MLIP_RAT
ID MLIP_RAT Reviewed; 807 AA.
AC A0A096MK47; D4A3C4; Q569A0;
DT 25-OCT-2017, integrated into UniProtKB/Swiss-Prot.
DT 26-NOV-2014, sequence version 1.
DT 03-AUG-2022, entry version 44.
DE RecName: Full=Muscular LMNA-interacting protein {ECO:0000312|RGD:1590513};
DE AltName: Full=Cardiac Isl1-interacting protein {ECO:0000303|PubMed:22343712};
DE Short=CIP {ECO:0000303|PubMed:22343712};
GN Name=Mlip {ECO:0000312|RGD:1590513};
GN Synonyms=Cip {ECO:0000303|PubMed:22343712};
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 24-807 (ISOFORM 2).
RC 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 [3]
RP FUNCTION, AND TISSUE SPECIFICITY.
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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-85 AND SER-442, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [5]
RP FUNCTION, 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:22343712, PubMed:26436652). Acts as a
CC transcriptional cofactor, represses transactivator activity of ISL1 and
CC MYOCD (By similarity). {ECO:0000250|UniProtKB:Q5FW52,
CC ECO:0000269|PubMed:22343712, ECO:0000269|PubMed:26436652}.
CC -!- SUBUNIT: Interacts with LMNA. Interacts with ISL1 (via N-terminal
CC domain); the interaction represses ISL1 transactivator activity.
CC {ECO:0000250|UniProtKB:Q5FW52}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q5FW52}. Nucleus
CC envelope {ECO:0000250|UniProtKB:Q5FW52}. Nucleus, PML body
CC {ECO:0000250|UniProtKB:Q5FW52}. Cell membrane, sarcolemma
CC {ECO:0000250|UniProtKB:Q5FW52}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q5FW52}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q5FW52}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=A0A096MK47-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A0A096MK47-2; Sequence=VSP_059123;
CC Name=3;
CC IsoId=A0A096MK47-3; Sequence=VSP_059122;
CC -!- TISSUE SPECIFICITY: Expressed in cardiomyoctes. Expression is highly
CC reduced in hypertrophic cardiomyocytes. {ECO:0000269|PubMed:22343712,
CC ECO:0000269|PubMed:26436652}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH92625.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AABR07070794; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07070795; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07070796; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC092625; AAH92625.1; ALT_INIT; mRNA.
DR AlphaFoldDB; A0A096MK47; -.
DR STRING; 10116.ENSRNOP00000068377; -.
DR iPTMnet; A0A096MK47; -.
DR Ensembl; ENSRNOT00000064754; ENSRNOP00000061707; ENSRNOG00000005934. [A0A096MK47-3]
DR RGD; 1590513; Mlip.
DR VEuPathDB; HostDB:ENSRNOG00000005934; -.
DR eggNOG; ENOG502QTJV; Eukaryota.
DR OMA; MNSCILA; -.
DR TreeFam; TF330818; -.
DR PRO; PR:A0A096MK47; -.
DR Proteomes; UP000002494; Chromosome 8.
DR Bgee; ENSRNOG00000005934; Expressed in heart and 11 other tissues.
DR ExpressionAtlas; A0A096MK47; baseline and differential.
DR GO; GO:0005635; C:nuclear envelope; ISO:RGD.
DR GO; GO:0031981; C:nuclear lumen; ISO:RGD.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0016605; C:PML body; ISO:RGD.
DR GO; GO:0042383; C:sarcolemma; ISO:RGD.
DR GO; GO:0005521; F:lamin binding; ISO:RGD.
DR GO; GO:0003714; F:transcription corepressor activity; ISO:RGD.
DR GO; GO:0010614; P:negative regulation of cardiac muscle hypertrophy; ISS:UniProtKB.
DR GO; GO:1903243; P:negative regulation of cardiac muscle hypertrophy in response to stress; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR InterPro; IPR029331; MLIP.
DR PANTHER; PTHR31514; PTHR31514; 1.
DR Pfam; PF15274; MLIP; 3.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Membrane; Nucleus; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..807
FT /note="Muscular LMNA-interacting protein"
FT /id="PRO_0000441849"
FT REGION 32..69
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 88..109
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 100..738
FT /note="Required for interaction with ISL1"
FT /evidence="ECO:0000250|UniProtKB:Q5FW52"
FT REGION 138..163
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 259..293
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 310..344
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 390..518
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 553..640
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 695..769
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 32..47
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 263..293
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 390..481
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 592..640
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 700..737
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 748..766
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 85
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 442
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 719
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5FW52"
FT VAR_SEQ 155..692
FT /note="Missing (in isoform 3)"
FT /id="VSP_059122"
FT VAR_SEQ 155..179
FT /note="Missing (in isoform 2)"
FT /id="VSP_059123"
SQ SEQUENCE 807 AA; 86186 MW; 523C77B36EB2ED6E CRC64;
MEFEKHEQGN ALKKNEKLEE RVTFEYSDHM TFSCESKEER DQRILDYPSE VSGKNSQRKE
FNTKEPQGMQ KGDLFKAEYV FIVDSDGEDE ATCRQGEQGP PGATGNIATR PKSLAISSSL
ASDVVRPKVR GVDVKVSSHP EIPHGIAPQQ KHGQLTSPTT SEQLAHKPPA FSFVSPTNQK
TPPVPAKVSG TTVLEEFHIR RLDVHGASEE ETATYFHTTA HDSPLPAWKG ASTLVFSPSA
QLPGSSLCGS NVADHTRGLA PEAQKKVSTS SALNPREDVR TSPSPASGAS LRSPSASYIP
VRIVMHSLSP SPKPLTSSSH GSLSTVCSQT SSSGNLSKSG LKSPVPSRLS LLTAILKSNP
SHQRPLSPAS CPTFSLNSLA SSTLTLDQKI KQTPSTPKKS LSSCSLTTGS TEQEQASAES
HQPCHLSFFS KTTPLSQAQP PSPPALASSS YAATDTEKIP GSTLRSSTTP PQSQTDLFSL
ADVPSVTPGL SPLSSSKGRK DGDLRAPEKN RNICTRPSTL SFIPPINEST ALSSSGKCFH
PSPALSDLID RSKRTCSQRH SDQRPNPSAL PTPPVSRAGS ASHPHLGYSI LPPESSLTQA
LQRSPSALHP SCGSATCPSR TGMPDSTASN RSSRVSTPSL PVSLTRTKEL ISPCALSMSA
GPENKKPKQY KTKSSYKAFA AIPTNTLLLE QKALDEPART ESNSKASVSD LPVEHSSDSP
SRPSQTMLGS ETIKTPTTHP RAAGRETKYA NLSSSSSTTS ESQLTKPGVI RPVPIKSKLF
LKKEEEVYEP NPFSKYLEDS SGLFSEQ
