SAP1A is one of a family of
proteins that contains a unique
DNA binding domain
A DNA-binding domain (DBD) is an independently folded protein domain that contains at least one structural motif that recognizes double- or single-stranded DNA. A DBD can recognize a specific DNA sequence (a recognition sequence) or have a genera ...
termed the ETS domain.
Transcription
The transcriptional activation domain of SAP1a resides within the
C-terminal region, the function of which may be impeded by the
N-terminus
The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...
. Several potential
ERK consensus sites within the C-terminal region of SAP1a can modulate its transactivation efficacy, implicating that SAP1a is a direct target of ERKs.
Interactions
SAP1a has been shown to interact with the
c-fos
Protein c-Fos is a proto-oncogene that is the human homolog of the retroviral oncogene v-fos. It is encoded in humans by the ''FOS'' gene. It was first discovered in rat fibroblasts as the transforming gene of the FBJ MSV (Finkel–Biskis–Jinkin ...
serum response element upon recruitment by the serum response factor.
SAP1a is a nuclear protein stimulating
transcription
Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including:
Genetics
* Transcription (biology), the copying of DNA into RNA, the fir ...
via the c-fos serum response element, and additionally via an Ets binding site independently of the serum response factor.
Insulin activated the human INSIG2 promoter in a process mediated by phosphorylated SAP1a.
Sap1a is phosphorylated efficiently by ERKs but not by SAPK/JNKs. Serum response factor-dependent ternary complex formation by Sap1a is stimulated by ERK phosphorylation but not by SAPK/JNKs. Moreover, Sap1a-mediated transcription is activated by mitogenic signals but not by cell stress.
and SAP1a have been shown to form ternary complexes with
SRF on the serum response elements (SRE) located in the c-fos promoter.
ELK1, SAPla,
FLI1
Friend leukemia integration 1 transcription factor (FLI1), also known as transcription factor ERGB, is a protein that in humans is encoded by the ''FLI1'' gene, which is a proto-oncogene.
Function
Fli-1 is a member of the ETS transcription fa ...
and
EWS-FLI1 are able to form ternary complexes with SRF on
EGR1 SREs. In addition, ELK1 and SAP1a can also form quaternary complexes on the Egr1 SREI.
Clinical significance
SAP1a activation by ERK may play an important role in the transformation of extracellular stimuli into a nuclear response.
References
{{reflist
Human proteins