P20160 (CAP7_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Azurocidin

Alternative name(s):
Cationic antimicrobial protein CAP37
Heparin-binding protein
Short name=HBP

Gene names

Name:

AZU1

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	251 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	This is a neutrophil granule-derived antibacterial and monocyte- and fibroblast-specific chemotactic glycoprotein. Binds heparin. The cytotoxic action is limited to many species of Gram-negative bacteria; this specificity may be explained by a strong affinity of the very basic N-terminal half for the negatively charged lipopolysaccharides that are unique to the Gram-negative bacterial outer envelope. It may play a role in mediating recruitment of monocytes in the second wave of inflammation. Has antibacterial activity against the Gram-nagative bacterium P.aeruginosa, this activity is inhibited by LPS from P.aeruginosa. Acting alone, it does not have antimicrobial activity against the Gram-negative bacteria A.actinomycetemcomitans ATCC 29532, A.actinomycetemcomitans NCTC 9709, A.actinomycetemcomitans FDC-Y4, H.aphrophilus ATCC 13252, E.corrodens ATCC 23834, C.sputigena ATCC 33123, Capnocytophaga sp ATCC 33124, Capnocytophaga sp ATCC 27872 or E.coli ML-35. Has antibacterial activity against C.sputigena ATCC 33123 when acting synergistically with either elastase or cathepsin G. Ref.10 Ref.14
Subunit structure	Monomer.
Subcellular location	Cytoplasmic granule. Note: Cytoplasmic granules of neutrophils.
Sequence similarities	Belongs to the peptidase S1 family. Elastase subfamily. Contains 1 peptidase S1 domain.

Ontologies

Keywords
Biological process	Chemotaxis
Coding sequence diversity	Polymorphism
Domain	Signal
Ligand	Heparin-binding
Molecular function	Antibiotic Antimicrobial Serine protease homolog
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	activation of protein kinase C activity by G-protein coupled receptor protein signaling pathway Traceable author statement. Source: UniProtKB anti-apoptosis Non-traceable author statement. Source: UniProtKB cellular extravasation Non-traceable author statement. Source: UniProtKB defense response to Gram-negative bacterium Traceable author statement. Source: UniProtKB glial cell migration Inferred from direct assay. Source: UniProtKB induction of positive chemotaxis Non-traceable author statement. Source: UniProtKB inflammatory response Non-traceable author statement. Source: UniProtKB macrophage chemotaxis Non-traceable author statement Ref.1. Source: UniProtKB microglial cell activation Inferred from expression pattern. Source: UniProtKB monocyte activation Traceable author statement. Source: UniProtKB positive regulation of MHC class II biosynthetic process Inferred from expression pattern. Source: UniProtKB positive regulation of cell adhesion Inferred from direct assay. Source: UniProtKB positive regulation of fractalkine biosynthetic process Inferred from direct assay. Source: UniProtKB positive regulation of interleukin-1 beta biosynthetic process Inferred from direct assay. Source: UniProtKB positive regulation of phagocytosis Inferred from direct assay. Source: UniProtKB positive regulation of tumor necrosis factor biosynthetic process Inferred from direct assay. Source: UniProtKB proteolysis Inferred from electronic annotation. Source: InterPro regulation of vascular permeability Non-traceable author statement. Source: UniProtKB
Cellular component	azurophil granule Inferred from direct assay. Source: UniProtKB extracellular region Non-traceable author statement. Source: UniProtKB
Molecular function	heparin binding Non-traceable author statement. Source: UniProtKB serine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro toxin binding Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 26

26

Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14

Chain

27 – 248

222

Azurocidin

PRO_0000027705

Propeptide

249 – 251

3

PRO_0000027706

Regions

Domain

27 – 244

218

Peptidase S1

Region

46 – 70

25

Possesses antibiotic activity

Region

52 – 84

33

Hydrophobic

Amino acid modifications

Glycosylation

126

1

N-linked (GlcNAc...); partial Ref.6 Ref.17

Glycosylation

140

1

N-linked (GlcNAc...) Ref.6 Ref.17

Glycosylation

171

1

N-linked (GlcNAc...); partial Ref.6 Ref.17

Disulfide bond

52 ↔ 68

Ref.8

Disulfide bond

149 ↔ 207

Disulfide bond

180 ↔ 186

Disulfide bond

197 ↔ 222

Natural variations

Natural variant

248

1

Missing in 50% of the molecules.

VAR_006496

Experimental info

Mutagenesis

52

1

C → S: Loss of antibiotic activity.

Mutagenesis

68

1

C → S: Loss of antibiotic activity.

Sequence conflict

36

1

R → H AA sequence Ref.13

Sequence conflict

130

1

S → N AA sequence Ref.7

Secondary structure

1

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251

Helix Strand Turn

Details...

Beta strand

41 – 46

6

Beta strand

49 – 58

10

Beta strand

61 – 64

4

Helix

66 – 68

3

Beta strand

76 – 82

7

Turn

91 – 93

3

Beta strand

95 – 103

9

Turn

109 – 112

4

Beta strand

117 – 123

7

Beta strand

148 – 154

7

Beta strand

168 – 174

7

Helix

177 – 179

3

Beta strand

184 – 188

5

Beta strand

190 – 193

4

Beta strand

204 – 207

4

Beta strand

210 – 218

9

Beta strand

227 – 231

5

Helix

232 – 235

4

Helix

236 – 244

9

Sequences

	Sequence		Length	Mass (Da)
	P20160 [UniParc]. Last modified October 1, 1993. Version 3. Checksum: 22F80D9EBE87DE60	FASTA	251	26,886
	10 20 30 40 50 60 MTRLTVLALL AGLLASSRAG SSPLLDIVGG RKARPRQFPF LASIQNQGRH FCGGALIHAR 70 80 90 100 110 120 FVMTAASCFQ SQNPGVSTVV LGAYDLRRRE RQSRQTFSIS SMSENGYDPQ QNLNDLMLLQ 130 140 150 160 170 180 LDREANLTSS VTILPLPLQN ATVEAGTRCQ VAGWGSQRSG GRLSRFPRFV NVTVTPEDQC 190 200 210 220 230 240 RPNNVCTGVL TRRGGICNGD GGTPLVCEGL AHGVASFSLG PCGRGPDFFT RVALFRDWID 250 GVLNNPGPGP A

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of the cDNA for the serine protease homolog CAP37/azurocidin, a microbicidal and chemotactic protein from human granulocytes." Morgan J.G., Sukiennicki T., Pereira H.A., Spitznagel J.K., Guerra M.E., Larrick J.L. J. Immunol. 147:3210-3214(1991) [PubMed: 1919011] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Three human elastase-like genes coordinately expressed in the myelomonocyte lineage are organized as a single genetic locus on 19pter." Zimmer M., Medcalf R.L., Fink T.M., Mattmann C., Lichter P., Jenne D.E. Proc. Natl. Acad. Sci. U.S.A. 89:8215-8219(1992) [PubMed: 1518849] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed: 15057824] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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].
[5]	"Complementary DNA sequence of human neutrophil azurocidin, an antibiotic with extensive homology to serine proteases." Almeida R.P., Melchior M., Campanelli D., Nathan C., Gabay J.E. Biochem. Biophys. Res. Commun. 177:688-695(1991) [PubMed: 2049091] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 3-251. Tissue: Neutrophil.
[6]	"Amino acid sequence of CAP37, a human neutrophil granule-derived antibacterial and monocyte-specific chemotactic glycoprotein structurally similar to neutrophil elastase." Pohl J., Pereira H.A., Martin N.M., Spitznagel J.K. FEBS Lett. 272:200-204(1990) [PubMed: 2226832] [Abstract] Cited for: PROTEIN SEQUENCE OF 27-248.
[7]	"Covalent structure of two novel neutrophile leucocyte-derived proteins of porcine and human origin. Neutrophile elastase homologues with strong monocyte and fibroblast chemotactic activities." Flodgaard H., Oestergaard E., Bayne S., Svendsen A., Thomsen J., Engels M., Wollmer A. Eur. J. Biochem. 197:535-547(1991) [PubMed: 2026172] [Abstract] Cited for: PROTEIN SEQUENCE OF 27-248. Tissue: Neutrophil.
[8]	"CAP37, a human neutrophil-derived chemotactic factor with monocyte specific activity." Pereira H.A., Shafer W.M., Pohl J., Martin L.E., Spitznagel J.K. J. Clin. Invest. 85:1468-1476(1990) [PubMed: 2332502] [Abstract] Cited for: PROTEIN SEQUENCE OF 27-68. Tissue: Neutrophil.
[9]	"CAP 37, a 37 kD human neutrophil granule cationic protein shares homology with inflammatory proteinases." Pereira H.A., Spitznagel J.K., Pohl J., Wilson D.E., Morgan J., Palings I., Larrick J.W. Life Sci. 46:189-196(1990) [PubMed: 2406527] [Abstract] Cited for: PROTEIN SEQUENCE OF 27-67. Tissue: Neutrophil.
[10]	"Comparison of granule proteins from human polymorphonuclear leukocytes which are bactericidal toward Pseudomonas aeruginosa." Wasiluk K.R., Skubitz K.M., Gray B.H. Infect. Immun. 59:4193-4200(1991) [PubMed: 1937776] [Abstract] Cited for: PROTEIN SEQUENCE OF 27-48, FUNCTION. Tissue: Leukocyte.
[11]	"PMN elastases: a comparison of the specificity of human isozymes and the enzyme from other species toward substrates and inhibitors." Green B.G., Weston H., Ashe B.M., Doherty J., Finke P., Hagmann W., Lark M., Mao J., Maycock A., Moore V., Mumford R., Shah S., Walakovits L., Knight W.B. Arch. Biochem. Biophys. 286:284-292(1991) [PubMed: 1897955] [Abstract] Cited for: PROTEIN SEQUENCE OF 27-47.
[12]	"Antibiotic proteins of human polymorphonuclear leukocytes." Gabay J.E., Scott R.W., Campanelli D., Griffith J., Wilde C., Marra M.N., Seeger M., Nathan C.F. Proc. Natl. Acad. Sci. U.S.A. 86:5610-5614(1989) [PubMed: 2501794] [Abstract] Cited for: PROTEIN SEQUENCE OF 27-46.
[13]	"Characterization of two azurphil granule proteases with active-site homology to neutrophil elastase." Wilde C.G., Snable J.L., Griffith J.E., Scott R.W. J. Biol. Chem. 265:2038-2041(1990) [PubMed: 2404977] [Abstract] Cited for: PROTEIN SEQUENCE OF 27-46 AND 194-217.
[14]	"Human neutrophil azurocidin synergizes with leukocyte elastase and cathepsin G in the killing of Capnocytophaga sputigena." Miyasaki K.T., Bodeau A.L. Infect. Immun. 60:4973-4975(1992) [PubMed: 1399008] [Abstract] Cited for: PROTEIN SEQUENCE OF 27-46, FUNCTION.
[15]	"Human neutrophil granule cationic protein CAP37 is a specific macrophage chemotaxin that shares homology with inflammatory proteinases." Morgan J.G., Pereira H.A., Sukiennicki T., Spitznagel J.K., Larrick J.W. Adv. Exp. Med. Biol. 305:89-96(1991) [PubMed: 1755383] [Abstract] Cited for: REVIEW.
[16]	"Synthetic bactericidal peptide based on CAP37: a 37-kDa human neutrophil granule-associated cationic antimicrobial protein chemotactic for monocytes." Pereira H.A., Erdem I., Pohl J., Spitznagel J.K. Proc. Natl. Acad. Sci. U.S.A. 90:4733-4737(1993) [PubMed: 8506327] [Abstract] Cited for: SYNTHESIS OF 46-70.
[17]	"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-126; ASN-140 AND ASN-171, MASS SPECTROMETRY. Tissue: Liver.
[18]	"Structure of HBP, a multifunctional protein with a serine proteinase fold." Iversen L.F., Kastrup J.S., Bjoern S.E., Rasmussen P.B., Wiberg F.C., Flodgaard H.J., Larsen I.K. Nat. Struct. Biol. 4:265-268(1997) [PubMed: 9095193] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
[19]	"Atomic resolution structure of human HBP/CAP37/azurocidin." Karlsen S., Iversen L.F., Larsen I.K., Flodgaard H.J., Kastrup J.S. Acta Crystallogr. D 54:598-609(1998) [PubMed: 9761855] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.12 ANGSTROMS).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M96326 Genomic DNA. Translation: AAB59353.1.
AC004799 Genomic DNA. No translation available.
BC069495 mRNA. Translation: AAH69495.1.
BC093931 mRNA. Translation: AAH93931.1.
BC093933 mRNA. Translation: AAH93933.1.
X58794 mRNA. Translation: CAA41601.1.

IPI

IPI00022246.

PIR

TRHUAZ. A46268.

RefSeq

NP_001691.1. NM_001700.3.

UniGene

Hs.72885.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1A7S	X-ray	1.12	A	27-251	[»]
1AE5	X-ray	2.30	A	27-251	[»]
1FY1	X-ray	2.50	A	27-251	[»]
1FY3	X-ray	1.89	A	27-251	[»]

ProteinModelPortal

P20160.

SMR

P20160. Positions 27-251.

ModBase

Search...

Protein-protein interaction databases

IntAct

P20160. 1 interaction.

MINT

MINT-4054423.

STRING

P20160.

Protein family/group databases

MEROPS

S01.971.

Polymorphism databases

DMDM

416746.

Proteomic databases

PRIDE

P20160.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000233997; ENSP00000233997; ENSG00000172232.

GeneID

566.

KEGG

hsa:566.

UCSC

uc002lpz.1. human.

Organism-specific databases

CTD

566.

GeneCards

GC19P000825.

H-InvDB

HIX0040110.

HGNC

HGNC:913. AZU1.

MIM

162815. gene.

neXtProt

NX_P20160.

PharmGKB

PA25206.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG06680.

GeneTree

ENSGT00580000081367.

HOGENOM

HBG755338.

HOVERGEN

HBG013304.

InParanoid

P20160.

OMA

GRGPDFF.

PhylomeDB

P20160.

Gene expression databases

ArrayExpress

P20160.

Bgee

P20160.

CleanEx

HS_AZU1.

Genevestigator

P20160.

GermOnline

ENSG00000172232. Homo sapiens.

Family and domain databases

InterPro

IPR009003. Pept_cys/ser_Trypsin-like.
IPR001254. Peptidase_S1_S6.
IPR001314. Peptidase_S1A.
[Graphical view]

Pfam

PF00089. Trypsin. 1 hit.
[Graphical view]

PRINTS

PR00722. CHYMOTRYPSIN.

SMART

SM00020. Tryp_SPc. 1 hit.
[Graphical view]

SUPFAM

SSF50494. Pept_Ser_Cys. 1 hit.

PROSITE

PS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. False negative.
PS00135. TRYPSIN_SER. False negative.
[Graphical view]

ProtoNet

Search...

Other

NextBio

2309.

SOURCE

Search...

Entry information

Entry name

CAP7_HUMAN

Accession

Primary (citable) accession number: P20160
Secondary accession number(s): P80014 , Q52LG4, Q9UCM1, Q9UCT5

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	October 1, 1993
Last modified:	January 25, 2012
This is version 126 of the entry and version 3 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.