ASPN_MOUSE
ID ASPN_MOUSE Reviewed; 373 AA.
AC Q99MQ4; Q9D6A2;
DT 20-JUN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Asporin;
DE AltName: Full=Periodontal ligament-associated protein 1;
DE Short=PLAP-1;
DE Flags: Precursor;
GN Name=Aspn;
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/6 X 129/SvJ; TISSUE=Aorta;
RX PubMed=11152692; DOI=10.1074/jbc.m010932200;
RA Lorenzo P., Aspberg A., Oennerfjord P., Bayliss M.T., Neame P.J.,
RA Heinegaard D.;
RT "Identification and characterization of asporin. A novel member of the
RT leucine-rich repeat protein family closely related to decorin and
RT biglycan.";
RL J. Biol. Chem. 276:12201-12211(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE.
RX PubMed=11152695; DOI=10.1074/jbc.m011290200;
RA Henry S.P., Takanosu M., Boyd T.C., Mayne P.M., Eberspaecher H., Zhou W.,
RA de Crombrugghe B., Hoeoek M., Mayne R.;
RT "Expression pattern and gene characterization of asporin. A newly
RT discovered member of the leucine-rich repeat protein family.";
RL J. Biol. Chem. 276:12212-12221(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Skin;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Mammary gland;
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 FUNCTION, TISSUE SPECIFICITY, AND INTERACTION WITH BMP2.
RX PubMed=17522060; DOI=10.1074/jbc.m611181200;
RA Yamada S., Tomoeda M., Ozawa Y., Yoneda S., Terashima Y., Ikezawa K.,
RA Ikegawa S., Saito M., Toyosawa S., Murakami S.;
RT "PLAP-1/asporin, a novel negative regulator of periodontal ligament
RT mineralization.";
RL J. Biol. Chem. 282:23070-23080(2007).
RN [6]
RP FUNCTION, AND INTERACTION WITH TGFB1; TGFB2 AND TGFB3.
RX PubMed=17827158; DOI=10.1074/jbc.m700522200;
RA Nakajima M., Kizawa H., Saitoh M., Kou I., Miyazono K., Ikegawa S.;
RT "Mechanisms for asporin function and regulation in articular cartilage.";
RL J. Biol. Chem. 282:32185-32192(2007).
RN [7]
RP INDUCTION BY TGFB1, AND TISSUE SPECIFICITY.
RX PubMed=17804408; DOI=10.1074/jbc.m706262200;
RA Kou I., Nakajima M., Ikegawa S.;
RT "Expression and regulation of the osteoarthritis-associated protein
RT asporin.";
RL J. Biol. Chem. 282:32193-32199(2007).
RN [8]
RP FUNCTION, MUTAGENESIS OF ARG-170; GLU-194 AND ARG-219, AND DOMAIN LRR.
RX PubMed=18407830; DOI=10.1016/j.bbrc.2008.03.158;
RA Tomoeda M., Yamada S., Shirai H., Ozawa Y., Yanagita M., Murakami S.;
RT "PLAP-1/asporin inhibits activation of BMP receptor via its leucine-rich
RT repeat motif.";
RL Biochem. Biophys. Res. Commun. 371:191-196(2008).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, and Pancreas;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [10]
RP FUNCTION, AND INTERACTION WITH TGFB1 AND TYPE II COLLAGEN.
RX PubMed=20052601; DOI=10.1007/s00774-009-0145-8;
RA Kou I., Nakajima M., Ikegawa S.;
RT "Binding characteristics of the osteoarthritis-associated protein
RT asporin.";
RL J. Bone Miner. Metab. 28:395-402(2010).
CC -!- FUNCTION: Binds calcium and plays a role in osteoblast-driven collagen
CC biomineralization activity (By similarity). Critical regulator of TGF-
CC beta in articular cartilage and plays an essential role in cartilage
CC homeostasis and osteoarthritis (OA) pathogenesis. Negatively regulates
CC chondrogenesis in the articular cartilage by blocking the TGF-
CC beta/receptor interaction on the cell surface and inhibiting the
CC canonical TGF-beta/Smad signal. Negatively regulates periodontal
CC ligament (PDL) differentiation and mineralization to ensure that the
CC PDL is not ossified and to maintain homeostasis of the tooth-supporting
CC system. Inhibits BMP2-induced cytodifferentiation of PDL cells by
CC preventing its binding to BMPR1B/BMP type-1B receptor, resulting in
CC inhibition of BMP-dependent activation of SMAD proteins. Inhibits the
CC interaction between TGFB1 and TGF-beta receptor type II in the presence
CC of heparin/heparan sulfate in vitro. {ECO:0000250,
CC ECO:0000269|PubMed:17522060, ECO:0000269|PubMed:17827158,
CC ECO:0000269|PubMed:18407830, ECO:0000269|PubMed:20052601}.
CC -!- SUBUNIT: Interacts with type I collagen. DCN can inhibit collagen
CC binding (By similarity). Interacts with TGFB1, TGFB2 and TGFB3. DCN,
CC BGN, and FMOD inhibit binding to TGFB1. Interacts with BMP2. Interacts
CC in vitro with type II collagen. {ECO:0000250,
CC ECO:0000269|PubMed:17522060, ECO:0000269|PubMed:17827158,
CC ECO:0000269|PubMed:20052601}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Higher expression in heart, also detected in
CC kidney, stomach, testes, and skin but only weakly in lung, skeletal
CC muscle, small intestine, and thymus. Expressed specifically and
CC predominantly in the periodontal ligament (PDL). During tooth
CC development, strong expression is seen in the dental follicle, which is
CC the progenitor tissue that forms cementum, alveolar bone, and the PDL.
CC Expressed in the perichondria of the maxilla, mandible, vertebrae, and
CC long bones. Predominantly expressed in the perichondrium/periosteum of
CC long bones (at protein level). {ECO:0000269|PubMed:17522060,
CC ECO:0000269|PubMed:17804408}.
CC -!- DEVELOPMENTAL STAGE: At 12.5 dpc, it is present in the mandibular as
CC well as maxillary components of the first branchial arch. Also detected
CC in the thoracic body wall adjacent to the heart. At 13.5 dpc, it is
CC detected in the mesenchyme lateral to Meckel's cartilage. Pronounced
CC expression is observed in the perichondrium of the humerus, ribs, and
CC scapula. At 14.5 dpc, it is detected in the mesenchymal condensations
CC lateral to Meckel's cartilage, in the perichondrium surrounding the
CC central cartilaginous elements of the vertebra and also in the dermal
CC mesenchyme. At 15.5 dpc, it is expressed in the
CC perichondrium/periosteum of the long bones (i.e. femur, tibia, and
CC fibula), some of the flat bones at the base of the skull (i.e. sphenoid
CC bone), ribs, clavicle, and vertebrae. Also detected in the
CC intramembranous bones of the maxilla and mandible (alveolar bone) and a
CC strong expression is observed in sagittal sections of the subcutaneous
CC muscles or panniculus carnosus of the thorax, trunk, and head/ neck
CC (platysma muscle) region. Very little expression is detected in the
CC major parenchymal organs (with the exception of the large bronchi of
CC the lung). Its expression is prominent in the developing mouse
CC skeleton, particularly in the perichondrium/periosteum of
CC cartilage/bone, and is also found in other specialized connective
CC tissues such as tendon, sclera, the connective tissue sheath
CC surrounding muscle and dermis. In the sclera of the eye it is first
CC detected at 15.5 dpc and stronger expression was detected at 17.5 dpc.
CC {ECO:0000269|PubMed:11152695}.
CC -!- INDUCTION: By TGFB1. Induction requires ALK5 kinase activity and SMAD3.
CC {ECO:0000269|PubMed:17804408}.
CC -!- DOMAIN: The repeats LRR 9, LRR 10 and LRR 11 are involved in binding
CC type I collagen. The poly-Asp region is involved in binding calcium (By
CC similarity). The LRR 5 repeat can inhibit BMP2-induced
CC cytodifferentiation and may be involved in the interaction with BMP2.
CC {ECO:0000250, ECO:0000269|PubMed:18407830}.
CC -!- SIMILARITY: Belongs to the small leucine-rich proteoglycan (SLRP)
CC family. SLRP class I subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AK014504; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF316825; AAK35162.1; -; mRNA.
DR EMBL; AK014504; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC034888; AAH34888.1; -; mRNA.
DR CCDS; CCDS26503.1; -.
DR RefSeq; NP_001165952.1; NM_001172481.1.
DR RefSeq; NP_079987.2; NM_025711.3.
DR AlphaFoldDB; Q99MQ4; -.
DR SMR; Q99MQ4; -.
DR IntAct; Q99MQ4; 2.
DR MINT; Q99MQ4; -.
DR STRING; 10090.ENSMUSP00000021820; -.
DR GlyGen; Q99MQ4; 2 sites.
DR PhosphoSitePlus; Q99MQ4; -.
DR MaxQB; Q99MQ4; -.
DR PaxDb; Q99MQ4; -.
DR PRIDE; Q99MQ4; -.
DR ProteomicsDB; 281924; -.
DR Antibodypedia; 2015; 201 antibodies from 27 providers.
DR DNASU; 66695; -.
DR Ensembl; ENSMUST00000021820; ENSMUSP00000021820; ENSMUSG00000021388.
DR Ensembl; ENSMUST00000177948; ENSMUSP00000136728; ENSMUSG00000021388.
DR GeneID; 66695; -.
DR KEGG; mmu:66695; -.
DR UCSC; uc007qjm.2; mouse.
DR CTD; 54829; -.
DR MGI; MGI:1913945; Aspn.
DR VEuPathDB; HostDB:ENSMUSG00000021388; -.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00940000157444; -.
DR HOGENOM; CLU_000288_186_0_1; -.
DR InParanoid; Q99MQ4; -.
DR OMA; DFIRYKN; -.
DR OrthoDB; 826997at2759; -.
DR PhylomeDB; Q99MQ4; -.
DR TreeFam; TF334562; -.
DR BioGRID-ORCS; 66695; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Aspn; mouse.
DR PRO; PR:Q99MQ4; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; Q99MQ4; protein.
DR Bgee; ENSMUSG00000021388; Expressed in diaphysis of femur and 222 other tissues.
DR ExpressionAtlas; Q99MQ4; baseline and differential.
DR Genevisible; Q99MQ4; MM.
DR GO; GO:0042995; C:cell projection; ISO:MGI.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0031012; C:extracellular matrix; IDA:MGI.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0005518; F:collagen binding; IEA:InterPro.
DR GO; GO:0030282; P:bone mineralization; ISS:UniProtKB.
DR GO; GO:0070171; P:negative regulation of tooth mineralization; IDA:UniProtKB.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:1902617; P:response to fluoride; IEA:Ensembl.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR028548; Asporin.
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 InterPro; IPR016352; SLRP_I_decor/aspor/byglycan.
DR PANTHER; PTHR45712:SF2; PTHR45712:SF2; 1.
DR Pfam; PF13855; LRR_8; 3.
DR Pfam; PF01462; LRRNT; 1.
DR PIRSF; PIRSF002490; SLRP_I; 1.
DR SMART; SM00369; LRR_TYP; 7.
DR SMART; SM00013; LRRNT; 1.
DR PROSITE; PS51450; LRR; 7.
PE 1: Evidence at protein level;
KW Biomineralization; Calcium; Disulfide bond; Extracellular matrix;
KW Glycoprotein; Leucine-rich repeat; Reference proteome; Repeat; Secreted;
KW Signal.
FT SIGNAL 1..15
FT /evidence="ECO:0000255"
FT PROPEP 16..32
FT /evidence="ECO:0000255"
FT /id="PRO_0000032729"
FT CHAIN 33..373
FT /note="Asporin"
FT /id="PRO_0000032730"
FT DOMAIN 59..95
FT /note="LRRNT"
FT REPEAT 96..117
FT /note="LRR 1"
FT REPEAT 120..141
FT /note="LRR 2"
FT REPEAT 144..166
FT /note="LRR 3"
FT REPEAT 167..186
FT /note="LRR 4"
FT REPEAT 189..212
FT /note="LRR 5"
FT REPEAT 235..255
FT /note="LRR 6"
FT REPEAT 259..280
FT /note="LRR 7"
FT REPEAT 283..305
FT /note="LRR 8"
FT REPEAT 306..327
FT /note="LRR 9"
FT REPEAT 328..349
FT /note="LRR 10"
FT REPEAT 350..373
FT /note="LRR 11"
FT REGION 159..205
FT /note="Interaction with TGFB1"
FT CARBOHYD 48
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000250"
FT CARBOHYD 275
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 68..74
FT /evidence="ECO:0000250|UniProtKB:P21809"
FT DISULFID 72..81
FT /evidence="ECO:0000250|UniProtKB:P21809"
FT DISULFID 326..359
FT /evidence="ECO:0000250|UniProtKB:P21809"
FT MUTAGEN 170
FT /note="R->E: Partial inhibition of BMP2-induced
FT cytodifferentiation; when associated with E-219."
FT /evidence="ECO:0000269|PubMed:18407830"
FT MUTAGEN 194
FT /note="E->G,K: Rescues the inhibitory effects of ASPN on
FT BMP2-induced cytodifferentiation."
FT /evidence="ECO:0000269|PubMed:18407830"
FT MUTAGEN 219
FT /note="R->E: Partial inhibition of BMP2-induced
FT cytodifferentiation; when associated with E-170."
FT /evidence="ECO:0000269|PubMed:18407830"
SQ SEQUENCE 373 AA; 42573 MW; A50C4C82AABCFC35 CRC64;
MKEYVMLLLL AVCSAKPFFS PSHTALKNMM LKDMEDTDDD DNDDDDNSLF PTKEPVNPFF
PFDLFPTCPF GCQCYSRVVH CSDLGLTSVP NNIPFDTRMV DLQNNKIKEI KENDFKGLTS
LYALILNNNK LTKIHPKTFL TTKKLRRLYL SHNQLSEIPL NLPKSLAELR IHDNKVKKIQ
KDTFKGMNAL HVLEMSANPL ENNGIEPGAF EGVTVFHIRI AEAKLTSIPK GLPPTLLELH
LDFNKISTVE LEDLKRYREL QRLGLGNNRI TDIENGTFAN IPRVREIHLE HNKLKKIPSG
LQELKYLQII FLHYNSIAKV GVNDFCPTVP KMKKSLYSAI SLFNNPMKYW EIQPATFRCV
LGRMSVQLGN VGK
