MKLN1_MOUSE
ID MKLN1_MOUSE Reviewed; 735 AA.
AC O89050;
DT 10-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Muskelin;
GN Name=Mkln1;
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, AND SUBCELLULAR LOCATION.
RX PubMed=9724633; DOI=10.1093/emboj/17.17.4964;
RA Adams J.C., Seed B., Lawler J.;
RT "Muskelin, a novel intracellular mediator of cell adhesive and cytoskeletal
RT responses to thrombospondin-1.";
RL EMBO J. 17:4964-4974(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary tumor;
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 FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH RANBP9, DOMAIN, AND
RP MUTAGENESIS OF 182-LYS-HIS-183; 701-ASP--LEU-735 AND THR-723.
RX PubMed=18710924; DOI=10.1083/jcb.200801133;
RA Valiyaveettil M., Bentley A.A., Gursahaney P., Hussien R., Chakravarti R.,
RA Kureishy N., Prag S., Adams J.C.;
RT "Novel role of the muskelin-RanBP9 complex as a nucleocytoplasmic mediator
RT of cell morphology regulation.";
RL J. Cell Biol. 182:727-739(2008).
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, FUNCTION, INTERACTION WITH GABRA1, AND TISSUE
RP SPECIFICITY.
RX PubMed=21482357; DOI=10.1016/j.neuron.2011.03.008;
RA Heisler F.F., Loebrich S., Pechmann Y., Maier N., Zivkovic A.R., Tokito M.,
RA Hausrat T.J., Schweizer M., Baehring R., Holzbaur E.L., Schmitz D.,
RA Kneussel M.;
RT "Muskelin regulates actin filament- and microtubule-based GABA(A) receptor
RT transport in neurons.";
RL Neuron 70:66-81(2011).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 12-167.
RX PubMed=25372678; DOI=10.1107/s139900471401894x;
RA Kim K.H., Hong S.K., Hwang K.Y., Kim E.E.;
RT "Structure of mouse muskelin discoidin domain and biochemical
RT characterization of its self-association.";
RL Acta Crystallogr. D 70:2863-2874(2014).
CC -!- FUNCTION: Component of the CTLH E3 ubiquitin-protein ligase complex
CC that selectively accepts ubiquitin from UBE2H and mediates
CC ubiquitination and subsequent proteasomal degradation of the
CC transcription factor HBP1 (By similarity). Required for internalization
CC of the GABA receptor GABRA1 from the cell membrane via endosomes and
CC subsequent GABRA1 degradation (PubMed:21482357). Acts as a mediator of
CC cell spreading and cytoskeletal responses to the extracellular matrix
CC component THBS1 (PubMed:9724633, PubMed:18710924).
CC {ECO:0000250|UniProtKB:Q9UL63, ECO:0000269|PubMed:18710924,
CC ECO:0000269|PubMed:21482357, ECO:0000269|PubMed:9724633}.
CC -!- SUBUNIT: Homodimer; may form higher oligomers (By similarity).
CC Identified in the CTLH complex that contains GID4, RANBP9 and/or
CC RANBP10, MKLN1, MAEA, RMND5A (or alternatively its paralog RMND5B),
CC GID8, ARMC8, WDR26 and YPEL5. Within this complex, MAEA, RMND5A (or
CC alternatively its paralog RMND5B), GID8, WDR26, and RANBP9 and/or
CC RANBP10 form the catalytic core, while GID4, MKLN1, ARMC8 and YPEL5
CC have ancillary roles (By similarity). Interacts with RANBP9
CC (PubMed:18710924). Part of a complex consisting of RANBP9, MKLN1 and
CC GID8 (By similarity). Interacts with GABRA1 (PubMed:21482357).
CC Interacts with the C-terminal tail of PTGER3 (By similarity).
CC {ECO:0000250|UniProtKB:Q99PV3, ECO:0000250|UniProtKB:Q9UL63,
CC ECO:0000269|PubMed:18710924, ECO:0000269|PubMed:21482357}.
CC -!- INTERACTION:
CC O89050; O89050: Mkln1; NbExp=4; IntAct=EBI-11017656, EBI-11017656;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:9724633}.
CC Cytoplasm, cytosol {ECO:0000269|PubMed:18710924}. Nucleus, nucleoplasm
CC {ECO:0000269|PubMed:18710924}. Cell projection, ruffle
CC {ECO:0000269|PubMed:9724633}. Cytoplasm, cell cortex
CC {ECO:0000269|PubMed:9724633}. Synapse {ECO:0000269|PubMed:21482357}.
CC Postsynapse {ECO:0000269|PubMed:21482357}. Note=Colocalizes with GABRA1
CC at synapses and in postsynaptic regions (PubMed:21482357). Colocalizes
CC with actin fibers in the cell cortex. {ECO:0000269|PubMed:21482357,
CC ECO:0000269|PubMed:9724633}.
CC -!- TISSUE SPECIFICITY: Detected in brain, especially in hippocampus and
CC cerebellum (at protein level). {ECO:0000269|PubMed:21482357}.
CC -!- DOMAIN: The LisH domain contains a nuclear targeting signal
CC (PubMed:18710924). The LisH domain mediates head to tail dimerization
CC (By similarity). {ECO:0000250|UniProtKB:Q99PV3,
CC ECO:0000269|PubMed:18710924}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype. Hippocampus slices from
CC mutant mice show minor differences in the amplitude of miniature
CC inhibitory postsynaptic currents, and somewhat slower decay times.
CC {ECO:0000269|PubMed:21482357}.
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DR EMBL; U72194; AAC63849.1; -; mRNA.
DR EMBL; BC013703; AAH13703.1; -; mRNA.
DR CCDS; CCDS19982.1; -.
DR RefSeq; NP_038819.1; NM_013791.2.
DR PDB; 4PQQ; X-ray; 1.55 A; A=12-167.
DR PDBsum; 4PQQ; -.
DR AlphaFoldDB; O89050; -.
DR SMR; O89050; -.
DR BioGRID; 205222; 8.
DR DIP; DIP-61380N; -.
DR IntAct; O89050; 7.
DR STRING; 10090.ENSMUSP00000026699; -.
DR iPTMnet; O89050; -.
DR PhosphoSitePlus; O89050; -.
DR EPD; O89050; -.
DR MaxQB; O89050; -.
DR PaxDb; O89050; -.
DR PeptideAtlas; O89050; -.
DR PRIDE; O89050; -.
DR ProteomicsDB; 290255; -.
DR Antibodypedia; 18008; 154 antibodies from 22 providers.
DR DNASU; 27418; -.
DR Ensembl; ENSMUST00000026699; ENSMUSP00000026699; ENSMUSG00000025609.
DR GeneID; 27418; -.
DR KEGG; mmu:27418; -.
DR UCSC; uc009bgf.1; mouse.
DR CTD; 4289; -.
DR MGI; MGI:1351638; Mkln1.
DR VEuPathDB; HostDB:ENSMUSG00000025609; -.
DR eggNOG; KOG2437; Eukaryota.
DR GeneTree; ENSGT00390000001702; -.
DR HOGENOM; CLU_004210_1_0_1; -.
DR InParanoid; O89050; -.
DR OMA; DPISENV; -.
DR OrthoDB; 145268at2759; -.
DR PhylomeDB; O89050; -.
DR TreeFam; TF323659; -.
DR BioGRID-ORCS; 27418; 3 hits in 71 CRISPR screens.
DR ChiTaRS; Mkln1; mouse.
DR PRO; PR:O89050; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; O89050; protein.
DR Bgee; ENSMUSG00000025609; Expressed in spermatocyte and 256 other tissues.
DR ExpressionAtlas; O89050; baseline and differential.
DR Genevisible; O89050; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005938; C:cell cortex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR GO; GO:0098794; C:postsynapse; IEA:UniProtKB-SubCell.
DR GO; GO:0001726; C:ruffle; IDA:UniProtKB.
DR GO; GO:0000151; C:ubiquitin ligase complex; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; IMP:UniProtKB.
DR GO; GO:0007160; P:cell-matrix adhesion; IMP:UniProtKB.
DR GO; GO:0008360; P:regulation of cell shape; IMP:UniProtKB.
DR GO; GO:0002090; P:regulation of receptor internalization; ISS:UniProtKB.
DR Gene3D; 2.120.10.80; -; 2.
DR InterPro; IPR006595; CTLH_C.
DR InterPro; IPR011043; Gal_Oxase/kelch_b-propeller.
DR InterPro; IPR008979; Galactose-bd-like_sf.
DR InterPro; IPR015915; Kelch-typ_b-propeller.
DR InterPro; IPR006652; Kelch_1.
DR InterPro; IPR006594; LisH.
DR InterPro; IPR010565; Muskelin_N.
DR Pfam; PF01344; Kelch_1; 1.
DR Pfam; PF06588; Muskelin_N; 1.
DR SMART; SM00667; LisH; 1.
DR SUPFAM; SSF117281; SSF117281; 1.
DR SUPFAM; SSF49785; SSF49785; 1.
DR SUPFAM; SSF50965; SSF50965; 1.
DR PROSITE; PS50897; CTLH; 1.
DR PROSITE; PS50896; LISH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cell projection; Cytoplasm; Kelch repeat;
KW Nucleus; Reference proteome; Repeat; Synapse.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q9UL63"
FT CHAIN 2..735
FT /note="Muskelin"
FT /id="PRO_0000119139"
FT DOMAIN 172..204
FT /note="LisH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00126"
FT DOMAIN 206..258
FT /note="CTLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00058"
FT REPEAT 284..330
FT /note="Kelch 1"
FT REPEAT 339..391
FT /note="Kelch 2"
FT REPEAT 400..458
FT /note="Kelch 3"
FT REPEAT 469..515
FT /note="Kelch 4"
FT REPEAT 526..578
FT /note="Kelch 5"
FT REPEAT 597..651
FT /note="Kelch 6"
FT REGION 701..735
FT /note="Important for location in the cytosol"
FT /evidence="ECO:0000269|PubMed:18710924"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q9UL63"
FT MUTAGEN 182..183
FT /note="KH->AA: Abolishes targeting to the nucleus."
FT /evidence="ECO:0000269|PubMed:18710924"
FT MUTAGEN 701..735
FT /note="Missing: Strongly increased location in the
FT nucleus."
FT /evidence="ECO:0000269|PubMed:18710924"
FT MUTAGEN 723
FT /note="T->A: No effect on predominant location in the
FT cytosol."
FT /evidence="ECO:0000269|PubMed:18710924"
FT MUTAGEN 723
FT /note="T->D: Strongly increased location in the nucleus."
FT /evidence="ECO:0000269|PubMed:18710924"
FT STRAND 18..24
FT /evidence="ECO:0007829|PDB:4PQQ"
FT HELIX 32..36
FT /evidence="ECO:0007829|PDB:4PQQ"
FT STRAND 45..48
FT /evidence="ECO:0007829|PDB:4PQQ"
FT STRAND 52..54
FT /evidence="ECO:0007829|PDB:4PQQ"
FT STRAND 58..73
FT /evidence="ECO:0007829|PDB:4PQQ"
FT STRAND 83..94
FT /evidence="ECO:0007829|PDB:4PQQ"
FT STRAND 97..104
FT /evidence="ECO:0007829|PDB:4PQQ"
FT STRAND 108..110
FT /evidence="ECO:0007829|PDB:4PQQ"
FT STRAND 113..116
FT /evidence="ECO:0007829|PDB:4PQQ"
FT STRAND 128..141
FT /evidence="ECO:0007829|PDB:4PQQ"
FT STRAND 150..155
FT /evidence="ECO:0007829|PDB:4PQQ"
FT HELIX 158..161
FT /evidence="ECO:0007829|PDB:4PQQ"
FT HELIX 162..164
FT /evidence="ECO:0007829|PDB:4PQQ"
SQ SEQUENCE 735 AA; 84878 MW; 7B0C8D2CB8C242AA CRC64;
MAAGGAVAVA PECRLLPYAL HKWSSFSSTY LPENILVDKP NDQSSRWSSE SNYPPQYLIL
KLERPAIVQN ITFGKYEKTH VCNLKKFKVF GGMNEENMTE LLSSGLKNDY NKETFTLKHK
IDEQMFPCRF IKIVPLLSWG PSFNFSIWYV ELSGIDDPDI VQPCLNWYSK YREQEAIRLC
LKHFRQHNYT EAFESLQKKT KIALEHPMLT DMHDKLVLKG DFDACEELIE KAVNDGLFNQ
YISQQEYKPR WSQIIPKSTK GDGEDNRPGM RGGHQMVIDV QTETVYLFGG WDGTQDLADF
WAYSVKENQW TCISRDTEKE NGPSARSCHK MCIDIQRRQI YTLGRYLDSS VRNSKSLKSD
FYRYDIDTNT WMLLSEDTAA DGGPKLVFDH QMCMDSEKHM IYTFGGRILT CNGSVDDSRA
SEPQFSGLFA FNCQCQTWKL LREDSCNAGP EDIQSRIGHC MLFHSKNRCL YVFGGQRSKT
YLNDFFSYDV DSDHVDIISD GTKKDSGMVP MTGFTQRATI DPELNEIHVL SGLSKDKEKR
EENVRNSFWI YDIVRNSWSC VYKNDQATKD NLSKSLQEEE PCPRFAHQLV YDELHKVHYL
FGGNPGKSCS PKMRLDDFWS LKLCRPSKDY LLRHCKYLIR KHRFEEKAQM DPLSALKYLQ
NDLYITVDHS DPEETKEFQL LASALFKSGS DFTALGFSDV DHTYAQRTQL FDTLVNFFPD
SMTPPKGNLV DLITL
