Conserved Protein Domain Family
RING-HC_MKRN1_3

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cd16730: RING-HC_MKRN1_3 
RING finger, HC subclass, found in makorin-1 (MKRN1), makorin-3 (MKRN3), and similar proteins
MKRN1, also known as makorin RING finger protein 1 or RING finger protein 61 (RNF61), is an E3 ubiquitin-protein ligase targeting the telomerase catalytic subunit (TERT) for proteasome processing. It regulates the ubiquitination and degradation of peroxisome-proliferator-activated receptor gamma (PPARgamma), a nuclear receptor that is linked to obesity and metabolic diseases. It also mediates the posttranslational regulation of p14ARF, and thus potentially regulates cellular senescence and tumorigenesis in gastric cancer. Moreover, MKRN1 functions as a differentially negative regulator of p53 and p21, and controls cell cycle arrest and apoptosis. It induces degradation of West Nile virus (WNV) capsid protein to protect cells from WNV. Furthermore, MKRN1 may represent a nuclear protein with multiple nuclear functions, including regulating RNA polymerase II-catalyzed transcription. It is a RNA-binding protein involved in the modulation of cellular stress and apoptosis. It predominantly associates with proteins involved in mRNA metabolism including regulators of mRNA turnover, transport, and/or translation, and acts as a component of a ribonucleoprotein complex in embryonic stem cells (ESCs) that is recruited to stress granules upon exposure to environmental stress. Meanwhile, MKRN1 interacts with poly(A)-binding protein (PABP), a key component of different ribonucleoprotein complexes, in an RNA-independent manner, and stimulates translation in nerve cells. In addition, MKRN1 is a novel SEREX (serological identification of antigens by recombinant cDNA expression cloning) antigen of esophageal squamous cell carcinoma (SCC). It may be involved in carcinogenesis of the well-differentiated type of tumors possibly via ubiquitination of filamin A interacting protein 1 (L-FILIP). Human MKRN1 contains three N-terminal C3H1-type zinc fingers, a motif rich in Cys and His residues (CH), a C3HC4-type RING-HC finger, and another C3H1-type zinc finger at the C-terminus. MKRN3, also known as makorin RING finger protein 3, RING finger protein 63 (RNF63), or zinc finger protein 127 (ZNF127), is a therian mammal-specific retrocopy of MKRN1. It acts as a putative E3 ubiquitin-protein ligase involved in ubiquitination and cell signaling. MKRN3 shows a potential inhibitory effect on hypothalamic gonadotropin-releasing hormone (GnRH) secretion. Its defects represent the most frequent known genetic cause of familial central precocious puberty (CPP). In contrast to human MKRN1, human MKRN3 lacks the second C3H1-type zinc finger at the N-terminal region. The RING-HC finger of mammalian MKRN4 shows high sequence similarity with that of MKRN3, and is also included in this subfamily.
Statistics
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PSSM-Id: 319644
View PSSM: cd16730
Aligned: 10 rows
Threshold Bit Score: 121.834
Threshold Setting Gi: 321472082
Created: 25-Mar-2015
Updated: 18-Aug-2016
Structure
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Aligned Rows:
 
Zn binding siteRING-HC finger
Feature 1:Zn binding site [ion binding site]
Evidence:
  • Comment:Based on the structural evidence that Homo sapiens RNF144A (1WIM) binds two Zn2+ ions through its C4C4-type RING finger.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
Feature 1           #  #                    # #  #  #                 #  #    
gi 67477468  278 DMVCGICMEVVYEKanPSERRFGILSNCNHTYCLKCIRKWRSAKQFEsKIIKSCPECRITS 338
gi 82200985  244 DIVCGICMEVVYEKtnPSERRFGILSNCSHSYCLKCIRKWRSAKQFEsKIIKSCPECRITS 304
gi 45382057  268 DMVCGICMEVVYEKanPSERRFGILSNCNHTYCLKCIRKWRSAKQFEsKIIKSCPECRITS 328
gi 82226282  233 DMMCGVCMEVVFEKtnPSERRFGILSNCCHCYCLKCIRKWRSAKQFEsKIIKSCPECRITS 293
gi 632961353 219 DIICGICMEIIYEKvnASERRFGILSNCCHTYCLNCIRKWRSAKQFEnKIVKSCPECRITS 279
gi 17368438  308 DKVCGICMEVVYEKanPNDRRFGILSNCNHSFCIRCIRRWRSARQFEnRIVKSCPQCRVTS 368
gi 17368441  313 DKVCGICMEVVYEKanPNEHRFGILSNCNHTFCLKCIRKWRSAKEFEsRIVKSCPQCRITS 373
gi 443694791 191 DKTCGICMEVVYEKepPPKRKFGILSSCSHVYCLDCIRQWRSSKQFEhKVIKACPECRVKS 251
gi 321472082 200 DKACGICMEIIWEKlpSTKQRFGLLPNCSHCFCLDCIRKWRQEKQFEnKIIRSCPECRVQS 260
gi 919042953 238 DKVCGICMETVLEKmpPSERRFGILSNCIHVFCLSCIRKWRSAKQFEnKIIRACPECRVKS 298

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