SENP8

SENP8
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	1XT9, 2BKQ, 2BKR
Identifikatori
Aliasi	SENP8
Vanjski ID-jevi	OMIM: 608659 MGI: 1918849 HomoloGene: 14084 GeneCards: SENP8
Lokacija gena (čovjek)
Hrom.	Hromosom 15 (čovjek)
Kraj	72,143,692 bp
Lokacija gena (miš)
Hrom.	Hromosom 9 (miš)
Kraj	59,657,993 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• GO:0070122 peptidase activity; • cysteine-type peptidase activity; • hydrolase activity; • NEDD8-specific protease activity; • endopeptidase activity;
Ćelijska komponenta	• citosol; • jedro;
Biološki proces	• Proteoliza; • protein deubiquitination; • protein desumoylation; • Posttranslacione modifikacije;
	Izvori:Amigo / QuickGO
Ortolozi
	123228
	71599
	ENSG00000166192
	ENSMUSG00000051705
	Q96LD8
	Q9D2Z4
	NM_001166340; NM_001172109; NM_001172110; NM_001172111; NM_145204
	NM_001172068; NM_001172069; NM_001172070; NM_001172071; NM_027838
	NP_001159812; NP_001165580; NP_001165581; NP_001165582; NP_660205
	NP_001165539; NP_001165540; NP_001165541; NP_001165542; NP_082114
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Mali EDRK-bogati faktor 8 je protein koji je kod ljudi kodiran genom SERF8.^[5]^[6]

Međunarodni konzorcij za radijacijsko hibridno mapiranje locirao je gen NEDP1 na hromosomu 15 (SGC33966).

NEDD8 je protein sličan ubikvitinu koji postaje konjugiran sa podjedinicom kulina nekoliko ubikvitinskih ligaza. Ova konjugacija, koja se naziva nedilacija, potrebna je za optimalnu aktivnost ubikvitin-ligaze. NEDD8-specifične denedilaze, poput NEDP1 ili DEN1, potrebne su za obradu NEDD8 propeptida na C-terminalnom motivu diglicina i uklanjanje NEDD8 iz kulina (Gan-Erdene et al., 2003).

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 212 aminokiselina, a molekulska težina 24.107 Da.^[7].

10	20	30	40	50
MDPVVLSYMD	SLLRQSDVSL	LDPPSWLNDH	IIGFAFEYFA	NSQFHDCSDH
VSFISPEVTQ	FIKCTSNPAE	IAMFLEPLDL	PNKRVVFLAI	NDNSNQAAGG
THWSLLVYLQ	DKNSFFHYDS	HSRSNSVHAK	QVAEKLEAFL	GRKGDKLAFV
EEKAPAQQNS	YDCGMYVICN	TEALCQNFFR	QQTESLLQLL	TPAYITKKRG
EWKDLITTLA	KK

Simboli

C: Cistein
D: Asparaginska kiselina
E: Glutaminska kiselina
F: Fenilalanin
G: Glicin
H: Histidin
I: Izoleucin
K: Lizin
L: Leucin
M: Metionin
N: Asparagin
P: Prolin
Q: Glutamin
R: Arginin
S: Serin
T: Treonin
V: Valin
W: Triptofan
Y: Tirozin

Kloniranje i ekspresija

Pretragom baze podataka za sekvence slične kvascu Ulp1, nakon čega slijedi PCR biblioteke cDNK bubrega, Mendoza et al. (2003) klonirali su NEDP1. Izvedeni protein od 212 aminokiselina sadrži cisteinski domen proteaze uz bok kratkim produženjima N– i C-kraja. PCR analiza pokazala je široku ekspresiju NEDP1, sa najvećom ekspresijom u bubrezima i gušterači.

Wu et al. (2003) prečistili su DEN1 iz HeLa ćelija, na osnovu njegove sposobnosti da dededilira CUL1 supstrat. Tragajući za sekvencama sličnim tipskom DEN1 fragmentu, praćenom PCR bibliotekom cDNK fetusnog mozga, klonirali su DEN1. Western blot analiza otkrila je pročišćeni protein pri prividnoj molekulskoj masi od 24 kD.

Funkcija gena

Mendoza et al (2003) potvrdili su da je rekombinantni NEDP1 eksprimiran u bakterijama obrađivao proteinski prekursor NEDD8, nakon druge glije u motivu diglicina, ali nije obrađivao protein SUMO1 ili ubikvitin. NEDP1 nije pokazao nikakvu aktivnost protiv SUMO1 pune dužine, SUMO2 ili SUMO3. Studije inhibicije i mutageneze pokazale su da je NEDP1 cistein-proteaza. NEDP1 je dekonjugirao NEDD8 iz CUL2 in vitro i iz modificiranog CUL4A in vivo.^[8] Wu et al. (2003) utvrdili su da je rekombinantni DEN1 vezao NEDD8 u in vitro padajućem testu, ali je pokazao mnogo niže vezivanje za SUMO1 i ubikvitin. Pokazali su da je DEN1 obrađivao prekursorske proteine NEDD8 u zreli protein i da je DEN1 dekonjugirao hipernedilirani CUL1.^[9] Gan-Erdene et al. (2003) otkrili su da je DEN1 katalizirao hidrolizu supstrata NEDD8 mnogo većom brzinom od supstrata ubikvitina. Nije katalizirao hidrolizu supstrata SUMO1.^[10]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000166192 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000051705 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Scharf JM, Endrizzi MG, Wetter A, Huang S, Thompson TG, Zerres K, Dietrich WF, Wirth B, Kunkel LM (septembar 1998). "Identification of a candidate modifying gene for spinal muscular atrophy by comparative genomics". Nature Genetics. 20 (1): 83–6. doi:10.1038/1753. PMID 9731538.
^ "Entrez Gene: SERF2 small EDRK-rich factor 2".
^ "UniProt, Q96LD8". Pristupljeno 18. 7. 2021.
^ Mendoza, H. M., Shen, L., Botting, C., Lewis, A., Chen, J., Ink, B., Hay, R. T. NEDP1, a highly conserved cysteine protease that deNEDDylates cullins. J. Biol. Chem. 278: 25637-25643, 2003. [PubMed: 12730221
^ Wu, K., Yamoah, K., Dolios, G., Gan-Erdene, T., Tan, P., Chen, A., Lee, C., Wei, N., Wilkinson, K. D., Wang, R., Pan, Z.-Q. DEN1 is a dual function protease capable of processing the C terminus of Nedd8 and deconjugating hyper-neddylated CUL1. J. Biol. Chem. 278: 28882-28891, 2003. PubMed: 12759363
^ Gan-Erdene, T., Nagamalleswari, K., Yin, L., Wu, K., Pan, Z.-Q., Wilkinson, K. D. Identification and characterization of DEN1, a deneddylase of the ULP family. J. Biol. Chem. 278: 28892-28900, 2003. PubMed: 12759362

Dopunska literatura

Bonaldo MF, Lennon G, Soares MB (septembar 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
Faber PW, Barnes GT, Srinidhi J, Chen J, Gusella JF, MacDonald ME (septembar 1998). "Huntingtin interacts with a family of WW domain proteins". Human Molecular Genetics. 7 (9): 1463–74. doi:10.1093/hmg/7.9.1463. PMID 9700202.
Zhang QH, Ye M, Wu XY, Ren SX, Zhao M, Zhao CJ, Fu G, Shen Y, Fan HY, Lu G, Zhong M, Xu XR, Han ZG, Zhang JW, Tao J, Huang QH, Zhou J, Hu GX, Gu J, Chen SJ, Chen Z (oktobar 2000). "Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells". Genome Research. 10 (10): 1546–60. doi:10.1101/gr.140200. PMC 310934. PMID 11042152.
Kim SC, Sprung R, Chen Y, Xu Y, Ball H, Pei J, Cheng T, Kho Y, Xiao H, Xiao L, Grishin NV, White M, Yang XJ, Zhao Y (august 2006). "Substrate and functional diversity of lysine acetylation revealed by a proteomics survey". Molecular Cell. 23 (4): 607–18. doi:10.1016/j.molcel.2006.06.026. PMID 16916647.

Vanjski linkovi

SERF2 lokacija ljudskog genoma UCSC Genome Browser.

SERF2 human gene details in the UCSC Genome Browser.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000166192 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000051705 - Ensembl, maj 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid9731538-5] Scharf JM, Endrizzi MG, Wetter A, Huang S, Thompson TG, Zerres K, Dietrich WF, Wirth B, Kunkel LM (septembar 1998). "Identification of a candidate modifying gene for spinal muscular atrophy by comparative genomics". Nature Genetics. 20 (1): 83–6. doi:10.1038/1753. PMID 9731538.

[entrez-6] "Entrez Gene: SERF2 small EDRK-rich factor 2".

[UniProt-7] "UniProt, Q96LD8". Pristupljeno 18. 7. 2021.

[8] Mendoza, H. M., Shen, L., Botting, C., Lewis, A., Chen, J., Ink, B., Hay, R. T. NEDP1, a highly conserved cysteine protease that deNEDDylates cullins. J. Biol. Chem. 278: 25637-25643, 2003. [PubMed: 12730221

[9] Wu, K., Yamoah, K., Dolios, G., Gan-Erdene, T., Tan, P., Chen, A., Lee, C., Wei, N., Wilkinson, K. D., Wang, R., Pan, Z.-Q. DEN1 is a dual function protease capable of processing the C terminus of Nedd8 and deconjugating hyper-neddylated CUL1. J. Biol. Chem. 278: 28882-28891, 2003. PubMed: 12759363

[10] Gan-Erdene, T., Nagamalleswari, K., Yin, L., Wu, K., Pan, Z.-Q., Wilkinson, K. D. Identification and characterization of DEN1, a deneddylase of the ULP family. J. Biol. Chem. 278: 28892-28900, 2003. PubMed: 12759362

[5]