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 tumors, including breast cancer, colon cancer, and lung cancer. Necdin, a pleiotropic protein that promotes differentiation and survival of mammalian neurons, can suppress 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. It binds a single Zn ion, instead of two ions bound by typical RING fingers.
Statistics
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PSSM-Id: 438467
Aligned: 6 rows
Threshold Bit Score: 122.085
Created: 22-Mar-2015
Updated: 17-Oct-2022
Structure
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Aligned Rows:
 
Zn binding site
Feature 1: Zn binding site [ion binding site], 4 residue positions
Conserved feature residue pattern:C H C CClick to see conserved feature residue pattern help
Evidence:
  • Comment:based on the structures of human Sumo ligases Pias2 and Pias3 with bound Zn2+ ion through their SP-RING fingers
  • Comment:The SP-RING finger is a variant of RING finger; it binds a single Zn ion and lacks the second, fifth, and sixth zinc-binding residues of the consensus C3H2C3-/C3HC4-type RING fingers.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                # #                    #  #         
O75925       327 TSLRVSLLCPLGKMRLTIPCRALTCSHLQCFDATLYIQMNEKKPTWVCPVCDKKAPYEHL 386 human
NP_001079161 326 TSLRVSLLCPLGKMRLTIPCRSLTCSHLQCFDATLYIQMNEKKPTWVCPVCDKKAPYEHL 385 African clawed frog
CAF98368     317 TSLRVSLLCPLGKMRLTIPCRAITCSHLQCFDATLYIQMNEKKPTWVCPVCDKKAPYEHL 376 spotted green pufferfish
NP_001026627 327 TSLRVSLLCPLGKMRLTIPCRALTCSHLQCFDATLYIQMNEKKPTWVCPVCDKKAPYEHL 386 chicken
XP_007908213 320 TSLRVSLLCPLGKMRLTIACRAITCSHLQCFDATLYIQMNEKKPTWVCPVCDKKAPYEYL 379 elephant shark
XP_005997134 329 TSLRVSLLCPLGKMRLTIPCRALTCSHLQCFDATLYIQMNEKKPTWVCPVCDKKAPYEHL 388 coelacanth

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