TRIM18 (Kr.X22.2) MID1 , (C-I COS, FN3, PRYSPRY)

TRIM18, (Kr.23q22.2) MID1, MIDIN

Tämä TRIM18 esiintyy X-kromosomissa. Ja ilmenee runsaimmin prostatassa ja virstarakossa ja 24 muussa kudoksessa. Geenillä on useita nimiä. OS; FXY; OSX; OGS1; XPRF; BBBG1; GBBB1; MIDIN; RNF59; ZNFXY; TRIM18 . Rakenne on tyypillinen TRIM rakenne RBCC N-terminaalisesti ja kuuluu C-I alaluokkaan C-terminaalisen rakenteen mukaan (COS, FN3,PRYSPRY). Proteiini muodsotaa homodimeerejä, jotka assosioituvat sytoplasman mikrotubuluksiin. Proteiini todennäköisesti osallistuu multiproteiinirakenteiden muodostamiseen toimien mikrotubulusten ankkurikohtina. Tämän geenin mutaatio liittyy X-kromosomiin linkkiytyneeseen Opitzin oireyhtymään, jolle on tyypillistä kehon keskiviivaan liittyvät anomaliat kuten huuli ja kitlakihalkiot , sydänanomaliat, hypospadiat ja corpus callosum(aivokurkiaisen) muodostumattomuus. Geenin alternatiivi pleissaus tai alternatiivinen polyadenylaatio johtavat moniin transkripteihin, joilla on erilaisia kudosspesifisyyksiä. Geeniä ilmenee yleisesti kehossa 26 kudoksessa .

Nimistä ensisijainen on E3 ubikitiiniligaasi Midline-1, MID1

Preferred Names E3 ubiquitin-protein ligase Midline-1

Names

Opitz/BBB syndrome

RING finger protein 59

RING finger protein Midline-1

RING-type E3 ubiquitin transferase Midline-1

midline 1 RING finger protein

putative transcription factor XPRF

tripartite motif protein TRIM18

tripartite motif-containing protein 18

zinc finger on X and Y, mouse, homolog of

• https://www.ncbi.nlm.nih.gov/gene/4281
• Official Symbol MID1provided by HGNC Official Full Name midline 1provided by HGNC Also known as OS; FXY; OSX; OGS1; XPRF; BBBG1; GBBB1; MIDIN; RNF59; ZNFXY; TRIM18 Summary The protein encoded by this gene is a member of the tripartite motif (TRIM) family, also known as the 'RING-B box-coiled coil' (RBCC) subgroup of RING finger proteins. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. This protein forms homodimers which associate with microtubules in the cytoplasm. The protein is likely involved in the formation of multiprotein structures acting as anchor points to microtubules. Mutations in this gene have been associated with the X-linked form of Opitz syndrome, which is characterized by midline abnormalities such as cleft lip, laryngeal cleft, heart defects, hypospadias, and agenesis of the corpus callosum. This gene was also the first example of a gene subject to X inactivation in human while escaping it in mouse. Alternative promoter use, alternative splicing and alternative polyadenylation result in multiple transcript variants that have different tissue specificities. [provided by RefSeq, Dec 2016] Expression Ubiquitous expression in prostate (RPKM 2.5), urinary bladder (RPKM 2.3) and 24 other tissues See more Orthologs mouse all

  • TRIM18 peptidirakenne ja detaljeja

Konservoidut domeenit

• Conserved Domains (5) summary

smart00336
Location:171 → 212

BBOX; B-Box-type zinc finger

cd00063
Location:381 → 481

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

cd12892
Location:485 → 661

SPRY_PRY_TRIM18; PRY/SPRY domain of TRIM18/MID1, also known as FXY or RNF59

cd16753
Location:8 → 61

RING-HC_MID1; RING finger, HC subclass, found in midline-1 (MID1) and similar proteins

cl25407
Location:219 → 344

ClassIIa_HDAC_Gln-rich-N; Glutamine-rich N-terminal helical domain of various Class IIa histone deacetylases (HDAC4, HDAC5 and HDCA9)

E3 ubiquitin-protein ligase Midline-1 isoform 1 [Homo sapiens]

NCBI Reference Sequence: NP_000372.1

Identical Proteins FASTA Graphics

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LOCUS       NP_000372                667 aa            linear   PRI 26-FEB-2018
DEFINITION  E3 ubiquitin-protein ligase Midline-1 isoform 1 [Homo sapiens].
ACCESSION   NP_000372
VERSION     NP_000372.1
DBSOURCE    REFSEQ: accession NM_000381.3
KEYWORDS    RefSeq.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 667)
  AUTHORS   Unterbruner K, Matthes F, Schilling J, Nalavade R, Weber S, Winter
            J and Krauss S.
  TITLE     MicroRNAs miR-19, miR-340, miR-374 and miR-542 regulate MID1
            protein expression
  JOURNAL   PLoS ONE 13 (1), e0190437 (2018)
   PUBMED   29293623
  REMARK    GeneRIF: identified four miRNAs, miR-19, miR-340, miR-374 and
            miR-542 that bind to the 3'-UTR of the MID1 mRNA. These miRNAs not
            only regulate MID1 expression but also mTOR signaling and
            translation of disease associated mRNAs and could therefore serve
            as potential drugs for future therapy development
            Publication Status: Online-Only
REFERENCE   2  (residues 1 to 667)
  AUTHORS   Zanchetta ME, Napolitano LMR, Maddalo D and Meroni G.
  TITLE     The E3 ubiquitin ligase MID1/TRIM18 promotes atypical
            ubiquitination of the BRCA2-associated factor 35, BRAF35
  JOURNAL   Biochim. Biophys. Acta 1864 (10), 1844-1854 (2017)
   PUBMED   28760657
  REMARK    GeneRIF: Our data reveal a novel role for MID1 and for atypical
            ubiquitination in balancing BRAF35 presence, and likely its
            activity, within nuclear and cytoplasmic compartments
REFERENCE   3  (residues 1 to 667)
  AUTHORS   Wright KM, Du H and Massiah MA.
  TITLE     Structural and functional observations of the P151L MID1 mutation
            reveal alpha4 plays a significant role in X-linked Opitz Syndrome
  JOURNAL   FEBS J. 284 (14), 2183-2193 (2017)
   PUBMED   28548391
  REMARK    GeneRIF: P151L MID1 mutation is associated with X-linked Opitz
            Syndrome.
REFERENCE   4  (residues 1 to 667)
  AUTHORS   Shi L, Cai G, Shi J, Guo Y, Chen D, Chen D and Yang H.
  TITLE     Ossification of the posterior ligament is mediated by osterix via
            inhibition of the beta-catenin signaling pathway
  JOURNAL   Exp. Cell Res. 349 (1), 53-59 (2016)
   PUBMED   27693496
  REMARK    GeneRIF: Osx is upregulated in patients with Ossification of the
            posterior longitudinal ligament.
REFERENCE   5  (residues 1 to 667)
  AUTHORS   Gaudenz K, Roessler E, Quaderi N, Franco B, Feldman G, Gasser DL,
            Wittwer B, Horst J, Montini E, Opitz JM, Ballabio A and Muenke M.
  TITLE     Opitz G/BBB syndrome in Xp22: mutations in the MID1 gene cluster in
            the carboxy-terminal domain
  JOURNAL   Am. J. Hum. Genet. 63 (3), 703-710 (1998)
   PUBMED   9718340
  REMARK    Erratum:[Am J Hum Genet 1998 Nov;63(5):1571]
REFERENCE   6  (residues 1 to 667)
  AUTHORS   Perry J, Feather S, Smith A, Palmer S and Ashworth A.
  TITLE     The human FXY gene is located within Xp22.3: implications for
            evolution of the mammalian X chromosome
  JOURNAL   Hum. Mol. Genet. 7 (2), 299-305 (1998)
   PUBMED   9425238
REFERENCE   7  (residues 1 to 667)
  AUTHORS   Quaderi NA, Schweiger S, Gaudenz K, Franco B, Rugarli EI, Berger W,
            Feldman GJ, Volta M, Andolfi G, Gilgenkrantz S, Marion RW, Hennekam
            RC, Opitz JM, Muenke M, Ropers HH and Ballabio A.
  TITLE     Opitz G/BBB syndrome, a defect of midline development, is due to
            mutations in a new RING finger gene on Xp22
  JOURNAL   Nat. Genet. 17 (3), 285-291 (1997)
   PUBMED   9354791
REFERENCE   8  (residues 1 to 667)
  AUTHORS   Robin NH, Feldman GJ, Aronson AL, Mitchell HF, Weksberg R, Leonard
            CO, Burton BK, Josephson KD, Laxova R, Aleck KA, Allanson JE,
            Guion-Almeida ML, Martin RA, Leichtman LG, Price RA, Opitz JM and
            Muenke M.
  TITLE     Opitz syndrome is genetically heterogeneous, with one locus on
            Xp22, and a second locus on 22q11.2
  JOURNAL   Nat. Genet. 11 (4), 459-461 (1995)
   PUBMED   7493033
REFERENCE   9  (residues 1 to 667)
  AUTHORS   Scott,D.A.
  TITLE     Esophageal Atresia/Tracheoesophageal Fistula Overview
  JOURNAL   (in) Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens
            K and Amemiya A (Eds.);
            GENEREVIEWS((R));
            (1993)
   PUBMED   20301753
REFERENCE   10 (residues 1 to 667)
  AUTHORS   Meroni,G.
  TITLE     X-Linked Opitz G/BBB Syndrome
  JOURNAL   (in) Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens
            K and Amemiya A (Eds.);
            GENEREVIEWS((R));
            (1993)
   PUBMED   20301502
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DC309977.1, BC053626.1 and
            EF217426.1.
            
            Summary: The protein encoded by this gene is a member of the
            tripartite motif (TRIM) family, also known as the 'RING-B
            box-coiled coil' (RBCC) subgroup of RING finger proteins. The TRIM
            motif includes three zinc-binding domains, a RING, a B-box type 1
            and a B-box type 2, and a coiled-coil region. This protein forms
            homodimers which associate with microtubules in the cytoplasm. The
            protein is likely involved in the formation of multiprotein
            structures acting as anchor points to microtubules. Mutations in
            this gene have been associated with the X-linked form of Opitz
            syndrome, which is characterized by midline abnormalities such as
            cleft lip, laryngeal cleft, heart defects, hypospadias, and
            agenesis of the corpus callosum. This gene was also the first
            example of a gene subject to X inactivation in human while escaping
            it in mouse. Alternative promoter use, alternative splicing and
            alternative polyadenylation result in multiple transcript variants
            that have different tissue specificities. [provided by RefSeq, Dec
            2016].
            
            Transcript Variant: This variant (1, also known as alpha) is the
            longest transcript. Variants 1-4 and variant 10 encode the same
            isoform (1).
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR1660805.16033.1,
                                           SRR1660807.78880.1 [ECO:0000332]
            RNAseq introns              :: mixed/partial sample support
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000350]
            ##Evidence-Data-END##
FEATURES             Location/Qualifiers
     source          1..667
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="X"
                     /map="Xp22.2"
     Protein         1..667
                     /product="E3 ubiquitin-protein ligase Midline-1 isoform 1"
                     /EC_number="2.3.2.27"
                     /note="putative transcription factor XPRF; tripartite
                     motif protein TRIM18; zinc finger on X and Y, mouse,
                     homolog of; tripartite motif-containing protein 18; RING
                     finger protein 59; midline 1 RING finger protein; RING
                     finger protein Midline-1; E3 ubiquitin-protein ligase
                     Midline-1; Opitz/BBB syndrome; RING-type E3 ubiquitin
                     transferase Midline-1"
                     /calculated_mol_wt=75120
     Region          8..61
                     /region_name="RING-HC_MID1"
                     /note="RING finger, HC subclass, found in midline-1 (MID1)
                     and similar proteins; cd16753"
                     /db_xref="CDD:319667"
     Region          10..59
                     /region_name="RING-HC finger (C3HC4-type)"
                     /note="RING-HC finger (C3HC4-type) [structural motif]"
                     /db_xref="CDD:319667"
     Site            order(10,13,25,27,30,33,56,59)
                     /site_type="other"
                     /note="Zn binding site [ion binding]"
                     /db_xref="CDD:319667"
     Site            92
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000244|PubMed:21406692,
                     ECO:0000244|PubMed:23186163}; propagated from
                     UniProtKB/Swiss-Prot (O15344.1)"
     Site            96
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000244|PubMed:23186163};
                     propagated from UniProtKB/Swiss-Prot (O15344.1)"
     Region          114..160
                     /region_name="BBOX"
                     /note="B-Box-type zinc finger; smart00336"
                     /db_xref="CDD:197662"
     Region          171..212
                     /region_name="BBOX"
                     /note="B-Box-type zinc finger; smart00336"
                     /db_xref="CDD:197662"
     Site            order(175,178,198,204)
                     /site_type="other"
                     /note="Zn2+ binding site [ion binding]"
                     /db_xref="CDD:237988"
     Region          219..344
                     /region_name="ClassIIa_HDAC_Gln-rich-N"
                     /note="Glutamine-rich N-terminal helical domain of various
                     Class IIa histone deacetylases (HDAC4, HDAC5 and HDCA9);
                     cl25407"
                     /db_xref="CDD:330228"
     Region          381..481
                     /region_name="FN3"
                     /note="Fibronectin type 3 domain; One of three types of
                     internal repeats found in the plasma protein fibronectin.
                     Its tenth fibronectin type III repeat contains an RGD cell
                     recognition sequence in a flexible loop between 2 strands.
                     Approximately 2% of all...; cd00063"
                     /db_xref="CDD:238020"
     Region          485..661
                     /region_name="SPRY_PRY_TRIM18"
                     /note="PRY/SPRY domain of TRIM18/MID1, also known as FXY
                     or RNF59; cd12892"
                     /db_xref="CDD:240472"
     Site            511
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000244|PubMed:23186163};
                     propagated from UniProtKB/Swiss-Prot (O15344.1)"
     CDS             1..667
                     /gene="MID1"
                     /gene_synonym="BBBG1; FXY; GBBB1; MIDIN; OGS1; OS; OSX;
                     RNF59; TRIM18; XPRF; ZNFXY"
                     /coded_by="NM_000381.3:402..2405"
                     /note="isoform 1 is encoded by transcript variant 1"
                     /db_xref="CCDS:CCDS14138.1"
                     /db_xref="GeneID:4281"
                     /db_xref="HGNC:HGNC:7095"
                     /db_xref="MIM:300552"
ORIGIN      
        1 metleseltc piclelfedp lllpcahslc fncahrilvs hcatnesves itafqcptcr
       61 hvitlsqrgl dglkrnvtlq niidrfqkas vsgpnspset rrerafdant mtsaekvlcq
      121 fcdqdpaqda vktcvtcevs ycdeclkath pnkkpftghr liepipdshi rglmclehed
      181 ekvnmycvtd dqlicalckl vgrhrdhqva alserydklk qnlesnltnl ikrnteletl
      241 lakliqtcqh vevnasrqea klteecdlli eiiqqrrqii gtkikegkvm rlrklaqqia
      301 nckqciersa slisqaehsl kendharflq taknitervs matassqvli peinlndtfd
      361 tfaldfsrek kllecldylt apnpptiree lctasydtit vhwtsddefs vvsyelqyti
      421 ftgqanvvsl cnsadswmiv pnikqnhytv hglqsgtkyi fmvkainqag srssepgklk
      481 tnsqpfkldp ksahrklkvs hdnltverde ssskkshtpe rftsqgsygv agnvfidsgr
      541 hywevvisgs twyaiglayk sapkhewigk nsaswalcrc nnnwvvrhns keipiepaph
      601 lrrvgilldy dngsiafyda lnsihlytfd vafaqpvcpt ftvwnkclti itglpipdhl
      661 dcteqlp
//

Related articles in PubMed

1. Structural and functional observations of the P151L MID1 mutation reveal alpha4 plays a significant role in X-linked Opitz Syndrome. Wright KM, et al. FEBS J, 2017 Jul. PMID 28548391
2. Ossification of the posterior ligament is mediated by osterix via inhibition of the β-catenin signaling pathway. Shi L, et al. Exp Cell Res, 2016 Nov 15. PMID 27693496
3. Solution structure of the microtubule-targeting COS domain of MID1. Wright KM, et al. FEBS J, 2016 Aug. PMID 27367845
4. Molecular dynamics simulation reveals insights into the mechanism of unfolding by the A130T/V mutations within the MID1 zinc-binding Bbox1 domain. Zhao Y, et al. PLoS One, 2015. PMID 25874572, Free PMC Article
5. R368X mutation in MID1 among recurrent mutations in patients with X-linked Opitz G/BBB syndrome. Preiksaitiene E, et al. Clin Dysmorphol, 2015 Jan. PMID 25304119
   

GeneRIFs: Gene References Into Functions

1. identified four miRNAs, miR-19, miR-340, miR-374 and miR-542 that bind to the 3'-UTR of the MID1 mRNA. These miRNAs not only regulate MID1 expression but also mTOR signaling and translation of disease associated mRNAs and could therefore serve as potential drugs for future therapy development
2. Our data reveal a novel role for MID1 and for atypical ubiquitination in balancing BRAF35 presence, and likely its activity, within nuclear and cytoplasmic compartments
3. P151L MID1 mutation is associated with X-linked Opitz Syndrome.
4. the coiled-coil and COS domain (CC-COS) bind to microtubules, demonstrating for the first time that MID1 can directly associate with the microtubules
5. Osx is upregulated in patients with Ossification of the posterior longitudinal ligament.
6. A130T/V mutations within the MID1 zinc-binding Bbox1 domain affects protein folding.
7. MID1 catalyzes the ubiquitination of protein phosphatase 2A and mutations within its Bbox1 domain disrupt polyubiquitination of alpha4 but not of PP2Ac in X-linked Opitz syndrome.
8. TRAIL regulates MID1 and TSLP, inflammation, fibrosis, smooth muscle hypertrophy, and expression of inflammatory effector chemokines and cytokines in experimental eosinophilic esophagitis.
9. These studies provide insight into the mechanism by which mutations observed in X-linked Opitz G syndrome affect the structure and function of the MID1 Bbox1 domain
10. A familial c.1102C>T (p.R368X) mutation in the MID1 gene, is reported.