ADIPL_MOUSE
ID ADIPL_MOUSE Reviewed; 308 AA.
AC Q8R2Z0; Q9CQI8;
DT 17-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 17-APR-2007, sequence version 2.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=Adipolin {ECO:0000303|PubMed:21849507};
DE AltName: Full=Adipose-derived insulin-sensitizing factor {ECO:0000303|PubMed:21849507};
DE AltName: Full=Complement C1q tumor necrosis factor-related protein 12;
DE Contains:
DE RecName: Full=Adipolin fC1QTNF12;
DE AltName: Full=Adipolin fCTRP12 {ECO:0000303|PubMed:22942287};
DE AltName: Full=Adipolin full-length form;
DE Contains:
DE RecName: Full=Adipolin gC1QTNF12;
DE AltName: Full=Adipolin cleaved form;
DE AltName: Full=Adipolin gCTRP12 {ECO:0000303|PubMed:22942287};
DE Flags: Precursor;
GN Name=C1qtnf12; Synonyms=C1qdc2, Ctrp12, Fam132a;
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], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP INDUCTION.
RC STRAIN=C57BL/6J;
RX PubMed=21849507; DOI=10.1074/jbc.m111.277319;
RA Enomoto T., Ohashi K., Shibata R., Higuchi A., Maruyama S., Izumiya Y.,
RA Walsh K., Murohara T., Ouchi N.;
RT "Adipolin/C1qdc2/CTRP12 protein functions as an adipokine that improves
RT glucose metabolism.";
RL J. Biol. Chem. 286:34552-34558(2011).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Kidney;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 [5]
RP PARTIAL PROTEIN SEQUENCE, FUNCTION, SUBCELLULAR LOCATION, PROTEOLYTIC
RP PROCESSING, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=22275362; DOI=10.1074/jbc.m111.303651;
RA Wei Z., Peterson J.M., Lei X., Cebotaru L., Wolfgang M.J., Baldeviano G.C.,
RA Wong G.W.;
RT "C1q/TNF-related protein-12 (CTRP12), a novel adipokine that improves
RT insulin sensitivity and glycemic control in mouse models of obesity and
RT diabetes.";
RL J. Biol. Chem. 287:10301-10315(2012).
RN [6]
RP PROTEOLYTIC PROCESSING, INDUCTION, AND MUTAGENESIS OF 90-LYS--ARG-93.
RX PubMed=23068097; DOI=10.1016/j.bbrc.2012.10.031;
RA Enomoto T., Shibata R., Ohashi K., Kambara T., Kataoka Y., Uemura Y.,
RA Yuasa D., Murohara T., Ouchi N.;
RT "Regulation of adipolin/CTRP12 cleavage by obesity.";
RL Biochem. Biophys. Res. Commun. 428:155-159(2012).
RN [7]
RP INTERACTION WITH ERFE.
RX PubMed=22351773; DOI=10.1074/jbc.m111.336834;
RA Seldin M.M., Peterson J.M., Byerly M.S., Wei Z., Wong G.W.;
RT "Myonectin (CTRP15), a novel myokine that links skeletal muscle to systemic
RT lipid homeostasis.";
RL J. Biol. Chem. 287:11968-11980(2012).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, GLYCOSYLATION AT ASN-39, DISULFIDE
RP BOND, PROTEOLYTIC PROCESSING, AND MUTAGENESIS OF ASN-39; CYS-85;
RP 90-LYS--ARG-93 AND ARG-93.
RX PubMed=22942287; DOI=10.1074/jbc.m112.365965;
RA Wei Z., Lei X., Seldin M.M., Wong G.W.;
RT "Endopeptidase cleavage generates a functionally distinct isoform of
RT C1q/tumor necrosis factor-related protein-12 (CTRP12) with an altered
RT oligomeric state and signaling specificity.";
RL J. Biol. Chem. 287:35804-35814(2012).
RN [9]
RP INDUCTION.
RX PubMed=23633521; DOI=10.2337/db12-1745;
RA Bell-Anderson K.S., Funnell A.P., Williams H., Mat Jusoh H., Scully T.,
RA Lim W.F., Burdach J.G., Mak K.S., Knights A.J., Hoy A.J., Nicholas H.R.,
RA Sainsbury A., Turner N., Pearson R.C., Crossley M.;
RT "Loss of Kruppel-like factor 3 (KLF3/BKLF) leads to upregulation of the
RT insulin-sensitizing factor adipolin (FAM132A/CTRP12/C1qdc2).";
RL Diabetes 62:2728-2737(2013).
RN [10]
RP INDUCTION.
RX PubMed=24358263; DOI=10.1371/journal.pone.0083183;
RA Enomoto T., Ohashi K., Shibata R., Kambara T., Uemura Y., Yuasa D.,
RA Kataoka Y., Miyabe M., Matsuo K., Joki Y., Hayakawa S., Hiramatsu-Ito M.,
RA Ito M., Murohara T., Ouchi N.;
RT "Transcriptional regulation of an insulin-sensitizing adipokine
RT adipolin/CTRP12 in adipocytes by Krueppel-like factor 15.";
RL PLoS ONE 8:E83183-E83183(2013).
CC -!- FUNCTION: Insulin-sensitizing adipocyte-secreted protein (adipokine)
CC that regulates glucose metabolism in liver and adipose tissue. Promotes
CC glucose uptake in adipocytes and suppresses de novo glucose production
CC in hepatocytes via the PI3K-Akt signaling pathway. Administration lead
CC to reduction of blood glucose. Able to attenuate inflammation in fat
CC tissue (PubMed:21849507, PubMed:22275362).
CC {ECO:0000269|PubMed:21849507, ECO:0000269|PubMed:22275362}.
CC -!- FUNCTION: [Adipolin fC1QTNF12]: Acts by activating the Akt signaling in
CC hepatocytes and adipocytes. Not able to increase insulin-stimulated
CC glucose uptake in adipocytes (PubMed:22942287).
CC {ECO:0000269|PubMed:22942287}.
CC -!- FUNCTION: [Adipolin gC1QTNF12]: Acts by activating the MAP kinase.
CC Increases insulin-stimulated glucose uptake in adipocytes
CC (PubMed:22942287). {ECO:0000269|PubMed:22942287}.
CC -!- SUBUNIT: Homomultimer; disulfide-linked (PubMed:22942287). Adipolin
CC fC1QTNF12: homotrimer; disulfide-linked (PubMed:22942287). Adipolin
CC gC1QTNF12: homodimer; disulfide-linked (PubMed:22942287). May interact
CC with ERFE. {ECO:0000269|PubMed:22942287}.
CC -!- SUBCELLULAR LOCATION: [Adipolin fC1QTNF12]: Secreted
CC {ECO:0000269|PubMed:22275362, ECO:0000269|PubMed:22942287}.
CC -!- SUBCELLULAR LOCATION: [Adipolin gC1QTNF12]: Secreted
CC {ECO:0000269|PubMed:22275362, ECO:0000269|PubMed:22942287}. Note=In
CC serum is the predominant form. {ECO:0000269|PubMed:22275362}.
CC -!- TISSUE SPECIFICITY: Widely expressed, with high expression in
CC subcutaneous and epididymal white adipose tissues and brown adipose
CC tissue. Expressed in adipocytes (at protein level).
CC {ECO:0000269|PubMed:21849507, ECO:0000269|PubMed:22275362}.
CC -!- INDUCTION: During adipogenesis. Upon insulin treatment. Up-regulated in
CC obeses mice. Transcription is activated by KLF3 and KLF15.
CC {ECO:0000269|PubMed:21849507, ECO:0000269|PubMed:22275362,
CC ECO:0000269|PubMed:23068097, ECO:0000269|PubMed:23633521,
CC ECO:0000269|PubMed:24358263}.
CC -!- PTM: Processed into Adipolin fC1QTNF12 and Adipolin gC1QTNF12 by FURIN
CC (PubMed:22942287). Insulin enhances endogenous C1QTNF12 cleavage
CC (PubMed:22942287). {ECO:0000269|PubMed:22942287}.
CC -!- SIMILARITY: Belongs to the adipolin/erythroferrone family.
CC {ECO:0000305}.
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DR EMBL; DQ002404; AAY21936.1; -; mRNA.
DR EMBL; AK002876; BAB22423.1; -; mRNA.
DR EMBL; AK004116; BAB23178.1; -; mRNA.
DR EMBL; AL627204; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC026939; AAH26939.1; -; mRNA.
DR CCDS; CCDS19052.1; -.
DR RefSeq; NP_080401.1; NM_026125.3.
DR AlphaFoldDB; Q8R2Z0; -.
DR STRING; 10090.ENSMUSP00000024338; -.
DR GlyGen; Q8R2Z0; 1 site.
DR iPTMnet; Q8R2Z0; -.
DR PhosphoSitePlus; Q8R2Z0; -.
DR CPTAC; non-CPTAC-3558; -.
DR MaxQB; Q8R2Z0; -.
DR PaxDb; Q8R2Z0; -.
DR PeptideAtlas; Q8R2Z0; -.
DR PRIDE; Q8R2Z0; -.
DR ProteomicsDB; 296068; -.
DR Antibodypedia; 12127; 49 antibodies from 13 providers.
DR DNASU; 67389; -.
DR Ensembl; ENSMUST00000024338; ENSMUSP00000024338; ENSMUSG00000023571.
DR GeneID; 67389; -.
DR KEGG; mmu:67389; -.
DR UCSC; uc008wfp.2; mouse.
DR CTD; 388581; -.
DR MGI; MGI:1914639; C1qtnf12.
DR VEuPathDB; HostDB:ENSMUSG00000023571; -.
DR eggNOG; ENOG502QQVR; Eukaryota.
DR GeneTree; ENSGT00940000160300; -.
DR HOGENOM; CLU_057344_1_0_1; -.
DR InParanoid; Q8R2Z0; -.
DR OMA; RCRGRDK; -.
DR OrthoDB; 1462460at2759; -.
DR PhylomeDB; Q8R2Z0; -.
DR TreeFam; TF331282; -.
DR BioGRID-ORCS; 67389; 1 hit in 76 CRISPR screens.
DR ChiTaRS; Fam132a; mouse.
DR PRO; PR:Q8R2Z0; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q8R2Z0; protein.
DR Bgee; ENSMUSG00000023571; Expressed in metanephric renal vesicle and 249 other tissues.
DR Genevisible; Q8R2Z0; MM.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0005179; F:hormone activity; IDA:UniProtKB.
DR GO; GO:0051649; P:establishment of localization in cell; IMP:MGI.
DR GO; GO:0006094; P:gluconeogenesis; IDA:MGI.
DR GO; GO:0046323; P:glucose import; IMP:MGI.
DR GO; GO:0045721; P:negative regulation of gluconeogenesis; IDA:MGI.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IDA:MGI.
DR GO; GO:0046326; P:positive regulation of glucose import; IMP:MGI.
DR GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; IDA:MGI.
DR GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; IDA:MGI.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IDA:MGI.
DR GO; GO:0043491; P:protein kinase B signaling; IDA:MGI.
DR GO; GO:0046324; P:regulation of glucose import; IDA:UniProtKB.
DR GO; GO:0010906; P:regulation of glucose metabolic process; IDA:MGI.
DR Gene3D; 2.60.120.40; -; 1.
DR InterPro; IPR001073; C1q_dom.
DR InterPro; IPR008983; Tumour_necrosis_fac-like_dom.
DR SUPFAM; SSF49842; SSF49842; 1.
DR PROSITE; PS50871; C1Q; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Hormone;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..308
FT /note="Adipolin fC1QTNF12"
FT /id="PRO_0000284355"
FT CHAIN 92..308
FT /note="Adipolin gC1QTNF12"
FT /id="PRO_0000430249"
FT DOMAIN 153..308
FT /note="C1q"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00368"
FT REGION 36..119
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 98..115
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 91..92
FT /note="Cleavage; by FURIN"
FT /evidence="ECO:0000269|PubMed:22942287"
FT SITE 287
FT /note="Not glycosylated"
FT /evidence="ECO:0000269|PubMed:22942287"
FT SITE 297
FT /note="Not glycosylated"
FT /evidence="ECO:0000269|PubMed:22942287"
FT CARBOHYD 39
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22942287"
FT MUTAGEN 39
FT /note="N->A: Decreased N-glycosylation."
FT /evidence="ECO:0000269|PubMed:22942287"
FT MUTAGEN 85
FT /note="C->A: Abolishes multimeric complex formation."
FT /evidence="ECO:0000269|PubMed:22942287"
FT MUTAGEN 90..93
FT /note="KKSR->AASA: Nearly abolishes protein processing."
FT /evidence="ECO:0000269|PubMed:22942287,
FT ECO:0000269|PubMed:23068097"
FT MUTAGEN 90..93
FT /note="Missing: Abolishes protein processing."
FT /evidence="ECO:0000269|PubMed:22942287,
FT ECO:0000269|PubMed:23068097"
FT MUTAGEN 93
FT /note="R->A: Enhances protein processing."
FT /evidence="ECO:0000269|PubMed:22942287"
FT CONFLICT 117
FT /note="G -> D (in Ref. 4; AAH26939)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 308 AA; 33267 MW; 888681DBDCDD5835 CRC64;
MWAWGWAAAA LLWLQTAGAG ARQELKKSRQ LFARVDSPNI TTSNREGFPG SVKPPEASGP
ELSDAHMTWL NFVRRPDDGS SRKRCRGRDK KSRGLSGLPG PPGPPGPPGP PGSPGVGVTP
EALLQEFQEI LKEATELRFS GLPDTLLPQE PSQRLVVEAF YCRLKGPVLV DKKTLVELQG
FQAPTTQGAF LRGSGLSLSL GRFTAPVSAI FQFSASLHVD HSELQGRGRL RTRDMVRVLI
CIESLCHRHT SLEAVSGLES NSRVFTVQVQ GLLHLQSGQY VSVFVDNSSG AVLTIQNTSS
FSGMLLGT
