: ASB2 (14q32.13 ) ASB E3 ligaasien alaryhmä CRL ubikitiiniligaaseissa (Cul-RING ligaasit)

Olen katsomassa filamiiniryhmää ja aloitin etsimällä Filamiini- proteiinin hajoittajaa  proteosomijärjstelmästä. Löysin uuden E3 ubikitiiniligaasin, josta en ole aiemmnin tehnyt merkintöjä.
Asetan etiketin:  E3 ubikitiiniligaasit (muut) Muut, kuin  jo minun  havaitsemani luokitellut ryhmät.
 PubMed viiteistä löytyy tämän E3 ubikitiiniligaasin ryhmäksi 

ASB2α cullin-ring E3 ubiquitin ligase

( Tässä  E3 ub. ligaasien ala ryhmissä  on jo:
_  SCF-type,
VHL-type,
 BTH-type,
 APL- type,
 mutta en velä tiedä mikä alatyyppi on tämä ASB-tyyppi. 


https://www.ncbi.nlm.nih.gov/gene/51676

 ASB2 geeni (14q32.12) 
Tämä geeni kuuluu perheeseen, jonka nimi on ankyriinitoiston(ANK) ja SOCS- boxin omaavien proteiinien perhe.
Nämä proteiinit  omaavat osaa proteiinien hajoituksessa  kytkemällä sytokiinisignalointia vaimentvia proteiineja elongiin iBC- kompleksiinsa.
. Geenin koodaama proteiini on eräs alayksikköä  multimeerisessä E3 ubikitiiniligaasikomplesissa, joka välittää aktiiniin sitoutuvien proteiinien hajoittamista. Tällä geenillä  on osuutta  retiinihapon indusoimassa  myeloisten leukemiasolujen kasvun estossa ja erilaistumisessa . Alternatiivisesti pleissautuneet transkriptivariantit koodavat monia isoformeja.  Geeniä ilmenee sydämessä, eturauhasessa ja 12 muussa kudoksessa.

• Also known as ASB-2
• Summary  This gene encodes a member of the ankyrin repeat and SOCS box-containing (ASB) protein family. These proteins play a role in protein degradation by coupling suppressor of cytokine signalling (SOCS) proteins with the elongin BC complex. The encoded protein is a subunit of a multimeric E3 ubiquitin ligase complex that mediates the degradation of actin-binding proteins. This gene plays a role in retinoic acid-induced growth inhibition and differentiation of myeloid leukemia cells. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2011]
• Expression  Biased expression in heart (RPKM 15.5), prostate (RPKM 8.6) and 12 other tissues 

 ( Mitä tietoja tästä geenistä on?  Sillä ei ole  vaihtoehtoisia nimiä valaisemassa sen olemusta).

Conserved Domains (4) summary

cd00204
Location:232 → 357

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example).  ANK repeats may occur in combinations with other types of domains. The structural repeat unit contains two antiparallel helices and a beta-hairpin, repeats are stacked in a superhelical arrangement; this alignment contains 4 consecutive repeats.

cd03721
Location:591 → 635

SOCS_ASB2; SOCS (suppressors of cytokine signaling) box of ASB2-like proteins. ASB family members have a C-terminal SOCS box and an N-terminal ankyrin-related sequence.  ASB2 targets specific proteins to destruction by the proteasome in leukemia cells that have been induced to differentiate. The general function of the SOCS box is the recruitment of the ubiquitin-transferase system. The SOCS box interacts with Elongins B and C, Cullin-5 or Cullin-2, Rbx-1, and E2. Therefore, SOCS-box-containing proteins probably function as E3 ubiquitin ligases and mediate the degradation of proteins associated through their N-terminal regions.

pfam12796
Location:308 → 396

Ank_2; Ankyrin repeats (3 copies)

sd00045
Location:237 → 268

ANK; ANK repeat [structural motif]

ORIGIN      
        1 matqistrgs qctigqeeys lysslsedel vqmaieqsla dktrgpttae atasactnrq
       61 pahfypwtrs tappesspar apmglfqgvm qkyssslfkt sqlapadpli kaikdgdeea
      121 lktmikegkn laepnkegwl plheaayygq vgclkvlqra ypgtidqrtl qeetavylat
      181 crghldclls llqagaepdi snksretply kacerknaea vkilvqhnad tnhrcnrgwt
      241 alhesvsrnd levmqilvsg gakvesknay gitplfvaaq sgqlealrfl akygadintq
      301 asdnasalye ackneheevv efllsqgada nktnkdgllp lhiaskkgny rivqmllpvt
      361 srtrirrsgv splhlaaern hdevlealls arfdvntpla perarlyedr rssalyfavv
      421 nnnvyatell lqhgadpnrd vispllvair hgclrtmqll ldhganiday iathptafpa
      481 timfamkcls llkflmdlgc dgepcfscly gngphppapq pssrfndapa adkepsvvqf
      541 cefvsapevs rwagpiidvl ldyvgnvqlc srlkehidsf edwavikeka epprplahlc
      601 rlrvrkaigk yriklldtlp lpgrlirylk yentq

Related articles in PubMed

1. Filamins but not Janus kinases are substrates of the ASB2α cullin-ring E3 ubiquitin ligase in hematopoietic cells. Lamsoul I, et al. PLoS One, 2012. PMID 22916308, Free PMC Article
2. The ASB2β Ubiquitin-interacting motif is involved in its monoubiquitination. Nishiyama T, et al. Biochem Biophys Res Commun, 2012 Apr 13. PMID 22382022
3. A label-free quantitative proteomics strategy to identify E3 ubiquitin ligase substrates targeted to proteasome degradation. Burande CF, et al. Mol Cell Proteomics, 2009 Jul. PMID 19376791, Free PMC Article
4. ASB-2 inhibits growth and promotes commitment in myeloid leukemia cells. Guibal FC, et al. J Biol Chem, 2002 Jan 4. PMID 11682484
5. ATRA-regulated Asb-2 gene induced in differentiation of HL-60 leukemia cells. Kohroki J, et al. FEBS Lett, 2001 Sep 14. PMID 11566180

See all (33) citations in PubMed

FEBS Lett. 2001 Sep 14;505(2):223-8.

ATRA-regulated Asb-2 gene induced in differentiation of HL-60 leukemia cells.

Kohroki J¹, Fujita S, Itoh N, Yamada Y, Imai H, Yumoto N, Nakanishi T, Tanaka K.Abstract

Suppressors of cytokine signaling (SOCS) proteins possess common structures, a SOCS box at the C-terminus and a SH2 domain at their center. These suppressors are inducible in response to cytokines and act as negative regulators of cytokine signaling.
The ASB proteins also contain the SOCS box and the ankyrin repeat sequence at the N-terminus, but do not have the SH2 domain.
Although Socs genes are directly induced by several cytokines, no Asb gene inducers have been identified. In this study, we screened the specific genes expressed in the course of differentiation of HL-60 cells, and demonstrated that ASB-2, one of the ASB proteins, was rapidly induced by all-trans retinoic acid (ATRA). Typical retinoid receptors (RARs) or retinoid X receptors (RXRs) binding element (RARE/RXRE) were presented in the promoter of the Asb-2 gene. We showed that RARalpha, one of the RARs, binds to the RARE/RXRE in the Asb-2 promoter. In addition, we demonstrated by luciferase reporter assay that this element was a functional RARE/RXRE. These findings indicate that ASB-2 is directly induced by ATRA and may act as a significant regulator, underlying such physiological processes as cell differentiation.

GeneRIFs: Gene References Into Functions

1. Notch signaling can initiate Asb2 transcription and NF-kappa B activation in T cell acute lymphoblastic leukemia cells.
2. Using ASB2 conditional knockout mice.
3. Phosphorylation of serine 323 of ASB2 alpha by Erk kinases is critical for ASB2alpha-mediated degradation of FLNA.
4. data therefore reveal ubiquitin acceptor sites in FLNa and establish that ASB2alpha-mediated effects on cell spreading are due to loss of filamins.
5. Data show that neither endogenous nor exogenously expressed ASB2alpha induces degradation of JAK proteins in hematopoietic cells
6. These results suggest that ASB2beta but not ASB2alpha might be monoubiquitinated and that the ASB2beta UIM motif, but not its E3 Ub ligase activity, plays a pivotal role in this monoubiquitination.
7. A model whereby ASB2 contributes to hematopoietic differentiation, in part, through MLL degradation and HOX gene down-regulation.
8. ASB2alpha is a novel regulator of integrin-dependent adhesion of hematopoietic cells
9. By shifting monomeric E3 ligase complexes to dimeric forms through activation of Asb2 transcription, Notch could effectively control the turnover of a variety of substrates and it exerts diverse effects on cell proliferation and differentiation.
10. ASB2 may regulate hematopoietic cell differentiation by modulating cell spreading and actin remodeling through targeting of filamins A and B for degradation.

Cell Res. 2011 May;21(5):754-69. doi: 10.1038/cr.2010.165. Epub 2010 Nov 30.

Notch-induced Asb2 expression promotes protein ubiquitination by forming non-canonical E3 ligase complexes.Nie L¹, Zhao Y, Wu W, Yang YZ, Wang HC, Sun XH. Abstract

Notch signaling controls multiple developmental processes, thus demanding versatile functions. We have previously shown that this may be partly achieved by accelerating ubiquitin-mediated degradation of important regulators of differentiation. However, the underlying mechanism was unknown. We now find that Notch signaling transcriptionally activates the gene encoding ankyrin-repeat SOCS box-containing protein 2 (Asb2).
Asb2 promotes the ubiquitination of Notch targets such as E2A and Janus kinase (Jak) 2, and a dominant-negative (DN) mutant of Asb2 blocks Notch-induced degradation of these proteins. Asb2 likely binds Jak2 directly but associates with E2A through Skp2. We next provide evidence to suggest that Asb2 bridges the formation of non-canonical cullin-based complexes through interaction with not only ElonginB/C and Cullin (Cul) 5, but also the F-box-containing protein, Skp2, which is known to associate with Skp1 and Cul1. Consistently, ablating the function of Cul1 or Cul5 using DN mutants or siRNAs protected both E2A and Jak2 from Asb2-mediated or Notch-induced degradation. By shifting monomeric E3 ligase complexes to dimeric forms through activation of Asb2 transcription, Notch could effectively control the turnover of a variety of substrates and it exerts diverse effects on cell proliferation and differentiation.PMID:21119685DOI:10.1038/cr.2010.165