ID   GRB1L_MOUSE             Reviewed;        1913 AA.
AC   B9EJV3; Q5DTN6;
DT   21-MAR-2012, integrated into UniProtKB/Swiss-Prot.
DT   24-MAR-2009, sequence version 1.
DT   03-AUG-2022, entry version 72.
DE   RecName: Full=GREB1-like protein;
GN   Name=Greb1l; Synonyms=Kiaa4095;
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 GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1089-1913.
RC   TISSUE=Fetal brain;
RA   Okazaki N., Kikuno R.F., Ohara R., Inamoto S., Nagase T., Ohara O.,
RA   Koga H.;
RT   "Prediction of the coding sequences of mouse homologues of KIAA gene. The
RT   complete nucleotide sequences of mouse KIAA-homologous cDNAs identified by
RT   screening of terminal sequences of cDNA clones randomly sampled from size-
RT   fractionated libraries.";
RL   Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   DEVELOPMENTAL STAGE.
RX   PubMed=29100090; DOI=10.1016/j.ajhg.2017.09.018;
RA   Sanna-Cherchi S., Khan K., Westland R., Krithivasan P., Fievet L.,
RA   Rasouly H.M., Ionita-Laza I., Capone V.P., Fasel D.A., Kiryluk K.,
RA   Kamalakaran S., Bodria M., Otto E.A., Sampson M.G., Gillies C.E.,
RA   Vega-Warner V., Vukojevic K., Pediaditakis I., Makar G.S., Mitrotti A.,
RA   Verbitsky M., Martino J., Liu Q., Na Y.J., Goj V., Ardissino G.,
RA   Gigante M., Gesualdo L., Janezcko M., Zaniew M., Mendelsohn C.L., Shril S.,
RA   Hildebrandt F., van Wijk J.A.E., Arapovic A., Saraga M., Allegri L.,
RA   Izzi C., Scolari F., Tasic V., Ghiggeri G.M., Latos-Bielenska A.,
RA   Materna-Kiryluk A., Mane S., Goldstein D.B., Lifton R.P., Katsanis N.,
RA   Davis E.E., Gharavi A.G.;
RT   "Exome-wide association study identifies GREB1L mutations in congenital
RT   kidney malformations.";
RL   Am. J. Hum. Genet. 101:789-802(2017).
RN   [5]
RP   FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX   PubMed=29100091; DOI=10.1016/j.ajhg.2017.09.026;
RA   De Tomasi L., David P., Humbert C., Silbermann F., Arrondel C., Tores F.,
RA   Fouquet S., Desgrange A., Niel O., Bole-Feysot C., Nitschke P., Roume J.,
RA   Cordier M.P., Pietrement C., Isidor B., Khau Van Kien P., Gonzales M.,
RA   Saint-Frison M.H., Martinovic J., Novo R., Piard J., Cabrol C., Verma I.C.,
RA   Puri R., Journel H., Aziza J., Gavard L., Said-Menthon M.H., Heidet L.,
RA   Saunier S., Jeanpierre C.;
RT   "Mutations in GREB1L cause bilateral kidney agenesis in humans and mice.";
RL   Am. J. Hum. Genet. 101:803-814(2017).
RN   [6]
RP   TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX   PubMed=29955957; DOI=10.1007/s00439-018-1898-8;
RA   Schrauwen I., Kari E., Mattox J., Llaci L., Smeeton J., Naymik M.,
RA   Raible D.W., Knowles J.A., Crump J.G., Huentelman M.J., Friedman R.A.;
RT   "De novo variants in GREB1L are associated with non-syndromic inner ear
RT   malformations and deafness.";
RL   Hum. Genet. 137:459-470(2018).
CC   -!- FUNCTION: Plays a major role in early metanephros and genital
CC       development. {ECO:0000269|PubMed:29100091}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC       protein {ECO:0000255}.
CC   -!- TISSUE SPECIFICITY: Expressed in the inner ear, with a high presence in
CC       the spiral ganglia, cochlear nerve bundles, and hair cells.
CC       {ECO:0000269|PubMed:29955957}.
CC   -!- DEVELOPMENTAL STAGE: At 15.5 dpc, expressed in kidney, ureter and
CC       bladder (PubMed:29100090). At 16.0 dpc, strong expression in the liver,
CC       thymus, intestine, kidney, and brain. In the brain, high levels in the
CC       ventricular zone and in the neopallial cortex. In the kidney, highest
CC       levels in the nephrogenic zone located in the cortical region of the
CC       kidney. Also observed in epithelial cells of the differentiating renal
CC       tubules. At P0, strong expression in the nephrogenic zone
CC       (PubMed:29100091). In the inner ear, prominent expression is observed
CC       between 13 and 16 dpc (PubMed:29955957). {ECO:0000269|PubMed:29100090,
CC       ECO:0000269|PubMed:29100091, ECO:0000269|PubMed:29955957}.
CC   -!- DISRUPTION PHENOTYPE: Embryonic lethal at the homozygous state. At 13.5
CC       dpc, all homozygous embryos are significantly smaller compared to wild-
CC       type and heterozygous littermates and present with exencephaly. Male
CC       and female embryos lack kidney and show absence of Wolffian and
CC       Muellerian ducts, respectively. However, mesonephric tubules are
CC       consistently observed. Some potential remnants of ureteric bud are
CC       present in most mutant embryos. In male mutant embryos, the gonads are
CC       severely affected, being small and with poorly organized sex-cords
CC       compared to wild-type littermates. Mutant embryos also show cardiac
CC       morphogenesis defects with superimposed ventricles.
CC       {ECO:0000269|PubMed:29100091}.
CC   -!- SIMILARITY: Belongs to the GREB1 family. {ECO:0000305}.
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DR   EMBL; AC102441; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC124740; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC147570; AAI47571.1; -; mRNA.
DR   EMBL; AK220484; BAD90285.1; -; mRNA.
DR   CCDS; CCDS37736.1; -.
DR   RefSeq; NP_001077097.1; NM_001083628.1.
DR   AlphaFoldDB; B9EJV3; -.
DR   STRING; 10090.ENSMUSP00000049003; -.
DR   iPTMnet; B9EJV3; -.
DR   PhosphoSitePlus; B9EJV3; -.
DR   PaxDb; B9EJV3; -.
DR   PRIDE; B9EJV3; -.
DR   ProteomicsDB; 271295; -.
DR   Antibodypedia; 70466; 12 antibodies from 6 providers.
DR   Ensembl; ENSMUST00000048977; ENSMUSP00000049003; ENSMUSG00000042942.
DR   GeneID; 381157; -.
DR   KEGG; mmu:381157; -.
DR   UCSC; uc008eat.1; mouse.
DR   CTD; 80000; -.
DR   MGI; MGI:3576497; Greb1l.
DR   VEuPathDB; HostDB:ENSMUSG00000042942; -.
DR   eggNOG; ENOG502QQXD; Eukaryota.
DR   GeneTree; ENSGT00390000008041; -.
DR   HOGENOM; CLU_237163_0_0_1; -.
DR   InParanoid; B9EJV3; -.
DR   OMA; LCTEQID; -.
DR   OrthoDB; 70299at2759; -.
DR   PhylomeDB; B9EJV3; -.
DR   TreeFam; TF329531; -.
DR   BioGRID-ORCS; 381157; 2 hits in 72 CRISPR screens.
DR   ChiTaRS; Greb1l; mouse.
DR   PRO; PR:B9EJV3; -.
DR   Proteomes; UP000000589; Chromosome 18.
DR   RNAct; B9EJV3; protein.
DR   Bgee; ENSMUSG00000042942; Expressed in presomitic mesoderm and 168 other tissues.
DR   ExpressionAtlas; B9EJV3; baseline and differential.
DR   Genevisible; B9EJV3; MM.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; IMP:MGI.
DR   GO; GO:0003231; P:cardiac ventricle development; IMP:MGI.
DR   GO; GO:0060562; P:epithelial tube morphogenesis; IMP:MGI.
DR   GO; GO:0001822; P:kidney development; IMP:MGI.
DR   GO; GO:0030539; P:male genitalia development; IMP:MGI.
DR   GO; GO:0072177; P:mesonephric duct development; IMP:MGI.
DR   GO; GO:0001656; P:metanephros development; IMP:MGI.
DR   GO; GO:0061205; P:paramesonephric duct development; IMP:MGI.
DR   GO; GO:0060065; P:uterus development; IMP:MGI.
DR   InterPro; IPR028422; GREB1.
DR   InterPro; IPR024840; GREB1-like.
DR   PANTHER; PTHR15720; PTHR15720; 2.
DR   PANTHER; PTHR15720:SF12; PTHR15720:SF12; 2.
DR   Pfam; PF15782; GREB1; 1.
PE   2: Evidence at transcript level;
KW   Developmental protein; Membrane; Reference proteome; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..1913
FT                   /note="GREB1-like protein"
FT                   /id="PRO_0000416127"
FT   TRANSMEM        1832..1852
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   REGION          86..111
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          281..309
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1097..1157
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1179..1207
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1098..1114
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1115..1157
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1182..1206
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   1913 AA;  213628 MW;  531E8AF95AD9ECFC CRC64;
     MGNSYAGQLK SARFEEALHN SIEASLRCST AVPRPIFSQL YLDPDQHPFS TADVKPKVED
     LDKDLVHPYT QNGSVDFSHN VAMNEMEDDE DEEEMSDSNS PPIPYSQKPA PEGSCTTDGF
     CQAGKDLRLV SLCMEQIDIP AGFLLVGAKS PNLPEHILVC AVDKRFLPDD HGKNALLGFS
     GNCIGCGERG FRYFTEFSNH INLKLTTQPK KQKHLKYYLV RTSQGVLSKG PLICWKECRS
     RQSSALCHST KPISSVSSAV APENGTANGY KAGFTVTEAA NGTSGHGGKS SSCSSTPSRP
     GNYSLSPRPT FTSVDQANMF ISGPPKKRHR GWYPGSPVSQ SALVVPAPTV RPLSRTEPLL
     STPVPQTPLT GILQPRPVLA GETVIVPENL LSNSGVRPVI LIGYGTLPYF YGNVGDIVVS
     PLLVNCYKIP QLENKDLEQL GLTSTHLLSV ENMILLTIQY LVRLGPDQIP LREEFEQIML
     TAMQEFSVRE RALPLGAPCA PMSPAQLPWL ARLAASVSQD LVHVIVTQNS LAEGISETLR
     LLSEMKHYQR LPDYVVAICA SKIRGNEFCV VVLGQHQSRA LAESMLTTSE FLKEISYELI
     TGKVSFLASH FKTTSLGDDL DKLLEKMQQR RGDSVVTPFN GDLDECVSPQ EAAAMIPTQN
     LDVDNETFQI YQPQLTVARR LLSQVCAIAD SGSQSLDLGH FSKVDFIIIV PRSEVLVQQT
     LQRVRQSGVL VDLGLEESGL AHQRAERYVV RLDNEIQSKF EVFMRRVKQN PYTLFVLVHD
     NSHVELTSVI SGSLSHGEPT HGLADRVINC REVLEAFNLL VLQVSSFPYT LQTQQSRISS
     SNEVHWIQLD TMEDAGCEKL YFGLDEYSKS LQWGITSPLL RCDETFEKMV STLLERYPRL
     HSMVVRCYLL IQQYSEALMA LTTMASLRDH STPETLSIMD DLITSPGKNK SGKGHMLVIR
     VPSVQLAMLA KERLQEVRDK LGLQYRFEII LGSPASELTV ETHFVTRLKT WRGNDQDEWI
     PRTYQDLEGL PCIVILTGKD PLGETFPRSL KYCDLRLIDS SYLTRTALEQ EVGLACCYVS
     KEVIRGPAAA LDLSAKEAER VPASENDSEE LLIDLERPQS NSSAVTGTSG SIMENGVSSS
     STAGKPQQQL LTPTSSIRLD EGVSASTAVV GEILKQECDS LDPPMASSTT SKPSSSSSSS
     AQALAWSRQP RGLHTALPPV IILSKAAYSL LGSQKGGRLP SSSSLLPHAD VAWVSSLRPG
     LHKDMSSEEQ SLYYRQWTSA RQHHADYSNQ PDPISGARTL HPRRLLLTGP PQVGKTGSYL
     QFLRILFRML IRLLEVDVYN EEEINTDHSD DSELSQSEGE PWPDIETFSK MPFDVSVHDP
     KYRLMSLVYS EKLAGIKQEV IKEYKVEEPR QRETMSMMLT QYAAYNTFHH CEQCQQYMAF
     TPASQMSDST LHAFTFSSSM LGEEVQLYFI IPKSKESHFV FSKQGRHLES MRLPLVSDKN
     LNAVKSPIFT PSSGRHEHGL LNLFHAMEGI SHLHLLVVKE YEMPLYRKYW PNHIMLVLPG
     MFNNAGVGAA RFLIKELSYH NLELERNRLE ELGVKRQCVW PFIVVMDDSC VLWNIHSVQE
     QTSQPTEAGI SSKNVSLKSV LQHIEATPKI IHYAILGIQK WNSKLTSQSL KAPFSRCHVH
     DFILLNIDLT QNVQYDFNRY FCEDVDFNLR TNSSGLLICR FNNFSLMKKH VQVGGQRDFI
     IKPKLMVSEN VVPILPLQYV CAPDSEHTLL AAPAQFLLEK FLQHASYKLF PKAIHNFKSP
     VLAIDCYLNI GQEVAICYVS SRPHSSNVNC EGVFFSGLLL YLCDSFVGAD LLKKFKFLKG
     ATLCVICQDR SSLRQTIVRL ELEDEWQFRL RDEFQTANSS DDKPLYFLTG RHV