LARP7_HUMAN
ID LARP7_HUMAN Reviewed; 582 AA.
AC Q4G0J3; B2ZHN6; Q3B7A9; Q9P1S7; Q9Y3Z8;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 30-AUG-2005, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=La-related protein 7 {ECO:0000303|PubMed:18483487};
DE AltName: Full=La ribonucleoprotein domain family member 7 {ECO:0000303|PubMed:18483487};
DE Short=hLARP7 {ECO:0000303|PubMed:27679474};
DE AltName: Full=P-TEFb-interaction protein for 7SK stability {ECO:0000303|PubMed:18249148};
DE Short=PIP7S {ECO:0000303|PubMed:18249148};
GN Name=LARP7 {ECO:0000303|PubMed:18483487, ECO:0000312|HGNC:HGNC:24912};
GN ORFNames=HDCMA18P {ECO:0000303|Ref.2};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, SUBCELLULAR LOCATION, AND
RP IDENTIFICATION IN THE 7SK RNP COMPLEX.
RX PubMed=18483487; DOI=10.1038/embor.2008.72;
RA Markert A., Grimm M., Martinez J., Wiesner J., Meyerhans A., Meyuhas O.,
RA Sickmann A., Fischer U.;
RT "The La-related protein LARP7 is a component of the 7SK ribonucleoprotein
RT and affects transcription of cellular and viral polymerase II genes.";
RL EMBO Rep. 9:569-575(2008).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Dendritic cell;
RA Zhao Z., Huang X., Li N., Zhu X., Cao X.;
RT "A novel gene from human dendritic cell.";
RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 293-582 (ISOFORM 1).
RC TISSUE=Fetal brain;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [8]
RP FUNCTION, AND MUTAGENESIS OF TYR-128.
RX PubMed=18249148; DOI=10.1016/j.molcel.2008.01.003;
RA He N., Jahchan N.S., Hong E., Li Q., Bayfield M.A., Maraia R.J., Luo K.,
RA Zhou Q.;
RT "A La-related protein modulates 7SK snRNP integrity to suppress P-TEFb-
RT dependent transcriptional elongation and tumorigenesis.";
RL Mol. Cell 29:588-599(2008).
RN [9]
RP FUNCTION, AND IDENTIFICATION IN THE 7SK RNP COMPLEX.
RX PubMed=18281698; DOI=10.1093/nar/gkn061;
RA Krueger B.J., Jeronimo C., Roy B.B., Bouchard A., Barrandon C., Byers S.A.,
RA Searcey C.E., Cooper J.J., Bensaude O., Cohen E.A., Coulombe B.,
RA Price D.H.;
RT "LARP7 is a stable component of the 7SK snRNP while P-TEFb, HEXIM1 and
RT hnRNP A1 are reversibly associated.";
RL Nucleic Acids Res. 36:2219-2229(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-257; SER-258; SER-261;
RP SER-273; SER-337 AND THR-338, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=18318008; DOI=10.1002/pmic.200700884;
RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA Zou H., Gu J.;
RT "Large-scale phosphoproteome analysis of human liver tissue by enrichment
RT and fractionation of phosphopeptides with strong anion exchange
RT chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-337 AND THR-338, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [15]
RP IDENTIFICATION IN THE 7SK RNP COMPLEX.
RX PubMed=19906723; DOI=10.1093/nar/gkp977;
RA Xue Y., Yang Z., Chen R., Zhou Q.;
RT "A capping-independent function of MePCE in stabilizing 7SK snRNA and
RT facilitating the assembly of 7SK snRNP.";
RL Nucleic Acids Res. 38:360-369(2010).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-258; SER-261; SER-337 AND
RP THR-338, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [18]
RP INVOLVEMENT IN ALAZS.
RX PubMed=21937992; DOI=10.1038/nature10423;
RA Najmabadi H., Hu H., Garshasbi M., Zemojtel T., Abedini S.S., Chen W.,
RA Hosseini M., Behjati F., Haas S., Jamali P., Zecha A., Mohseni M.,
RA Puettmann L., Vahid L.N., Jensen C., Moheb L.A., Bienek M., Larti F.,
RA Mueller I., Weissmann R., Darvish H., Wrogemann K., Hadavi V.,
RA Lipkowitz B., Esmaeeli-Nieh S., Wieczorek D., Kariminejad R.,
RA Firouzabadi S.G., Cohen M., Fattahi Z., Rost I., Mojahedi F., Hertzberg C.,
RA Dehghan A., Rajab A., Banavandi M.J., Hoffer J., Falah M., Musante L.,
RA Kalscheuer V., Ullmann R., Kuss A.W., Tzschach A., Kahrizi K., Ropers H.H.;
RT "Deep sequencing reveals 50 novel genes for recessive cognitive
RT disorders.";
RL Nature 478:57-63(2011).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-258; SER-261; SER-337 AND
RP THR-338, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [20]
RP INVOLVEMENT IN ALAZS.
RX PubMed=22865833; DOI=10.1002/humu.22175;
RA Alazami A.M., Al-Owain M., Alzahrani F., Shuaib T., Al-Shamrani H.,
RA Al-Falki Y.H., Al-Qahtani S.M., Alsheddi T., Colak D., Alkuraya F.S.;
RT "Loss of function mutation in LARP7, chaperone of 7SK ncRNA, causes a
RT syndrome of facial dysmorphism, intellectual disability, and primordial
RT dwarfism.";
RL Hum. Mutat. 33:1429-1434(2012).
RN [21]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-258; SER-261; SER-298;
RP SER-299; SER-300; SER-337; THR-338 AND SER-351, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-261; SER-337 AND THR-338, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [24]
RP INVOLVEMENT IN ALAZS.
RX PubMed=26374271; DOI=10.1002/ajmg.a.37396;
RA Ling T.T., Sorrentino S.;
RT "Compound heterozygous variants in the LARP7 gene as a cause of Alazami
RT syndrome in a Caucasian female with significant failure to thrive, short
RT stature, and developmental disability.";
RL Am. J. Med. Genet. A 170A:217-219(2016).
RN [25]
RP INVOLVEMENT IN ALAZS.
RX PubMed=27766953; DOI=10.1186/s12864-016-3093-4;
RA Holohan B., Kim W., Lai T.P., Hoshiyama H., Zhang N., Alazami A.M.,
RA Wright W.E., Meyn M.S., Alkuraya F.S., Shay J.W.;
RT "Impaired telomere maintenance in Alazami syndrome patients with LARP7
RT deficiency.";
RL BMC Genomics 17:749-749(2016).
RN [26]
RP FUNCTION.
RX PubMed=28254838; DOI=10.15252/embj.201695740;
RA Egloff S., Vitali P., Tellier M., Raffel R., Murphy S., Kiss T.;
RT "The 7SK snRNP associates with the little elongation complex to promote
RT snRNA gene expression.";
RL EMBO J. 36:934-948(2017).
RN [27]
RP INTERACTION WITH METTL16.
RX PubMed=29051200; DOI=10.15252/embr.201744940;
RA Warda A.S., Kretschmer J., Hackert P., Lenz C., Urlaub H., Hoebartner C.,
RA Sloan K.E., Bohnsack M.T.;
RT "Human METTL16 is a N6-methyladenosine (m6A) methyltransferase that targets
RT pre-mRNAs and various non-coding RNAs.";
RL EMBO Rep. 18:2004-2014(2017).
RN [28]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-237 AND LYS-410, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [29]
RP INVOLVEMENT IN ALAZS.
RX PubMed=29619239; DOI=10.1038/hgv.2018.14;
RA Dateki S., Kitajima T., Kihara T., Watanabe S., Yoshiura K.I., Moriuchi H.;
RT "Novel compound heterozygous variants in the LARP7 gene in a patient with
RT Alazami syndrome.";
RL Hum. Genome Var. 5:18014-18014(2018).
RN [30]
RP INVOLVEMENT IN ALAZS.
RX PubMed=29576627; DOI=10.1038/s10038-017-0373-z;
RA Hollink I.H.I.M., Alfadhel M., Al-Wakeel A.S., Ababneh F., Pfundt R.,
RA de Man S.A., Abou Jamra R., Rolfs A., Bertoli-Avella A.M.,
RA van de Laar I.M.B.H.;
RT "Correction: Broadening the phenotypic spectrum of pathogenic LARP7
RT variants: two cases with intellectual disability, variable growth
RT retardation and distinct facial features.";
RL J. Hum. Genet. 63:539-539(2018).
RN [31]
RP INVOLVEMENT IN ALAZS.
RX PubMed=30006060; DOI=10.1016/j.ejmg.2018.07.003;
RA Imbert-Bouteille M., Mau Them F.T., Thevenon J., Guignard T., Gatinois V.,
RA Riviere J.B., Boland A., Meyer V., Deleuze J.F., Sanchez E., Apparailly F.,
RA Genevieve D., Willems M.;
RT "LARP7 variants and further delineation of the Alazami syndrome phenotypic
RT spectrum among primordial dwarfisms: 2 sisters.";
RL Eur. J. Med. Genet. 62:161-166(2019).
RN [32]
RP INTERACTION WITH RBM7.
RX PubMed=30824372; DOI=10.1016/j.molcel.2019.01.033;
RA Bugai A., Quaresma A.J.C., Friedel C.C., Lenasi T., Duester R.,
RA Sibley C.R., Fujinaga K., Kukanja P., Hennig T., Blasius M., Geyer M.,
RA Ule J., Doelken L., Barboric M.;
RT "P-TEFb Activation by RBM7 Shapes a Pro-survival Transcriptional Response
RT to Genotoxic Stress.";
RL Mol. Cell 74:254-267(2019).
RN [33]
RP FUNCTION, RNA-BINDING, ASSOCIATION WITH THE BOX C/D RNP COMPLEX, VARIANT
RP ALAZS 558-ILE--ASP-582 DELINS
RP LYS-ARG-LEU-ASP-TRP-GLN-ARG-LEU-ASN-LYS-ARG-VAL-ASN-ILE, MUTAGENESIS OF
RP PHE-44 AND TYR-483, AND CHARACTERIZATION OF VARIANT ALAZS 558-ILE--ASP-582
RP DELINS LYS-ARG-LEU-ASP-TRP-GLN-ARG-LEU-ASN-LYS-ARG-VAL-ASN-ILE.
RX PubMed=32017898; DOI=10.1016/j.molcel.2020.01.001;
RA Hasler D., Meduri R., Bak M., Lehmann G., Heizinger L., Wang X., Li Z.T.,
RA Sement F.M., Bruckmann A., Dock-Bregeon A.C., Merkl R., Kalb R., Grauer E.,
RA Kunstmann E., Zavolan M., Liu M.F., Fischer U., Meister G.;
RT "The Alazami syndrome-associated protein LARP7 guides U6 small nuclear RNA
RT modification and contributes to splicing robustness.";
RL Mol. Cell 0:0-0(2020).
RN [34] {ECO:0007744|PDB:4WKR}
RP X-RAY CRYSTALLOGRAPHY (3.20 ANGSTROMS) OF 1-208, RNA-BINDING, AND
RP MUTAGENESIS OF GLU-130 AND PHE-168.
RX PubMed=25753663; DOI=10.1093/nar/gkv173;
RA Uchikawa E., Natchiar K.S., Han X., Proux F., Roblin P., Zhang E.,
RA Durand A., Klaholz B.P., Dock-Bregeon A.C.;
RT "Structural insight into the mechanism of stabilization of the 7SK small
RT nuclear RNA by LARP7.";
RL Nucleic Acids Res. 43:3373-3388(2015).
RN [35] {ECO:0007744|PDB:5KNW}
RP STRUCTURE BY NMR OF 445-561, RNA-BINDING, AND DOMAIN.
RX PubMed=27679474; DOI=10.1093/nar/gkw833;
RA Eichhorn C.D., Chug R., Feigon J.;
RT "hLARP7 C-terminal domain contains an xRRM that binds the 3' hairpin of 7SK
RT RNA.";
RL Nucleic Acids Res. 44:9977-9989(2016).
RN [36] {ECO:0007744|PDB:6D12}
RP X-RAY CRYSTALLOGRAPHY (2.21 ANGSTROMS) OF 445-556, RNA-BINDING, DOMAIN, AND
RP MUTAGENESIS OF PHE-451; ARG-472; TYR-483 AND ARG-496.
RX PubMed=29946027; DOI=10.1073/pnas.1806276115;
RA Eichhorn C.D., Yang Y., Repeta L., Feigon J.;
RT "Structural basis for recognition of human 7SK long noncoding RNA by the
RT La-related protein Larp7.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:E6457-E6466(2018).
CC -!- FUNCTION: RNA-binding protein that specifically binds distinct small
CC nuclear RNA (snRNAs) and regulates their processing and function
CC (PubMed:18249148, PubMed:32017898). Specifically binds the 7SK snRNA
CC (7SK RNA) and acts as a core component of the 7SK ribonucleoprotein
CC (RNP) complex, thereby acting as a negative regulator of transcription
CC elongation by RNA polymerase II (PubMed:18249148, PubMed:18483487). The
CC 7SK RNP complex sequesters the positive transcription elongation factor
CC b (P-TEFb) in a large inactive 7SK RNP complex preventing RNA
CC polymerase II phosphorylation and subsequent transcriptional elongation
CC (PubMed:18249148, PubMed:18483487). The 7SK RNP complex also promotes
CC snRNA gene transcription by RNA polymerase II via interaction with the
CC little elongation complex (LEC) (PubMed:28254838). LARP7 specifically
CC binds to the highly conserved 3'-terminal U-rich stretch of 7SK RNA; on
CC stimulation, remains associated with 7SK RNA, whereas P-TEFb is
CC released from the complex (PubMed:18483487, PubMed:18281698). LARP7
CC also acts as a regulator of mRNA splicing fidelity by promoting U6
CC snRNA processing (PubMed:32017898). Specifically binds U6 snRNAs and
CC associates with a subset of box C/D RNP complexes: promotes U6 snRNA
CC 2'-O-methylation by facilitating U6 snRNA loading into box C/D RNP
CC complexes (PubMed:32017898). U6 snRNA 2'-O-methylation is required for
CC mRNA splicing fidelity (PubMed:32017898). Binds U6 snRNAs with a 5'-
CC CAGGG-3' sequence motif (PubMed:32017898). U6 snRNA processing is
CC required for spermatogenesis (By similarity).
CC {ECO:0000250|UniProtKB:Q05CL8, ECO:0000269|PubMed:18249148,
CC ECO:0000269|PubMed:18281698, ECO:0000269|PubMed:18483487,
CC ECO:0000269|PubMed:28254838, ECO:0000269|PubMed:32017898}.
CC -!- SUBUNIT: Core component of the 7SK RNP complex, at least composed of
CC 7SK RNA, LARP7, MEPCE, HEXIM1 (or HEXIM2) and P-TEFb (composed of CDK9
CC and CCNT1/cyclin-T1) (PubMed:18483487, PubMed:18281698,
CC PubMed:19906723). Interacts with METTL16 (PubMed:29051200). Interacts
CC with RBM7; upon genotoxic stress this interaction is enhanced,
CC triggering the release of inactive P-TEFb complex from the core,
CC yielding to P-TEFb complex activation (PubMed:30824372). Associates
CC with box C/D small nucleolar ribonucleoprotein (snoRNP) complexes
CC (PubMed:32017898). {ECO:0000269|PubMed:18281698,
CC ECO:0000269|PubMed:18483487, ECO:0000269|PubMed:19906723,
CC ECO:0000269|PubMed:29051200, ECO:0000269|PubMed:30824372,
CC ECO:0000269|PubMed:32017898}.
CC -!- INTERACTION:
CC Q4G0J3; P50750: CDK9; NbExp=12; IntAct=EBI-2371923, EBI-1383449;
CC Q4G0J3; O94992: HEXIM1; NbExp=10; IntAct=EBI-2371923, EBI-2832510;
CC Q4G0J3; Q5S007: LRRK2; NbExp=3; IntAct=EBI-2371923, EBI-5323863;
CC Q4G0J3; Q15646: OASL; NbExp=2; IntAct=EBI-2371923, EBI-3918068;
CC Q4G0J3; A0A142I5B9; Xeno; NbExp=2; IntAct=EBI-2371923, EBI-20625235;
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm
CC {ECO:0000269|PubMed:18483487}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q4G0J3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q4G0J3-2; Sequence=VSP_024021;
CC Name=3;
CC IsoId=Q4G0J3-3; Sequence=VSP_047390;
CC -!- DOMAIN: The xRRM domain binds the 3' end of 7SK snRNA (7SK RNA) at the
CC top of stem-loop 4. {ECO:0000269|PubMed:27679474,
CC ECO:0000269|PubMed:29946027}.
CC -!- DISEASE: Alazami syndrome (ALAZS) [MIM:615071]: A syndromic form of
CC primordial dwarfism, a condition characterized by severe growth
CC restriction that has its onset in utero, and results in short stature
CC and undersize. ALAZS patients manifest severe intellectual disability
CC and distinct facial features including malar hypoplasia, deep-set eyes,
CC broad nose, short philtrum, and macrostomia. Some patients have non-
CC specific and inconsistent skeletal findings, for example, scoliosis and
CC mild epiphyseal changes in the proximal phalanges, but no frank
CC dysplasia. {ECO:0000269|PubMed:21937992, ECO:0000269|PubMed:22865833,
CC ECO:0000269|PubMed:26374271, ECO:0000269|PubMed:27766953,
CC ECO:0000269|PubMed:29576627, ECO:0000269|PubMed:29619239,
CC ECO:0000269|PubMed:30006060, ECO:0000269|PubMed:32017898}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the LARP7 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH66945.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
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DR EMBL; EU667388; ACD13786.1; -; mRNA.
DR EMBL; AF068284; AAF65503.1; -; mRNA.
DR EMBL; AC106864; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471057; EAX06284.1; -; Genomic_DNA.
DR EMBL; BC066945; AAH66945.1; ALT_INIT; mRNA.
DR EMBL; BC107709; AAI07710.2; -; mRNA.
DR EMBL; AL049996; CAB43230.1; -; mRNA.
DR CCDS; CCDS3701.2; -. [Q4G0J3-1]
DR CCDS; CCDS58924.1; -. [Q4G0J3-1]
DR PIR; T08692; T08692.
DR RefSeq; NP_001253968.1; NM_001267039.1. [Q4G0J3-1]
DR RefSeq; NP_056269.1; NM_015454.2. [Q4G0J3-1]
DR RefSeq; NP_057732.2; NM_016648.3. [Q4G0J3-1]
DR PDB; 4WKR; X-ray; 3.20 A; A/B=1-208.
DR PDB; 5KNW; NMR; -; A=445-561.
DR PDB; 6D12; X-ray; 2.21 A; A/B=445-556.
DR PDB; 7SLP; EM; 4.10 A; B=1-582.
DR PDB; 7SLQ; EM; 3.70 A; B=1-582.
DR PDBsum; 4WKR; -.
DR PDBsum; 5KNW; -.
DR PDBsum; 6D12; -.
DR PDBsum; 7SLP; -.
DR PDBsum; 7SLQ; -.
DR AlphaFoldDB; Q4G0J3; -.
DR SMR; Q4G0J3; -.
DR BioGRID; 119619; 1079.
DR CORUM; Q4G0J3; -.
DR DIP; DIP-47624N; -.
DR IntAct; Q4G0J3; 80.
DR MINT; Q4G0J3; -.
DR STRING; 9606.ENSP00000422626; -.
DR BindingDB; Q4G0J3; -.
DR ChEMBL; CHEMBL4523314; -.
DR CarbonylDB; Q4G0J3; -.
DR GlyGen; Q4G0J3; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q4G0J3; -.
DR PhosphoSitePlus; Q4G0J3; -.
DR BioMuta; LARP7; -.
DR DMDM; 121945944; -.
DR EPD; Q4G0J3; -.
DR jPOST; Q4G0J3; -.
DR MassIVE; Q4G0J3; -.
DR MaxQB; Q4G0J3; -.
DR PaxDb; Q4G0J3; -.
DR PeptideAtlas; Q4G0J3; -.
DR PRIDE; Q4G0J3; -.
DR ProteomicsDB; 62106; -. [Q4G0J3-1]
DR ProteomicsDB; 62107; -. [Q4G0J3-2]
DR Antibodypedia; 15535; 211 antibodies from 28 providers.
DR DNASU; 51574; -.
DR Ensembl; ENST00000324052.10; ENSP00000314311.6; ENSG00000174720.17. [Q4G0J3-1]
DR Ensembl; ENST00000344442.10; ENSP00000344950.5; ENSG00000174720.17. [Q4G0J3-1]
DR Ensembl; ENST00000509061.5; ENSP00000422626.1; ENSG00000174720.17. [Q4G0J3-3]
DR Ensembl; ENST00000651579.1; ENSP00000499190.1; ENSG00000174720.17. [Q4G0J3-1]
DR GeneID; 51574; -.
DR KEGG; hsa:51574; -.
DR MANE-Select; ENST00000344442.10; ENSP00000344950.5; NM_016648.4; NP_057732.2.
DR UCSC; uc003iay.5; human. [Q4G0J3-1]
DR CTD; 51574; -.
DR DisGeNET; 51574; -.
DR GeneCards; LARP7; -.
DR HGNC; HGNC:24912; LARP7.
DR HPA; ENSG00000174720; Low tissue specificity.
DR MalaCards; LARP7; -.
DR MIM; 612026; gene.
DR MIM; 615071; phenotype.
DR neXtProt; NX_Q4G0J3; -.
DR OpenTargets; ENSG00000174720; -.
DR Orphanet; 319671; Alazami syndrome.
DR PharmGKB; PA145148525; -.
DR VEuPathDB; HostDB:ENSG00000174720; -.
DR eggNOG; KOG1855; Eukaryota.
DR GeneTree; ENSGT00940000154949; -.
DR HOGENOM; CLU_020946_2_0_1; -.
DR InParanoid; Q4G0J3; -.
DR OMA; RKAVHKM; -.
DR OrthoDB; 1499213at2759; -.
DR PhylomeDB; Q4G0J3; -.
DR TreeFam; TF314476; -.
DR PathwayCommons; Q4G0J3; -.
DR SignaLink; Q4G0J3; -.
DR SIGNOR; Q4G0J3; -.
DR BioGRID-ORCS; 51574; 52 hits in 1089 CRISPR screens.
DR ChiTaRS; LARP7; human.
DR GenomeRNAi; 51574; -.
DR Pharos; Q4G0J3; Tchem.
DR PRO; PR:Q4G0J3; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q4G0J3; protein.
DR Bgee; ENSG00000174720; Expressed in calcaneal tendon and 209 other tissues.
DR ExpressionAtlas; Q4G0J3; baseline and differential.
DR Genevisible; Q4G0J3; HS.
DR GO; GO:0120259; C:7SK snRNP; IDA:FlyBase.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:1990904; C:ribonucleoprotein complex; IDA:UniProtKB.
DR GO; GO:0030532; C:small nuclear ribonucleoprotein complex; IBA:GO_Central.
DR GO; GO:0097322; F:7SK snRNA binding; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0017070; F:U6 snRNA binding; IDA:UniProtKB.
DR GO; GO:0000494; P:box C/D RNA 3'-end processing; IMP:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:FlyBase.
DR GO; GO:0034244; P:negative regulation of transcription elongation from RNA polymerase II promoter; IC:FlyBase.
DR GO; GO:0032897; P:negative regulation of viral transcription; IMP:FlyBase.
DR GO; GO:1904871; P:positive regulation of protein localization to Cajal body; IDA:UniProtKB.
DR GO; GO:1905382; P:positive regulation of snRNA transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0048024; P:regulation of mRNA splicing, via spliceosome; IMP:UniProtKB.
DR GO; GO:0008380; P:RNA splicing; IEA:UniProtKB-KW.
DR GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB.
DR GO; GO:1990438; P:U6 2'-O-snRNA methylation; IMP:UniProtKB.
DR CDD; cd08032; LARP_7; 1.
DR CDD; cd12290; RRM1_LARP7; 1.
DR CDD; cd12542; RRM2_LARP7; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 3.30.70.330; -; 2.
DR InterPro; IPR045180; La_dom_prot.
DR InterPro; IPR006630; La_HTH.
DR InterPro; IPR014886; La_xRRM.
DR InterPro; IPR034946; LARP7_La.
DR InterPro; IPR034887; LARP7_RRM1.
DR InterPro; IPR034910; LARP7_RRM2.
DR InterPro; IPR002344; Lupus_La.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf.
DR InterPro; IPR035979; RBD_domain_sf.
DR InterPro; IPR000504; RRM_dom.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR PANTHER; PTHR22792; PTHR22792; 1.
DR Pfam; PF05383; La; 1.
DR Pfam; PF00076; RRM_1; 1.
DR Pfam; PF08777; RRM_3; 1.
DR PRINTS; PR00302; LUPUSLA.
DR SMART; SM00715; LA; 1.
DR SMART; SM00360; RRM; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF54928; SSF54928; 2.
DR PROSITE; PS50961; HTH_LA; 1.
DR PROSITE; PS50102; RRM; 1.
DR PROSITE; PS51939; XRRM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Differentiation;
KW Disease variant; Dwarfism; Intellectual disability; Isopeptide bond;
KW mRNA processing; mRNA splicing; Nucleus; Phosphoprotein;
KW Reference proteome; RNA-binding; Spermatogenesis; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..582
FT /note="La-related protein 7"
FT /id="PRO_0000281143"
FT DOMAIN 28..122
FT /note="HTH La-type RNA-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00332"
FT DOMAIN 125..203
FT /note="RRM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT DOMAIN 450..563
FT /note="xRRM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01288"
FT REGION 1..27
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 188..368
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 410..442
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 239..254
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 268..353
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 410..429
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 257
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 258
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 261
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 273
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 298
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 299
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 300
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 337
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 338
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 351
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CROSSLNK 237
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 410
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1..368
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_024021"
FT VAR_SEQ 1
FT /note="M -> MIPNIEGM (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:18483487"
FT /id="VSP_047390"
FT VARIANT 558..582
FT /note="ITKAEKIRLAKTQQASKHIRFSEYD -> KRLDWQRLNKRVNI (in
FT ALAZS; reduced 2'-O-methylation of U6 snRNAs and defects in
FT mRNA splicing)"
FT /evidence="ECO:0000269|PubMed:32017898"
FT /id="VAR_083351"
FT MUTAGEN 44
FT /note="F->A: Reduced binding to U6 snRNA without affecting
FT binding to 7SK RNA. Reduced 2'-O-methylation of U6 snRNAs."
FT /evidence="ECO:0000269|PubMed:32017898"
FT MUTAGEN 128
FT /note="Y->D: Loss of 7SK RNA-binding and marked decrease in
FT 7SK RNP complex formation."
FT /evidence="ECO:0000269|PubMed:18249148"
FT MUTAGEN 130
FT /note="E->A: Decreased RNA-binding."
FT /evidence="ECO:0000269|PubMed:25753663"
FT MUTAGEN 168
FT /note="F->A: Does not affect RNA-binding."
FT /evidence="ECO:0000269|PubMed:25753663"
FT MUTAGEN 451
FT /note="F->A: Does not affect binding to the 7SK RNA."
FT /evidence="ECO:0000269|PubMed:29946027"
FT MUTAGEN 472
FT /note="R->A: Does not affect binding to the 7SK RNA."
FT /evidence="ECO:0000269|PubMed:29946027"
FT MUTAGEN 483
FT /note="Y->A: Reduced binding to the 7SK RNA. Does not
FT affect binding to U6 snRNA."
FT /evidence="ECO:0000269|PubMed:29946027,
FT ECO:0000269|PubMed:32017898"
FT MUTAGEN 483
FT /note="Y->F: Does not affect binding to the 7SK RNA."
FT /evidence="ECO:0000269|PubMed:29946027"
FT MUTAGEN 496
FT /note="R->A: Strongly reduced binding to the stem loop 4 of
FT 7SK RNA."
FT /evidence="ECO:0000269|PubMed:29946027"
FT CONFLICT 295
FT /note="R -> G (in Ref. 5; AAI07710)"
FT /evidence="ECO:0000305"
FT CONFLICT 516
FT /note="K -> R (in Ref. 2; AAF65503 and 6; CAB43230)"
FT /evidence="ECO:0000305"
FT CONFLICT 560
FT /note="K -> Q (in Ref. 6; CAB43230)"
FT /evidence="ECO:0000305"
FT HELIX 30..45
FT /evidence="ECO:0007829|PDB:4WKR"
FT HELIX 48..53
FT /evidence="ECO:0007829|PDB:4WKR"
FT HELIX 55..62
FT /evidence="ECO:0007829|PDB:4WKR"
FT HELIX 71..75
FT /evidence="ECO:0007829|PDB:4WKR"
FT HELIX 78..81
FT /evidence="ECO:0007829|PDB:4WKR"
FT HELIX 87..93
FT /evidence="ECO:0007829|PDB:4WKR"
FT STRAND 106..110
FT /evidence="ECO:0007829|PDB:4WKR"
FT HELIX 122..125
FT /evidence="ECO:0007829|PDB:4WKR"
FT STRAND 127..130
FT /evidence="ECO:0007829|PDB:4WKR"
FT HELIX 137..146
FT /evidence="ECO:0007829|PDB:4WKR"
FT STRAND 151..155
FT /evidence="ECO:0007829|PDB:4WKR"
FT STRAND 160..162
FT /evidence="ECO:0007829|PDB:4WKR"
FT STRAND 167..175
FT /evidence="ECO:0007829|PDB:4WKR"
FT HELIX 176..183
FT /evidence="ECO:0007829|PDB:4WKR"
FT TURN 184..187
FT /evidence="ECO:0007829|PDB:4WKR"
FT STRAND 456..463
FT /evidence="ECO:0007829|PDB:6D12"
FT HELIX 468..476
FT /evidence="ECO:0007829|PDB:6D12"
FT STRAND 481..485
FT /evidence="ECO:0007829|PDB:6D12"
FT STRAND 491..499
FT /evidence="ECO:0007829|PDB:6D12"
FT HELIX 500..508
FT /evidence="ECO:0007829|PDB:6D12"
FT HELIX 510..515
FT /evidence="ECO:0007829|PDB:6D12"
FT STRAND 519..523
FT /evidence="ECO:0007829|PDB:6D12"
FT HELIX 526..544
FT /evidence="ECO:0007829|PDB:6D12"
FT STRAND 551..555
FT /evidence="ECO:0007829|PDB:5KNW"
SQ SEQUENCE 582 AA; 66899 MW; 04209B8159A5738C CRC64;
METESGNQEK VMEEESTEKK KEVEKKKRSR VKQVLADIAK QVDFWFGDAN LHKDRFLREQ
IEKSRDGYVD ISLLVSFNKM KKLTTDGKLI ARALRSSAVV ELDLEGTRIR RKKPLGERPK
DEDERTVYVE LLPKNVNHSW IERVFGKCGN VVYISIPHYK STGDPKGFAF VEFETKEQAA
KAIEFLNNPP EEAPRKPGIF PKTVKNKPIP ALRVVEEKKK KKKKKGRMKK EDNIQAKEEN
MDTSNTSISK MKRSRPTSEG SDIESTEPQK QCSKKKKKRD RVEASSLPEV RTGKRKRSSS
EDAESLAPRS KVKKIIQKDI IKEASEASKE NRDIEISTEE EKDTGDLKDS SLLKTKRKHK
KKHKERHKMG EEVIPLRVLS KSEWMDLKKE YLALQKASMA SLKKTISQIK SESEMETDSG
VPQNTGMKNE KTANREECRT QEKVNATGPQ FVSGVIVKII STEPLPGRKQ VRDTLAAISE
VLYVDLLEGD TECHARFKTP EDAQAVINAY TEINKKHCWK LEILSGDHEQ RYWQKILVDR
QAKLNQPREK KRGTEKLITK AEKIRLAKTQ QASKHIRFSE YD
