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Q9Y2U8 (MAN1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 129. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Inner nuclear membrane protein Man1
Alternative name(s):
LEM domain-containing protein 3
Gene names
Name:LEMD3
Synonyms:MAN1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length911 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Can function as a specific repressor of TGF-beta, activin, and BMP signaling through its interaction with the R-SMAD proteins. Antagonizes TGF-beta-induced cell proliferation arrest. Ref.4 Ref.5

Subunit structure

Interacts with SMAD1, SMAD2, SMAD3 and SMAD5. Binds to both phosphorylated and unphosphorylated R-SMADS. Ref.4 Ref.5

Subcellular location

Nucleus inner membrane; Multi-pass membrane protein Ref.5.

Tissue specificity

Heart, brain, placenta, lung, liver and skeletal muscle.

Involvement in disease

Buschke-Ollendorff syndrome (BOS) [MIM:166700]: A disease characterized by osteopoikilosis and disseminated connective-tissue nevi. Osteopoikilosis is a skeletal dysplasia characterized by a symmetric but unequal distribution of multiple hyperostotic areas in different parts of the skeleton. Elastic-type nevi (juvenile elastoma) and collagen-type nevi (dermatofibrosis lenticularis disseminata) have been described in BOS. Skin or bony lesions can be absent in some family members, whereas other relatives may have both.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.3

Melorheostosis (MEL) [MIM:155950]: Rare mesenchymal dysplasia and one of the sclerosing bone disorders. It is caused by a developmental error, with a sclerotomal distribution, frequently involving one limb. It may be asymptomatic, but pain, stiffness with limitation of motion, leg-length discrepancy and limb deformity may occur.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.3

Sequence similarities

Contains 1 LEM domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.13
Chain2 – 911910Inner nuclear membrane protein Man1
PRO_0000206149

Regions

Transmembrane475 – 49521Helical; Potential
Transmembrane628 – 64821Helical; Potential
Domain6 – 5045LEM
DNA binding707 – 72620 Ref.14
Region699 – 911213Interaction with SMAD1, SMAD2, SMAD3 and SMAD5
Compositional bias65 – 706Poly-Asn
Compositional bias72 – 8716Ala-rich
Compositional bias82 – 876Poly-Ala
Compositional bias155 – 1584Poly-Gly
Compositional bias265 – 2684Poly-Asp
Compositional bias312 – 3154Poly-Gly
Compositional bias322 – 3254Poly-Ala
Compositional bias337 – 3404Poly-Ala
Compositional bias635 – 6406Poly-Leu
Compositional bias659 – 6624Poly-Glu

Amino acid modifications

Modified residue21N-acetylalanine Ref.13
Modified residue1401Phosphoserine Ref.9
Modified residue1411Phosphoserine Ref.9
Modified residue1441Phosphoserine Ref.9 Ref.10
Modified residue1851Phosphoserine Ref.8
Modified residue1871Phosphoserine Ref.8 Ref.10
Modified residue2591Phosphoserine Ref.8 Ref.12
Modified residue2611Phosphoserine Ref.8 Ref.9 Ref.12
Modified residue2801Phosphoserine Ref.8
Modified residue3521Phosphoserine Ref.8
Modified residue3651Phosphothreonine Ref.8
Modified residue4021Phosphoserine Ref.7 Ref.8
Modified residue7771Phosphoserine Ref.8
Modified residue8831Phosphothreonine Ref.10
Modified residue9111Phosphoserine Ref.8

Natural variations

Natural variant2601D → Y.
Corresponds to variant rs7487311 [ dbSNP | Ensembl ].
VAR_034605

Experimental info

Mutagenesis703 – 7042LI → ED: Impairs binding to SMAD1. Loss of ability to repress transcriptional activation in response to TGF-beta, BMP2 and activin signaling. Ref.5
Mutagenesis835 – 8362YV → DD: Impairs binding to SMAD1. Ref.5
Sequence conflict508 – 5092IE → K in AAF73293. Ref.1

Secondary structure

..................... 911
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9Y2U8 [UniParc].

Last modified October 1, 2000. Version 2.
Checksum: 21D1E6BB0D499131

FASTA91199,997
        10         20         30         40         50         60 
MAAAAASAPQ QLSDEELFSQ LRRYGLSPGP VTESTRPVYL KKLKKLREEE QQQHRSGGRG 

        70         80         90        100        110        120 
NKTRNSNNNN TAAATVAAAG PAAAAAAGMG VRPVSGDLSY LRTPGGLCRI SASGPESLLG 

       130        140        150        160        170        180 
GPGGASAAPA AGSKVLLGFS SDESDVEASP RDQAGGGGRK DRASLQYRGL KAPPAPLAAS 

       190        200        210        220        230        240 
EVTNSNSAER RKPHSWWGAR RPAGPELQTP PGKDGAVEDE EGEGEDGEER DPETEEPLWA 

       250        260        270        280        290        300 
SRTVNGSRLV PYSCRENYSD SEEEDDDDVA SSRQVLKDDS LSRHRPRRTH SKPLPPLTAK 

       310        320        330        340        350        360 
SAGGRLETSV QGGGGLAMND RAAAAGSLDR SRNLEEAAAA EQGGGCDQVD SSPVPRYRVN 

       370        380        390        400        410        420 
AKKLTPLLPP PLTDMDSTLD SSTGSLLKTN NHIGGGAFSV DSPRIYSNSL PPSAAVAASS 

       430        440        450        460        470        480 
SLRINHANHT GSNHTYLKNT YNKPKLSEPE EELLQQFKRE EVSPTGSFSA HYLSMFLLTA 

       490        500        510        520        530        540 
ACLFFLILGL TYLGMRGTGV SEDGELSIEN PFGETFGKIQ ESEKTLMMNT LYKLHDRLAQ 

       550        560        570        580        590        600 
LAGDHECGSS SQRTLSVQEA AAYLKDLGPE YEGIFNTSLQ WILENGKDVG IRCVGFGPEE 

       610        620        630        640        650        660 
ELTNITDVQF LQSTRPLMSF WCRFRRAFVT VTHRLLLLCL GVVMVCVVLR YMKYRWTKEE 

       670        680        690        700        710        720 
EETRQMYDMV VKIIDVLRSH NEACQENKDL QPYMPIPHVR DSLIQPHDRK KMKKVWDRAV 

       730        740        750        760        770        780 
DFLAANESRV RTETRRIGGA DFLVWRWIQP SASCDKILVI PSKVWQGQAF HLDRRNSPPN 

       790        800        810        820        830        840 
SLTPCLKIRN MFDPVMEIGD QWHLAIQEAI LEKCSDNDGI VHIAVDKNSR EGCVYVKCLS 

       850        860        870        880        890        900 
PEYAGKAFKA LHGSWFDGKL VTVKYLRLDR YHHRFPQALT SNTPLKPSNK HMNSMSHLRL 

       910 
RTGLTNSQGS S 

« Hide

References

« Hide 'large scale' references
[1]"MAN1, an inner nuclear membrane protein that shares the LEM domain with lamina-associated polypeptide 2 and emerin."
Lin F., Blake D.L., Callebaut I., Skerjanc I.S., Holmer L., McBurney M.W., Paulin-Levasseur M., Worman H.J.
J. Biol. Chem. 275:4840-4847(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[2]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 714-911.
Tissue: Testis.
[3]"Loss-of-function mutations in LEMD3 result in osteopoikilosis, Buschke-Ollendorff syndrome and melorheostosis."
Hellemans J., Preobrazhenska O., Willaert A., Debeer P., Verdonk P.C.M., Costa T., Janssens K., Menten B., Van Roy N., Vermeulen S.J.T., Savarirayan R., Van Hul W., Vanhoenacker F., Huylebroeck D., De Paepe A., Naeyaert J.-M., Vandesompele J., Speleman F. expand/collapse author list , Verschueren K., Coucke P.J., Mortier G.R.
Nat. Genet. 36:1213-1218(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN BOS AND MEL.
[4]"MAN1, an integral protein of the inner nuclear membrane, binds Smad2 and Smad3 and antagonizes transforming growth factor-beta signaling."
Lin F., Morrison J.M., Wu W., Worman H.J.
Hum. Mol. Genet. 14:437-445(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH SMAD2 AND SMAD3.
[5]"The integral inner nuclear membrane protein MAN1 physically interacts with the R-Smad proteins to repress signaling by the transforming growth factor-{beta} superfamily of cytokines."
Pan D., Estevez-Salmeron L.D., Stroschein S.L., Zhu X., He J., Zhou S., Luo K.
J. Biol. Chem. 280:15992-16001(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SMAD1; SMAD2; SMAD3 AND SMAD5, MUTAGENESIS OF 703-LEU-ILE-704 AND 835-TYR-VAL-836.
[6]"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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[7]"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis."
Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III
J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-402, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[8]"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-185; SER-187; SER-259; SER-261; SER-280; SER-352; THR-365; SER-402; SER-777 AND SER-911, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"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-140; SER-141; SER-144 AND SER-261, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[10]"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-144; SER-187 AND THR-883, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[11]"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].
[12]"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-259 AND SER-261, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[14]"The carboxyl-terminal nucleoplasmic region of MAN1 exhibits a DNA binding winged helix domain."
Caputo S., Couprie J., Duband-Goulet I., Konde E., Lin F., Braud S., Gondry M., Gilquin B., Worman H.J., Zinn-Justin S.
J. Biol. Chem. 281:18208-18215(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 655-775, DNA-BINDING.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF112299 mRNA. Translation: AAD31593.2.
AF263918 expand/collapse EMBL AC list , AF180135, AF180136, AF180137, AF180138, AF180139, AF180140, AF180141, AF180142 Genomic DNA. Translation: AAF73293.1.
AL137533 mRNA. Translation: CAB70796.1. Sequence problems.
CCDSCCDS8972.1.
PIRT46377.
RefSeqNP_001161086.1. NM_001167614.1.
NP_055134.2. NM_014319.4.
UniGeneHs.744150.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2CH0NMR-A655-775[»]
ProteinModelPortalQ9Y2U8.
SMRQ9Y2U8. Positions 9-49, 653-780, 783-888.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid117127. 9 interactions.
IntActQ9Y2U8. 7 interactions.
MINTMINT-1199446.
STRING9606.ENSP00000308369.

PTM databases

PhosphoSiteQ9Y2U8.

Polymorphism databases

DMDM13629600.

Proteomic databases

MaxQBQ9Y2U8.
PaxDbQ9Y2U8.
PeptideAtlasQ9Y2U8.
PRIDEQ9Y2U8.

Protocols and materials databases

DNASU23592.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000308330; ENSP00000308369; ENSG00000174106.
GeneID23592.
KEGGhsa:23592.
UCSCuc001ssl.2. human.

Organism-specific databases

CTD23592.
GeneCardsGC12P065563.
HGNCHGNC:28887. LEMD3.
HPAHPA025078.
MIM155950. phenotype.
166700. phenotype.
607844. gene.
neXtProtNX_Q9Y2U8.
Orphanet94063. 12q14 microdeletion syndrome.
1306. Buschke-Ollendorff syndrome.
166119. Isolated osteopoikilosis.
1879. Melorheostosis with osteopoikilosis.
PharmGKBPA134907442.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG70255.
HOGENOMHOG000063699.
HOVERGENHBG006319.
InParanoidQ9Y2U8.
OMASPIPRYR.
OrthoDBEOG75J0MP.
PhylomeDBQ9Y2U8.
TreeFamTF315385.

Enzyme and pathway databases

ReactomeREACT_115566. Cell Cycle.
REACT_21300. Mitotic M-M/G1 phases.

Gene expression databases

ArrayExpressQ9Y2U8.
BgeeQ9Y2U8.
CleanExHS_LEMD3.
GenevestigatorQ9Y2U8.

Family and domain databases

Gene3D1.10.720.40. 1 hit.
3.30.70.330. 1 hit.
InterProIPR018996. Inner-Nucl-membr_MAN1.
IPR011015. LEM/LEM-like_dom.
IPR003887. LEM_dom.
IPR012677. Nucleotide-bd_a/b_plait.
[Graphical view]
PfamPF03020. LEM. 1 hit.
PF09402. MSC. 1 hit.
[Graphical view]
SMARTSM00540. LEM. 1 hit.
[Graphical view]
SUPFAMSSF63451. SSF63451. 1 hit.
PROSITEPS50954. LEM. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ9Y2U8.
GenomeRNAi23592.
NextBio46240.
PROQ9Y2U8.
SOURCESearch...

Entry information

Entry nameMAN1_HUMAN
AccessionPrimary (citable) accession number: Q9Y2U8
Secondary accession number(s): Q9NT47, Q9NYA5
Entry history
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: October 1, 2000
Last modified: July 9, 2014
This is version 129 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM