Conserved Protein Domain Family
SP-RING_PIAS1

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cd16818: SP-RING_PIAS1 
SP-RING finger found in protein inhibitor of activated STAT protein 1 (PIAS1) and similar proteins
PIAS1, also known as DEAD/H box-binding protein 1, Gu-binding protein (GBP), or RNA helicase II-binding protein, was initially identified as an inhibitor of STAT1 that blocks the DNA-binding activity of STAT1 and specifically inhibits STAT1-mediated gene transcription in response to cytokine stimulation. It selectively inhibits interferon-inducible gene expression and plays an important role in the IFN-gamma- or IFN-beta-mediated innate immune response through negative regulation of STAT1. It also regulates the activity of other transcription factors to regulate immune response, such as NF-kappaB and Smad4. Moreover, PIAS1 functions as an E3 small ubiquitin-like modifier (SUMO)-protein ligase specifying target proteins for SUMO conjugation by Ubc9. The sumoylation activity of PIAS1 can suppress cytokine transforming growth factor beta (TGFbeta)-induced epithelial mesenchymal transition (EMT) in non-transformed epithelial cells to promote activation of the matrix metalloproteinase 2 (MMP2). It thus regulates TGFbeta-induced cancer cell invasion and metastasis. PIAS1 may also be involved in spatial learning and memory formation through its SUMOylation of cAMP-responsive element binding protein (CREB). In addition, PIAS1 is the E3 ligase responsible for SUMOylation of High mobility group nucleosomal binding domain 2 (HMGN2), which is a small and unique non-histone protein that has many functions in a variety of cellular processes, including regulation of chromatin structure, transcription, and DNA repair, as well as antimicrobial activity, cell homing, and regulating cytokine release. Furthermore, PIAS1 is a genuine chromatin-bound androgen receptor (AR) co-regulator that functions in a target gene selective fashion to regulate prostate cancer cell growth. It also mediates the SUMOylation of c-Myc, which is the most frequently overexpressed oncogene in tumours, including breast cancer, colon cancer, and lung cancer. Necdin, a pleiotropic protein that promotes differentiation and survival of mammalian neurons, can suppresses PIAS1 both by inhibiting SUMO E3 ligase activity and by promoting ubiquitin-dependent degradation. PIAS1 contains an N-terminal SAP (scaffold attachment factor A/B (SAF-A/B), acinus and PIAS) box with the LXXLL signature, a PINT motif, a specific RING finger known as Siz/PIAS (protein inhibitor of activated signal transducer and activator of transcription) RING (SP-RING) finger, and the acidic C-terminal domain. The SP-RING finger mediates the interaction of PIAS1 with the SUMO E2 conjugating enzyme Ubc9.
Statistics
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PSSM-Id: 319732
View PSSM: cd16818
Aligned: 6 rows
Threshold Bit Score: 104.38
Threshold Setting Gi: 632982579
Created: 22-Mar-2015
Updated: 18-Aug-2016
Structure
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Aligned Rows:
 
Zn binding siteSP-RING finger
Feature 1:Zn binding site [ion binding site]
Evidence:
  • Comment:Based on the structural evidence that Homo sapiens E3 Sumo Ligase Pias2 (4FO9) binds one Zn2+ ion through its SP-RING finger.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
Feature 1                           # #                    #  #     
gi 20138891  332 SLLCPLGKMRLTIPCRALTCSHLQCFDATLYIQMNEKKPTWVCPVCDKKAP 382
gi 147906733 331 SLLCPLGKMRLTIPCRSLTCSHLQCFDATLYIQMNEKKPTWVCPVCDKKAP 381
gi 47225888  322 SLLCPLGKMRLTIPCRAITCSHLQCFDATLYIQMNEKKPTWVCPVCDKKAP 372
gi 71895425  332 SLLCPLGKMRLTIPCRALTCSHLQCFDATLYIQMNEKKPTWVCPVCDKKAP 382
gi 632982579 325 SLLCPLGKMRLTIACRAITCSHLQCFDATLYIQMNEKKPTWVCPVCDKKAP 375
gi 556981173 334 SLLCPLGKMRLTIPCRALTCSHLQCFDATLYIQMNEKKPTWVCPVCDKKAP 384

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