The organisation representing the views of loyalist paramilitary groups has told Boris Johnson that they are withdrawing their support for the Good Friday Agreement until the Irish Sea border is removed.
The letter to the Prime Minister from the Loyalist Communities Council (LCC) will raise fears about the future of the loyalist ceasefire.
It claimed that the basis on which the paramilitaries committed to end violence in 1994 had been undermined.
The LCC is an umbrella organisation representing the views of groups including the UDA, UVF and Red Hand Commando. The two-page letter from its chairman David Campbell calls on the Prime Minister to trigger Article 16.
Mr Campbell said that he had been "instructed to write in similar terms to the Irish Taoiseach".
Arlene Foster, Michelle O'Neill, European Commission vice-president Maros Sefkovic and the US consul-general are copied into the correspondence.
Mr Campbell told the Prime Minister: "The protocol gives effect to the Irish nationalist position at the expense of the unionist position. This renders it in variance with the Agreement it purports to uphold and undermines the basis on which the Combined Loyalist Military Command (CLMC) agreed their 1994 ceasefire and subsequent support for the Belfast Agreement.
"The LCC leadership is determined that unionist opposition to the protocol should be peaceful and democratic. However, please do not underestimate the strength of feeling on this issue right across the unionist family.
"The only time I can remember such unanimity of opposition was following the imposition of the Anglo-lrish Agreement in 1985."
He continued: "Accordingly, I have been instructed to advise you that the loyalist groupings are herewith withdrawing their support for the Belfast Agreement and its institutions until our rights under the Agreement are restored and the protocol is amended to ensure unfettered access for goods, services, and citizens throughout the UK.
"If the EU is not prepared to honour the entirety of the Agreement then it will be responsible for the permanent destruction of the Agreement."
He rounded on EU chief negotiator Michel Barnier for "repeatedly (refusing) to meet with our representatives, who were signatories to the Belfast Agreement, even though we pointed out the one-sided and disingenuous representations being made to him from republicans and the Irish Government".
He was scathing of Irish Foreign Minister Simon Coveney, who did meet the LCC but "chose to ignore" its views.
"Indeed, his actions and remarks served to heighten tensions in Northern Ireland throughout the negotiations and he is responsible for destroying the positive relationships with the Irish Government built up over the past 20 years," the letter stated.
Mr Campbell said he wished to "place on record the unanimous opposition of all the groups that are represented by the LCC to the protocol and our determination that it should be replaced".
He stressed that the organisation's concerns were "much more fundamental" than the trade disruption caused by the protocol.
The LCC told the Prime Minister that "no consent" had been sought for the protocol from the people of Northern Ireland, "and our political representatives are unanimous in their opposition to it". The organisation said it understood nationalist arguments that there must be no hard border in Ireland.
"Equally, it should be self-evident that there should be no hard border, either physical or regulatory, between Northern Ireland and the rest of the UK," it added.
The LCC told the Prime Minister that it was "prepared to play a meaningful role in seeking a workable solution".
"However, a starting point has to be the acceptance that a hard border on the island of Ireland, or between Northern Ireland and the rest of the UK, has no cross-community support here and is therefore untenable.
"It must be patently obvious to you that the triggers detailed in Article 16 of the protocol, ie the extreme economic and societal difficulties, now pertain and must be acted upon without further delay."
The announcement came after graffiti threatening Cabinet Office Minister Michael Gove appeared in a loyalist area of south Belfast. DUP MLA Christopher Stalford said those responsible for spraying the minister's name, address and a threatening message saying 'we don't forget, we don't forgive' across a series of hoardings should be ashamed.