Q86U70 (LDB1_HUMAN) 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=hLdb1
Nuclear LIM interactor

Gene names

Name:	LDB1
Synonyms:	CLIM2

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	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. May play a role in the development of motor neurons. 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 By similarity.
Subunit structure	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 By similarity. Interacts with ESR1. Ref.11
Subcellular location	Nucleus Probable.
Tissue specificity	Expressed in a wide range of adult tissues including brain, heart, skeletal muscle, colon, thymus, spleen, kidney, liver, small intestine, lung and peripheral blood leukocytes. Ref.4
Domain	The dimerization domain is located in the N-terminus By similarity.
Post-translational modification	Ubiquitinated by RLIM/RNF12, leading to its degradation by the proteasome By similarity.
Miscellaneous	Acts as a negative coregulator of ESR1-mediated transcription in breast cancer cells.
Sequence similarities	Belongs to the LDB family.
Sequence caution	The sequence CAB45409.1 differs from that shown. Reason: Erroneous initiation. The sequence CAH72217.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Molecular function	Developmental protein
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	histone H3-K4 acetylation Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of erythrocyte differentiation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of transcription, DNA-dependent Inferred from direct assay. Source: UniProtKB positive regulation of hemoglobin biosynthetic process Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype. Source: BHF-UCL regulation of transcription elongation, DNA-dependent Inferred from sequence or structural similarity. Source: BHF-UCL transcription-dependent tethering of RNA polymerase II gene DNA at nuclear periphery Inferred from sequence or structural similarity. Source: BHF-UCL
Cellular component	nuclear chromatin Inferred from direct assay. Source: BHF-UCL protein complex Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	LIM domain binding Inferred from physical interaction. Source: UniProtKB protein homodimerization activity Inferred from sequence or structural similarity. Source: UniProtKB transcription corepressor activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q86U70-1)

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.

Note: No experimental confirmation available.

Isoform 2 (identifier: Q86U70-3)

Also known as: b;

The sequence of this isoform differs from the canonical sequence as follows:
     1-36: Missing.
     336-352: DVMVVGEPTLMGGEFGD → VSISAFFSLLGCPTTHP
     353-411: Missing.

Note: Due to intron retention. Lacks LIM-binding domain.

Isoform 3 (identifier: Q86U70-2)

Also known as: 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_0000084384

Regions

Region

336 – 374

39

LIM-binding domain (LID) By similarity

Amino acid modifications

Modified residue

302

1

Phosphoserine Ref.10

Modified residue

306

1

Phosphothreonine Ref.10

Natural variations

Alternative sequence

1 – 36

36

Missing in isoform 2 and isoform 3.

VSP_027830

Alternative sequence

336 – 352

17

DVMVV…GEFGD → VSISAFFSLLGCPTTHP in isoform 2.

VSP_027831

Alternative sequence

353 – 411

59

Missing in isoform 2.

VSP_027832

Natural variant

299

1

R → Q in a colorectal cancer sample; somatic mutation. Ref.12

VAR_036366

Experimental info

Mutagenesis

245 – 249

5

LCVIL → ACVAA: Abolishes interaction with ESR1. Ref.11

Secondary structure

1

.

.

.

411

Helix Strand Turn

Details...

Beta strand

359 – 362

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified September 11, 2007. Version 2. Checksum: 5BB5348A36044580	FASTA	411	46,533
	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 MVAPPAEPTR 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 (b) [UniParc]. Checksum: B086EB4D28FC8E56	FASTA	316	36,428
	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 EPTRQQPSKR RKRKMSGGST MSSGGGNTNN SNSKKKSPAS TFALSSQVPV 310 SISAFFSLLG CPTTHP
	Isoform 3 (a) [UniParc]. Checksum: 698AC67CB5BD2DE7	FASTA	375	42,809
	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 EPTRQQPSKR 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]	"Cloning and chromosomal localization of two novel human genes encoding LIM-domain binding factors CLIM1 and CLIM2/LDB1/NLI." Semina E.V., Altherr M.R., Murray J.C. Mamm. Genome 9:921-924(1998) [PubMed: 9799849] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). Tissue: Craniofacial.
[2]	"Genomic structure, alternative transcripts and chromosome location of the human LIM domain binding protein gene LDB1." Drechsler M., Schumacher V., Friedrich S., Wildhardt G., Giesler S., Schroth A., Bodem J., Royer-Pokora B. Cytogenet. Cell Genet. 87:119-124(1999) [PubMed: 10640831] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Isolation and chromosomal assignment of human genes encoding cofactor of LIM homeodomain proteins, CLIM1 and CLIM2." Ueki N., Seki N., Yano K., Ohira M., Saito T., Masuho Y., Muramatsu M. J. Hum. Genet. 44:112-115(1999) [PubMed: 10083735] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). Tissue: Brain.
[4]	"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: 16815859] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING, TISSUE SPECIFICITY. Tissue: Fetal brain.
[5]	"Cloning, characterization, and physical mapping of the human homologs of the mouse C-LIM gene." Phillips J.C., Goldman D.A., Wiggs J.L. Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). Tissue: Fetal brain.
[6]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
[7]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[8]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed: 15164054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"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] (ISOFORM 3). Tissue: Muscle.
[10]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-302 AND THR-306, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[11]	"Regulation of estrogen-dependent transcription by the LIM cofactors CLIM and RLIM in breast cancer." Johnsen S.A., Guengoer C., Prenzel T., Riethdorf S., Riethdorf L., Taniguchi-Ishigaki N., Rau T., Tursun B., Furlow J.D., Sauter G., Scheffner M., Pantel K., Gannon F., Bach I. Cancer Res. 69:128-136(2009) [PubMed: 19117995] [Abstract] Cited for: INTERACTION WITH ESR1, MUTAGENESIS OF 245-LEU--LEU-249, MISCELLANEOUS.
[12]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] GLN-299.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF068652 mRNA. Translation: AAC77818.1.
AJ243098 Genomic DNA. Translation: CAB45409.1. Different initiation.
AB016485 mRNA. Translation: BAA31991.1.
AB250384 mRNA. Translation: BAE95402.1.
AF064491 mRNA. Translation: AAC28341.1.
BT007054 mRNA. Translation: AAP35703.1.
AK300588 mRNA. Translation: BAG62286.1.
AL500527 Genomic DNA. Translation: CAH72217.1. Different initiation.
BC000482 mRNA. Translation: AAH00482.1.
BC009246 mRNA. Translation: AAH09246.1.

IPI

IPI00428954.
IPI00760574.
IPI00856078.

RefSeq

NP_001106878.1. NM_001113407.1.
NP_003884.1. NM_003893.4.

UniGene

Hs.454418.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2XJY	X-ray	2.40	B	334-368	[»]
2XJZ	X-ray	2.80	I/J/K/L/M	334-368	[»]

ProteinModelPortal

Q86U70.

SMR

Q86U70. Positions 331-375.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-31826N.

IntAct

Q86U70. 15 interactions.

MINT

MINT-233462.

STRING

Q86U70.

PTM databases

PhosphoSite

Q86U70.

Polymorphism databases

DMDM

158518615.

Proteomic databases

PRIDE

Q86U70.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000425280; ENSP00000392466; ENSG00000198728.

GeneID

8861.

KEGG

hsa:8861.

UCSC

uc001kuk.2. human.
uc001kul.2. human.
uc009xwz.1. human.

Organism-specific databases

CTD

8861.

GeneCards

GC10M103857.

HGNC

HGNC:6532. LDB1.

HPA

HPA034488.

MIM

603451. gene.

neXtProt

NX_Q86U70.

PharmGKB

PA30316.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG04154.

GeneTree

ENSGT00390000005639.

HOGENOM

HBG505202.

HOVERGEN

HBG000135.

InParanoid

Q86U70.

OMA

GSNSPWN.

OrthoDB

EOG4XWFXV.

PhylomeDB

Q86U70.

Gene expression databases

ArrayExpress

Q86U70.

Bgee

Q86U70.

CleanEx

HS_LDB1.

Genevestigator

Q86U70.

GermOnline

ENSG00000198728. Homo sapiens.

Family and domain databases

InterPro

IPR002691. LIM-bd.
[Graphical view]

KO

K15617.

PANTHER

PTHR10378. LIM_bd. 1 hit.

Pfam

PF01803. LIM_bind. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

33273.

SOURCE

Search...

Entry information

Entry name

LDB1_HUMAN

Accession

Primary (citable) accession number: Q86U70
Secondary accession number(s): B4DUC4 , O75479, O96010, Q1EQX1, Q9UGM4

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 5, 2005
Last sequence update:	September 11, 2007
Last modified:	January 25, 2012
This is version 85 of the entry and version 2 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.