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Protein

LIM domain-containing protein 1

Gene

LIMD1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.5 Publications

GO - Molecular functioni

  • transcription corepressor activity Source: UniProtKB
  • zinc ion binding Source: ProtInc

GO - Biological processi

  • cell migration Source: UniProtKB
  • cytoplasmic mRNA processing body assembly Source: MGI
  • cytoskeleton organization Source: UniProtKB
  • gene silencing by miRNA Source: MGI
  • multicellular organism development Source: ProtInc
  • negative regulation of canonical Wnt signaling pathway Source: UniProtKB
  • negative regulation of hippo signaling Source: UniProtKB
  • negative regulation of osteoblast differentiation Source: UniProtKB
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • osteoblast development Source: UniProtKB
  • phosphorylation Source: UniProtKB
  • positive regulation of gene silencing by miRNA Source: UniProtKB
  • regulation of cell shape Source: UniProtKB
  • regulation of transcription, DNA-templated Source: ProtInc
  • response to hypoxia Source: UniProtKB
  • signal transduction Source: ProtInc
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Repressor

Keywords - Biological processi

RNA-mediated gene silencing, Transcription, Transcription regulation

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000144791-MONOMER.
ReactomeiR-HSA-1234176. Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.

Names & Taxonomyi

Protein namesi
Recommended name:
LIM domain-containing protein 1
Gene namesi
Name:LIMD1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:6612. LIMD1.

Subcellular locationi

  • 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.

GO - Cellular componenti

  • adherens junction Source: UniProtKB
  • cell-cell junction Source: GO_Central
  • cytoplasm Source: UniProtKB
  • cytoplasmic mRNA processing body Source: MGI
  • focal adhesion Source: UniProtKB
  • nucleus Source: UniProtKB
  • RISC complex Source: MGI
  • transcription factor complex Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cytoplasm, Nucleus

Pathology & Biotechi

Keywords - Diseasei

Tumor suppressor

Organism-specific databases

DisGeNETi8994.
OpenTargetsiENSG00000144791.
PharmGKBiPA30385.

Polymorphism and mutation databases

BioMutaiLIMD1.
DMDMi47605932.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000758011 – 676LIM domain-containing protein 1Add BLAST676

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei145PhosphoserineCombined sources1
Modified residuei233PhosphoserineCombined sources1
Modified residuei239PhosphoserineBy similarity1
Modified residuei272PhosphoserineCombined sources1
Modified residuei277PhosphoserineCombined sources1
Modified residuei304PhosphoserineCombined sources1
Modified residuei316PhosphoserineBy similarity1
Modified residuei421PhosphoserineCombined sources1
Modified residuei424PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated during mitosis.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9UGP4.
MaxQBiQ9UGP4.
PaxDbiQ9UGP4.
PeptideAtlasiQ9UGP4.
PRIDEiQ9UGP4.

PTM databases

iPTMnetiQ9UGP4.
PhosphoSitePlusiQ9UGP4.

Expressioni

Tissue specificityi

Expressed in normal and breast cancer tissues (at protein level). Ubiquitous.2 Publications

Inductioni

Down-regulated in lung cancer.1 Publication

Gene expression databases

BgeeiENSG00000144791.
CleanExiHS_LIMD1.
ExpressionAtlasiQ9UGP4. baseline and differential.
GenevisibleiQ9UGP4. HS.

Interactioni

Subunit structurei

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 1 and isoform 3 of VHL. Interacts (via LIM domains) with SNAI1 (via SNAG domain).By similarity6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ORFQ9Q2G45EBI-2652871,EBI-6248094From a different organism.

Protein-protein interaction databases

BioGridi114475. 53 interactors.
IntActiQ9UGP4. 18 interactors.
MINTiMINT-1193166.
STRINGi9606.ENSP00000273317.

Structurei

3D structure databases

ProteinModelPortaliQ9UGP4.
SMRiQ9UGP4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini470 – 531LIM zinc-binding 1PROSITE-ProRule annotationAdd BLAST62
Domaini535 – 595LIM zinc-binding 2PROSITE-ProRule annotationAdd BLAST61
Domaini595 – 664LIM zinc-binding 3PROSITE-ProRule annotationAdd BLAST70

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni54 – 134Mediates nuclear exportAdd BLAST81
Regioni186 – 260Interaction with EGLN1/PHD2Add BLAST75
Regioni404 – 442Interaction with RB11 PublicationAdd BLAST39
Regioni472 – 676Necessary for nuclear localizationAdd BLAST205

Sequence similaritiesi

Belongs to the zyxin/ajuba family.Curated
Contains 3 LIM zinc-binding domains.PROSITE-ProRule annotation

Keywords - Domaini

LIM domain, Repeat

Phylogenomic databases

eggNOGiKOG1701. Eukaryota.
ENOG410Y3GP. LUCA.
GeneTreeiENSGT00760000119039.
HOGENOMiHOG000072700.
HOVERGENiHBG052327.
InParanoidiQ9UGP4.
KOiK16682.
OMAiPLNHRQL.
OrthoDBiEOG091G057U.
PhylomeDBiQ9UGP4.
TreeFamiTF320310.

Family and domain databases

Gene3Di2.10.110.10. 3 hits.
InterProiIPR028734. LIMD1.
IPR001781. Znf_LIM.
[Graphical view]
PANTHERiPTHR24219:SF3. PTHR24219:SF3. 1 hit.
PfamiPF00412. LIM. 3 hits.
[Graphical view]
SMARTiSM00132. LIM. 3 hits.
[Graphical view]
PROSITEiPS00478. LIM_DOMAIN_1. 2 hits.
PS50023. LIM_DOMAIN_2. 3 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9UGP4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDKYDDLGLE ASKFIEDLNM YEASKDGLFR VDKGAGNNPE FEETRRVFAT
60 70 80 90 100
KMAKIHLQQQ QQQLLQEETL PRGSRGPVNG GGRLGPQARW EVVGSKLTVD
110 120 130 140 150
GAAKPPLAAS TGAPGAVTTL AAGQPPYPPQ EQRSRPYLHG TRHGSQDCGS
160 170 180 190 200
RESLATSEMS AFHQPGPCED PSCLTHGDYY DNLSLASPKW GDKPGVSPSI
210 220 230 240 250
GLSVGSGWPS SPGSDPPLPK PCGDHPLNHR QLSLSSSRSS EGSLGGQNSG
260 270 280 290 300
IGGRSSEKPT GLWSTASSQR VSPGLPSPNL ENGAPAVGPV QPRTPSVSAP
310 320 330 340 350
LALSCPRQGG LPRSNSGLGG EVSGVMSKPN VDPQPWFQDG PKSYLSSSAP
360 370 380 390 400
SSSPAGLDGS QQGAVPGLGP KPGCTDLGTG PKLSPTSLVH PVMSTLPELS
410 420 430 440 450
CKEGPLGWSS DGSLGSVLLD SPSSPRVRLP CQPLVPGPEL RPSAAELKLE
460 470 480 490 500
ALTQRLEREM DAHPKADYFG ACVKCSKGVF GAGQACQAMG NLYHDTCFTC
510 520 530 540 550
AACSRKLRGK AFYFVNGKVF CEEDFLYSGF QQSADRCFLC GHLIMDMILQ
560 570 580 590 600
ALGKSYHPGC FRCVICNECL DGVPFTVDSE NKIYCVRDYH KVLAPKCAAC
610 620 630 640 650
GLPILPPEGS DETIRVVSMD RDYHVECYHC EDCGLELNDE DGHRCYPLED
660 670
HLFCHSCHVK RLEKRPSSTA LHQHHF
Length:676
Mass (Da):72,190
Last modified:May 1, 2000 - v1
Checksum:i085DF06F047B49E6
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05014736G → D.Corresponds to variant rs2578662dbSNPEnsembl.1
Natural variantiVAR_021993415G → R.Corresponds to variant rs3733113dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS2729.1.
RefSeqiNP_055055.1. NM_014240.2.
UniGeneiHs.193370.
Hs.621057.

Genome annotation databases

EnsembliENST00000273317; ENSP00000273317; ENSG00000144791.
GeneIDi8994.
KEGGihsa:8994.
UCSCiuc003coq.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS2729.1.
RefSeqiNP_055055.1. NM_014240.2.
UniGeneiHs.193370.
Hs.621057.

3D structure databases

ProteinModelPortaliQ9UGP4.
SMRiQ9UGP4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114475. 53 interactors.
IntActiQ9UGP4. 18 interactors.
MINTiMINT-1193166.
STRINGi9606.ENSP00000273317.

PTM databases

iPTMnetiQ9UGP4.
PhosphoSitePlusiQ9UGP4.

Polymorphism and mutation databases

BioMutaiLIMD1.
DMDMi47605932.

Proteomic databases

EPDiQ9UGP4.
MaxQBiQ9UGP4.
PaxDbiQ9UGP4.
PeptideAtlasiQ9UGP4.
PRIDEiQ9UGP4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000273317; ENSP00000273317; ENSG00000144791.
GeneIDi8994.
KEGGihsa:8994.
UCSCiuc003coq.4. human.

Organism-specific databases

CTDi8994.
DisGeNETi8994.
GeneCardsiLIMD1.
HGNCiHGNC:6612. LIMD1.
MIMi604543. gene.
neXtProtiNX_Q9UGP4.
OpenTargetsiENSG00000144791.
PharmGKBiPA30385.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1701. Eukaryota.
ENOG410Y3GP. LUCA.
GeneTreeiENSGT00760000119039.
HOGENOMiHOG000072700.
HOVERGENiHBG052327.
InParanoidiQ9UGP4.
KOiK16682.
OMAiPLNHRQL.
OrthoDBiEOG091G057U.
PhylomeDBiQ9UGP4.
TreeFamiTF320310.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000144791-MONOMER.
ReactomeiR-HSA-1234176. Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.

Miscellaneous databases

ChiTaRSiLIMD1. human.
GeneWikiiLIMD1.
GenomeRNAii8994.
PROiQ9UGP4.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000144791.
CleanExiHS_LIMD1.
ExpressionAtlasiQ9UGP4. baseline and differential.
GenevisibleiQ9UGP4. HS.

Family and domain databases

Gene3Di2.10.110.10. 3 hits.
InterProiIPR028734. LIMD1.
IPR001781. Znf_LIM.
[Graphical view]
PANTHERiPTHR24219:SF3. PTHR24219:SF3. 1 hit.
PfamiPF00412. LIM. 3 hits.
[Graphical view]
SMARTiSM00132. LIM. 3 hits.
[Graphical view]
PROSITEiPS00478. LIM_DOMAIN_1. 2 hits.
PS50023. LIM_DOMAIN_2. 3 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiLIMD1_HUMAN
AccessioniPrimary (citable) accession number: Q9UGP4
Secondary accession number(s): Q17RQ1, Q9BQQ9, Q9NQ47
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 24, 2004
Last sequence update: May 1, 2000
Last modified: November 30, 2016
This is version 144 of the entry and version 1 of the sequence. [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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.