Reviewed, UniProtKB/Swiss-Prot P04004 (VTNC_HUMAN)

Names and origin

Protein names

Recommended name:
    Vitronectin
Alternative name(s):
    Serum-spreading factor
      Short name=S-protein
    V75
Cleaved into the following 3 chains:
    1- Recommended name:
            Vitronectin V65 subunit
    2- Recommended name:
            Vitronectin V10 subunit
    3- Recommended name:
            Somatomedin-B

Gene names

Name:

VTN

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	478 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	Vitronectin is a cell adhesion and spreading factor found in serum and tissues. Vitronectin interact with glycosaminoglycans and proteoglycans. Is recognized by certain members of the integrin family and serves as a cell-to-substrate adhesion molecule. Inhibitor of the membrane-damaging effect of the terminal cytolytic complement pathway. Somatomedin-B is a growth hormone-dependent serum factor with protease-inhibiting activity.
Subunit structure	Exists in two forms: a single chain 75 kDa form (V75) and a clipped form composed of two chains (65 kDa and 10 kDa) (V65+V10) which are held together by a disulfide bond. Interacts with SERPINE1/PAI1 and insulin. Ref.9 Ref.10 Ref.15
Subcellular location	Secreted › extracellular space.
Tissue specificity	Plasma.
Domain	The SMB domain mediates interaction with SERPINE1/PAI1. The heparin-binding domain mediates interaction with insulin.
Post-translational modification	Sulfated on 2 tyrosine residues. N- and O-glycosylated By similarity. Phosphorylation on Thr-69 and Thr-76 favors cell adhesion and spreading. It has been suggested that the active SMB domain may be permitted considerable disulfide bond heterogeneity or variability, thus two alternate disulfide patterns based on 3D structures are described with 1 disulfide bond conserved in both.
Sequence similarities	Contains 4 hemopexin-like domains. Contains 1 SMB (somatomedin-B) domain.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Repeat Signal
Ligand	Heparin-binding
PTM	Disulfide bond Glycoprotein Phosphoprotein Sulfation
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	immune response Traceable author statement. Source: ProtInc
Cellular component	extracellular space Traceable author statement. Source: ProtInc
Molecular function	heparin binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Ref.25 Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
SERPINE1	P05121	1	EBI-1036653,EBI-953978

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 19

19

Ref.9 Ref.8

Chain

20 – 478

459

Vitronectin

PRO_0000036394

Chain

20 – 398

379

Vitronectin V65 subunit

PRO_0000036395

Peptide

20 – 63

44

Somatomedin-B

PRO_0000036396

Chain

399 – 478

80

Vitronectin V10 subunit

PRO_0000036397

Regions

Domain

20 – 63

44

SMB

Domain

161 – 204

44

Hemopexin-like 1

Domain

206 – 252

47

Hemopexin-like 2

Domain

254 – 304

51

Hemopexin-like 3

Domain

425 – 472

48

Hemopexin-like 4

Region

362 – 395

34

Heparin-binding

Motif

64 – 66

3

Cell attachment site

Sites

Site

398 – 399

2

Cleavage

Amino acid modifications

Modified residue

69

1

Phosphothreonine; by CK2; in vitro Ref.16

Modified residue

75

1

Sulfotyrosine

Modified residue

76

1

Phosphothreonine; by CK2; in vitro Ref.16

Modified residue

78

1

Sulfotyrosine

Modified residue

171

1

Phosphoserine Ref.20

Modified residue

282

1

Sulfotyrosine Potential

Modified residue

312

1

Phosphoserine Ref.21 Ref.22 Ref.23

Modified residue

397

1

Phosphoserine; by PKA Ref.11 Ref.14

Modified residue

417

1

Sulfotyrosine Potential

Modified residue

420

1

Sulfotyrosine Potential

Glycosylation

86

1

N-linked (GlcNAc...) Ref.22 Ref.18 Ref.19

Glycosylation

169

1

N-linked (GlcNAc...) Ref.18 Ref.19

Glycosylation

242

1

N-linked (GlcNAc...) Ref.18 Ref.19

Disulfide bond

24 ↔ 40

Alternate By similarity

Disulfide bond

24 ↔ 28

Alternate Ref.17

Disulfide bond

28 ↔ 58

Alternate By similarity

Disulfide bond

38 ↔ 51

Alternate By similarity

Disulfide bond

38 ↔ 40

Alternate Ref.17

Disulfide bond

44 ↔ 50

Ref.17

Disulfide bond

51 ↔ 58

Alternate Ref.17

Disulfide bond

293 ↔ 430

Ref.17

Natural variations

Natural variant

122

1

A → S: dbSNP rs2227741. Ref.6

VAR_012983

Natural variant

268

1

R → Q: dbSNP rs2227723. Ref.6

VAR_012984

Natural variant

400

1

T → M: dbSNP rs704. Ref.6 Ref.7

VAR_012985

Experimental info

Mutagenesis

69

1

T → A: Abolishes phosphorylation by CK2 and inhibits adhesion and spreading; when associated with A-76. Ref.16

Mutagenesis

69

1

T → E: Abolishes phosphorylation by CK2 and enhances adhesion and spreading; when associated with E-76. Ref.16

Mutagenesis

76

1

T → A: Abolishes phosphorylation by CK2 and inhibits adhesion and spreading; when associated with A-69. Ref.16

Mutagenesis

76

1

T → E: Abolishes phosphorylation by CK2 and enhances adhesion and spreading; when associated with E-69. Ref.16

Sequence conflict

50

1

C → N AA sequence Ref.8

Sequence conflict

225

1

S → N Ref.3

Sequence conflict

225

1

S → N Ref.4

Sequence conflict

366

1

A → T in CAA26933. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

478

Helix Strand Turn

Details...

Beta strand

36 – 39

4

Helix

44 – 47

4

Helix

54 – 57

4

Beta strand

65 – 68

4

Sequences

	Sequence		Length	Mass (Da)
	P04004-1 [UniParc]. Last modified October 23, 1986. Version 1. Checksum: 0D6DB5591CBFEF45	FASTA	478	54,306
	10 20 30 40 50 60 MAPLRPLLIL ALLAWVALAD QESCKGRCTE GFNVDKKCQC DELCSYYQSC CTDYTAECKP 70 80 90 100 110 120 QVTRGDVFTM PEDEYTVYDD GEEKNNATVH EQVGGPSLTS DLQAQSKGNP EQTPVLKPEE 130 140 150 160 170 180 EAPAPEVGAS KPEGIDSRPE TLHPGRPQPP AEEELCSGKP FDAFTDLKNG SLFAFRGQYC 190 200 210 220 230 240 YELDEKAVRP GYPKLIRDVW GIEGPIDAAF TRINCQGKTY LFKGSQYWRF EDGVLDPDYP 250 260 270 280 290 300 RNISDGFDGI PDNVDAALAL PAHSYSGRER VYFFKGKQYW EYQFQHQPSQ EECEGSSLSA 310 320 330 340 350 360 VFEHFAMMQR DSWEDIFELL FWGRTSAGTR QPQFISRDWH GVPGQVDAAM AGRIYISGMA 370 380 390 400 410 420 PRPSLAKKQR FRHRNRKGYR SQRGHSRGRN QNSRRPSRAT WLSLFSSEES NLGANNYDDY 430 440 450 460 470 RMDWLVPATC EPIQSVFFFS GDKYYRVNLR TRRVDTVDPP YPRSIAQYWL GCPAPGHL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complete amino acid sequence of human vitronectin deduced from cDNA. Similarity of cell attachment sites in vitronectin and fibronectin." Suzuki S., Oldberg A., Hayman E.G., Pierschbacher M.D., Ruoslahti E. EMBO J. 4:2519-2524(1985) [PubMed: 2414098] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	Suzuki S., Oldberg A., Hayman E.G., Pierschbacher M.D., Ruoslahti E. Submitted (JUN-1986) to the PIR data bank Cited for: SEQUENCE REVISION.
[3]	"Molecular cloning of S-protein, a link between complement, coagulation and cell-substrate adhesion." Jenne D.E., Stanley K.K. EMBO J. 4:3153-3157(1985) [PubMed: 3004934] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Nucleotide sequence and organization of the human S-protein gene: repeating peptide motifs in the 'pexin' family and a model for their evolution." Jenne D.E., Stanley K.K. Biochemistry 26:6735-6742(1987) [PubMed: 2447940] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Mammary gland.
[6]	SeattleSNPs variation discovery resource Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS SER-122; GLN-268 AND MET-400.
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT MET-400. Tissue: Lung.
[8]	"Primary structure of somatomedin B: a growth hormone-dependent serum factor with protease inhibiting activity." Fryklund L., Sievertsson H. FEBS Lett. 87:55-60(1978) [PubMed: 631332] [Abstract] Cited for: PROTEIN SEQUENCE OF 20-63.
[9]	"Identification of a PAI-1 binding site in vitronectin." Sigurdardottir O., Wiman B. Biochim. Biophys. Acta 1208:104-110(1994) [PubMed: 7522053] [Abstract] Cited for: PROTEIN SEQUENCE OF 20-44, INTERACTION WITH SERPINE1/PAI1.
[10]	"Insulin binds to type V collagen with retention of mitogenic activity." Yaoi Y., Hashimoto K., Takahara K., Kato I. Exp. Cell Res. 194:180-185(1991) [PubMed: 1709100] [Abstract] Cited for: PROTEIN SEQUENCE OF 360-368, INTERACTION WITH INSULIN.
[11]	"Phosphorylation of vitronectin by a protein kinase in human plasma. Identification of a unique phosphorylation site in the heparin-binding domain." McGuire E.A., Peacock M.E., Inhorn R.C., Siegel N.R., Tollefsen D.M. J. Biol. Chem. 263:1942-1945(1988) [PubMed: 2448300] [Abstract] Cited for: PROTEIN SEQUENCE OF 393-400, PHOSPHORYLATION AT SER-397.
[12]	Hochstrasser D.F., Frutiger S., Paquet N., Bairoch A., Ravier F., Pasquali C., Sanchez J.-C., Tissot J.-D., Bjellqvist B., Vargas R., Appel R.D., Hughes G.J. Submitted (JUN-1992) to UniProtKB Cited for: PROTEIN SEQUENCE OF 399-413. Tissue: Plasma.
[13]	"Sulfation of two tyrosine-residues in human complement S-protein (vitronectin)." Jenne D.E., Hille A., Stanley K.K., Huttner W.B. Eur. J. Biochem. 185:391-395(1989) [PubMed: 2479556] [Abstract] Cited for: SULFATION.
[14]	"The phosphorylation of the two-chain form of vitronectin by protein kinase A is heparin dependent." Chain D., Korc-Grodzicki B., Kreizman T., Shaltiel S. FEBS Lett. 269:221-225(1990) [PubMed: 1696913] [Abstract] Cited for: PHOSPHORYLATION AT SER-397.
[15]	"Evidence that type 1 plasminogen activator inhibitor binds to the somatomedin B domain of vitronectin." Seiffert D., Loskutoff D.J. J. Biol. Chem. 266:2824-2830(1991) [PubMed: 1704366] [Abstract] Cited for: INTERACTION WITH SERPINE1/PAI1.
[16]	"Phosphorylation of vitronectin by casein kinase II. Identification of the sites and their promotion of cell adhesion and spreading." Seger D., Gechtman Z., Shaltiel S. J. Biol. Chem. 273:24805-24813(1998) [PubMed: 9733784] [Abstract] Cited for: PHOSPHORYLATION AT THR-69 AND THR-76, MUTAGENESIS OF THR-69 AND THR-76.
[17]	"Identification of the disulfide bonds in the recombinant somatomedin B domain of human vitronectin." Kamikubo Y., Okumura Y., Loskutoff D.J. J. Biol. Chem. 277:27109-27119(2002) [PubMed: 12019263] [Abstract] Cited for: DISULFIDE BONDS IN SOMATOMEDIN-B.
[18]	"Screening for N-glycosylated proteins by liquid chromatography mass spectrometry." Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R. Proteomics 4:454-465(2004) [PubMed: 14760718] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-86; ASN-169 AND ASN-242, MASS SPECTROMETRY. Tissue: Plasma.
[19]	"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry." Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D. J. Proteome Res. 4:2070-2080(2005) [PubMed: 16335952] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-86; ASN-169 AND ASN-242, MASS SPECTROMETRY. Tissue: Plasma.
[20]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-171, MASS SPECTROMETRY. Tissue: Epithelium.
[21]	"Phosphoproteomic analysis of the human pituitary." Beranova-Giorgianni S., Zhao Y., Desiderio D.M., Giorgianni F. Pituitary 9:109-120(2006) [PubMed: 16807684] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-312, MASS SPECTROMETRY. Tissue: Pituitary.
[22]	"Determination of the sites of tyrosine O-sulfation in peptides and proteins." Yu Y., Hoffhines A.J., Moore K.L., Leary J.A. Nat. Methods 4:583-588(2007) [PubMed: 17558413] [Abstract] Cited for: SULFATION AT TYR-75 AND TYR-78, PHOSPHORYLATION AT SER-312, GLYCOSYLATION AT ASN-86, MASS SPECTROMETRY.
[23]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed: 18088087] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-312, MASS SPECTROMETRY. Tissue: Platelet.
[24]	"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: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-86; ASN-169 AND ASN-242, MASS SPECTROMETRY. Tissue: Liver.
[25]	"How vitronectin binds PAI-1 to modulate fibrinolysis and cell migration." Zhou A., Huntington J.A., Pannu N.S., Carrell R.W., Read R.J. Nat. Struct. Biol. 10:541-544(2003) [PubMed: 12808446] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.28 ANGSTROMS) OF 22-58 IN COMPLEX WITH SERPINE1/PAI1.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

X03168 mRNA. Translation: CAA26933.1. Sequence problems.
X05006 Genomic DNA. Translation: CAA28659.1. Sequence problems.
AK312968 mRNA. Translation: BAG35807.1.
AF382388 Genomic DNA. Translation: AAK60270.1.
BC005046 mRNA. Translation: AAH05046.1.

IPI

IPI00298971.

PIR

SGHU1V. A29744.

RefSeq

NP_000629.3.

UniGene

Hs.2257

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1OC0	X-ray	2.28	B	20-70	[»]
1S4G	NMR	-	A	20-70	[»]
1SSU	NMR	-	A	20-70	[»]
2JQ8	NMR	-	A	20-66	[»]
3BT1	X-ray	2.80	B	21-60	[»]
3BT2	X-ray	2.50	B	21-60	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P04004. 3 interactions.

PTM databases

GlycoSuiteDB

P04004.

PhosphoSite

P04004.

2-D gel databases

SWISS-2DPAGE

P04004.

DOSAC-COBS-2DPAGE

P04004.

Proteomic databases

PeptideAtlas

P04004.

PRIDE

P04004.

Genome annotation databases

Ensembl

ENSG00000109072. Homo sapiens. [Contig view]

GeneID

7448.

KEGG

hsa:7448.

Organism-specific databases

GeneCards

GC17M023718.

H-InvDB

HIX0013644.

HGNC

HGNC:12724. VTN.

HPA

CAB016695.
CAB016765.

MIM

193190. gene.

PharmGKB

PA37335.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P04004.

HOVERGEN

P04004.

OMA

P04004. WGIEGPI.

Enzyme and pathway databases

Pathway_Interaction_DB

amb2_neutrophils_pathway. amb2 Integrin signaling.
hnf3apathway. FOXA1 transcription factor network.
avb3_integrin_pathway. Integrins in angiogenesis.

Reactome

REACT_13552. Integrin cell surface interactions.

Gene expression databases

ArrayExpress

P04004.

Bgee

P04004.

CleanEx

HS_VTN.

GermOnline

ENSG00000109072. Homo sapiens.

Family and domain databases

InterPro

IPR000585. Hemopexin/matrixin.
IPR018486. Hemopexin/matrixin_CS.
IPR018487. Hemopexin/matrixin_repeat.
IPR001212. Somatomedin_B.
[Graphical view]

Gene3D

G3DSA:2.110.10.10. Hemopexin. 2 hits.

Pfam

PF00045. Hemopexin. 4 hits.
PF01033. Somatomedin_B. 1 hit.
[Graphical view]

SMART

SM00120. HX. 4 hits.
SM00201. SO. 1 hit.
[Graphical view]

PROSITE

PS00024. HEMOPEXIN. 2 hits.
PS00524. SMB_1. 1 hit.
PS50958. SMB_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00013. Urokinase.

NextBio

29166.

PMAP-CutDB

P04004.

SOURCE

Search...

Entry information

Entry name

VTNC_HUMAN

Accession

Primary (citable) accession number: P04004
Secondary accession number(s): B2R7G0, P01141, Q9BSH7

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 23, 1986
Last sequence update:	October 23, 1986
Last modified:	June 16, 2009
This is version 124 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)