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Q9UGP4 (LIMD1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 122. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
LIM domain-containing protein 1
Gene names
Name:LIMD1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length676 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Adapter or scaffold protein which participates in the assembly of numerous protein complexes and is involved in several cellular processes such as cell fate determination, cytoskeletal organization, repression of gene transcription, cell-cell adhesion, cell differentiation, proliferation and migration. Positively regulates microRNA (miRNA)-mediated gene silencing and is essential for P-body formation and integrity. Acts as a hypoxic regulator by bridging an association between the prolyl hydroxylases and VHL enabling efficient degradation of HIF1A. Acts as a transcriptional corepressor for SNAI1- and SNAI2/SLUG-dependent repression of E-cadherin transcription. Negatively regulates the Hippo signaling pathway and antagonizes phosphorylation of YAP1. Inhibits E2F-mediated transcription, and suppresses the expression of the majority of genes with E2F1-responsive elements. Regulates osteoblast development, function, differentiation and stress osteoclastogenesis. Enhances the ability of TRAF6 to activate adapter protein complex 1 (AP-1) and negatively regulates the canonical Wnt receptor signaling pathway in osteoblasts. May act as a tumor suppressor by inhibiting cell proliferation. Ref.5 Ref.13 Ref.14 Ref.16 Ref.19

Subunit structure

Interacts (via LIM domains) with TRAF6. Found in a complex with TRAF6, PRKCZ and SQSTM1. Interacts (via LIM domains) SNAI2/SLUG (via SNAG domain) and SCRT1 (via SNAG domain) By similarity. Interacts with SQSTM1 and RB1. Found in a complex composed of LIMD1, VHL, EGLN1/PHD2, TCEB2 AND CUL2. Interacts with EIF4E, AGO1, AGO2, DCP2, DDX6, LATS1, LATS2, EGLN1/PHD2, EGLN2/PHD1 and EGLN3/PHD3. Interacts (via LIM zinc-binding 2) with isoform 1and isoform 3of VHL. Interacts (via LIM domains) with SNAI1 (via SNAG domain). Ref.5 Ref.6 Ref.8 Ref.13 Ref.14 Ref.19

Subcellular location

Cytoplasm. Nucleus. CytoplasmP-body. Cell junctionadherens junction. Cell junctionfocal adhesion. Note: Shuttles between cytoplasm and nucleus but is localized predominantly to the cytoplasm. Found in the nucleus but not nucleoli. Colocalizes with VCL in the focal adhesions. Down-regulation and/or elimination of its expression from the nucleus of neoplastic cells correlates strongly with poor patient prognosis and aggressive forms of breast carcinoma. Conversely, strong nuclear localization correlates with low-tumor grade and better patient prognosis. Ref.5 Ref.7 Ref.9 Ref.13 Ref.14

Tissue specificity

Expressed in normal and breast cancer tissues (at protein level). Ubiquitous. Ref.1 Ref.9

Induction

Down-regulated in lung cancer. Ref.5

Post-translational modification

Phosphorylated during mitosis. Ref.7

Sequence similarities

Belongs to the zyxin/ajuba family.

Contains 3 LIM zinc-binding domains.

Ontologies

Keywords
   Biological processRNA-mediated gene silencing
Transcription
Transcription regulation
   Cellular componentCell junction
Cytoplasm
Nucleus
   Coding sequence diversityPolymorphism
   DiseaseTumor suppressor
   DomainLIM domain
Repeat
   LigandMetal-binding
Zinc
   Molecular functionRepressor
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell migration

Inferred from mutant phenotype Ref.16. Source: UniProtKB

cytoplasmic mRNA processing body assembly

Inferred from mutant phenotype Ref.14. Source: MGI

cytoskeleton organization

Inferred from mutant phenotype Ref.16. Source: UniProtKB

gene silencing by miRNA

Inferred from mutant phenotype Ref.14. Source: MGI

multicellular organismal development

Traceable author statement Ref.1. Source: ProtInc

negative regulation of canonical Wnt signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of hippo signaling

Inferred from direct assay Ref.13. Source: UniProtKB

negative regulation of osteoblast differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of transcription, DNA-templated

Inferred from direct assay Ref.5. Source: UniProtKB

osteoblast development

Inferred from sequence or structural similarity. Source: UniProtKB

phosphorylation

Inferred from direct assay Ref.7. Source: UniProtKB

positive regulation of gene silencing by miRNA

Inferred from mutant phenotype Ref.14. Source: UniProtKB

regulation of cell shape

Inferred from mutant phenotype Ref.16. Source: UniProtKB

regulation of transcription, DNA-templated

Traceable author statement Ref.1. Source: ProtInc

response to hypoxia

Inferred from direct assay Ref.19. Source: UniProtKB

signal transduction

Traceable author statement Ref.1. Source: ProtInc

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentRISC complex

Inferred from direct assay Ref.14. Source: MGI

adherens junction

Inferred from direct assay Ref.13. Source: UniProtKB

cytoplasm

Inferred from direct assay Ref.5Ref.7. Source: UniProtKB

cytoplasmic mRNA processing body

Inferred from direct assay Ref.14. Source: MGI

focal adhesion

Inferred from direct assay Ref.7. Source: UniProtKB

nucleus

Inferred from direct assay Ref.5Ref.7. Source: UniProtKB

   Molecular_functionprotein binding

Inferred from physical interaction Ref.5Ref.8Ref.13Ref.14Ref.19. Source: UniProtKB

transcription corepressor activity

Inferred from sequence or structural similarity. Source: UniProtKB

zinc ion binding

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

ORFQ9Q2G45EBI-2652871,EBI-6248094From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 676676LIM domain-containing protein 1
PRO_0000075801

Regions

Domain470 – 53162LIM zinc-binding 1
Domain535 – 59561LIM zinc-binding 2
Domain595 – 66470LIM zinc-binding 3
Region54 – 13481Mediates nuclear export
Region186 – 26075Interaction with EGLN1/PHD2
Region404 – 44239Interaction with RB1
Region472 – 676205Necessary for nuclear localization

Amino acid modifications

Modified residue2721Phosphoserine Ref.4 Ref.15
Modified residue2771Phosphoserine Ref.4 Ref.15
Modified residue3041Phosphoserine Ref.10
Modified residue4211Phosphoserine Ref.10 Ref.15
Modified residue4241Phosphoserine Ref.10 Ref.12

Natural variations

Natural variant361G → D.
Corresponds to variant rs2578662 [ dbSNP | Ensembl ].
VAR_050147
Natural variant4151G → R.
Corresponds to variant rs3733113 [ dbSNP | Ensembl ].
VAR_021993

Sequences

Sequence LengthMass (Da)Tools
Q9UGP4 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: 085DF06F047B49E6

FASTA67672,190
        10         20         30         40         50         60 
MDKYDDLGLE ASKFIEDLNM YEASKDGLFR VDKGAGNNPE FEETRRVFAT KMAKIHLQQQ 

        70         80         90        100        110        120 
QQQLLQEETL PRGSRGPVNG GGRLGPQARW EVVGSKLTVD GAAKPPLAAS TGAPGAVTTL 

       130        140        150        160        170        180 
AAGQPPYPPQ EQRSRPYLHG TRHGSQDCGS RESLATSEMS AFHQPGPCED PSCLTHGDYY 

       190        200        210        220        230        240 
DNLSLASPKW GDKPGVSPSI GLSVGSGWPS SPGSDPPLPK PCGDHPLNHR QLSLSSSRSS 

       250        260        270        280        290        300 
EGSLGGQNSG IGGRSSEKPT GLWSTASSQR VSPGLPSPNL ENGAPAVGPV QPRTPSVSAP 

       310        320        330        340        350        360 
LALSCPRQGG LPRSNSGLGG EVSGVMSKPN VDPQPWFQDG PKSYLSSSAP SSSPAGLDGS 

       370        380        390        400        410        420 
QQGAVPGLGP KPGCTDLGTG PKLSPTSLVH PVMSTLPELS CKEGPLGWSS DGSLGSVLLD 

       430        440        450        460        470        480 
SPSSPRVRLP CQPLVPGPEL RPSAAELKLE ALTQRLEREM DAHPKADYFG ACVKCSKGVF 

       490        500        510        520        530        540 
GAGQACQAMG NLYHDTCFTC AACSRKLRGK AFYFVNGKVF CEEDFLYSGF QQSADRCFLC 

       550        560        570        580        590        600 
GHLIMDMILQ ALGKSYHPGC FRCVICNECL DGVPFTVDSE NKIYCVRDYH KVLAPKCAAC 

       610        620        630        640        650        660 
GLPILPPEGS DETIRVVSMD RDYHVECYHC EDCGLELNDE DGHRCYPLED HLFCHSCHVK 

       670 
RLEKRPSSTA LHQHHF 

« Hide

References

« Hide 'large scale' references
[1]"A novel gene containing LIM domains (LIMD1) is located within the common eliminated region 1 (C3CER1) in 3p21.3."
Kiss H., Kedra D., Yang Y., Kost-Alimova M., Kiss C., O'Brien K.P., Fransson I., Klein G., Imreh S., Dumanski J.P.
Hum. Genet. 105:552-559(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
[2]"The LZTFL1 gene is a part of a transcriptional map covering 250 kb within the common eliminated region 1 (C3CER1) in 3p21.3."
Kiss H., Kedra D., Kiss C., Kost-Alimova M., Yang Y., Klein G., Imreh S., Dumanski J.P.
Genomics 73:10-19(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"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: Brain.
[4]"Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry."
Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., Peters E.C.
Anal. Chem. 76:2763-2772(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-272 AND SER-277, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[5]"LIM domains-containing protein 1 (LIMD1), a tumor suppressor encoded at chromosome 3p21.3, binds pRB and represses E2F-driven transcription."
Sharp T.V., Munoz F., Bourboulia D., Presneau N., Darai E., Wang H.-W., Cannon M., Butcher D.N., Nicholson A.G., Klein G., Imreh S., Boshoff C.
Proc. Natl. Acad. Sci. U.S.A. 101:16531-16536(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH RB1, SUBCELLULAR LOCATION, INDUCTION.
[6]"The LIM protein Ajuba influences interleukin-1-induced NF-kappaB activation by affecting the assembly and activity of the protein kinase Czeta/p62/TRAF6 signaling complex."
Feng Y., Longmore G.D.
Mol. Cell. Biol. 25:4010-4022(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SQSTM1.
[7]"Cell cycle regulated phosphorylation of LIMD1 in cell lines and expression in human breast cancers."
Huggins C.J., Andrulis I.L.
Cancer Lett. 267:55-66(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION.
[8]"Ajuba LIM proteins are snail/slug corepressors required for neural crest development in Xenopus."
Langer E.M., Feng Y., Zhaoyuan H., Rauscher F.J. III, Kroll K.L., Longmore G.D.
Dev. Cell 14:424-436(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SNAI1.
[9]"Differential subcellular localisation of the tumour suppressor protein LIMD1 in breast cancer correlates with patient survival."
Spendlove I., Al-Attar A., Watherstone O., Webb T.M., Ellis I.O., Longmore G.D., Sharp T.V.
Int. J. Cancer 123:2247-2253(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[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] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-304; SER-421 AND SER-424, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[11]"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] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-424, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[13]"Ajuba LIM proteins are negative regulators of the Hippo signaling pathway."
Das Thakur M., Feng Y., Jagannathan R., Seppa M.J., Skeath J.B., Longmore G.D.
Curr. Biol. 20:657-662(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH LATS1 AND LATS2.
[14]"LIM-domain proteins, LIMD1, Ajuba, and WTIP are required for microRNA-mediated gene silencing."
James V., Zhang Y., Foxler D.E., de Moor C.H., Kong Y.W., Webb T.M., Self T.J., Feng Y., Lagos D., Chu C.Y., Rana T.M., Morley S.J., Longmore G.D., Bushell M., Sharp T.V.
Proc. Natl. Acad. Sci. U.S.A. 107:12499-12504(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH EIF4E; AGO1; AGO2; DCP2 AND DDX6.
[15]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-272; SER-277 AND SER-421, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[16]"Identification and characterization of a set of conserved and new regulators of cytoskeletal organisation, cell morphology and migration."
Bai S.W., Herrera-Abreu M.T., Rohn J.L., Racine V., Tajadura V., Suryavanshi N., Bechtel S., Wiemann S., Baum B., Ridley A.J.
BMC Biol. 9:54-54(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[17]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[18]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[19]"The LIMD1 protein bridges an association between the prolyl hydroxylases and VHL to repress HIF-1 activity."
Foxler D.E., Bridge K.S., James V., Webb T.M., Mee M., Wong S.C., Feng Y., Constantin-Teodosiu D., Petursdottir T.E., Bjornsson J., Ingvarsson S., Ratcliffe P.J., Longmore G.D., Sharp T.V.
Nat. Cell Biol. 14:201-208(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH EGLN1/PHD2; EGLN2/PHD1; EGLN3/PHD3 AND VHL, IDENTIFICATION IN A COMPLEX WITH CUL2; EGLN1/PHD2; VHL AND TCEB2.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ132408 mRNA. Translation: CAB63652.1.
AJ312686 Genomic DNA. Translation: CAC35917.1.
AJ297357 Genomic DNA. Translation: CAB95944.1.
BC117236 mRNA. Translation: AAI17237.1.
BC117238 mRNA. Translation: AAI17239.1.
CCDSCCDS2729.1.
RefSeqNP_055055.1. NM_014240.2.
UniGeneHs.193370.
Hs.621057.

3D structure databases

ProteinModelPortalQ9UGP4.
SMRQ9UGP4. Positions 470-658.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114475. 23 interactions.
IntActQ9UGP4. 8 interactions.
MINTMINT-1193166.
STRING9606.ENSP00000273317.

PTM databases

PhosphoSiteQ9UGP4.

Polymorphism databases

DMDM47605932.

Proteomic databases

MaxQBQ9UGP4.
PaxDbQ9UGP4.
PRIDEQ9UGP4.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000273317; ENSP00000273317; ENSG00000144791.
GeneID8994.
KEGGhsa:8994.
UCSCuc003coq.3. human.

Organism-specific databases

CTD8994.
GeneCardsGC03P045611.
HGNCHGNC:6612. LIMD1.
MIM604543. gene.
neXtProtNX_Q9UGP4.
PharmGKBPA30385.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG331290.
HOGENOMHOG000072700.
HOVERGENHBG052327.
InParanoidQ9UGP4.
KOK16682.
OMASLASPKW.
PhylomeDBQ9UGP4.
TreeFamTF320310.

Gene expression databases

ArrayExpressQ9UGP4.
BgeeQ9UGP4.
CleanExHS_LIMD1.
GenevestigatorQ9UGP4.

Family and domain databases

Gene3D2.10.110.10. 3 hits.
InterProIPR028734. LIMD1.
IPR001781. Znf_LIM.
[Graphical view]
PANTHERPTHR24219:SF3. PTHR24219:SF3. 1 hit.
PfamPF00412. LIM. 3 hits.
[Graphical view]
SMARTSM00132. LIM. 3 hits.
[Graphical view]
PROSITEPS00478. LIM_DOMAIN_1. 2 hits.
PS50023. LIM_DOMAIN_2. 3 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSLIMD1. human.
GeneWikiLIMD1.
GenomeRNAi8994.
NextBio33727.
PROQ9UGP4.
SOURCESearch...

Entry information

Entry nameLIMD1_HUMAN
AccessionPrimary (citable) accession number: Q9UGP4
Secondary accession number(s): Q17RQ1, Q9BQQ9, Q9NQ47
Entry history
Integrated into UniProtKB/Swiss-Prot: May 24, 2004
Last sequence update: May 1, 2000
Last modified: July 9, 2014
This is version 122 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM