GLMN_MOUSE
ID GLMN_MOUSE Reviewed; 596 AA.
AC Q8BZM1; Q3TFR5; Q99LB8;
DT 14-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Glomulin;
DE AltName: Full=FK506-binding protein-associated protein;
DE Short=FAP;
DE AltName: Full=FKBP-associated protein;
GN Name=Glmn; Synonyms=Fap48;
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 [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=CD-1; TISSUE=Embryo;
RX PubMed=15053987; DOI=10.1016/j.modgep.2003.09.007;
RA McIntyre B.A.S., Brouillard P., Aerts V., Gutierrez-Roelens I., Vikkula M.;
RT "Glomulin is predominantly expressed in vascular smooth muscle cells in the
RT embryonic and adult mouse.";
RL Gene Expr. Patterns 4:351-358(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Diencephalon, and Kidney;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=22405651; DOI=10.1016/j.molcel.2012.02.005;
RA Tron A.E., Arai T., Duda D.M., Kuwabara H., Olszewski J.L., Fujiwara Y.,
RA Bahamon B.N., Signoretti S., Schulman B.A., DeCaprio J.A.;
RT "The glomuvenous malformation protein Glomulin binds Rbx1 and regulates
RT cullin RING ligase-mediated turnover of Fbw7.";
RL Mol. Cell 46:67-78(2012).
CC -!- FUNCTION: Regulatory component of cullin-RING-based SCF (SKP1-Cullin-F-
CC box protein) E3 ubiquitin-protein ligase complexes. Inhibits E3
CC ubiquitin ligase activity by binding to the RING domain of RBX1 and
CC inhibiting its interaction with the E2 ubiquitin-conjugating enzyme
CC CDC34. Inhibits RBX1-mediated neddylation of CUL1 (By similarity).
CC Required for normal stability and normal cellular levels of key
CC components of SCF ubiquitin ligase complexes, including FBXW7, RBX1,
CC CUL1, CUL2, CUL3, CUL4A, and thereby contributes to the regulation of
CC CCNE1 and MYC levels (PubMed:22405651). Essential for normal
CC development of the vasculature (PubMed:22405651). Contributes to the
CC regulation of RPS6KB1 phosphorylation (By similarity).
CC {ECO:0000250|UniProtKB:Q92990, ECO:0000269|PubMed:22405651}.
CC -!- SUBUNIT: Interacts with FKBP4 and FKBP1A. Interacts with RBX1 (via RING
CC domain). Identified in complexes that contain RBX1 plus one of the
CC cullins CUL1, CUL2, CUL3, and CUL4A. Identified in a SCF complex
CC composed of CUL1, RBX1, SKP1, FBXW7 and GLMN. Component of a SCF-like
CC complex consisting of CUL7, RBX1, SKP1, FBXW8 and GLMN. Interacts with
CC unphosphorylated MET and is released upon MET phosphorylation.
CC {ECO:0000250|UniProtKB:Q92990}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. Detected in embryonic vasculature and
CC embryonic perichondrium, and in adult eye, brain, heart, testis,
CC kidney, smooth muscle and skeletal muscle.
CC {ECO:0000269|PubMed:15053987}.
CC -!- DOMAIN: The C-terminal half of the protein is important for interaction
CC with RBX1. {ECO:0000250|UniProtKB:Q92990}.
CC -!- PTM: Phosphorylated on tyrosine residues.
CC {ECO:0000250|UniProtKB:Q92990}.
CC -!- DISRUPTION PHENOTYPE: Complete embryonic lethality. Embryos are present
CC at the expected Mendelian rate at 10.5 dpc, but all are dead by 12.5
CC dpc. Mutant embryos display decreased growth, delayed neural tube
CC closure, incomplete axial turning, pericardial effusion and a failure
CC to form an organized, functional vascular network. Mutant embryos have
CC reduced protein levels of FBXW7, RBX1, CUL1, CUL2, CUL3 and CUL4A, due
CC to increased proteasome-mediated degradation, and increased levels of
CC CCNE1 and MYC. {ECO:0000269|PubMed:22405651}.
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; AJ566083; CAD92739.1; -; mRNA.
DR EMBL; AK034160; BAC28612.1; -; mRNA.
DR EMBL; AK169045; BAE40833.1; -; mRNA.
DR EMBL; BC003446; AAH03446.1; -; mRNA.
DR CCDS; CCDS19505.1; -.
DR RefSeq; NP_001155210.1; NM_001161738.1.
DR RefSeq; NP_001155211.1; NM_001161739.1.
DR RefSeq; NP_573511.2; NM_133248.2.
DR RefSeq; XP_006534863.1; XM_006534800.3.
DR AlphaFoldDB; Q8BZM1; -.
DR SMR; Q8BZM1; -.
DR BioGRID; 228459; 2.
DR STRING; 10090.ENSMUSP00000077168; -.
DR PhosphoSitePlus; Q8BZM1; -.
DR EPD; Q8BZM1; -.
DR MaxQB; Q8BZM1; -.
DR PaxDb; Q8BZM1; -.
DR PRIDE; Q8BZM1; -.
DR ProteomicsDB; 270994; -.
DR Antibodypedia; 33642; 253 antibodies from 27 providers.
DR DNASU; 170823; -.
DR Ensembl; ENSMUST00000078021; ENSMUSP00000077168; ENSMUSG00000029276.
DR Ensembl; ENSMUST00000082121; ENSMUSP00000080766; ENSMUSG00000029276.
DR GeneID; 170823; -.
DR KEGG; mmu:170823; -.
DR UCSC; uc008ymm.2; mouse.
DR CTD; 11146; -.
DR MGI; MGI:2141180; Glmn.
DR VEuPathDB; HostDB:ENSMUSG00000029276; -.
DR eggNOG; ENOG502QQAV; Eukaryota.
DR GeneTree; ENSGT00390000018446; -.
DR HOGENOM; CLU_029654_3_0_1; -.
DR InParanoid; Q8BZM1; -.
DR OMA; CIFMYKQ; -.
DR OrthoDB; 1088011at2759; -.
DR PhylomeDB; Q8BZM1; -.
DR TreeFam; TF105319; -.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR BioGRID-ORCS; 170823; 12 hits in 72 CRISPR screens.
DR ChiTaRS; Glmn; mouse.
DR PRO; PR:Q8BZM1; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q8BZM1; protein.
DR Bgee; ENSMUSG00000029276; Expressed in retinal neural layer and 246 other tissues.
DR ExpressionAtlas; Q8BZM1; baseline and differential.
DR Genevisible; Q8BZM1; MM.
DR GO; GO:0031462; C:Cul2-RING ubiquitin ligase complex; ISO:MGI.
DR GO; GO:0031463; C:Cul3-RING ubiquitin ligase complex; ISO:MGI.
DR GO; GO:0031464; C:Cul4A-RING E3 ubiquitin ligase complex; ISO:MGI.
DR GO; GO:0031461; C:cullin-RING ubiquitin ligase complex; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005171; F:hepatocyte growth factor receptor binding; ISS:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0055105; F:ubiquitin-protein transferase inhibitor activity; ISO:MGI.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; ISO:MGI.
DR GO; GO:0072359; P:circulatory system development; IMP:MGI.
DR GO; GO:0042692; P:muscle cell differentiation; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0042130; P:negative regulation of T cell proliferation; ISS:UniProtKB.
DR GO; GO:0001843; P:neural tube closure; IMP:MGI.
DR GO; GO:0001819; P:positive regulation of cytokine production; ISS:UniProtKB.
DR GO; GO:0032743; P:positive regulation of interleukin-2 production; ISS:UniProtKB.
DR GO; GO:0042327; P:positive regulation of phosphorylation; ISS:UniProtKB.
DR GO; GO:0040029; P:regulation of gene expression, epigenetic; ISS:UniProtKB.
DR GO; GO:0032434; P:regulation of proteasomal ubiquitin-dependent protein catabolic process; ISO:MGI.
DR GO; GO:0001570; P:vasculogenesis; ISS:UniProtKB.
DR InterPro; IPR019516; Glomulin/ALF4.
DR InterPro; IPR013877; YAP-bd/ALF4/Glomulin.
DR PANTHER; PTHR15430; PTHR15430; 1.
DR Pfam; PF08568; Kinetochor_Ybp2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Phosphoprotein; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q92990"
FT CHAIN 2..596
FT /note="Glomulin"
FT /id="PRO_0000087514"
FT REGION 2..555
FT /note="Alpha-helical region with structural similarity to
FT HEAT repeats"
FT /evidence="ECO:0000250|UniProtKB:Q92990"
FT REGION 299..596
FT /note="Important for interaction with RBX1"
FT /evidence="ECO:0000250|UniProtKB:Q92990"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q92990"
FT CONFLICT 270
FT /note="Y -> S (in Ref. 3; AAH03446)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 596 AA; 67756 MW; 4C306B16F3C206DB CRC64;
MAVEELQSII KRCQILEEHD FKEEDFGLFQ LAGQRCIEDG YINQLLEIIQ DEKNKTIIKS
MGWNLVGPVV RCLLRGREED KREECFLIFD LLVKLCNPKE LLLGLLELIE EPSGKQISQI
ILLLLQPLQT VIQKLPNNKA YSVGLALSTL WSQLSLLPVP HSEEQIQADD YGLCQCCKAL
IEFTKPFVEE VISDKENKEN AKLKDELLKF CFKGLKCPLL TAQFLEQSED VGNDPFRCFA
SEIIGFLSKI GHPVPQIILN HGRKKRTWDY LEFEEEEDKQ LAESVASLTY LVFVQGIGID
QLPMVLSPSY LLQLNMEHIE VFLQRTEQSI YSKGLELLET SLLRLEDNSL CYQYLEIKSF
LAVPQGLVKV MTLCPIETLR KKGLSMLQLF IDKLDSQGKY TLFRCLLNTS NHSGVEAFVI
QNIKNQIDLS FKKTYNKWFA GAQLISLLDL VLSLPEGAET DLLQNSDRIM ASLNLLRYLV
IKDNEDDNQT GLWTELGKIE NNFLKPLHIG LNMSKAHYEA EIKNSQQNNQ VASMCKGVCS
VTVGGEEIPS MPPEMQLKVL HSALFTFDLI ESVLARVEEL IEIKSKSTSE ENVGIK
