MLIP_HUMAN
ID MLIP_HUMAN Reviewed; 458 AA.
AC Q5VWP3; B7Z2N0; D6RE05; Q96H08; Q96NF7;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 3.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Muscular LMNA-interacting protein {ECO:0000312|HGNC:HGNC:21355};
DE AltName: Full=Cardiac Isl1-interacting protein {ECO:0000303|PubMed:26436652};
DE Short=CIP {ECO:0000303|PubMed:26436652};
DE AltName: Full=Muscular-enriched A-type laminin-interacting protein;
GN Name=MLIP {ECO:0000312|HGNC:HGNC:21355};
GN Synonyms=C6orf142, Cip {ECO:0000303|PubMed:26436652};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND VARIANTS
RP ILE-159 AND THR-320.
RC TISSUE=Brain, and Heart;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANTS ILE-159
RP AND THR-320.
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 [4]
RP INTERACTION WITH LMNA, 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 TISSUE SPECIFICITY, AND INVOLVEMENT IN DISEASE.
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. Acts as a transcriptional cofactor, represses
CC transactivator activity of ISL1 and MYOCD.
CC {ECO:0000250|UniProtKB:A0A096MK47, ECO:0000250|UniProtKB:Q5FW52}.
CC -!- SUBUNIT: Interacts with LMNA (PubMed:21498514). Interacts with ISL1
CC (via N-terminal domain); the interaction represses ISL1 transactivator
CC activity (By similarity). {ECO:0000250|UniProtKB:Q5FW52,
CC ECO:0000269|PubMed:21498514}.
CC -!- INTERACTION:
CC Q5VWP3-2; P45984: MAPK9; NbExp=5; IntAct=EBI-12320785, EBI-713568;
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=4;
CC Comment=Additional isoforms seem to exist according to
CC PubMed:21498514.;
CC Name=1;
CC IsoId=Q5VWP3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5VWP3-2; Sequence=VSP_015320, VSP_015321, VSP_015322;
CC Name=3;
CC IsoId=Q5VWP3-3; Sequence=VSP_041463, VSP_041464;
CC Name=4;
CC IsoId=Q5VWP3-4; Sequence=VSP_041464, VSP_055202, VSP_055203;
CC -!- TISSUE SPECIFICITY: Primarily expressed in heart and skeletal muscle.
CC Also detected in liver. {ECO:0000269|PubMed:21498514,
CC ECO:0000269|PubMed:26436652}.
CC -!- DISEASE: Note=Expression is reduced in patients with dilated
CC cardiomyocytes. In murine cardiomyopathy models, deletion of the
CC encoding gene accelerates progress from hypertrophy to heart failure.
CC {ECO:0000269|PubMed:26436652}.
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DR EMBL; AK055530; BAB70942.1; -; mRNA.
DR EMBL; AK294890; BAH11916.1; -; mRNA.
DR EMBL; AL139389; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL359380; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL365328; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC009010; AAH09010.1; -; mRNA.
DR EMBL; AL033384; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS4954.1; -. [Q5VWP3-1]
DR CCDS; CCDS64448.1; -. [Q5VWP3-4]
DR CCDS; CCDS64449.1; -. [Q5VWP3-3]
DR RefSeq; NP_001268675.1; NM_001281746.1. [Q5VWP3-4]
DR RefSeq; NP_001268676.1; NM_001281747.1. [Q5VWP3-3]
DR RefSeq; NP_612636.2; NM_138569.2. [Q5VWP3-1]
DR AlphaFoldDB; Q5VWP3; -.
DR SMR; Q5VWP3; -.
DR BioGRID; 124729; 7.
DR IntAct; Q5VWP3; 2.
DR GlyGen; Q5VWP3; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q5VWP3; -.
DR PhosphoSitePlus; Q5VWP3; -.
DR BioMuta; MLIP; -.
DR DMDM; 296439407; -.
DR EPD; Q5VWP3; -.
DR MassIVE; Q5VWP3; -.
DR MaxQB; Q5VWP3; -.
DR PaxDb; Q5VWP3; -.
DR PeptideAtlas; Q5VWP3; -.
DR PRIDE; Q5VWP3; -.
DR ProteomicsDB; 14218; -.
DR ProteomicsDB; 65548; -. [Q5VWP3-1]
DR ProteomicsDB; 65549; -. [Q5VWP3-2]
DR ProteomicsDB; 65550; -. [Q5VWP3-3]
DR Antibodypedia; 59659; 55 antibodies from 18 providers.
DR DNASU; 90523; -.
DR Ensembl; ENST00000274897.9; ENSP00000274897.5; ENSG00000146147.15. [Q5VWP3-1]
DR Ensembl; ENST00000370876.6; ENSP00000359913.2; ENSG00000146147.15. [Q5VWP3-2]
DR Ensembl; ENST00000502396.6; ENSP00000426290.1; ENSG00000146147.15. [Q5VWP3-3]
DR Ensembl; ENST00000514921.5; ENSP00000425142.1; ENSG00000146147.15. [Q5VWP3-4]
DR GeneID; 90523; -.
DR KEGG; hsa:90523; -.
DR MANE-Select; ENST00000502396.6; ENSP00000426290.1; NM_001281747.2; NP_001268676.1. [Q5VWP3-3]
DR UCSC; uc003pcf.2; human. [Q5VWP3-1]
DR CTD; 90523; -.
DR DisGeNET; 90523; -.
DR GeneCards; MLIP; -.
DR HGNC; HGNC:21355; MLIP.
DR HPA; ENSG00000146147; Group enriched (heart muscle, liver, skeletal muscle, tongue).
DR MIM; 614106; gene.
DR neXtProt; NX_Q5VWP3; -.
DR OpenTargets; ENSG00000146147; -.
DR PharmGKB; PA134918634; -.
DR VEuPathDB; HostDB:ENSG00000146147; -.
DR eggNOG; ENOG502QTJV; Eukaryota.
DR GeneTree; ENSGT00390000015862; -.
DR HOGENOM; CLU_047719_0_1_1; -.
DR InParanoid; Q5VWP3; -.
DR OMA; MNSCILA; -.
DR OrthoDB; 838301at2759; -.
DR PhylomeDB; Q5VWP3; -.
DR TreeFam; TF330818; -.
DR PathwayCommons; Q5VWP3; -.
DR SignaLink; Q5VWP3; -.
DR BioGRID-ORCS; 90523; 8 hits in 1067 CRISPR screens.
DR ChiTaRS; MLIP; human.
DR GeneWiki; C6orf142; -.
DR GenomeRNAi; 90523; -.
DR Pharos; Q5VWP3; Tdark.
DR PRO; PR:Q5VWP3; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q5VWP3; protein.
DR Bgee; ENSG00000146147; Expressed in left ventricle myocardium and 119 other tissues.
DR ExpressionAtlas; Q5VWP3; baseline and differential.
DR Genevisible; Q5VWP3; HS.
DR GO; GO:0005635; C:nuclear envelope; ISS:UniProtKB.
DR GO; GO:0031981; C:nuclear lumen; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0016605; C:PML body; ISS:UniProtKB.
DR GO; GO:0042383; C:sarcolemma; ISS:UniProtKB.
DR GO; GO:0005521; F:lamin binding; IBA:GO_Central.
DR GO; GO:0003714; F:transcription corepressor activity; IBA:GO_Central.
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; ISS:UniProtKB.
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; 2.
DR Pfam; PF15274; MLIP; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Membrane; Nucleus; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..458
FT /note="Muscular LMNA-interacting protein"
FT /id="PRO_0000089538"
FT REGION 1..40
FT /note="Interaction with LMNA"
FT /evidence="ECO:0000269|PubMed:21498514"
FT REGION 60..79
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 150..302
FT /note="Required for interaction with ISL1"
FT /evidence="ECO:0000250|UniProtKB:Q5FW52"
FT REGION 176..205
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 276..329
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 276..301
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 313..329
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 135
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5FW52"
FT MOD_RES 283
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5FW52"
FT VAR_SEQ 1..73
FT /note="MELEKREKRSLLNKNLEEKLTVSAGGSEAKPLIFTFVPTVRRLPTHTQLADT
FT SKFLVKIPEESSDKSPETVNR -> MCSWYLGFECS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_015320"
FT VAR_SEQ 1..21
FT /note="MELEKREKRSLLNKNLEEKLT -> MLSEQGLLSDCGNNYFQMTSCILSGSI
FT QTTPQ (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_041463"
FT VAR_SEQ 204
FT /note="Q -> QLTSSPTTSEQLACKPPAFSFVSPTNPNTPPDPVNLEGASVLEEFHT
FT RRLDVGGAVVEESATYFQTTAHSTPFSASKGTSSTLLFPHSTQLSGSNLPSSTAADPKP
FT GLTSEVLKKTTLTSHVLSHGESPRTSSSPPSSSASLKSNSASYIPVRIVTHSLSPSPKP
FT FTSSFHGSSSTICSQMSSSGNLSKSGVKSPVPSRLALLTAILKSNPSHQRPFSPASCPT
FT FSLNSPASSTLTLDQKEKQTPPTPKKSLSSCSLRAGSPDQGELQVSELTQQSFHLPVFT
FT KSTPLSQAPSLSPTKQASSSLASMNVERTPSPTLKSNTMLSLLQTSTSSSVGLPPVPPS
FT SSLSSLKSKQDGDLRGPENPRNIHTYPSTLASSALSSLSPPINQRATFSSSEKCFHPSP
FT ALSSLINRSKRASSQLSGQELNPSALPSLPVSSADFASLPNLRSSSLPHANLPTLVPQL
FT SPSALHPHCGSGTLPSRLGKSESTTPNHRSPVSTPSLPISLTRTEELISPCALSMSTGP
FT ENKKSK (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_041464"
FT VAR_SEQ 205..298
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_015321"
FT VAR_SEQ 372..439
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_015322"
FT VAR_SEQ 372..391
FT /note="DVTVPPKPVSLHPLYQTKLY -> AAHSVDSYCNGSDTSGPWLL (in
FT isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_055202"
FT VAR_SEQ 392..458
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_055203"
FT VARIANT 6
FT /note="R -> H (in dbSNP:rs17625497)"
FT /id="VAR_033676"
FT VARIANT 159
FT /note="V -> I (in dbSNP:rs4712056)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_023381"
FT VARIANT 320
FT /note="S -> T (in dbSNP:rs6934690)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_023382"
FT VARIANT 376
FT /note="P -> S (in dbSNP:rs2275769)"
FT /id="VAR_056800"
FT CONFLICT 355
FT /note="N -> T (in Ref. 3; AAH09010)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 458 AA; 50429 MW; 51B3A35106551BF7 CRC64;
MELEKREKRS LLNKNLEEKL TVSAGGSEAK PLIFTFVPTV RRLPTHTQLA DTSKFLVKIP
EESSDKSPET VNRSKSNDYL TLNAGSQQER DQAKLTCPSE VSGTILQERE FEANKLQGMQ
QSDLFKAEYV LIVDSEGEDE AASRKVEQGP PGGIGTAAVR PKSLAISSSL VSDVVRPKTQ
GTDLKTSSHP EMLHGMAPQQ KHGQQYKTKS SYKAFAAIPT NTLLLEQKAL DEPAKTESVS
KDNTLEPPVE LYFPAQLRQQ TEELCATIDK VLQDSLSMHS SDSPSRSPKT LLGSDTVKTP
TTLPRAAGRE TKYANLSSPS STVSESQLTK PGVIRPVPVK SRILLKKEEE VYEPNPFSKY
LEDNSDLFSE QDVTVPPKPV SLHPLYQTKL YPPAKSLLHP QTLSHADCLA PGPFSHLSFS
LSDEQENSHT LLSHNACNKL SHPMVAIPEH EALDSKEQ
