C1QT4_MOUSE
ID C1QT4_MOUSE Reviewed; 326 AA.
AC Q8R066; A2AFW1; Q4ZJN5; Q9D0W2; Q9DCB6;
DT 21-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Complement C1q tumor necrosis factor-related protein 4;
DE AltName: Full=C1q/TNF-related protein 4 {ECO:0000303|PubMed:24366864};
DE Flags: Precursor;
GN Name=C1qtnf4; Synonyms=Ctrp4 {ECO:0000303|PubMed:24366864};
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 STRAIN=C57BL/6J; TISSUE=Brain;
RA Wong G.W.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain, and Embryo;
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 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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT "Comprehensive identification of phosphorylation sites in postsynaptic
RT density preparations.";
RL Mol. Cell. Proteomics 5:914-922(2006).
RN [6]
RP FUNCTION, CHARACTERIZATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP SUBUNIT, AND CAUTION.
RC STRAIN=C57BL/6J {ECO:0000303|PubMed:24366864};
RX PubMed=24366864; DOI=10.1074/jbc.m113.506956;
RA Byerly M.S., Petersen P.S., Ramamurthy S., Seldin M.M., Lei X., Provost E.,
RA Wei Z., Ronnett G.V., Wong G.W.;
RT "C1q/TNF-related protein 4 (CTRP4) is a unique secreted protein with two
RT tandem C1q domains that functions in the hypothalamus to modulate food
RT intake and body weight.";
RL J. Biol. Chem. 289:4055-4069(2014).
RN [7]
RP INDUCTION.
RC STRAIN=C57BL/6J {ECO:0000303|PubMed:27086950};
RX PubMed=27086950; DOI=10.1038/cmi.2016.16;
RA Luo Y., Wu X., Ma Z., Tan W., Wang L., Na D., Zhang G., Yin A., Huang H.,
RA Xia D., Zhang Y., Shi X., Wang L.;
RT "Expression of the novel adipokine C1qTNF-related protein 4 (CTRP4)
RT suppresses colitis and colitis-associated colorectal cancer in mice.";
RL Cell. Mol. Immunol. 13:688-699(2016).
CC -!- FUNCTION: May be involved in the regulation of the inflammatory
CC network. The role as pro- or anti-inflammatory seems to be context
CC dependent (By similarity). Seems to have some role in regulating food
CC intake and energy balance when administered in the brain. This effect
CC is sustained over a two-day period, and it is accompanied by decreased
CC expression of orexigenic neuropeptides in the hypothalamus 3 hours
CC post-injection (Probable). {ECO:0000250|UniProtKB:Q9BXJ3,
CC ECO:0000269|PubMed:24366864}.
CC -!- SUBUNIT: Homomultimer. Forms trimers, hexamers and high molecular
CC weight oligomers. {ECO:0000269|PubMed:24366864}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:24366864,
CC ECO:0000269|PubMed:27086950}.
CC -!- TISSUE SPECIFICITY: High expression in testis, kidney, and brain.
CC Expressed in brain and kidney (at protein level). Within the brain,
CC highly expressed in cerebellum, cortex, hippocampus and hippothalamus,
CC and lower expression in hindbrain (at protein level). Serum levels were
CC increased in leptin-deficient ob/ob mice (a genetic model of
CC hyperphagia and morbid obesity) relative to age-matched lean controls.
CC No difference in serum levels were detected between mice fed a low-fat
CC versus high-fat diet for 14 weeks (PubMed:24366864).
CC {ECO:0000269|PubMed:24366864}.
CC -!- INDUCTION: Up-regulated during acute colitis induced by injection of
CC dextran sulfate sodium (DSS). {ECO:0000269|PubMed:27086950}.
CC -!- CAUTION: There are conflicting results in its involvement in the
CC inflammatory network. It was first described to be a pro-inflammatory
CC cytokine by inducing the activation of NF-kappa-B signaling pathway and
CC up-regulates IL6 production in liver carcinoma cells. While it seems to
CC have the opposite effect in macrophages.
CC {ECO:0000250|UniProtKB:Q9BXJ3}.
CC -!- CAUTION: Involvement in food intake and energy was only observed when
CC the protein was externally administered in the brain, but not when this
CC protein was overexpressed in vivo (PubMed:24366864).
CC {ECO:0000269|PubMed:24366864}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB22473.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAB23268.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; DQ002397; AAY21929.1; -; mRNA.
DR EMBL; AK002948; BAB22473.1; ALT_FRAME; mRNA.
DR EMBL; AK004340; BAB23268.1; ALT_FRAME; mRNA.
DR EMBL; AL672241; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC027315; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS16417.2; -.
DR RefSeq; NP_080437.2; NM_026161.3.
DR RefSeq; XP_006500142.1; XM_006500079.1.
DR RefSeq; XP_006500143.1; XM_006500080.3.
DR AlphaFoldDB; Q8R066; -.
DR SMR; Q8R066; -.
DR STRING; 10090.ENSMUSP00000107091; -.
DR PhosphoSitePlus; Q8R066; -.
DR SwissPalm; Q8R066; -.
DR MaxQB; Q8R066; -.
DR PaxDb; Q8R066; -.
DR PeptideAtlas; Q8R066; -.
DR PRIDE; Q8R066; -.
DR ProteomicsDB; 265460; -.
DR Antibodypedia; 13803; 183 antibodies from 30 providers.
DR DNASU; 67445; -.
DR Ensembl; ENSMUST00000111466; ENSMUSP00000107091; ENSMUSG00000040794.
DR GeneID; 67445; -.
DR KEGG; mmu:67445; -.
DR UCSC; uc008ktq.1; mouse.
DR CTD; 114900; -.
DR MGI; MGI:1914695; C1qtnf4.
DR VEuPathDB; HostDB:ENSMUSG00000040794; -.
DR eggNOG; ENOG502QX94; Eukaryota.
DR GeneTree; ENSGT00940000161832; -.
DR HOGENOM; CLU_048377_0_0_1; -.
DR InParanoid; Q8R066; -.
DR OMA; IYSEAQP; -.
DR OrthoDB; 872445at2759; -.
DR PhylomeDB; Q8R066; -.
DR TreeFam; TF329591; -.
DR BioGRID-ORCS; 67445; 4 hits in 71 CRISPR screens.
DR PRO; PR:Q8R066; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q8R066; protein.
DR Bgee; ENSMUSG00000040794; Expressed in striatum and 57 other tissues.
DR ExpressionAtlas; Q8R066; baseline and differential.
DR Genevisible; Q8R066; MM.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISO:MGI.
DR GO; GO:0070105; P:positive regulation of interleukin-6-mediated signaling pathway; ISO:MGI.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; ISO:MGI.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISO:MGI.
DR Gene3D; 2.60.120.40; -; 2.
DR InterPro; IPR001073; C1q_dom.
DR InterPro; IPR008983; Tumour_necrosis_fac-like_dom.
DR Pfam; PF00386; C1q; 2.
DR PRINTS; PR00007; COMPLEMNTC1Q.
DR SMART; SM00110; C1Q; 2.
DR SUPFAM; SSF49842; SSF49842; 2.
DR PROSITE; PS50871; C1Q; 2.
PE 1: Evidence at protein level;
KW Cytokine; Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..16
FT /evidence="ECO:0000250"
FT CHAIN 17..326
FT /note="Complement C1q tumor necrosis factor-related protein
FT 4"
FT /id="PRO_0000003534"
FT DOMAIN 24..161
FT /note="C1q 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00368"
FT DOMAIN 170..315
FT /note="C1q 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00368"
FT REGION 164..193
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 273
FT /note="M -> R (in Ref. 1; AAY21929 and 2; BAB22473)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 326 AA; 35058 MW; 72339172B7B1051A CRC64;
MLLLLLGFLG PAACWALGPA GPGSSELRSA FSAARTTPLE GTSEMAVTFD KVYVNIGGDF
DAATGRFRCR VPGAYFFSFT AGKAPHKSLS VMLVRNRDEV QALAFDEQRR PGARRAASQS
AMLQLDYGDT VWLRLHGAPQ YALGAPGATF SGYLVYADAD ADAPARGPAA PEPRSAFSAA
RTRSLVGSDA APGPRHRPLA FDTELVNIGG DFDAAAGVFR CRLPGAYFFS FTLGKLPRKT
LSVKLMKNRD EVQAMIYDDG ASRRREMQSQ SVMLPLRRGD AVWLLSHDHD GYGAYSNHGK
YITFSGFLVY PDLAAAGPPA LKPPEL
