Q9BXN1 (ASPN_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Asporin

Alternative name(s):
Periodontal ligament-associated protein 1
Short name=PLAP-1

Gene names

Name:	ASPN
Synonyms:	PLAP1, SLRR1C
ORF Names:	UNQ215/PRO241

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	380 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Negatively regulates periodontal ligament (PDL) differentiation and mineralization to ensure that the PDL is not ossified and to maintain homeostasis of the tooth-supporting system. Inhibits BMP2-induced cytodifferentiation of PDL cells by preventing its binding to BMPR1B/BMP type-1B receptor, resulting in inhibition of BMP-dependent activation of SMAD proteins By similarity. Critical regulator of TGF-beta in articular cartilage and plays an essential role in cartilage homeostasis and osteoarthritis (OA) pathogenesis. Negatively regulates chondrogenesis in the articular cartilage by blocking the TGF-beta/receptor interaction on the cell surface and inhibiting the canonical TGF-beta/Smad signal. Binds calcium and plays a role in osteoblast-driven collagen biomineralization activity. Ref.9 Ref.11
Subunit structure	Interacts with TGFB1, TGFB2 and TGFB3. DCN, BGN, and FMOD inhibit binding to TGFB1. Interacts with BMP2. Interacts in vitro with type II collagen By similarity. Interacts with type I collagen. DCN can inhibit collagen binding. Ref.11
Subcellular location	Secreted › extracellular space › extracellular matrix Ref.9.
Tissue specificity	Higher levels in osteoarthritic articular cartilage, aorta, uterus. Moderate expression in small intestine, heart, liver, bladder, ovary, stomach, and in the adrenal, thyroid, and mammary glands. Low expression in trachea, bone marrow, and lung. Co-localizes with TGFB1 in chondrocytes within osteoarthritic (OA) lesions of articular cartilage. Ref.9
Induction	By TGFB1. Ref.9
Domain	The LRR 5 repeat can inhibit BMP2-induced cytodifferentiation and may be involved in the interaction with BMP2 By similarity. The repeats LRR 10, LRR 11 and LRR 12 are involved in binding type I collagen. The poly-Asp region is involved in binding calcium. Ref.11
Post-translational modification	There is no serine/glycine dipeptide sequence expected for the attachment of O-linked glycosaminoglycans and this is probably not a proteoglycan. The O-linked polysaccharide on 54-Ser is probably the mucin type linked to GalNAc. The N-linked glycan at Asn-282 is composed of variable structures of GlcNAc, mannose, fucose, HexNAc and hexose.
Polymorphism	The poly-Asp region of ASPN is polymorphic and ranges at least from 11 to 17 Asp.
Involvement in disease	Osteoarthritis 3 (OS3) [MIM:607850]: A degenerative disease of the joints characterized by degradation of the hyaline articular cartilage and remodeling of the subchondral bone with sclerosis. Clinical symptoms include pain and joint stiffness often leading to significant disability and joint replacement. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Susceptibility to osteoarthritis is conferred by a triplet repeat expansion polymorphism. ASPN allele having 14 aspartic acid repeats in the N-terminal region of the protein (D14), is overrepresented relative to the common allele having 13 aspartic acid repeats (D13). The frequency of the D14 allele increases with disease severity. The D14 allele is also overrepresented in individuals with hip osteoarthritis. Ref.8 Intervertebral disc disease (IDD) [MIM:603932]: A common musculo-skeletal disorder caused by degeneration of intervertebral disks of the lumbar spine. It results in low-back pain and unilateral leg pain. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Susceptibility to intervertebral disk disease, particularly lumbar disk degeneration, is conferred by a triplet repeat expansion polymorphism. ASPN allele having 14 aspartic acid repeats in the N-terminal region of the protein (D14), is associated with the disorder in some populations (Ref.10). Ref.10
Sequence similarities	Belongs to the small leucine-rich proteoglycan (SLRP) family. SLRP class I subfamily. Contains 11 LRR (leucine-rich) repeats. Contains 1 LRRNT domain.
Sequence caution	The sequence BAA90967.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Biomineralization
Cellular component	Extracellular matrix Secreted
Coding sequence diversity	Polymorphism Triplet repeat expansion
Domain	Leucine-rich repeat Repeat Signal
Ligand	Calcium
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	bone mineralization Inferred from direct assay Ref.11. Source: UniProtKB negative regulation of tooth mineralization Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of transforming growth factor beta receptor signaling pathway Inferred from direct assay Ref.9. Source: UniProtKB
Cellular_component	proteinaceous extracellular matrix Inferred from direct assay Ref.9. Source: UniProtKB
Molecular_function	calcium ion binding Inferred from direct assay Ref.11. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 14	14	Potential
	Propeptide	15 – 32	18	Potential		PRO_0000032727
	Chain	33 – 380	348	Asporin		PRO_0000032728
Regions
	Domain	66 – 102	37	LRRNT
	Repeat	103 – 124	22	LRR 1
	Repeat	127 – 148	22	LRR 2
	Repeat	151 – 173	23	LRR 3
	Repeat	174 – 193	20	LRR 4
	Repeat	196 – 219	24	LRR 5
	Repeat	242 – 263	22	LRR 6
	Repeat	266 – 287	22	LRR 7
	Repeat	290 – 312	23	LRR 8
	Repeat	313 – 334	22	LRR 9
	Repeat	335 – 357	23	LRR 10
	Repeat	358 – 380	23	LRR 11
	Region	166 – 212	47	Interaction with TGFB1 By similarity
	Compositional bias	35 – 53	19	Poly-Asp
	Compositional bias	77 – 90	14	Cys-rich
Amino acid modifications
	Glycosylation	55	1	O-linked (GalNAc...) Probable
	Glycosylation	282	1	N-linked (GlcNAc...) Ref.1 Ref.12
	Disulfide bond	75 ↔ 81		Ref.11
	Disulfide bond	79 ↔ 88		Ref.11
	Disulfide bond	333 ↔ 366		Ref.11
Experimental info
	Sequence conflict	238 – 243	6	GLPPTL → DNLPSF in BAB55060. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q9BXN1 [UniParc]. Last modified October 14, 2008. Version 2. Checksum: 2746A977FDCEBA5F	FASTA	380	43,417
	10 20 30 40 50 60 MKEYVLLLFL ALCSAKPFFS PSHIALKNMM LKDMEDTDDD DDDDDDDDDD DEDNSLFPTR 70 80 90 100 110 120 EPRSHFFPFD LFPMCPFGCQ CYSRVVHCSD LGLTSVPTNI PFDTRMLDLQ NNKIKEIKEN 130 140 150 160 170 180 DFKGLTSLYG LILNNNKLTK IHPKAFLTTK KLRRLYLSHN QLSEIPLNLP KSLAELRIHE 190 200 210 220 230 240 NKVKKIQKDT FKGMNALHVL EMSANPLDNN GIEPGAFEGV TVFHIRIAEA KLTSVPKGLP 250 260 270 280 290 300 PTLLELHLDY NKISTVELED FKRYKELQRL GLGNNKITDI ENGSLANIPR VREIHLENNK 310 320 330 340 350 360 LKKIPSGLPE LKYLQIIFLH SNSIARVGVN DFCPTVPKMK KSLYSAISLF NNPVKYWEMQ 370 380 PATFRCVLSR MSVQLGNFGM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification and characterization of asporin. A novel member of the leucine-rich repeat protein family closely related to decorin and biglycan." Lorenzo P., Aspberg A., Oennerfjord P., Bayliss M.T., Neame P.J., Heinegaard D. J. Biol. Chem. 276:12201-12211(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, GLYCOSYLATION AT SER-55 AND ASN-282, MASS SPECTROMETRY, POLYMORPHISM OF POLY-ASP REGION. Tissue: Cartilage.
[2]	"Expression profile of active genes in human periodontal ligament and isolation of PLAP-1, a novel SLRP family gene." Yamada S., Murakami S., Matoba R., Ozawa Y., Yokokoji T., Nakahira Y., Ikezawa K., Takayama S., Matsubara K., Okada H. Gene 275:279-286(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Colon and Embryo.
[4]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"Expression pattern and gene characterization of asporin. A newly discovered member of the leucine-rich repeat protein family." Henry S.P., Takanosu M., Boyd T.C., Mayne P.M., Eberspaecher H., Zhou W., de Crombrugghe B., Hoeoek M., Mayne R. J. Biol. Chem. 276:12212-12221(2001) [PubMed] [Europe PMC] [Abstract] Cited for: PARTIAL NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Heart.
[8]	"An aspartic acid repeat polymorphism in asporin inhibits chondrogenesis and increases susceptibility to osteoarthritis." Kizawa H., Kou I., Iida A., Sudo A., Miyamoto Y., Fukuda A., Mabuchi A., Kotani A., Kawakami A., Yamamoto S., Uchida A., Nakamura K., Notoya K., Nakamura Y., Ikegawa S. Nat. Genet. 37:138-144(2005) [PubMed] [Europe PMC] [Abstract] Cited for: ASSOCIATION WITH OS3.
[9]	"Mechanisms for asporin function and regulation in articular cartilage." Nakajima M., Kizawa H., Saitoh M., Kou I., Miyazono K., Ikegawa S. J. Biol. Chem. 282:32185-32192(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INDUCTION BY TGFB1, TISSUE SPECIFICITY.
[10]	"Association of the asporin D14 allele with lumbar-disc degeneration in Asians." Song Y.Q., Cheung K.M., Ho D.W., Poon S.C., Chiba K., Kawaguchi Y., Hirose Y., Alini M., Grad S., Yee A.F., Leong J.C., Luk K.D., Yip S.P., Karppinen J., Cheah K.S., Sham P., Ikegawa S., Chan D. Am. J. Hum. Genet. 82:744-747(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO IDD.
[11]	"Asporin competes with decorin for collagen binding, binds calcium and promotes osteoblast collagen mineralization." Kalamajski S., Aspberg A., Lindblom K., Heinegaard D., Oldberg A. Biochem. J. 423:53-59(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MASS SPECTROMETRY, INTERACTION WITH TYPE I COLLAGEN, DISULFIDE BOND, DOMAIN.
[12]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-282, MASS SPECTROMETRY. Tissue: Liver.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF316824 mRNA. Translation: AAK35161.1. AY029191 mRNA. Translation: AAK31800.1. AK000136 mRNA. Translation: BAA90967.1. Different initiation. AK027359 mRNA. Translation: BAB55060.1. AY358329 mRNA. Translation: AAQ88695.1. AL137848 Genomic DNA. Translation: CAI16697.1. CH471089 Genomic DNA. Translation: EAW62822.1.
IPI	IPI00418431.
RefSeq	NP_001180264.1. NM_001193335.1. NP_060150.4. NM_017680.4.
UniGene	Hs.435655.
3D structure databases
ProteinModelPortal	Q9BXN1.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000364694.
PTM databases
PhosphoSite	Q9BXN1.
Polymorphism databases
DMDM	209572589.
Proteomic databases
PaxDb	Q9BXN1.
PRIDE	Q9BXN1.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000375544; ENSP00000364694; ENSG00000106819.
GeneID	54829.
KEGG	hsa:54829.
UCSC	uc004ase.2. human.
Organism-specific databases
CTD	54829.
GeneCards	GC09M095218.
HGNC	HGNC:14872. ASPN.
HPA	HPA008435. HPA024230.
MIM	603932. phenotype. 607850. phenotype. 608135. gene.
neXtProt	NX_Q9BXN1.
PharmGKB	PA25057.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG4886.
HOVERGEN	HBG016052.
InParanoid	Q9BXN1.
KO	K08120.
OMA	LCSAKPL.
OrthoDB	EOG4KWJT1.
PhylomeDB	Q9BXN1.
Gene expression databases
ArrayExpress	Q9BXN1.
Bgee	Q9BXN1.
CleanEx	HS_ASPN.
Genevestigator	Q9BXN1.
GermOnline	ENSG00000106819. Homo sapiens.
Family and domain databases
InterPro	IPR001611. Leu-rich_rpt. IPR000372. LRR-contain_N. IPR016352. SLRP_I_decor/aspor/byglycan. [Graphical view]
Pfam	PF01462. LRRNT. 1 hit. [Graphical view]
PIRSF	PIRSF002490. SLRP_I. 1 hit.
SMART	SM00013. LRRNT. 1 hit. [Graphical view]
PROSITE	PS51450. LRR. 7 hits. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	54829.
NextBio	57604.
SOURCE	Search...

Entry information

Entry name

ASPN_HUMAN

Accession

Primary (citable) accession number: Q9BXN1
Secondary accession number(s): Q5TBF3 , Q96K79, Q96LD0, Q9NXP3

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 20, 2002
Last sequence update:	October 14, 2008
Last modified:	May 1, 2013
This is version 117 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.