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Protein

Inner nuclear membrane protein Man1

Gene

LEMD3

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

Functioni

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.2 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi707 – 726Add BLAST20

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000174106-MONOMER.
ReactomeiR-HSA-2993913. Clearance of Nuclear Envelope Membranes from Chromatin.
R-HSA-2995383. Initiation of Nuclear Envelope Reformation.
R-HSA-4419969. Depolymerisation of the Nuclear Lamina.

Names & Taxonomyi

Protein namesi
Recommended name:
Inner nuclear membrane protein Man1
Alternative name(s):
LEM domain-containing protein 3
Gene namesi
Name:LEMD3
Synonyms:MAN1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:28887. LEMD3.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei475 – 495HelicalSequence analysisAdd BLAST21
Transmembranei628 – 648HelicalSequence analysisAdd BLAST21

GO - Cellular componenti

  • integral component of membrane Source: MGI
  • integral component of nuclear inner membrane Source: ProtInc
  • membrane Source: ProtInc
  • nuclear inner membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

Buschke-Ollendorff syndrome (BOS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:166700
Melorheostosis (MEL)
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionRare 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.
See also OMIM:155950

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi703 – 704LI → ED: Impairs binding to SMAD1. Loss of ability to repress transcriptional activation in response to TGF-beta, BMP2 and activin signaling. 1 Publication2
Mutagenesisi835 – 836YV → DD: Impairs binding to SMAD1. 1 Publication2

Organism-specific databases

DisGeNETi23592.
MalaCardsiLEMD3.
MIMi155950. phenotype.
166700. phenotype.
OpenTargetsiENSG00000174106.
Orphaneti94063. 12q14 microdeletion syndrome.
1306. Buschke-Ollendorff syndrome.
166119. Isolated osteopoikilosis.
1879. Melorheostosis with osteopoikilosis.
PharmGKBiPA134907442.

Polymorphism and mutation databases

BioMutaiLEMD3.
DMDMi13629600.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00002061492 – 911Inner nuclear membrane protein Man1Add BLAST910

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei27PhosphoserineCombined sources1
Modified residuei140PhosphoserineCombined sources1
Modified residuei141PhosphoserineCombined sources1
Modified residuei144PhosphoserineCombined sources1
Modified residuei185PhosphoserineCombined sources1
Modified residuei187PhosphoserineCombined sources1
Modified residuei209PhosphothreonineCombined sources1
Modified residuei259PhosphoserineCombined sources1
Modified residuei261PhosphoserineCombined sources1
Modified residuei280PhosphoserineCombined sources1
Modified residuei352PhosphoserineCombined sources1
Modified residuei365PhosphothreonineCombined sources1
Modified residuei402PhosphoserineCombined sources1
Modified residuei777PhosphoserineCombined sources1
Modified residuei883PhosphothreonineCombined sources1
Modified residuei911PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9Y2U8.
MaxQBiQ9Y2U8.
PaxDbiQ9Y2U8.
PeptideAtlasiQ9Y2U8.
PRIDEiQ9Y2U8.

PTM databases

iPTMnetiQ9Y2U8.
PhosphoSitePlusiQ9Y2U8.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000174106.
CleanExiHS_LEMD3.
ExpressionAtlasiQ9Y2U8. baseline and differential.
GenevisibleiQ9Y2U8. HS.

Organism-specific databases

HPAiHPA025078.

Interactioni

Subunit structurei

Interacts with SMAD1, SMAD2, SMAD3 and SMAD5. Binds to both phosphorylated and unphosphorylated R-SMADS.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
SMAD1Q157973EBI-2561428,EBI-1567153

Protein-protein interaction databases

BioGridi117127. 46 interactors.
IntActiQ9Y2U8. 17 interactors.
MINTiMINT-1199446.
STRINGi9606.ENSP00000308369.

Structurei

Secondary structure

1911
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi659 – 663Combined sources5
Turni664 – 669Combined sources6
Helixi670 – 684Combined sources15
Helixi696 – 701Combined sources6
Helixi709 – 712Combined sources4
Helixi713 – 723Combined sources11
Turni724 – 726Combined sources3
Beta strandi730 – 737Combined sources8
Beta strandi740 – 746Combined sources7
Beta strandi751 – 753Combined sources3
Beta strandi765 – 768Combined sources4
Beta strandi771 – 774Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2CH0NMR-A655-775[»]
ProteinModelPortaliQ9Y2U8.
SMRiQ9Y2U8.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9Y2U8.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini6 – 50LEMPROSITE-ProRule annotationAdd BLAST45

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni699 – 911Interaction with SMAD1, SMAD2, SMAD3 and SMAD51 PublicationAdd BLAST213

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi65 – 70Poly-Asn6
Compositional biasi72 – 87Ala-richAdd BLAST16
Compositional biasi82 – 87Poly-Ala6
Compositional biasi155 – 158Poly-Gly4
Compositional biasi265 – 268Poly-Asp4
Compositional biasi312 – 315Poly-Gly4
Compositional biasi322 – 325Poly-Ala4
Compositional biasi337 – 340Poly-Ala4
Compositional biasi635 – 640Poly-Leu6
Compositional biasi659 – 662Poly-Glu4

Sequence similaritiesi

Contains 1 LEM domain.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0147. Eukaryota.
ENOG410XP20. LUCA.
GeneTreeiENSGT00530000063791.
HOGENOMiHOG000063699.
HOVERGENiHBG006319.
InParanoidiQ9Y2U8.
KOiK19410.
OMAiQYRGLKP.
OrthoDBiEOG091G09QP.
PhylomeDBiQ9Y2U8.
TreeFamiTF315385.

Family and domain databases

Gene3Di1.10.720.40. 1 hit.
3.30.70.330. 1 hit.
InterProiIPR018996. Inner-Nucl-membr_MAN1.
IPR011015. LEM/LEM-like_dom.
IPR003887. LEM_dom.
IPR012677. Nucleotide-bd_a/b_plait.
[Graphical view]
PfamiPF03020. LEM. 1 hit.
PF09402. MSC. 1 hit.
[Graphical view]
SMARTiSM00540. LEM. 1 hit.
[Graphical view]
SUPFAMiSSF54928. SSF54928. 1 hit.
SSF63451. SSF63451. 1 hit.
PROSITEiPS50954. LEM. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9Y2U8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAAAAASAPQ QLSDEELFSQ LRRYGLSPGP VTESTRPVYL KKLKKLREEE
60 70 80 90 100
QQQHRSGGRG NKTRNSNNNN TAAATVAAAG PAAAAAAGMG VRPVSGDLSY
110 120 130 140 150
LRTPGGLCRI SASGPESLLG GPGGASAAPA AGSKVLLGFS SDESDVEASP
160 170 180 190 200
RDQAGGGGRK DRASLQYRGL KAPPAPLAAS EVTNSNSAER RKPHSWWGAR
210 220 230 240 250
RPAGPELQTP PGKDGAVEDE EGEGEDGEER DPETEEPLWA SRTVNGSRLV
260 270 280 290 300
PYSCRENYSD SEEEDDDDVA SSRQVLKDDS LSRHRPRRTH SKPLPPLTAK
310 320 330 340 350
SAGGRLETSV QGGGGLAMND RAAAAGSLDR SRNLEEAAAA EQGGGCDQVD
360 370 380 390 400
SSPVPRYRVN AKKLTPLLPP PLTDMDSTLD SSTGSLLKTN NHIGGGAFSV
410 420 430 440 450
DSPRIYSNSL PPSAAVAASS SLRINHANHT GSNHTYLKNT YNKPKLSEPE
460 470 480 490 500
EELLQQFKRE EVSPTGSFSA HYLSMFLLTA ACLFFLILGL TYLGMRGTGV
510 520 530 540 550
SEDGELSIEN PFGETFGKIQ ESEKTLMMNT LYKLHDRLAQ LAGDHECGSS
560 570 580 590 600
SQRTLSVQEA AAYLKDLGPE YEGIFNTSLQ WILENGKDVG IRCVGFGPEE
610 620 630 640 650
ELTNITDVQF LQSTRPLMSF WCRFRRAFVT VTHRLLLLCL GVVMVCVVLR
660 670 680 690 700
YMKYRWTKEE EETRQMYDMV VKIIDVLRSH NEACQENKDL QPYMPIPHVR
710 720 730 740 750
DSLIQPHDRK KMKKVWDRAV DFLAANESRV RTETRRIGGA DFLVWRWIQP
760 770 780 790 800
SASCDKILVI PSKVWQGQAF HLDRRNSPPN SLTPCLKIRN MFDPVMEIGD
810 820 830 840 850
QWHLAIQEAI LEKCSDNDGI VHIAVDKNSR EGCVYVKCLS PEYAGKAFKA
860 870 880 890 900
LHGSWFDGKL VTVKYLRLDR YHHRFPQALT SNTPLKPSNK HMNSMSHLRL
910
RTGLTNSQGS S
Length:911
Mass (Da):99,997
Last modified:October 1, 2000 - v2
Checksum:i21D1E6BB0D499131
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti508 – 509IE → K in AAF73293 (PubMed:10671519).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_034605260D → Y.Corresponds to variant rs7487311dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF112299 mRNA. Translation: AAD31593.2.
AF263918
, AF180135, AF180136, AF180137, AF180138, AF180139, AF180140, AF180141, AF180142 Genomic DNA. Translation: AAF73293.1.
AL137533 mRNA. Translation: CAB70796.1. Sequence problems.
CCDSiCCDS8972.1.
PIRiT46377.
RefSeqiNP_001161086.1. NM_001167614.1.
NP_055134.2. NM_014319.4.
UniGeneiHs.744150.

Genome annotation databases

EnsembliENST00000308330; ENSP00000308369; ENSG00000174106.
GeneIDi23592.
KEGGihsa:23592.
UCSCiuc001ssl.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF112299 mRNA. Translation: AAD31593.2.
AF263918
, AF180135, AF180136, AF180137, AF180138, AF180139, AF180140, AF180141, AF180142 Genomic DNA. Translation: AAF73293.1.
AL137533 mRNA. Translation: CAB70796.1. Sequence problems.
CCDSiCCDS8972.1.
PIRiT46377.
RefSeqiNP_001161086.1. NM_001167614.1.
NP_055134.2. NM_014319.4.
UniGeneiHs.744150.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2CH0NMR-A655-775[»]
ProteinModelPortaliQ9Y2U8.
SMRiQ9Y2U8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117127. 46 interactors.
IntActiQ9Y2U8. 17 interactors.
MINTiMINT-1199446.
STRINGi9606.ENSP00000308369.

PTM databases

iPTMnetiQ9Y2U8.
PhosphoSitePlusiQ9Y2U8.

Polymorphism and mutation databases

BioMutaiLEMD3.
DMDMi13629600.

Proteomic databases

EPDiQ9Y2U8.
MaxQBiQ9Y2U8.
PaxDbiQ9Y2U8.
PeptideAtlasiQ9Y2U8.
PRIDEiQ9Y2U8.

Protocols and materials databases

DNASUi23592.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000308330; ENSP00000308369; ENSG00000174106.
GeneIDi23592.
KEGGihsa:23592.
UCSCiuc001ssl.3. human.

Organism-specific databases

CTDi23592.
DisGeNETi23592.
GeneCardsiLEMD3.
HGNCiHGNC:28887. LEMD3.
HPAiHPA025078.
MalaCardsiLEMD3.
MIMi155950. phenotype.
166700. phenotype.
607844. gene.
neXtProtiNX_Q9Y2U8.
OpenTargetsiENSG00000174106.
Orphaneti94063. 12q14 microdeletion syndrome.
1306. Buschke-Ollendorff syndrome.
166119. Isolated osteopoikilosis.
1879. Melorheostosis with osteopoikilosis.
PharmGKBiPA134907442.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0147. Eukaryota.
ENOG410XP20. LUCA.
GeneTreeiENSGT00530000063791.
HOGENOMiHOG000063699.
HOVERGENiHBG006319.
InParanoidiQ9Y2U8.
KOiK19410.
OMAiQYRGLKP.
OrthoDBiEOG091G09QP.
PhylomeDBiQ9Y2U8.
TreeFamiTF315385.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000174106-MONOMER.
ReactomeiR-HSA-2993913. Clearance of Nuclear Envelope Membranes from Chromatin.
R-HSA-2995383. Initiation of Nuclear Envelope Reformation.
R-HSA-4419969. Depolymerisation of the Nuclear Lamina.

Miscellaneous databases

ChiTaRSiLEMD3. human.
EvolutionaryTraceiQ9Y2U8.
GenomeRNAii23592.
PROiQ9Y2U8.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000174106.
CleanExiHS_LEMD3.
ExpressionAtlasiQ9Y2U8. baseline and differential.
GenevisibleiQ9Y2U8. HS.

Family and domain databases

Gene3Di1.10.720.40. 1 hit.
3.30.70.330. 1 hit.
InterProiIPR018996. Inner-Nucl-membr_MAN1.
IPR011015. LEM/LEM-like_dom.
IPR003887. LEM_dom.
IPR012677. Nucleotide-bd_a/b_plait.
[Graphical view]
PfamiPF03020. LEM. 1 hit.
PF09402. MSC. 1 hit.
[Graphical view]
SMARTiSM00540. LEM. 1 hit.
[Graphical view]
SUPFAMiSSF54928. SSF54928. 1 hit.
SSF63451. SSF63451. 1 hit.
PROSITEiPS50954. LEM. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMAN1_HUMAN
AccessioniPrimary (citable) accession number: Q9Y2U8
Secondary accession number(s): Q9NT47, Q9NYA5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: October 1, 2000
Last modified: November 30, 2016
This is version 154 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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: 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
  6. SIMILARITY comments
    Index of protein domains and families

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.