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Q14192 (FHL2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 139. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Four and a half LIM domains protein 2

Short name=FHL-2
Alternative name(s):
LIM domain protein DRAL
Skeletal muscle LIM-protein 3
Short name=SLIM-3
Gene names
Name:FHL2
Synonyms:DRAL, SLIM3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length279 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

May function as a molecular transmitter linking various signaling pathways to transcriptional regulation. Negatively regulates the transcriptional repressor E4F1 and may function in cell growth. Inhibits the transcriptional activity of FOXO1 and its apoptotic function by enhancing the interaction of FOXO1 with SIRT1 and FOXO1 deacetylation. Ref.9 Ref.10 Ref.12

Subunit structure

Interacts with ZNF638 and TTN/titin. Interacts with E4F1. Interacts with GRB7. Interacts with SIRT1 and FOXO1. Ref.7 Ref.8 Ref.9 Ref.10 Ref.12

Subcellular location

Cytoplasm. Nucleus Ref.7 Ref.10.

Tissue specificity

Expressed in skeletal muscle and heart. Ref.7

Domain

The third LIM zinc-binding mediates interaction with E4F1.

Sequence similarities

Contains 4 LIM zinc-binding domains.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityPolymorphism
   DomainLIM domain
Repeat
Zinc-finger
   LigandMetal-binding
Zinc
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processandrogen receptor signaling pathway

Non-traceable author statement PubMed 15572661. Source: UniProtKB

atrial cardiac muscle cell development

Inferred from electronic annotation. Source: Ensembl

cellular lipid metabolic process

Traceable author statement. Source: Reactome

heart trabecula formation

Inferred from electronic annotation. Source: Ensembl

negative regulation of apoptotic process

Inferred from direct assay Ref.9. Source: UniProtKB

negative regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.9. Source: UniProtKB

osteoblast differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription, DNA-templated

Non-traceable author statement PubMed 15572661. Source: UniProtKB

response to hormone

Inferred from mutant phenotype PubMed 17975004. Source: BHF-UCL

small molecule metabolic process

Traceable author statement. Source: Reactome

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

ventricular cardiac muscle cell development

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentM band

Inferred from electronic annotation. Source: Ensembl

Z disc

Inferred from electronic annotation. Source: Ensembl

actin cytoskeleton

Inferred from direct assay. Source: HPA

focal adhesion

Inferred from direct assay. Source: HPA

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay. Source: HPA

   Molecular_functionandrogen receptor binding

Non-traceable author statement PubMed 15572661. Source: UniProtKB

identical protein binding

Inferred from physical interaction PubMed 10906324PubMed 18255255. Source: IntAct

protein binding

Inferred from physical interaction PubMed 14550570Ref.9PubMed 16888242PubMed 18255255PubMed 21988832. Source: IntAct

transcription coactivator activity

Non-traceable author statement PubMed 15572661. Source: UniProtKB

transcription factor binding

Inferred from physical interaction Ref.9. Source: UniProtKB

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 279279Four and a half LIM domains protein 2
PRO_0000075737

Regions

Domain40 – 9253LIM zinc-binding 1
Domain101 – 15353LIM zinc-binding 2
Domain162 – 21251LIM zinc-binding 3
Domain221 – 27555LIM zinc-binding 4
Zinc finger7 – 3125C4-type Potential

Amino acid modifications

Modified residue2381Phosphoserine Ref.11

Natural variations

Natural variant1671K → M. Ref.2 Ref.4 Ref.6
Corresponds to variant rs1127588 [ dbSNP | Ensembl ].
VAR_067455

Secondary structure

............................................................... 279
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q14192 [UniParc].

Last modified October 17, 2006. Version 3.
Checksum: E94E3A7F6601F9F3

FASTA27932,193
        10         20         30         40         50         60 
MTERFDCHHC NESLFGKKYI LREESPYCVV CFETLFANTC EECGKPIGCD CKDLSYKDRH 

        70         80         90        100        110        120 
WHEACFHCSQ CRNSLVDKPF AAKEDQLLCT DCYSNEYSSK CQECKKTIMP GTRKMEYKGS 

       130        140        150        160        170        180 
SWHETCFICH RCQQPIGTKS FIPKDNQNFC VPCYEKQHAM QCVQCKKPIT TGGVTYREQP 

       190        200        210        220        230        240 
WHKECFVCTA CRKQLSGQRF TARDDFAYCL NCFCDLYAKK CAGCTNPISG LGGTKYISFE 

       250        260        270 
ERQWHNDCFN CKKCSLSLVG RGFLTERDDI LCPDCGKDI 

« Hide

References

« Hide 'large scale' references
[1]"Subtractive cloning and characterization of DRAL, a novel LIM-domain protein down-regulated in rhabdomyosarcoma."
Genini M., Schwalbe P., Scholl F.A., Remppis A., Mattei M.-G., Schaefer B.W.
DNA Cell Biol. 16:433-442(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Skeletal muscle.
[2]"Molecular cloning and characterization of FHL2, a novel LIM domain protein preferentially expressed in human heart."
Chan K.K., Tsui S.K.W., Lee S.M.Y., Luk S.C.W., Liew C.C., Fung K.P., Waye M.M.Y., Lee C.Y.
Gene 210:345-350(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT MET-167.
Tissue: Heart.
[3]"Alzheimer's disease-associated presenilin 2 interacts with DRAL, an LIM-domain protein."
Tanahashi H., Tabira T.
Hum. Mol. Genet. 9:2281-2289(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Leukocyte.
[4]"The FHL2 LIM-domain protein is implicated in hematopoiesis and leukemogenesis."
Qian Z., Mao L., Fernald A., Yu H., Luo R., Anastasi J., Le Beau M.M.
Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT MET-167.
Tissue: Bone marrow.
[5]"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].
Tissue: Placenta.
[6]"Slim defines a novel family of LIM-proteins expressed in skeletal muscle."
Morgan M.J., Madgwick A.J.A.
Biochem. Biophys. Res. Commun. 225:632-638(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 127-279, VARIANT MET-167.
Tissue: Heart muscle.
[7]"Interaction of the heart-specific LIM domain protein, FHL2, with DNA-binding nuclear protein, hNP220."
Ng E.K.O., Chan K.K., Wong C.H., Tsui S.K.W., Ngai S.M., Lee S.M.Y., Kotaka M., Lee C.Y., Waye M.M.Y., Fung K.P.
J. Cell. Biochem. 84:556-566(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH ZNF638.
[8]"Subcellular targeting of metabolic enzymes to titin in heart muscle may be mediated by DRAL/FHL-2."
Lange S., Auerbach D., McLoughlin P., Perriard E., Schafer B.W., Perriard J.-C., Ehler E.
J. Cell Sci. 115:4925-4936(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TTN.
[9]"Suppression of FOXO1 activity by FHL2 through SIRT1-mediated deacetylation."
Yang Y., Hou H., Haller E.M., Nicosia S.V., Bai W.
EMBO J. 24:1021-1032(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH SIRT1 AND FOXO1.
[10]"The LIM-only protein FHL2 is a negative regulator of E4F1."
Paul C., Lacroix M., Iankova I., Julien E., Schaefer B.W., Labalette C., Wei Y., Le Cam A., Le Cam L., Sardet C.
Oncogene 25:5475-5484(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH E4F1, SUBCELLULAR LOCATION.
[11]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-238, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[12]"The cell migration protein Grb7 associates with transcriptional regulator FHL2 in a Grb7 phosphorylation-dependent manner."
Siamakpour-Reihani S., Argiros H.J., Wilmeth L.J., Haas L.L., Peterson T.A., Johnson D.L., Shuster C.B., Lyons B.A.
J. Mol. Recognit. 22:9-17(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH GRB7.
[13]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]"Solution structure of LIM domains in LIM-protein 3."
RIKEN structural genomics initiative (RSGI)
Submitted (JUN-2006) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 98-279.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L42176 mRNA. Translation: AAA85333.1.
U29332 mRNA. Translation: AAC52073.1.
AB038794 Genomic DNA. Translation: BAA92253.1.
DQ307067 mRNA. Translation: ABC25549.1.
BC014397 mRNA. Translation: AAH14397.1.
U60117 mRNA. Translation: AAC50794.1.
CCDSCCDS2070.1.
PIRJC6565.
RefSeqNP_001034581.1. NM_001039492.2.
NP_001441.4. NM_001450.3.
NP_963849.1. NM_201555.1.
NP_963851.2. NM_201557.3.
XP_005263961.1. XM_005263904.1.
XP_005263963.1. XM_005263906.1.
UniGeneHs.443687.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1X4KNMR-A101-159[»]
1X4LNMR-A221-279[»]
2D8ZNMR-A162-218[»]
2MIUNMR-A1-98[»]
ProteinModelPortalQ14192.
SMRQ14192. Positions 1-159, 162-218, 225-279.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108565. 64 interactions.
DIPDIP-5980N.
IntActQ14192. 61 interactions.
MINTMINT-120725.
STRING9606.ENSP00000322909.

PTM databases

PhosphoSiteQ14192.

Polymorphism databases

DMDM116241364.

2D gel databases

UCD-2DPAGEQ14192.

Proteomic databases

MaxQBQ14192.
PaxDbQ14192.
PRIDEQ14192.

Protocols and materials databases

DNASU2274.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000322142; ENSP00000322909; ENSG00000115641.
ENST00000358129; ENSP00000350846; ENSG00000115641.
ENST00000393352; ENSP00000377020; ENSG00000115641.
ENST00000393353; ENSP00000377021; ENSG00000115641.
ENST00000408995; ENSP00000386633; ENSG00000115641.
ENST00000409807; ENSP00000386665; ENSG00000115641.
GeneID2274.
KEGGhsa:2274.
UCSCuc002tct.3. human.

Organism-specific databases

CTD2274.
GeneCardsGC02M105974.
HGNCHGNC:3703. FHL2.
HPACAB008368.
HPA005922.
HPA006028.
MIM602633. gene.
neXtProtNX_Q14192.
Orphanet154. Familial isolated dilated cardiomyopathy.
PharmGKBPA164.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG314122.
HOGENOMHOG000231075.
HOVERGENHBG074526.
InParanoidQ14192.
KOK14380.
OrthoDBEOG7P8P7M.
PhylomeDBQ14192.
TreeFamTF321684.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressQ14192.
BgeeQ14192.
CleanExHS_FHL2.
GenevestigatorQ14192.

Family and domain databases

Gene3D2.10.110.10. 5 hits.
InterProIPR001781. Znf_LIM.
[Graphical view]
PfamPF00412. LIM. 4 hits.
[Graphical view]
SMARTSM00132. LIM. 4 hits.
[Graphical view]
PROSITEPS00478. LIM_DOMAIN_1. 4 hits.
PS50023. LIM_DOMAIN_2. 4 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSFHL2. human.
EvolutionaryTraceQ14192.
GeneWikiFHL2.
GenomeRNAi2274.
NextBio9247.
PROQ14192.
SOURCESearch...

Entry information

Entry nameFHL2_HUMAN
AccessionPrimary (citable) accession number: Q14192
Secondary accession number(s): Q13229 expand/collapse secondary AC list , Q13644, Q2I5I4, Q9P294
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: October 17, 2006
Last modified: July 9, 2014
This is version 139 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM