UniProtKB - Q86UE4 (LYRIC_HUMAN)
Protein
Protein LYRIC
Gene
MTDH
Organism
Homo sapiens (Human)
Status
Functioni
Downregulates SLC1A2/EAAT2 promoter activity when expressed ectopically. Activates the nuclear factor kappa-B (NF-kappa-B) transcription factor. Promotes anchorage-independent growth of immortalized melanocytes and astrocytes which is a key component in tumor cell expansion. Promotes lung metastasis and also has an effect on bone and brain metastasis, possibly by enhancing the seeding of tumor cells to the target organ endothelium. Induces chemoresistance.4 Publications
Miscellaneous
Knockdown significantly reduces the adhesion of cancer cells to lung microvascular endothelial cells and the reciprocal effect is observed following overexpression.
Caution
Was originally thought to be a type II membrane protein but this is inconsistent with the results of multiple phosphorylation studies because this topology would locate the phosphorylation sites in the lumen or extracellularly rather than in the cytoplasm.1 Publication
GO - Molecular functioni
- double-stranded RNA binding Source: MGI
- NF-kappaB binding Source: UniProtKB
- RNA binding Source: UniProtKB
- RNA polymerase II transcription factor binding Source: UniProtKB
- transcription coactivator activity Source: UniProtKB
- transcription coregulator activity Source: GO_Central
GO - Biological processi
- bicellular tight junction assembly Source: Ensembl
- lipopolysaccharide-mediated signaling pathway Source: UniProtKB
- negative regulation of apoptotic process Source: UniProtKB
- negative regulation of transcription by RNA polymerase II Source: UniProtKB
- positive regulation of angiogenesis Source: UniProtKB
- positive regulation of autophagy Source: UniProtKB
- positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
- positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
- positive regulation of protein kinase B signaling Source: UniProtKB
- regulation of transcription by RNA polymerase II Source: GO_Central
Enzyme and pathway databases
PathwayCommonsi | Q86UE4 |
Names & Taxonomyi
Protein namesi | Recommended name: Protein LYRICAlternative name(s): 3D3/LYRIC Astrocyte elevated gene-1 protein Short name: AEG-1 Lysine-rich CEACAM1 co-isolated protein Metadherin Metastasis adhesion protein |
Gene namesi | Name:MTDH Synonyms:AEG1, LYRIC |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:29608, MTDH |
MIMi | 610323, gene |
neXtProti | NX_Q86UE4 |
VEuPathDBi | HostDB:ENSG00000147649.9 |
Subcellular locationi
Endoplasmic reticulum
Nucleus
- Nucleus membrane By similarity; Single-pass membrane protein By similarity
- nucleolus By similarity
Other locations
- tight junction By similarity
- perinuclear region
Note: In epithelial cells, recruited to tight junctions (TJ) during the maturation of the TJ complexes. A nucleolar staining may be due to nuclear targeting of an isoform lacking the transmembrane domain (By similarity). TNF-alpha causes translocation from the cytoplasm to the nucleus.By similarity
Endoplasmic reticulum
- endoplasmic reticulum Source: UniProtKB
- endoplasmic reticulum membrane Source: UniProtKB
Nucleus
- fibrillar center Source: HPA
- nuclear body Source: UniProtKB
- nuclear membrane Source: UniProtKB-SubCell
- nucleus Source: UniProtKB
Plasma Membrane
- apical plasma membrane Source: UniProtKB
Other locations
- bicellular tight junction Source: UniProtKB
- cytoplasm Source: UniProtKB
- integral component of membrane Source: UniProtKB-KW
- intercellular canaliculus Source: UniProtKB
- perinuclear region of cytoplasm Source: UniProtKB
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 48 | LumenalSequence analysisAdd BLAST | 48 | |
Transmembranei | 49 – 69 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 70 – 582 | CytoplasmicSequence analysisAdd BLAST | 513 |
Keywords - Cellular componenti
Cell junction, Cytoplasm, Endoplasmic reticulum, Membrane, Nucleus, Tight junctionPathology & Biotechi
Organism-specific databases
DisGeNETi | 92140 |
OpenTargetsi | ENSG00000147649 |
PharmGKBi | PA142671307 |
Miscellaneous databases
Pharosi | Q86UE4, Tbio |
Genetic variation databases
BioMutai | MTDH |
DMDMi | 56749088 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000084533 | 1 – 582 | Protein LYRICAdd BLAST | 582 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 143 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 180 | PhosphoserineCombined sources | 1 | |
Modified residuei | 216 | PhosphoserineCombined sources | 1 | |
Modified residuei | 251 | PhosphoserineCombined sources | 1 | |
Modified residuei | 264 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 298 | PhosphoserineCombined sources | 1 | |
Modified residuei | 306 | PhosphoserineCombined sources | 1 | |
Modified residuei | 308 | PhosphoserineCombined sources | 1 | |
Modified residuei | 311 | PhosphoserineCombined sources | 1 | |
Modified residuei | 323 | PhosphoserineCombined sources | 1 | |
Modified residuei | 339 | PhosphoserineCombined sources | 1 | |
Modified residuei | 344 | PhosphoserineCombined sources | 1 | |
Modified residuei | 369 | PhosphoserineCombined sources | 1 | |
Modified residuei | 415 | PhosphoserineCombined sources | 1 | |
Modified residuei | 426 | PhosphoserineCombined sources | 1 | |
Modified residuei | 457 | PhosphoserineBy similarity | 1 | |
Modified residuei | 458 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 478 | PhosphoserineCombined sources | 1 | |
Modified residuei | 494 | PhosphoserineCombined sources | 1 | |
Modified residuei | 496 | PhosphoserineCombined sources | 1 | |
Modified residuei | 568 | PhosphoserineCombined sources | 1 |
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
EPDi | Q86UE4 |
jPOSTi | Q86UE4 |
MassIVEi | Q86UE4 |
MaxQBi | Q86UE4 |
PaxDbi | Q86UE4 |
PeptideAtlasi | Q86UE4 |
PRIDEi | Q86UE4 |
ProteomicsDBi | 69809 |
TopDownProteomicsi | Q86UE4 |
PTM databases
iPTMneti | Q86UE4 |
PhosphoSitePlusi | Q86UE4 |
SwissPalmi | Q86UE4 |
Expressioni
Tissue specificityi
Widely expressed with highest levels in muscle-dominating organs such as skeletal muscle, heart, tongue and small intestine and in endocrine glands such as thyroid and adrenal gland. Overexpressed in various cancers including breast, brain, prostate, melanoma and glioblastoma multiforme.1 Publication
Inductioni
By TNF (at protein level). By HIV-1 infection of primary fetal astrocytes.2 Publications
Gene expression databases
Bgeei | ENSG00000147649, Expressed in calcaneal tendon and 255 other tissues |
ExpressionAtlasi | Q86UE4, baseline and differential |
Genevisiblei | Q86UE4, HS |
Organism-specific databases
HPAi | ENSG00000147649, Low tissue specificity |
Interactioni
Subunit structurei
Interacts with BCCIP, CREBBP/CBP and RELA/p65.
3 PublicationsBinary interactionsi
Hide detailsQ86UE4
With | #Exp. | IntAct |
---|---|---|
AGO2 [Q9UKV8] | 3 | EBI-1046588,EBI-528269 |
CREBBP [Q92793] | 2 | EBI-1046588,EBI-81215 |
SND1 [Q7KZF4] | 5 | EBI-1046588,EBI-1044112 |
GO - Molecular functioni
- NF-kappaB binding Source: UniProtKB
- RNA polymerase II transcription factor binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 124913, 299 interactors |
IntActi | Q86UE4, 36 interactors |
MINTi | Q86UE4 |
STRINGi | 9606.ENSP00000338235 |
Miscellaneous databases
RNActi | Q86UE4, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 71 | Activation of NF-kappa-BAdd BLAST | 71 | |
Regioni | 72 – 169 | Interaction with BCCIP1 PublicationAdd BLAST | 98 | |
Regioni | 101 – 205 | Interaction with RELA1 PublicationAdd BLAST | 105 | |
Regioni | 381 – 443 | Lung-homing for mammary tumorsBy similarityAdd BLAST | 63 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 59 – 67 | Poly-Leu | 9 | |
Compositional biasi | 441 – 451 | Poly-LysAdd BLAST | 11 | |
Compositional biasi | 573 – 577 | Poly-Lys | 5 |
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | ENOG502QU7P, Eukaryota |
GeneTreei | ENSGT00940000154181 |
HOGENOMi | CLU_034908_0_0_1 |
InParanoidi | Q86UE4 |
OMAi | HIDDEWS |
OrthoDBi | 1432988at2759 |
PhylomeDBi | Q86UE4 |
TreeFami | TF331350 |
Family and domain databases
InterProi | View protein in InterPro IPR031402, LYRIC |
Pfami | View protein in Pfam PF15686, LYRIC, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 4 potential isoforms that are computationally mapped.Show allAlign All
Q86UE4-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MAARSWQDEL AQQAEEGSAR LREMLSVGLG FLRTELGLDL GLEPKRYPGW
60 70 80 90 100
VILVGTGALG LLLLFLLGYG WAAACAGARK KRRSPPRKRE EAAAVPAAAP
110 120 130 140 150
DDLALLKNLR SEEQKKKNRK KLSEKPKPNG RTVEVAEGEA VRTPQSVTAK
160 170 180 190 200
QPPEIDKKNE KSKKNKKKSK SDAKAVQNSS RHDGKEVDEG AWETKISHRE
210 220 230 240 250
KRQQRKRDKV LTDSGSLDST IPGIENTITV TTEQLTTASF PVGSKKNKGD
260 270 280 290 300
SHLNVQVSNF KSGKGDSTLQ VSSGLNENLT VNGGGWNEKS VKLSSQISAG
310 320 330 340 350
EEKWNSVSPA SAGKRKTEPS AWSQDTGDAN TNGKDWGRSW SDRSIFSGIG
360 370 380 390 400
STAEPVSQST TSDYQWDVSR NQPYIDDEWS GLNGLSSADP NSDWNAPAEE
410 420 430 440 450
WGNWVDEERA SLLKSQEPIP DDQKVSDDDK EKGEGALPTG KSKKKKKKKK
460 470 480 490 500
KQGEDNSTAQ DTEELEKEIR EDLPVNTSKT RPKQEKAFSL KTISTSDPAE
510 520 530 540 550
VLVKNSQPIK TLPPATSTEP SVILSKSDSD KSSSQVPPIL QETDKSKSNT
560 570 580
KQNSVPPSQT KSETSWESPK QIKKKKKARR ET
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketE5RJU9 | E5RJU9_HUMAN | Protein LYRIC | MTDH | 526 | Annotation score: | ||
H0YBJ8 | H0YBJ8_HUMAN | Protein LYRIC | MTDH | 188 | Annotation score: | ||
H0YB56 | H0YB56_HUMAN | Protein LYRIC | MTDH | 224 | Annotation score: | ||
H0YBE0 | H0YBE0_HUMAN | Protein LYRIC | MTDH | 60 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 78 | A → S in AAH09324 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 78 | A → S in AAH45642 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 145 | Q → H in AAX84832 (Ref. 4) Curated | 1 | |
Sequence conflicti | 543 | T → A in AAX84832 (Ref. 4) Curated | 1 | |
Sequence conflicti | 581 | E → D in AAX84832 (Ref. 4) Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_054661 | 317 | T → A1 PublicationCorresponds to variant dbSNP:rs17854374Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF501310 mRNA Translation: AAP30791.1 AY082966 mRNA Translation: AAL92861.1 AF411226 mRNA Translation: AAO65771.1 AY974040 mRNA Translation: AAX84832.1 BC009324 mRNA Translation: AAH09324.1 BC014977 mRNA Translation: AAH14977.1 BC045642 mRNA Translation: AAH45642.1 AK000745 mRNA No translation available. |
CCDSi | CCDS6274.1 |
RefSeqi | NP_848927.2, NM_178812.3 |
Genome annotation databases
Ensembli | ENST00000336273; ENSP00000338235; ENSG00000147649 |
GeneIDi | 92140 |
KEGGi | hsa:92140 |
UCSCi | uc003yhz.4, human |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF501310 mRNA Translation: AAP30791.1 AY082966 mRNA Translation: AAL92861.1 AF411226 mRNA Translation: AAO65771.1 AY974040 mRNA Translation: AAX84832.1 BC009324 mRNA Translation: AAH09324.1 BC014977 mRNA Translation: AAH14977.1 BC045642 mRNA Translation: AAH45642.1 AK000745 mRNA No translation available. |
CCDSi | CCDS6274.1 |
RefSeqi | NP_848927.2, NM_178812.3 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
4QMG | X-ray | 2.70 | F/G/H/I/J | 386-407 | [»] | |
SMRi | Q86UE4 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 124913, 299 interactors |
IntActi | Q86UE4, 36 interactors |
MINTi | Q86UE4 |
STRINGi | 9606.ENSP00000338235 |
PTM databases
iPTMneti | Q86UE4 |
PhosphoSitePlusi | Q86UE4 |
SwissPalmi | Q86UE4 |
Genetic variation databases
BioMutai | MTDH |
DMDMi | 56749088 |
Proteomic databases
EPDi | Q86UE4 |
jPOSTi | Q86UE4 |
MassIVEi | Q86UE4 |
MaxQBi | Q86UE4 |
PaxDbi | Q86UE4 |
PeptideAtlasi | Q86UE4 |
PRIDEi | Q86UE4 |
ProteomicsDBi | 69809 |
TopDownProteomicsi | Q86UE4 |
Protocols and materials databases
Antibodypediai | 2507, 377 antibodies |
DNASUi | 92140 |
Genome annotation databases
Ensembli | ENST00000336273; ENSP00000338235; ENSG00000147649 |
GeneIDi | 92140 |
KEGGi | hsa:92140 |
UCSCi | uc003yhz.4, human |
Organism-specific databases
CTDi | 92140 |
DisGeNETi | 92140 |
GeneCardsi | MTDH |
HGNCi | HGNC:29608, MTDH |
HPAi | ENSG00000147649, Low tissue specificity |
MIMi | 610323, gene |
neXtProti | NX_Q86UE4 |
OpenTargetsi | ENSG00000147649 |
PharmGKBi | PA142671307 |
VEuPathDBi | HostDB:ENSG00000147649.9 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502QU7P, Eukaryota |
GeneTreei | ENSGT00940000154181 |
HOGENOMi | CLU_034908_0_0_1 |
InParanoidi | Q86UE4 |
OMAi | HIDDEWS |
OrthoDBi | 1432988at2759 |
PhylomeDBi | Q86UE4 |
TreeFami | TF331350 |
Enzyme and pathway databases
PathwayCommonsi | Q86UE4 |
Miscellaneous databases
BioGRID-ORCSi | 92140, 3 hits in 879 CRISPR screens |
ChiTaRSi | MTDH, human |
GeneWikii | MTDH |
GenomeRNAii | 92140 |
Pharosi | Q86UE4, Tbio |
PROi | PR:Q86UE4 |
RNActi | Q86UE4, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000147649, Expressed in calcaneal tendon and 255 other tissues |
ExpressionAtlasi | Q86UE4, baseline and differential |
Genevisiblei | Q86UE4, HS |
Family and domain databases
InterProi | View protein in InterPro IPR031402, LYRIC |
Pfami | View protein in Pfam PF15686, LYRIC, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | LYRIC_HUMAN | |
Accessioni | Q86UE4Primary (citable) accession number: Q86UE4 Secondary accession number(s): Q05DH2 Q8TCX3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 21, 2004 |
Last sequence update: | December 21, 2004 | |
Last modified: | February 10, 2021 | |
This is version 154 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 8
Human chromosome 8: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references