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Protein

Fermitin family homolog 2

Gene

FERMT2

Organism
Homo sapiens (Human)
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.6 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei383Phosphatidylinositol phosphate1

GO - Molecular functioni

GO - Biological processi

  • cell junction assembly Source: Reactome
  • cell-matrix adhesion Source: UniProtKB
  • focal adhesion assembly Source: UniProtKB
  • integrin activation Source: UniProtKB
  • integrin-mediated signaling pathway Source: UniProtKB
  • protein localization to membrane Source: UniProtKB
  • regulation of cell shape Source: UniProtKB-KW
  • substrate adhesion-dependent cell spreading Source: UniProtKB
  • transforming growth factor beta receptor signaling pathway Source: UniProtKB
  • Wnt signaling pathway Source: UniProtKB

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-446353 Cell-extracellular matrix interactions

Names & Taxonomyi

Protein namesi
Recommended name:
Fermitin family homolog 2
Alternative name(s):
Kindlin-2
Mitogen-inducible gene 2 protein
Short name:
MIG-2
Pleckstrin homology domain-containing family C member 1
Short name:
PH domain-containing family C member 1
Gene namesi
Name:FERMT2
Synonyms:KIND2, MIG2, PLEKHC1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

EuPathDBiHostDB:ENSG00000073712.14
HGNCiHGNC:15767 FERMT2
MIMi607746 gene
neXtProtiNX_Q96AC1

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

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi40H → A: Abolishes lipid-binding via the N-terminus; when associated with 74-A--A-81. 1 Publication1
Mutagenesisi74 – 81KTHWTLDK → ATAATLDA: Abolishes lipid-binding via the N-terminus; when associated with A-40. 1 Publication8
Mutagenesisi383K → A: Reduces phosphatidylinositol phosphate binding. Reduces integrin activation; when associated with A-385. 1 Publication1
Mutagenesisi385K → A: Reduces integrin activation; when associated with A-383. 1 Publication1
Mutagenesisi390K → A: Abolishes phosphatidylinositol phosphate binding. 1 Publication1
Mutagenesisi393K → A: Reduces phosphatidylinositol phosphate binding. 1 Publication1
Mutagenesisi614 – 615QW → AA: Impairs ITGB3 binding. Abolishes enhancement of talin-mediated integrin activation. 1 Publication2

Organism-specific databases

DisGeNETi10979
OpenTargetsiENSG00000073712
PharmGKBiPA162388349

Polymorphism and mutation databases

BioMutaiFERMT2
DMDMi38258220

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002194561 – 680Fermitin family homolog 2Add BLAST680

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei159PhosphoserineCombined sources1
Modified residuei181PhosphoserineCombined sources1
Modified residuei339PhosphoserineCombined sources1
Modified residuei351PhosphoserineCombined sources1
Modified residuei666PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ96AC1
MaxQBiQ96AC1
PaxDbiQ96AC1
PeptideAtlasiQ96AC1
PRIDEiQ96AC1
ProteomicsDBi75949
75950 [Q96AC1-2]
75951 [Q96AC1-3]

PTM databases

iPTMnetiQ96AC1
PhosphoSitePlusiQ96AC1
SwissPalmiQ96AC1

Expressioni

Tissue specificityi

Ubiquitous. Found in numerous tumor tissues.

Inductioni

By serum in lung fetal fibroblast cultured cells.1 Publication

Gene expression databases

BgeeiENSG00000073712
CleanExiHS_FERMT2
ExpressionAtlasiQ96AC1 baseline and differential
GenevisibleiQ96AC1 HS

Organism-specific databases

HPAiHPA040505

Interactioni

Subunit structurei

Interacts with ILK (By similarity). Interacts with FBLIM1. Interacts with ITGB1 and ITGB3. Interacts with active, unphosphorylated CTNNB1. Identified in a complex with CTNNB1 and TCF7L2/TCF4. Interacts with ITGB1; the interaction is inhibited in presence of ITGB1BP1.By similarity6 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi116175, 61 interactors
IntActiQ96AC1, 15 interactors
MINTiQ96AC1
STRINGi9606.ENSP00000342858

Structurei

Secondary structure

1680
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni9 – 11Combined sources3
Beta strandi12 – 16Combined sources5
Turni25 – 28Combined sources4
Helixi41 – 51Combined sources11
Beta strandi58 – 65Combined sources8
Turni66 – 68Combined sources3
Helixi79 – 82Combined sources4
Turni347 – 353Combined sources7
Helixi354 – 357Combined sources4
Helixi369 – 371Combined sources3
Beta strandi375 – 382Combined sources8
Beta strandi393 – 400Combined sources8
Beta strandi403 – 408Combined sources6
Helixi410 – 412Combined sources3
Beta strandi418 – 422Combined sources5
Beta strandi427 – 433Combined sources7
Turni434 – 437Combined sources4
Beta strandi438 – 447Combined sources10
Beta strandi450 – 460Combined sources11
Helixi461 – 475Combined sources15
Helixi484 – 495Combined sources12

3D structure databases

ProteinModelPortaliQ96AC1
SMRiQ96AC1
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96AC1

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 phosphateAdd 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 (PubMed:22030399).1 Publication
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.1 Publication

Sequence similaritiesi

Belongs to the kindlin family.Curated

Phylogenomic databases

eggNOGiKOG3727 Eukaryota
ENOG410XS1B LUCA
GeneTreeiENSGT00390000013444
HOGENOMiHOG000231715
HOVERGENiHBG020688
InParanoidiQ96AC1
KOiK17083
OMAiLKTWRYN
OrthoDBiEOG091G03SD
PhylomeDBiQ96AC1
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

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q96AC1-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MALDGIRMPD GCYADGTWEL SVHVTDLNRD VTLRVTGEVH IGGVMLKLVE
60 70 80 90 100
KLDVKKDWSD HALWWEKKRT WLLKTHWTLD KYGIQADAKL QFTPQHKLLR
110 120 130 140 150
LQLPNMKYVK VKVNFSDRVF KAVSDICKTF NIRHPEELSL LKKPRDPTKK
160 170 180 190 200
KKKKLDDQSE DEALELEGPL ITPGSGSIYS SPGLYSKTMT PTYDAHDGSP
210 220 230 240 250
LSPTSAWFGD SALSEGNPGI LAVSQPITSP EILAKMFKPQ ALLDKAKINQ
260 270 280 290 300
GWLDSSRSLM EQDVKENEAL LLRFKYYSFF DLNPKYDAIR INQLYEQAKW
310 320 330 340 350
AILLEEIECT EEEMMMFAAL QYHINKLSIM TSENHLNNSD KEVDEVDAAL
360 370 380 390 400
SDLEITLEGG KTSTILGDIT SIPELADYIK VFKPKKLTLK GYKQYWCTFK
410 420 430 440 450
DTSISCYKSK EESSGTPAHQ MNLRGCEVTP DVNISGQKFN IKLLIPVAEG
460 470 480 490 500
MNEIWLRCDN EKQYAHWMAA CRLASKGKTM ADSSYNLEVQ NILSFLKMQH
510 520 530 540 550
LNPDPQLIPE QITTDITPEC LVSPRYLKKY KNKQITARIL EAHQNVAQMS
560 570 580 590 600
LIEAKMRFIQ AWQSLPEFGI THFIARFQGG KKEELIGIAY NRLIRMDAST
610 620 630 640 650
GDAIKTWRFS NMKQWNVNWE IKMVTVEFAD EVRLSFICTE VDCKVVHEFI
660 670 680
GGYIFLSTRA KDQNESLDEE MFYKLTSGWV
Length:680
Mass (Da):77,861
Last modified:December 1, 2001 - v1
Checksum:iBAFF5AF2CD91C43C
GO
Isoform 2 (identifier: Q96AC1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     534-534: Q → QPGYIRDL
     625-626: TV → NS
     627-680: Missing.

Note: May be due to an exon inclusion and an intron retention.
Show »
Length:633
Mass (Da):72,397
Checksum:iEF95EB667653A1B4
GO
Isoform 3 (identifier: Q96AC1-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     534-534: Q → QPGYIRDL

Show »
Length:687
Mass (Da):78,675
Checksum:iA94A73D8399A348B
GO

Sequence cautioni

The sequence CAA80852 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti31V → I in CAA80852 (PubMed:8175911).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_008783534Q → QPGYIRDL in isoform 2 and isoform 3. 2 Publications1
Alternative sequenceiVSP_008784625 – 626TV → NS in isoform 2. 1 Publication2
Alternative sequenceiVSP_008785627 – 680Missing in isoform 2. 1 PublicationAdd BLAST54

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z24725 mRNA Translation: CAA80852.1 Different initiation.
AF443279 mRNA Translation: AAN75823.1
EU979385 mRNA Translation: ACH73257.1
BX161467 mRNA Translation: CAD61925.1
AL139317 Genomic DNA No translation available.
AL352979 Genomic DNA No translation available.
BC011125 mRNA No translation available.
BC017327 mRNA Translation: AAH17327.1
CCDSiCCDS45107.1 [Q96AC1-3]
CCDS45108.1 [Q96AC1-2]
CCDS9713.1 [Q96AC1-1]
PIRiS69890
RefSeqiNP_001128471.1, NM_001134999.1 [Q96AC1-3]
NP_001128472.1, NM_001135000.1 [Q96AC1-2]
NP_006823.1, NM_006832.2 [Q96AC1-1]
UniGeneiHs.509343

Genome annotation databases

EnsembliENST00000341590; ENSP00000340391; ENSG00000073712 [Q96AC1-1]
ENST00000343279; ENSP00000342858; ENSG00000073712 [Q96AC1-3]
ENST00000395631; ENSP00000378993; ENSG00000073712 [Q96AC1-1]
ENST00000399304; ENSP00000382243; ENSG00000073712 [Q96AC1-2]
ENST00000553373; ENSP00000451084; ENSG00000073712 [Q96AC1-3]
GeneIDi10979
KEGGihsa:10979
UCSCiuc001xac.4 human [Q96AC1-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiFERM2_HUMAN
AccessioniPrimary (citable) accession number: Q96AC1
Secondary accession number(s): B5TJY2, Q14840, Q86TY7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 7, 2003
Last sequence update: December 1, 2001
Last modified: July 18, 2018
This is version 156 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

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