Q86UE4 (LYRIC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	MTDH
Synonyms:	AEG1, LYRIC

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	582 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.3 Ref.9 Ref.12 Ref.15
Subunit structure	Interacts with BCCIP, CREBBP/CBP and RELA/p65. Ref.9 Ref.11 Ref.12
Subcellular location	Endoplasmic reticulum membrane; Single-pass membrane protein. Nucleus membrane; Single-pass membrane protein By similarity. Cell junction › tight junction By similarity. Nucleus › nucleolus By similarity. Cytoplasm › 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. Ref.1 Ref.2 Ref.3
Tissue specificity	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. Ref.3
Induction	By TNF (at protein level). By HIV-1 infection of primary fetal astrocytes. Ref.3 Ref.9
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 (Ref.8) 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.

Ontologies

Keywords
Cellular component	Cell junction Cytoplasm Endoplasmic reticulum Membrane Nucleus Tight junction
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	lipopolysaccharide-mediated signaling pathway Inferred from mutant phenotype PubMed 19740331. Source: UniProtKB negative regulation of apoptotic process Inferred from direct assay PubMed 17704808. Source: UniProtKB negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay Ref.3. Source: UniProtKB positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from direct assay Ref.9Ref.12. Source: UniProtKB positive regulation of NF-kappaB transcription factor activity Inferred from direct assay Ref.9Ref.12. Source: UniProtKB positive regulation of angiogenesis Inferred from direct assay PubMed 19940250. Source: UniProtKB positive regulation of autophagy Inferred from direct assay PubMed 21127263. Source: UniProtKB positive regulation of protein kinase B signaling cascade Inferred from direct assay PubMed 17704808. Source: UniProtKB tight junction assembly Inferred from electronic annotation. Source: Compara
Cellular_component	apical plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB endoplasmic reticulum membrane Inferred from sequence or structural similarity. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW intercellular canaliculus Inferred from sequence or structural similarity. Source: UniProtKB nuclear body Inferred from direct assay PubMed 19648967. Source: UniProtKB nuclear membrane Inferred from electronic annotation. Source: UniProtKB-SubCell nucleolus Inferred from direct assay. Source: HPA perinuclear region of cytoplasm Inferred from direct assay Ref.1Ref.3. Source: UniProtKB tight junction Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	transcription coactivator activity Inferred from mutant phenotype Ref.12. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CREBBP	Q92793	2	EBI-1046588,EBI-81215

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 582	582	Protein LYRIC		PRO_0000084533
Regions
	Topological domain	1 – 48	48	Lumenal Potential
	Transmembrane	49 – 69	21	Helical; Potential
	Topological domain	70 – 582	513	Cytoplasmic Potential
	Region	1 – 71	71	Activation of NF-kappa-B
	Region	72 – 169	98	Interaction with BCCIP
	Region	101 – 205	105	Interaction with RELA
	Region	381 – 443	63	Lung-homing for mammary tumors By similarity
	Compositional bias	59 – 67	9	Poly-Leu
	Compositional bias	441 – 451	11	Poly-Lys
	Compositional bias	573 – 577	5	Poly-Lys
Amino acid modifications
	Modified residue	143	1	Phosphothreonine Ref.14 Ref.17
	Modified residue	295	1	Phosphoserine By similarity
	Modified residue	298	1	Phosphoserine Ref.10 Ref.13 Ref.14 Ref.17 Ref.19
	Modified residue	306	1	Phosphoserine Ref.17
	Modified residue	308	1	Phosphoserine Ref.14 Ref.17
	Modified residue	311	1	Phosphoserine Ref.14
	Modified residue	344	1	Phosphoserine Ref.16
	Modified residue	369	1	Phosphoserine Ref.16
	Modified residue	415	1	Phosphoserine Ref.10
	Modified residue	426	1	Phosphoserine Ref.10 Ref.13 Ref.14 Ref.17 Ref.19
	Modified residue	458	1	Phosphothreonine Ref.14
	Modified residue	568	1	Phosphoserine Ref.14
Natural variations
	Natural variant	317	1	T → A. Ref.5 Corresponds to variant rs17854374 [ dbSNP | Ensembl ].		VAR_054661
Experimental info
	Sequence conflict	78	1	A → S in AAH09324. Ref.5
	Sequence conflict	78	1	A → S in AAH45642. Ref.5
	Sequence conflict	145	1	Q → H in AAX84832. Ref.4
	Sequence conflict	543	1	T → A in AAX84832. Ref.4
	Sequence conflict	581	1	E → D in AAX84832. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Q86UE4 [UniParc]. Last modified December 21, 2004. Version 2. Checksum: 2460D6218FD3A4C4	FASTA	582	63,837
	10 20 30 40 50 60 MAARSWQDEL AQQAEEGSAR LREMLSVGLG FLRTELGLDL GLEPKRYPGW VILVGTGALG 70 80 90 100 110 120 LLLLFLLGYG WAAACAGARK KRRSPPRKRE EAAAVPAAAP DDLALLKNLR SEEQKKKNRK 130 140 150 160 170 180 KLSEKPKPNG RTVEVAEGEA VRTPQSVTAK QPPEIDKKNE KSKKNKKKSK SDAKAVQNSS 190 200 210 220 230 240 RHDGKEVDEG AWETKISHRE KRQQRKRDKV LTDSGSLDST IPGIENTITV TTEQLTTASF 250 260 270 280 290 300 PVGSKKNKGD SHLNVQVSNF KSGKGDSTLQ VSSGLNENLT VNGGGWNEKS VKLSSQISAG 310 320 330 340 350 360 EEKWNSVSPA SAGKRKTEPS AWSQDTGDAN TNGKDWGRSW SDRSIFSGIG STAEPVSQST 370 380 390 400 410 420 TSDYQWDVSR NQPYIDDEWS GLNGLSSADP NSDWNAPAEE WGNWVDEERA SLLKSQEPIP 430 440 450 460 470 480 DDQKVSDDDK EKGEGALPTG KSKKKKKKKK KQGEDNSTAQ DTEELEKEIR EDLPVNTSKT 490 500 510 520 530 540 RPKQEKAFSL KTISTSDPAE VLVKNSQPIK TLPPATSTEP SVILSKSDSD KSSSQVPPIL 550 560 570 580 QETDKSKSNT KQNSVPPSQT KSETSWESPK QIKKKKKARR ET

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"3D3/lyric: a novel transmembrane protein of the endoplasmic reticulum and nuclear envelope, which is also present in the nucleolus." Sutherland H.G.E., Lam Y.W., Briers S., Lamond A.I., Bickmore W.A. Exp. Cell Res. 294:94-105(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION.
[2]	"Identification of a novel protein, LYRIC, localized to tight junctions of polarized epithelial cells." Britt D.E., Yang D.-F., Yang D.-Q., Flanagan D.L., Callanan H., Lim Y.-P., Lin S.-H., Hixson D.C. Exp. Cell Res. 300:134-148(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION. Tissue: Colon carcinoma.
[3]	"Cloning and characterization of HIV-1-inducible astrocyte elevated gene-1, AEG-1." Kang D.-C., Su Z.-Z., Sarkar D., Emdad L., Volsky D.J., Fisher P.B. Gene 353:8-15(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION. Tissue: Fetal astrocyte.
[4]	"LYRIC protein induces cell migration dependent on its cytoplasmic localization." Liang Y., Liu G. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	"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], VARIANT ALA-317. Tissue: Brain, Skin and Testis.
[6]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 97-582. Tissue: Hepatoma.
[7]	"Gene expression profiling predicts clinical outcome of breast cancer." van 't Veer L.J., Dai H., van de Vijver M.J., He Y.D., Hart A.A.A., Mao M., Peterse H.L., van der Kooy K., Marton M.J., Witteveen A.T., Schreiber G.J., Kerkhoven R.M., Roberts C., Linsley P.S., Bernards R., Friend S.H. Nature 415:530-536(2002) [PubMed] [Europe PMC] [Abstract] Cited for: OVEREXPRESSION IN MAMMARY TUMORS.
[8]	"Metadherin, a cell surface protein in breast tumors that mediates lung metastasis." Brown D.M., Ruoslahti E. Cancer Cell 5:365-374(2004) [PubMed] [Europe PMC] [Abstract] Cited for: OVEREXPRESSION IN TUMORS.
[9]	"Activation of the nuclear factor kappaB pathway by astrocyte elevated gene-1: implications for tumor progression and metastasis." Emdad L., Sarkar D., Su Z.-Z., Randolph A., Boukerche H., Valerie K., Fisher P.B. Cancer Res. 66:1509-1516(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH RELA, INDUCTION.
[10]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-298; SER-415 AND SER-426, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"LYRIC/AEG-1 overexpression modulates BCCIPalpha protein levels in prostate tumor cells." Ash S.C., Yang D.Q., Britt D.E. Biochem. Biophys. Res. Commun. 371:333-338(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH BCCIP.
[12]	"Molecular basis of nuclear factor-kappaB activation by astrocyte elevated gene-1." Sarkar D., Park E.S., Emdad L., Lee S.-G., Su Z.-Z., Fisher P.B. Cancer Res. 68:1478-1484(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH CREBBP.
[13]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-298 AND SER-426, MASS SPECTROMETRY. Tissue: Platelet.
[14]	"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 THR-143; SER-298; SER-308; SER-311; SER-426; THR-458 AND SER-568, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[15]	"MTDH activation by 8q22 genomic gain promotes chemoresistance and metastasis of poor-prognosis breast cancer." Hu G., Chong R.A., Yang Q., Wei Y., Blanco M.A., Li F., Reiss M., Au J.L.-S., Haffty B.G., Kang Y. Cancer Cell 15:9-20(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[16]	"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-344 AND SER-369, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[17]	"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 THR-143; SER-298; SER-306; SER-308 AND SER-426, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[18]	"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].
[19]	"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-298 AND SER-426, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00328715.
RefSeq	NP_848927.2. NM_178812.3.
UniGene	Hs.377155.
3D structure databases
ProteinModelPortal	Q86UE4.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q86UE4. 8 interactions.
STRING	9606.ENSP00000338235.
PTM databases
PhosphoSite	Q86UE4.
Polymorphism databases
DMDM	56749088.
Proteomic databases
PaxDb	Q86UE4.
PeptideAtlas	Q86UE4.
PRIDE	Q86UE4.
Protocols and materials databases
DNASU	92140.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000336273; ENSP00000338235; ENSG00000147649.
GeneID	92140.
KEGG	hsa:92140.
UCSC	uc003yhz.3. human.
Organism-specific databases
CTD	92140.
GeneCards	GC08P098658.
HGNC	HGNC:29608. MTDH.
HPA	HPA010932. HPA015104.
MIM	610323. gene.
neXtProt	NX_Q86UE4.
PharmGKB	PA142671307.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG45896.
HOGENOM	HOG000113417.
HOVERGEN	HBG052379.
InParanoid	Q86UE4.
OMA	GWNEKSV.
OrthoDB	EOG4WWRJD.
PhylomeDB	Q86UE4.
Gene expression databases
ArrayExpress	Q86UE4.
Bgee	Q86UE4.
CleanEx	HS_MTDH.
Genevestigator	Q86UE4.
GermOnline	ENSG00000147649. Homo sapiens.
Family and domain databases
ProtoNet	Search...
Other
ChiTaRS	MTDH. human.
GenomeRNAi	92140.
NextBio	77609.
SOURCE	Search...

Entry information

Entry name

LYRIC_HUMAN

Accession

Primary (citable) accession number: Q86UE4
Secondary accession number(s): Q05DH2 , Q52QU9, Q6PK07, Q8TCX3

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 21, 2004
Last sequence update:	December 21, 2004
Last modified:	April 3, 2013
This is version 92 of the entry and version 2 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.