FOXP1

FOXP1
Dostupne strukture
PDB	Pretraga Human UniProta: PDBe RCSB
Spisak PDB ID kodova
	2KIU
Identifikatori
Aliasi	FOXP1
Vanjski ID-jevi	OMIM: 605515 HomoloGene: 136512 GeneCards: FOXP1
Lokacija gena (čovjek)
Hrom.	Hromosom 3 (čovjek)
Kraj	71,583,978 bp
Ontologija gena
Molekularna funkcija	• vezivanje iona metala; • sequence-specific DNA binding; • protein self-association; • androgen receptor binding; • GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity; • vezivanje sa DNK; • GO:0001948, GO:0016582 vezivanje za proteine; • vezivanje identičnih proteina; • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific; • GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding; • chromatin binding; • transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding; • transcription factor binding; • protein homodimerization activity; • protein heterodimerization activity;
Ćelijska komponenta	• jedro; • nukleoplazma; • citoplazma;
Biološki proces	• regulation of monocyte differentiation; • negative regulation of androgen receptor signaling pathway; • negative regulation of B cell apoptotic process; • positive regulation of endothelial cell migration; • transcription, DNA-templated; • response to lipopolysaccharide; • regulation of defense response to bacterium; • endothelial cell activation; • regulation of endothelial tube morphogenesis; • macrophage activation; • osteoclast development; • positive regulation of smooth muscle cell proliferation; • T follicular helper cell differentiation; • regulation of macrophage colony-stimulating factor production; • regulation of tumor necrosis factor production; • regulation of inflammatory response; • osteoclast differentiation; • monocyte activation; • GO:0009373 regulation of transcription, DNA-templated; • GO:0045996 negative regulation of transcription, DNA-templated; • GO:0044324, GO:0003256, GO:1901213, GO:0046019, GO:0046020, GO:1900094, GO:0061216, GO:0060994, GO:1902064, GO:0003258, GO:0072212 regulation of transcription by RNA polymerase II; • somatic stem cell population maintenance; • GO:1901227 negative regulation of transcription by RNA polymerase II; • in utero embryonic development; • positive regulation of mesenchymal cell proliferation; • pre-B cell differentiation; • positive regulation of immunoglobulin production; • heart development; • skeletal muscle tissue development; • motor neuron axon guidance; • ventral spinal cord development; • striatum development; • lung development; • forebrain development; • immunoglobulin V(D)J recombination; • response to testosterone; • sarcomere organization; • GO:0060469, GO:0009371 positive regulation of transcription, DNA-templated; • GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II; • smooth muscle tissue development; • positive regulation of epithelial cell proliferation; • cardiac muscle cell differentiation; • regulation of cardiac muscle cell proliferation; • negative regulation of cell growth involved in cardiac muscle cell development; • lung secretory cell differentiation; • cellular response to tumor necrosis factor; • innate vocalization behavior; • regulation of action potential; • regulation of lung goblet cell differentiation; • negative regulation of lung goblet cell differentiation; • cellular response to ionomycin; • positive regulation of hydrogen peroxide-induced cell death; • positive regulation of cardiac muscle cell differentiation; • cellular response to DNA damage stimulus; • negative regulation of gene expression; • positive regulation of B cell receptor signaling pathway;
	Izvori:Amigo / QuickGO
Ortolozi
	27086
	n/a
	ENSG00000114861
	n/a
	Q9H334
	n/a
NM_001012505; NM_001244808; NM_001244810; NM_001244812; NM_001244813;
	NM_001244814; NM_001244815; NM_001244816; NM_032682; NM_001349338; NM_001349340; NM_001349341; NM_001349342; NM_001349343; NM_001349344; NM_001349337; NM_001370548
	n/a
NP_001012523; NP_001231737; NP_001231739; NP_001231741; NP_001231742;
	NP_001231743; NP_001231744; NP_001231745; NP_116071; NP_001336267; NP_001336269; NP_001336270; NP_001336271; NP_001336272; NP_001336273; NP_001336266
	n/a
	Wikipodaci
Pogledaj/uredi – čovjek

Protein P1 viljuškaste kutije jest protein koji je kod ljudi kodiran genom FOXP1 sa hromosoma 3. FOXP1 je neophodan za pravilan razvoj mozga, srca i pluća kod sisara. Član je velike porodice transkripcijskih faktora FOX.

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 677 aminokiselina, а molekulska težina 75.317 Da.^[3]

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
MMQESGTETK	SNGSAIQNGS	GGSNHLLECG	GLREGRSNGE	TPAVDIGAAD
LAHAQQQQQQ	ALQVARQLLL	QQQQQQQVSG	LKSPKRNDKQ	PALQVPVSVA
MMTPQVITPQ	QMQQILQQQV	LSPQQLQVLL	QQQQALMLQQ	QQLQEFYKKQ
QEQLQLQLLQ	QQHAGKQPKE	QQQVATQQLA	FQQQLLQMQQ	LQQQHLLSLQ
RQGLLTIQPG	QPALPLQPLA	QGMIPTELQQ	LWKEVTSAHT	AEETTGNNHS
SLDLTTTCVS	SSAPSKTSLI	MNPHASTNGQ	LSVHTPKRES	LSHEEHPHSH
PLYGHGVCKW	PGCEAVCEDF	QSFLKHLNSE	HALDDRSTAQ	CRVQMQVVQQ
LELQLAKDKE	RLQAMMTHLH	VKSTEPKAAP	QPLNLVSSVT	LSKSASEASP
QSLPHTPTTP	TAPLTPVTQG	PSVITTTSMH	TVGPIRRRYS	DKYNVPISSA
DIAQNQEFYK	NAEVRPPFTY	ASLIRQAILE	SPEKQLTLNE	IYNWFTRMFA
YFRRNAATWK	NAVRHNLSLH	KCFVRVENVK	GAVWTVDEVE	FQKRRPQKIS
GNPSLIKNMQ	SSHAYCTPLN	AALQASMAEN	SIPLYTTASM	GNPTLGNLAS
AIREELNGAM	EHTNSNESDS	SPGRSPMQAV	HPVHVKEEPL	DPEEAEGPLS
LVTTANHSPD	FDHDRDYEDE	PVNEDME

Funkcija

Ovaj gen pripada potporodici P porodice transkripcionih faktora viljuškaste kutije (FOX). Faktori transkripcije ove kutije imaju važnu ulogu u regulaciji transkripcije gena specifične za tkivo i tip ćelije tokom razvoja i odrasle dobi. P1 protein viljuškaste kutije sadrži i DNK-vezujući domen – i domene za vezivanje protein-protein. Ovaj gen može djelovati kao tumorski supresor jer se gubi u nekoliko tipova tumora i mapira na hromozomskoj regiji (3p14.1) za koju se navodi da sadrži tumor supresorski gen(e). Alternativna prerada rezultira višestrukim varijantama transkripta koje kodiraju različite izoforme.^[4]

Foxp1 je faktor transkripcije; konkretno, to je transkripcijski represor. Geni FOX-a su dio porodičnog domena koji se vezuje za DNK. Ovaj domen se vezuje za sekvence u promotorima i pojačivačima mnogih gena. Foxp1 regulira niz važnih aspekata razvoja, uključujući razvoj tkiva: pluća, mozga, timusa i srca. U srcu Foxp1 ima tri vitalne uloge, koje uključuju regulaciju sazrijevanja i proliferacije kardiomiocita, odvajanje odlivnog trakta plućne arterije i aorte i ekspresiju Sox4 u holsterima i miokardu. Foxp1 je također važan gen u razvoju mišića i epitela jednjaka. Foxp1 je takođe važan regulator morfogeneze plućnih disajnih puteva. Embrioni Foxp1 nokaut-miševa pokazuju ozbiljne defekte u srčanoj morfogenezi. Neki od ovih defekata uključuju greške sazrijevanja i proliferacije miocita koji uzrokuju tanku ventrikularnu kompaktnu zonu miokarda, nerazdvajanje plućne arterije i aorte i povećanje proliferacije kardiomiocita i defektnu diferencijaciju. Ovi defekti, uzrokovani inaktivacijom Foxp1, dovode do smrti fetusa. Poremećaji FoxP1 su identificirani kod vrlo rijetkih ljudskih pacijenata i – slično kao i FoxP2 – dovode do kognitivne disfunkcije, uključujući intelektualnu invalidnost i poremećaj iz autističkog spektra, zajedno s oštećenjem jezika.^[5]

Pokazalo se da (ESC)-specifična izoforma FOXP1 embrionske matične ćelije stimulira ekspresiju gena transkripcijskik faktora potrebnih za pluripotencijju, uključujući OCT4, NANOG, NR5A2 i GDF3, dok istovremeno potiskuju gene potrebne za diferencijaciju ESC-a. Ova izoforma također promovira održavanje pluripotentnosti ESC i doprinosi efikasnom reprogramiranju somatskih ćelija u inducirane pluripotentne matične ćelije. Ovi rezultati otkrivaju ključnu ulogu za događanje alternativne prerade u regulaciji pluripotencije putem kontrole kritičnih ESC-specifičnih transkripcijskih programa.^[6]

Također pogledajte

FOXP2
FOXP3

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000114861 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "UniProt, Q9H334" (jezik: engleski). Pristupljeno 3. 11. 2021.
^ "Entrez Gene: FOXP1 forkhead box P1".
^ Bacon C, Rappold GA (Nov 2012). "The distinct and overlapping phenotypic spectra of FOXP1 and FOXP2 in cognitive disorders". Human Genetics. 131 (11): 1687–98. doi:10.1007/s00439-012-1193-z. PMC 3470686. PMID 22736078.
^ Gabut M, Samavarchi-Tehrani P, Wang X, Slobodeniuc V, O'Hanlon D, Sung HK, Alvarez M, Talukder S, Pan Q, Mazzoni EO, Nedelec S, Wichterle H, Woltjen K, Hughes TR, Zandstra PW, Nagy A, Wrana JL, Blencowe BJ (septembar 2011). "An alternative splicing switch regulates embryonic stem cell pluripotency and reprogramming". Cell. 147 (1): 132–46. doi:10.1016/j.cell.2011.08.023. PMID 21924763. S2CID 4978953.

Dopunska literatura

Katoh M, Katoh M (2005). "Human FOX gene family (Review)". Int. J. Oncol. 25 (5): 1495–500. doi:10.3892/ijo.25.5.1495. PMID 15492844.
Li C, Tucker PW (1994). "DNA-binding properties and secondary structural model of the hepatocyte nuclear factor 3/fork head domain". Proc. Natl. Acad. Sci. U.S.A. 90 (24): 11583–7. doi:10.1073/pnas.90.24.11583. PMC 48028. PMID 8265594.
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 (2001). "Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells". Genome Res. 10 (10): 1546–60. doi:10.1101/gr.140200. PMC 310934. PMID 11042152.
Banham AH, Beasley N, Campo E, Fernandez PL, Fidler C, Gatter K, Jones M, Mason DY, Prime JE, Trougouboff P, Wood K, Cordell JL (2002). "The FOXP1 winged helix transcription factor is a novel candidate tumor suppressor gene on chromosome 3p". Cancer Res. 61 (24): 8820–9. PMID 11751404.
Wolska MK, Bukowski K, Jakubczak A (2002). "[Occurrence of beta-lactamase type ESBL and IBL in Pseudomonas aeruginosa rods]". Medycyna doświadczalna i mikrobiologia. 53 (1): 45–51. PMID 11757404.
Wang B, Lin D, Li C, Tucker P (2003). "Multiple domains define the expression and regulatory properties of Foxp1 forkhead transcriptional repressors". J. Biol. Chem. 278 (27): 24259–68. doi:10.1074/jbc.M207174200. PMID 12692134.
Li S, Weidenfeld J, Morrisey EE (2004). "Transcriptional and DNA binding activity of the Foxp1/2/4 family is modulated by heterotypic and homotypic protein interactions". Mol. Cell. Biol. 24 (2): 809–22. doi:10.1128/MCB.24.2.809-822.2004. PMC 343786. PMID 14701752.
Teramitsu, Ikuko; Kudo, Lili C.; London, Sarah E.; Geschwind, Daniel H.; White, Stephanie A. (31. 3. 2004). "Parallel FoxP1 and FoxP2 Expression in Songbird and Human Brain Predicts Functional Interaction". Journal of Neuroscience (jezik: engleski). 24 (13): 3152–3163. doi:10.1523/JNEUROSCI.5589-03.2004. ISSN 0270-6474. PMC 6730014.
Fox SB, Brown P, Han C, Ashe S, Leek RD, Harris AL, Banham AH (2004). "Expression of the forkhead transcription factor FOXP1 is associated with estrogen receptor alpha and improved survival in primary human breast carcinomas". Clin. Cancer Res. 10 (10): 3521–7. doi:10.1158/1078-0432.CCR-03-0461. PMID 15161711.
Shi C, Zhang X, Chen Z, Sulaiman K, Feinberg MW, Ballantyne CM, Jain MK, Simon DI (2004). "Integrin engagement regulates monocyte differentiation through the forkhead transcription factor Foxp1". J. Clin. Invest. 114 (3): 408–18. doi:10.1172/JCI21100. PMC 484980. PMID 15286807.
Streubel B, Vinatzer U, Lamprecht A, Raderer M, Chott A (2005). "T(3;14)(p14.1;q32) involving IGH and FOXP1 is a novel recurrent chromosomal aberration in MALT lymphoma". Leukemia. 19 (4): 652–8. doi:10.1038/sj.leu.2403644. PMID 15703784.
Banham AH, Connors JM, Brown PJ, Cordell JL, Ott G, Sreenivasan G, Farinha P, Horsman DE, Gascoyne RD (2005). "Expression of the FOXP1 transcription factor is strongly associated with inferior survival in patients with diffuse large B-cell lymphoma". Clin. Cancer Res. 11 (3): 1065–72. PMID 15709173.
Brown P, Marafioti T, Kusec R, Banham AH (2007). "The FOXP1 transcription factor is expressed in the majority of follicular lymphomas but is rarely expressed in classical and lymphocyte predominant Hodgkin's lymphoma". J. Mol. Histol. 36 (4): 249–56. doi:10.1007/s10735-005-6521-3. PMID 16200457. S2CID 10290316.
Giatromanolaki A, Koukourakis MI, Sivridis E, Gatter KC, Harris AL, Banham AH (2006). "Loss of expression and nuclear/cytoplasmic localization of the FOXP1 forkhead transcription factor are common events in early endometrial cancer: relationship with estrogen receptors and HIF-1alpha expression". Mod. Pathol. 19 (1): 9–16. doi:10.1038/modpathol.3800494. PMID 16258506.
Sagaert X, de Paepe P, Libbrecht L, Vanhentenrijk V, Verhoef G, Thomas J, Wlodarska I, De Wolf-Peeters C (2006). "Forkhead box protein P1 expression in mucosa-associated lymphoid tissue lymphomas predicts poor prognosis and transformation to diffuse large B-cell lymphoma". J. Clin. Oncol. 24 (16): 2490–7. doi:10.1200/JCO.2006.05.6150. PMID 16636337.
Haralambieva E, Adam P, Ventura R, Katzenberger T, Kalla J, Höller S, Hartmann M, Rosenwald A, Greiner A, Muller-Hermelink HK, Banham AH, Ott G (2007). "Genetic rearrangement of FOXP1 is predominantly detected in a subset of diffuse large B-cell lymphomas with extranodal presentation". Leukemia. 20 (7): 1300–3. doi:10.1038/sj.leu.2404244. PMID 16673020.
Hannenhalli S, Putt ME, Gilmore JM, Wang J, Parmacek MS, Epstein JA, Morrisey EE, Margulies KB, Cappola TP (2006). "Transcriptional genomics associates FOX transcription factors with human heart failure". Circulation. 114 (12): 1269–76. doi:10.1161/CIRCULATIONAHA.106.632430. PMID 16952980.
Shu W, Min Lu M, Zhang Y, Tucker PW, Zhou D, Morrisey EE (2007). "Foxp2 and Foxp1 cooperatively regulate lung and esophagus development". Development. 134 (10): 1991–2000. doi:10.1242/dev.02846. PMID 17428829.
Wang B, Weidenfeld J, Min Lu M, Maika S, Kuziel WA, Morrisey EE, Tucker PW (2004). "Foxp1 regulates cardiac outflow tract, endocardial cushion morphogenesis and myocyte proliferation and maturation". Development. 131 (18): 4477–4487. doi:10.1242/dev.01287. PMID 15342473.

Vanjski linkovi

Further clinical details at OMIM Entry #613670 (Mental Retardation With Language Impairment and with or without Austistic Features)
Additional information also at OMIM Entry #605515 (Forkhead Box P1)
FOXP1 protein, human na US National Library of Medicine Medical Subject Headings (MeSH)
Q9H334

Ovaj članak uključuje tekst iz Nacionalne medicinske biblioteke Sjedinjenih Država, koji je u javnom vlasništvu.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000114861 - Ensembl, maj 2017

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

[UniProt-3] "UniProt, Q9H334" (jezik: engleski). Pristupljeno 3. 11. 2021.

[entrez-4] "Entrez Gene: FOXP1 forkhead box P1".

[5] Bacon C, Rappold GA (Nov 2012). "The distinct and overlapping phenotypic spectra of FOXP1 and FOXP2 in cognitive disorders". Human Genetics. 131 (11): 1687–98. doi:10.1007/s00439-012-1193-z. PMC 3470686. PMID 22736078.

[pmid21924763-6] Gabut M, Samavarchi-Tehrani P, Wang X, Slobodeniuc V, O'Hanlon D, Sung HK, Alvarez M, Talukder S, Pan Q, Mazzoni EO, Nedelec S, Wichterle H, Woltjen K, Hughes TR, Zandstra PW, Nagy A, Wrana JL, Blencowe BJ (septembar 2011). "An alternative splicing switch regulates embryonic stem cell pluripotency and reprogramming". Cell. 147 (1): 132–46. doi:10.1016/j.cell.2011.08.023. PMID 21924763. S2CID 4978953.

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