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Q14192

- FHL2_HUMAN

UniProt

Q14192 - FHL2_HUMAN

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Protein
Four and a half LIM domains protein 2
Gene
FHL2, DRAL, SLIM3
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.3 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri7 – 3125C4-type Reviewed prediction
Add
BLAST

GO - Molecular functioni

  1. androgen receptor binding Source: UniProtKB
  2. identical protein binding Source: IntAct
  3. protein binding Source: IntAct
  4. transcription coactivator activity Source: UniProtKB
  5. transcription factor binding Source: UniProtKB
  6. zinc ion binding Source: InterPro

GO - Biological processi

  1. androgen receptor signaling pathway Source: UniProtKB
  2. atrial cardiac muscle cell development Source: Ensembl
  3. cellular lipid metabolic process Source: Reactome
  4. heart trabecula formation Source: Ensembl
  5. negative regulation of apoptotic process Source: UniProtKB
  6. negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  7. osteoblast differentiation Source: Ensembl
  8. positive regulation of transcription, DNA-templated Source: UniProtKB
  9. response to hormone Source: BHF-UCL
  10. small molecule metabolic process Source: Reactome
  11. transcription, DNA-templated Source: UniProtKB-KW
  12. ventricular cardiac muscle cell development Source: Ensembl
Complete GO annotation...

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_116145. PPARA activates gene expression.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:FHL2
Synonyms:DRAL, SLIM3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 2

Organism-specific databases

HGNCiHGNC:3703. FHL2.

Subcellular locationi

Cytoplasm. Nucleus 2 Publications

GO - Cellular componenti

  1. M band Source: Ensembl
  2. Z disc Source: Ensembl
  3. actin cytoskeleton Source: HPA
  4. focal adhesion Source: HPA
  5. nucleoplasm Source: Reactome
  6. nucleus Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

Orphaneti154. Familial isolated dilated cardiomyopathy.
PharmGKBiPA164.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 279279Four and a half LIM domains protein 2
PRO_0000075737Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei238 – 2381Phosphoserine1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ14192.
PaxDbiQ14192.
PRIDEiQ14192.

2D gel databases

UCD-2DPAGEQ14192.

PTM databases

PhosphoSiteiQ14192.

Expressioni

Tissue specificityi

Expressed in skeletal muscle and heart.1 Publication

Gene expression databases

ArrayExpressiQ14192.
BgeeiQ14192.
CleanExiHS_FHL2.
GenevestigatoriQ14192.

Organism-specific databases

HPAiCAB008368.
HPA005922.
HPA006028.

Interactioni

Subunit structurei

Interacts with ZNF638 and TTN/titin. Interacts with E4F1. Interacts with GRB7. Interacts with SIRT1 and FOXO1.5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-701903,EBI-701903
ATF3P188473EBI-701903,EBI-712767
BRCA1P383986EBI-701903,EBI-349905
FOXO1Q127788EBI-701903,EBI-1108782
SIRT1Q96EB62EBI-701903,EBI-1802965
SPHK1Q9NYA17EBI-701903,EBI-985303
ZNF408Q9H9D43EBI-701903,EBI-347633

Protein-protein interaction databases

BioGridi108565. 64 interactions.
DIPiDIP-5980N.
IntActiQ14192. 61 interactions.
MINTiMINT-120725.
STRINGi9606.ENSP00000322909.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni8 – 103
Beta strandi20 – 223
Beta strandi25 – 273
Helixi29 – 368
Turni41 – 433
Beta strandi45 – 473
Beta strandi53 – 564
Beta strandi59 – 624
Turni63 – 653
Turni69 – 713
Beta strandi76 – 783
Helixi90 – 978
Beta strandi101 – 1044
Beta strandi110 – 1123
Beta strandi114 – 1174
Beta strandi120 – 1234
Turni124 – 1274
Beta strandi130 – 1323
Beta strandi138 – 1447
Beta strandi147 – 1504
Helixi151 – 1577
Beta strandi163 – 1653
Beta strandi171 – 18212
Turni183 – 1853
Beta strandi189 – 1913
Beta strandi201 – 2088
Helixi210 – 2167
Turni222 – 2254
Beta strandi231 – 2333
Turni246 – 2483
Beta strandi252 – 2543
Beta strandi267 – 2715
Helixi273 – 2775

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1X4KNMR-A101-159[»]
1X4LNMR-A221-279[»]
2D8ZNMR-A162-218[»]
2MIUNMR-A1-98[»]
ProteinModelPortaliQ14192.
SMRiQ14192. Positions 1-159, 162-218, 225-279.

Miscellaneous databases

EvolutionaryTraceiQ14192.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini40 – 9253LIM zinc-binding 1
Add
BLAST
Domaini101 – 15353LIM zinc-binding 2
Add
BLAST
Domaini162 – 21251LIM zinc-binding 3
Add
BLAST
Domaini221 – 27555LIM zinc-binding 4
Add
BLAST

Domaini

The third LIM zinc-binding mediates interaction with E4F1.

Sequence similaritiesi

Keywords - Domaini

LIM domain, Repeat, Zinc-finger

Phylogenomic databases

eggNOGiNOG314122.
HOGENOMiHOG000231075.
HOVERGENiHBG074526.
InParanoidiQ14192.
KOiK14380.
OrthoDBiEOG7P8P7M.
PhylomeDBiQ14192.
TreeFamiTF321684.

Family and domain databases

Gene3Di2.10.110.10. 5 hits.
InterProiIPR001781. Znf_LIM.
[Graphical view]
PfamiPF00412. LIM. 4 hits.
[Graphical view]
SMARTiSM00132. LIM. 4 hits.
[Graphical view]
PROSITEiPS00478. LIM_DOMAIN_1. 4 hits.
PS50023. LIM_DOMAIN_2. 4 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q14192-1 [UniParc]FASTAAdd to Basket

« Hide

MTERFDCHHC NESLFGKKYI LREESPYCVV CFETLFANTC EECGKPIGCD    50
CKDLSYKDRH WHEACFHCSQ CRNSLVDKPF AAKEDQLLCT DCYSNEYSSK 100
CQECKKTIMP GTRKMEYKGS SWHETCFICH RCQQPIGTKS FIPKDNQNFC 150
VPCYEKQHAM QCVQCKKPIT TGGVTYREQP WHKECFVCTA CRKQLSGQRF 200
TARDDFAYCL NCFCDLYAKK CAGCTNPISG LGGTKYISFE ERQWHNDCFN 250
CKKCSLSLVG RGFLTERDDI LCPDCGKDI 279
Length:279
Mass (Da):32,193
Last modified:October 17, 2006 - v3
Checksum:iE94E3A7F6601F9F3
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti167 – 1671K → M.3 Publications
Corresponds to variant rs1127588 [ dbSNP | Ensembl ].
VAR_067455

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS2070.1.
PIRiJC6565.
RefSeqiNP_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.
UniGeneiHs.443687.

Genome annotation databases

EnsembliENST00000322142; ENSP00000322909; ENSG00000115641.
ENST00000358129; ENSP00000350846; ENSG00000115641.
ENST00000393352; ENSP00000377020; ENSG00000115641.
ENST00000393353; ENSP00000377021; ENSG00000115641.
ENST00000408995; ENSP00000386633; ENSG00000115641.
ENST00000409807; ENSP00000386665; ENSG00000115641.
GeneIDi2274.
KEGGihsa:2274.
UCSCiuc002tct.3. human.

Polymorphism databases

DMDMi116241364.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS2070.1.
PIRi JC6565.
RefSeqi NP_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.
UniGenei Hs.443687.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1X4K NMR - A 101-159 [» ]
1X4L NMR - A 221-279 [» ]
2D8Z NMR - A 162-218 [» ]
2MIU NMR - A 1-98 [» ]
ProteinModelPortali Q14192.
SMRi Q14192. Positions 1-159, 162-218, 225-279.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 108565. 64 interactions.
DIPi DIP-5980N.
IntActi Q14192. 61 interactions.
MINTi MINT-120725.
STRINGi 9606.ENSP00000322909.

PTM databases

PhosphoSitei Q14192.

Polymorphism databases

DMDMi 116241364.

2D gel databases

UCD-2DPAGE Q14192.

Proteomic databases

MaxQBi Q14192.
PaxDbi Q14192.
PRIDEi Q14192.

Protocols and materials databases

DNASUi 2274.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000322142 ; ENSP00000322909 ; ENSG00000115641 .
ENST00000358129 ; ENSP00000350846 ; ENSG00000115641 .
ENST00000393352 ; ENSP00000377020 ; ENSG00000115641 .
ENST00000393353 ; ENSP00000377021 ; ENSG00000115641 .
ENST00000408995 ; ENSP00000386633 ; ENSG00000115641 .
ENST00000409807 ; ENSP00000386665 ; ENSG00000115641 .
GeneIDi 2274.
KEGGi hsa:2274.
UCSCi uc002tct.3. human.

Organism-specific databases

CTDi 2274.
GeneCardsi GC02M105974.
HGNCi HGNC:3703. FHL2.
HPAi CAB008368.
HPA005922.
HPA006028.
MIMi 602633. gene.
neXtProti NX_Q14192.
Orphaneti 154. Familial isolated dilated cardiomyopathy.
PharmGKBi PA164.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG314122.
HOGENOMi HOG000231075.
HOVERGENi HBG074526.
InParanoidi Q14192.
KOi K14380.
OrthoDBi EOG7P8P7M.
PhylomeDBi Q14192.
TreeFami TF321684.

Enzyme and pathway databases

Reactomei REACT_116145. PPARA activates gene expression.

Miscellaneous databases

ChiTaRSi FHL2. human.
EvolutionaryTracei Q14192.
GeneWikii FHL2.
GenomeRNAii 2274.
NextBioi 9247.
PROi Q14192.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q14192.
Bgeei Q14192.
CleanExi HS_FHL2.
Genevestigatori Q14192.

Family and domain databases

Gene3Di 2.10.110.10. 5 hits.
InterProi IPR001781. Znf_LIM.
[Graphical view ]
Pfami PF00412. LIM. 4 hits.
[Graphical view ]
SMARTi SM00132. LIM. 4 hits.
[Graphical view ]
PROSITEi PS00478. LIM_DOMAIN_1. 4 hits.
PS50023. LIM_DOMAIN_2. 4 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. Cited for: FUNCTION, INTERACTION WITH E4F1, SUBCELLULAR LOCATION.
  11. 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. 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.

Entry informationi

Entry nameiFHL2_HUMAN
AccessioniPrimary (citable) accession number: Q14192
Secondary accession number(s): Q13229
, Q13644, Q2I5I4, Q9P294
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: October 17, 2006
Last modified: September 3, 2014
This is version 140 of the entry and version 3 of the sequence. [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 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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