LPXN_MOUSE
ID LPXN_MOUSE Reviewed; 386 AA.
AC Q99N69;
DT 10-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 2.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Leupaxin;
GN Name=Lpxn;
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].
RC TISSUE=Spleen;
RA Ishizuka H., Amano N., Watanabe N., Mashima K.;
RT "The noncatalytic domain of protein-tyrosine phosphatase-PEST forms a
RT complex with leupaxin that is a novel LIM domain protein.";
RL Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, INTERACTION
RP WITH PTK2/FAK, AND DOMAIN LIM-3.
RC TISSUE=Spleen;
RX PubMed=19917054; DOI=10.1111/j.1349-7006.2009.01398.x;
RA Tanaka T., Moriwaki K., Murata S., Miyasaka M.;
RT "LIM domain-containing adaptor, leupaxin, localizes in focal adhesion and
RT suppresses the integrin-induced tyrosine phosphorylation of paxillin.";
RL Cancer Sci. 101:363-368(2010).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH
RP PTK2/FAK; PTPN12 AND PTK2B/PYK2, AND PHOSPHORYLATION.
RX PubMed=12674328; DOI=10.1359/jbmr.2003.18.4.669;
RA Gupta A., Lee B.S., Khadeer M.A., Tang Z., Chellaiah M., Abu-Amer Y.,
RA Goldknopf J., Hruska K.A.;
RT "Leupaxin is a critical adaptor protein in the adhesion zone of the
RT osteoclast.";
RL J. Bone Miner. Res. 18:669-685(2003).
RN [4]
RP INTERACTION WITH PTPN22 AND PTPN12.
RX PubMed=15786712; DOI=10.1007/s11010-005-2149-6;
RA Watanabe N., Amano N., Ishizuka H., Mashima K.;
RT "Leupaxin binds to PEST domain tyrosine phosphatase PEP.";
RL Mol. Cell. Biochem. 269:13-17(2005).
RN [5]
RP FUNCTION, PHOSPHORYLATION AT TYR-72 BY LYN, AND INTERACTION WITH LYN.
RX PubMed=17640867; DOI=10.1074/jbc.m704625200;
RA Chew V., Lam K.P.;
RT "Leupaxin negatively regulates B cell receptor signaling.";
RL J. Biol. Chem. 282:27181-27191(2007).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-22; TYR-62 AND TYR-72, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Mast cell;
RX PubMed=17947660; DOI=10.4049/jimmunol.179.9.5864;
RA Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,
RA Kawakami T., Salomon A.R.;
RT "Quantitative time-resolved phosphoproteomic analysis of mast cell
RT signaling.";
RL J. Immunol. 179:5864-5876(2007).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=18497331; DOI=10.1161/circresaha.107.170357;
RA Sundberg-Smith L.J., DiMichele L.A., Sayers R.L., Mack C.P., Taylor J.M.;
RT "The LIM protein leupaxin is enriched in smooth muscle and functions as an
RT serum response factor cofactor to induce smooth muscle cell gene
RT transcription.";
RL Circ. Res. 102:1502-1511(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-54, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung, and Spleen;
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).
CC -!- FUNCTION: Transcriptional coactivator for androgen receptor (AR) and
CC serum response factor (SRF). Contributes to the regulation of cell
CC adhesion, spreading and cell migration and acts as a negative regulator
CC in integrin-mediated cell adhesion events. Suppresses the integrin-
CC induced tyrosine phosphorylation of paxillin (PXN). May play a critical
CC role as an adapter protein in the formation of the adhesion zone in
CC osteoclasts. Negatively regulates B-cell antigen receptor (BCR)
CC signaling. {ECO:0000269|PubMed:12674328, ECO:0000269|PubMed:17640867,
CC ECO:0000269|PubMed:18497331, ECO:0000269|PubMed:19917054}.
CC -!- SUBUNIT: Interacts with unphosphorylated ITGA4. Interacts with AR and
CC SRF (By similarity). Interacts with PTK2B/PYK2, PTPN22 and PTPN12.
CC Interacts (via LD motif 3) with LYN and the interaction is induced upon
CC B-cell antigen receptor (BCR) activation. Interacts (via LD motif 3)
CC with PTK2/FAK. {ECO:0000250, ECO:0000269|PubMed:12674328,
CC ECO:0000269|PubMed:15786712, ECO:0000269|PubMed:17640867,
CC ECO:0000269|PubMed:19917054}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell junction, focal
CC adhesion. Nucleus. Cytoplasm, perinuclear region. Cell projection,
CC podosome. Cell membrane. Note=Shuttles between the cytoplasm and
CC nucleus. Recruited to the cell membrane following B-cell antigen
CC receptor (BCR) cross-linking in B-cells. Enhanced focal adhesion kinase
CC activity (PTK2/FAK) attenuates its nuclear accumulation and limits its
CC ability to enhance serum response factor (SRF)-dependent gene
CC transcription. Targeting to focal adhesions is essential for its
CC tyrosine phosphorylation in response to bombesin (By similarity).
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in osteoclasts (at protein level). Highly
CC expressed in vascular smooth muscle. {ECO:0000269|PubMed:12674328,
CC ECO:0000269|PubMed:18497331}.
CC -!- DOMAIN: The LIM domain 3 is critical for focal adhesion targeting and
CC the suppression of paxillin (PXN) tyrosine phosphorylation. The LIM
CC domain 3 alone or both LIM domains 3 and 4 can mediate interaction with
CC AR. {ECO:0000269|PubMed:19917054}.
CC -!- PTM: Phosphorylated on tyrosine residues. Phosphorylation on Tyr-72 is
CC important for its inhibitory function. Bombesin stimulates
CC phosphorylation on Tyr-22, Tyr-62 and Tyr-72 (By similarity).
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the paxillin family. {ECO:0000305}.
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DR EMBL; AB053936; BAB40667.2; -; mRNA.
DR EMBL; AB071194; BAC22615.1; -; mRNA.
DR CCDS; CCDS29638.1; -.
DR RefSeq; NP_598913.1; NM_134152.3.
DR AlphaFoldDB; Q99N69; -.
DR SMR; Q99N69; -.
DR BioGRID; 223241; 52.
DR IntAct; Q99N69; 2.
DR STRING; 10090.ENSMUSP00000025601; -.
DR iPTMnet; Q99N69; -.
DR PhosphoSitePlus; Q99N69; -.
DR EPD; Q99N69; -.
DR jPOST; Q99N69; -.
DR MaxQB; Q99N69; -.
DR PaxDb; Q99N69; -.
DR PeptideAtlas; Q99N69; -.
DR PRIDE; Q99N69; -.
DR ProteomicsDB; 252662; -.
DR Antibodypedia; 27661; 184 antibodies from 25 providers.
DR DNASU; 107321; -.
DR Ensembl; ENSMUST00000025601; ENSMUSP00000025601; ENSMUSG00000024696.
DR GeneID; 107321; -.
DR KEGG; mmu:107321; -.
DR UCSC; uc008guq.1; mouse.
DR CTD; 9404; -.
DR MGI; MGI:2147677; Lpxn.
DR VEuPathDB; HostDB:ENSMUSG00000024696; -.
DR eggNOG; KOG1703; Eukaryota.
DR GeneTree; ENSGT00940000160259; -.
DR HOGENOM; CLU_001357_1_1_1; -.
DR InParanoid; Q99N69; -.
DR OMA; THCKKEI; -.
DR OrthoDB; 1593918at2759; -.
DR PhylomeDB; Q99N69; -.
DR TreeFam; TF314113; -.
DR BioGRID-ORCS; 107321; 0 hits in 72 CRISPR screens.
DR ChiTaRS; Lpxn; mouse.
DR PRO; PR:Q99N69; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q99N69; protein.
DR Bgee; ENSMUSG00000024696; Expressed in mesenteric lymph node and 82 other tissues.
DR ExpressionAtlas; Q99N69; baseline and differential.
DR Genevisible; Q99N69; MM.
DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005925; C:focal adhesion; IDA:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0002102; C:podosome; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003712; F:transcription coregulator activity; IDA:UniProtKB.
DR GO; GO:0043542; P:endothelial cell migration; IBA:GO_Central.
DR GO; GO:0050859; P:negative regulation of B cell receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0007162; P:negative regulation of cell adhesion; ISO:MGI.
DR GO; GO:0033628; P:regulation of cell adhesion mediated by integrin; IMP:UniProtKB.
DR GO; GO:0034446; P:substrate adhesion-dependent cell spreading; IBA:GO_Central.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IBA:GO_Central.
DR InterPro; IPR017305; Tgfb1i1/Leupaxin/TGFB1I1.
DR InterPro; IPR001781; Znf_LIM.
DR Pfam; PF00412; LIM; 4.
DR PIRSF; PIRSF037881; Leupaxin; 1.
DR SMART; SM00132; LIM; 4.
DR PROSITE; PS00478; LIM_DOMAIN_1; 4.
DR PROSITE; PS50023; LIM_DOMAIN_2; 4.
PE 1: Evidence at protein level;
KW Acetylation; Activator; Cell adhesion; Cell junction; Cell membrane;
KW Cell projection; Cytoplasm; LIM domain; Membrane; Metal-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; Transcription;
KW Transcription regulation; Zinc.
FT CHAIN 1..386
FT /note="Leupaxin"
FT /id="PRO_0000075837"
FT DOMAIN 150..208
FT /note="LIM zinc-binding 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT DOMAIN 209..267
FT /note="LIM zinc-binding 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT DOMAIN 268..326
FT /note="LIM zinc-binding 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT DOMAIN 327..386
FT /note="LIM zinc-binding 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT REGION 19..52
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 3..15
FT /note="LD motif 1"
FT MOTIF 70..82
FT /note="LD motif 2"
FT MOTIF 92..103
FT /note="LD motif 3"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:O60711"
FT MOD_RES 19
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O60711"
FT MOD_RES 22
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:17947660"
FT MOD_RES 54
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319"
FT MOD_RES 62
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:17947660"
FT MOD_RES 72
FT /note="Phosphotyrosine; by LYN"
FT /evidence="ECO:0000269|PubMed:17640867,
FT ECO:0007744|PubMed:17947660"
FT MOD_RES 81
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O60711"
SQ SEQUENCE 386 AA; 43478 MW; AA7EB76AEF5983C7 CRC64;
MEELDALLEE LERCTFQDSE EYSNPVSCHL DQQSTEESKI PQTPKTLSSQ GNTSPLKVQL
VYATNIQEPN VYSEVQEPKE SVLPPKTSAA AQLDELMAHL SEMQAKVSVK ADTSRKPLPD
QQDHKASLDS MLGDLEQELQ DLGIATVPKG YCASCQKPIA GKVIHALGQS WHPEHFVCTH
CKEELGSSPF FERSGLAYCS KDYHRLFSPR CAYCAAPITD KVLTAMNKTW HPEHFFCSHC
GEVFGAEGFH EKDKKPYCRK DFLAMFSPKC GGCNRPVLEN YLSAMNTVWH PECFVCGDCF
SSFSSGSFFE LDGRPFCELH YHHRRGTLCH DCGQPITGRC ISAMGHKFHP EHFVCAFCLT
QLPKGIFKEQ NNKTYCEKCF TKLFSQ
