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 27-MAR-2024, entry version 170. 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 --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 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 EMDB; EMD-25197; -. DR EMDB; EMD-25198; -. DR SMR; Q4G0J3; -. DR BioGRID; 119619; 1114. DR CORUM; Q4G0J3; -. DR DIP; DIP-47624N; -. DR IntAct; Q4G0J3; 82. DR MINT; Q4G0J3; -. DR STRING; 9606.ENSP00000422626; -. DR BindingDB; Q4G0J3; -. DR ChEMBL; CHEMBL4523314; -. DR CarbonylDB; Q4G0J3; -. DR GlyCosmos; Q4G0J3; 1 site, 1 glycan. 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; 9606-ENSP00000422626; -. DR PeptideAtlas; Q4G0J3; -. DR ProteomicsDB; 62106; -. [Q4G0J3-1] DR ProteomicsDB; 62107; -. [Q4G0J3-2] DR Pumba; Q4G0J3; -. DR Antibodypedia; 15535; 238 antibodies from 28 providers. DR DNASU; 51574; -. DR Ensembl; ENST00000344442.10; ENSP00000344950.5; ENSG00000174720.18. [Q4G0J3-1] DR Ensembl; ENST00000505034.6; ENSP00000421541.2; ENSG00000174720.18. [Q4G0J3-1] DR Ensembl; ENST00000509061.5; ENSP00000422626.2; ENSG00000174720.18. [Q4G0J3-1] DR Ensembl; ENST00000651579.1; ENSP00000499190.1; ENSG00000174720.18. [Q4G0J3-1] DR Ensembl; ENST00000694894.1; ENSP00000511572.1; ENSG00000174720.18. [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 AGR; HGNC:24912; -. 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; ANASHDW; -. DR OrthoDB; 169507at2759; -. DR PhylomeDB; Q4G0J3; -. DR TreeFam; TF314476; -. DR PathwayCommons; Q4G0J3; -. DR SignaLink; Q4G0J3; -. DR SIGNOR; Q4G0J3; -. DR BioGRID-ORCS; 51574; 58 hits in 1166 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 210 other cell types or tissues. DR ExpressionAtlas; Q4G0J3; baseline and differential. 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:0005844; C:polysome; IBA:GO_Central. DR GO; GO:1990904; C:ribonucleoprotein complex; IDA:UniProtKB. DR GO; GO:0097322; F:7SK snRNA binding; IDA:UniProtKB. DR GO; GO:0003729; F:mRNA binding; IBA:GO_Central. 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 by RNA polymerase II; 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; 3.30.70.330; -; 2. DR Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 1. 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:SF140; LA-RELATED PROTEIN 7; 1. DR PANTHER; PTHR22792; LUPUS LA PROTEIN-RELATED; 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; SSF54928; RNA-binding domain, RBD; 2. DR SUPFAM; SSF46785; Winged helix' DNA-binding domain; 1. DR PROSITE; PS50961; HTH_LA; 1. DR PROSITE; PS50102; RRM; 1. DR PROSITE; PS51939; XRRM; 1. DR Genevisible; Q4G0J3; HS. 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 7SKRNA. Reduced 2'-O-methylation of U6 snRNAs." FT /evidence="ECO:0000269|PubMed:32017898" FT MUTAGEN 128 FT /note="Y->D: Loss of 7SKRNA-binding and marked decrease in FT 7SKRNP 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 7SKRNA." FT /evidence="ECO:0000269|PubMed:29946027" FT MUTAGEN 472 FT /note="R->A: Does not affect binding to the 7SKRNA." FT /evidence="ECO:0000269|PubMed:29946027" FT MUTAGEN 483 FT /note="Y->A: Reduced binding to the 7SKRNA. Does not affect FT 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 7SKRNA." FT /evidence="ECO:0000269|PubMed:29946027" FT MUTAGEN 496 FT /note="R->A: Strongly reduced binding to the stem loop 4 of FT 7SKRNA." 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 //