FBX38_MOUSE
ID FBX38_MOUSE Reviewed; 1194 AA.
AC Q8BMI0; Q8BTQ4; Q8C0H4;
DT 31-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=F-box only protein 38 {ECO:0000305};
DE AltName: Full=Modulator of KLF7 activity {ECO:0000303|PubMed:14729953};
DE Short=MoKA {ECO:0000303|PubMed:14729953};
GN Name=Fbxo38 {ECO:0000312|MGI:MGI:2444639};
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], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, DEVELOPMENTAL STAGE, AND INTERACTION WITH KLF7.
RC STRAIN=FVB/N;
RX PubMed=14729953; DOI=10.1128/mcb.24.3.1058-1069.2004;
RA Smaldone S., Laub F., Else C., Dragomir C., Ramirez F.;
RT "Identification of MoKA, a novel F-box protein that modulates Krueppel-like
RT transcription factor 7 activity.";
RL Mol. Cell. Biol. 24:1058-1069(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Forelimb, Testis, and Thymus;
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].
RC STRAIN=C57BL/6J; 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 [4]
RP FUNCTION, SUBCELLULAR LOCATION, NUCLEAR LOCALIZATION SIGNAL, NUCLEAR EXPORT
RP SIGNALS, AND MUTAGENESIS OF 194-LEU--LEU-196; 264-LEU--LEU-275 AND
RP 902-LYS--LYS-904.
RX PubMed=16990251; DOI=10.1093/nar/gkl659;
RA Smaldone S., Ramirez F.;
RT "Multiple pathways regulate intracellular shuttling of MoKA, a co-activator
RT of transcription factor KLF7.";
RL Nucleic Acids Res. 34:5060-5068(2006).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-592; SER-599; SER-601;
RP SER-607 AND SER-746, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Brain, Kidney, Liver, Lung, 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 [6]
RP FUNCTION, DISRUPTION PHENOTYPE, AND INDUCTION.
RX PubMed=30487606; DOI=10.1038/s41586-018-0756-0;
RA Meng X., Liu X., Guo X., Jiang S., Chen T., Hu Z., Liu H., Bai Y., Xue M.,
RA Hu R., Sun S.C., Liu X., Zhou P., Huang X., Wei L., Yang W., Xu C.;
RT "FBXO38 mediates PD-1 ubiquitination and regulates anti-tumour immunity of
RT T cells.";
RL Nature 564:130-135(2018).
CC -!- FUNCTION: Substrate recognition component of a SCF (SKP1-CUL1-F-box
CC protein) E3 ubiquitin-protein ligase complex which mediates the
CC ubiquitination and subsequent proteasomal degradation of PDCD1/PD-1,
CC thereby regulating T-cells-mediated immunity (PubMed:30487606).
CC Required for anti-tumor activity of T-cells by promoting the
CC degradation of PDCD1/PD-1; the PDCD1-mediated inhibitory pathway being
CC exploited by tumors to attenuate anti-tumor immunity and facilitate
CC tumor survival (PubMed:30487606). May indirectly stimulate the activity
CC of transcription factor KLF7, a regulator of neuronal differentiation,
CC without promoting KLF7 ubiquitination (PubMed:14729953,
CC PubMed:16990251). {ECO:0000269|PubMed:14729953,
CC ECO:0000269|PubMed:16990251, ECO:0000269|PubMed:30487606}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:Q6PIJ6}.
CC -!- SUBUNIT: Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase
CC complex SCF(FBXO38) composed of CUL1, SKP1, RBX1 and FBXO38 (By
CC similarity). Interacts with KLF7 (PubMed:14729953). Interacts with
CC PDCD1/PD-1 (By similarity). {ECO:0000250|UniProtKB:Q6PIJ6,
CC ECO:0000269|PubMed:14729953}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:14729953,
CC ECO:0000269|PubMed:16990251}. Nucleus {ECO:0000269|PubMed:14729953,
CC ECO:0000269|PubMed:16990251}. Note=Accumulates predominantly in the
CC cytosol (PubMed:16990251). Exported from the nucleus in a XPO1/CRM1-
CC dependent manner (PubMed:16990251). {ECO:0000269|PubMed:16990251}.
CC -!- TISSUE SPECIFICITY: Expressed at high levels in embryo (developing
CC brain, spinal chord, branchial arms and limbs) (PubMed:14729953).
CC Widely expressed at low levels in adult tissues, with highest
CC expression in testis. Expressed in postmeiotic spermatids
CC (PubMed:14729953). {ECO:0000269|PubMed:14729953}.
CC -!- DEVELOPMENTAL STAGE: In embryo expressed at 11 dpc, 15 dpc and 17 dpc.
CC {ECO:0000269|PubMed:14729953}.
CC -!- INDUCTION: Up-regulated by IL2 (PubMed:30487606). Down-regulated in
CC tumor-infiltrating T-cells (PubMed:30487606).
CC {ECO:0000269|PubMed:30487606}.
CC -!- DISRUPTION PHENOTYPE: Conditional deletion in T-cells does not affect
CC the development, peripheral homeostasis and population of memory T-
CC cells, but leads to faster tumor progression (PubMed:30487606). Faster
CC tumor progression is caused by higher levels of Pdcd1/PD-1 in tumor-
CC infiltrating T-cells (PubMed:30487606). {ECO:0000269|PubMed:30487606}.
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DR EMBL; AY267463; AAP31028.1; -; mRNA.
DR EMBL; AK089046; BAC40718.1; -; mRNA.
DR EMBL; AK031096; BAC27250.1; -; mRNA.
DR EMBL; AK031347; BAC27358.1; -; mRNA.
DR EMBL; BC056348; AAH56348.1; -; mRNA.
DR CCDS; CCDS37841.1; -.
DR RefSeq; NP_598897.2; NM_134136.3.
DR AlphaFoldDB; Q8BMI0; -.
DR STRING; 10090.ENSMUSP00000047541; -.
DR GlyConnect; 2309; 1 N-Linked glycan (1 site).
DR GlyGen; Q8BMI0; 1 site, 1 N-linked glycan (1 site).
DR iPTMnet; Q8BMI0; -.
DR PhosphoSitePlus; Q8BMI0; -.
DR EPD; Q8BMI0; -.
DR jPOST; Q8BMI0; -.
DR MaxQB; Q8BMI0; -.
DR PaxDb; Q8BMI0; -.
DR PeptideAtlas; Q8BMI0; -.
DR PRIDE; Q8BMI0; -.
DR ProteomicsDB; 271675; -.
DR Antibodypedia; 27733; 73 antibodies from 15 providers.
DR Ensembl; ENSMUST00000048688; ENSMUSP00000047541; ENSMUSG00000042211.
DR GeneID; 107035; -.
DR KEGG; mmu:107035; -.
DR UCSC; uc012bdv.1; mouse.
DR CTD; 81545; -.
DR MGI; MGI:2444639; Fbxo38.
DR VEuPathDB; HostDB:ENSMUSG00000042211; -.
DR eggNOG; ENOG502QSUC; Eukaryota.
DR GeneTree; ENSGT00390000013163; -.
DR HOGENOM; CLU_010774_0_0_1; -.
DR InParanoid; Q8BMI0; -.
DR OMA; CKEEYPR; -.
DR OrthoDB; 63661at2759; -.
DR PhylomeDB; Q8BMI0; -.
DR TreeFam; TF331125; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 107035; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Fbxo38; mouse.
DR PRO; PR:Q8BMI0; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; Q8BMI0; protein.
DR Bgee; ENSMUSG00000042211; Expressed in saccule of membranous labyrinth and 253 other tissues.
DR ExpressionAtlas; Q8BMI0; baseline and differential.
DR Genevisible; Q8BMI0; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IDA:MGI.
DR GO; GO:0002842; P:positive regulation of T cell mediated immune response to tumor cell; ISS:UniProtKB.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR036047; F-box-like_dom_sf.
DR InterPro; IPR001810; F-box_dom.
DR InterPro; IPR042354; FBX38.
DR InterPro; IPR032675; LRR_dom_sf.
DR PANTHER; PTHR14753; PTHR14753; 1.
DR Pfam; PF00646; F-box; 1.
DR SUPFAM; SSF81383; SSF81383; 1.
PE 1: Evidence at protein level;
KW Adaptive immunity; Cytoplasm; Immunity; Nucleus; Phosphoprotein;
KW Reference proteome; Ubl conjugation pathway.
FT CHAIN 1..1194
FT /note="F-box only protein 38"
FT /id="PRO_0000119934"
FT DOMAIN 30..75
FT /note="F-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00080"
FT REGION 59..119
FT /note="Interaction with KLF7"
FT /evidence="ECO:0000269|PubMed:14729953"
FT REGION 487..529
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 577..776
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 793..879
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 896..915
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 194..201
FT /note="Nuclear export signal 1"
FT /evidence="ECO:0000269|PubMed:16990251"
FT MOTIF 307..316
FT /note="Nuclear export signal 2"
FT /evidence="ECO:0000269|PubMed:16990251"
FT MOTIF 451..460
FT /note="Nuclear export signal 3"
FT /evidence="ECO:0000269|PubMed:16990251"
FT MOTIF 902..905
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:16990251"
FT COMPBIAS 487..510
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 511..529
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 619..634
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 685..702
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 703..749
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 818..838
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 592
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 599
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 601
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 607
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 742
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6PIJ6"
FT MOD_RES 746
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MUTAGEN 194..196
FT /note="LHL->AHA: Decreased cytoplasmic localization."
FT /evidence="ECO:0000269|PubMed:16990251"
FT MUTAGEN 264..275
FT /note="LEHLEMVRVPFL->AEHAEMVRVPFA: Decreased cytoplasmic
FT localization."
FT /evidence="ECO:0000269|PubMed:16990251"
FT MUTAGEN 902..904
FT /note="KRK->RRR: Impaired nuclear localization."
FT /evidence="ECO:0000269|PubMed:16990251"
FT CONFLICT 659
FT /note="T -> M (in Ref. 2; BAC40718)"
FT /evidence="ECO:0000305"
FT CONFLICT 712
FT /note="Missing (in Ref. 1; AAP31028 and 2; BAC40718)"
FT /evidence="ECO:0000305"
FT CONFLICT 715
FT /note="A -> T (in Ref. 2; BAC40718)"
FT /evidence="ECO:0000305"
FT CONFLICT 1163
FT /note="M -> K (in Ref. 2; BAC27358)"
FT /evidence="ECO:0000305"
FT CONFLICT 1185
FT /note="N -> H (in Ref. 2; BAC27358)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1194 AA; 133928 MW; 40F973C9638824A8 CRC64;
MGPRKKSAKV CVMDSEVAEE MTADEEKDYM NQLSHEVLCH IFRYLPLQDI MCMECLSRKL
KEAVTLYLRV VRVVDLCAGR WWEYMPSGFT DSSFLTLLKK MPDVEQLYGL HPRYLERRRV
RGQEAFSIPG VLEALQACPN LVGVETSHLE LVESIWTYMP HVHILGKFRN RNGAFPIPPE
NKLKIPIGAK IQTLHLVGVN VPEIPCIPML RHLYMKWVRL TKPQPFKDFL CISLRTFVMR
NCAGPTNSLK YVPLVTGLAS ARNLEHLEMV RVPFLGGLIQ HVVEDSWRSG GFRNLHTIVL
GACKNALEVD LGYLIITAAR RLHEVRIQPS LTKDGVFSAL KMAELEFPQF ETLHLGYVDE
FLLQSRMANA DLVKYGLADV VENPGIITDI GMKAVNEVFS CIKYLAIYNC PHLHNPYNWI
SDHSRWMRLV DINLVRCHAL KLDSFGQFVE LLPSLEFISL DQMFREPPKG CARVGLSAGT
GIGVSSALVS NQNSNNDNDN NAPNNNANLH DNNHHHPDDS DDDNDFRPDL QAGEAQFAAD
ALNEMEDMVQ EDGELVAESG NGMPAHNREV LPVDADEEQA GPSGLQRVVK PTPIADHDSE
SDDEEDSLEL QEVWAPKNGT RRYSEREEKT GDSGQSRETA VSGKGKTPLR KRCNNSHQTG
QAKPFPLEES SCEKGCQVTS EQIKADMKAA RDVSEKKKSK DVYPSCSSSS SSTAASTAGN
ASSPSTASQS PDFARTVTSS GSSEPSPPEV DVSRQCVCSP GGSEDSEAME EGDAESSVCP
RCCCLRPQES QRRTGRCSDE ERPSTSRACV VNGADGTRSA FSFRTLPQGG SSGPAHDERT
NGSGCGATGE DRRGSSQPES CDVQSNEDYP RRPLTRARSR LSHVPLISES EVAKTKPCHA
MKRKRTADKS TSTSDPVIED DHVQVLVLKS KNLVGVTMTN CGITDLVLKD CPKMMFIHAT
RCRVLKHLKV ENAPIVNRFD YAQCKKLNMD QVLDQILRMP PERNRIIYLR PMQQVDTLTL
EQKLFSGPYP YHICIIHEFS NPPNVRNKVR IRNWMDTIAN INQELIKYEF FLEATRTEED
LKKYPKYPWG REIYTLEGVV DGAPYSMISD FPWLRSLRTA EPNSFARYDF EDDEESTIYA
PRRKGQLSAD ICMETIGEEI SEMRQMKRGI FQRVVAIFIH YCDVNGEPVE DDYI
