CXXC5

CXXC5
Identifikatori
Aliasi	CXXC5
Vanjski ID-jevi	OMIM: 612752 MGI: 1914643 HomoloGene: 9517 GeneCards: CXXC5
Lokacija gena (čovjek)
Hrom.	Hromosom 5 (čovjek)
Kraj	139,683,882 bp
Lokacija gena (miš)
Hrom.	Hromosom 18 (miš)
Kraj	35,994,741 bp
Ontologija gena
Molekularna funkcija	• sequence-specific DNA binding; • vezivanje sa DNK; • vezivanje iona cinka; • transcription factor binding; • GO:0001948, GO:0016582 vezivanje za proteine; • signal transducer activity; • vezivanje iona metala;
Ćelijska komponenta	• jedro; • nukleoplazma; • citoplazma; • citosol;
Biološki proces	• positive regulation of I-kappaB kinase/NF-kappaB signaling; • GO:1901227 negative regulation of transcription by RNA polymerase II; • transcription, DNA-templated; • GO:0072468 Transdukcija signala;
	Izvori:Amigo / QuickGO
Ortolozi
	51523
	67393
	ENSG00000171604
	ENSMUSG00000046668
	Q7LFL8
	Q91WA4
NM_016463; NM_001317199; NM_001317200; NM_001317201; NM_001317202;
	NM_001317203; NM_001317204; NM_001317205; NM_001317206; NM_001317207; NM_001317208; NM_001317209; NM_001317210; NM_001317211
	NM_133687; NM_001357458; NM_001357459
NP_001304128; NP_001304129; NP_001304130; NP_001304131; NP_001304132;
	NP_001304133; NP_001304134; NP_001304135; NP_001304136; NP_001304137; NP_001304138; NP_001304139; NP_001304140; NP_057547
	NP_598448; NP_001344387; NP_001344388
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Protein 5 cinkovog prsta tipa CXXC jest protein koji je kod ljudi kodiran genom CXXC5.^[5]^[6]^[7]^[8]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 322 aminokiseline, а molekulska težina 32.977 Da.^[9]

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

10	20	30	40	50
MSSLGGGSQD	AGGSSSSSTN	GSGGSGSSGP	KAGAADKSAV	VAAAAPASVA
DDTPPPERRN	KSGIISEPLN	KSLRRSRPLS	HYSSFGSSGG	SGGGSMMGGE
SADKATAAAA	AASLLANGHD	LAAAMAVDKS	NPTSKHKSGA	VASLLSKAER
ATELAAEGQL	TLQQFAQSTE	MLKRVVQEHL	PLMSEAGAGL	PDMEAVAGAE
ALNGQSDFPY	LGAFPINPGL	FIMTPAGVFL	AESALHMAGL	AEYPMQGELA
SAISSGKKKR	KRCGMCAPCR	RRINCEQCSS	CRNRKTGHQI	CKFRKCEELK
KKPSAALEKV	MLPTGAAFRW	FQ

Funkcija

Kako mu je naznačeno imenom, CXXC5 ima ulogu transkripcijskog faktora u ćelijskom jedru , te sudjeluje u mijelopoezi, endotelnoj diferencijaciji, stvaranju krvnih sudova i diferencijaciji oligodendrocita.^[7]^[10]^[11]

CXXC5 je također okarakteriziran kao regulator negativne povratne sprege Wnt/β-kateninskog signalnog puta koji funkcionira direktnom interakcijom s neuređenim (Dvl) proteinom u citosolu.^[6]^[10]^[12]^[13]^[14] Citosolna prekomjerna ekspresija CXXC5 izazvana je zbog nekoliko patofizioloških stanja, kao što su osteoporoza, alopecija, starenje ploče za rast, kožne rane i obnavljanje potisnute signalizacije Wnt/β-katenina, blokadom njegove funkcije vezivanja Dvl pogoršavajući patološke značajke primijećene kod miševa a genotipCxxc5 ^–/–.^[10]^[13]^[14]^[15] Ovi rezultati ukazuju da bi vezivanje Dvl s citosolnim CXXC5 moglo biti meta za razvoj sredstava za liječenje alopecije, akutnih rana i niskog rasta u djetinjstvu i adolescenciji, koji pokazuju potisnutu signalizaciju Wnt/β-katenina citosolnom prekomjernom ekspresijom CXXC5 odgovornih ćelija tkiva.^[12]^[14]^[15] The CXXC5-Dvl Interakcija protein-protein (PPI) kao meta za razvoj agenasa kod opadanja kose ili akutne rane također je potvrđena konstrukcijom i ispitivanjem funkcije PTD-DBM, peptida koji inhibira CXXC5-Dvl PPIl.^[12]^[14]

Pobgoršanje abnormalnosti pomoću CXXC5-Dvl PPI inhibitora pripisuje se obnavljanju oštećenih tkiva aktiviranjem matičnih ćelija putem restorativne aktivacije potisnute signalizacije Wnt/β-katenina i njegovih ciljnih gena koji uključuju regeneraciju.

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000171604 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000046668 - 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.
^ Zhang QH, Ye M, Wu XY, Ren SX, Zhao M, Zhao CJ, et al. (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.
^ ^a ^b Andersson T, Södersten E, Duckworth JK, Cascante A, Fritz N, Sacchetti P, et al. (februar 2009). "CXXC5 is a novel BMP4-regulated modulator of Wnt signaling in neural stem cells". The Journal of Biological Chemistry. 284 (6): 3672–81. doi:10.1074/jbc.M808119200. PMID 19001364.
^ ^a ^b Pendino F, Nguyen E, Jonassen I, Dysvik B, Azouz A, Lanotte M, et al. (april 2009). "Functional involvement of RINF, retinoid-inducible nuclear factor (CXXC5), in normal and tumoral human myelopoiesis". Blood. 113 (14): 3172–81. doi:10.1182/blood-2008-07-170035. PMID 19182210.
^ "Entrez Gene: CXXC5 CXXC finger 5".
^ "UniProt, Q7LFL8" (jezik: engleski). Pristupljeno 13. 10. 2021.
^ ^a ^b ^c Kim HY, Yoon JY, Yun JH, Cho KW, Lee SH, Rhee YM, et al. (juni 2015). "CXXC5 is a negative-feedback regulator of the Wnt/β-catenin pathway involved in osteoblast differentiation". Cell Death and Differentiation. 22 (6): 912–20. doi:10.1038/cdd.2014.238. PMID 25633194.
^ Kim HY, Yang DH, Shin SW, Kim MY, Yoon JH, Kim S, et al. (februar 2014). "CXXC5 is a transcriptional activator of Flk-1 and mediates bone morphogenic protein-induced endothelial cell differentiation and vessel formation". FASEB Journal. 28 (2): 615–26. doi:10.1096/fj.13-236216. PMID 24136587.
^ ^a ^b ^c Lee SH, Kim MY, Kim HY, Lee YM, Kim H, Nam KA, et al. (juni 2015). "The Dishevelled-binding protein CXXC5 negatively regulates cutaneous wound healing". The Journal of Experimental Medicine. 212 (7): 1061–80. doi:10.1084/jem.20141601. PMID 26056233.
^ ^a ^b Kim HY, Choi S, Yoon JH, Lim HJ, Lee H, Choi J, et al. (april 2016). "Small molecule inhibitors of the Dishevelled-CXXC5 interaction are new drug candidates for bone anabolic osteoporosis therapy". EMBO Molecular Medicine. 8 (4): 375–87. doi:10.15252/emmm.201505714. PMID 26941261.
^ ^a ^b ^c ^d Lee SH, Seo SH, Lee DH, Pi LQ, Lee WS, Choi KY (novembar 2017). "Targeting of CXXC5 by a Competing Peptide Stimulates Hair Regrowth and Wound–Induced Hair Neogenesis". The Journal of Investigative Dermatology. 137 (11): 2260–2269. doi:10.1016/j.jid.2017.04.038. PMID 28595998.
^ ^a ^b Choi S, Kim HY, Cha PH, Seo SH, Lee C, Choi Y, et al. (april 2019). "CXXC5 mediates growth plate senescence and is a target for enhancement of longitudinal bone growth". Life Science Alliance. 2 (2): e201800254. doi:10.26508/lsa.201800254. PMID 30971423.

Dopunska literatura

Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, et al. (oktobar 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
Colland F, Jacq X, Trouplin V, Mougin C, Groizeleau C, Hamburger A, et al. (juli 2004). "Functional proteomics mapping of a human signaling pathway". Genome Research. 14 (7): 1324–32. doi:10.1101/gr.2334104. PMC 442148. PMID 15231748.
Matsuda A, Suzuki Y, Honda G, Muramatsu S, Matsuzaki O, Nagano Y, et al. (maj 2003). "Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways". Oncogene. 22 (21): 3307–18. doi:10.1038/sj.onc.1206406. PMID 12761501.
Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, et al. (april 1997). "Large-scale concatenation cDNA sequencing". Genome Research. 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174.
Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (april 1996). "A "double adaptor" method for improved shotgun library construction". Analytical Biochemistry. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID 8619474.

Vanjski linkovi

Lokacija ljudskog genoma CXXC5 i stranica sa detaljima o genu CXXC5 u UCSC Genome Browseru.
GRCh38: Ensembl release 89: ENSG00000171604 - Ensembl, May 2017
GRCm38: Ensemble release 89: ENSMUSG00000046668 - Ensembl, May 2017
"Human PubMed Reference" National Center for Biotechnology Information, U.S. National Library of Medicine.
"Human PubMed Reference" National Center for Biotechnology Information, U.S. National Library of Medicine.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000171604 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000046668 - 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.

[pmid11042152-5] Zhang QH, Ye M, Wu XY, Ren SX, Zhao M, Zhao CJ, et al. (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.

[pmid19001364-6] Andersson T, Södersten E, Duckworth JK, Cascante A, Fritz N, Sacchetti P, et al. (februar 2009). "CXXC5 is a novel BMP4-regulated modulator of Wnt signaling in neural stem cells". The Journal of Biological Chemistry. 284 (6): 3672–81. doi:10.1074/jbc.M808119200. PMID 19001364.

[pmid19182210-7] Pendino F, Nguyen E, Jonassen I, Dysvik B, Azouz A, Lanotte M, et al. (april 2009). "Functional involvement of RINF, retinoid-inducible nuclear factor (CXXC5), in normal and tumoral human myelopoiesis". Blood. 113 (14): 3172–81. doi:10.1182/blood-2008-07-170035. PMID 19182210.

[entrez-8] "Entrez Gene: CXXC5 CXXC finger 5".

[UniProt-9] "UniProt, Q7LFL8" (jezik: engleski). Pristupljeno 13. 10. 2021.

[Kim_2015-10] Kim HY, Yoon JY, Yun JH, Cho KW, Lee SH, Rhee YM, et al. (juni 2015). "CXXC5 is a negative-feedback regulator of the Wnt/β-catenin pathway involved in osteoblast differentiation". Cell Death and Differentiation. 22 (6): 912–20. doi:10.1038/cdd.2014.238. PMID 25633194.

[11] Kim HY, Yang DH, Shin SW, Kim MY, Yoon JH, Kim S, et al. (februar 2014). "CXXC5 is a transcriptional activator of Flk-1 and mediates bone morphogenic protein-induced endothelial cell differentiation and vessel formation". FASEB Journal. 28 (2): 615–26. doi:10.1096/fj.13-236216. PMID 24136587.

[Lee_2015-12] Lee SH, Kim MY, Kim HY, Lee YM, Kim H, Nam KA, et al. (juni 2015). "The Dishevelled-binding protein CXXC5 negatively regulates cutaneous wound healing". The Journal of Experimental Medicine. 212 (7): 1061–80. doi:10.1084/jem.20141601. PMID 26056233.

[Kim_2016-13] Kim HY, Choi S, Yoon JH, Lim HJ, Lee H, Choi J, et al. (april 2016). "Small molecule inhibitors of the Dishevelled-CXXC5 interaction are new drug candidates for bone anabolic osteoporosis therapy". EMBO Molecular Medicine. 8 (4): 375–87. doi:10.15252/emmm.201505714. PMID 26941261.

[Lee_2017-14] Lee SH, Seo SH, Lee DH, Pi LQ, Lee WS, Choi KY (novembar 2017). "Targeting of CXXC5 by a Competing Peptide Stimulates Hair Regrowth and Wound–Induced Hair Neogenesis". The Journal of Investigative Dermatology. 137 (11): 2260–2269. doi:10.1016/j.jid.2017.04.038. PMID 28595998.

[CXXC5_mediates_growth_plate_senesce-15] Choi S, Kim HY, Cha PH, Seo SH, Lee C, Choi Y, et al. (april 2019). "CXXC5 mediates growth plate senescence and is a target for enhancement of longitudinal bone growth". Life Science Alliance. 2 (2): e201800254. doi:10.26508/lsa.201800254. PMID 30971423.

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