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Q8CIB5 (FERM2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 97. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Fermitin family homolog 2
Alternative name(s):
Kindlin-2
Pleckstrin homology domain-containing family C member 1
Gene names
Name:Fermt2
Synonyms:Plekhc1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length680 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.3 Ref.4 Ref.5

Subunit structure

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. Ref.4

Subcellular location

Cytoplasm By similarity. Cytoplasmcell cortex By similarity. Cytoplasmcytoskeleton By similarity. Cell junctionfocal adhesion By similarity. Membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Cell projectionlamellipodium membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Nucleus By similarity. CytoplasmmyofibrilsarcomereI band. Cell surface. Note: Colocalizes with actin stress fibers at cell-ECM focal adhesion sites. Colocalizes with ITGB3 at lamellipodia at the leading edge of spreading cells. Binds to membranes that contain phosphatidylinositides By similarity. Ref.3 Ref.6

Tissue specificity

Detected in adult heart muscle (at protein level). Detected in heart, skeletal muscle and testis. Ref.3

Domain

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.

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.

Disruption phenotype

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. Ref.3 Ref.4 Ref.5

Sequence similarities

Belongs to the kindlin family.

Contains 1 FERM domain.

Contains 1 PH domain.

Sequence caution

The sequence AAH34168.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   Biological processCell adhesion
Cell shape
Wnt signaling pathway
   Cellular componentCell junction
Cell membrane
Cell projection
Cytoplasm
Cytoskeleton
Membrane
Nucleus
   LigandLipid-binding
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processWnt signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

cell-matrix adhesion

Inferred from mutant phenotype Ref.4. Source: UniProtKB

focal adhesion assembly

Inferred from mutant phenotype Ref.4. Source: UniProtKB

integrin activation

Inferred from mutant phenotype Ref.4. Source: UniProtKB

integrin-mediated signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

protein localization to membrane

Inferred from mutant phenotype Ref.4. Source: UniProtKB

regulation of cell shape

Inferred from electronic annotation. Source: UniProtKB-KW

substrate adhesion-dependent cell spreading

Inferred from mutant phenotype Ref.4. Source: UniProtKB

transforming growth factor beta receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentI band

Inferred from electronic annotation. Source: UniProtKB-SubCell

cell cortex

Inferred from electronic annotation. Source: UniProtKB-SubCell

cell surface

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

cytoskeleton

Inferred from electronic annotation. Source: UniProtKB-SubCell

extrinsic component of cytoplasmic side of plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

focal adhesion

Inferred from sequence or structural similarity. Source: UniProtKB

lamellipodium membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionphosphatidylinositol-3,4,5-trisphosphate binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 680680Fermitin family homolog 2
PRO_0000219457

Regions

Domain189 – 661473FERM
Domain380 – 47697PH
Region40 – 8142Interaction with membranes containing phosphatidylinositol phosphate By similarity

Sites

Binding site3831Phosphatidylinositol phosphate By similarity

Amino acid modifications

Modified residue1591Phosphoserine By similarity
Modified residue1811Phosphoserine By similarity
Modified residue3391Phosphoserine By similarity
Modified residue3511Phosphoserine By similarity
Modified residue6661Phosphoserine By similarity

Experimental info

Mutagenesis614 – 6152QW → AA: Abolishes interaction with integrins ITGB1 and ITGB3. Ref.4
Sequence conflict1491K → R in BAC37692. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q8CIB5 [UniParc].

Last modified March 1, 2003. Version 1.
Checksum: 89767FA0E34B543B

FASTA68077,800
        10         20         30         40         50         60 
MALDGIRMPD GCYADGTWEL SVHVTDLNRD VTLRVTGEVH IGGVMLKLVE KLDVKKDWSD 

        70         80         90        100        110        120 
HALWWEKKRT WLLKTHWTLD KCGIQADAKL QFTPQHKLLR LQLPNMKYVK VKVNFSDRVF 

       130        140        150        160        170        180 
KAVSDICKTF NIRHPEELSL LKKPRDPTKK KKKKLDDQSE DEALELEGPL IMPGSGSIYS 

       190        200        210        220        230        240 
SPGLYSKTMT PTYDAHDGSP LSPTSAWFGD SALSEGNPGI LAVSQPVTSP EILAKMFKPQ 

       250        260        270        280        290        300 
ALLDKAKTNQ GWLDSSRSLM EQDVKENEAL LLRFKYYSFF DLNPKYDAIR INQLYEQAKW 

       310        320        330        340        350        360 
ALLLEEIECT EEEMMMFAAL QYHINKLSIM TSENHLNNSD KEVDEVDAAL SDLEITLEGG 

       370        380        390        400        410        420 
KTSTILGDIT SIPELADYIK VFKPKKLTLK GYKQYWCTFK DTSISCYKSR EESSGTPAHQ 

       430        440        450        460        470        480 
LNLRGCEVTP DVNISGQKFN IKLLIPVAEG MNEIWLRCDN EKQYAHWMAA CRLASKGKTM 

       490        500        510        520        530        540 
ADSSYNLEVQ NILSFLKMQH LNPDPQLIPD QITTDVNPEC LVSPRYLKKY KSKQITARIL 

       550        560        570        580        590        600 
EAHQNVAQMS LIEAKMRFIQ AWQSLPEFGI THFIARFQGG KREELIGIAY NRLIRMDAST 

       610        620        630        640        650        660 
GDAIKTWRFS NMKQWNVNWE IKMVTVEFAD EVRLSFICTE VDCKVVHEFI GGYIFLSTRA 

       670        680 
KDQNESLDEE MFYKLTSGWV 

« Hide

References

« Hide 'large scale' references
[1]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: FVB/N.
Tissue: Mammary tumor.
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-149.
Strain: C57BL/6J.
Tissue: Spinal cord.
[3]"Kindlin-2 is an essential component of intercalated discs and is required for vertebrate cardiac structure and function."
Dowling J.J., Gibbs E., Russell M., Goldman D., Minarcik J., Golden J.A., Feldman E.L.
Circ. Res. 102:423-431(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[4]"Kindlin-2 controls bidirectional signaling of integrins."
Montanez E., Ussar S., Schifferer M., Bosl M., Zent R., Moser M., Fassler R.
Genes Dev. 22:1325-1330(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION, INTERACTION WITH ILK; ITGB1 AND ITGB3, MUTAGENESIS OF 614-GLN-TRP-615.
[5]"The integrin coactivator kindlin-2 plays a critical role in angiogenesis in mice and zebrafish."
Pluskota E., Dowling J.J., Gordon N., Golden J.A., Szpak D., West X.Z., Nestor C., Ma Y.Q., Bialkowska K., Byzova T., Plow E.F.
Blood 117:4978-4987(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION.
[6]"Osteoblast mineralization requires beta1 integrin/ICAP-1-dependent fibronectin deposition."
Brunner M., Millon-Fremillon A., Chevalier G., Nakchbandi I.A., Mosher D., Block M.R., Albiges-Rizo C., Bouvard D.
J. Cell Biol. 194:307-322(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
BC033436 mRNA. Translation: AAH33436.1.
BC034168 mRNA. Translation: AAH34168.1. Different initiation.
AK079588 mRNA. Translation: BAC37692.1.
CCDSCCDS26977.1.
RefSeqNP_666166.2. NM_146054.2.
UniGeneMm.210018.

3D structure databases

ProteinModelPortalQ8CIB5.
SMRQ8CIB5. Positions 1-94, 365-499, 528-654.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid230085. 2 interactions.
IntActQ8CIB5. 2 interactions.
MINTMINT-4107681.

PTM databases

PhosphoSiteQ8CIB5.

Proteomic databases

MaxQBQ8CIB5.
PaxDbQ8CIB5.
PRIDEQ8CIB5.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000045905; ENSMUSP00000044554; ENSMUSG00000037712.
GeneID218952.
KEGGmmu:218952.
UCSCuc007tgq.1. mouse.

Organism-specific databases

CTD10979.
MGIMGI:2385001. Fermt2.

Phylogenomic databases

eggNOGNOG238024.
GeneTreeENSGT00390000013444.
HOGENOMHOG000231715.
HOVERGENHBG020688.
InParanoidQ8CIB5.
KOK17083.
OMAMTPTYDS.
OrthoDBEOG7T7GSC.
PhylomeDBQ8CIB5.
TreeFamTF314677.

Gene expression databases

ArrayExpressQ8CIB5.
BgeeQ8CIB5.
CleanExMM_FERMT2.
GenevestigatorQ8CIB5.

Family and domain databases

Gene3D1.20.80.10. 2 hits.
2.30.29.30. 2 hits.
InterProIPR019749. Band_41_domain.
IPR014352. FERM/acyl-CoA-bd_prot_3-hlx.
IPR019748. FERM_central.
IPR018979. FERM_N.
IPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
[Graphical view]
PfamPF00373. FERM_M. 1 hit.
PF09379. FERM_N. 1 hit.
PF00169. PH. 1 hit.
[Graphical view]
SMARTSM00295. B41. 1 hit.
SM00233. PH. 1 hit.
[Graphical view]
SUPFAMSSF47031. SSF47031. 2 hits.
PROSITEPS50003. PH_DOMAIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSFERMT2. mouse.
NextBio376495.
PROQ8CIB5.
SOURCESearch...

Entry information

Entry nameFERM2_MOUSE
AccessionPrimary (citable) accession number: Q8CIB5
Secondary accession number(s): Q8C542, Q8K035
Entry history
Integrated into UniProtKB/Swiss-Prot: November 7, 2003
Last sequence update: March 1, 2003
Last modified: July 9, 2014
This is version 97 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot