Q14192 (FHL2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	FHL2
Synonyms:	DRAL, SLIM3

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	279 AA.
Sequence status	Complete.
Protein existence	Evidence 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.8 Ref.9 Ref.11
Subunit structure	Interacts with ZNF638 and TTN/titin. Interacts with E4F1. Interacts with GRB7. Interacts with SIRT1 and FOXO1. Ref.6 Ref.7 Ref.8 Ref.9 Ref.11
Subcellular location	Cytoplasm. Nucleus Ref.6 Ref.9.
Tissue specificity	Expressed in skeletal muscle and heart. Ref.6
Domain	The third LIM zinc-binding mediates interaction with E4F1.
Sequence similarities	Contains 4 LIM zinc-binding domains.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Domain	LIM domain Repeat Zinc-finger
Ligand	Metal-binding Zinc
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	androgen receptor signaling pathway Non-traceable author statement. Source: UniProtKB cellular lipid metabolic process Traceable author statement. Source: Reactome negative regulation of apoptotic process Inferred from direct assay Ref.8. Source: UniProtKB negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay Ref.8. Source: UniProtKB positive regulation of transcription, DNA-dependent Non-traceable author statement. Source: UniProtKB response to hormone stimulus Inferred from mutant phenotype. Source: BHF-UCL transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	actin cytoskeleton Inferred from direct assay. Source: HPA focal adhesion Inferred from direct assay. Source: HPA nucleoplasm Traceable author statement. Source: Reactome
Molecular function	androgen receptor binding Non-traceable author statement. Source: UniProtKB identical protein binding Inferred from physical interaction. Source: IntAct transcription coactivator activity Non-traceable author statement. Source: UniProtKB transcription factor binding Inferred from physical interaction Ref.8. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		2	EBI-701903,EBI-701903
ATF3	P18847	3	EBI-701903,EBI-712767
FOXO1	Q12778	8	EBI-701903,EBI-1108782
SIRT1	Q96EB6	2	EBI-701903,EBI-1802965
SPHK1	Q9NYA1	7	EBI-701903,EBI-985303
ZNF408	Q9H9D4	3	EBI-701903,EBI-347633

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 279

279

Four and a half LIM domains protein 2

PRO_0000075737

Regions

Domain

40 – 92

53

LIM zinc-binding 1

Domain

101 – 153

53

LIM zinc-binding 2

Domain

162 – 212

51

LIM zinc-binding 3

Domain

221 – 275

55

LIM zinc-binding 4

Zinc finger

7 – 31

25

C4-type Potential

Amino acid modifications

Modified residue

238

1

Phosphoserine Ref.10

Experimental info

Sequence conflict

167

1

K → M in AAC52073. Ref.2

Sequence conflict

167

1

K → M in AAC50794. Ref.5

Secondary structure

1

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279

Helix Strand Turn

Details...

Beta strand

101 – 104

4

Beta strand

110 – 112

3

Beta strand

114 – 117

4

Beta strand

120 – 123

4

Turn

124 – 127

4

Beta strand

130 – 132

3

Beta strand

138 – 144

7

Beta strand

147 – 150

4

Helix

151 – 157

7

Turn

222 – 225

4

Beta strand

231 – 233

3

Turn

246 – 248

3

Beta strand

252 – 254

3

Beta strand

267 – 271

5

Helix

273 – 277

5

Sequences

	Sequence		Length	Mass (Da)
	Q14192 [UniParc]. Last modified October 17, 2006. Version 3. Checksum: E94E3A7F6601F9F3	FASTA	279	32,193
	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

References

	« Hide 'large scale' referencesShow '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: 9150430] [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: 9573400] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. 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: 11001931] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Leukocyte.
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta.
[5]	"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: 8753811] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 127-279. Tissue: Heart muscle.
[6]	"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: 11813260] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH ZNF638.
[7]	"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: 12432079] [Abstract] Cited for: INTERACTION WITH TTN.
[8]	"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: 15692560] [Abstract] Cited for: FUNCTION, INTERACTION WITH SIRT1 AND FOXO1.
[9]	"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: 16652157] [Abstract] Cited for: FUNCTION, INTERACTION WITH E4F1, SUBCELLULAR LOCATION.
[10]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-238, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"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: 18853468] [Abstract] Cited for: FUNCTION, INTERACTION WITH GRB7.
[12]	"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.
BC014397 mRNA. Translation: AAH14397.1.
U60117 mRNA. Translation: AAC50794.1.

IPI

IPI00743342.

PIR

JC6565.

RefSeq

NP_001034581.1. NM_001039492.2.
NP_001441.4. NM_001450.3.
NP_963849.1. NM_201555.1.
NP_963851.2. NM_201557.3.

UniGene

Hs.443687.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1X4K	NMR	-	A	98-159	[»]
1X4L	NMR	-	A	221-279	[»]
2D8Z	NMR	-	A	162-218	[»]

ProteinModelPortal

Q14192.

SMR

Q14192. Positions 3-76, 98-159, 162-279.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-5980N.

IntAct

Q14192. 49 interactions.

MINT

MINT-120725.

STRING

Q14192.

PTM databases

PhosphoSite

Q14192.

Polymorphism databases

DMDM

116241364.

2D gel databases

UCD-2DPAGE

Q14192.

Proteomic databases

PRIDE

Q14192.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000322142; ENSP00000322909; ENSG00000115641.
ENST00000344213; ENSP00000344266; ENSG00000115641.
ENST00000358129; ENSP00000350846; ENSG00000115641.
ENST00000393352; ENSP00000377020; ENSG00000115641.
ENST00000393353; ENSP00000377021; ENSG00000115641.
ENST00000408995; ENSP00000386633; ENSG00000115641.
ENST00000409177; ENSP00000386892; ENSG00000115641.
ENST00000409807; ENSP00000386665; ENSG00000115641.

GeneID

2274.

KEGG

hsa:2274.

UCSC

uc002tcu.1. human.

Organism-specific databases

CTD

2274.

GeneCards

GC02M105974.

H-InvDB

HIX0002345.

HGNC

HGNC:3703. FHL2.

HPA

CAB008368.
HPA005922.
HPA006028.

MIM

602633. gene.

neXtProt

NX_Q14192.

Orphanet

154. Familial isolated dilated cardiomyopathy.

PharmGKB

PA164.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG11875.

HOVERGEN

HBG074526.

InParanoid

Q14192.

OrthoDB

EOG4XKV7B.

Enzyme and pathway databases

Pathway_Interaction_DB

ar_pathway. Coregulation of Androgen receptor activity.
hdac_classiii_pathway. Signaling events mediated by HDAC Class III.

Reactome

REACT_22258. Metabolism of lipids and lipoproteins.

Gene expression databases

ArrayExpress

Q14192.

Bgee

Q14192.

CleanEx

HS_FHL2.

Genevestigator

Q14192.

GermOnline

ENSG00000115641. Homo sapiens.

Family and domain databases

InterPro

IPR001781. Znf_LIM.
[Graphical view]

Gene3D

G3DSA:2.10.110.10. Znf_LIM. 5 hits.

KO

K14380.

Pfam

PF00412. LIM. 4 hits.
[Graphical view]

SMART

SM00132. LIM. 4 hits.
[Graphical view]

PROSITE

PS00478. LIM_DOMAIN_1. 4 hits.
PS50023. LIM_DOMAIN_2. 4 hits.
[Graphical view]

ProtoNet

Search...

Other

NextBio

9247.

SOURCE

Search...

Entry information

Entry name

FHL2_HUMAN

Accession

Primary (citable) accession number: Q14192
Secondary accession number(s): Q13229, Q13644, Q9P294

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	October 17, 2006
Last modified:	January 25, 2012
This is version 114 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.