ID C1QT4_HUMAN Reviewed; 329 AA.
AC Q9BXJ3; Q8IV25;
DT 16-APR-2002, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 24-JAN-2024, entry version 161.
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;
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 [MRNA].
RA Holloway J.L., Lok S.;
RT "Homo sapiens complement-c1q tumor necrosis factor-related protein.";
RL Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 PROTEIN SEQUENCE OF N-TERMINUS, FUNCTION, SUBCELLULAR LOCATION, INDUCTION,
RP TISSUE SPECIFICITY, AND CAUTION.
RX PubMed=21658842; DOI=10.1016/j.canlet.2011.05.005;
RA Li Q., Wang L., Tan W., Peng Z., Luo Y., Zhang Y., Zhang G., Na D., Jin P.,
RA Shi T., Ma D., Wang L.;
RT "Identification of C1qTNF-related protein 4 as a potential cytokine that
RT stimulates the STAT3 and NF-kappaB pathways and promotes cell survival in
RT human cancer cells.";
RL Cancer Lett. 308:203-214(2011).
RN [4]
RP TISSUE SPECIFICITY.
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 [5]
RP FUNCTION, AND CAUTION.
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).
RN [6]
RP VARIANT GLN-198, AND CHARACTERIZATION OF VARIANT GLN-198.
RX PubMed=29177435; DOI=10.1093/hmg/ddx407;
RA Pullabhatla V., Roberts A.L., Lewis M.J., Mauro D., Morris D.L.,
RA Odhams C.A., Tombleson P., Liljedahl U., Vyse S., Simpson M.A., Sauer S.,
RA de Rinaldis E., Syvaenen A.C., Vyse T.J.;
RT "De novo mutations implicate novel genes in systemic lupus erythematosus.";
RL Hum. Mol. Genet. 27:421-429(2018).
RN [7]
RP VARIANT ASP-301.
RX PubMed=29721947; DOI=10.1007/978-3-319-75402-4_27;
RA Biswas P., Naeem M.A., Ali M.H., Assir M.Z., Khan S.N., Riazuddin S.,
RA Hejtmancik J.F., Riazuddin S.A., Ayyagari R.;
RT "Whole-Exome Sequencing Identifies Novel Variants that Co-segregates with
RT Autosomal Recessive Retinal Degeneration in a Pakistani Pedigree.";
RL Adv. Exp. Med. Biol. 1074:219-228(2018).
CC -!- FUNCTION: May be involved in the regulation of the inflammatory
CC network. Its role as pro- or anti-inflammatory seems to be context
CC dependent (PubMed:21658842, PubMed:27086950). Seems to have some role
CC in regulating food intake and energy balance when administered in the
CC brain. This effect is sustained over a two-day period, and it is
CC accompanied by decreased expression of orexigenic neuropeptides in the
CC hypothalamus 3 hours post-injection (By similarity).
CC {ECO:0000250|UniProtKB:Q8R066, ECO:0000269|PubMed:21658842,
CC ECO:0000269|PubMed:27086950}.
CC -!- SUBUNIT: Homomultimer. Forms trimers, hexamers and high molecular
CC weight oligomers (By similarity). {ECO:0000250|UniProtKB:Q8R066}.
CC -!- INTERACTION:
CC Q9BXJ3; Q96JM7-2: L3MBTL3; NbExp=3; IntAct=EBI-11955105, EBI-11985629;
CC Q9BXJ3; Q96N21: TEPSIN; NbExp=3; IntAct=EBI-11955105, EBI-11139477;
CC Q9BXJ3; Q9UMX0: UBQLN1; NbExp=3; IntAct=EBI-11955105, EBI-741480;
CC Q9BXJ3; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-11955105, EBI-947187;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:21658842}.
CC -!- TISSUE SPECIFICITY: Widely expressed at low levels (PubMed:21658842).
CC Highest levels in adipocyte tissue and brain (PubMed:24366864).
CC {ECO:0000269|PubMed:21658842, ECO:0000269|PubMed:24366864}.
CC -!- INDUCTION: Up-regulated by IL6. {ECO:0000269|PubMed:21658842}.
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 (PubMed:21658842).
CC While it seems to have the opposite effect in macrophages
CC (PubMed:27086950). {ECO:0000269|PubMed:21658842,
CC ECO:0000269|PubMed:27086950}.
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. {ECO:0000250|UniProtKB:Q8R066}.
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DR EMBL; AF329838; AAK17962.1; -; mRNA.
DR EMBL; BC035628; AAH35628.1; -; mRNA.
DR CCDS; CCDS7942.1; -.
DR RefSeq; NP_114115.2; NM_031909.2.
DR RefSeq; XP_016872654.1; XM_017017165.1.
DR RefSeq; XP_016872655.1; XM_017017166.1.
DR AlphaFoldDB; Q9BXJ3; -.
DR SMR; Q9BXJ3; -.
DR BioGRID; 125391; 5.
DR IntAct; Q9BXJ3; 5.
DR STRING; 9606.ENSP00000302274; -.
DR iPTMnet; Q9BXJ3; -.
DR PhosphoSitePlus; Q9BXJ3; -.
DR BioMuta; C1QTNF4; -.
DR DMDM; 116241274; -.
DR EPD; Q9BXJ3; -.
DR MassIVE; Q9BXJ3; -.
DR PaxDb; 9606-ENSP00000302274; -.
DR PeptideAtlas; Q9BXJ3; -.
DR ProteomicsDB; 79435; -.
DR Antibodypedia; 13803; 201 antibodies from 30 providers.
DR DNASU; 114900; -.
DR Ensembl; ENST00000302514.4; ENSP00000302274.3; ENSG00000172247.4.
DR Ensembl; ENST00000642567.2; ENSP00000496508.1; ENSG00000284838.2.
DR GeneID; 114900; -.
DR KEGG; hsa:114900; -.
DR MANE-Select; ENST00000302514.4; ENSP00000302274.3; NM_031909.3; NP_114115.2.
DR UCSC; uc001ngc.3; human.
DR AGR; HGNC:14346; -.
DR CTD; 114900; -.
DR DisGeNET; 114900; -.
DR GeneCards; C1QTNF4; -.
DR HGNC; HGNC:14346; C1QTNF4.
DR HPA; ENSG00000172247; Tissue enriched (brain).
DR MIM; 614911; gene.
DR neXtProt; NX_Q9BXJ3; -.
DR NIAGADS; ENSG00000172247; -.
DR OpenTargets; ENSG00000172247; -.
DR PharmGKB; PA25631; -.
DR VEuPathDB; HostDB:ENSG00000172247; -.
DR eggNOG; ENOG502QX94; Eukaryota.
DR GeneTree; ENSGT00940000161832; -.
DR HOGENOM; CLU_048377_0_0_1; -.
DR InParanoid; Q9BXJ3; -.
DR OMA; GTDEKQT; -.
DR OrthoDB; 4625069at2759; -.
DR PhylomeDB; Q9BXJ3; -.
DR TreeFam; TF329591; -.
DR PathwayCommons; Q9BXJ3; -.
DR SignaLink; Q9BXJ3; -.
DR BioGRID-ORCS; 114900; 177 hits in 1146 CRISPR screens.
DR GenomeRNAi; 114900; -.
DR Pharos; Q9BXJ3; Tbio.
DR PRO; PR:Q9BXJ3; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9BXJ3; Protein.
DR Bgee; ENSG00000172247; Expressed in primary visual cortex and 91 other cell types or tissues.
DR ExpressionAtlas; Q9BXJ3; baseline and differential.
DR Genevisible; Q9BXJ3; HS.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IDA:UniProtKB.
DR GO; GO:0070105; P:positive regulation of interleukin-6-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:1901224; P:positive regulation of non-canonical NF-kappaB signal transduction; IDA:UniProtKB.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IDA:UniProtKB.
DR Gene3D; 2.60.120.40; -; 2.
DR InterPro; IPR001073; C1q_dom.
DR InterPro; IPR008983; Tumour_necrosis_fac-like_dom.
DR PANTHER; PTHR22923; CEREBELLIN-RELATED; 1.
DR PANTHER; PTHR22923:SF107; COMPLEMENT C1Q TUMOR NECROSIS FACTOR-RELATED PROTEIN 4; 1.
DR Pfam; PF00386; C1q; 2.
DR PRINTS; PR00007; COMPLEMNTC1Q.
DR SMART; SM00110; C1Q; 2.
DR SUPFAM; SSF49842; TNF-like; 2.
DR PROSITE; PS50871; C1Q; 2.
PE 1: Evidence at protein level;
KW Cytokine; Direct protein sequencing; Disease variant; Reference proteome;
KW Repeat; Secreted; Signal.
FT SIGNAL 1..16
FT /evidence="ECO:0000269|PubMed:21658842"
FT CHAIN 17..329
FT /note="Complement C1q tumor necrosis factor-related protein
FT 4"
FT /id="PRO_0000003533"
FT DOMAIN 25..162
FT /note="C1q 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00368"
FT DOMAIN 172..317
FT /note="C1q 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00368"
FT REGION 164..195
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 198
FT /note="H -> Q (found in a patient with systemic lupus
FT erythematosus; uncertain significance; inhibits TNF-
FT mediated NF-kB activation)"
FT /evidence="ECO:0000269|PubMed:29177435"
FT /id="VAR_081086"
FT VARIANT 301
FT /note="G -> D (found in a patient with autosomal recessive
FT retinitis pigmentosa; uncertain significance;
FT dbSNP:rs1418830230)"
FT /evidence="ECO:0000269|PubMed:29721947"
FT /id="VAR_081087"
FT CONFLICT 141
FT /note="Q -> H (in Ref. 1; AAK17962)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 329 AA; 35256 MW; 16064DA8182A6732 CRC64;
MLPLLLGLLG PAACWALGPT PGPGSSELRS AFSAARTTPL EGTSEMAVTF DKVYVNIGGD
FDVATGQFRC RVPGAYFFSF TAGKAPHKSL SVMLVRNRDE VQALAFDEQR RPGARRAASQ
SAMLQLDYGD TVWLRLHGAP QYALGAPGAT FSGYLVYADA DADAPARGPP APPEPRSAFS
AARTRSLVGS DAGPGPRHQP LAFDTEFVNI GGDFDAAAGV FRCRLPGAYF FSFTLGKLPR
KTLSVKLMKN RDEVQAMIYD DGASRRREMQ SQSVMLALRR GDAVWLLSHD HDGYGAYSNH
GKYITFSGFL VYPDLAPAAP PGLGASELL
//
