FMOD_HUMAN
ID FMOD_HUMAN Reviewed; 376 AA.
AC Q06828; Q15331; Q8IV47;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 10-FEB-2009, sequence version 2.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=Fibromodulin;
DE Short=FM;
DE AltName: Full=Collagen-binding 59 kDa protein;
DE AltName: Full=Keratan sulfate proteoglycan fibromodulin;
DE Short=KSPG fibromodulin;
DE Flags: Precursor;
GN Name=FMOD; Synonyms=FM, SLRR2E;
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 [GENOMIC DNA].
RX PubMed=8357838; DOI=10.1016/0167-4781(93)90117-v;
RA Antonsson P., Heinegaard D., Oldberg A.;
RT "Structure and deduced amino acid sequence of the human fibromodulin
RT gene.";
RL Biochim. Biophys. Acta 1174:204-206(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8093006; DOI=10.1042/bj3020527;
RA Hildebrand A., Romaris M., Rasmussen L.M., Heinegard D., Twardzik D.R.,
RA Border W.A., Ruoslahti E.;
RT "Interaction of the small interstitial proteoglycans biglycan, decorin and
RT fibromodulin with transforming growth factor beta.";
RL Biochem. J. 302:527-534(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
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 [7]
RP SULFATION AT TYR-20; TYR-38; TYR-39; TYR-45; TYR-47; TYR-53 AND TYR-55,
RP LACK OF SULFATION AT TYR-63 AND TYR-65, PYROGLUTAMATE FORMATION AT GLN-19,
RP AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=14551184; DOI=10.1074/jbc.m308689200;
RA Onnerfjord P., Heathfield T.F., Heinegaard D.;
RT "Identification of tyrosine sulfation in extracellular leucine-rich repeat
RT proteins using mass spectrometry.";
RL J. Biol. Chem. 279:26-33(2004).
RN [8]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-201.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
CC -!- FUNCTION: Affects the rate of fibrils formation. May have a primary
CC role in collagen fibrillogenesis (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Binds to type I and type II collagen. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix.
CC -!- PTM: Binds keratan sulfate chains. {ECO:0000269|PubMed:14551184}.
CC -!- SIMILARITY: Belongs to the small leucine-rich proteoglycan (SLRP)
CC family. SLRP class II subfamily. {ECO:0000305}.
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DR EMBL; X72913; CAA51418.1; -; Genomic_DNA.
DR EMBL; X75546; CAA53233.1; -; mRNA.
DR EMBL; AK291632; BAF84321.1; -; mRNA.
DR EMBL; AL359837; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471067; EAW91477.1; -; Genomic_DNA.
DR EMBL; BC035281; AAH35281.1; -; mRNA.
DR CCDS; CCDS30976.1; -.
DR PIR; S55275; S55275.
DR RefSeq; NP_002014.2; NM_002023.4.
DR PDB; 5MX0; X-ray; 2.21 A; A/B=18-376.
DR PDBsum; 5MX0; -.
DR AlphaFoldDB; Q06828; -.
DR SMR; Q06828; -.
DR BioGRID; 108618; 47.
DR IntAct; Q06828; 4.
DR MINT; Q06828; -.
DR STRING; 9606.ENSP00000347041; -.
DR GlyConnect; 1242; 54 N-Linked glycans (3 sites).
DR GlyGen; Q06828; 7 sites, 62 N-linked glycans (3 sites), 2 O-linked glycans (1 site).
DR PhosphoSitePlus; Q06828; -.
DR BioMuta; FMOD; -.
DR DMDM; 223590208; -.
DR jPOST; Q06828; -.
DR MassIVE; Q06828; -.
DR PaxDb; Q06828; -.
DR PeptideAtlas; Q06828; -.
DR PRIDE; Q06828; -.
DR ProteomicsDB; 58485; -.
DR Antibodypedia; 34544; 294 antibodies from 28 providers.
DR DNASU; 2331; -.
DR Ensembl; ENST00000354955.5; ENSP00000347041.4; ENSG00000122176.12.
DR GeneID; 2331; -.
DR KEGG; hsa:2331; -.
DR MANE-Select; ENST00000354955.5; ENSP00000347041.4; NM_002023.5; NP_002014.2.
DR UCSC; uc001gzr.5; human.
DR CTD; 2331; -.
DR DisGeNET; 2331; -.
DR GeneCards; FMOD; -.
DR HGNC; HGNC:3774; FMOD.
DR HPA; ENSG00000122176; Low tissue specificity.
DR MIM; 600245; gene.
DR neXtProt; NX_Q06828; -.
DR OpenTargets; ENSG00000122176; -.
DR PharmGKB; PA28190; -.
DR VEuPathDB; HostDB:ENSG00000122176; -.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00940000157007; -.
DR HOGENOM; CLU_000288_186_4_1; -.
DR InParanoid; Q06828; -.
DR OMA; YVRMSHN; -.
DR OrthoDB; 826997at2759; -.
DR PhylomeDB; Q06828; -.
DR TreeFam; TF334562; -.
DR PathwayCommons; Q06828; -.
DR Reactome; R-HSA-2022854; Keratan sulfate biosynthesis.
DR Reactome; R-HSA-2022857; Keratan sulfate degradation.
DR Reactome; R-HSA-3000178; ECM proteoglycans.
DR Reactome; R-HSA-3656225; Defective CHST6 causes MCDC1.
DR Reactome; R-HSA-3656243; Defective ST3GAL3 causes MCT12 and EIEE15.
DR Reactome; R-HSA-3656244; Defective B4GALT1 causes B4GALT1-CDG (CDG-2d).
DR SignaLink; Q06828; -.
DR BioGRID-ORCS; 2331; 5 hits in 1066 CRISPR screens.
DR ChiTaRS; FMOD; human.
DR GeneWiki; FMOD_(gene); -.
DR GenomeRNAi; 2331; -.
DR Pharos; Q06828; Tbio.
DR PRO; PR:Q06828; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q06828; protein.
DR Bgee; ENSG00000122176; Expressed in calcaneal tendon and 171 other tissues.
DR ExpressionAtlas; Q06828; baseline and differential.
DR Genevisible; Q06828; HS.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0031012; C:extracellular matrix; TAS:ProtInc.
DR GO; GO:0005576; C:extracellular region; HDA:BHF-UCL.
DR GO; GO:0005615; C:extracellular space; HDA:BHF-UCL.
DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR GO; GO:0043202; C:lysosomal lumen; TAS:Reactome.
DR GO; GO:0030199; P:collagen fibril organization; IEA:Ensembl.
DR GO; GO:0007181; P:transforming growth factor beta receptor complex assembly; TAS:ProtInc.
DR Gene3D; 3.80.10.10; -; 3.
DR InterPro; IPR027215; Fibromodulin.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR000372; LRRNT.
DR PANTHER; PTHR45712:SF4; PTHR45712:SF4; 1.
DR Pfam; PF13855; LRR_8; 3.
DR Pfam; PF01462; LRRNT; 1.
DR SMART; SM00369; LRR_TYP; 8.
DR SMART; SM00013; LRRNT; 1.
DR PROSITE; PS51450; LRR; 10.
PE 1: Evidence at protein level;
KW 3D-structure; Disulfide bond; Extracellular matrix; Glycoprotein;
KW Leucine-rich repeat; Proteoglycan; Pyrrolidone carboxylic acid;
KW Reference proteome; Repeat; Secreted; Signal; Sulfation.
FT SIGNAL 1..18
FT /evidence="ECO:0000250"
FT CHAIN 19..376
FT /note="Fibromodulin"
FT /id="PRO_0000032739"
FT DOMAIN 67..105
FT /note="LRRNT"
FT REPEAT 106..127
FT /note="LRR 1"
FT REPEAT 130..151
FT /note="LRR 2"
FT REPEAT 156..176
FT /note="LRR 3"
FT REPEAT 177..198
FT /note="LRR 4"
FT REPEAT 201..222
FT /note="LRR 5"
FT REPEAT 224..245
FT /note="LRR 6"
FT REPEAT 246..266
FT /note="LRR 7"
FT REPEAT 269..289
FT /note="LRR 8"
FT REPEAT 294..315
FT /note="LRR 9"
FT REPEAT 316..335
FT /note="LRR 10"
FT REPEAT 344..365
FT /note="LRR 11"
FT SITE 63
FT /note="Not sulfated"
FT /evidence="ECO:0000269|PubMed:14551184"
FT SITE 65
FT /note="Not sulfated"
FT /evidence="ECO:0000269|PubMed:14551184"
FT MOD_RES 19
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000269|PubMed:14551184"
FT MOD_RES 20
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000269|PubMed:14551184"
FT MOD_RES 38
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000305|PubMed:14551184"
FT MOD_RES 39
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000305|PubMed:14551184"
FT MOD_RES 45
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000305|PubMed:14551184"
FT MOD_RES 47
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000305|PubMed:14551184"
FT MOD_RES 53
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000269|PubMed:14551184"
FT MOD_RES 55
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000269|PubMed:14551184"
FT CARBOHYD 127
FT /note="N-linked (GlcNAc...) (keratan sulfate) asparagine"
FT /evidence="ECO:0000250"
FT CARBOHYD 166
FT /note="N-linked (GlcNAc...) (keratan sulfate) asparagine"
FT /evidence="ECO:0000250"
FT CARBOHYD 201
FT /note="N-linked (GlcNAc...) (keratan sulfate) asparagine"
FT /evidence="ECO:0000250"
FT CARBOHYD 291
FT /note="N-linked (GlcNAc...) (keratan sulfate) asparagine"
FT /evidence="ECO:0000250"
FT CARBOHYD 341
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 334..367
FT /evidence="ECO:0000250"
FT CONFLICT 4
FT /note="T -> A (in Ref. 2; CAA53233)"
FT /evidence="ECO:0000305"
FT CONFLICT 87
FT /note="P -> L (in Ref. 2; CAA53233)"
FT /evidence="ECO:0000305"
FT CONFLICT 210
FT /note="N -> D (in Ref. 2; CAA53233)"
FT /evidence="ECO:0000305"
FT CONFLICT 226
FT /note="I -> Y (in Ref. 1; CAA51418)"
FT /evidence="ECO:0000305"
FT CONFLICT 344
FT /note="K -> Q (in Ref. 1; CAA51418)"
FT /evidence="ECO:0000305"
FT CONFLICT 348
FT /note="L -> V (in Ref. 1; CAA51418 and 2; CAA53233)"
FT /evidence="ECO:0000305"
FT CONFLICT 355
FT /note="I -> M (in Ref. 1; CAA51418)"
FT /evidence="ECO:0000305"
FT CONFLICT 363
FT /note="D -> E (in Ref. 1; CAA51418)"
FT /evidence="ECO:0000305"
FT STRAND 89..91
FT /evidence="ECO:0007829|PDB:5MX0"
FT STRAND 108..111
FT /evidence="ECO:0007829|PDB:5MX0"
FT TURN 122..125
FT /evidence="ECO:0007829|PDB:5MX0"
FT STRAND 133..135
FT /evidence="ECO:0007829|PDB:5MX0"
FT HELIX 143..145
FT /evidence="ECO:0007829|PDB:5MX0"
FT TURN 148..153
FT /evidence="ECO:0007829|PDB:5MX0"
FT STRAND 159..161
FT /evidence="ECO:0007829|PDB:5MX0"
FT STRAND 164..166
FT /evidence="ECO:0007829|PDB:5MX0"
FT STRAND 179..182
FT /evidence="ECO:0007829|PDB:5MX0"
FT TURN 193..198
FT /evidence="ECO:0007829|PDB:5MX0"
FT STRAND 204..206
FT /evidence="ECO:0007829|PDB:5MX0"
FT TURN 216..221
FT /evidence="ECO:0007829|PDB:5MX0"
FT STRAND 227..229
FT /evidence="ECO:0007829|PDB:5MX0"
FT STRAND 248..250
FT /evidence="ECO:0007829|PDB:5MX0"
FT TURN 261..266
FT /evidence="ECO:0007829|PDB:5MX0"
FT STRAND 272..274
FT /evidence="ECO:0007829|PDB:5MX0"
FT HELIX 282..284
FT /evidence="ECO:0007829|PDB:5MX0"
FT TURN 287..290
FT /evidence="ECO:0007829|PDB:5MX0"
FT STRAND 297..299
FT /evidence="ECO:0007829|PDB:5MX0"
FT STRAND 317..319
FT /evidence="ECO:0007829|PDB:5MX0"
FT HELIX 330..332
FT /evidence="ECO:0007829|PDB:5MX0"
FT STRAND 338..340
FT /evidence="ECO:0007829|PDB:5MX0"
FT STRAND 347..349
FT /evidence="ECO:0007829|PDB:5MX0"
FT STRAND 352..354
FT /evidence="ECO:0007829|PDB:5MX0"
FT HELIX 357..359
FT /evidence="ECO:0007829|PDB:5MX0"
FT HELIX 364..366
FT /evidence="ECO:0007829|PDB:5MX0"
FT STRAND 373..375
FT /evidence="ECO:0007829|PDB:5MX0"
SQ SEQUENCE 376 AA; 43179 MW; DC19D5E6724AB004 CRC64;
MQWTSLLLLA GLFSLSQAQY EDDPHWWFHY LRSQQSTYYD PYDPYPYETY EPYPYGVDEG
PAYTYGSPSP PDPRDCPQEC DCPPNFPTAM YCDNRNLKYL PFVPSRMKYV YFQNNQITSI
QEGVFDNATG LLWIALHGNQ ITSDKVGRKV FSKLRHLERL YLDHNNLTRM PGPLPRSLRE
LHLDHNQISR VPNNALEGLE NLTALYLQHN EIQEVGSSMR GLRSLILLDL SYNHLRKVPD
GLPSALEQLY MEHNNVYTVP DSYFRGAPKL LYVRLSHNSL TNNGLASNTF NSSSLLELDL
SYNQLQKIPP VNTNLENLYL QGNRINEFSI SSFCTVVDVV NFSKLQVLRL DGNEIKRSAM
PADAPLCLRL ASLIEI
