CUL3

CUL3
사용 가능한 구조
PDB	Ortholog 검색: PDBe RCSB
PDB ID 코드 목록
	2MYL, 2MYM, 4AP2, 4APF, 4EOZ, 4HXI
식별자
에일리어스	CUL3, CUL-3, PHA2E, Cullin3, NEDAUS
외부 ID	OMIM : 603136 MGI : 1347360 HomoloGene : 2661 GenCard : CUL3
유전자 위치(인간)
크르.	2번 염색체(인간)
끝.	224,585,397 bp
유전자 위치(마우스)
크르.	1번 염색체(마우스)
끝.	80,318,190 bp
RNA발현패턴
	상단 표시 위치:
	정자; ; 양수; ; 아킬레스건; ; 이하선; ; 구강; ; 안검결막; ; 상완 삼두근; ; 신경절 융기; ; 제주날 점막; ; 경골;
	추가 참조 표현식 데이터
	; ; ; ;
	추가 참조 표현식 데이터
유전자 존재론
분자 함수	POZ 도메인바인딩; 단백질 호모다이머화; GO:1904264, GO:1904822, GO:0090622, GO:0090302 유비퀴틴단백질리가수분해효소활성; 유비퀴틴산전달효소활성; GO:0001948 단백질 결합; 단백질 헤테로다이머화 활성; 유비퀴틴단백질리가수분해효소결합; 사이클린 결합; 노치 바인딩;
셀룰러 컴포넌트	세포질; 컬린-링유비퀴틴리가수분해효소복합체; 세포; 골지 장치; 막; Cul3-RIN 유비퀴틴리가수분해효소복합체; 핵소체; 극미소관; 세포외 엑소좀; 핵; 골지막; 섬모; SCF유비퀴틴리가아제복합체; 운동성 섬모; 정자 편모; 세포 투영;
생물학적 과정	태아의 분열; RNA중합효소II에 의한 전사조절; G1 단계; Rho단백질신호전달부조절; 단백질 폴리유비퀴티네이션; 자궁 내 태아 발달; RNA중합효소II에 의한 전사 음성 조절; Wnt 시그널링 패스; 단백질단백질단백질화; 응력 섬유 조립체; MAPK 캐스케이드; 사이토키네시스 양성 조절; 내인성 아포토시스 시그널링 경로; 골지 소포 매개 수송에 대한 소포체; 유사분열성 중기/아파기 전이 양성 조절; COPII 소포 코팅; 섬유아세포아포토시스 과정; 세포투영조직; 위조절; 줄기세포 분열; 단백질유비퀴티네이션; 세포형태형성; 세포군 증식의 양성 조절; GO:0007067 유사분열세포 사이클; 인테그린결합신호경로; 유사분열성 중기판 조립; 세포이동; 표준 Wnt 시그널링 경로의 음성; 소포체 수송; 간 형태 형성; 프로테아솜유비퀴틴의존성단백질이화과정; 대뇌피세포형태형성; 유비퀴틴의존성 단백질 이화 과정; 아나phase-complex-의존성 이화 과정; 유비퀴틴-아미노솜 시스템에 의한 핵단백질 품질관리; 발육 후 단백질 수식; 운송; 유사분열세포주기의 G1/S 전이; SCF 의존성 프로테아솜 유비퀴틴 의존성 단백질 이화 과정; 단백질 유비퀴티네이션의 양성 조절; 단백질 불안정화;
	출처:아미고 / QuickGO
맞춤법
	8452
	26554
	ENSG000036257
	ENSMUSG00000004364
	문제 13618
	Q9JLV5
	NM_001257197; NM_001257198; NM_003590
	NM_016716; NM_001313728
	NP_001244126; NP_001244127; NP_003581
	NP_001300657; NP_057925
	위키데이터
인간 보기/편집	마우스 표시/편집

Cullin 3는 인간의 CUL3 ^[5]^[6]^[7]유전자에 의해 암호화되는 단백질이다.

Cullin 3 단백질은 포유류에서 8개의 단백질(Cullin 1, Cullin 2, Cullin 3, Cullin 4A, Cullin 4B, Cullin 5, Cullin 7, Cullin 9)^[8]을 포함하는 Cullin 과에 속합니다.컬린 단백질은 효모, 식물, ^[9]포유동물 전반에 걸쳐 진화적으로 보존된 단백질 패밀리입니다.

단백질 기능

Cullin 3은 단백질 유비쿼티화에 관여하는 Cullin-RING E3 유비퀴틴 연결효소 복합체(CRLs)의 구성 요소이며, 유비퀴틴-단백질 시스템(UPS)의 일부를 나타낸다.CRL에 의해 리신 잔기에 유비퀴틴 성분이 첨가된 후 단백질 분해의 ^[10]표적이 된다.Cullin-RING E3 유비퀴틴 결합효소는 세포주기 조절, 스트레스 반응, 단백질 밀매, 신호 변환, DNA 복제, 전사, 단백질 품질 제어, 일주기 시계 및 ^[11]^[12]발달을 담당하는 많은 세포 과정에 관여한다.

생쥐에서 CUL3 유전자의 결실은 태아의 ^[13]치사율을 유발한다.

Cullin 3-RING E3 유비퀴틴 연결효소

Cullin 3-RING 복합체는 Cullin 3 단백질, 유비퀴틴 결합효소(E2)를 신병용하는 RING 박스 단백질 1(RBX1) 및 기질 인식 서브 유닛인 Bric-a-brac/Tramtrack/Broad(BTB) 단백질로 구성된다.Cullin 3 단백질은 CRL ^[14]복합체의 다른 성분을 배위하는 핵심 골격 단백질이다.Cullin 3-RING 복합체는 또한 BTB 도메인을 통해 2개의 기질 수용체와 2개의 촉매 RING ^[15]도메인을 생성할 수 있다.

복합체의 활성화는 유비퀴틴 유사 단백질 NEDD8이 컬린 호몰로지 도메인의 보존된 Lys 잔기에 부착됨으로써 조절되며,^[16] 이를 네딜화라고 한다.탈데딜화는 NEDD8과 컬린 단백질 사이의 ^[17]이소펩티드 결합의 분열을 매개하는 8개의 서브유닛 CSN 복합체에 의해 이루어진다.Cullin과 상호작용하는 또 다른 단백질은 Cullin 단백질의 탈질된 형태에 결합하고 Cullin과 복합체의 다른 서브유닛 간의 상호작용을 방해하여 E3 유비퀴틴 연결효소 활성을 ^[18]억제하는 CAND1이다.따라서 CRL 복합활성 ^[19]조절에 있어 컬린의 동적 네딜화 및 탈디딜화는 중요하다.

임상적 의의

가족성 고칼륨성 고혈압

CUL3 유전자의 돌연변이는 가족성 고칼륨성 고혈압 질환과 관련이 있다.Cullin 3을 포함한 CRL 복합체는 With-no-Lysine [K] 키나아제 WNK1 및 WNK4의 프로테아솜 분해를 조절함으로써 신장 내 NaCl⁻ cotransporter(NCC)의⁺ 활성을 제어한다.CUL3 유전자의 돌연변이가 WNKs ^[20]축적을 유도하는 것으로 나타났다.이러한 키나아제들의 풍부함은 NCC의 인산화 증가와 활성화로 이어진다.그⁺ 결과,^[21] Na 재흡수가 증가하여 고혈압이 발생하고 있습니다.

암

인간 암에서 Cullin 3 발현 수준의 규제 완화가 관찰되었다.Cullin 3은 침습성 암에서 과압되어 있으며 단백질 발현 수준은 종양 단계와 긍정적인 상관관계가 있는 것으로 나타났다.유방암에서 Cullin 3 단백질의 과잉발현은 Nrf2 단백질 수치를 감소시킨다.이 단백질은 일부 해독 및 항산화 효소의 발현을 조절하는 전사 인자입니다.CRL 복합체의 또 다른 기질은 후보종양억제단백질 RhoBTB2이다.^[22]

상호 작용

CUL3는 다음과 상호작용하는 것으로 나타났습니다.

레퍼런스

^ ^a ^b ^c GRCh38: 앙상블 릴리즈 89: ENSG000036257 - 앙상블, 2017년 5월
^ ^a ^b ^c GRCm38: 앙상블 릴리즈 89: ENSMUSG00000004364 - 앙상블, 2017년 5월
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^ Cheng J, Guo J, Wang Z, North BJ, Tao K, Dai X, Wei W (January 2018). "Functional analysis of Cullin 3 E3 ligases in tumorigenesis". Biochimica et Biophysica Acta (BBA) - Reviews on Cancer. 1869 (1): 11–28. doi:10.1016/j.bbcan.2017.11.001. PMC 7076836. PMID 29128526.
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추가 정보

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외부 링크

UCSC 게놈 브라우저의 인간 CUL3 게놈 위치 및 CUL3 유전자 상세 페이지.

[refGRCh38Ensembl-1] GRCh38: 앙상블 릴리즈 89: ENSG000036257 - 앙상블, 2017년 5월

[refGRCm38Ensembl-2] GRCm38: 앙상블 릴리즈 89: ENSMUSG00000004364 - 앙상블, 2017년 5월

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