| Tbio | Latent-transforming growth factor beta-binding protein 4 |
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) (By similarity).
The protein encoded by this gene binds transforming growth factor beta (TGFB) as it is secreted and targeted to the extracellular matrix. TGFB is biologically latent after secretion and insertion into the extracellular matrix, and sheds TGFB and other proteins upon activation. Defects in this gene may be a cause of cutis laxa and severe pulmonary, gastrointestinal, and urinary abnormalities. Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2010]
The protein encoded by this gene binds transforming growth factor beta (TGFB) as it is secreted and targeted to the extracellular matrix. TGFB is biologically latent after secretion and insertion into the extracellular matrix, and sheds TGFB and other proteins upon activation. Defects in this gene may be a cause of cutis laxa and severe pulmonary, gastrointestinal, and urinary abnormalities. Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2010]
Comments
| Disease | Target Count | P-value |
|---|---|---|
| non-small cell lung cancer | 2798 | 2.5e-18 |
| lung carcinoma | 2844 | 1.6e-14 |
| lung adenocarcinoma | 2714 | 2.7e-11 |
| ovarian cancer | 8491 | 7.1e-11 |
| psoriasis | 6685 | 1.3e-10 |
| breast carcinoma | 1614 | 1.0e-05 |
| non-inflammatory breast cancer | 208 | 5.2e-05 |
| atypical teratoid / rhabdoid tumor | 4369 | 5.5e-05 |
| sonic hedgehog group medulloblastoma | 1482 | 2.3e-04 |
| ductal carcinoma in situ | 1745 | 2.6e-04 |
| intraductal papillary-mucinous adenoma (IPMA) | 2956 | 5.3e-04 |
| invasive ductal carcinoma | 2950 | 9.4e-04 |
| primary pancreatic ductal adenocarcinoma | 1271 | 4.6e-03 |
| interstitial cystitis | 2299 | 9.6e-03 |
| intraductal papillary-mucinous neoplasm (IPMN) | 3289 | 1.0e-02 |
| fibroadenoma | 557 | 1.4e-02 |
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| Cutis laxa | 28 | 4.934 | 2.5 |
| Duchenne muscular dystrophy | 602 | 4.225 | 2.1 |
| Pulmonary emphysema | 34 | 3.631 | 1.8 |
| Arterial tortuosity syndrome | 6 | 3.329 | 1.7 |
| Tracheomalacia | 13 | 3.016 | 1.5 |
| Disease | Target Count |
|---|---|
| Cutis Laxa, Autosomal Recessive, Type 1C | 1 |
| Muscular Dystrophy, Duchenne Type | 2 |
| Disease | Target Count |
|---|---|
| Urban-Rifkin-Davis syndrome | 1 |
| Disease | log2 FC | p |
|---|---|---|
| psoriasis | -1.700 | 1.3e-10 |
| atypical teratoid / rhabdoid tumor | 1.200 | 5.5e-05 |
| primary pancreatic ductal adenocarcinoma | 1.030 | 4.6e-03 |
| non-small cell lung cancer | -1.581 | 2.5e-18 |
| intraductal papillary-mucinous adenoma (... | -1.200 | 5.3e-04 |
| intraductal papillary-mucinous neoplasm ... | -1.100 | 1.0e-02 |
| breast carcinoma | -1.400 | 1.0e-05 |
| fibroadenoma | -1.100 | 1.4e-02 |
| interstitial cystitis | -1.400 | 9.6e-03 |
| sonic hedgehog group medulloblastoma | 1.500 | 2.3e-04 |
| lung adenocarcinoma | -1.900 | 2.7e-11 |
| invasive ductal carcinoma | -1.900 | 9.4e-04 |
| non-inflammatory breast cancer | -1.300 | 5.2e-05 |
| lung carcinoma | -1.500 | 1.6e-14 |
| ductal carcinoma in situ | -1.700 | 2.6e-04 |
| ovarian cancer | -2.200 | 7.1e-11 |
| PMID | Text | |
|---|---|---|
| 26918958 | The LTBP4 VTTT allele is associated with increased risk of dilated cardiomyopathy in European Americans. LTBP4 protein with the IAAM residues bound more latent TGFbeta compared to the LTBP4 VTTT protein. | |
| 25882708 | Our results show that LTBP4 interacts with TGFBR2 and stabilizes TGFbeta receptors by preventing their endocytosis and lysosomal degradation in a ligand-dependent and receptor kinase activity-dependent manner. | |
| 25675815 | It recruits elastin to microfibrils via fibulin-5. | |
| 25641372 | In Caucasians with Duchenne muscular dystrophy and LTBP4 genotype there was a protective effect on age at loss of ambulation. | |
| 25476005 | We show that corticosteroid treatment and the IAAM haplotype of the LTBP4 gene are significantly associated with prolonged ambulation in patients with Duchenne muscular dystrophy | |
| 25338755 | In the mdx mouse model of Duchenne muscular dystrophy, the human LTBP4 transgene exacerbated muscular dystrophy symptoms and resulted in weaker muscles with an increased inflammatory infiltrate. | |
| 23741501 | Latent transforming growth factor beta-binding protein 4 is downregulated in esophageal cancer via promoter methylation. | |
| 23440719 | LTBP4 haplotype influences age at loss of ambulation, and should be considered in the management of Duchenne muscular dystrophy patients. | |
| 22829427 | Data indicate mutations of FBLN4, FBLN5, and LTBP4 in 12 probands presenting with type 1 recessive cutis laxa. | |
| 21505857 | the G1 and G3 domains of versican were upregulated and LTBP-4 was downregulated in breast cancer stroma | |
| 21468687 | The lack of LTBP4-mediated targeting in malignant mammary tumor tissues may lead to a possible modification of TGF-ss1 and BMP bioavailability and function. | |
| 20800603 | Observational study of gene-disease association. (HuGE Navigator) | |
| 20628086 | Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator) | |
| 20587546 | Observational study of gene-disease association. (HuGE Navigator) | |
| 20424473 | Observational study of gene-disease association. (HuGE Navigator) | |
| 20175115 | These data suggest that LTBP-4 functions are modified by tissue-specific expression of the two N-terminally distinct variants, which in addition exhibit significant differences in cellular processing and targeting. | |
| 19998449 | Observational study of gene-disease association. (HuGE Navigator) | |
| 19913121 | Observational study of gene-disease association. (HuGE Navigator) | |
| 19897194 | Meta-analysis of abdominal aortic aneurysm size and growth rates demonstrated a significant association with the LTBP4 21011A>T genotype (a 2% decrease in AAA diameter, or a 0.53 mm/year reduction in AAA growth rate, per T allele [p=0.03, p=0.01]). | |
| 19897194 | Observational study of gene-disease association. (HuGE Navigator) | |
| 19836010 | Mutations in LTBP4 cause a syndrome of impaired pulmonary, gastrointestinal, genitourinary, musculoskeletal, and dermal development. | |
| 18585707 | Novel functions for LTBP-4 as an adhesion molecule. | |
| 18487557 | Our findings suggest that variations in or near the HPN and LTBP4 genes do not play a role in the susceptibility to IA in the Dutch population. | |
| 18487557 | Observational study of gene-disease association. (HuGE Navigator) | |
| 16456143 | Observational study of gene-disease association. (HuGE Navigator) | |
| 16157329 | Extracellular matrix is an important site of deposition for LTBP-3 and LTBP-4. |
MPRPGTSGRRPLLLVLLLPLFAAATSAASPSPSPSQVVEVPGVPSRPASVAVCRCCPGQTSRRSRCIRAF 1 - 70 CRVRSCQPKKCAGPQRCLNPVPAVPSPSPSVRKRQVSLNWQPLTLQEARALLKRRRPRGPGGRGLLRRRP 71 - 140 PQRAPAGKAPVLCPLICHNGGVCVKPDRCLCPPDFAGKFCQLHSSGARPPAPAVPGLTRSVYTMPLANHR 141 - 210 DDEHGVASMVSVHVEHPQEASVVVHQVERVSGPWEEADAEAVARAEAAARAEAAAPYTVLAQSAPREDGY 211 - 280 SDASGFGYCFRELRGGECASPLPGLRTQEVCCRGAGLAWGVHDCQLCSERLGNSERVSAPDGPCPTGFER 281 - 350 VNGSCEDVDECATGGRCQHGECANTRGGYTCVCPDGFLLDSSRSSCISQHVISEAKGPCFRVLRDGGCSL 351 - 420 PILRNITKQICCCSRVGKAWGRGCQLCPPFGSEGFREICPAGPGYHYSASDLRYNTRPLGQEPPRVSLSQ 421 - 490 PRTLPATSRPSAGFLPTHRLEPRPEPRPDPRPGPELPLPSIPAWTGPEIPESGPSSGMCQRNPQVCGPGR 491 - 560 CISRPSGYTCACDSGFRLSPQGTRCIDVDECRRVPPPCAPGRCENSPGSFRCVCGPGFRAGPRAAECLDV 561 - 630 DECHRVPPPCDLGRCENTPGSFLCVCPAGYQAAPHGASCQDVDECTQSPGLCGRGACKNLPGSFRCVCPA 631 - 700 GFRGSACEEDVDECAQEPPPCGPGRCDNTAGSFHCACPAGFRSRGPGAPCQDVDECARSPPPCTYGRCEN 701 - 770 TEGSFQCVCPMGFQPNTAGSECEDVDECENHLACPGQECVNSPGSFQCRTCPSGHHLHRGRCTDVDECSS 771 - 840 GAPPCGPHGHCTNTEGSFRCSCAPGYRAPSGRPGPCADVNECLEGDFCFPHGECLNTDGSFACTCAPGYR 841 - 910 PGPRGASCLDVDECSEEDLCQSGICTNTDGSFECICPPGHRAGPDLASCLDVDECRERGPALCGSQRCEN 911 - 980 SPGSYRCVRDCDPGYHAGPEGTCDDVDECQEYGPEICGAQRCENTPGSYRCTPACDPGYQPTPGGGCQDV 981 - 1050 DECRNRSFCGAHAVCQNLPGSFQCLCDQGYEGARDGRHCVDVNECETLQGVCGAALCENVEGSFLCVCPN 1051 - 1120 SPEEFDPMTGRCVPPRTSAGTFPGSQPQAPASPVLPARPPPPPLPRRPSTPRQGPVGSGRRECYFDTAAP 1121 - 1190 DACDNILARNVTWQECCCTVGEGWGSGCRIQQCPGTETAEYQSLCPHGRGYLAPSGDLSLRRDVDECQLF 1191 - 1260 RDQVCKSGVCVNTAPGYSCYCSNGYYYHTQRLECIDNDECADEEPACEGGRCVNTVGSYHCTCEPPLVLD 1261 - 1330 GSQRRCVSNESQSLDDNLGVCWQEVGADLVCSHPRLDRQATYTECCCLYGEAWGMDCALCPAQDSDDFEA 1331 - 1400 LCNVLRPPAYSPPRPGGFGLPYEYGPDLGPPYQGLPYGPELYPPPALPYDPYPPPPGPFARREAPYGAPR 1401 - 1470 FDMPDFEDDGGPYGESEAPAPPGPGTRWPYRSRDTRRSFPEPEEPPEGGSYAGSLAEPYEELEAEECGIL 1471 - 1540 DGCTNGRCVRVPEGFTCRCFDGYRLDMTRMACVDINECDEAEAASPLCVNARCLNTDGSFRCICRPGFAP 1541 - 1610 THQPHHCAPARPRA 1611 - 1624 //
| PMID | Year | Title | |
|---|---|---|---|
| 26918958 | 2016 | Genotype-Specific Interaction of Latent TGF? Binding Protein 4 with TGF?. | |
| 25882708 | 2015 | Latent transforming growth factor binding protein 4 regulates transforming growth factor beta receptor stability. | |
| 25675815 | 2014 | [Essential role of LTBP-4 in elastic fiber assembly]. | |
| 25641372 | 2015 | Genetic modifiers of ambulation in the Cooperative International Neuromuscular Research Group Duchenne Natural History Study. | |
| 25476005 | 2015 | Validation of genetic modifiers for Duchenne muscular dystrophy: a multicentre study assessing SPP1 and LTBP4 variants. | |
| 25338755 | 2014 | Targeting latent TGF? release in muscular dystrophy. | |
| 24275569 | 2014 | An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. | |
| 23741501 | 2013 | Latent transforming growth factor ?-binding protein 4 is downregulated in esophageal cancer via promoter methylation. | |
| 23440719 | 2013 | LTBP4 genotype predicts age of ambulatory loss in Duchenne muscular dystrophy. | |
| 23376485 | 2013 | Proteomic analysis of podocyte exosome-enriched fraction from normal human urine. | |
| 22829427 | 2013 | Comprehensive clinical and molecular analysis of 12 families with type 1 recessive cutis laxa. | |
| 21505857 | 2012 | Versican G1 and G3 domains are upregulated and latent transforming growth factor-? binding protein-4 is downregulated in breast cancer stroma. | |
| 21468687 | 2011 | Latent transforming growth factor binding protein 4 (LTBP4) is downregulated in mouse and human DCIS and mammary carcinomas. | |
| 21078624 | 2011 | Comparison of an expanded ataxia interactome with patient medical records reveals a relationship between macular degeneration and ataxia. | |
| 20800603 | 2010 | Investigation of genetic susceptibility factors for human longevity - a targeted nonsynonymous SNP study. | |
| 20628086 | 2010 | Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. | |
| 20587546 | 2010 | Interferon gamma receptor 2 gene variants are associated with liver fibrosis in patients with chronic hepatitis C infection. | |
| 20551380 | 2010 | Proteomics characterization of extracellular space components in the human aorta. | |
| 20424473 | 2010 | L-type voltage-dependent calcium channel alpha subunit 1C is a novel candidate gene associated with secondary hyperparathyroidism: an application of haplotype-based analysis for multiple linked single nucleotide polymorphisms. | |
| 20175115 | 2010 | Independent regulation of short and long forms of latent TGF-beta binding protein (LTBP)-4 in cultured fibroblasts and human tissues. | |
| 19998449 | 2010 | Polymorphisms in the transforming growth factor beta 1 pathway in relation to colorectal cancer progression. | |
| 19913121 | 2009 | Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip. | |
| 19897194 | 2010 | Assessment of the association between genetic polymorphisms in transforming growth factor beta, and its binding protein (LTBP), and the presence, and expansion, of Abdominal Aortic Aneurysm. | |
| 19836010 | 2009 | Mutations in LTBP4 cause a syndrome of impaired pulmonary, gastrointestinal, genitourinary, musculoskeletal, and dermal development. | |
| 18585707 | 2008 | Fibronectin and heparin binding domains of latent TGF-beta binding protein (LTBP)-4 mediate matrix targeting and cell adhesion. | |
| 18487557 | 2008 | Genes involved in the transforming growth factor beta signalling pathway and the risk of intracranial aneurysms. | |
| 16713569 | 2006 | A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration. | |
| 16456143 | 2006 | Genetic association analysis of functional impairment in chronic obstructive pulmonary disease. | |
| 16157329 | 2005 | Sequential deposition of latent TGF-beta binding proteins (LTBPs) during formation of the extracellular matrix in human lung fibroblasts. | |
| 15057824 | 2004 | The DNA sequence and biology of human chromosome 19. | |
| 14702039 | 2004 | Complete sequencing and characterization of 21,243 full-length human cDNAs. | |
| 12429738 | 2003 | Latent transforming growth factor beta-binding protein 1 interacts with fibrillin and is a microfibril-associated protein. | |
| 11683420 | 2001 | Novel non-TGF-beta-binding splice variant of LTBP-4 in human cells and tissues provides means to decrease TGF-beta deposition. | |
| 11104663 | 2000 | The latent transforming growth factor beta binding protein (LTBP) family. | |
| 10930463 | 2000 | 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. | |
| 9660815 | 1998 | Identification and characterization of a new latent transforming growth factor-beta-binding protein, LTBP-4. | |
| 9271198 | 1997 | Sequence and expression of a novel member (LTBP-4) of the family of latent transforming growth factor-beta binding proteins. |
