MKLN1_RAT
ID MKLN1_RAT Reviewed; 735 AA.
AC Q99PV3;
DT 10-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=Muskelin;
GN Name=Mkln1; Synonyms=Msk;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH PTGER3, AND SUBCELLULAR
RP LOCATION.
RX PubMed=11006128; DOI=10.1006/bbrc.2000.3467;
RA Hasegawa H., Katoh H., Fujita H., Mori K., Negishi M.;
RT "Receptor isoform-specific interaction of prostaglandin EP3 receptor with
RT muskelin.";
RL Biochem. Biophys. Res. Commun. 276:350-354(2000).
RN [2]
RP INTERACTION WITH GABRA1.
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 [3] {ECO:0007744|PDB:4OYU}
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 12-205, FUNCTION, SUBUNIT,
RP DOMAIN, SUBCELLULAR LOCATION, AND MUTAGENESIS OF TYR-53; PHE-143; ASN-144;
RP CYS-180; PHE-184; ARG-185 AND LEU-196.
RX PubMed=25579817; DOI=10.1016/j.str.2014.11.016;
RA Delto C.F., Heisler F.F., Kuper J., Sander B., Kneussel M., Schindelin H.;
RT "The LisH motif of muskelin is crucial for oligomerization and governs
RT intracellular localization.";
RL Structure 23:364-373(2015).
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:25579817). Acts as a mediator of
CC cell spreading and cytoskeletal responses to the extracellular matrix
CC component THBS1 (By similarity). {ECO:0000250|UniProtKB:O89050,
CC ECO:0000250|UniProtKB:Q9UL63, ECO:0000269|PubMed:25579817}.
CC -!- SUBUNIT: Homodimer; may form higher oligomers (PubMed:25579817).
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 (By
CC similarity). Part of a complex consisting of RANBP9, MKLN1 and GID8 (By
CC similarity). Interacts with GABRA1 (PubMed:21482357). Interacts with
CC the C-terminal tail of PTGER3 (PubMed:11006128).
CC {ECO:0000250|UniProtKB:O89050, ECO:0000250|UniProtKB:Q9UL63,
CC ECO:0000269|PubMed:11006128, ECO:0000269|PubMed:21482357,
CC ECO:0000269|PubMed:25579817}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11006128,
CC ECO:0000269|PubMed:25579817}. Cell projection, ruffle
CC {ECO:0000250|UniProtKB:O89050}. Cytoplasm, cell cortex
CC {ECO:0000250|UniProtKB:O89050}. Synapse {ECO:0000250|UniProtKB:O89050}.
CC Postsynapse {ECO:0000250|UniProtKB:O89050}. Note=Colocalizes with
CC GABRA1 at synapses and in postsynaptic regions. Colocalizes with actin
CC fibers in the cell cortex. {ECO:0000250|UniProtKB:O89050}.
CC -!- DOMAIN: The LisH mediates head to tail dimerization.
CC {ECO:0000269|PubMed:25579817}.
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DR EMBL; AB046442; BAB21439.1; -; mRNA.
DR RefSeq; NP_112649.1; NM_031359.1.
DR PDB; 4OYU; X-ray; 1.80 A; A/B=12-205.
DR PDBsum; 4OYU; -.
DR AlphaFoldDB; Q99PV3; -.
DR SMR; Q99PV3; -.
DR STRING; 10116.ENSRNOP00000016633; -.
DR PaxDb; Q99PV3; -.
DR PRIDE; Q99PV3; -.
DR Ensembl; ENSRNOT00000081707; ENSRNOP00000075084; ENSRNOG00000054514.
DR GeneID; 83536; -.
DR KEGG; rno:83536; -.
DR UCSC; RGD:620076; rat.
DR CTD; 4289; -.
DR RGD; 620076; Mkln1.
DR eggNOG; KOG2437; Eukaryota.
DR GeneTree; ENSGT00390000001702; -.
DR InParanoid; Q99PV3; -.
DR OrthoDB; 145268at2759; -.
DR PhylomeDB; Q99PV3; -.
DR TreeFam; TF323659; -.
DR PRO; PR:Q99PV3; -.
DR Proteomes; UP000002494; Chromosome 4.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005938; C:cell cortex; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:RGD.
DR GO; GO:0098794; C:postsynapse; IEA:UniProtKB-SubCell.
DR GO; GO:0001726; C:ruffle; ISS:UniProtKB.
DR GO; GO:0000151; C:ubiquitin ligase complex; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; ISS:UniProtKB.
DR GO; GO:0007160; P:cell-matrix adhesion; ISS:UniProtKB.
DR GO; GO:0008360; P:regulation of cell shape; ISS:UniProtKB.
DR GO; GO:0002090; P:regulation of receptor internalization; IMP: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 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_0000119140"
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 MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q9UL63"
FT MUTAGEN 53
FT /note="Y->A: Reduced head to tail dimerization."
FT /evidence="ECO:0000269|PubMed:25579817"
FT MUTAGEN 143
FT /note="F->A: Strongly reduced head to tail dimerization."
FT /evidence="ECO:0000269|PubMed:25579817"
FT MUTAGEN 144
FT /note="N->R: Loss of head to tail dimerization. Causes loss
FT of location in the cytosol and accumulation in the nucleus.
FT No effect on GABA receptor internalization."
FT /evidence="ECO:0000269|PubMed:25579817"
FT MUTAGEN 180
FT /note="C->S: Reduced head to tail dimerization."
FT /evidence="ECO:0000269|PubMed:25579817"
FT MUTAGEN 184
FT /note="F->A: Reduced head to tail dimerization."
FT /evidence="ECO:0000269|PubMed:25579817"
FT MUTAGEN 184
FT /note="F->E: Strongly reduced head to tail dimerization and
FT strongly reduced GABA receptor internalization; when
FT associated with Q-196. Causes loss of location in the
FT cytosol and accumulation in the nucleus; when associated
FT with Q-196."
FT /evidence="ECO:0000269|PubMed:25579817"
FT MUTAGEN 185
FT /note="R->A: Reduced head to tail dimerization."
FT /evidence="ECO:0000269|PubMed:25579817"
FT MUTAGEN 196
FT /note="L->Q: Strongly reduced head to tail dimerization and
FT strongly reduced GABA receptor internalization; when
FT associated with E-184. Causes loss of location in the
FT cytosol and accumulation in the nucleus; when associated
FT with E-184."
FT /evidence="ECO:0000269|PubMed:25579817"
FT STRAND 18..24
FT /evidence="ECO:0007829|PDB:4OYU"
FT HELIX 32..36
FT /evidence="ECO:0007829|PDB:4OYU"
FT STRAND 46..48
FT /evidence="ECO:0007829|PDB:4OYU"
FT STRAND 52..54
FT /evidence="ECO:0007829|PDB:4OYU"
FT STRAND 58..74
FT /evidence="ECO:0007829|PDB:4OYU"
FT STRAND 83..97
FT /evidence="ECO:0007829|PDB:4OYU"
FT STRAND 99..104
FT /evidence="ECO:0007829|PDB:4OYU"
FT STRAND 108..110
FT /evidence="ECO:0007829|PDB:4OYU"
FT STRAND 113..116
FT /evidence="ECO:0007829|PDB:4OYU"
FT STRAND 128..140
FT /evidence="ECO:0007829|PDB:4OYU"
FT STRAND 149..155
FT /evidence="ECO:0007829|PDB:4OYU"
FT HELIX 158..186
FT /evidence="ECO:0007829|PDB:4OYU"
SQ SEQUENCE 735 AA; 84834 MW; 79BD0BBF74419E76 CRC64;
MAAGGAVAAA 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 VYKNDQAAKE NLSKSLQEEE PCPRFAHQLV YDELHKVHYL
FGGNPGKSCS PKMRLDDFWS LKLCRPSKDY LLRHCKYLIR KHRFEEKAQM DPLSALKYLQ
NDLYITVDHS DPEETKEFQL LASALFKSGS DFTALGFSDV DHTYAQRTQL FDTLVNFFPD
SMTPPKGNLV DLITL
