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onsdag 13 juni 2018

RNF proteiinien MARCH alaryhmä Membraaniin assosioituneet RING-CH finger proteinit

MARCH perheen jäsenet

 Membrane Associated RING-CH type Zn finger proteins. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4021871/

Ihmisillä on vain 11 kappaletta RING-CH tyyppistä domeenia ja ne kaikki ovat MARCH proteiiniperheessä. Kuten nimestä näkyy ” kalvoon assosioitunut RING-CH” niin nämä MARCH proteiinit ovat integroituneina solujen kalvoon. Niissäkin on poikkeuksena kaksi jäsentä MARCH7(RNF177) ja MARCH10 (RNF190), joilla ei ole TM-domeenia, transmembraania jaksoa.
Kahdella transmembraanityyppisellä MARCH-proteiinilla on PDZ- domaania sitova motiivi C-terminaalissaan. Erotetaan I-IV- tyyppiä näissä motiiveissa:
tyyppi I: S/T-X-Φ;
tyyppi II; Φ-X-Φ;
tyyppi III; D/E-X-Φ;
tyyppi IV; X-Ψ-D/E,
Kreikkalaiset kirjaimet Φ ja Ψ edustavat hydrofobisia ja aromaattisia aminohappoa vastaavasti.
S= seriini, T = threoniini, D on aspartaatti ja E on glutamaatti. X tarkoittaa mitä tahansa aminohappoa.
PDZ- domaanit ovat proteiini-proteiini-interaktioita tekeviä moduleja, joita löytyy tukiraknteena olevista proteiineista. Kalvoproteiinien ( reseptorien, jonikanavien,a kuljettajaproteiinien) sitoutuminen PDZ-domeeneihin nopeuttaa niiden liikehdintää, lokalisoitumista ja koostumista. Useissa muissakin transmembraanisissa RNF-proteiineissa on havaitavissa PDZ-sitoutumismotiivi. Kolmella MARCH proteiinilla on N-terminaalisessa alueessa proliinipitoinen sekvenssi, joka välittää proteiini-proteiini-interaktioita. Nämä ovat MARCH4 (RNF174), MARCH9 (RNF179) ja MARCH11 (RNF172). Tössö i 11 MARCH proteiinia ja niihin liittyy linkki PubMed GENE hakuosoiteeseen josta saa lisätietoa. 
  • 2.3. The MARCH Family Members

  • There are only 11 proteins containing the RING-CH finger domain in humans and they are all contained in the MARCH family [36]. As the name membrane-associated RING-CH suggests, the MARCH proteins are integrated into the cellular membrane, with the exception of the two members MARCH7/RNF177 and MARCH10/RNF190, which have no transmembrane domain [37,38].
  • Two-transmembrane type MARCH proteins contain putative PDZ domain-binding motifs at their C-termini (type I: S/T-X-Φ; type II; Φ-X-Φ; type III; D/E-X-Φ; type IV; X-Ψ-D/E, where Φ and Ψ represent hydrophobic and aromatic residues, respectively) [39]. PDZ domains are protein–protein interaction modules often found in scaffold proteins. Binding to the PDZ domain facilitates the trafficking, localization and assembly of membrane proteins such as receptors, ion channels and transporters.
  • The PDZ-binding motif is also found in several other transmembrane RNF proteins [19].
  • The N-terminal regions of MARCH4/RNF174, MARCH9/RNF179 and MARCH11 (RNF226) contain proline-rich sequences, which mediate protein–protein interactions (Figure 3) [40].

(1) MARCH1 , MARCH-I (RNF171) (4q32.2-q32.3)

    MARCH1 is a member of the MARCH family of membrane-bound E3 ubiquitin ligases.MARCH proteins add ubiquitin to target lysines in substrate proteins, thereby signaling their vesicular transport between membrane compartments. MARCH1 downregulates the surface expression of major histocompatibility complex (MHC) class II molecules and other glycoproteins by directing them to the late endosomal/lysosomal compartment
    Expression: Lymph node, spleen +21 other tissues

(2) MARCH2, MARCH-II (RNF172) (19p13.2)

    MARCH2 reduces surface accumulation of several glycoproteins and appears to regulate early endosome-to-trans-Golgi network (TGN) trafficking.
    Expression: Fat, heart + 25 other tissues .

(3) MARCH3, MARCH-III (RNF173) (5q23.2)

    This gene encodes a member of the membrane-associated RING-CH (MARCH) family. The encoded protein is an E3 ubiquitin-protein ligase that may be involved in regulation of the endosomal transport pathway. [provided by RefSeq, Mar 2013]
    Expression: Testis, heart +22 other tissues.

(4) MARCH4, MARCH-IV (RNF174)(2q35)

MARCH4 is a member of the MARCH family of membrane-bound E3 ubiquitin ligases MARCH enzymes add ubiquitin to target lysines in substrate proteins, thereby signaling their vesicular transport between membrane compartments. MARCH4 reduces surface accumulation of several membrane glycoproteins by directing them to the endosomal compartment.Proline rich sequence in N-terminal.
Expression: Brain, stomach + 2 other tissues.

(5) MARCH5, MARCH-V (RNF153) (10q23.32-q23.33), MITOL.

    MARCH5 is a ubiquitin ligase of the mitochondrial outer membrane that plays a role in the control of mitochondrial morphology by regulating mitofusin-2 (MFN2; MIM 608507) and DRP1 (DNM1L; MIM 603850) (Nakamura et al., 2006 [PubMed 16936636]).[supplied by OMIM, Mar 2008]
    Expression: Thyroid, prostate +25 other.

(6) MARCH6, MARCH-VI (RNF176) (5p15.2), DOA10, TBB4.

    This gene encodes a member of a family of membrane-associated E3 ubiquitin ligases containing RING-CH-type zinc finger motifs. Ubiquitination of type II deiodinase by the encoded protein is an important regulatory step in thyroid hormone signalling. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]
    Expression: Brain, Bone marrow + 25 other tissues

(7) MARCH7, MARCH-VII (RNF177) (2q24.2), AXO, AXOT.

    (No TM- domain).
    MARCH7 is a member of the MARCH family of membrane-bound E3 ubiquitin ligases (EC 6.3.2.19). MARCH proteins add ubiquitin to target lysines in substrate proteins, thereby signaling their vesicular transport between membrane compartments (Bartee et al., 2004 [PubMed 14722266]).[supplied by OMIM, Mar 2010]
    Expression: Esophagus, testis, 25 other tissues.

(8) MARCH8, MARCH-VIII (RNF178)(10q11.21-q11.22).CMIR, MIR, c-MIR.

    MARCH8 is a member of the MARCH family of membrane-bound E3 ubiquitin ligases (EC 6.3.2.19). MARCH enzymes add ubiquitin to target lysines in substrate proteins, thereby signaling their vesicular transport between membrane compartments. MARCH8 induces the internalization of several membrane glycoproteins (Goto et al., 2003 [PubMed 12582153]; Bartee et al., 2004 [PubMed 14722266]).[supplied by OMIM, Apr 2010]
    Expression: Testis, bone marrow +25 other tissues.

(9) MARCH9, MARCH-IX (RNF179) (12q14.1).

    (Proline-rich sequence in N-terminal).
    MARCH9 is a member of the MARCH family of membrane-bound E3 ubiquitin ligases (EC 6.3.2.19). MARCH enzymes add ubiquitin to target lysines in substrate proteins, thereby signaling their vesicular transport between membrane compartments. MARCH9 induces internalization of several membrane glycoproteins and directs them to the endosomal compartment (Bartee et al., 2004 [PubMed 14722266]; Hoer et al., 2007 [PubMed 17174307]).[supplied by OMIM, Apr 2010]
    Expression: kidney, spleen +25 other tissues.

(10) MARCH10, MARCH-X. (RNF190) (17q23.2)

    (No TM- domain).
    MARCH10 is a member of the MARCH family of membrane-bound E3 ubiquitin ligases (EC 6.3.2.19). MARCH enzymes add ubiquitin to target lysines in substrate proteins, thereby signaling their vesicular transport between membrane compartments (Morokuma et al., 2007 [PubMed 17604280]).[supplied by OMIM, Apr 2010]
    Expression: restricted towards testis.

(11) MARCH11, MARCH-XI (RNF226) (5p.15.1).

    MARCH11 is a member of the MARCH family of membrane-bound E3 ubiquitin ligases . These enzymes add ubiquitin to target lysines in substrate proteins, thereby signaling their intracellular transport. March11 appears to have a role in ubiquitin-mediated protein sorting in the trans-Golgi network (TGN)-multivesicular body (MVB) transport pathway (Morokuma et al., 2007 [PubMed 17604280]).[supplied by OMIM, Apr 2010]
    Expression: restricted towards testis.

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