CRLF3_HUMAN
ID CRLF3_HUMAN Reviewed; 442 AA.
AC Q8IUI8; A6NJF3; B2R8C3; Q2MLY7; Q9UNI3; Q9Y6M8;
DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2004, sequence version 2.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Cytokine receptor-like factor 3;
DE AltName: Full=Cytokine receptor-like molecule 9;
DE Short=CREME-9;
DE AltName: Full=Cytokine receptor-related protein 4;
DE AltName: Full=Type I cytokine receptor-like factor p48;
GN Name=CRLF3; Synonyms=CREME9, CRLM9, CYTOR4, P48;
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] (ISOFORM 2), ALTERNATIVE SPLICING, FUNCTION,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Erythroleukemia;
RX PubMed=19427400; DOI=10.1016/j.biocel.2009.04.022;
RA Yang F., Xu Y.P., Li J., Duan S.S., Fu Y.J., Zhang Y., Zhao Y., Qiao W.T.,
RA Chen Q.M., Geng Y.Q., Che C.Y., Cao Y.L., Wang Y., Zhang L., Long L.,
RA He J., Cui Q.C., Chen S.C., Wang S.H., Liu L.;
RT "Cloning and characterization of a novel intracellular protein p48.2 that
RT negatively regulates cell cycle progression.";
RL Int. J. Biochem. Cell Biol. 41:2240-2250(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Farrah T., Adams R., Kho C.-J., Yamagiwa T.M., Madden K.L., Whitmore T.,
RA Jelmberg A., Pownder T., Lofton-Day C.E., Lok S.;
RT "An extended gap penalty scheme for profiles results in the discovery of a
RT novel cytokine receptor related transcript in an EST database.";
RL Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Liver;
RA Maeda M., Nomura H.;
RT "Cloning of a novel cytokine receptor-like molecule.";
RL Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Synovial cell;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=B-cell;
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 [7]
RP TISSUE SPECIFICITY.
RX PubMed=16865251;
RA Dang C., Gottschling M., Manning K., O'Currain E., Schneider S., Sterry W.,
RA Stockfleth E., Nindl I.;
RT "Identification of dysregulated genes in cutaneous squamous cell
RT carcinoma.";
RL Oncol. Rep. 16:513-519(2006).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 (ISOFORM 2), AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC -!- FUNCTION: May play a role in the negative regulation of cell cycle
CC progression. {ECO:0000269|PubMed:19427400}.
CC -!- INTERACTION:
CC Q8IUI8; P54253: ATXN1; NbExp=6; IntAct=EBI-2872414, EBI-930964;
CC Q8IUI8; P54252: ATXN3; NbExp=3; IntAct=EBI-2872414, EBI-946046;
CC Q8IUI8; P46379-2: BAG6; NbExp=3; IntAct=EBI-2872414, EBI-10988864;
CC Q8IUI8; Q8IUI8: CRLF3; NbExp=4; IntAct=EBI-2872414, EBI-2872414;
CC Q8IUI8; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-2872414, EBI-742054;
CC Q8IUI8; G5E9A7: DMWD; NbExp=3; IntAct=EBI-2872414, EBI-10976677;
CC Q8IUI8; P21333-2: FLNA; NbExp=3; IntAct=EBI-2872414, EBI-9641086;
CC Q8IUI8; P14136: GFAP; NbExp=3; IntAct=EBI-2872414, EBI-744302;
CC Q8IUI8; P04792: HSPB1; NbExp=3; IntAct=EBI-2872414, EBI-352682;
CC Q8IUI8; Q9UMF0: ICAM5; NbExp=3; IntAct=EBI-2872414, EBI-6398041;
CC Q8IUI8; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-2872414, EBI-1055254;
CC Q8IUI8; Q4G0X4: KCTD21; NbExp=3; IntAct=EBI-2872414, EBI-11976683;
CC Q8IUI8; O60333-2: KIF1B; NbExp=3; IntAct=EBI-2872414, EBI-10975473;
CC Q8IUI8; O14901: KLF11; NbExp=3; IntAct=EBI-2872414, EBI-948266;
CC Q8IUI8; Q96JM7-2: L3MBTL3; NbExp=3; IntAct=EBI-2872414, EBI-11985629;
CC Q8IUI8; Q8TCE9: LGALS14; NbExp=6; IntAct=EBI-2872414, EBI-10274069;
CC Q8IUI8; P31153: MAT2A; NbExp=3; IntAct=EBI-2872414, EBI-1050743;
CC Q8IUI8; Q8TDC0: MYOZ3; NbExp=3; IntAct=EBI-2872414, EBI-5662487;
CC Q8IUI8; P19404: NDUFV2; NbExp=3; IntAct=EBI-2872414, EBI-713665;
CC Q8IUI8; P07196: NEFL; NbExp=3; IntAct=EBI-2872414, EBI-475646;
CC Q8IUI8; P29474: NOS3; NbExp=3; IntAct=EBI-2872414, EBI-1391623;
CC Q8IUI8; O14832: PHYH; NbExp=3; IntAct=EBI-2872414, EBI-721853;
CC Q8IUI8; Q8N2W9: PIAS4; NbExp=3; IntAct=EBI-2872414, EBI-473160;
CC Q8IUI8; D3DTS7: PMP22; NbExp=3; IntAct=EBI-2872414, EBI-25882629;
CC Q8IUI8; P60891: PRPS1; NbExp=3; IntAct=EBI-2872414, EBI-749195;
CC Q8IUI8; Q96PK6: RBM14; NbExp=3; IntAct=EBI-2872414, EBI-954272;
CC Q8IUI8; P37840: SNCA; NbExp=3; IntAct=EBI-2872414, EBI-985879;
CC Q8IUI8; P14678-2: SNRPB; NbExp=3; IntAct=EBI-2872414, EBI-372475;
CC Q8IUI8; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-2872414, EBI-5235340;
CC Q8IUI8; Q13148: TARDBP; NbExp=6; IntAct=EBI-2872414, EBI-372899;
CC Q8IUI8; Q86WV8: TSC1; NbExp=3; IntAct=EBI-2872414, EBI-12806590;
CC Q8IUI8; Q9BRG1: VPS25; NbExp=12; IntAct=EBI-2872414, EBI-741945;
CC Q8IUI8; Q6P2D0: ZFP1; NbExp=3; IntAct=EBI-2872414, EBI-2555749;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19427400}. Note=The
CC EGFP- and MYC-tagged protein has been shown to be cytoplasmic.
CC {ECO:0000269|PubMed:19427400}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=p48.6;
CC IsoId=Q8IUI8-1; Sequence=Displayed;
CC Name=2; Synonyms=p48.2;
CC IsoId=Q8IUI8-2; Sequence=VSP_044648;
CC -!- TISSUE SPECIFICITY: Expressed in several embryonic and adult tissues,
CC including adult and fetal brain, liver, spleen and pancreas. Expressed
CC in adult, but not fetal kidney. Expressed in skin and squamous cell
CC carcinoma (SCC) and in several other cancer types. Also detected in
CC lesion actinic keratosis (AK). {ECO:0000269|PubMed:16865251,
CC ECO:0000269|PubMed:19427400}.
CC -!- SIMILARITY: Belongs to the cytokine receptor-like factor 3 family.
CC {ECO:0000305}.
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DR EMBL; DQ298450; ABC55264.1; -; mRNA.
DR EMBL; AF046059; AAD02422.1; -; mRNA.
DR EMBL; AF120151; AAD31758.1; -; mRNA.
DR EMBL; AK313315; BAG36120.1; -; mRNA.
DR EMBL; AC127024; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC023567; AAH23567.2; -; mRNA.
DR CCDS; CCDS32607.1; -. [Q8IUI8-1]
DR RefSeq; NP_057070.3; NM_015986.3. [Q8IUI8-1]
DR AlphaFoldDB; Q8IUI8; -.
DR SMR; Q8IUI8; -.
DR BioGRID; 119511; 30.
DR IntAct; Q8IUI8; 48.
DR MINT; Q8IUI8; -.
DR STRING; 9606.ENSP00000318804; -.
DR CarbonylDB; Q8IUI8; -.
DR GlyGen; Q8IUI8; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q8IUI8; -.
DR MetOSite; Q8IUI8; -.
DR PhosphoSitePlus; Q8IUI8; -.
DR BioMuta; CRLF3; -.
DR DMDM; 74762472; -.
DR OGP; Q9Y6M8; -.
DR EPD; Q8IUI8; -.
DR jPOST; Q8IUI8; -.
DR MassIVE; Q8IUI8; -.
DR MaxQB; Q8IUI8; -.
DR PaxDb; Q8IUI8; -.
DR PeptideAtlas; Q8IUI8; -.
DR PRIDE; Q8IUI8; -.
DR ProteomicsDB; 70577; -. [Q8IUI8-1]
DR Antibodypedia; 1925; 127 antibodies from 23 providers.
DR DNASU; 51379; -.
DR Ensembl; ENST00000324238.7; ENSP00000318804.6; ENSG00000176390.12. [Q8IUI8-1]
DR GeneID; 51379; -.
DR KEGG; hsa:51379; -.
DR MANE-Select; ENST00000324238.7; ENSP00000318804.6; NM_015986.4; NP_057070.3.
DR UCSC; uc002hfr.5; human. [Q8IUI8-1]
DR CTD; 51379; -.
DR DisGeNET; 51379; -.
DR GeneCards; CRLF3; -.
DR HGNC; HGNC:17177; CRLF3.
DR HPA; ENSG00000176390; Tissue enhanced (lymphoid).
DR MIM; 614853; gene.
DR neXtProt; NX_Q8IUI8; -.
DR OpenTargets; ENSG00000176390; -.
DR PharmGKB; PA26884; -.
DR VEuPathDB; HostDB:ENSG00000176390; -.
DR eggNOG; ENOG502QQI2; Eukaryota.
DR GeneTree; ENSGT00940000153469; -.
DR HOGENOM; CLU_057983_0_0_1; -.
DR InParanoid; Q8IUI8; -.
DR OMA; CNNNEGG; -.
DR OrthoDB; 881161at2759; -.
DR PhylomeDB; Q8IUI8; -.
DR TreeFam; TF328682; -.
DR PathwayCommons; Q8IUI8; -.
DR SignaLink; Q8IUI8; -.
DR BioGRID-ORCS; 51379; 17 hits in 1092 CRISPR screens.
DR ChiTaRS; CRLF3; human.
DR GeneWiki; CRLF3; -.
DR GenomeRNAi; 51379; -.
DR Pharos; Q8IUI8; Tbio.
DR PRO; PR:Q8IUI8; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q8IUI8; protein.
DR Bgee; ENSG00000176390; Expressed in trabecular bone tissue and 209 other tissues.
DR ExpressionAtlas; Q8IUI8; baseline and differential.
DR Genevisible; Q8IUI8; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0003677; F:DNA binding; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0030308; P:negative regulation of cell growth; IDA:UniProtKB.
DR GO; GO:2000134; P:negative regulation of G1/S transition of mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR CDD; cd00063; FN3; 1.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR003961; FN3_dom.
DR InterPro; IPR036116; FN3_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR SUPFAM; SSF49265; SSF49265; 1.
DR PROSITE; PS50853; FN3; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Coiled coil; Cytoplasm;
KW Reference proteome.
FT CHAIN 1..442
FT /note="Cytokine receptor-like factor 3"
FT /id="PRO_0000288936"
FT DOMAIN 181..274
FT /note="Fibronectin type-III"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT COILED 10..57
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..4
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:19427400, ECO:0000303|Ref.3"
FT /id="VSP_044648"
FT VARIANT 202
FT /note="V -> M (in dbSNP:rs3764418)"
FT /id="VAR_049180"
FT VARIANT 389
FT /note="L -> P (in dbSNP:rs11867457)"
FT /id="VAR_032539"
FT CONFLICT 42
FT /note="R -> K (in Ref. 2; AAD02422)"
FT /evidence="ECO:0000305"
FT CONFLICT 66
FT /note="L -> V (in Ref. 3; AAD31758)"
FT /evidence="ECO:0000305"
FT CONFLICT 189
FT /note="I -> L (in Ref. 1; ABC55264)"
FT /evidence="ECO:0000305"
FT MOD_RES Q8IUI8-2:1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
SQ SEQUENCE 442 AA; 49766 MW; 89F6CACD76397AF8 CRC64;
MRGAMELEPE LLLQEARENV EAAQSYRREL GHRLEGLREA RRQIKESASQ TRDVLKQHFN
DLKGTLGKLL DERLVTLLQE VDTIEQETIK PLDDCQKLIE HGVNTAEDLV REGEIAMLGG
VGEENEKLWS FTKKASHIQL DSLPEVPLLV DVPCLSAQLD DSILNIVKDH IFKHGTVASR
PPVQIEELIE KPGGIIVRWC KVDDDFTAQD YRLQFRKCTS NHFEDVYVGS ETEFIVLHID
PNVDYQFRVC ARGDGRQEWS PWSVPQIGHS TLVPHEWTAG FEGYSLSSRR NIALRNDSES
SGVLYSRAPT YFCGQTLTFR VETVGQPDRR DSIGVCAEKQ DGYDSLQRDQ AVCISTNGAV
FVNGKEMTNQ LPAVTSGSTV TFDIEAVTLG TTSNNEGGHF KLRVTISSNN REVVFDWLLD
QSCGSLYFGC SFFYPGWKVL VF