FNDC4_HUMAN
ID FNDC4_HUMAN Reviewed; 234 AA.
AC Q9H6D8; D6W560;
DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Fibronectin type III domain-containing protein 4;
DE AltName: Full=Fibronectin type III repeat-containing protein 1;
DE Flags: Precursor;
GN Name=FNDC4; Synonyms=FRCP1; ORFNames=UNQ6389/PRO21134;
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].
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 MRNA].
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Uterus;
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 [6]
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=27066907; DOI=10.1038/ncomms11314;
RA Bosma M., Gerling M., Pasto J., Georgiadi A., Graham E., Shilkova O.,
RA Iwata Y., Almer S., Soederman J., Toftgaard R., Wermeling F.,
RA Bostroem E.A., Bostroem P.A.;
RT "FNDC4 acts as an anti-inflammatory factor on macrophages and improves
RT colitis in mice.";
RL Nat. Commun. 7:11314-11314(2016).
CC -!- FUNCTION: Acts as an anti-inflammatory factor in the intestine and
CC colon. Binds to and acts on macrophages to down-regulate pro-
CC inflammatory gene expression. Affects key macrophage functions,
CC including phagocytosis, by down-regulating many key pathways for
CC macrophage activation, partly via by STAT3 activation and signaling.
CC May be required to dampen the immunological response in colitis.
CC {ECO:0000250|UniProtKB:Q3TR08}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000305}. Secreted
CC {ECO:0000250|UniProtKB:Q3TR08}. Note=The N-terminus is probably cleaved
CC to release a secreted extracellular portion of the protein.
CC {ECO:0000250|UniProtKB:Q3TR08}.
CC -!- TISSUE SPECIFICITY: Up-regulated in colon cells of patients with
CC inflammatory bowel disease (IBD). {ECO:0000269|PubMed:27066907}.
CC -!- INDUCTION: Induced by TGFB1. {ECO:0000269|PubMed:27066907}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AK026015; BAB15321.1; -; mRNA.
DR EMBL; AY358136; AAQ88503.1; -; mRNA.
DR EMBL; AC074117; AAY14849.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00569.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00570.1; -; Genomic_DNA.
DR EMBL; BC032725; AAH32725.1; -; mRNA.
DR CCDS; CCDS1756.1; -.
DR RefSeq; NP_073734.1; NM_022823.2.
DR AlphaFoldDB; Q9H6D8; -.
DR SMR; Q9H6D8; -.
DR BioGRID; 122314; 29.
DR IntAct; Q9H6D8; 12.
DR STRING; 9606.ENSP00000264703; -.
DR GlyConnect; 2008; 1 N-Linked glycan (1 site).
DR GlyGen; Q9H6D8; 3 sites, 1 N-linked glycan (1 site).
DR iPTMnet; Q9H6D8; -.
DR PhosphoSitePlus; Q9H6D8; -.
DR BioMuta; FNDC4; -.
DR DMDM; 74762739; -.
DR MassIVE; Q9H6D8; -.
DR PaxDb; Q9H6D8; -.
DR PeptideAtlas; Q9H6D8; -.
DR PRIDE; Q9H6D8; -.
DR Antibodypedia; 28574; 287 antibodies from 22 providers.
DR DNASU; 64838; -.
DR Ensembl; ENST00000264703.4; ENSP00000264703.3; ENSG00000115226.10.
DR GeneID; 64838; -.
DR KEGG; hsa:64838; -.
DR MANE-Select; ENST00000264703.4; ENSP00000264703.3; NM_022823.3; NP_073734.1.
DR UCSC; uc002rkx.4; human.
DR CTD; 64838; -.
DR DisGeNET; 64838; -.
DR GeneCards; FNDC4; -.
DR HGNC; HGNC:20239; FNDC4.
DR HPA; ENSG00000115226; Tissue enhanced (adrenal gland, liver).
DR MIM; 611905; gene.
DR neXtProt; NX_Q9H6D8; -.
DR OpenTargets; ENSG00000115226; -.
DR PharmGKB; PA134883376; -.
DR VEuPathDB; HostDB:ENSG00000115226; -.
DR eggNOG; ENOG502QQ99; Eukaryota.
DR GeneTree; ENSGT00390000004923; -.
DR HOGENOM; CLU_089166_0_0_1; -.
DR InParanoid; Q9H6D8; -.
DR OMA; PMGARQK; -.
DR OrthoDB; 1198350at2759; -.
DR PhylomeDB; Q9H6D8; -.
DR TreeFam; TF325415; -.
DR PathwayCommons; Q9H6D8; -.
DR SignaLink; Q9H6D8; -.
DR BioGRID-ORCS; 64838; 10 hits in 1071 CRISPR screens.
DR GenomeRNAi; 64838; -.
DR Pharos; Q9H6D8; Tbio.
DR PRO; PR:Q9H6D8; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9H6D8; protein.
DR Bgee; ENSG00000115226; Expressed in left adrenal gland cortex and 135 other tissues.
DR Genevisible; Q9H6D8; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0050728; P:negative regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0071559; P:response to transforming growth factor beta; IEP: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 Pfam; PF00041; fn3; 1.
DR SMART; SM00060; FN3; 1.
DR SUPFAM; SSF49265; SSF49265; 1.
DR PROSITE; PS50853; FN3; 1.
PE 2: Evidence at transcript level;
KW Glycoprotein; Membrane; Reference proteome; Secreted; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..44
FT /evidence="ECO:0000255"
FT CHAIN 45..234
FT /note="Fibronectin type III domain-containing protein 4"
FT /id="PRO_0000271379"
FT TOPO_DOM 45..167
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 168..188
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 189..234
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 47..140
FT /note="Fibronectin type-III"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT REGION 122..160
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 197..234
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 216..234
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 52
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 97
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 147
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 234 AA; 25159 MW; 5BCD23C12F583727 CRC64;
MPSGCHSSPP SGLRGDMASL VPLSPYLSPT VLLLVSCDLG FVRADRPPSP VNVTVTHLRA
NSATVSWDVP EGNIVIGYSI SQQRQNGPGQ RVIREVNTTT RACALWGLAE DSDYTVQVRS
IGLRGESPPG PRVHFRTLKG SDRLPSNSSS PGDITVEGLD GERPLQTGEV VIIVVVLLMW
AAVIGLFCRQ YDIIKDNDSN NNPKEKGKGP EQSPQGRPVG TRQKKSPSIN TIDV
