TRIM44 (Kr. 11p13) AN3, DIPB, MC7, USP-kaltaisen TRIM , Luokittelematon C-terminaali

TRIM44,DIPB, MC7, USP-like TRIM, AN3, HSA249128

TRIM44 geeni koodaa TRIM44 proteiinia, joka kuuluu luokittelemattomiin TRIM perheen jäseniin  (UC).  Sillä on useita nimiä.  Nimi AN3 tulee taudista aniridia 3 ( iiriksen puutos 3) . Tällä geenillä on osuutta kehityksen aikana neuronaalisten solujen erilaistumiseen ja kehitykseen. Proteiinin rakenteessa on konservoitu domeeni B box Zn Finger ja siinä on sinkkijonit CHCH- motiivilla haksossa 174..215. Asemassa 336 ja 339 on fosforylaatio ( fosfoseriini).

Jos katsoo aminohappojärjestystä, huomiota kiinnittää hyvin glutamiinihappopitoinen jakso 74..172. Siinä on aminohapoista 50 % glutamiinihappoja E ja kaksi glutamiinia Q. N-terminaalisessa alueessa on Zn UBP-domeeni, joka löytyy monista ubikitiiniproteosomisysteemin proteiineista, erityisesti niistä, jotka ovat erikoistuneet poistamaan substraatista ubikitiinin ennen proteosomaalista tunnistamista, mikä johtaa substraatin hajoittamisen estämiseen. USP-kaltaisen TRIM-ominaisuutensa takia TRIM44 saattaa säädellä deubikitinaatiota ja kohdeproteiinin stabiloitumista, kuten se tekee MAVS- proteiinille ( mitokondriaaliselle antivirussignaaliproteiinille, jolla on muitakin nimiä VISA, Gardif, ISP1)-- ja täten TRIM44 edistää MAVS- välitteistä antivirus vastetta. (http://www.jimmunol.org/content/190/7/3613 )

TRIM44 tautiyhteydessä näkyy  runsaista  PubMed artikkeleista. TRIM44 säätelee PAX6 tekijää. TRIM44 variantti saattaa estää PAX6 tekijää johtaen kongenitaaliseen aniridiaan. (Variants in TRIM44 Cause Aniridia by Impairing PAX6 Expression)

Asetan proteiinirakenteen esiin PubMed lähteestä .TRIM44 geeniä ilmenee eniten aivoissa, kilpirauhasessa ja 25 muussa kudoksessa. 

• AN3; MC7; DIPB; HSA249128 Summary This gene encodes a member of the tripartite motif (TRIM) family. [provided by RefSeq, Jul 2008] Expression Ubiquitous expression in brain (RPKM 26.6), thyroid (RPKM 23.0) and 25 other tissues See more

Tuo glutamiinihappopitoinen kohta mainitaan immunogeeniseksi lähteessä Uniprot. http://www.uniprot.org/uniprot/Q96DX7

Swiss Prot Num: Q96DX7 Immunogen: The immunogen for anti-TRIM44 antibody: synthetic peptide directed towards the middle region of human TRIM44. Synthetic peptide located within the following region: SEEESETEEESEDESDEESEEDSEEEMEDEQESEAEEDNQEEGESEAEGE. GeneID: 54765

TRIM44 proteiinitiedot PubMed lähtessä:

USP-like TRIM, Interaktio TRIM17/terf kanssa. Rakenne luokittelematon UC.

            ##Evidence-Data-END##
FEATURES             Location/Qualifiers
     source          1..344
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="11"
                     /map="11p13"
     Protein         1..344
                     /product="tripartite motif-containing protein 44"
                     /calculated_mol_wt=38341
     Region          176..215
                     /region_name="zf-B_box"
                     /note="B-box zinc finger; pfam00643"
                     /db_xref="CDD:306989"
     Site            order(179,182,201,207)
                     /site_type="other"
                     /note="Zn2+ binding site [ion binding]"
                     /db_xref="CDD:237988"
     Site            336
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000250|UniProtKB:Q9QXA7};
                     propagated from UniProtKB/Swiss-Prot (Q96DX7.1)"
     Site            339
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000250|UniProtKB:Q9QXA7};
                     propagated from UniProtKB/Swiss-Prot (Q96DX7.1)"
     CDS             1..344
                     /gene="TRIM44"
                     /gene_synonym="AN3; DIPB; HSA249128; MC7"
                     /coded_by="NM_017583.5:361..1395"
                     /db_xref="CCDS:CCDS31461.1"
                     /db_xref="GeneID:54765"
                     /db_xref="HGNC:HGNC:19016"
                     /db_xref="MIM:612298"
ORIGIN      
        1 masgvgaafe elphdgtcde cepdeapgae evcrecgfcy crrhaeahrq kflshhlaey
       61 vhgsqawtpp adgegagkee aevkveqere ieseageese seeeseseee seteeesede
      121 sdeeseedse eemedeqese aeednqeege seaegeteae sefdpeieme aervakrkcp
      181 dhgldlstyc qedrqlicvl cpvigahqgh qlstldeafe elrskdsggl kaamielver
      241 lkfkssdpkv trdqmkmfiq qefkkvqkvi adeeqkalhl vdiqeamata hvteiladiq
      301 shmdrlmtqm aqakeqldts nesaepkaeg deegpsgase eedt
//

TRIM44:n kohdemolekyyli, jonka se stabiloi on MAVS, kriittinen adaptorimolekyyli 1-tyypin interferonin tuotannossa ja luonnollisen immuniteetin antivirusvasteessa

http://www.jimmunol.org/content/190/7/3613

Novel function of Trim44 promotes an antiviral response by stabilizing VISA.

Yang B¹, Wang J, Wang Y, Zhou H, Wu X, Tian Z, Sun B. Abstract
Virus-induced signaling adaptor (VISA, MAVS, cardif, IPS-1) functions as a critical adaptor in the regulation of both the production of type I IFNs and the subsequent control of the innate antiviral response. In this study, we demonstrate that tripartite motif (Trim)44 interacts with VISA and promotes VISA-mediated antiviral responses. The overexpression of Trim44 enhances the cellular response to viral infection, whereas Trim44 knockdown yields the opposite effect. Trim44 stabilizes VISA by preventing VISA ubiquitination and degradation. These findings suggest that Trim44 functions as a positive regulator of the virus-triggered immune response by enhancing the stability of VISA.PMID: 23460740 DOI: 10.4049/jimmunol.1202507
 

Artikkeleita TRIM44 osuudesta taudeissa (jatkoa)

Related articles in PubMed

1. Overexpression of TRIM44 is related to invasive potential and malignant outcomes in esophageal squamous cell carcinoma. Kawaguchi T, et al. Tumour Biol, 2017 Jun. PMID 28618928
2. A novel prognostic factor TRIM44 promotes cell proliferation and migration, and inhibits apoptosis in testicular germ cell tumor. Yamada Y, et al. Cancer Sci, 2017 Jan. PMID 27754579, Free PMC Article
3. High expression of TRIM44 is associated with enhanced cell proliferation, migration, invasion, and resistance to doxorubicin in hepatocellular carcinoma. Zhu X, et al. Tumour Biol, 2016 Nov. PMID 27619678
4. Overexpression of TRIM44 contributes to malignant outcome in gastric carcinoma. Kashimoto K, et al. Cancer Sci, 2012 Nov. PMID 22862969
5. TRIM44 promotes proliferation and metastasis in non‑small cell lung cancer via mTOR signaling pathway. Xing Y, et al. Oncotarget, 2016 May 24. PMID 27058415, Free PMC Article
   

See all (29) citations in PubMed
See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

1. Data show that the TRIM44-mTOR axis increases metastasis and proliferation.
2. These results suggest that tripartite motif-containing protein 44 protein could play a crucial role in tumor invasion through its overexpression and highlight its usefulness as a predictor and potential therapeutic target in esophageal squamous cell carcinoma
3. results suggest that high expression of TRIM44 is associated with poor prognosis and that TRIM44 plays significant role in cell proliferation, migration, and anti-apoptosis in testicular germ cell tumor
4. High expression of TRIM44 is associated with enhanced cell proliferation, migration, invasion, and resistance to doxorubicin in hepatocellular carcinoma.
5. Variants in TRIM44 Cause Aniridia by Impairing PAX6 Expression
6. Trim44 promotes non-small cell lung cancer development through activation of NF-kappaB signaling via upregulating CXCL16 and MMP9 expression.
7. Trim44 functions as a positive regulator of the virus-triggered immune response by enhancing the stability of VISA (MAVS, CARDIF, IPS-1)).
8. Overexpression of the TRIM44 protein was significantly correlated with an advanced type of macroscopic appearance.
9. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
10. terf interacts with TRIM44;TRIM44 inhibited ubiquitination of terf (TRIM17) , and thus stabilized the protein.
    

Select item 294462532.
Elevated TRIM44 promotes intrahepatic cholangiocarcinoma progression by inducing cell EMT via MAPK signaling.
Peng R, Zhang PF, Zhang C, Huang XY, Ding YB, Deng B, Bai DS, Xu YP.
Cancer Med. 2018 Mar;7(3):796-808. doi: 10.1002/cam4.1313. Epub 2018 Feb 15.
 https://www.ncbi.nlm.nih.gov/pubmed/18314910https://www.ncbi.nlm.nih.gov/pubmed/18314910

Löydän suomalisen tutkimuksen,  jossa TRIM44 mainitaan kromosomi 11 geenien joukossa  tutkittaessa assosiaatiota pään ja kaulan alueen levyepiteelikarsinoomaan. 

Genes Chromosomes Cancer. 2008 Jun;47(6):500-9. doi: 10.1002/gcc.20551.

High-resolution copy number and gene expression microarray analyses of head and neck squamous cell carcinoma cell lines of tongue and larynx.

Järvinen AK¹, Autio R, Kilpinen S, Saarela M, Leivo I, Grénman R, Mäkitie AA, Monni O.

Gene amplifications and deletions are frequent in head and neck squamous cell carcinomas (SCC) but the association of these alterations with gene expression is mostly unknown. Here, we characterized genome-wide copy number and gene expression changes on microarrays for 18 oral tongue SCC (OTSCC) cell lines. We identified a number of altered regions including nine high-level amplifications such as 

6q12-q14 (CD109, MYO6), 

9p24 (JAK2, CD274, SLC1A1, RLN1),

 11p12-p13 (TRAF6, COMMD9, TRIM44, FJX1, CD44, PDHX, APIP), 

11q13 (FADD, PPFIA1, CTTN), and

 14q24 (ABCD4, HBLD1, LTBP2, ZNF410, COQ6, ACYP1, JDP2) where 9% to 64% of genes showed overexpression. Across the whole genome, 26% of the amplified genes had associated overexpression in OTSCC. Furthermore, our data implicated that OTSCC cell lines harbored similar genomic alterations as laryngeal SCC cell lines We have previously analyzed, suggesting that despite differences in clinicopathological features there are no marked differences in molecular genetic alterations of these two HNSCC sites. To identify genes whose expression was associated with copy number increase in head and neck SCC, a statistical analysis for oral tongue and laryngeal SCC cell line data were performed. We pinpointed 1,192 genes that had a statistically significant association between copy number and gene expression. These results suggest that genomic alterations with associated gene expression changes play an important role in the malignant behavior of head and neck SCC. The identified genes provide a basis for further functional validation and may lead to the identification of novel candidates for targeted therapies. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat.