P70662 (LDB1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
LIM domain-binding protein 1
Short name=LDB-1

Alternative name(s):
Carboxyl-terminal LIM domain-binding protein 2
Short name=CLIM-2
LIM domain-binding factor CLIM2
Short name=mLdb1
Nuclear LIM interactor

Gene names

Name:	Ldb1
Synonyms:	Nli

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	411 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Binds to the LIM domain of a wide variety of LIM domain-containing transcription factors. May regulate the transcriptional activity of LIM-containing proteins by determining specific partner interactions. Play a role in the development of interneurons and motor neurons in cooperation with LHX3 and ISL1. Acts synergistically with LHX1/LIM1 in axis formation and activation of gene expression. Acts with LMO2 in the regulation of red blood cell development, maintaining erythroid precursors in an immature state. Ref.1 Ref.2 Ref.3 Ref.4 Ref.6 Ref.8
Subunit structure	Interacts with ESR1 By similarity. Forms homodimers and heterodimers. Interacts with and activates LHX1/LIM1. Interacts with the LIM domains of ISL1 and LMO2. Can assemble in a complex with LMO2 and TAL1/SCL but does not interact with TAL1/SCL directly. Strongly interacts with the LIM2 domain of LMX1A and more weakly with the LIM1 domain. Homodimerization is not required for, and does not effect, LMX1A-binding. Component of a nuclear TAL-1 complex composed at least of CBFA2T3, LDB1, TAL1 and TCF3. Interacts with LHX6 and LHX9. At neuronal promoters, forms a complex with LHX3 ivolved in the specification of interneurons, in motor neurons, it is displaced by ISL1 to form a ternary complex in which ISL1 contacts both LHX3 and LDB1. Ref.1 Ref.4 Ref.8 Ref.9 Ref.10 Ref.11 Ref.13 Ref.14
Subcellular location	Nucleus Ref.2 Ref.4 Ref.8.
Tissue specificity	Expression overlaps that of LIM domain-containing proteins. Expressed widely in the embryo with highest expression in several regions of the brain the central nervous system ganglia. Also expressed in fetal liver, lung, kidney, thymus and olfactory epithelium. Expressed in multiple adult tissues including heart, brain, liver, kidney, testis, lung and muscle and a diverse range of neuronal cell types, with expression highest in the pituitary gland and skin. Expressed in both embryonic and adult hemopoietic cells, including the erythroid lineage. Ref.1 Ref.3 Ref.4 Ref.6
Domain	The dimerization domain is located in the N-terminus. Ref.8 Ref.9
Post-translational modification	Ubiquitinated by RLIM/RNF12, leading to its degradation by the proteasome. Ref.13
Sequence similarities	Belongs to the LDB family.

Ontologies

Keywords
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Molecular function	Developmental protein
PTM	Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Wnt receptor signaling pathway Inferred from mutant phenotype PubMed 12490556. Source: MGI anterior/posterior axis specification Inferred from mutant phenotype PubMed 12490556. Source: MGI cellular component assembly Inferred from genetic interaction PubMed 17991461. Source: MGI cerebellar Purkinje cell differentiation Inferred from mutant phenotype PubMed 17664423. Source: MGI epithelial structure maintenance Inferred from genetic interaction PubMed 17991461. Source: MGI gastrulation with mouth forming second Inferred from mutant phenotype PubMed 12490556. Source: MGI hair follicle development Inferred from genetic interaction PubMed 17991461. Source: MGI head development Inferred from genetic interaction PubMed 15857913. Source: UniProtKB histone H3-K4 acetylation Inferred from mutant phenotype PubMed 20570862. Source: BHF-UCL negative regulation of erythrocyte differentiation Inferred from mutant phenotype Ref.4. Source: UniProtKB negative regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: Compara positive regulation of cell adhesion Inferred from genetic interaction PubMed 17991461. Source: MGI positive regulation of hemoglobin biosynthetic process Inferred from mutant phenotype PubMed 20570862. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype PubMed 20570862. Source: BHF-UCL primitive erythrocyte differentiation Traceable author statement PubMed 20570862. Source: BHF-UCL regulation of DNA-dependent transcription, elongation Inferred from mutant phenotype PubMed 20570862. Source: BHF-UCL somatic stem cell maintenance Inferred from genetic interaction PubMed 17991461. Source: MGI transcription from RNA polymerase II promoter Inferred from direct assay PubMed 15857913. Source: UniProtKB transcription-dependent tethering of RNA polymerase II gene DNA at nuclear periphery Inferred from mutant phenotype PubMed 20570862. Source: BHF-UCL
Cellular_component	cell-cell junction Inferred from direct assay PubMed 10882525. Source: MGI nuclear chromatin Inferred from electronic annotation. Source: Compara nucleoplasm part Inferred from direct assay PubMed 10882525. Source: MGI protein complex Inferred from direct assay PubMed 15857913. Source: UniProtKB transcription factor complex Inferred from electronic annotation. Source: Compara
Molecular_function	LIM domain binding Inferred from direct assay Ref.2Ref.8. Source: UniProtKB chromatin binding Inferred from direct assay PubMed 18550854PubMed 19011221. Source: MGI enhancer sequence-specific DNA binding Inferred from direct assay PubMed 19323994. Source: MGI protein homodimerization activity Inferred from direct assay Ref.8Ref.9. Source: UniProtKB transcription cofactor activity Inferred from electronic annotation. Source: InterPro transcription factor binding transcription factor activity Inferred from physical interaction PubMed 17991461Ref.1Ref.3. Source: MGI
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P70662-1)

Also known as: Visvader-a;

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.

Isoform 2 (identifier: P70662-2)

Also known as: Tran-b;

The sequence of this isoform differs from the canonical sequence as follows:
     1-36: Missing.
     336-355: DVMVVGEPTLMGGEFGDEDE → VSISAFFSSGLPHCSPLTPV
     356-411: Missing.

Note: Due to intron retention. Lacks LIM-binding domain. Lacks ability to activate LIM domain-dependent transcription.

Isoform 3 (identifier: P70662-3)

Also known as: Tran-a;

The sequence of this isoform differs from the canonical sequence as follows:
     1-36: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 411

411

LIM domain-binding protein 1

PRO_0000084385

Regions

Region

336 – 374

39

LIM-binding domain (LID)

Natural variations

Alternative sequence

1 – 36

36

Missing in isoform 2 and isoform 3.

VSP_027833

Alternative sequence

336 – 355

20

DVMVV…GDEDE → VSISAFFSSGLPHCSPLTPV in isoform 2.

VSP_027834

Alternative sequence

356 – 411

56

Missing in isoform 2.

VSP_027835

Experimental info

Sequence conflict

262

1

Y → C in AAB96885. Ref.3

Sequence conflict

334

1

V → A in AAB96885. Ref.3

Sequence conflict

389 – 390

2

PW → QR in AAB96885. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

411

Helix Strand Turn

Details...

Beta strand

336 – 344

9

Beta strand

346 – 349

4

Turn

352 – 354

3

Beta strand

355 – 357

3

Beta strand

359 – 362

4

Beta strand

368 – 370

3

Beta strand

372 – 375

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Visvader-a) [UniParc]. Last modified September 11, 2007. Version 2. Checksum: 47C53DFA23044580	FASTA	411	46,503
	10 20 30 40 50 60 MSVGCACPGC SSKSFKLYSP KEPPNGNAFP PFHPGTMLDR DVGPTPMYPP TYLEPGIGRH 70 80 90 100 110 120 TPYGNQTDYR IFELNKRLQN WTEECDNLWW DAFTTEFFED DAMLTITFCL EDGPKRYTIG 130 140 150 160 170 180 RTLIPRYFRS IFEGGATELY YVLKHPKEAF HSNFVSLDCD QGSMVTQHGK PMFTQVCVEG 190 200 210 220 230 240 RLYLEFMFDD MMRIKTWHFS IRQHRELIPR SILAMHAQDP QMLDQLSKNI TRCGLSNSTL 250 260 270 280 290 300 NYLRLCVILE PMQELMSRHK TYSLSPRDCL KTCLFQKWQR MVAPPAEPAR QQPSKRRKRK 310 320 330 340 350 360 MSGGSTMSSG GGNTNNSNSK KKSPASTFAL SSQVPDVMVV GEPTLMGGEF GDEDERLITR 370 380 390 400 410 LENTQFDAAN GIDDEDSFNN SPALGANSPW NSKPPSSQES KSENPTSQAS Q
	Isoform 2 (Tran-b) [UniParc]. Checksum: 2FD1D15303732E5E	FASTA	319	36,667
	10 20 30 40 50 60 MLDRDVGPTP MYPPTYLEPG IGRHTPYGNQ TDYRIFELNK RLQNWTEECD NLWWDAFTTE 70 80 90 100 110 120 FFEDDAMLTI TFCLEDGPKR YTIGRTLIPR YFRSIFEGGA TELYYVLKHP KEAFHSNFVS 130 140 150 160 170 180 LDCDQGSMVT QHGKPMFTQV CVEGRLYLEF MFDDMMRIKT WHFSIRQHRE LIPRSILAMH 190 200 210 220 230 240 AQDPQMLDQL SKNITRCGLS NSTLNYLRLC VILEPMQELM SRHKTYSLSP RDCLKTCLFQ 250 260 270 280 290 300 KWQRMVAPPA EPARQQPSKR RKRKMSGGST MSSGGGNTNN SNSKKKSPAS TFALSSQVPV 310 SISAFFSSGL PHCSPLTPV
	Isoform 3 (Tran-a) [UniParc]. Checksum: 75FACF0CA0BD2DE7	FASTA	375	42,779
	10 20 30 40 50 60 MLDRDVGPTP MYPPTYLEPG IGRHTPYGNQ TDYRIFELNK RLQNWTEECD NLWWDAFTTE 70 80 90 100 110 120 FFEDDAMLTI TFCLEDGPKR YTIGRTLIPR YFRSIFEGGA TELYYVLKHP KEAFHSNFVS 130 140 150 160 170 180 LDCDQGSMVT QHGKPMFTQV CVEGRLYLEF MFDDMMRIKT WHFSIRQHRE LIPRSILAMH 190 200 210 220 230 240 AQDPQMLDQL SKNITRCGLS NSTLNYLRLC VILEPMQELM SRHKTYSLSP RDCLKTCLFQ 250 260 270 280 290 300 KWQRMVAPPA EPARQQPSKR RKRKMSGGST MSSGGGNTNN SNSKKKSPAS TFALSSQVPD 310 320 330 340 350 360 VMVVGEPTLM GGEFGDEDER LITRLENTQF DAANGIDDED SFNNSPALGA NSPWNSKPPS 370 SQESKSENPT SQASQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Interactions of the LIM-domain-binding factor Ldb1 with LIM homeodomain proteins." Agulnick A.D., Taira M., Breen J.J., Tanaka T., Dawid I.B., Westphal H. Nature 384:270-272(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, INTERACTION WITH LHX1, TISSUE SPECIFICITY. Strain: Swiss Webster. Tissue: Embryo.
[2]	"Nuclear LIM interactor, a rhombotin and LIM homeodomain interacting protein, is expressed early in neuronal development." Jurata L.W., Kenny D.A., Gill G.N. Proc. Natl. Acad. Sci. U.S.A. 93:11693-11698(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, SUBCELLULAR LOCATION. Tissue: Embryo.
[3]	"A family of LIM domain-associated cofactors confer transcriptional synergism between LIM and Otx homeodomain proteins." Bach I., Carriere C., Ostendorff H.P., Andersen B., Rosenfeld M.G. Genes Dev. 11:1370-1380(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, TISSUE SPECIFICITY. Tissue: Embryonic head.
[4]	"The LIM-domain binding protein Ldb1 and its partner LMO2 act as negative regulators of erythroid differentiation." Visvader J.E., Mao X., Fujiwara Y., Hahm K., Orkin S.H. Proc. Natl. Acad. Sci. U.S.A. 94:13707-13712(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH LMO2, IDENTIFICATION IN A COMPLEX WITH LMO2 AND TAL1. Tissue: Yolk sac.
[5]	"Genomic structure and chromosomal localization of the mouse LIM domain-binding protein 1 gene, Ldb1." Yamashita T., Agulnick A.D., Copeland N.G., Gilbert D.J., Jenkins N.A., Westphal H. Genomics 48:87-92(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: 129/Sv.
[6]	"Spliced isoforms of LIM-domain-binding protein (CLIM/NLI/Ldb) lacking the LIM-interaction domain." Tran Y.H., Xu Z., Kato A., Mistry A.C., Goya Y., Taira M., Brandt S.J., Hirose S. J. Biochem. 140:105-119(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, ALTERNATIVE SPLICING, TISSUE SPECIFICITY. Tissue: Heart.
[7]	"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] (ISOFORM 3). Strain: FVB/N. Tissue: Mammary gland.
[8]	"Functional analysis of the nuclear LIM domain interactor NLI." Jurata L.W., Gill G.N. Mol. Cell. Biol. 17:5688-5698(1997) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH ISL1; LMO2 AND LMX1A, HOMODIMERIZATION, SUBCELLULAR LOCATION, IDENTIFICATION OF LIM-BINDING DOMAIN.
[9]	"Interactions between LIM domains and the LIM domain-binding protein Ldb1." Breen J.J., Agulnick A.D., Westphal H., Dawid I.B. J. Biol. Chem. 273:4712-4717(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH LHX1, DOMAIN, HOMODIMERIZATION.
[10]	"A brain region-specific gene product Lhx6.1 interacts with Ldb1 through tandem LIM-domains." Kimura N., Ueno M., Nakashima K., Taga T. J. Biochem. 126:180-187(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH LHX6. Tissue: Fetal brain.
[11]	"Characterization of Lhx9, a novel LIM/homeobox gene expressed by the pioneer neurons in the mouse cerebral cortex." Bertuzzi S., Porter F.D., Pitts A., Kumar M., Agulnick A., Wassif C., Westphal H. Mech. Dev. 81:193-198(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH LHX9.
[12]	"LIM factor Lhx3 contributes to the specification of motor neuron and interneuron identity through cell-type-specific protein-protein interactions." Thaler J.P., Lee S.K., Jurata L.W., Gill G.N., Pfaff S.L. Cell 110:237-249(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH LHX3 AND ISL1.
[13]	"Ubiquitination-dependent cofactor exchange on LIM homeodomain transcription factors." Ostendorff H.P., Peirano R.I., Peters M.A., Schluter A., Bossenz M., Scheffner M., Bach I. Nature 416:99-103(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RLIM, UBIQUITINATION.
[14]	"ETO2 coordinates cellular proliferation and differentiation during erythropoiesis." Goardon N., Lambert J.A., Rodriguez P., Nissaire P., Herblot S., Thibault P., Dumenil D., Strouboulis J., Romeo P.-H., Hoang T. EMBO J. 25:357-366(2006) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN A NUCLEAR TAL-1 COMPLEX.
[15]	"Structural basis for the recognition of ldb1 by the N-terminal LIM domains of LMO2 and LMO4." Deane J.E., Mackay J.P., Kwan A.H.Y., Sum E.Y.M., Visvader J.E., Matthews J.M. EMBO J. 22:2224-2233(2003) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 336-375 IN COMPLEXES WITH LMO2 AND LMO4.
[16]	"Tandem LIM domains provide synergistic binding in the LMO4:Ldb1 complex." Deane J.E., Ryan D.P., Sunde M., Maher M.J., Guss J.M., Visvader J.E., Matthews J.M. EMBO J. 23:3589-3598(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS) OF 336-375 IN COMPLEX WITH LMO4.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U70375 mRNA. Translation: AAC52933.1.
U69270 mRNA. Translation: AAC52887.1.
U89488 mRNA. Translation: AAB96885.1.
AF030333 mRNA. Translation: AAB94131.1.
AF024524 Genomic DNA. Translation: AAC40064.1.
AB250383 mRNA. Translation: BAE95401.1.
BC013624 mRNA. Translation: AAH13624.1.

IPI

IPI00111789.
IPI00624850.
IPI00762229.

RefSeq

NP_001106879.1. NM_001113408.1.
NP_034827.1. NM_010697.1.

UniGene

Mm.327442.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1J2O	NMR	-	A	336-375	[»]
1M3V	NMR	-	A	336-375	[»]
1RUT	X-ray	1.30	X	336-375	[»]
2JTN	NMR	-	A	331-375	[»]
2L6Y	NMR	-	B	336-348	[»]
2L6Z	NMR	-	C	336-348	[»]
2LXD	NMR	-	A	336-375	[»]

ProteinModelPortal

P70662.

SMR

P70662. Positions 336-363.

ModBase

Search...

Protein-protein interaction databases

IntAct

P70662. 1 interaction.

MINT

MINT-2779250.

PTM databases

PhosphoSite

P70662.

Proteomic databases

PaxDb

P70662.

PRIDE

P70662.

Protocols and materials databases

DNASU

16825.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000026252; ENSMUSP00000026252; ENSMUSG00000025223.
ENSMUST00000056931; ENSMUSP00000053680; ENSMUSG00000025223.
ENSMUST00000137771; ENSMUSP00000114667; ENSMUSG00000025223.
ENSMUST00000156585; ENSMUSP00000118546; ENSMUSG00000025223.

GeneID

16825.

KEGG

mmu:16825.

UCSC

uc008hrz.1. mouse.
uc008hsa.1. mouse.

Organism-specific databases

CTD

8861.

MGI

MGI:894762. Ldb1.

Phylogenomic databases

eggNOG

NOG282114.

GeneTree

ENSGT00390000005639.

HOGENOM

HOG000030908.

HOVERGEN

HBG000135.

InParanoid

P70662.

KO

K15617.

OMA

GSNSPWN.

OrthoDB

EOG4XWFXV.

Gene expression databases

ArrayExpress

P70662.

Bgee

P70662.

CleanEx

MM_LDB1.

Genevestigator

P70662.

GermOnline

ENSMUSG00000025223. Mus musculus.

Family and domain databases

InterPro

IPR002691. LIM-dom-bd.
[Graphical view]

PANTHER

PTHR10378. PTHR10378. 1 hit.

ProtoNet

Search...

Other

ChiTaRS

LDB1. mouse.

EvolutionaryTrace

P70662.

NextBio

290724.

SOURCE

Search...

Entry information

Entry name

LDB1_MOUSE

Accession

Primary (citable) accession number: P70662
Secondary accession number(s): O55204, Q1EQX2, Q71V68

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	September 11, 2007
Last modified:	May 29, 2013
This is version 112 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program