Kromosomi 12 ei sisällä TRIM jäseniä , mitä siinä sitten on luonnollista immuunipuolustusarsenaalia?

https://www.genenames.org/cgi-bin/genefamilies/set/58

 Zinc finger, RING finger- proteiineja ja E3 ligaseja kuitenkin on muitakin kuin TRIM suku.  Otan tästä hierarkiakartasta  löytämiäni  geeniesimerkkejä kromosomista  12.

MDM2 (kr.12q15) on  E3 ubikitiiniligaesiproteiini, joka sitoutuu p53 proteiiniin. MDM2 on proto-onkogeeni. Sen rakenne on  Zinc finger RANBP2- tyyppiä.

CHFR (Kr. 12q24.33) (RNF196)  on on ligaasi, joka ubikitinoi Plk1 kinaasia ja estää Cdc2  solusykliä G2-vaiheessa siirtymästä M-transitioon.  

• Chfr defines a mitotic stress checkpoint that delays entry into metaphase. Scolnick DM et al. Nature 2000 Jul;406(6794):430-435PMID: 10935642 Europe PMC Pubmed 

• The checkpoint protein Chfr is a ligase that ubiquitinates Plk1 and inhibits Cdc2 at the G2 to M transition. Kang D et al. J. Cell Biol. 2002 Jan;156(2):249-259 PMID: 11807090 Europe PMC Pubmed 

 BRAP /Kr.12q24.12) (IMP, RNF52) Geeinimi  tulee sanoista   BRCA1- associated protein.  BRAP2 on sytoplasminenproteiini, joka sitoutuu spesifisesti  NLS motiiveihin  tumaan lokalisoivaan signaaliin). 

Identification of a novel cytoplasmic protein that specifically binds to nuclear localization signal motifs.

Li S et al. J. Biol. Chem. 1998 Mar;273(11):6183-6189

PMID: 9497340 Europe PMC Pubmed 

SNPs in BRAP associated with risk of myocardial infarction in Asian populations.

Ozaki K et al. Nat. Genet. 2009 Mar;41(3):329-333

PMID: 19198608 Europe PMC Pubmed 

MARCH (Kr. 12q14.1) (RNF179)  kalvoon assosioituva RING-CH-tyyppinen finger  (C3HC4)9.

Downregulation of major histocompatibility complex class I by human ubiquitin ligases related to viral immune evasion proteins.

Bartee E et al. J. Virol. 2004 Feb;78(3):1109-1120

PMID: 14722266 Europe PMC Pubmed Poxviruses and gamma-2 herpesviruses share the K3 family of viral immune evasion proteins that inhibit the surface expression of glycoproteins such as major histocompatibility complex class I (MHC-I), B7.2, ICAM-1, and CD95(Fas). K3 family proteins contain an amino-terminal PHD/LAP or RING-CH domain followed by two transmembrane domains.

 To examine whether human homologues are functionally related to the viral immunoevasins, we studied seven membrane-associated RING-CH (MARCH) proteins. All MARCH proteins located to subcellular membranes, and several MARCH proteins reduced surface levels of known substrates of the viral K3 family. Two closely related proteins, MARCH-IV and MARCH-IX, reduced surface expression of MHC-I molecules. In the presence of MARCH-IV or MARCH-IX, MHC-I was ubiquitinated and rapidly internalized by endocytosis, whereas MHC-I molecules lacking lysines in their cytoplasmic tail were resistant to downregulation. The amino-terminal regions containing the RING-CH domain of several MARCH proteins examined catalyzed multiubiquitin formation in vitro, suggesting that MARCH proteins are ubiquitin ligases. The functional similarity of the MARCH family and the K3 family suggests that the viral immune evasion proteins were derived from MARCH proteins, a novel family of transmembrane ubiquitin ligases that seems to target glycoproteins for lysosomal destruction via ubiquitination of the cytoplasmic tail.

RNFT 1, RING finger proteiini, transmembraani2. (Kr.12q24.22) Näitä selvitellään!

Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.

Strausberg RL et al. Proc. Natl. Acad. Sci. U.S.A. 2002 Dec;99(26):16899-16903

PMID: 12477932 Europe PMC Pubmed 

SCAF11 (Kr.12q12), S1P1, CASP11, SRRP129, (SR related CTD associated factor 11" . Essentielli pre-mRNA:n pleissaukselle. Splicing Factor  R/S rich 2 interacting protein, SFRS2IP,  ( arginiini, seriinipitoinen).

A novel SR-related protein specifically interacts with the carboxy-terminal domain (CTD) of RNA polymerase II through a conserved interaction domain.

Tanner S et al. Biol. Chem. 1997 Jun;378(6):565-571

PMID: 9224939 Europe PMC Pubmed 

Sip1, a novel RS domain-containing protein essential for pre-mRNA splicing.

Zhang WJ et al. Mol. Cell. Biol. 1998 Feb;18(2):676-684

PMID: 9447963 Europe PMC Pubmed 

Gene family hierarchy map
 Zinc fingersRing finger proteinsRBR E3 ubiquitin ligases

RING finger domain: In molecular biology, a RING (Really Interesting New Gene) finger domain is a protein structural domain of zinc finger type which contains a Cys 3 HisCys 4 amino acid motif which binds two zinc cations. This protein domain contains from 40 to 60 amino acids. Many proteins containing a RING finger play a key role in the ubiquitination pathway. [Source: Wikipedia]

 MDM2

PDZRN4

 RNFT2

 RNF10

 RNF34

 RNF41

BRAP

MKRN9P 

DTX1

DTX3 

MARCH9

CHFR
 
SCAF11