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Q9NS15 (LTBP3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 126. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Latent-transforming growth factor beta-binding protein 3

Short name=LTBP-3
Gene names
Name:LTBP3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1303 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

May be involved in the assembly, secretion and targeting of TGFB1 to sites at which it is stored and/or activated. May play critical roles in controlling and directing the activity of TGFB1. May have a structural role in the extra cellular matrix (ECM).

Subunit structure

Forms part of the large latent transforming growth factor beta precursor complex; removal is essential for activation of complex.

Subcellular location

Secreted By similarity. Note: Secretion occurs after coexpression with TGFB1 and requires complexing with 'Cys-33' of the TGFB1 propeptide By similarity.

Tissue specificity

Isoform 2 is expressed prominently in heart, skeletal muscle, prostate, testis, small intestine and ovary. Isoform 1 is strongly expressed in pancreas and liver.

Post-translational modification

Contains hydroxylated asparagine residues By similarity.

Two intrachain disulfide bonds from the TB3 domain are rearranged upon TGFB1 binding, and form interchain bonds with TGFB1 propeptide, anchoring it to the extracellular matrix.

Involvement in disease

Tooth agenesis selective 6 (STHAG6) [MIM:613097]: A form of selective tooth agenesis, a common anomaly characterized by the congenital absence of one or more teeth. Selective tooth agenesis without associated systemic disorders has sometimes been divided into 2 types: oligodontia, defined as agenesis of 6 or more permanent teeth, and hypodontia, defined as agenesis of less than 6 teeth. The number in both cases does not include absence of third molars (wisdom teeth). In tooth agenesis selective type 6, alveolar bone is absent where the teeth are missing. Some individuals have short stature.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9

Sequence similarities

Belongs to the LTBP family.

Contains 13 EGF-like domains.

Contains 4 TB (TGF-beta binding) domains.

Sequence caution

The sequence BAB15767.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Cellular componentSecreted
   Coding sequence diversityAlternative splicing
   DomainEGF-like domain
Repeat
Signal
   LigandGrowth factor binding
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processbone morphogenesis

Inferred from electronic annotation. Source: Ensembl

bone remodeling

Inferred from electronic annotation. Source: Ensembl

extracellular matrix organization

Traceable author statement. Source: Reactome

lung saccule development

Inferred from electronic annotation. Source: Ensembl

negative regulation of bone mineralization

Inferred from electronic annotation. Source: Ensembl

negative regulation of chondrocyte differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of bone resorption

Inferred from electronic annotation. Source: Ensembl

positive regulation of mesenchymal stem cell differentiation

Inferred from mutant phenotype PubMed 18672106. Source: UniProt

positive regulation of mesenchymal stem cell proliferation

Inferred from mutant phenotype PubMed 18672106. Source: UniProt

transforming growth factor beta activation

Inferred from mutant phenotype PubMed 18672106. Source: UniProt

transforming growth factor beta receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentextracellular matrix

Inferred from direct assay PubMed 16157329. Source: UniProt

extracellular region

Traceable author statement. Source: Reactome

extracellular vesicular exosome

Inferred from direct assay PubMed 19199708. Source: UniProt

   Molecular_functioncalcium ion binding

Inferred from electronic annotation. Source: InterPro

transforming growth factor beta binding

Inferred from physical interaction Ref.6PubMed 18672106. Source: UniProt

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9NS15-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q9NS15-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1082-1128: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 4343 Potential
Chain44 – 13031260Latent-transforming growth factor beta-binding protein 3
PRO_0000007646

Regions

Domain109 – 14133EGF-like 1
Domain277 – 33155TB 1
Domain355 – 39541EGF-like 2; calcium-binding Potential
Domain403 – 45553TB 2
Domain574 – 61542EGF-like 3
Domain616 – 65944EGF-like 4; calcium-binding Potential
Domain660 – 70243EGF-like 5; calcium-binding Potential
Domain744 – 78441EGF-like 6; calcium-binding Potential
Domain785 – 82541EGF-like 7; calcium-binding Potential
Domain826 – 86540EGF-like 8; calcium-binding Potential
Domain866 – 90843EGF-like 9; calcium-binding Potential
Domain917 – 97155TB 3
Domain993 – 103543EGF-like 10; calcium-binding Potential
Domain1036 – 107641EGF-like 11; calcium-binding Potential
Domain1082 – 112241EGF-like 12; calcium-binding Potential
Domain1136 – 118651TB 4
Domain1254 – 129845EGF-like 13; calcium-binding Potential
Compositional bias3 – 167165Gly-rich
Compositional bias578 – 894317Cys-rich

Amino acid modifications

Glycosylation891N-linked (GlcNAc...) Potential
Glycosylation3491N-linked (GlcNAc...) Potential
Glycosylation8451N-linked (GlcNAc...) Potential
Glycosylation9361N-linked (GlcNAc...) Potential
Glycosylation12751N-linked (GlcNAc...) Potential
Disulfide bond113 ↔ 123 By similarity
Disulfide bond117 ↔ 129 By similarity
Disulfide bond131 ↔ 140 By similarity
Disulfide bond359 ↔ 370 By similarity
Disulfide bond365 ↔ 379 By similarity
Disulfide bond381 ↔ 394 By similarity
Disulfide bond578 ↔ 590 By similarity
Disulfide bond585 ↔ 599 By similarity
Disulfide bond601 ↔ 614 By similarity
Disulfide bond620 ↔ 632 By similarity
Disulfide bond625 ↔ 641 By similarity
Disulfide bond643 ↔ 658 By similarity
Disulfide bond664 ↔ 676 By similarity
Disulfide bond670 ↔ 685 By similarity
Disulfide bond687 ↔ 701 By similarity
Disulfide bond748 ↔ 759 By similarity
Disulfide bond754 ↔ 768 By similarity
Disulfide bond770 ↔ 783 By similarity
Disulfide bond789 ↔ 800 By similarity
Disulfide bond795 ↔ 809 By similarity
Disulfide bond811 ↔ 824 By similarity
Disulfide bond830 ↔ 841 By similarity
Disulfide bond836 ↔ 850 By similarity
Disulfide bond852 ↔ 864 By similarity
Disulfide bond870 ↔ 883 By similarity
Disulfide bond877 ↔ 892 By similarity
Disulfide bond894 ↔ 907 By similarity
Disulfide bond997 ↔ 1010 By similarity
Disulfide bond1005 ↔ 1019 By similarity
Disulfide bond1021 ↔ 1034 By similarity
Disulfide bond1040 ↔ 1051 By similarity
Disulfide bond1046 ↔ 1060 By similarity
Disulfide bond1062 ↔ 1075 By similarity
Disulfide bond1086 ↔ 1097 By similarity
Disulfide bond1092 ↔ 1106 By similarity
Disulfide bond1108 ↔ 1121 By similarity
Disulfide bond1258 ↔ 1273 By similarity
Disulfide bond1268 ↔ 1282 By similarity
Disulfide bond1284 ↔ 1297 By similarity

Natural variations

Alternative sequence1082 – 112847Missing in isoform 2.
VSP_009241

Experimental info

Sequence conflict351Missing in BAB15767. Ref.2
Sequence conflict4771D → H in AAB64201. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 17, 2006. Version 4.
Checksum: 3BC6B1EE19198414

FASTA1,303139,359
        10         20         30         40         50         60 
MPGPRGAAGG LAPEMRGAGA AGLLALLLLL LLLLLGLGGR VEGGPAGERG AGGGGALARE 

        70         80         90        100        110        120 
RFKVVFAPVI CKRTCLKGQC RDSCQQGSNM TLIGENGHST DTLTGSGFRV VVCPLPCMNG 

       130        140        150        160        170        180 
GQCSSRNQCL CPPDFTGRFC QVPAGGAGGG TGGSGPGLSR TGALSTGALP PLAPEGDSVA 

       190        200        210        220        230        240 
SKHAIYAVQV IADPPGPGEG PPAQHAAFLV PLGPGQISAE VQAPPPVVNV RVHHPPEASV 

       250        260        270        280        290        300 
QVHRIESSNA ESAAPSQHLL PHPKPSHPRP PTQKPLGRCF QDTLPKQPCG SNPLPGLTKQ 

       310        320        330        340        350        360 
EDCCGSIGTA WGQSKCHKCP QLQYTGVQKP GPVRGEVGAD CPQGYKRLNS THCQDINECA 

       370        380        390        400        410        420 
MPGVCRHGDC LNNPGSYRCV CPPGHSLGPS RTQCIADKPE EKSLCFRLVS PEHQCQHPLT 

       430        440        450        460        470        480 
TRLTRQLCCC SVGKAWGARC QRCPTDGTAA FKEICPAGKG YHILTSHQTL TIQGESDFSL 

       490        500        510        520        530        540 
FLHPDGPPKP QQLPESPSQA PPPEDTEEER GVTTDSPVSE ERSVQQSHPT ATTTPARPYP 

       550        560        570        580        590        600 
ELISRPSPPT MRWFLPDLPP SRSAVEIAPT QVTETDECRL NQNICGHGEC VPGPPDYSCH 

       610        620        630        640        650        660 
CNPGYRSHPQ HRYCVDVNEC EAEPCGPGRG ICMNTGGSYN CHCNRGYRLH VGAGGRSCVD 

       670        680        690        700        710        720 
LNECAKPHLC GDGGFCINFP GHYKCNCYPG YRLKASRPPV CEDIDECRDP SSCPDGKCEN 

       730        740        750        760        770        780 
KPGSFKCIAC QPGYRSQGGG ACRDVNECAE GSPCSPGWCE NLPGSFRCTC AQGYAPAPDG 

       790        800        810        820        830        840 
RSCLDVDECE AGDVCDNGIC SNTPGSFQCQ CLSGYHLSRD RSHCEDIDEC DFPAACIGGD 

       850        860        870        880        890        900 
CINTNGSYRC LCPQGHRLVG GRKCQDIDEC SQDPSLCLPH GACKNLQGSY VCVCDEGFTP 

       910        920        930        940        950        960 
TQDQHGCEEV EQPHHKKECY LNFDDTVFCD SVLATNVTQQ ECCCSLGAGW GDHCEIYPCP 

       970        980        990       1000       1010       1020 
VYSSAEFHSL CPDGKGYTQD NNIVNYGIPA HRDIDECMLF GSEICKEGKC VNTQPGYECY 

      1030       1040       1050       1060       1070       1080 
CKQGFYYDGN LLECVDVDEC LDESNCRNGV CENTRGGYRC ACTPPAEYSP AQRQCLSPEE 

      1090       1100       1110       1120       1130       1140 
MDVDECQDPA ACRPGRCVNL PGSYRCECRP PWVPGPSGRD CQLPESPAER APERRDVCWS 

      1150       1160       1170       1180       1190       1200 
QRGEDGMCAG PLAGPALTFD DCCCRQGRGW GAQCRPCPPR GAGSHCPTSQ SESNSFWDTS 

      1210       1220       1230       1240       1250       1260 
PLLLGKPPRD EDSSEEDSDE CRCVSGRCVP RPGGAVCECP GGFQLDASRA RCVDIDECRE 

      1270       1280       1290       1300 
LNQRGLLCKS ERCVNTSGSF RCVCKAGFAR SRPHGACVPQ RRR 

« Hide

Isoform 2 [UniParc].

Checksum: 1D930E5D208601E2
Show »

FASTA1,256134,292

References

« Hide 'large scale' references
[1]"Secretion of human latent TGF-beta-binding protein-3 (LTBP-3) is dependent on co-expression of TGF-beta."
Penttinen C., Saharinen J., Weikkolainen K., Hyytiainen M., Keski-Oja J.
J. Cell Sci. 115:3457-3468(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION (ISOFORM 2).
[2]"The nucleotide sequence of a long cDNA clone isolated from human spleen."
Ohara O., Nagase T., Kikuno R., Okumura K.
Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Spleen.
[3]"Analysis of the expression pattern of the latent transforming growth factor beta binding protein isoforms in normal and diseased human liver reveals a new splice variant missing the proteinase-sensitive hinge region."
Michel K., Roth S., Trautwein C., Gong W., Flemming P., Gressner A.M.
Hepatology 27:1592-1599(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 394-573.
Tissue: Liver.
[4]"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] OF 514-1303 (ISOFORM 2).
Tissue: Colon.
[5]"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 793-1303.
Tissue: Uterus.
[6]"Specific sequence motif of 8-Cys repeats of TGF-beta binding proteins, LTBPs, creates a hydrophobic interaction surface for binding of small latent TGF-beta."
Saharinen J., Keski-Oja J.
Mol. Biol. Cell 11:2691-2704(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TGFB1.
[7]"Latent transforming growth factor-beta binding proteins (LTBPs) --structural extracellular matrix proteins for targeting TGF-beta action."
Saharinen J., Hyytiainen M., Taipale J., Keski-Oja J.
Cytokine Growth Factor Rev. 10:99-117(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[8]"The latent transforming growth factor beta binding protein (LTBP) family."
Oklu R., Hesketh R.
Biochem. J. 352:601-610(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[9]"Oligodontia is caused by mutation in LTBP3, the gene encoding latent TGF-beta binding protein 3."
Noor A., Windpassinger C., Vitcu I., Orlic M., Rafiq M.A., Khalid M., Malik M.N., Ayub M., Alman B., Vincent J.B.
Am. J. Hum. Genet. 84:519-523(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN STHAG6.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF135960 mRNA. Translation: AAF62352.3.
AK024477 mRNA. Translation: BAB15767.1. Different initiation.
AF011407 mRNA. Translation: AAB64201.1.
BC008761 mRNA. Translation: AAH08761.2.
AL117551 mRNA. Translation: CAB55988.1.
CCDSCCDS44647.1. [Q9NS15-1]
CCDS8103.1. [Q9NS15-2]
PIRT17298.
RefSeqNP_001123616.1. NM_001130144.2. [Q9NS15-1]
NP_001157738.1. NM_001164266.1.
NP_066548.2. NM_021070.4. [Q9NS15-2]
UniGeneHs.289019.

3D structure databases

ProteinModelPortalQ9NS15.
SMRQ9NS15. Positions 296-461, 573-1122, 1234-1297.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110232. 8 interactions.
IntActQ9NS15. 6 interactions.
MINTMINT-1184940.
STRING9606.ENSP00000301873.

PTM databases

PhosphoSiteQ9NS15.

Polymorphism databases

DMDM116242623.

Proteomic databases

MaxQBQ9NS15.
PaxDbQ9NS15.
PRIDEQ9NS15.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000301873; ENSP00000301873; ENSG00000168056. [Q9NS15-1]
ENST00000322147; ENSP00000326647; ENSG00000168056. [Q9NS15-2]
GeneID4054.
KEGGhsa:4054.
UCSCuc001oei.3. human. [Q9NS15-2]
uc001oej.3. human. [Q9NS15-1]

Organism-specific databases

CTD4054.
GeneCardsGC11M065306.
HGNCHGNC:6716. LTBP3.
MIM602090. gene.
613097. phenotype.
neXtProtNX_Q9NS15.
Orphanet2227. Hypodontia.
99798. Oligodontia.
PharmGKBPA30479.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG261244.
HOGENOMHOG000293153.
HOVERGENHBG052370.
InParanoidQ9NS15.
KOK08023.
OMAEGPPAQH.
PhylomeDBQ9NS15.
TreeFamTF317514.

Enzyme and pathway databases

ReactomeREACT_118779. Extracellular matrix organization.

Gene expression databases

ArrayExpressQ9NS15.
BgeeQ9NS15.
CleanExHS_LTBP3.
GenevestigatorQ9NS15.

Family and domain databases

Gene3D3.90.290.10. 5 hits.
InterProIPR026823. cEGF.
IPR000742. EG-like_dom.
IPR001881. EGF-like_Ca-bd_dom.
IPR013032. EGF-like_CS.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
IPR009030. Growth_fac_rcpt_N_dom.
IPR017878. TB_dom.
[Graphical view]
PfamPF12662. cEGF. 1 hit.
PF07645. EGF_CA. 10 hits.
PF00683. TB. 4 hits.
[Graphical view]
SMARTSM00181. EGF. 3 hits.
SM00179. EGF_CA. 12 hits.
[Graphical view]
SUPFAMSSF57184. SSF57184. 4 hits.
SSF57581. SSF57581. 4 hits.
PROSITEPS00010. ASX_HYDROXYL. 11 hits.
PS00022. EGF_1. 1 hit.
PS01186. EGF_2. 8 hits.
PS50026. EGF_3. 13 hits.
PS01187. EGF_CA. 12 hits.
PS51364. TB. 4 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSLTBP3. human.
GeneWikiLTBP3.
GenomeRNAi4054.
NextBio15884.
PROQ9NS15.
SOURCESearch...

Entry information

Entry nameLTBP3_HUMAN
AccessionPrimary (citable) accession number: Q9NS15
Secondary accession number(s): O15107 expand/collapse secondary AC list , Q96HB9, Q9H7K2, Q9UFN4
Entry history
Integrated into UniProtKB/Swiss-Prot: January 16, 2004
Last sequence update: October 17, 2006
Last modified: July 9, 2014
This is version 126 of the entry and version 4 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

MIM cross-references

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

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM