WLLKTHWTLD KCGIQADAKL QFTPQHKLLR
110 120 130 140 150
LQLPNMKYVK VKVNFSDRVF KAVSDICKTF NIRHPEELSL LKKPRDPTKK
160 170 180 190 200
KKKKLDDQSE DEALELEGPL IMPGSGSIYS SPGLYSKTMT PTYDAHDGSP
210 220 230 240 250
LSPTSAWFGD SALSEGNPGI LAVSQPVTSP EILAKMFKPQ ALLDKAKTNQ
260 270 280 290 300
GWLDSSRSLM EQDVKENEAL LLRFKYYSFF DLNPKYDAIR INQLYEQAKW
310 320 330 340 350
ALLLEEIECT EEEMMMFAAL QYHINKLSIM TSENHLNNSD KEVDEVDAAL
360 370 380 390 400
SDLEITLEGG KTSTILGDIT SIPELADYIK VFKPKKLTLK GYKQYWCTFK
410 420 430 440 450
DTSISCYKSR EESSGTPAHQ LNLRGCEVTP DVNISGQKFN IKLLIPVAEG
460 470 480 490 500
MNEIWLRCDN EKQYAHWMAA CRLASKGKTM ADSSYNLEVQ NILSFLKMQH
510 520 530 540 550
LNPDPQLIPD QITTDVNPEC LVSPRYLKKY KSKQITARIL EAHQNVAQMS
560 570 580 590 600
LIEAKMRFIQ AWQSLPEFGI THFIARFQGG KREELIGIAY NRLIRMDAST
610 620 630 640 650
GDAIKTWRFS NMKQWNVNWE IKMVTVEFAD EVRLSFICTE VDCKVVHEFI
660 670 680
GGYIFLSTRA KDQNESLDEE MFYKLTSGWV
Length:680
Mass (Da):77,800
Last modified:March 1, 2003 - v1
Checksum:i89767FA0E34B543B
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A6X941A6X941_MOUSE
Fermitin family homolog 2
Fermt2
180Annotation score:
A6X940A6X940_MOUSE
Fermitin family homolog 2
Fermt2
258Annotation score:
A0A2I3BPQ7A0A2I3BPQ7_MOUSE
Fermitin family homolog 2
Fermt2
72Annotation score:

Sequence cautioni

The sequence AAH34168 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti149K → R in BAC37692 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC033436 mRNA Translation: AAH33436.1
BC034168 mRNA Translation: AAH34168.1 Different initiation.
AK079588 mRNA Translation: BAC37692.1
CCDSiCCDS26977.1
RefSeqiNP_666166.2, NM_146054.2
UniGeneiMm.210018

Genome annotation databases

EnsembliENSMUST00000045905; ENSMUSP00000044554; ENSMUSG00000037712
GeneIDi218952
KEGGimmu:218952
UCSCiuc007tgq.1 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC033436 mRNA Translation: AAH33436.1
BC034168 mRNA Translation: AAH34168.1 Different initiation.
AK079588 mRNA Translation: BAC37692.1
CCDSiCCDS26977.1
RefSeqiNP_666166.2, NM_146054.2
UniGeneiMm.210018

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5XPYX-ray2.10A15-680[»]
5XPZX-ray2.60A/B1-680[»]
5XQ0X-ray2.75A/B1-680[»]
5XQ1X-ray2.95A/B1-680[»]
ProteinModelPortaliQ8CIB5
SMRiQ8CIB5
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi230085, 4 interactors
IntActiQ8CIB5, 4 interactors
MINTiQ8CIB5
STRINGi10090.ENSMUSP00000044554

PTM databases

iPTMnetiQ8CIB5
PhosphoSitePlusiQ8CIB5
SwissPalmiQ8CIB5

Proteomic databases

EPDiQ8CIB5
MaxQBiQ8CIB5
PaxDbiQ8CIB5
PRIDEiQ8CIB5

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000045905; ENSMUSP00000044554; ENSMUSG00000037712
GeneIDi218952
KEGGimmu:218952
UCSCiuc007tgq.1 mouse

Organism-specific databases

CTDi10979
MGIiMGI:2385001 Fermt2

Phylogenomic databases

eggNOGiKOG3727 Eukaryota
ENOG410XS1B LUCA
GeneTreeiENSGT00390000013444
HOGENOMiHOG000231715
HOVERGENiHBG020688
InParanoidiQ8CIB5
KOiK17083
OMAiVNWEVKH
OrthoDBiEOG091G03SD
PhylomeDBiQ8CIB5
TreeFamiTF314677

Enzyme and pathway databases

ReactomeiR-MMU-446353 Cell-extracellular matrix interactions

Miscellaneous databases

ChiTaRSiFermt2 mouse
PROiPR:Q8CIB5
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000037712 Expressed in 294 organ(s), highest expression level in ureter smooth muscle
CleanExiMM_FERMT2
ExpressionAtlasiQ8CIB5 baseline and differential
GenevisibleiQ8CIB5 MM

Family and domain databases

CDDicd14473 FERM_B-lobe, 1 hit
cd01237 PH_fermitin, 1 hit
Gene3Di2.30.29.30, 2 hits
InterProiView protein in InterPro
IPR019749 Band_41_domain
IPR035963 FERM_2
IPR019748 FERM_central
IPR037843 Kindlin/fermitin
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
IPR037837 PH_Kindlin/fermitin
PANTHERiPTHR16160 PTHR16160, 1 hit
PfamiView protein in Pfam
PF00373 FERM_M, 1 hit
PF00169 PH, 1 hit
SMARTiView protein in SMART
SM00295 B41, 1 hit
SM00233 PH, 1 hit
SUPFAMiSSF47031 SSF47031, 2 hits
PROSITEiView protein in PROSITE
PS50003 PH_DOMAIN, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiFERM2_MOUSE
AccessioniPrimary (citable) accession number: Q8CIB5
Secondary accession number(s): Q8C542, Q8K035
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 7, 2003
Last sequence update: March 1, 2003
Last modified: November 7, 2018
This is version 130 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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