PITX2

PITX2
已やめ知的ちてき結構けっこう
PDB	直系ちょっけい同どう源みなもと搜索そうさく: PDBe RCSB
PDBID列れつ表ひょう
	2L7F、2L7M、2LKX
識別しきべつ號ごう
别名	PITX2；, ARP1, Brx1, IDG2, IGDS, IGDS2, IHG2, IRID2, Otlx2, PTX2, RGS, RIEG, RIEG1, RS, paired like homeodomain 2, ASGD4
外部がいぶID	OMIM：601542 MGI：109340 HomoloGene：55454 GeneCards：PITX2
相關そうかん疾病しっぺい
	Axenfeld-Rieger syndrome type 1、虹にじ膜まく發育はついく不良ふりょう綜合そうごう徵ちょう、ring dermoid of cornea、Rieger anomaly
基もと因いん位置いち（人ひと类）
染色せんしょく体たい	4號ごう染色せんしょく體たい
终止	110,642,123 bp
基もと因いん位置いち（小しょう鼠ねずみ）
染色せんしょく体たい	小しょう鼠ねずみ3号ごう染色せんしょく体たい
终止	129,013,240 bp
RNA表ひょう达模も式しき
	查阅更さら多た表ひょう达数据すえ
基もと因いん本體ほんたい
分子ぶんし功こう能のう	• 相あい同どう蛋白たんぱく质结合あい; • protein homodimerization activity; • transcription cis-regulatory region binding; • sequence-specific DNA binding; • DNA结合; • 转录共ども激げき活かつ因子いんし活性かっせい; • chromatin DNA binding; • DNA-binding transcription activator activity, RNA polymerase II-specific; • 血ち浆蛋白しろ结合; • RNA polymerase II cis-regulatory region sequence-specific DNA binding; • chromatin binding; • ribonucleoprotein complex binding; • DNA结合转录因子いんし活性かっせい; • DNA结合转录阻遏物ぶつ活性かっせい，RNA聚合酶II特とく异性; • 转录因子いんし结合; • 磷蛋白しろ结合; • DNA-binding transcription factor activity, RNA polymerase II-specific;
細胞さいぼう組ぐみ分ぶん	• 细胞核かく; • 細胞さいぼう質しつ; • 轉てん錄ろく調節ちょうせつ複ふく合ごう物ぶつ; • 核かく质;
生物せいぶつ學がく過程かてい	• response to vitamin A; • female gonad development; • vascular associated smooth muscle cell differentiation; • regulation of transcription by RNA polymerase II; • skeletal muscle tissue development; • cell proliferation involved in outflow tract morphogenesis; • prolactin secreting cell differentiation; • in utero embryonic development; • 垂たれ体たい的てき发生; • 血管けっかん發生はっせい; • regulation of cell population proliferation; • myoblast fusion; • hair cell differentiation; • 脾的发生; • regulation of transcription, DNA-templated; • transcription by RNA polymerase II; • embryonic camera-type eye development; • ventricular septum morphogenesis; • endodermal digestive tract morphogenesis; • determination of left/right symmetry; • cardiac muscle tissue development; • positive regulation of transcription, DNA-templated; • subthalamic nucleus development; • ventricular cardiac muscle cell development; • left/right axis specification; • hypothalamus cell migration; • animal organ morphogenesis; • regulation of cell migration; • 心こころ脏发育いく; • embryonic digestive tract morphogenesis; • branching involved in blood vessel morphogenesis; • cardiac muscle cell differentiation; • digestive system development; • multicellular organism development; • atrioventricular valve development; • pulmonary vein morphogenesis; • cardiac neural crest cell migration involved in outflow tract morphogenesis; • embryonic hindlimb morphogenesis; • lung development; • superior vena cava morphogenesis; • positive regulation of DNA binding; • extraocular skeletal muscle development; • pulmonary myocardium development; • deltoid tuberosity development; • atrial cardiac muscle tissue morphogenesis; • male gonad development; • anatomical structure morphogenesis; • brain development; • neuron differentiation; • odontogenesis of dentin-containing tooth; • Wnt信号しんごう通路つうろ; • left lung morphogenesis; • somatotropin secreting cell differentiation; • positive regulation of myoblast proliferation; • camera-type eye development; • response to hormone; • odontogenesis; • iris morphogenesis; • neuron migration; • negative regulation of transcription by RNA polymerase II; • positive regulation of transcription by RNA polymerase II;
	Sources:Amigo / QuickGO
直系ちょっけい同どう源みなもと
	5308
	18741
	ENSG00000164093
	ENSMUSG00000028023
	Q99697
	P97474
NM_000325; NM_001204397; NM_001204398; NM_001204399; NM_153426;
	NM_153427
	NM_001042502; NM_001042504; NM_001286942; NM_001287048; NM_011098
NP_000316; NP_001191326; NP_001191327; NP_001191328; NP_700475;
	NP_700476
	NP_001035967; NP_001035969; NP_001273871; NP_001273977; NP_035228
	維基數すう據よりどころ
檢視けんし/編輯へんしゅう人類じんるい	檢視けんし/編輯へんしゅう小しょう鼠ねずみ

PITX2（Paired-like homeodomain transcription factor 2（類るい成なり對たい同どう源みなもと框かまち轉てん錄ろく因子いんし2）/pituitary homeobox 2（垂たれ體たい同どう源みなもと框かまち2））是ぜ一個位於人第四號染色體上的基因，由よし其編碼的蛋白たんぱく為ためPITX2^[6]^[7]^[8]。

功こう能のう

PITX2蛋白たんぱく屬ぞく於RIEG/PITX同どう源みなもと框かまち蛋白たんぱく家族かぞく，有ゆう一いち個こ屬ぞく於Bicoid（英えい语：Bicoid）蛋白たんぱく家族かぞく的てき同どう源みなもと結構けっこう域いき。從したがえ功こう能のう上じょう說せつ，PITX2是ぜ一いち種しゅ轉てん錄ろく因子いんし^[9]，主要しゅよう調ちょう控ひかえ前ぜん膠にかわ原はら賴よりゆき氨酰羥化酶（英えい语：lysyl hydroxylase）（procollagen lysyl hydroxylase）基もと因いん的てき表ひょう達たち。賴よりゆき氨酰羥化酶參與さんよ眼め、牙きば，以及腹部ふくぶ器官きかん的てき發育はついく過程かてい。PITX2的てき轉てん錄ろく調節ちょうせつ活性かっせい受到催乳素もと的てき調節ちょうせつ。已やめ發現はつげん人體じんたい內的PITX2有ゆう三さん種しゅ轉てん錄ろく變體へんたい^[8]。

PITX2在ざい發育はついく中ちゅう與あずか左ひだり—右みぎ軸じく的てき建立こんりゅう及左右さゆう不ふ對稱たいしょう性的せいてき形成けいせい有ゆう關せき，比ひ如左側がわ中ちゅう胚はい層そう（英えい语：lateral mesoderm）、心臟しんぞう、肺はい、脾的不ふ對稱たいしょう發育はついく及早起おこり胃腸いちょう道どう的てき彎折。已やめ證明しょうめい在ざい非人ひにん脊椎動物せきついどうぶつ中ちゅう，PITX2的てき同どう源みなもと基はじめ因いん亦また有ゆう這樣的てき功こう能のう。敲除小しょう鼠ねずみ的てきPitx2基き因いん後ご，會かい導しるべ致身體しんたい左側ひだりがわ器官きかん形態けいたい發育はついく異常いじょう。PITX2本身ほんみ的てき表ひょう達たち受到ASE增強ぞうきょう子こ和わNODAL（英えい语：NODAL）蛋白たんぱく的てき調ちょう控ひかえ。目前もくぜん的てき研究けんきゅう證據しょうこ顯示けんじNODAL蛋白たんぱく主要しゅよう調ちょう控ひかえ頭部とうぶ的てきPITX2基き因いん表ひょう達たち，而ASE主要しゅよう調ちょう控ひかえ控ひかえ制せい不ふ對稱たいしょう發展はってん的てきPITX2基き因いん的てき發展はってん，如肝、脾的不ふ對稱たいしょう發展はってん。在ざい眼め部ぶ發育はついく中ちゅう，PITX2能のう抑制よくせい眼め外がい肌はだ的てき自じ噬，並なみ能のう控ひかえ制せい其生長せいちょう^[10]^[11]^[12]。PITX2的てき三さん種しゅ轉てん錄ろく變體へんたいPITX2a、PITX2b、PITX2c各自かくじ都みやこ有ゆう不ふ重疊ちょうじょう的てき不同ふどう功こう能のう^[13]。

PITX2亦また參與さんよ了りょう附ふ肢し形態けいたい形成けいせい。PITX2能のう調ちょう控ひかえMyoD基もと因いん的てき表ひょう達たち，使つかい其在附ふ肢し形成けいせい過程かてい中ちゅう一いち直ちょく表ひょう達たち。MyoD基もと因いん與あずか骨骼こっかく形態けいたい發生はっせい有ゆう關せき。研究けんきゅう表明ひょうめいPixt2在ざい肌はだ肉にく中ちゅう先さき於MyoD表ひょう達たち。要よう激げき活かつMyoD基もと因いん表ひょう達たち，PITX2首しゅ先さき會かい募集ぼしゅう到いたMyoD的てき核心かくしん增強ぞうきょう子こ上じょう，然しか後こう激げき活かつMyoD的てき表ひょう達たち。Myf5、Myf6基き因いん亦また能のう調ちょう控ひかえMyoD的てき表ひょう達たち，但ただし與あずかPITX2之これ間あいだ互不影響えいきょう。PITX2對たい附ふ肢し發育はついく的てき調ちょう控ひかえ依賴いらいPAX3蛋白たんぱく。在ざい缺乏けつぼうPAX3的てき情況じょうきょう下か，即そく使つかいPITX2表ひょう達たち附ふ肢し也無法ほう形成けいせい。該實驗じっけん結果けっか提示ていじ在ざい調ちょう控ひかえ通路つうろ中ちゅうPITX2處しょ於PAX3的てき下か游ゆう，充當じゅうとう了りょうPAX3和わMyoD之の間あいだ的中てきちゅう間あいだ體たい。總そう而言之の，PITX2在ざい附ふ肢し發育はついく中ちゅう是ぜ不可ふか或ある缺かけ的てき^[14]。

另外，有ゆう證據しょうこ表明ひょうめいPitx2在ざい大だい鼠ねずみ體たい內與性腺せいせん生成せいせい障礙しょうがい有ゆう關せき^[15]。

臨床りんしょう意義いぎ

PITX2基き因いん突變可能かのう導しるべ致阿おもね克かつ森もり費ひ爾しか德とく綜合そうごう徵ちょう（英えい语：Axenfeld-Rieger syndrome）（Axenfeld-Rieger syndrome, ARS）、虹にじ膜まく發育はついく不良ふりょう綜合そうごう徵ちょう（英えい语：iridogoniodysgenesis, dominant type）（iridogoniodysgenesis syndrome, IGDS）等とう表現ひょうげん爲ため眼前がんぜん間あいだ充たかし質しつ發育はついく不良ふりょう（英えい语：Anterior segment mesenchymal dysgenesis）的まと病びょう徵ちょう^[8]。

在ざい惡性あくせい腫しゅ瘤こぶ中ちゅう，PITX2常常つねづね會かい過か表ひょう達たち。比ひ如，甲狀腺こうじょうせん癌がん^[16]、卵巢らんそう癌がん^[17]和かず結腸けっちょう癌がん^[18]的てきPITX2表ひょう達たち水平すいへい都と高だか於正常せいじょう的てき非ひ腫しゅ瘤こぶ組織そしき。研究けんきゅう人員じんいん推測すいそく，腫しゅ瘤こぶ細胞さいぼう的てきPITX2表ひょう達たち異常いじょう開ひらけ啓けい，造成ぞうせい了りょう細胞さいぼう的てき惡性あくせい增殖ぞうしょく。此前的てき研究けんきゅう表明ひょうめいPITX2會かい調ちょう控ひかえC-Myc以及細胞さいぼう週しゅう期き蛋白たんぱくD1、D2的てき表ひょう達たち，這些事實じじつ支持しじ上述じょうじゅつ假說かせつ^[19]^[20]^[20]

研究けんきゅう表明ひょうめい，腎じん癌がん組織そしき內，PITX2的てき表ひょう達たち能のう提ひさげ高だかABCB1（英えい语：ABCB1）基もと因いん的てき表ひょう達たち強度きょうど。進一しんいち步ふ研究けんきゅう表明ひょうめい，PITX2能のう與あずかABCB1基もと因いん的てき啓けい動どう子こ結合けつごう，使つかい該基因いん表ひょう達たち。該基因いん編へん碼的蛋白たんぱく能のう夠轉運うん多種たしゅ藥物やくぶつ，使つかい細胞さいぼう對たい化か療藥りょうやく物的ぶってき耐たい藥やく性せい增強ぞうきょう。如果降くだ低てい腎じん癌がん細胞さいぼう內PITX2的てき表ひょう達たち強度きょうど，那な麼細胞さいぼう的てき增殖ぞうしょく速度そくど會かい減げん緩なる，化か療藥りょうやく物ぶつ多た柔やわら比ひ星ぼし（doxorubicin）對たい細胞さいぼう的てき殺傷さっしょう力也りきや會かい增加ぞうか^[21]。

在ざい人ひと食管しょっかん立方りっぽう細胞さいぼう瘤こぶ（esophageal squamous cell carcinoma（ESCC））中ちゅう，PITX2的てき表ひょう達たち水平すいへい亦また高こう於正常つね組織そしき。臨床りんしょう數すう據よりどころ表明ひょうめいPITX2的てき表ひょう達たち強度きょうど與あずか該腫瘤こぶ的てき擴散かくさん性せい成なり正せい比ひ。患該癌がん症しょう的てき病人びょうにん，如果腫しゅ瘤こぶPITX2表ひょう達たち強度きょうど較高，那な麼對化か療藥りょうやく物ぶつ會かい有ゆう較高的てき耐たい藥やく性せい.醫い生せい因いん而可以通過つうかPITX2的てき表ひょう達たち強度きょうど來らい預あずか測はか食管しょっかん立方りっぽう細胞さいぼう瘤こぶ病人びょうにん接受せつじゅ化か療後病びょう情じょう能のう得え到いた多大ただい程度ていど的てき緩解かんかい^[22]。

PITX2的てき雜ざつ合あい突變可能かのう導しるべ致法ほう洛らく四よん聯れん症しょう、室しつ間隔かんかく缺損けっそん、房ぼう間隔かんかく缺損けっそん、大動脈だいどうみゃく轉位てんい、心こころ內膜缺損けっそん（英えい语：endocardial cushion defect）（ECD）等とう先天せんてん性せい心臟しんぞう病びょう^[23]^[24]^[25]。PITX2的てき突變是ぜ由ゆかり可變かへん剪接模も式しき的てき改變かいへん引起。PITX2C的てき變體へんたいPITX2C對たい心しん血管けっかん發生はっせい最さい爲ため重要じゅうよう。如果該變體へんたい不ふ表ひょう達たち，心こころ血管けっかん發生はっせい就會出現しゅつげん問題もんだい。PITX2的てき一些突變會顯著降低PITX2的てき轉てん錄ろく活性かっせい，以及PITX2和わNKX2（英えい语：NKX2）（NKX2在ざい心しん血管けっかん發生はっせい中ちゅう也扮演えんじ重要じゅうよう角かく色しょく）之の間あいだ的てき協同きょうどう活性かっせい^[23]。由よしPITX2突變產さん生せい的てき表ひょう型がた多樣たよう，可能かのう是ぜ由よし不同ふどう的てき遺傳いでん背景はいけい、表ひょう觀かん遺傳いでん修飾しゅうしょく蛋白たんぱく以及不同ふどう/延のべ遲おそ的てき外がい顯あらわ率りつ造成ぞうせい^[24]。值得注意ちゅうい的てき是ぜPITX2的てき突變並なみ不ふ是ぜ造成ぞうせい先さき天性てんせい心臟しんぞう病的びょうてき主導しゅどう因いん素もと，但ただし會かい影響えいきょう這些疾病しっぺい的てき發展はってん^[25]。

參考さんこう

^ 與あずかPITX2相關そうかん的てき疾病しっぺい；在ざい維基數すう據よりどころ上じょう查看/編輯へんしゅう參考さんこう.
^ ^2.0 ^2.1 ^2.2 GRCh38: Ensembl release 89: ENSG00000164093 - Ensembl, May 2017
^ ^3.0 ^3.1 ^3.2 GRCm38: Ensembl release 89: ENSMUSG00000028023 - Ensembl, May 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.
^ Arakawa H, Nakamura T, Zhadanov AB, Fidanza V, Yano T, Bullrich F, Shimizu M, Blechman J, Mazo A, Canaani E, Croce CM. Identification and characterization of the ARP1 gene, a target for the human acute leukemia ALL1 gene. Proceedings of the National Academy of Sciences of the United States of America. Apr 1998, 95 (8): 4573–8. PMC 22531 . PMID 9539779. doi:10.1073/pnas.95.8.4573.
^ Héon E, Sheth BP, Kalenak JW, Sunden SL, Streb LM, Taylor CM, Alward WL, Sheffield VC, Stone EM. Linkage of autosomal dominant iris hypoplasia to the region of the Rieger syndrome locus (4q25). Human Molecular Genetics. Aug 1995, 4 (8): 1435–9. PMID 7581385. doi:10.1093/hmg/4.8.1435.
^ ^8.0 ^8.1 ^8.2 Entrez Gene: PITX2 paired-like homeodomain transcription factor 2.
^ Logan M, Pagán-Westphal SM, Smith DM, Paganessi L, Tabin CJ. The transcription factor Pitx2 mediates situs-specific morphogenesis in response to left-right asymmetric signals. Cell. Aug 1998, 94 (3): 307–17. PMID 9708733. doi:10.1016/S0092-8674(00)81474-9.
^ Campione M, Steinbeisser H, Schweickert A, Deissler K, van Bebber F, Lowe LA, Nowotschin S, Viebahn C, Haffter P, Kuehn MR, Blum M. The homeobox gene Pitx2: mediator of asymmetric left-right signaling in vertebrate heart and gut looping. Development. Mar 1999, 126 (6): 1225–34. PMID 10021341.
^ Shiratori H, Yashiro K, Shen MM, Hamada H. Conserved regulation and role of Pitx2 in situs-specific morphogenesis of visceral organs. Development. Aug 2006, 133 (15): 3015–25. PMID 16835440. doi:10.1242/dev.02470.
^ Zacharias AL, Lewandoski M, Rudnicki MA, Gage PJ. Pitx2 is an upstream activator of extraocular myogenesis and survival. Developmental Biology. Jan 2011, 349 (2): 395–405. PMC 3019256 . PMID 21035439. doi:10.1016/j.ydbio.2010.10.028.
^ Essner JJ, Branford WW, Zhang J, Yost HJ. Mesendoderm and left-right brain, heart and gut development are differentially regulated by pitx2 isoforms. Development. Mar 2000, 127 (5): 1081–93. PMID 10662647.
^ L'honoré A, Ouimette JF, Lavertu-Jolin M, Drouin J. Pitx2 defines alternate pathways acting through MyoD during limb and somitic myogenesis. Development. Nov 2010, 137 (22): 3847–56. PMID 20978076. doi:10.1242/dev.053421.
^ Nandi SS, Ghosh P, Roy SS. Expression of PITX2 homeodomain transcription factor during rat gonadal development in a sexually dimorphic manner. Cellular Physiology and Biochemistry. 2011, 27 (2): 159–70. PMID 21325833. doi:10.1159/000325218.
^ Huang Y, Guigon CJ, Fan J, Cheng SY, Zhu GZ. Pituitary homeobox 2 (PITX2) promotes thyroid carcinogenesis by activation of cyclin D2. Cell Cycle. Apr 2010, 9 (7): 1333–41. PMID 20372070. doi:10.4161/cc.9.7.11126.
^ Fung FK, Chan DW, Liu VW, Leung TH, Cheung AN, Ngan HY. Increased expression of PITX2 transcription factor contributes to ovarian cancer progression. PLOS ONE. 2012, 7 (5): e37076. PMC 3352869 . PMID 22615897. doi:10.1371/journal.pone.0037076.
^ Hirose H, Ishii H, Mimori K, Tanaka F, Takemasa I, Mizushima T, Ikeda M, Yamamoto H, Sekimoto M, Doki Y, Mori M. The significance of PITX2 overexpression in human colorectal cancer. Annals of Surgical Oncology. Oct 2011, 18 (10): 3005–12. PMID 21479692. doi:10.1245/s10434-011-1653-z.
^ Kioussi C, Briata P, Baek SH, Rose DW, Hamblet NS, Herman T, Ohgi KA, Lin C, Gleiberman A, Wang J, Brault V, Ruiz-Lozano P, Nguyen HD, Kemler R, Glass CK, Wynshaw-Boris A, Rosenfeld MG. Identification of a Wnt/Dvl/beta-Catenin --> Pitx2 pathway mediating cell-type-specific proliferation during development. Cell. Nov 2002, 111 (5): 673–85. PMID 12464179. doi:10.1016/s0092-8674(02)01084-x.
^ ^20.0 ^20.1 Baek SH, Kioussi C, Briata P, Wang D, Nguyen HD, Ohgi KA, Glass CK, Wynshaw-Boris A, Rose DW, Rosenfeld MG. Regulated subset of G1 growth-control genes in response to derepression by the Wnt pathway. Proceedings of the National Academy of Sciences of the United States of America. Mar 2003, 100 (6): 3245–3250. PMC 152277 . PMID 12629224. doi:10.1073/pnas.0330217100.
^ Lee WK, Chakraborty PK, Thévenod F. Pituitary homeobox 2 (PITX2) protects renal cancer cell lines against doxorubicin toxicity by transcriptional activation of the multidrug transporter ABCB1. International Journal of Cancer. Journal International Du Cancer. Aug 2013, 133 (3): 556–67. PMID 23354914. doi:10.1002/ijc.28060.
^ Zhang JX, Tong ZT, Yang L, Wang F, Chai HP, Zhang F, Xie MR, Zhang AL, Wu LM, Hong H, Yin L, Wang H, Wang HY, Zhao Y. PITX2: a promising predictive biomarker of patients' prognosis and chemoradioresistance in esophageal squamous cell carcinoma. International Journal of Cancer. Journal International Du Cancer. Jun 2013, 132 (11): 2567–2577. PMID 23132660. doi:10.1002/ijc.27930.
^ ^23.0 ^23.1 Sun, Y. PITX2 loss-of-function mutation contributes to tetralogy of Fallot. Gene. 2016-02-15, 577: 258–264. PMID 26657035. doi:10.1016/j.gene.2015.12.001.
^ ^24.0 ^24.1 Zhao, C. PITX2 Loss-of-Function Mutation contributes to Congenital Endocardial Cushion Defect and Axenfold-Rieger Syndrome. PLOS ONE. 2015-04-20, 10: e0124409. PMC 4404345 . PMID 25893250. doi:10.1371/journal.pone.0124409.
^ ^25.0 ^25.1 Dong, Wei. Novel Pitx2c loss-of-function mutations associated with complex congenital heart disease. International Journal of Molecular Medicine. 2014-01-14. doi:10.3892/ijmm.2014.168.

拓つぶせ展てん閱讀

Franco D, Campione M. The role of Pitx2 during cardiac development. Linking left-right signaling and congenital heart diseases. Trends in Cardiovascular Medicine. May 2003, 13 (4): 157–63. PMID 12732450. doi:10.1016/S1050-1738(03)00039-2.
Hjalt TA, Semina EV. Current molecular understanding of Axenfeld-Rieger syndrome. Expert Reviews in Molecular Medicine. Nov 2005, 7 (25): 1–17. PMID 16274491. doi:10.1017/S1462399405010082.
Murray JC, Bennett SR, Kwitek AE, Small KW, Schinzel A, Alward WL, Weber JL, Bell GI, Buetow KH. Linkage of Rieger syndrome to the region of the epidermal growth factor gene on chromosome 4. Nature Genetics. Sep 1992, 2 (1): 46–9. PMID 1303248. doi:10.1038/ng0992-46.
Walter MA, Mirzayans F, Mears AJ, Hickey K, Pearce WG. Autosomal-dominant iridogoniodysgenesis and Axenfeld-Rieger syndrome are genetically distinct. Ophthalmology. Nov 1996, 103 (11): 1907–15. PMID 8942889. doi:10.1016/s0161-6420(96)30408-9.
Semina EV, Reiter R, Leysens NJ, Alward WL, Small KW, Datson NA, Siegel-Bartelt J, Bierke-Nelson D, Bitoun P, Zabel BU, Carey JC, Murray JC. Cloning and characterization of a novel bicoid-related homeobox transcription factor gene, RIEG, involved in Rieger syndrome. Nature Genetics. Dec 1996, 14 (4): 392–9. PMID 8944018. doi:10.1038/ng1296-392.
Alward WL, Semina EV, Kalenak JW, Héon E, Sheth BP, Stone EM, Murray JC. Autosomal dominant iris hypoplasia is caused by a mutation in the Rieger syndrome (RIEG/PITX2) gene. American Journal of Ophthalmology. Jan 1998, 125 (1): 98–100. PMID 9437321. doi:10.1016/S0002-9394(99)80242-6.
Kulak SC, Kozlowski K, Semina EV, Pearce WG, Walter MA. Mutation in the RIEG1 gene in patients with iridogoniodysgenesis syndrome. Human Molecular Genetics. Jul 1998, 7 (7): 1113–7. PMID 9618168. doi:10.1093/hmg/7.7.1113.
Amendt BA, Sutherland LB, Semina EV, Russo AF. The molecular basis of Rieger syndrome. Analysis of Pitx2 homeodomain protein activities. The Journal of Biological Chemistry. Aug 1998, 273 (32): 20066–72. PMID 9685346. doi:10.1074/jbc.273.32.20066.
Yoshioka H, Meno C, Koshiba K, Sugihara M, Itoh H, Ishimaru Y, Inoue T, Ohuchi H, Semina EV, Murray JC, Hamada H, Noji S. Pitx2, a bicoid-type homeobox gene, is involved in a lefty-signaling pathway in determination of left-right asymmetry. Cell. Aug 1998, 94 (3): 299–305. PMID 9708732. doi:10.1016/S0092-8674(00)81473-7.
Doward W, Perveen R, Lloyd IC, Ridgway AE, Wilson L, Black GC. A mutation in the RIEG1 gene associated with Peters' anomaly. Journal of Medical Genetics. Feb 1999, 36 (2): 152–5. PMC 1734311 . PMID 10051017. doi:10.1136/jmg.36.2.152.
Pellegrini-Bouiller I, Manrique C, Gunz G, Grino M, Zamora AJ, Figarella-Branger D, Grisoli F, Jaquet P, Enjalbert A. Expression of the members of the Ptx family of transcription factors in human pituitary adenomas. The Journal of Clinical Endocrinology and Metabolism. Jun 1999, 84 (6): 2212–20. PMID 10372733. doi:10.1210/jc.84.6.2212.
Hjalt TA, Amendt BA, Murray JC. PITX2 regulates procollagen lysyl hydroxylase (PLOD) gene expression: implications for the pathology of Rieger syndrome. The Journal of Cell Biology. Feb 2001, 152 (3): 545–52. PMC 2196000 . PMID 11157981. doi:10.1083/jcb.152.3.545.
Priston M, Kozlowski K, Gill D, Letwin K, Buys Y, Levin AV, Walter MA, Héon E. Functional analyses of two newly identified PITX2 mutants reveal a novel molecular mechanism for Axenfeld-Rieger syndrome. Human Molecular Genetics. Aug 2001, 10 (16): 1631–8. PMID 11487566. doi:10.1093/hmg/10.16.1631.
Green PD, Hjalt TA, Kirk DE, Sutherland LB, Thomas BL, Sharpe PT, Snead ML, Murray JC, Russo AF, Amendt BA. Antagonistic regulation of Dlx2 expression by PITX2 and Msx2: implications for tooth development. Gene Expression. 2002, 9 (6): 265–81. PMID 11763998.
Vincent AL, Billingsley G, Buys Y, Levin AV, Priston M, Trope G, Williams-Lyn D, Héon E. Digenic inheritance of early-onset glaucoma: CYP1B1, a potential modifier gene. American Journal of Human Genetics. Feb 2002, 70 (2): 448–60. PMC 384919 . PMID 11774072. doi:10.1086/338709.
Borges AS, Susanna R, Carani JC, Betinjane AJ, Alward WL, Stone EM, Sheffield VC, Nishimura DY. Genetic analysis of PITX2 and FOXC1 in Rieger Syndrome patients from Brazil. Journal of Glaucoma. Feb 2002, 11 (1): 51–6. PMID 11821690. doi:10.1097/00061198-200202000-00010.
Cox CJ, Espinoza HM, McWilliams B, Chappell K, Morton L, Hjalt TA, Semina EV, Amendt BA. Differential regulation of gene expression by PITX2 isoforms. The Journal of Biological Chemistry. Jul 2002, 277 (28): 25001–10. PMID 11948188. doi:10.1074/jbc.M201737200.
Quentien MH, Pitoia F, Gunz G, Guillet MP, Enjalbert A, Pellegrini I. Regulation of prolactin, GH, and Pit-1 gene expression in anterior pituitary by Pitx2: An approach using Pitx2 mutants. Endocrinology. Aug 2002, 143 (8): 2839–51. PMID 12130547. doi:10.1210/en.143.8.2839.

外部がいぶ連結れんけつ

醫學いがく主題しゅだい詞し表ひょう（MeSH）：PITX2+protein,+human

PITX2引用いんよう了りょう美国びくに国家こっか医学いがく图书馆提供ていきょう的てき資料しりょう，这些資料しりょう属ぞく于公共こうきょう领域。

[1] 與あずかPITX2相關そうかん的てき疾病しっぺい；在ざい維基數すう據よりどころ上じょう查看/編輯へんしゅう參考さんこう.

[refGRCh38Ensembl-2] 2.0 ^2.1 ^2.2 GRCh38: Ensembl release 89: ENSG00000164093 - Ensembl, May 2017

[refGRCm38Ensembl-3] 3.0 ^3.1 ^3.2 GRCm38: Ensembl release 89: ENSMUSG00000028023 - Ensembl, May 2017

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

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

[pmid9539779-6] Arakawa H, Nakamura T, Zhadanov AB, Fidanza V, Yano T, Bullrich F, Shimizu M, Blechman J, Mazo A, Canaani E, Croce CM. Identification and characterization of the ARP1 gene, a target for the human acute leukemia ALL1 gene. Proceedings of the National Academy of Sciences of the United States of America. Apr 1998, 95 (8): 4573–8. PMC 22531 . PMID 9539779. doi:10.1073/pnas.95.8.4573.

[pmid7581385-7] Héon E, Sheth BP, Kalenak JW, Sunden SL, Streb LM, Taylor CM, Alward WL, Sheffield VC, Stone EM. Linkage of autosomal dominant iris hypoplasia to the region of the Rieger syndrome locus (4q25). Human Molecular Genetics. Aug 1995, 4 (8): 1435–9. PMID 7581385. doi:10.1093/hmg/4.8.1435.

[entrez-8] 8.0 ^8.1 ^8.2 Entrez Gene: PITX2 paired-like homeodomain transcription factor 2.

[tabin-9] Logan M, Pagán-Westphal SM, Smith DM, Paganessi L, Tabin CJ. The transcription factor Pitx2 mediates situs-specific morphogenesis in response to left-right asymmetric signals. Cell. Aug 1998, 94 (3): 307–17. PMID 9708733. doi:10.1016/S0092-8674(00)81474-9.

[pmid10021341-10] Campione M, Steinbeisser H, Schweickert A, Deissler K, van Bebber F, Lowe LA, Nowotschin S, Viebahn C, Haffter P, Kuehn MR, Blum M. The homeobox gene Pitx2: mediator of asymmetric left-right signaling in vertebrate heart and gut looping. Development. Mar 1999, 126 (6): 1225–34. PMID 10021341.

[pmid16835440-11] Shiratori H, Yashiro K, Shen MM, Hamada H. Conserved regulation and role of Pitx2 in situs-specific morphogenesis of visceral organs. Development. Aug 2006, 133 (15): 3015–25. PMID 16835440. doi:10.1242/dev.02470.

[pmid21035439-12] Zacharias AL, Lewandoski M, Rudnicki MA, Gage PJ. Pitx2 is an upstream activator of extraocular myogenesis and survival. Developmental Biology. Jan 2011, 349 (2): 395–405. PMC 3019256 . PMID 21035439. doi:10.1016/j.ydbio.2010.10.028.

[pmid10662647-13] Essner JJ, Branford WW, Zhang J, Yost HJ. Mesendoderm and left-right brain, heart and gut development are differentially regulated by pitx2 isoforms. Development. Mar 2000, 127 (5): 1081–93. PMID 10662647.

[Pitx2_and_Myogenesis-14] L'honoré A, Ouimette JF, Lavertu-Jolin M, Drouin J. Pitx2 defines alternate pathways acting through MyoD during limb and somitic myogenesis. Development. Nov 2010, 137 (22): 3847–56. PMID 20978076. doi:10.1242/dev.053421.

[pmid21325833-15] Nandi SS, Ghosh P, Roy SS. Expression of PITX2 homeodomain transcription factor during rat gonadal development in a sexually dimorphic manner. Cellular Physiology and Biochemistry. 2011, 27 (2): 159–70. PMID 21325833. doi:10.1159/000325218.

[pmid20372070-16] Huang Y, Guigon CJ, Fan J, Cheng SY, Zhu GZ. Pituitary homeobox 2 (PITX2) promotes thyroid carcinogenesis by activation of cyclin D2. Cell Cycle. Apr 2010, 9 (7): 1333–41. PMID 20372070. doi:10.4161/cc.9.7.11126.

[17] Fung FK, Chan DW, Liu VW, Leung TH, Cheung AN, Ngan HY. Increased expression of PITX2 transcription factor contributes to ovarian cancer progression. PLOS ONE. 2012, 7 (5): e37076. PMC 3352869 . PMID 22615897. doi:10.1371/journal.pone.0037076.

[18] Hirose H, Ishii H, Mimori K, Tanaka F, Takemasa I, Mizushima T, Ikeda M, Yamamoto H, Sekimoto M, Doki Y, Mori M. The significance of PITX2 overexpression in human colorectal cancer. Annals of Surgical Oncology. Oct 2011, 18 (10): 3005–12. PMID 21479692. doi:10.1245/s10434-011-1653-z.

[pmid12464179-19] Kioussi C, Briata P, Baek SH, Rose DW, Hamblet NS, Herman T, Ohgi KA, Lin C, Gleiberman A, Wang J, Brault V, Ruiz-Lozano P, Nguyen HD, Kemler R, Glass CK, Wynshaw-Boris A, Rosenfeld MG. Identification of a Wnt/Dvl/beta-Catenin --> Pitx2 pathway mediating cell-type-specific proliferation during development. Cell. Nov 2002, 111 (5): 673–85. PMID 12464179. doi:10.1016/s0092-8674(02)01084-x.

[ReferenceA-20] 20.0 ^20.1 Baek SH, Kioussi C, Briata P, Wang D, Nguyen HD, Ohgi KA, Glass CK, Wynshaw-Boris A, Rose DW, Rosenfeld MG. Regulated subset of G1 growth-control genes in response to derepression by the Wnt pathway. Proceedings of the National Academy of Sciences of the United States of America. Mar 2003, 100 (6): 3245–3250. PMC 152277 . PMID 12629224. doi:10.1073/pnas.0330217100.

[ReferenceB-21] Lee WK, Chakraborty PK, Thévenod F. Pituitary homeobox 2 (PITX2) protects renal cancer cell lines against doxorubicin toxicity by transcriptional activation of the multidrug transporter ABCB1. International Journal of Cancer. Journal International Du Cancer. Aug 2013, 133 (3): 556–67. PMID 23354914. doi:10.1002/ijc.28060.

[Zhang_J_2577-22] Zhang JX, Tong ZT, Yang L, Wang F, Chai HP, Zhang F, Xie MR, Zhang AL, Wu LM, Hong H, Yin L, Wang H, Wang HY, Zhao Y. PITX2: a promising predictive biomarker of patients' prognosis and chemoradioresistance in esophageal squamous cell carcinoma. International Journal of Cancer. Journal International Du Cancer. Jun 2013, 132 (11): 2567–2577. PMID 23132660. doi:10.1002/ijc.27930.

[:0-23] 23.0 ^23.1 Sun, Y. PITX2 loss-of-function mutation contributes to tetralogy of Fallot. Gene. 2016-02-15, 577: 258–264. PMID 26657035. doi:10.1016/j.gene.2015.12.001.

[:1-24] 24.0 ^24.1 Zhao, C. PITX2 Loss-of-Function Mutation contributes to Congenital Endocardial Cushion Defect and Axenfold-Rieger Syndrome. PLOS ONE. 2015-04-20, 10: e0124409. PMC 4404345 . PMID 25893250. doi:10.1371/journal.pone.0124409.

[:2-25] 25.0 ^25.1 Dong, Wei. Novel Pitx2c loss-of-function mutations associated with complex congenital heart disease. International Journal of Molecular Medicine. 2014-01-14. doi:10.3892/ijmm.2014.168.

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