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Protein

Protein LYRIC

Gene

MTDH

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

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

GO - Molecular functioni

  • double-stranded RNA binding Source: MGI
  • NF-kappaB binding Source: UniProtKB
  • poly(A) RNA binding Source: UniProtKB
  • RNA polymerase II transcription factor binding Source: UniProtKB
  • transcription coactivator activity Source: UniProtKB

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 from RNA polymerase II promoter 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
Complete GO annotation...

Names & Taxonomyi

Protein namesi
Recommended name:
Protein LYRIC
Alternative 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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:29608. MTDH.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 48LumenalSequence analysisAdd BLAST48
Transmembranei49 – 69HelicalSequence analysisAdd BLAST21
Topological domaini70 – 582CytoplasmicSequence analysisAdd BLAST513

GO - Cellular componenti

  • apical plasma membrane Source: UniProtKB
  • bicellular tight junction Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • endoplasmic reticulum Source: UniProtKB
  • endoplasmic reticulum membrane Source: UniProtKB
  • integral component of membrane Source: UniProtKB-KW
  • intercellular canaliculus Source: UniProtKB
  • nuclear body Source: UniProtKB
  • nuclear membrane Source: UniProtKB-SubCell
  • nucleolus Source: HPA
  • nucleus Source: UniProtKB
  • perinuclear region of cytoplasm Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cytoplasm, Endoplasmic reticulum, Membrane, Nucleus, Tight junction

Pathology & Biotechi

Organism-specific databases

DisGeNETi92140.
OpenTargetsiENSG00000147649.
PharmGKBiPA142671307.

Polymorphism and mutation databases

BioMutaiMTDH.
DMDMi56749088.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000845331 – 582Protein LYRICAdd BLAST582

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei143PhosphothreonineCombined sources1
Modified residuei180PhosphoserineCombined sources1
Modified residuei216PhosphoserineCombined sources1
Modified residuei251PhosphoserineCombined sources1
Modified residuei264N6-acetyllysineBy similarity1
Modified residuei298PhosphoserineCombined sources1
Modified residuei306PhosphoserineCombined sources1
Modified residuei308PhosphoserineCombined sources1
Modified residuei311PhosphoserineCombined sources1
Modified residuei323PhosphoserineCombined sources1
Modified residuei339PhosphoserineCombined sources1
Modified residuei344PhosphoserineCombined sources1
Modified residuei369PhosphoserineCombined sources1
Modified residuei415PhosphoserineCombined sources1
Modified residuei426PhosphoserineCombined sources1
Modified residuei457PhosphoserineBy similarity1
Modified residuei458PhosphothreonineCombined sources1
Modified residuei478PhosphoserineCombined sources1
Modified residuei494PhosphoserineCombined sources1
Modified residuei496PhosphoserineCombined sources1
Modified residuei568PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ86UE4.
MaxQBiQ86UE4.
PaxDbiQ86UE4.
PeptideAtlasiQ86UE4.
PRIDEiQ86UE4.
TopDownProteomicsiQ86UE4.

PTM databases

iPTMnetiQ86UE4.
PhosphoSitePlusiQ86UE4.
SwissPalmiQ86UE4.

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

BgeeiENSG00000147649.
CleanExiHS_MTDH.
ExpressionAtlasiQ86UE4. baseline and differential.
GenevisibleiQ86UE4. HS.

Organism-specific databases

HPAiCAB068204.
CAB068205.
HPA010932.
HPA015104.

Interactioni

Subunit structurei

Interacts with BCCIP, CREBBP/CBP and RELA/p65.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
AGO2Q9UKV83EBI-1046588,EBI-528269
CREBBPQ927932EBI-1046588,EBI-81215
SND1Q7KZF44EBI-1046588,EBI-1044112

GO - Molecular functioni

  • NF-kappaB binding Source: UniProtKB
  • RNA polymerase II transcription factor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi124913. 28 interactors.
IntActiQ86UE4. 15 interactors.
STRINGi9606.ENSP00000338235.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4QMGX-ray2.70F/G/H/I/J386-407[»]
ProteinModelPortaliQ86UE4.
SMRiQ86UE4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 71Activation of NF-kappa-BAdd BLAST71
Regioni72 – 169Interaction with BCCIP1 PublicationAdd BLAST98
Regioni101 – 205Interaction with RELA1 PublicationAdd BLAST105
Regioni381 – 443Lung-homing for mammary tumorsBy similarityAdd BLAST63

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi59 – 67Poly-Leu9
Compositional biasi441 – 451Poly-LysAdd BLAST11
Compositional biasi573 – 577Poly-Lys5

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IIV9. Eukaryota.
ENOG410YF4D. LUCA.
GeneTreeiENSGT00390000004343.
HOGENOMiHOG000113417.
HOVERGENiHBG052379.
InParanoidiQ86UE4.
OMAiDWGRSWS.
OrthoDBiEOG091G0889.
PhylomeDBiQ86UE4.
TreeFamiTF331350.

Family and domain databases

InterProiIPR031402. LYRIC.
[Graphical view]
PfamiPF15686. LYRIC. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q86UE4-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:582
Mass (Da):63,837
Last modified:December 21, 2004 - v2
Checksum:i2460D6218FD3A4C4
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti78A → S in AAH09324 (PubMed:15489334).Curated1
Sequence conflicti78A → S in AAH45642 (PubMed:15489334).Curated1
Sequence conflicti145Q → H in AAX84832 (Ref. 4) Curated1
Sequence conflicti543T → A in AAX84832 (Ref. 4) Curated1
Sequence conflicti581E → D in AAX84832 (Ref. 4) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_054661317T → A.1 PublicationCorresponds to variant rs17854374dbSNPEnsembl.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.
CCDSiCCDS6274.1.
RefSeqiNP_848927.2. NM_178812.3.
UniGeneiHs.377155.

Genome annotation databases

EnsembliENST00000336273; ENSP00000338235; ENSG00000147649.
GeneIDi92140.
KEGGihsa:92140.
UCSCiuc003yhz.4. human.

Keywords - Coding sequence diversityi

Polymorphism

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.
CCDSiCCDS6274.1.
RefSeqiNP_848927.2. NM_178812.3.
UniGeneiHs.377155.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4QMGX-ray2.70F/G/H/I/J386-407[»]
ProteinModelPortaliQ86UE4.
SMRiQ86UE4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124913. 28 interactors.
IntActiQ86UE4. 15 interactors.
STRINGi9606.ENSP00000338235.

PTM databases

iPTMnetiQ86UE4.
PhosphoSitePlusiQ86UE4.
SwissPalmiQ86UE4.

Polymorphism and mutation databases

BioMutaiMTDH.
DMDMi56749088.

Proteomic databases

EPDiQ86UE4.
MaxQBiQ86UE4.
PaxDbiQ86UE4.
PeptideAtlasiQ86UE4.
PRIDEiQ86UE4.
TopDownProteomicsiQ86UE4.

Protocols and materials databases

DNASUi92140.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000336273; ENSP00000338235; ENSG00000147649.
GeneIDi92140.
KEGGihsa:92140.
UCSCiuc003yhz.4. human.

Organism-specific databases

CTDi92140.
DisGeNETi92140.
GeneCardsiMTDH.
HGNCiHGNC:29608. MTDH.
HPAiCAB068204.
CAB068205.
HPA010932.
HPA015104.
MIMi610323. gene.
neXtProtiNX_Q86UE4.
OpenTargetsiENSG00000147649.
PharmGKBiPA142671307.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IIV9. Eukaryota.
ENOG410YF4D. LUCA.
GeneTreeiENSGT00390000004343.
HOGENOMiHOG000113417.
HOVERGENiHBG052379.
InParanoidiQ86UE4.
OMAiDWGRSWS.
OrthoDBiEOG091G0889.
PhylomeDBiQ86UE4.
TreeFamiTF331350.

Miscellaneous databases

ChiTaRSiMTDH. human.
GeneWikiiMTDH.
GenomeRNAii92140.
PROiQ86UE4.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000147649.
CleanExiHS_MTDH.
ExpressionAtlasiQ86UE4. baseline and differential.
GenevisibleiQ86UE4. HS.

Family and domain databases

InterProiIPR031402. LYRIC.
[Graphical view]
PfamiPF15686. LYRIC. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiLYRIC_HUMAN
AccessioniPrimary (citable) accession number: Q86UE4
Secondary accession number(s): Q05DH2
, Q52QU9, Q6PK07, Q8TCX3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 21, 2004
Last sequence update: December 21, 2004
Last modified: November 2, 2016
This is version 125 of the entry and version 2 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

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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

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.