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suppressin; deformed epidermal autoregulatory factor 1 homolog; nuclear DEAF-1-related transcriptional regulator; NUDR; zinc finger MYND domain-containing protein 5 (DEAF1, SPN, ZMYND5)
Function:
1) when secreted, inhibits of cell cycle in G0/G1
a) lymphocytes
b) colonic cells
2) binds to DNA with multiple copies of TTC[CG]G
a) present in its own promoter
b) present in HNRPA2B1 gene
c) own-regulates transcription of these genes
3) binds to the retinoic acid response element (RARE) (AGGGTTCACCGAAAGTTCA)
4) activates the proenkephalin gene independently of promoter binding
Structure:
- contains 1 MYND-type Zn+2 finger
- contains 1 SAND domain
Compartment:
- isoform 1: nucleus, cytoplasm
a) cytoplasmic in non-mucinous colorectal carcinoma
b) when expressed alone, localized almost exclusively in the nucleus but, when expressed with isoform 4, nuclear expression decreases to 32% & cytoplasmic expression increases by 270%
- isoform 2: secreted in some cell types
- isoform 3: secreted in some cell types
- isoform 4: cytoplasm, nucleus
- when expressed alone, localizes mainly in the cytoplasm but, when expressed with isoform 1, nuclear localization is enhanced
Alternative splicing:
- named isoforms=4
- no predictable signal peptide
Expression:
- expressed in various tissues & cells including peripheral blood mononuclear cells & hormone-secreting pituitary cells
Pathology:
1) nuclear localization of suppressin in colorectal carcinomas protends poor prognosis
2) defects in DEAF1 could confer a growth advantage to the mutated cell; implications for neoplasia
3) expression in pancreatic lymph nodes of patients with type 1 diabetes is 20 times higher than in healthy controls
Note:
- first described as suppressin (characterized in bovine neuroendocrine & immune cells); however, it is uncertain whether there is another protein suppressin
- DEAF1 has been described as a nuclear dimeric protein & suppressin as a secreted monomeric protein
General
nuclear protein
phosphoprotein
secreted protein
zinc finger protein
Properties
SIZE: entity length = 565 aa
MW = 59 kD
COMPARTMENT: cytoplasm
cell nucleus
MOTIF: alanine-rich region {2-122}
MOTIF: alanine residue (SEVERAL)
Ser phosphorylation site {S176}
Thr phosphorylation site {T179}
SAND {193-273}
nuclear translocation signal {301-316}
proline-rich region
SITE: 383-439
MOTIF: proline residue (SEVERAL)
Zinc finger
NAME: Zinc finger
SITE: 504-540
EFFECTOR-BOUND: Zn+2
Database Correlations
OMIM 602635
UniProt O75398
PFAM correlations
Entrez Gene 10522
Kegg hsa:10522
References
- Manne et al. Clinical Cancer Research 7:3495-503, 2001