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Protein

Four and a half LIM domains protein 2

Gene

FHL2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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)DescriptionActionsGraphical viewLength
Zinc fingeri7 – 31C4-typeSequence analysisAdd BLAST25

GO - Molecular functioni

  • androgen receptor binding Source: UniProtKB
  • identical protein binding Source: IntAct
  • metal ion binding Source: UniProtKB-KW
  • transcription coactivator activity Source: UniProtKB
  • transcription factor binding Source: UniProtKB

GO - Biological processi

  • androgen receptor signaling pathway Source: UniProtKB
  • atrial cardiac muscle cell development Source: Ensembl
  • heart trabecula formation Source: Ensembl
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of transcription by RNA polymerase II Source: UniProtKB
  • osteoblast differentiation Source: Ensembl
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • regulation of lipid metabolic process Source: Reactome
  • response to hormone Source: BHF-UCL
  • transcription, DNA-templated Source: UniProtKB-KW
  • ventricular cardiac muscle cell development Source: Ensembl

Keywordsi

Biological processTranscription, Transcription regulation
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-1989781. PPARA activates gene expression.
SIGNORiQ14192.

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
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000115641.18.
HGNCiHGNC:3703. FHL2.
MIMi602633. gene.
neXtProtiNX_Q14192.

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

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi2274.
MalaCardsiFHL2.
OpenTargetsiENSG00000115641.
Orphaneti154. Familial isolated dilated cardiomyopathy.
PharmGKBiPA164.

Polymorphism and mutation databases

BioMutaiFHL2.
DMDMi116241364.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000757371 – 279Four and a half LIM domains protein 2Add BLAST279

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki78Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki167Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki220Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei238PhosphoserineCombined sources1

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ14192.
PaxDbiQ14192.
PeptideAtlasiQ14192.
PRIDEiQ14192.

2D gel databases

UCD-2DPAGEiQ14192.

PTM databases

iPTMnetiQ14192.
PhosphoSitePlusiQ14192.
SwissPalmiQ14192.

Expressioni

Tissue specificityi

Expressed in skeletal muscle and heart.1 Publication

Gene expression databases

BgeeiENSG00000115641.
CleanExiHS_FHL2.
ExpressionAtlasiQ14192. baseline and differential.
GenevisibleiQ14192. HS.

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
itself4EBI-701903,EBI-701903
ARP102752EBI-701903,EBI-608057
ARHGAP9Q9BRR93EBI-701903,EBI-750254
ATF3P188473EBI-701903,EBI-712767
BANPA0A0S2Z5G43EBI-701903,EBI-16429704
BANPB4DE544EBI-701903,EBI-16429313
BANPQ8N9N53EBI-701903,EBI-744695
BANPQ8N9N5-25EBI-701903,EBI-11524452
BANPQ8N9N5-73EBI-701903,EBI-16429296
BLZF1Q9H2G95EBI-701903,EBI-2548012
BRCA1P383986EBI-701903,EBI-349905
CARD8Q9Y2G22EBI-701903,EBI-2808370
CCDC92Q53HC09EBI-701903,EBI-719994
CSN2W5RWE13EBI-701903,EBI-10330381
DCP1AQ9NPI65EBI-701903,EBI-374238
DTX2Q86UW96EBI-701903,EBI-740376
FAM129AQ9BZQ85EBI-701903,EBI-6916466
FHL3Q136432EBI-701903,EBI-741101
FOXO1Q127788EBI-701903,EBI-1108782
GLYR1Q49A263EBI-701903,EBI-2804292
GMEB2Q9UKD14EBI-701903,EBI-948296
GNG12Q9UBI66EBI-701903,EBI-358636
HCFC1P51610-15EBI-701903,EBI-396188
hCG_1987119A0A024R8L24EBI-701903,EBI-14103818
INCA1Q0VD863EBI-701903,EBI-6509505
ITGA3P26006-12EBI-701903,EBI-7354029
ITGA7Q136832EBI-701903,EBI-2565284
ITGB1P055562EBI-701903,EBI-703066
JUPP149235EBI-701903,EBI-702484
KANK2Q63ZY35EBI-701903,EBI-2556193
KIAA1217Q5T5P2-63EBI-701903,EBI-10188326
KIF5BP331764EBI-701903,EBI-355878
NRF1Q166563EBI-701903,EBI-2547810
NRF1Q16656-44EBI-701903,EBI-11742836
PHF21AQ96BD54EBI-701903,EBI-745085
POU6F2P784244EBI-701903,EBI-12029004
PSEN2P498103EBI-701903,EBI-2010251
RAI2Q9Y5P35EBI-701903,EBI-746228
RELQ048643EBI-701903,EBI-307352
REV1Q9UBZ92EBI-701903,EBI-7353917
RFX3P483806EBI-701903,EBI-742557
SAXO1Q8IYX73EBI-701903,EBI-3957636
SIGLEC6O436993EBI-701903,EBI-2814604
SIRT1Q96EB62EBI-701903,EBI-1802965
SP2Q020863EBI-701903,EBI-8651703
SPHK1Q9NYA17EBI-701903,EBI-985303
Trim54Q9ERP32EBI-701903,EBI-15626796From Mus musculus.
YY1P254904EBI-701903,EBI-765538
ZFP64Q9NPA53EBI-701903,EBI-711679
ZFP64Q9NTW73EBI-701903,EBI-745730
ZMYM4Q5VZL53EBI-701903,EBI-2514659
ZNF131P52739-25EBI-701903,EBI-10213055
ZNF408Q9H9D43EBI-701903,EBI-347633
ZNF417Q8TAU33EBI-701903,EBI-740727

GO - Molecular functioni

  • androgen receptor binding Source: UniProtKB
  • identical protein binding Source: IntAct
  • transcription factor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi108565. 151 interactors.
CORUMiQ14192.
DIPiDIP-5980N.
IntActiQ14192. 153 interactors.
MINTiQ14192.
STRINGi9606.ENSP00000322909.

Structurei

Secondary structure

1279
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni8 – 10Combined sources3
Beta strandi20 – 22Combined sources3
Beta strandi25 – 27Combined sources3
Helixi29 – 36Combined sources8
Turni41 – 43Combined sources3
Beta strandi45 – 47Combined sources3
Beta strandi53 – 56Combined sources4
Beta strandi59 – 62Combined sources4
Turni63 – 65Combined sources3
Turni69 – 71Combined sources3
Beta strandi76 – 78Combined sources3
Helixi90 – 97Combined sources8
Beta strandi101 – 104Combined sources4
Beta strandi110 – 112Combined sources3
Beta strandi114 – 117Combined sources4
Beta strandi120 – 123Combined sources4
Turni124 – 127Combined sources4
Beta strandi130 – 132Combined sources3
Beta strandi138 – 144Combined sources7
Beta strandi147 – 150Combined sources4
Helixi151 – 157Combined sources7
Beta strandi163 – 165Combined sources3
Beta strandi171 – 182Combined sources12
Turni183 – 185Combined sources3
Beta strandi189 – 191Combined sources3
Beta strandi201 – 208Combined sources8
Helixi210 – 216Combined sources7
Turni222 – 225Combined sources4
Beta strandi231 – 233Combined sources3
Turni246 – 248Combined sources3
Beta strandi252 – 254Combined sources3
Beta strandi267 – 271Combined sources5
Helixi273 – 277Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1X4KNMR-A101-159[»]
1X4LNMR-A221-279[»]
2D8ZNMR-A162-218[»]
2MIUNMR-A1-98[»]
ProteinModelPortaliQ14192.
SMRiQ14192.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ14192.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini40 – 92LIM zinc-binding 1PROSITE-ProRule annotationAdd BLAST53
Domaini101 – 153LIM zinc-binding 2PROSITE-ProRule annotationAdd BLAST53
Domaini162 – 212LIM zinc-binding 3PROSITE-ProRule annotationAdd BLAST51
Domaini221 – 275LIM zinc-binding 4PROSITE-ProRule annotationAdd BLAST55

Domaini

The third LIM zinc-binding mediates interaction with E4F1.

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri7 – 31C4-typeSequence analysisAdd BLAST25

Keywords - Domaini

LIM domain, Repeat, Zinc-finger

Phylogenomic databases

eggNOGiENOG410KCU4. Eukaryota.
ENOG410XRFY. LUCA.
GeneTreeiENSGT00760000118910.
HOGENOMiHOG000231075.
HOVERGENiHBG074526.
InParanoidiQ14192.
KOiK14380.
PhylomeDBiQ14192.
TreeFamiTF321684.

Family and domain databases

InterProiView protein in InterPro
IPR037987. FHL2/3/5.
IPR001781. Znf_LIM.
PANTHERiPTHR24205. PTHR24205. 1 hit.
PfamiView protein in Pfam
PF00412. LIM. 4 hits.
SMARTiView protein in SMART
SM00132. LIM. 4 hits.
PROSITEiView protein in PROSITE
PS00478. LIM_DOMAIN_1. 4 hits.
PS50023. LIM_DOMAIN_2. 4 hits.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q14192-1) [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
MTERFDCHHC NESLFGKKYI LREESPYCVV CFETLFANTC EECGKPIGCD
60 70 80 90 100
CKDLSYKDRH WHEACFHCSQ CRNSLVDKPF AAKEDQLLCT DCYSNEYSSK
110 120 130 140 150
CQECKKTIMP GTRKMEYKGS SWHETCFICH RCQQPIGTKS FIPKDNQNFC
160 170 180 190 200
VPCYEKQHAM QCVQCKKPIT TGGVTYREQP WHKECFVCTA CRKQLSGQRF
210 220 230 240 250
TARDDFAYCL NCFCDLYAKK CAGCTNPISG LGGTKYISFE ERQWHNDCFN
260 270
CKKCSLSLVG RGFLTERDDI LCPDCGKDI
Length:279
Mass (Da):32,193
Last modified:October 17, 2006 - v3
Checksum:iE94E3A7F6601F9F3
GO
Isoform 2 (identifier: Q14192-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     53-151: DLSYKDRHWH...IPKDNQNFCV → VPARWSTRAA...SQLAMTLPTA
     152-279: Missing.

Show »
Length:151
Mass (Da):15,890
Checksum:i72F31D2DB830DB20
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_067455167K → M3 Publications1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_05699953 – 151DLSYK…QNFCV → VPARWSTRAAAGMRPASSAT AASSQLEPRVSSPKTIRISV CPAMRNNMPCSAFSAKSPSP REGSLTGSSPGTRSASCAPP AGSSCLGSASQLAMTLPTA in isoform 2. 1 PublicationAdd BLAST99
Alternative sequenceiVSP_057000152 – 279Missing in isoform 2. 1 PublicationAdd BLAST128

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L42176 mRNA. Translation: AAA85333.1.
U29332 mRNA. Translation: AAC52073.1.
AB038794 Genomic DNA. Translation: BAA92253.1.
AB158503 mRNA. Translation: BAD69710.1.
DQ307067 mRNA. Translation: ABC25549.1.
AC012360 Genomic DNA. No translation available.
AC068273 Genomic DNA. No translation available.
AC108058 Genomic DNA. No translation available.
BC014397 mRNA. Translation: AAH14397.1.
U60117 mRNA. Translation: AAC50794.1.
CCDSiCCDS2070.1. [Q14192-1]
PIRiJC6565.
RefSeqiNP_001034581.1. NM_001039492.2. [Q14192-1]
NP_001305823.1. NM_001318894.1. [Q14192-1]
NP_001305824.1. NM_001318895.1. [Q14192-1]
NP_001305825.1. NM_001318896.1. [Q14192-1]
NP_001305826.1. NM_001318897.1.
NP_001441.4. NM_001450.3. [Q14192-1]
NP_963849.1. NM_201555.1. [Q14192-1]
NP_963851.2. NM_201557.3. [Q14192-1]
XP_011509100.1. XM_011510798.2. [Q14192-1]
UniGeneiHs.443687.

Genome annotation databases

EnsembliENST00000322142; ENSP00000322909; ENSG00000115641. [Q14192-1]
ENST00000358129; ENSP00000350846; ENSG00000115641. [Q14192-2]
ENST00000393352; ENSP00000377020; ENSG00000115641. [Q14192-1]
ENST00000393353; ENSP00000377021; ENSG00000115641. [Q14192-1]
ENST00000408995; ENSP00000386633; ENSG00000115641. [Q14192-1]
ENST00000409807; ENSP00000386665; ENSG00000115641. [Q14192-1]
GeneIDi2274.
KEGGihsa:2274.
UCSCiuc061mpc.1. human. [Q14192-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiFHL2_HUMAN
AccessioniPrimary (citable) accession number: Q14192
Secondary accession number(s): Q13229
, Q13644, Q2I5I4, Q5TM15, Q9P294
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: October 17, 2006
Last modified: March 28, 2018
This is version 176 of the entry and version 3 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