LRGUK_MOUSE
ID LRGUK_MOUSE Reviewed; 820 AA.
AC Q9D5S7;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Leucine-rich repeat and guanylate kinase domain-containing protein;
GN Name=Lrguk;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, INTERACTION WITH HOOK2, AND
RP FUNCTION.
RX PubMed=25781171; DOI=10.1371/journal.pgen.1005090;
RA Liu Y., DeBoer K., de Kretser D.M., O'Donnell L., O'Connor A.E.,
RA Merriner D.J., Okuda H., Whittle B., Jans D.A., Efthymiadis A.,
RA McLachlan R.I., Ormandy C.J., Goodnow C.C., Jamsai D., O'Bryan M.K.;
RT "LRGUK-1 is required for basal body and manchette function during
RT spermatogenesis and male fertility.";
RL PLoS Genet. 11:E1005090-E1005090(2015).
RN [3]
RP FUNCTION, INTERACTION WITH RIMBP3; HOOK1; HOOK2; HOOK3 AND KLC3, AND
RP SUBCELLULAR LOCATION.
RX PubMed=28003339; DOI=10.1096/fj.201600909r;
RA Okuda H., DeBoer K., O'Connor A.E., Merriner D.J., Jamsai D., O'Bryan M.K.;
RT "LRGUK1 is part of a multiprotein complex required for manchette function
RT and male fertility.";
RL FASEB J. 31:1141-1152(2017).
CC -!- FUNCTION: Involved in multiple aspects of sperm assembly including
CC acrosome attachment, shaping of the sperm head and in the early aspects
CC of axoneme development (PubMed:25781171). Not essential for primary
CC cilium biogenesis (PubMed:28003339). {ECO:0000269|PubMed:25781171,
CC ECO:0000269|PubMed:28003339}.
CC -!- SUBUNIT: Interacts (via guanylate kinase-like domain) with RIMBP3 (via
CC coiled-coil region) (PubMed:28003339). Interacts (via guanylate kinase-
CC like domain) with HOOK2 (PubMed:25781171, PubMed:28003339). Interacts
CC (via LRRCT domain) with KLC3. Interacts with HOOK1 and HOOK3
CC (PubMed:28003339). {ECO:0000269|PubMed:25781171,
CC ECO:0000269|PubMed:28003339}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, acrosome
CC {ECO:0000269|PubMed:25781171, ECO:0000269|PubMed:28003339}. Cytoplasm,
CC cytoskeleton {ECO:0000269|PubMed:28003339}. Cytoplasm, cytoskeleton,
CC cilium basal body {ECO:0000269|PubMed:28003339}. Note=Localizes to the
CC acrosome and acroplaxome in round spermatids. Localizes to the
CC manchette during spermiogenesis. Also found in the basal body of
CC elongating spermatids, and in primary cilia of somatic cells.
CC {ECO:0000269|PubMed:25781171, ECO:0000269|PubMed:28003339}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the testis (PubMed:25781171).
CC During spermatid development is initially localized to a supra-nuclear
CC region of round spermatids, and is particularly evident at the leading
CC edge of the developing acrosome and acroplaxome. As maturation
CC proceeded and nuclear elongation initiated, LRGUK moves distally to
CC ultimately reside on the microtubules of the manchette. LRGUK is also
CC evident in the sperm basal body and the sperm tail (PubMed:25781171).
CC {ECO:0000269|PubMed:25781171}.
CC -!- DEVELOPMENTAL STAGE: Detectable at low levels from birth, up-regulated
CC at day 14 coincident with the appearance of pachytene spermatocytes,
CC then maximal from day 18 coincident with the appearance of haploid germ
CC cells (PubMed:25781171). {ECO:0000269|PubMed:25781171}.
CC -!- MISCELLANEOUS: Mutagenesis with N-ethyl-N-nitrosourea (ENU) lead to the
CC discovery of the Kaos phenotype. The Kaos mutation results in the
CC conversion of Arg-528 to a stop codon. Homozygous males are
CC oligoasthenoteratospermic and sterile. {ECO:0000269|PubMed:25781171}.
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DR EMBL; AK014976; BAB29648.1; -; mRNA.
DR CCDS; CCDS51745.1; -.
DR RefSeq; NP_083162.1; NM_028886.1.
DR AlphaFoldDB; Q9D5S7; -.
DR SMR; Q9D5S7; -.
DR STRING; 10090.ENSMUSP00000065146; -.
DR iPTMnet; Q9D5S7; -.
DR PhosphoSitePlus; Q9D5S7; -.
DR jPOST; Q9D5S7; -.
DR MaxQB; Q9D5S7; -.
DR PaxDb; Q9D5S7; -.
DR PeptideAtlas; Q9D5S7; -.
DR PRIDE; Q9D5S7; -.
DR ProteomicsDB; 287271; -.
DR Antibodypedia; 18051; 63 antibodies from 17 providers.
DR DNASU; 74354; -.
DR Ensembl; ENSMUST00000070189; ENSMUSP00000065146; ENSMUSG00000056215.
DR GeneID; 74354; -.
DR KEGG; mmu:74354; -.
DR UCSC; uc009bgv.1; mouse.
DR CTD; 136332; -.
DR MGI; MGI:1921604; Lrguk.
DR VEuPathDB; HostDB:ENSMUSG00000056215; -.
DR eggNOG; KOG0531; Eukaryota.
DR eggNOG; KOG0707; Eukaryota.
DR GeneTree; ENSGT00940000157992; -.
DR HOGENOM; CLU_019293_0_0_1; -.
DR InParanoid; Q9D5S7; -.
DR OrthoDB; 156510at2759; -.
DR PhylomeDB; Q9D5S7; -.
DR TreeFam; TF329158; -.
DR BioGRID-ORCS; 74354; 4 hits in 72 CRISPR screens.
DR ChiTaRS; Lrguk; mouse.
DR PRO; PR:Q9D5S7; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q9D5S7; protein.
DR Bgee; ENSMUSG00000056215; Expressed in spermatocyte and 47 other tissues.
DR ExpressionAtlas; Q9D5S7; baseline and differential.
DR Genevisible; Q9D5S7; MM.
DR GO; GO:0001669; C:acrosomal vesicle; IDA:UniProtKB.
DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0002177; C:manchette; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004385; F:guanylate kinase activity; IBA:GO_Central.
DR GO; GO:0035082; P:axoneme assembly; IDA:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0007283; P:spermatogenesis; IMP:UniProtKB.
DR Gene3D; 3.40.50.300; -; 1.
DR Gene3D; 3.80.10.10; -; 2.
DR InterPro; IPR008145; GK/Ca_channel_bsu.
DR InterPro; IPR008144; Guanylate_kin-like_dom.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR027417; P-loop_NTPase.
DR Pfam; PF00625; Guanylate_kin; 1.
DR SMART; SM00072; GuKc; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS50052; GUANYLATE_KINASE_2; 1.
DR PROSITE; PS51450; LRR; 10.
PE 1: Evidence at protein level;
KW ATP-binding; Cell projection; Cytoplasm; Cytoplasmic vesicle; Cytoskeleton;
KW Differentiation; Kinase; Leucine-rich repeat; Nucleotide-binding;
KW Reference proteome; Repeat; Spermatogenesis; Transferase.
FT CHAIN 1..820
FT /note="Leucine-rich repeat and guanylate kinase domain-
FT containing protein"
FT /id="PRO_0000326409"
FT REPEAT 129..149
FT /note="LRR 1"
FT REPEAT 150..171
FT /note="LRR 2"
FT REPEAT 172..193
FT /note="LRR 3"
FT REPEAT 194..215
FT /note="LRR 4"
FT REPEAT 216..237
FT /note="LRR 5"
FT REPEAT 238..259
FT /note="LRR 6"
FT REPEAT 260..280
FT /note="LRR 7"
FT REPEAT 281..302
FT /note="LRR 8"
FT REPEAT 303..324
FT /note="LRR 9"
FT DOMAIN 337..375
FT /note="LRRCT"
FT DOMAIN 414..597
FT /note="Guanylate kinase-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00100"
FT REGION 72..96
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 800..820
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 79..96
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 421..428
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00100"
SQ SEQUENCE 820 AA; 93190 MW; 9C9B5F7851B12C18 CRC64;
MAAFERNPSR WKGTRFRRGL GASRIAAQAI LSLTEKQSQG RWPSFPLGLK SKGTFRSASS
YLLHQLIHRS HEAEAEQEEK QQEDGESEES EESEMQNLED KYDGILREET VAEAITGLGW
SGRGTEQVYL NLNLSHCELV DISILCGYVH LQKLNLSGNR IEDLSCVSCM PYLLELNASQ
NKLTTFFNFK PPQNLKKVDF SSNLISEMYD LSAYHTLTQL ILDNNEIEEI TGLENCISLT
HLSLAGNKIT TIKGLGTLPI KVLSLSNNMI ETITGLEELK ALQNLDLSHN QISSLQGLEN
HDLLEVINLE DNKIKELSEI EYIENLPILR VLNLLRNPIQ TKPEYWFFVI YMLLRLTELD
QQKIKVEEKV FAVNKYDPPP EVVAVQDHMT HVVNSMSQPQ RIWDSTLPSL DAPYPMLILT
GPAACGKREL AHRLCRQFST YFRYGACHTT RPPYFGEGDR VDYHFISQEV FDEMLNMGKF
ILTFNYGNHN YGLNRDTIEG IARDGLASCI HMELEGVRSL KYSYFEPRYI LVVPMDKEKY
EGYLRRKGLF SRAEIEIAVS RVDLYVKVNQ KYPGYFDAVI NADDMDIAYQ KLSELIREYL
GLTETAAKTL APTADTKTSY LKCEDYSRKS STVEFLDSTD RNYFTKLWAK LSSKKSPVER
ESLHRQHEAA RQALMGKTPR DHTLLFQRGP VPIPTVSGQQ YFATIDELQK TFELSDDLFK
TPSGTYPETS KDSNISKRYS TYFHTCPWSK ELPFQLPEGG ISSRPGSAGS DEVDGALKAL
RVASSMQEKV AQHKRLSAIT IMDPGSNTKP TLPPIPHGRR
