HEAT repeat

Representative examples of HEAT repeat proteins include importin β (also known as karyopherin β) family,{{cite journal | author = Malik HS, Eickbush TH, Goldfarb DS | title = Evolutionary specialization of the nuclear targeting apparatus | journal = Proc. Natl. Acad. Sci. USA| volume = 94 | issue = 25 | pages = 13738–13742 | year =1997 | doi = 10.1073/pnas.94.25.13738 | pmid = 9391096| pmc = 28376 | bibcode = 1997PNAS...9413738M | doi-access = free }} regulatory subunits of condensin and cohesin,{{cite journal | author = Neuwald AF, Hirano T | title = HEAT repeats associated with condensins, cohesins, and other complexes involved in chromosome-related functions | journal = Genome Res.| volume = 10 | issue = 10 | pages = 1445–52 | year = 2000 | doi = 10.1101/gr.147400 | pmid = 11042144| pmc = 310966 }} separase,{{cite journal | author= Jäger H, Herzig B, Herzig A, Sticht H, Lehner CF, Heidmann S | title= Structure predictions and interaction studies indicate homology of separase N-terminal regulatory domains and Drosophila THR | journal =Cell Cycle | volume= 3 | issue= 2 | pages =182–188 | year = 2004 | doi= 10.4161/cc.3.2.605 | pmid = 14712087| doi-access= free }} PIKKs (phosphatidylinositol 3-kinase-related protein kinases) such as ATM (Ataxia telangiectasia mutated) and ATR (Ataxia telangiectasia and Rad3 related),{{cite journal | author = Perry J, Kleckner N | title = The ATRs, ATMs, and TORs are giant HEAT repeat proteins | journal = Cell| volume = 112 | issue = 2 | pages = 151–155 | year = 2003 | doi = 10.1016/s0092-8674(03)00033-3 | pmid = 12553904| s2cid = 17261901 | doi-access = free }}{{cite journal | author = Baretić D, Williams RL | title = PIKKs--the solenoid nest where partners and kinases meet | journal = Curr. Opin. Struct. Biol. | volume = 29 | pages = 134–142 | year = 2014 | doi = 10.1016/j.sbi.2014.11.003 | pmid =25460276}} and the microtubule-binding protein XMAP215/Dis1/TOG{{cite journal |last1=Ohkura |first1=Hiroyuki |last2=Garcia |first2=Miguel A. |last3=Toda |first3=Takashi |title=Dis1/TOG universal microtubule adaptors - one MAP for all? |journal=Journal of Cell Science |date=1 November 2001 |volume=114 |issue=21 |pages=3805–3812 |doi=10.1242/jcs.114.21.3805 |pmid=11719547 |url=http://jcs.biologists.org/cgi/pmidlookup?view=long&pmid=11719547 |url-access=subscription }} and CLASP.{{cite journal | author = Al-Bassam J, Kim H, Brouhard G, van Oijen A, Harrison SC, Chang F | title = CLASP promotes microtubule rescue by recruiting tubulin dimers to the microtubule | journal = Dev. Cell| volume = 19 | issue = 2 | pages = 245–258 | year = 2010 | doi = 10.1016/j.devcel.2010.07.016 | pmid =20708587| pmc = 3156696 }} Thus, cellular functions of HEAT repeat proteins are highly variable.

The structure of the following HEAT repeat proteins have been determined so far:

• Protein modification and degradation
• A subunit{{cite journal |vauthors=Groves MR, Hanlon N, Turowski P, Hemmings BA, Barford D |title=The structure of the protein phosphatase 2A PR65/A subunit reveals the conformation of its 15 tandemly repeated HEAT motifs |journal=Cell |volume=96 |issue=1 |pages=99–110 |date=January 1999 |pmid=9989501 |doi= 10.1016/S0092-8674(00)80963-0|s2cid=14465060 |doi-access=free }} and holoenzyme{{cite journal | author = Xu Y, Xing Y, Chen Y, Chao Y, Lin Z, Fan E, Yu JW, Strack S, Jeffrey PD, Shi Y | title = Structure of the protein phosphatase 2A holoenzyme | journal = Cell| volume = 127 | issue = 6 | pages = 1239–1251 | year = 2006 | doi = 10.1016/j.cell.2006.11.033 | pmid =17174897| s2cid = 18584536 | doi-access = free }}{{cite journal | author = Cho US, Xu W | title = Crystal structure of a protein phosphatase 2A heterotrimeric holoenzyme | journal = Nature| volume = 445| issue = 7123 | pages = 53–57 | year = 2007 | doi = 10.1038/nature05351 | pmid =17086192 | bibcode = 2007Natur.445...53C | s2cid = 4408160 }} of PP2A
• SCFubiquitin ligase regulator Cand1{{cite journal | author = Goldenberg SJ, Cascio TC, Shumway SD, Garbutt KC, Liu J, Xiong Y, Zheng N | title = Structure of the Cand1-Cul1-Roc1 complex reveals regulatory mechanisms for the assembly of the multisubunit cullin-dependent ubiquitin ligases | journal = Cell | volume = 119 | issue = 4 | pages = 517–528 | year = 2004 | doi = 10.1016/j.cell.2004.10.019 | pmid =15537541| s2cid = 1606360 | doi-access = free }}
• Hsm3, a molecular chaperon involved in the assembly of 26Sproteasome{{cite journal | author = Takagi K, Kim S, Yukii H, Ueno M, Morishita R, Endo Y, Kato K, Tanaka K, Saeki Y, Mizushima T | title = Structural basis for specific recognition of Rpt1p, an ATPase subunit of 26 S proteasome, by proteasome-dedicated chaperone Hsm3p | journal = J. Biol. Chem. | volume = 287 | issue = 15 | pages = 12172–12182 | year = 2012 | doi = 10.1074/jbc.M112.345876 | pmid =22334676| pmc = 3320968 | doi-access = free }}
• Nucleo-cytoplasmic transport
• Importin β{{cite journal |author=Cingolani G, Petosa C, Weis K, Müller CW |title=Structure of importin-beta bound to the IBB domain of importin-alpha |journal=Nature |volume=399 |issue=6733 |pages=221–229 |year=1999|pmid=10353244 |doi= 10.1038/20367|bibcode=1999Natur.399..221C |s2cid=4425840 }}{{cite journal | author = Chook YM, Blobel G | title = Structure of the nuclear transport complex karyopherin-beta2-Ran x GppNHp | journal = Nature| volume = 399 | issue = 6733 | pages = 230–237 | year = 1999 | doi = 10.1038/20375 | pmid = 10353245| s2cid = 4413233 }}{{cite journal | author = Bayliss R, Littlewood T, Stewart M | title = Structural basis for the interaction between FxFG nucleoporin repeats and importin-beta in nuclear trafficking | journal = Cell| volume = 102 | issue = 1 | pages = 99–108 | year = 2000 | doi = 10.1016/s0092-8674(00)00014-3 | pmid = 10929717| s2cid = 17495979 | doi-access = free }}
• Exportin Cse1{{cite journal | author = Matsuura Y, Stewart M | title = Structural basis for the assembly of a nuclear export complex | journal = Nature| volume = 432 | issue = 7019 | pages = 872–877 | year = 2004 | doi = 10.1038/nature03144 | pmid = 15602554| bibcode = 2004Natur.432..872M | s2cid = 4406515 }}
• Transportin 1{{cite journal | author = Imasaki T, Shimizu T, Hashimoto H, Hidaka Y, Kose S, Imamoto N, Yamada M, Sato M | title = Structural basis for substrate recognition and dissociation by human transportin 1| journal = Molecular Cell| volume = 28 | issue = 1 | pages = 57–67 | year = 2007 | doi = 10.1016/j.molcel.2007.08.006| pmid =17936704| doi-access = free }}
• Nuleoporin Gle1;{{cite journal | author = Montpetit B, Thomsen ND, Helmke KJ, Seeliger MA, Berger JM, Weis K | title = A conserved mechanism of DEAD-box ATPase activation by nucleoporins and InsP6 in mRNA export | journal = Nature | volume = 472 | issue = 7342 | pages = 238–242 | year = 2011 | doi = 10.1038/nature09862 | pmid =21441902| pmc = 3078754 | bibcode = 2011Natur.472..238M }} Nup188;{{cite journal | author = Andersen KR, Onischenko E, Tang JH, Kumar P, Chen JZ, Ulrich A, Liphardt JT, Weis K, Schwartz TU | title = Scaffold nucleoporins Nup188 and Nup192 share structural and functional properties with nuclear transport receptors | journal = eLife | volume = 11 | issue = 2 | pages = e00745 | year = 2013 | doi = 10.7554/eLife.00745 | pmid =23795296| pmc = 3679522 | doi-access = free }} Nup192{{cite journal | author = Stuwe T, Lin DH, Collins LN, Hurt E, Hoelz A| title = Evidence for an evolutionary relationship between the large adaptor nucleoporin Nup192 and karyopherins | journal = Proc. Natl. Acad. Sci. | volume = 111 | issue = 7 | pages = 2530–2535 | year = 2014 | doi = 10.1073/pnas.1311081111 | pmid =24505056| pmc = 3932873 | bibcode = 2014PNAS..111.2530S | doi-access = free }}
• Transcriptional regulation
• TFIID subunit TAF6{{cite journal | author = Scheer E, Delbac F, Tora L, Moras D, Romier C| title = TFIID TAF6-TAF9 complex formation involves the HEAT repeat-containing C-terminal domain of TAF6 and is modulated by TAF5 protein | journal = J. Biol. Chem. | volume = 287 | issue = 33 | pages = 27580–27592 | year = 2012 | doi = 10.1074/jbc.M112.379206 | pmid =22696218| pmc = 3431708 | doi-access = free }}
• TBP regulator Mot1 (Modifier of transcription 1){{cite journal | author = Wollmann P, Cui S, Viswanathan R, Berninghausen O, Wells MN, Moldt M, Witte G, Butryn A, Wendler P, Beckmann R, Auble DT, Hopfner KP | title = Structure and mechanism of the Swi2/Snf2 remodeller Mot1 in complex with its substrate TBP | journal =Nature | volume = 475 | issue = 7356 | pages = 403–407 | year = 2011 | doi = 10.1038/nature10215 | pmid =21734658| pmc = 3276066 }}
• Transcriptional initiation factor Rrn3{{cite journal | author = Blattner C, Jennebach S, Herzog F, Mayer A, Cheung AC, Witte G, Lorenzen K, Hopfner KP, Heck AJ, Aebersold R, Cramer P | title = Molecular basis of Rrn3-regulated RNA polymerase I initiation and cell growth | journal = Genes Dev. | volume = 25 | issue = 19 | pages = 2093–2105 | year = 2011 | doi = 10.1101/gad.17363311 | pmid =21940764| pmc = 3197207 }}
• Translational regulation
• Elongation factor eEF3{{cite journal | author = Andersen CB, Becker T, Blau M, Anand M, Halic M, Balar B, Mielke T, Boesen T, Pedersen JS, Spahn CM, Kinzy TG, Andersen GR, Beckmann R | title = Structure of eEF3 and the mechanism of transfer RNA release from the E-site | journal = Nature | volume =443 | issue = 7112 | pages = 663–668 | year = 2006 | doi = 10.1038/nature05126 | pmid =16929303| bibcode = 2006Natur.443..663A | hdl = 11858/00-001M-0000-0010-8377-7 | s2cid = 14994883 | hdl-access = free }}
• Initiation factor eIF4G{{cite journal | author = Marcotrigiano J, Lomakin IB, Sonenberg N, Pestova TV, Hellen CU, Burley SK | title = A conserved HEAT domain within eIF4G directs assembly of the translation initiation machinery | journal = Mol. Cell | volume = 7 | issue = 1 | pages = 193–203 | year = 2001 | doi = 10.1016/s1097-2765(01)00167-8 | pmid =11172724| doi-access = free }}
• Aminoacyl tRNA synthetase transfer protein Cex1p{{cite journal | author = Nozawa K, Ishitani R, Yoshihisa T, Sato M, Arisaka F, Kanamaru S, Dohmae N, Mangroo D, Senger B, Becker HD, Nureki O | title = Crystal structure of Cex1p reveals the mechanism of tRNA trafficking between nucleus and cytoplasm | journal = Nucleic Acids Res. | volume = 41 | issue = 6 | pages = 3901–3914 | year = 2013 | doi = 10.1093/nar/gkt010 | pmid =23396276| pmc = 3616705 }}
• DNA repair
• DNA-PK (DNA-dependent protein kinase){{cite journal | author = Sibanda BL, Chirgadze DY, Blundell TL | title = Crystal structure of DNA-PKcs reveals a large open-ring cradle {{sic|comprised |hide=y|of}} HEAT repeats | journal = Nature | volume =463 | issue = 7277 | pages = 118–121 | year = 2010 | doi = 10.1038/nature08648 | pmid =20023628| pmc = 2811870 }}
• Fanconi anemia responsible protein FANCF (FANCF){{cite journal | author = Kowal P, Gurtan AM, Stuckert P, D'Andrea AD, Ellenberger T | title = Structural determinants of human FANCF protein that function in the assembly of a DNA damage signaling complex | journal = J. Biol. Chem. | volume = 282 | issue = 3 | pages = 2047–2055 | year = 2007 | doi = 10.1074/jbc.M608356200 | pmid =17082180| doi-access = free }}
• Damaged DNA-binding protein AlkD (Alkylpurin DNA glycosylase){{cite journal | author = Rubinson EH, Gowda AS, Spratt TE, Gold B, Eichman BF | title = An unprecedented nucleic acid capture mechanism for excision of DNA damage | journal = Nature | volume = 468 | issue = 7322 | pages = 406–411 | year = 2010 | doi = 10.1038/nature09428 | pmid =20927102| pmc = 4160814 | bibcode = 2010Natur.468..406R }}
• PIKKs chaperone Tel2{{cite journal | author = Takai H, Xie Y, de Lange T, Pavletich NP | title = Tel2 structure and function in the Hsp90-dependent maturation of mTOR and ATR complexes | journal = Genes Dev. | volume = 24 | issue = 18 | pages = 2019–2030 | year = 2010 | doi = 10.1101/gad.1956410 | pmid =20801936| pmc = 2939364 }}
• Chromosomal regulation
• Cohesin subunit SA2{{cite journal | author =Hara K, Zheng G, Qu Q, Liu H, Ouyang Z, Chen Z, Tomchick DR, Yu H | title = Structure of cohesin subcomplex pinpoints direct shugoshin-Wapl antagonism in centromeric cohesion | journal = Nat. Struct. Mol. Biol.| volume = 21 | issue = 10 | pages = 864–870 | year = 2014| doi = 10.1038/nsmb.2880 | pmid =25173175| pmc = 4190070 }}/Scc3{{cite journal | author =Roig MB, Löwe J, Chan KL, Beckouët F, Metson J, Nasmyth K | title = Structure and function of cohesin's Scc3/SA regulatory subunit. | journal = FEBS Lett | volume = 588 | issue = 20 | pages = 3692–3702 | year = 2014| doi = 10.1016/j.febslet.2014.08.015 | pmid =25171859| pmc = 4175184 }}{{cite journal | author =Li Y, Muir K, Bowler MW, Metz J, Haering CH, Panne D | title = Structural basis for Scc3-dependent cohesin recruitment to chromatin. | journal = eLife | volume = 7 | pages = e38356. doi: 10.7554/eLife.38356 | year = 2018| doi = 10.7554/eLife.38356 | pmid =30109982| pmc = 6120753 | doi-access = free }}
• Cohesin regulator Wapl{{cite journal | author = Chatterjee A, Zakian S, Hu XW, Singleton MR | title = Structural insights into the regulation of cohesion establishment by Wpl1 | journal = EMBO J. | volume = 32 | issue = 5 | pages = 677–687 | year = 2013 | doi = 10.1038/emboj.2013.16 | pmid =23395900| pmc = 3590988 }}{{cite journal | author = Ouyang Z, Zheng G, Song J, Borek DM, Otwinowski Z, Brautigam CA, Tomchick DR, Rankin S, Yu H | title = Structure of the human cohesin inhibitor Wapl | journal = Proc. Natl. Acad. Sci. USA| volume = 110 | issue = 28 | pages = 11355–11360 | year = 2013 | doi = 10.1073/pnas.1304594110 | pmid =23776203| pmc = 3710786 | bibcode = 2013PNAS..11011355O | doi-access = free }}
• Cohesin regulator Pds5{{cite journal | author = Muir KW, Kschonsak M, Li Y, Metz J, Haering CH, Panne D. | title = Structure of the Pds5-Scc1 complex and implications for cohesin function | journal = Cell Rep| year = 2016 | volume = 14 | issue = 9 | pages = 2116–2126 | doi = 10.1016/j.celrep.2016.01.078 | pmid =26923589| doi-access = free }}{{cite journal | author = Lee BG, Roig MB, Jansma M, Petela N, Metson J, Nasmyth K, Löwe J | title = Crystal structure of the cohesin gatekeeper Pds5 and in complex with kleisin Scc1 | journal = Cell Rep| year = 2016 | volume = 14 | issue = 9 | pages = 2108–2115 | doi = 10.1016/j.celrep.2016.02.020 | pmid =26923598| pmc = 4793087 }}{{cite journal | author = Ouyang Z, Zheng G, Tomchick DR, Luo X, Yu H. | title = Structural basis and IP6 requirement for Pds5-dependent cohesin dynamics | journal = Mol Cell| volume = 62 | issue = 2 | pages = 248–259 | year = 2016 | doi = 10.1016/j.molcel.2016.02.033 | pmid =26971492| pmc = 5560056 }}
• Cohesin loading factor Scc2{{cite journal | author = Kikuchi S, Borek DM, Otwinowski Z, Tomchick DR, Yu H | title = Crystal structure of the cohesin loader Scc2 and insight into cohesinopathy| journal = Proc Natl Acad Sci USA| volume = 113 | issue = 44 | pages = 12444–12449 | year = 2016 | doi = 10.1073/pnas.1611333113| pmid =27791135| pmc = 5098657| bibcode = 2016PNAS..11312444K| doi-access = free}}{{cite journal | author = Chao WC, Murayama Y, Muñoz S, Jones AW, Wade BO, Purkiss AG, Hu XW, Borg A, Snijders AP, Uhlmann F, Singleton MR | title = Structure of the cohesin loader Scc2| journal = Nat Commun| volume = 8 | pages = 13952 | year = 2017 | doi = 10.1038/ncomms13952| pmid =28059076| pmc = 5227109| bibcode = 2017NatCo...813952C}}
• Cohesin protease Separase{{cite journal | author = Bachmann G, Richards MW, Winter A, Beuron F, Morris E, Bayliss R| title =A closed conformation of the Caenorhabditis elegans separase-securin complex | journal = Open Biol | volume = 6 | issue = 4 | pages = 160032. doi: 10.1098/rsob.160032 | year = 2016 | doi =10.1098/rsob.160032 | pmid =27249343| pmc =4852461 }}{{cite journal | author = Luo S, Tong L | title = Molecular mechanism for the regulation of yeast separase by securin | journal = Nature | volume = 542 | issue = 7640 | pages = 255–259 | year = 2017 | doi = 10.1038/nature21061 | pmid =28146474| pmc = 5302053 | bibcode = 2017Natur.542..255L }}{{cite journal | author = Boland A, Martin TG, Zhang Z, Yang J, Bai XC, Chang L, Scheres SH, Barford D | title =Cryo-EM structure of a metazoan separase-securin complex at near-atomic resolution | journal = Nat Struct Mol Biol | volume = 24 | issue = 4 | pages = 414–418 | year = 2017 | doi =10.1038/nsmb.3386 | pmid =28263324| pmc =5385133 }}
• Condensin subunit CAP-G/ycg1{{cite journal | author = Kschonsak M, Merkel F, Bisht S, Metz J, Rybin V, Hassler M, Haering CH| title =Structural basis for a safety-belt mechanism that anchors condensin to chromosomes | journal = Cell | volume = 171 | issue = 3 | pages = 588–600.e24 | year = 2017 | doi =10.1016/j.cell.2017.09.008 | pmid =28988770| pmc =5651216 }}{{cite journal |last1=Hara |first1=Kodai |last2=Kinoshita |first2=Kazuhisa |last3=Migita |first3=Tomoko |last4=Murakami |first4=Kei |last5=Shimizu |first5=Kenichiro |last6=Takeuchi |first6=Kozo |last7=Hirano |first7=Tatsuya |last8=Hashimoto |first8=Hiroshi |title=Structural basis of HEAT -kleisin interactions in the human condensin I subcomplex |journal=EMBO Reports |date=12 March 2019 |volume=20 |issue=5 |doi=10.15252/embr.201847183 |pmid=30858338 |pmc=6501013 }}
• Condensin subunit CAP-D2/ycs4{{cite journal | author = Hassler M, Shaltiel IA, Kschonsak M, Simon B, Merkel F, Thärichen L, Bailey HJ, Macošek J, Bravo S, Metz J, Hennig J, Haering CH| title =Structural basis of an asymmetric condensin ATPase cycle | journal = Mol Cell | volume = 74 | issue = 6 | pages = 1175–1188.e24 | year = 2019 | doi =10.1016/j.molcel.2019.03.037 | pmid =31226277| pmc =6591010 }}
• Cytoskeletal regulation
• Microtubule-binding protein TOG{{cite journal | author = Al-Bassam J, Larsen NA, Hyman AA, Harrison SC | title = Crystal structure of a TOG domain: conserved features of XMAP215/Dis1-family TOG domains and implications for tubulin binding. | journal = Structure| volume = 15 | issue = 3 | pages = 355–362 | year = 2007 | doi = 10.1016/j.str.2007.01.012 | pmid = 17355870| doi-access = free }}{{cite journal | author = Slep KC, Vale RD. | title = Structural basis of microtubule plus end tracking by XMAP215, CLIP-170, and EB1 | journal = Molecular Cell| volume = 27 | issue = 6 | pages = 976–991 | year = 2007 | doi = 10.1016/j.molcel.2007.07.023 | pmid = 17889670| pmc = 2052927 }}/Stu2{{cite journal | author = Ayaz P, Ye X, Huddleston P, Brautigam CA, Rice LM. | title = A TOG:αβ-tubulin complex structure reveals conformation-based mechanisms for a microtubule polymerase. | journal = Science | volume = 337 | issue = 6096 | pages = 857–60 | year = 2012 | doi = 10.1126/science.1221698 | pmid = 22904013| pmc = 3734851 | bibcode = 2012Sci...337..857A }}
• Cell proliferation regulation
• TOR (target of rapamycin){{cite journal | author = Aylett CH, Sauer E, Imseng S, Boehringer D, Hall MN, Ban N, Maier T | title = Architecture of human mTOR complex 1 | journal = Science | volume = 351 | issue = 6268 | pages = 48–52 | year = 2016 | doi = 10.1126/science.aaa3870 | pmid = 26678875| bibcode = 2016Sci...351...48A | s2cid = 32663149 }}
• Others
• API5 (Apoptosis inhibitor 5){{cite journal | author = Han BG, Kim KH, Lee SJ, Jeong KC, Cho JW, Noh KH, Kim TW, Kim SJ, Yoon HJ, Suh SW, Lee S, Lee BI | title = Helical repeat structure of apoptosis inhibitor 5 reveals protein-protein interaction modules | journal = J. Biol. Chem. | volume = 287 | issue = 14 | pages = 10727–10737 | year = 2012 | doi = 10.1074/jbc.M111.317594 | pmid =22334682| pmc = 3322819 | doi-access = free }}
• V-type ATPase H subunit{{cite journal | author = Sagermann M, Stevens TH, Matthews BW | title = Crystal structure of the regulatory subunit H of the V-type ATPase of Saccharomyces cerevisiae | journal = Proc. Natl. Acad. Sci. USA | volume = 98 | issue = 13 | pages = 7134–7139 | year = 2001 | doi = 10.1073/pnas.131192798 | pmid =11416198| pmc = 34635 | bibcode = 2001PNAS...98.7134S | doi-access = free }}

{{Reflist}}

• {{ELM|LIG_PIKK_1}}
• {{ELM|DOC_PIKK_1}}

{{Protein tandem repeats}}