P09486 (SPRC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
SPARC

Alternative name(s):
Basement-membrane protein 40
Short name=BM-40
Osteonectin
Short name=ON
Secreted protein acidic and rich in cysteine

Gene names

Name:	SPARC
Synonyms:	ON

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	303 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	Appears to regulate cell growth through interactions with the extracellular matrix and cytokines. Binds calcium and copper, several types of collagen, albumin, thrombospondin, PDGF and cell membranes. There are two calcium binding sites; an acidic domain that binds 5 to 8 Ca2+ with a low affinity and an EF-hand loop that binds a Ca2+ ion with a high affinity.
Subcellular location	Secreted › extracellular space › extracellular matrix › basement membrane. Note: In or around the basement membrane. Ref.10 Ref.11 Ref.12 Ref.13
Developmental stage	Expressed at high levels in tissues undergoing morphogenesis, remodeling and wound repair.
Sequence similarities	Belongs to the SPARC family. Contains 1 EF-hand domain. Contains 1 follistatin-like domain. Contains 1 Kazal-like domain.
Sequence caution	The sequence AAA60993.1 differs from that shown. Reason: Contaminating sequence. Sequence of unknown origin in the C-terminal part.

Ontologies

Keywords
Cellular component	Basement membrane Extracellular matrix Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Ligand	Calcium Copper Metal-binding
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to growth factor stimulus Inferred from electronic annotation. Source: Compara heart development Inferred from electronic annotation. Source: Compara inner ear development Inferred from electronic annotation. Source: Compara lung development Inferred from electronic annotation. Source: Compara ossification Traceable author statement PubMed 7034958. Source: ProtInc platelet activation Traceable author statement. Source: Reactome platelet degranulation Traceable author statement. Source: Reactome regulation of cell proliferation Inferred from electronic annotation. Source: Compara response to L-ascorbic acid Inferred from electronic annotation. Source: Compara response to cAMP Inferred from electronic annotation. Source: Compara response to cadmium ion Inferred from electronic annotation. Source: Compara response to calcium ion Inferred from electronic annotation. Source: Compara response to cytokine stimulus Inferred from electronic annotation. Source: Compara response to ethanol Inferred from electronic annotation. Source: Compara response to glucocorticoid stimulus Inferred from electronic annotation. Source: Compara response to gravity Inferred from electronic annotation. Source: Compara response to lead ion Inferred from electronic annotation. Source: Compara response to lipopolysaccharide Inferred from electronic annotation. Source: Compara response to peptide hormone stimulus Inferred from electronic annotation. Source: Compara signal transduction Inferred from electronic annotation. Source: InterPro
Cellular_component	basement membrane Inferred from electronic annotation. Source: UniProtKB-SubCell extracellular space Inferred from electronic annotation. Source: InterPro nucleus Inferred from electronic annotation. Source: Compara platelet alpha granule lumen Traceable author statement. Source: Reactome proteinaceous extracellular matrix Traceable author statement PubMed 7034958. Source: ProtInc
Molecular_function	calcium ion binding Traceable author statement PubMed 7034958. Source: ProtInc collagen binding Traceable author statement PubMed 7034958. Source: ProtInc extracellular matrix binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
faf	Q2TV77	4	EBI-2800983,EBI-6405263	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 17

17

Ref.9 Ref.10

Chain

18 – 303

286

SPARC

PRO_0000020304

Regions

Domain

71 – 93

23

Follistatin-like

Domain

89 – 151

63

Kazal-like

Domain

261 – 296

36

EF-hand

Calcium binding

274 – 285

12

Compositional bias

22 – 69

48

Asp/Glu-rich (acidic; binds calcium)

Amino acid modifications

Glycosylation

116

1

N-linked (GlcNAc...) Ref.15 Ref.16

Disulfide bond

72 ↔ 83

Ref.15

Disulfide bond

77 ↔ 93

Ref.15

Disulfide bond

95 ↔ 130

Ref.15

Disulfide bond

101 ↔ 123

Ref.15

Disulfide bond

112 ↔ 149

Ref.15

Disulfide bond

155 ↔ 265

Ref.15

Disulfide bond

273 ↔ 289

Ref.15

Natural variations

Natural variant

19

1

P → S.
Corresponds to variant rs6874468 [ dbSNP | Ensembl ].

VAR_050431

Natural variant

70

1

N → S.
Corresponds to variant rs13359508 [ dbSNP | Ensembl ].

VAR_059530

Experimental info

Mutagenesis

166

1

R → A, L or K: Strongly reduced collagen binding. Ref.16

Mutagenesis

173

1

N → A or Q: Strongly reduced collagen binding. Ref.16

Mutagenesis

259

1

L → A: Loss of collagen binding. Ref.16

Mutagenesis

262

1

M → A: Strongly reduced collagen binding. Ref.16

Mutagenesis

263

1

E → A: Loss of collagen binding. Ref.16

Sequence conflict

42 – 43

2

SV → PT AA sequence Ref.9

Sequence conflict

205

1

R → L in AAA60993. Ref.3

Sequence conflict

269

1

F → L in AAA60993. Ref.3

Secondary structure

1

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303

Helix Strand Turn

Details...

Turn

71 – 74

4

Beta strand

81 – 85

5

Beta strand

91 – 95

5

Helix

98 – 100

3

Helix

107 – 109

3

Beta strand

111 – 113

3

Turn

114 – 116

3

Beta strand

118 – 121

4

Helix

122 – 131

10

Turn

132 – 134

3

Helix

136 – 140

5

Beta strand

143 – 148

6

Helix

157 – 181

25

Beta strand

183 – 188

6

Helix

190 – 201

12

Helix

213 – 222

10

Helix

224 – 227

4

Helix

228 – 238

11

Beta strand

244 – 247

4

Turn

249 – 252

4

Helix

253 – 256

4

Turn

257 – 259

3

Helix

260 – 262

3

Helix

263 – 265

3

Helix

266 – 273

8

Beta strand

278 – 282

5

Helix

283 – 289

7

Helix

294 – 296

3

Helix

299 – 301

3

Sequences

	Sequence		Length	Mass (Da)
	P09486 [UniParc]. Last modified July 1, 1989. Version 1. Checksum: B914599F79705945	FASTA	303	34,632
	10 20 30 40 50 60 MRAWIFFLLC LAGRALAAPQ QEALPDETEV VEETVAEVTE VSVGANPVQV EVGEFDDGAE 70 80 90 100 110 120 ETEEEVVAEN PCQNHHCKHG KVCELDENNT PMCVCQDPTS CPAPIGEFEK VCSNDNKTFD 130 140 150 160 170 180 SSCHFFATKC TLEGTKKGHK LHLDYIGPCK YIPPCLDSEL TEFPLRMRDW LKNVLVTLYE 190 200 210 220 230 240 RDEDNNLLTE KQKLRVKKIH ENEKRLEAGD HPVELLARDF EKNYNMYIFP VHWQFGQLDQ 250 260 270 280 290 300 HPIDGYLSHT ELAPLRAPLI PMEHCTTRFF ETCDLDNDKY IALDEWAGCF GIKQKDIDKD LVI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and complete amino acid sequences of human and murine basement membrane protein BM-40 (SPARC, osteonectin)." Lankat-Buttgereit B., Mann K., Deutzmann R., Timpl R., Krieg T. FEBS Lett. 236:352-356(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE. Tissue: Placenta.
[2]	"Molecular analysis of the cDNA for human SPARC/osteonectin/BM-40: sequence, expression, and localization of the gene to chromosome 5q31-q33." Swaroop A., Hogan B.L.M., Francke U. Genomics 2:37-47(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Structure of human osteonectin based upon analysis of cDNA and genomic sequences." Villarreal X.C., Mann K.G., Long G.L. Biochemistry 28:6483-6491(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Structure and expression of osteonectin mRNA in human tissue." Young M.F., Day A.A., Dominquez P., McQuillan C.I., Fisher L.W., Termine J.D. Connect. Tissue Res. 24:17-28(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Muscle, PNS and Skin.
[8]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-154.
[9]	"Purification and partial characterization of small proteoglycans I and II, bone sialoproteins I and II, and osteonectin from the mineral compartment of developing human bone." Fisher L.W., Hawkins G.R., Tuross N., Termine J.D. J. Biol. Chem. 262:9702-9708(1987) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 18-53, CHARACTERIZATION.
[10]	"Human platelet osteonectin: release, surface expression, and partial characterization." Kelm R.J. Jr., Mann K.G. Blood 75:1105-1113(1990) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 18-41, CHARACTERIZATION, SUBCELLULAR LOCATION.
[11]	"Osteonectin/SPARC/BM-40 in human decidua and carcinoma, tissues characterized by de novo formation of basement membrane." Wewer U.M., Albrechtsen R., Fisher L.W., Young M.F., Termine J.D. Am. J. Pathol. 132:345-355(1988) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[12]	"Immunolocalization of SPARC, tenascin, and thrombospondin in pulmonary fibrosis." Kuhn C., Mason R.J. Am. J. Pathol. 147:1759-1769(1995) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[13]	"BM-40 (osteonectin, SPARC) is expressed both in the epidermal and in the dermal compartment of adult human skin." Hunzelmann N., Hafner M., Anders S., Krieg T., Nischt R. J. Invest. Dermatol. 110:122-126(1998) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[14]	"Structure of a novel extracellular Ca(2+)-binding module in BM-40." Hohenester E., Maurer P., Hahoenadl C., Timpl R., Jansonius J.N., Engel J. Nat. Struct. Biol. 3:67-73(1996) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 153-303.
[15]	"Crystal structure of a pair of follistatin-like and EF-hand calcium-binding domains in BM-40." Hohenester E., Maurer P., Timpl R. EMBO J. 16:3778-3786(1997) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 71-303 IN COMPLEX WITH CALCIUM IONS, GLYCOSYLATION AT ASN-116, DISULFIDE BONDS.
[16]	"Crystal structure and mapping by site-directed mutagenesis of the collagen-binding epitope of an activated form of BM-40/SPARC/osteonectin." Sasaki T., Hohenester E., Gohring W., Timpl R. EMBO J. 17:1625-1634(1998) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 71-303 IN COMPLEX WITH CALCIUM IONS, GLYCOSYLATION AT ASN-116, INTERACTION WITH COLLAGEN, MUTAGENESIS OF ARG-166; ASN-173; LEU-259; MET-262 AND GLU-263.
+	Additional computationally mapped references.

Web resources

Wikipedia

Osteonectin entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Y00755 mRNA. Translation: CAA68724.1.
J03040 mRNA. Translation: AAA60570.1.
M25746 , M25738, M25739, M25740, M25741, M25742, M25743, M25744, M25745 Genomic DNA. Translation: AAA60993.1. Sequence problems.
CR456799 mRNA. Translation: CAG33080.1.
CH471062 Genomic DNA. Translation: EAW61668.1.
CH471062 Genomic DNA. Translation: EAW61669.1.
CH471062 Genomic DNA. Translation: EAW61670.1.
CH471062 Genomic DNA. Translation: EAW61672.1.
BC004974 mRNA. Translation: AAH04974.1.
BC008011 mRNA. Translation: AAH08011.1.
BC072457 mRNA. Translation: AAH72457.1.
AL709729 mRNA. No translation available.

IPI

IPI00014572.

PIR

GEHUN. A32821.

RefSeq

NP_003109.1. NM_003118.3.

UniGene

Hs.111779.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BMO	X-ray	3.10	A/B	71-303	[»]
1NUB	X-ray	2.80	A/B	71-303	[»]
1SRA	X-ray	2.00	A	153-303	[»]
2V53	X-ray	3.20	A	70-303	[»]

ProteinModelPortal

P09486.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-46426N.

IntAct

P09486. 2 interactions.

MINT

MINT-3006855.

STRING

9606.ENSP00000231061.

PTM databases

PhosphoSite

P09486.

Polymorphism databases

DMDM

129283.

2D gel databases

OGP

P09486.

Proteomic databases

PaxDb

P09486.

PeptideAtlas

P09486.

PRIDE

P09486.

Protocols and materials databases

DNASU

6678.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000231061; ENSP00000231061; ENSG00000113140.

GeneID

6678.

KEGG

hsa:6678.

UCSC

uc003lui.3. human.

Organism-specific databases

CTD

6678.

GeneCards

GC05M151021.

HGNC

HGNC:11219. SPARC.

HPA

CAB002306.
HPA002989.
HPA003020.

MIM

182120. gene.

neXtProt

NX_P09486.

PharmGKB

PA36055.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG147672.

HOVERGEN

HBG002746.

InParanoid

P09486.

OMA

CELDESN.

OrthoDB

EOG4T7842.

Enzyme and pathway databases

Reactome

REACT_604. Hemostasis.

Gene expression databases

ArrayExpress

P09486.

Bgee

P09486.

CleanEx

HS_SPARC.

Genevestigator

P09486.

GermOnline

ENSG00000113140. Homo sapiens.

Family and domain databases

Gene3D

1.10.238.10. 1 hit.

InterPro

IPR011992. EF-hand-like_dom.
IPR018247. EF_Hand_1_Ca_BS.
IPR003645. Fol_N.
IPR015369. Follistatin/Osteonectin_EGF.
IPR002350. Kazal_dom.
IPR001999. Osteonectin_CS.
IPR019577. SPARC/Testican_Ca-bd-dom.
[Graphical view]

Pfam

PF09289. FOLN. 1 hit.
PF00050. Kazal_1. 1 hit.
PF10591. SPARC_Ca_bdg. 1 hit.
[Graphical view]

SMART

SM00274. FOLN. 1 hit.
SM00280. KAZAL. 1 hit.
[Graphical view]

PROSITE

PS00018. EF_HAND_1. 1 hit.
PS50222. EF_HAND_2. False negative.
PS51465. KAZAL_2. 1 hit.
PS00612. OSTEONECTIN_1. 1 hit.
PS00613. OSTEONECTIN_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

SPARC. human.

DrugBank

DB00102. Becaplermin.

EvolutionaryTrace

P09486.

GenomeRNAi

6678.

NextBio

26041.

PMAP-CutDB

P09486.

SOURCE

Search...

Entry information

Entry name

SPRC_HUMAN

Accession

Primary (citable) accession number: P09486
Secondary accession number(s): D3DQH9, Q6IBK4

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	July 1, 1989
Last modified:	May 29, 2013
This is version 153 of the entry and version 1 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.