MLIP_MOUSE
ID MLIP_MOUSE Reviewed; 269 AA.
AC Q5FW52; Q9D6X9;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2005, sequence version 1.
DT 03-AUG-2022, entry version 107.
DE RecName: Full=Muscular LMNA-interacting protein {ECO:0000312|MGI:MGI:1916892};
DE AltName: Full=Cardiac Isl1-interacting protein {ECO:0000303|PubMed:22343712};
DE Short=CIP {ECO:0000303|PubMed:22343712};
DE AltName: Full=Muscular-enriched A-type laminin-interacting protein;
GN Name=Mlip {ECO:0000312|MGI:MGI:1916892};
GN Synonyms=Cip {ECO:0000303|PubMed:22343712};
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 [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Tongue;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Heart;
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-85 AND SER-181, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Heart;
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 [4]
RP INTERACTION WITH LMNA, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=21498514; DOI=10.1074/jbc.m110.165548;
RA Ahmady E., Deeke S.A., Rabaa S., Kouri L., Kenney L., Stewart A.F.,
RA Burgon P.G.;
RT "Identification of a novel muscle enriched A-type Lamin interacting protein
RT (MLIP).";
RL J. Biol. Chem. 286:19702-19713(2011).
RN [5]
RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE,
RP AND INTERACTION WITH ISL1.
RX PubMed=22343712; DOI=10.1161/circresaha.111.259663;
RA Huang Z.P., Young Seok H., Zhou B., Chen J., Chen J.F., Tao Y., Pu W.T.,
RA Wang D.Z.;
RT "CIP, a cardiac Isl1-interacting protein, represses cardiomyocyte
RT hypertrophy.";
RL Circ. Res. 110:818-830(2012).
RN [6]
RP FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=26359501; DOI=10.1074/jbc.m115.678433;
RA Cattin M.E., Wang J., Weldrick J.J., Roeske C.L., Mak E., Thorn S.L.,
RA DaSilva J.N., Wang Y., Lusis A.J., Burgon P.G.;
RT "Deletion of MLIP (muscle-enriched A-type lamin-interacting protein) leads
RT to cardiac hyperactivation of Akt/mammalian target of rapamycin (mTOR) and
RT impaired cardiac adaptation.";
RL J. Biol. Chem. 290:26699-26714(2015).
RN [7]
RP FUNCTION, DISRUPTION PHENOTYPE, INTERACTION WITH LMNA, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=26436652; DOI=10.1172/jci82423;
RA Huang Z.P., Kataoka M., Chen J., Wu G., Ding J., Nie M., Lin Z., Liu J.,
RA Hu X., Ma L., Zhou B., Wakimoto H., Zeng C., Kyselovic J., Deng Z.L.,
RA Seidman C.E., Seidman J.G., Pu W.T., Wang D.Z.;
RT "Cardiomyocyte-enriched protein CIP protects against pathophysiological
RT stresses and regulates cardiac homeostasis.";
RL J. Clin. Invest. 125:4122-4134(2015).
CC -!- FUNCTION: Required for precocious cardiac adaptation to stress through
CC integrated regulation of the AKT/mTOR pathways and FOXO1. Regulates
CC cardiac homeostasis and plays an important role in protection against
CC cardiac hypertrophy (PubMed:26359501, PubMed:22343712,
CC PubMed:26436652). Acts as a transcriptional cofactor, represses
CC transactivator activity of ISL1 and MYOCD (PubMed:22343712).
CC {ECO:0000269|PubMed:22343712, ECO:0000269|PubMed:26359501,
CC ECO:0000269|PubMed:26436652}.
CC -!- SUBUNIT: Interacts with LMNA (PubMed:21498514, PubMed:26436652).
CC Interacts with ISL1 (via N-terminal domain); the interaction represses
CC ISL1 transactivator activity (PubMed:22343712).
CC {ECO:0000269|PubMed:21498514, ECO:0000269|PubMed:22343712,
CC ECO:0000269|PubMed:26436652}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:21498514,
CC ECO:0000269|PubMed:22343712, ECO:0000269|PubMed:26436652}. Nucleus
CC envelope {ECO:0000269|PubMed:21498514}. Nucleus, PML body
CC {ECO:0000269|PubMed:21498514}. Cell membrane, sarcolemma
CC {ECO:0000269|PubMed:26359501}; Peripheral membrane protein
CC {ECO:0000269|PubMed:26359501}; Cytoplasmic side
CC {ECO:0000269|PubMed:26359501}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=Additional isoforms seem to exist. PubMed:21498514 identified
CC at least seven MLIP proteins ranging from 23 to 57 kDa,
CC differentially expressed in tissues which are probably alternative
CC splicing products.;
CC Name=1;
CC IsoId=Q5FW52-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5FW52-2; Sequence=VSP_015323;
CC -!- TISSUE SPECIFICITY: Ubiquitous but more abundantly expressed in heart,
CC skeletal and smooth muscle (at protein level). In brain, expressed by a
CC subpopulation of cells within the hippocampus and cortex. In heart,
CC expressed by ventricular cardiomyocytes. Expression is highly reduced
CC in hypertrophic hearts (PubMed:26359501, PubMed:22343712,
CC PubMed:26436652). {ECO:0000269|PubMed:21498514,
CC ECO:0000269|PubMed:22343712, ECO:0000269|PubMed:26359501,
CC ECO:0000269|PubMed:26436652}.
CC -!- DEVELOPMENTAL STAGE: First detected in heart at 8.5 dpc and restricted
CC to heart from 9.5 dpc to 15.5 dpc. At 9.5 dpc, transiently detected in
CC the truck. From 11.5 dpc to 15.5 dpc, expression is higher in the
CC ventricles of embryonic hearts. During embryogenesis, specifically
CC expressed in cardiomyocytes. Myocardial expression continue in the
CC adult heart. {ECO:0000269|PubMed:22343712}.
CC -!- DISRUPTION PHENOTYPE: Mutants are viable and exhibit normal cardiac
CC function despite myocardial metabolic abnormalities and cardiac-
CC specific overactivation of AKT/mTOR pathways (PubMed:26359501,
CC PubMed:26436652). In aged mutants, cardiac function is depressed with
CC increased left ventricular dimension (PubMed:26436652). They show an
CC impaired capacity to adapt to stress such as hypertrophy induced by
CC isoproterenol (ISO). After 9 days of continuous ISO treatment, they
CC display an increase in heart to body weight ratio, thickened
CC interventricular septum nad blunted contractile response compared to
CC their wild type littermates (PubMed:26359501). Upon transverse aortic
CC constriction (TAC), animals develop a dramatic cardiac dilation with a
CC significant increase in left ventricular internal dimension and
CC decreased in left ventricular wall thickness. While control mice
CC exhibit a trend toward decreased cardiac contraction, the cardiac
CC function in knockout animals is dramatically impaired after TAC. TAC
CC induces a greater increase in the size of cardiomyocytes and more
CC extensive fibrosis in hearts compared to the control ones
CC (PubMed:26436652). Double knockouts for MLIP and LMNA die sooner than
CC single LMNA knockout. They develop much more severe ventricular
CC dilation and cardiac dysfunction (PubMed:26436652).
CC {ECO:0000269|PubMed:26359501, ECO:0000269|PubMed:26436652}.
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DR EMBL; AK009836; BAB26534.1; -; mRNA.
DR EMBL; BC089626; AAH89626.1; -; mRNA.
DR CCDS; CCDS52861.1; -. [Q5FW52-1]
DR CCDS; CCDS90629.1; -. [Q5FW52-2]
DR RefSeq; NP_081426.1; NM_027150.1. [Q5FW52-1]
DR AlphaFoldDB; Q5FW52; -.
DR BioGRID; 213586; 1.
DR IntAct; Q5FW52; 4.
DR MINT; Q5FW52; -.
DR STRING; 10090.ENSMUSP00000034910; -.
DR iPTMnet; Q5FW52; -.
DR PhosphoSitePlus; Q5FW52; -.
DR MaxQB; Q5FW52; -.
DR PaxDb; Q5FW52; -.
DR PRIDE; Q5FW52; -.
DR ProteomicsDB; 252577; -. [Q5FW52-1]
DR ProteomicsDB; 252578; -. [Q5FW52-2]
DR Antibodypedia; 59659; 55 antibodies from 18 providers.
DR DNASU; 69642; -.
DR Ensembl; ENSMUST00000034910; ENSMUSP00000034910; ENSMUSG00000032355. [Q5FW52-1]
DR Ensembl; ENSMUST00000184848; ENSMUSP00000139242; ENSMUSG00000032355. [Q5FW52-2]
DR GeneID; 69642; -.
DR KEGG; mmu:69642; -.
DR UCSC; uc009qtg.2; mouse. [Q5FW52-1]
DR UCSC; uc009qth.2; mouse. [Q5FW52-2]
DR CTD; 90523; -.
DR MGI; MGI:1916892; Mlip.
DR VEuPathDB; HostDB:ENSMUSG00000032355; -.
DR eggNOG; ENOG502QTJV; Eukaryota.
DR GeneTree; ENSGT00390000015862; -.
DR InParanoid; Q5FW52; -.
DR OrthoDB; 838301at2759; -.
DR PhylomeDB; Q5FW52; -.
DR TreeFam; TF330818; -.
DR BioGRID-ORCS; 69642; 0 hits in 71 CRISPR screens.
DR ChiTaRS; Mlip; mouse.
DR PRO; PR:Q5FW52; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q5FW52; protein.
DR Bgee; ENSMUSG00000032355; Expressed in sciatic nerve and 106 other tissues.
DR ExpressionAtlas; Q5FW52; baseline and differential.
DR Genevisible; Q5FW52; MM.
DR GO; GO:0005635; C:nuclear envelope; IDA:UniProtKB.
DR GO; GO:0031981; C:nuclear lumen; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0016605; C:PML body; IDA:UniProtKB.
DR GO; GO:0042383; C:sarcolemma; IDA:UniProtKB.
DR GO; GO:0005521; F:lamin binding; IPI:UniProtKB.
DR GO; GO:0003714; F:transcription corepressor activity; IGI:MGI.
DR GO; GO:0010614; P:negative regulation of cardiac muscle hypertrophy; IDA:MGI.
DR GO; GO:1903243; P:negative regulation of cardiac muscle hypertrophy in response to stress; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IGI:MGI.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IGI:MGI.
DR InterPro; IPR029331; MLIP.
DR PANTHER; PTHR31514; PTHR31514; 2.
DR Pfam; PF15274; MLIP; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Membrane; Nucleus; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..269
FT /note="Muscular LMNA-interacting protein"
FT /id="PRO_0000089539"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 47..70
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 86..229
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 100..200
FT /note="Required for interaction with ISL1"
FT /evidence="ECO:0000269|PubMed:22343712"
FT COMPBIAS 49..65
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 180..199
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 210..227
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 85
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 181
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 155..196
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_015323"
FT CONFLICT 88
FT /note="E -> G (in Ref. 1; BAB26534)"
FT /evidence="ECO:0000305"
FT CONFLICT 119
FT /note="S -> N (in Ref. 1; BAB26534)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 269 AA; 29466 MW; 1F7FA9949A217E4B CRC64;
MEFGKHEPGS SLKRNKNLEE GVTFEYSDHM TFSSESKQER VQRILDYPSE VSGRNSQQKE
FNTKEPQGMQ KGDLFKAEYV FIVDSDGEDE ATCRQGEQGP PGGPGNIATR PKSLAISSSL
ASDVVRPKVR GADLKTSSHP EIPHGIAPQQ KHGLALDEPA RTESNSKASV LDLPVEHSSD
SPSRPPQTML GSETIKTPTT HPRAAGRETK YANLSSSSST ASESQLTKPG VIRPVPVKSK
LLLRKDEEVY EPNPFSKYLE DNSGLFSEQ
