Q9UGP4 (LIMD1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
LIM domain-containing protein 1

Gene names

Name:

LIMD1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	676 AA.
Sequence status	Complete.
Protein existence	Evidence 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.12 Ref.13 Ref.15 Ref.18
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, EIF2C1, EIF2C2, 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). Ref.5 Ref.6 Ref.8 Ref.12 Ref.13 Ref.18
Subcellular location	Cytoplasm. Nucleus. Cytoplasm › P-body. Cell junction › adherens junction. Cell junction › focal adhesion. Note: Shuttles between cytoplasm and nucleus but is localized predominantly to the cytoplasm. Found in the nucleus but not nucleoli. Co-localizes 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.12 Ref.13
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 process	RNA-mediated gene silencing Transcription Transcription regulation
Cellular component	Cell junction Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Disease	Tumor suppressor
Domain	LIM domain Repeat
Ligand	Metal-binding Zinc
Molecular function	Repressor
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell migration Inferred from mutant phenotype Ref.15. Source: UniProtKB cytoplasmic mRNA processing body assembly Inferred from mutant phenotype Ref.13. Source: MGI cytoskeleton organization Inferred from mutant phenotype Ref.15. Source: UniProtKB gene silencing by miRNA Inferred from mutant phenotype Ref.13. Source: MGI multicellular organismal development Traceable author statement Ref.1. Source: ProtInc negative regulation of canonical Wnt receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of hippo signaling cascade Inferred from direct assay Ref.12. Source: UniProtKB negative regulation of osteoblast differentiation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of transcription, DNA-dependent 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.13. Source: UniProtKB regulation of cell shape Inferred from mutant phenotype Ref.15. Source: UniProtKB response to hypoxia Inferred from direct assay Ref.18. Source: UniProtKB signal transduction Traceable author statement Ref.1. Source: ProtInc transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	RNA-induced silencing complex Inferred from direct assay Ref.13. Source: MGI cytoplasmic mRNA processing body Inferred from direct assay Ref.13. Source: MGI focal adhesion Inferred from direct assay Ref.7. Source: UniProtKB nucleus Inferred from direct assay Ref.5Ref.7. Source: UniProtKB
Molecular_function	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
ORF	Q9Q2G4	5	EBI-2652871,EBI-6248094	From a different organism.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 676	676	LIM domain-containing protein 1		PRO_0000075801
Regions
	Domain	470 – 531	62	LIM zinc-binding 1
	Domain	535 – 595	61	LIM zinc-binding 2
	Domain	595 – 664	70	LIM zinc-binding 3
	Region	54 – 134	81	Mediates nuclear export
	Region	186 – 260	75	Interaction with EGLN1/PHD2
	Region	404 – 442	39	Interaction with RB1
	Region	472 – 676	205	Necessary for nuclear localization
Amino acid modifications
	Modified residue	272	1	Phosphoserine Ref.4 Ref.14
	Modified residue	277	1	Phosphoserine Ref.4 Ref.14
	Modified residue	304	1	Phosphoserine Ref.10
	Modified residue	421	1	Phosphoserine Ref.10 Ref.14
	Modified residue	424	1	Phosphoserine Ref.10 Ref.11
Natural variations
	Natural variant	36	1	G → D. Corresponds to variant rs2578662 [ dbSNP | Ensembl ].		VAR_050147
	Natural variant	415	1	G → R. Corresponds to variant rs3733113 [ dbSNP | Ensembl ].		VAR_021993

Sequences

	Sequence		Length	Mass (Da)
	Q9UGP4 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 085DF06F047B49E6	FASTA	676	72,190
	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

References

	« Hide 'large scale' referencesShow '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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"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, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[12]	"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.
[13]	"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; EIF2C1; EIF2C2; DCP2 AND DDX6.
[14]	"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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[15]	"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.
[16]	"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].
[17]	"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].
[18]	"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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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.
IPI	IPI00003369.
RefSeq	NP_055055.1. NM_014240.2.
UniGene	Hs.193370. Hs.621057.
3D structure databases
ProteinModelPortal	Q9UGP4.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9UGP4. 4 interactions.
MINT	MINT-1193166.
STRING	9606.ENSP00000273317.
PTM databases
PhosphoSite	Q9UGP4.
Polymorphism databases
DMDM	47605932.
Proteomic databases
PaxDb	Q9UGP4.
PRIDE	Q9UGP4.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000273317; ENSP00000273317; ENSG00000144791.
GeneID	8994.
KEGG	hsa:8994.
UCSC	uc003coq.3. human.
Organism-specific databases
CTD	8994.
GeneCards	GC03P045611.
HGNC	HGNC:6612. LIMD1.
MIM	604543. gene.
neXtProt	NX_Q9UGP4.
PharmGKB	PA30385.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG331290.
HOGENOM	HOG000072700.
HOVERGEN	HBG052327.
InParanoid	Q9UGP4.
KO	K16682.
OMA	SLASPKW.
PhylomeDB	Q9UGP4.
Gene expression databases
ArrayExpress	Q9UGP4.
Bgee	Q9UGP4.
CleanEx	HS_LIMD1.
Genevestigator	Q9UGP4.
GermOnline	ENSG00000144791. Homo sapiens.
Family and domain databases
Gene3D	2.10.110.10. 3 hits.
InterPro	IPR001781. Znf_LIM. [Graphical view]
Pfam	PF00412. LIM. 3 hits. [Graphical view]
SMART	SM00132. LIM. 3 hits. [Graphical view]
PROSITE	PS00478. LIM_DOMAIN_1. 2 hits. PS50023. LIM_DOMAIN_2. 3 hits. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	LIMD1. human.
GenomeRNAi	8994.
NextBio	33727.
SOURCE	Search...

Entry information

Entry name

LIMD1_HUMAN

Accession

Primary (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:	May 29, 2013
This is version 110 of the entry and version 1 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.