HMBOX1

HMBOX1
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	2CUF, 4J19
Identifikatori
Aliasi	HMBOX1
Vanjski ID-jevi	MGI: 2445066 HomoloGene: 11589 GeneCards: HMBOX1
Lokacija gena (čovjek)
Hrom.	Hromosom 8 (čovjek)
Kraj	29,064,764 bp
Lokacija gena (miš)
Hrom.	Hromosom 14 (miš)
Kraj	65,187,320 bp
Ontologija gena
Molekularna funkcija	• vezivanje sa DNK; • telomerase activity; • double-stranded telomeric DNA binding; • GO:0001948, GO:0016582 vezivanje za proteine; • vezivanje identičnih proteina; • telomeric DNA binding; • GO:0001078, GO:0001214, GO:0001206 DNA-binding transcription repressor activity, RNA polymerase II-specific; • sequence-specific DNA binding; • GO:0032403 protein-containing complex binding; • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific;
Ćelijska komponenta	• citoplazma; • jedro; • telomerase holoenzyme complex; • nukleoplazma; • citosol; • nuclear body; • Telomera; • hromosom; • Cajal body; • PML body;
Biološki proces	• GO:0060469, GO:0009371 positive regulation of transcription, DNA-templated; • positive regulation of telomere maintenance via telomerase; • GO:0045996 negative regulation of transcription, DNA-templated; • GO:0009373 regulation of transcription, DNA-templated; • positive regulation of telomerase activity; • transcription, DNA-templated; • RNA-dependent DNA biosynthetic process; • positive regulation of chromatin binding; • GO:1901227 negative regulation of transcription by RNA polymerase II; • regulation of telomerase activity;
	Izvori:Amigo / QuickGO
Ortolozi
	79618
	219150
	ENSG00000147421
	ENSMUSG00000021972
	Q6NT76
	Q8BJA3
NM_001135726; NM_024567; NM_001324382; NM_001324383; NM_001324384;
	NM_001324385; NM_001324386; NM_001324387; NM_001324388; NM_001324389; NM_001324390; NM_001324391; NM_001324392; NM_001324393; NM_001324394; NM_001324395; NM_001330498
	NM_177338; NM_001347626; NM_001347627
NP_001129198; NP_001311311; NP_001311312; NP_001311313; NP_001311314;
	NP_001311315; NP_001311316; NP_001311317; NP_001311318; NP_001311319; NP_001311320; NP_001311321; NP_001311322; NP_001311323; NP_001311324; NP_001317427; NP_078843
	NP_001334555; NP_001334556; NP_796312
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Protein sa homeoboksom 1, znan i kao protein 1 sa homeoboksnim vezanjem telomere (HOT1), je protein koji je kod ljudi kodiran genom HMBOX1.^[5] HMBOX1 directly binds to the double-stranded repeat sequence of telomeres.^[6]^[7]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 420 aminokiselina, а molekulska težina 47.278 Da.^[8]

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
MLSSFPVVLL	ETMSHYTDEP	RFTIEQIDLL	QRLRRTGMTK	HEILHALETL
DRLDQEHSDK	FGRRSSYGGS	SYGNSTNNVP	ASSSTATAST	QTQHSGMSPS
PSNSYDTSPQ	PCTTNQNGRE	NNERLSTSNG	KMSPTRYHAN	SMGQRSYSFE
ASEEDLDVDD	KVEELMRRDS	SVIKEEIKAF	LANRRISQAV	VAQVTGISQS
RISHWLLQQG	SDLSEQKKRA	FYRWYQLEKT	NPGATLSMRP	APIPIEDPEW
RQTPPPVSAT	SGTFRLRRGS	RFTWRKECLA	VMESYFNENQ	YPDEAKREEI
ANACNAVIQK	PGKKLSDLER	VTSLKVYNWF	ANRRKEIKRR	ANIEAAILES
HGIDVQSPGG	HSNSDDVDGN	DYSEQDDSTS	HSDHQDPISL	AVEMAAVNHT
ILALARQGAN	EIKTEALDDD

Funkcija

HMBOX1 je prvobitno identificiran da se povezuje s telomernim hromatinom u ćelijama raka pozitivnim na telomerazu i ćelijama raka koje održavaju svoje telomere na osnovu alternativnog produženje telomera (ALT) pomoću obrnutog ChIP tehnika PICh (eng. skr. od proteomika izoliranih segmenata hromatina).^[6] Nakon toga je demonstrirano direktno vezivanje za telomernu DNK, preko kokristalnih struktura domen koji veže DNK HMBOX1 sa telomernom DNK.^[7] Eksperimenti s gubitkom i pojačanjem funkcije, klasificiraju HMBOX1 kao pozitivnog regulatora dužine telomera.^[7]^[9] HMBOX1 je prvobitno bio opisivan kao transkripcijski represor, na temelju testova reporteskih gena,^[10] ali pristupi cijelom genomu koji koriste RNK-seq i ChIP-seq ne vide takav učinak ili ga uopće nemaju, barem u nekoliko ćelijskih linija raka.^[11]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000147421 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000021972 - 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.
^ "Entrez Gene: Homeobox containing 1".
^ ^a ^b Déjardin J, Kingston RE (januar 2009). "Purification of proteins associated with specific genomic Loci". Cell. 136 (1): 175–86. doi:10.1016/j.cell.2008.11.045. PMC 3395431. PMID 19135898.
^ ^a ^b ^c Kappei D, Butter F, Benda C, Scheibe M, Draškovič I, Stevense M, Novo CL, Basquin C, Araki M, Araki K, Krastev DB, Kittler R, Jessberger R, Londoño-Vallejo JA, Mann M, Buchholz F (juni 2013). "HOT1 is a mammalian direct telomere repeat-binding protein contributing to telomerase recruitment". The EMBO Journal. 32 (12): 1681–701. doi:10.1038/emboj.2013.105. PMC 3680732. PMID 23685356.
^ "UniProt, Q6NT76" (jezik: engleski). Pristupljeno 19. 9. 2021.
^ Zhou S, Xiao Y, Zhuang Y, Liu Y, Zhao H, Yang H, Xie C, Zhou F, Zhou Y (juli 2017). "Knockdown of homeobox containing 1 increases the radiosensitivity of cervical cancer cells through telomere shortening". Oncology Reports. 38 (1): 515–521. doi:10.3892/or.2017.5707. PMID 28628186.
^ Chen S, Saiyin H, Zeng X, Xi J, Liu X, Li X, Yu L (2006). "Isolation and functional analysis of human HMBOX1, a homeobox containing protein with transcriptional repressor activity". Cytogenetic and Genome Research. 114 (2): 131–6. doi:10.1159/000093328. PMID 16825764. S2CID 21067536.
^ Jahn A, Rane G, Paszkowski-Rogacz M, Sayols S, Bluhm A, Han CT, Draškovič I, Londoño-Vallejo JA, Kumar AP, Buchholz F, Butter F, Kappei D (juni 2017). "ZBTB48 is both a vertebrate telomere-binding protein and a transcriptional activator". EMBO Reports. 18 (6): 929–946. doi:10.15252/embr.201744095. PMC 5452029. PMID 28500257.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000147421 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000021972 - 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.

[entrez-5] "Entrez Gene: Homeobox containing 1".

[Déjardin_2009-6] Déjardin J, Kingston RE (januar 2009). "Purification of proteins associated with specific genomic Loci". Cell. 136 (1): 175–86. doi:10.1016/j.cell.2008.11.045. PMC 3395431. PMID 19135898.

[Kappei_2013-7] Kappei D, Butter F, Benda C, Scheibe M, Draškovič I, Stevense M, Novo CL, Basquin C, Araki M, Araki K, Krastev DB, Kittler R, Jessberger R, Londoño-Vallejo JA, Mann M, Buchholz F (juni 2013). "HOT1 is a mammalian direct telomere repeat-binding protein contributing to telomerase recruitment". The EMBO Journal. 32 (12): 1681–701. doi:10.1038/emboj.2013.105. PMC 3680732. PMID 23685356.

[UniProt-8] "UniProt, Q6NT76" (jezik: engleski). Pristupljeno 19. 9. 2021.

[9] Zhou S, Xiao Y, Zhuang Y, Liu Y, Zhao H, Yang H, Xie C, Zhou F, Zhou Y (juli 2017). "Knockdown of homeobox containing 1 increases the radiosensitivity of cervical cancer cells through telomere shortening". Oncology Reports. 38 (1): 515–521. doi:10.3892/or.2017.5707. PMID 28628186.

[10] Chen S, Saiyin H, Zeng X, Xi J, Liu X, Li X, Yu L (2006). "Isolation and functional analysis of human HMBOX1, a homeobox containing protein with transcriptional repressor activity". Cytogenetic and Genome Research. 114 (2): 131–6. doi:10.1159/000093328. PMID 16825764. S2CID 21067536.

[11] Jahn A, Rane G, Paszkowski-Rogacz M, Sayols S, Bluhm A, Han CT, Draškovič I, Londoño-Vallejo JA, Kumar AP, Buchholz F, Butter F, Kappei D (juni 2017). "ZBTB48 is both a vertebrate telomere-binding protein and a transcriptional activator". EMBO Reports. 18 (6): 929–946. doi:10.15252/embr.201744095. PMC 5452029. PMID 28500257.

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