P80511 (S10AC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein S100-A12

Alternative name(s):
CGRP
Calcium-binding protein in amniotic fluid 1
Short name=CAAF1
Calgranulin-C
Short name=CAGC
Extracellular newly identified RAGE-binding protein
Short name=EN-RAGE
Neutrophil S100 protein
S100 calcium-binding protein A12
p6

Cleaved into the following chain:

1. Calcitermin

Gene names

Name:

S100A12

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	92 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	Calcitermin possesses antifungal activity against C.albicans and is also active against E.coli and P.aeruginosa but not L.monocytogenes and S.aureus. Binds calcium, zinc and copper. Presence of zinc increases the affinity for calcium. Plays an important role in the inflammatory response. Interaction with AGER on endothelium, mononuclear phagocytes, and lymphocytes triggers cellular activation, with generation of key proinflammatory mediators By similarity. Ref.9 Ref.10
Subunit structure	Homodimer. Homooligomer (tetramer or hexamer) in the presence of calcium and zinc ions. Interacts with AGER and both calcium and zinc are essential for the interaction. Ref.10
Tissue specificity	Monocytes and lymphocytes.
Sequence similarities	Belongs to the S-101 family. Contains 2 EF-hand domains.
Mass spectrometry	Molecular mass is 10444 Da from positions 2 - 92. Determined by ESI. Ref.9 Molecular mass is 1688.9 Da from positions 78 - 92. Determined by MALDI. Ref.9

Ontologies

Keywords
Biological process	Inflammatory response
Domain	Repeat
Ligand	Calcium Copper Metal-binding Zinc
Molecular function	Antibiotic Antimicrobial Fungicide
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	defense response to bacterium Inferred from electronic annotation. Source: UniProtKB-KW defense response to fungus Inferred from direct assay Ref.9. Source: UniProtKB inflammatory response Traceable author statement. Source: ProtInc innate immune response Traceable author statement. Source: Reactome killing of cells of other organism Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from direct assay. Source: UniProtKB xenobiotic metabolic process Inferred from direct assay Ref.9. Source: UniProtKB
Cellular component	cytosol Traceable author statement. Source: ProtInc extracellular region Traceable author statement. Source: Reactome insoluble fraction Traceable author statement. Source: ProtInc nucleus Inferred from direct assay. Source: UniProtKB
Molecular function	RAGE receptor binding Inferred from direct assay Ref.10. Source: UniProtKB calcium ion binding Traceable author statement. Source: ProtInc zinc ion binding Traceable author statement Ref.9. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.5 Ref.6 Ref.7 Ref.8

Chain

2 – 92

91

Protein S100-A12

PRO_0000045383

Peptide

78 – 92

15

Calcitermin Ref.9

PRO_0000004774

Regions

Domain

13 – 48

36

EF-hand 1

Domain

49 – 84

36

EF-hand 2

Calcium binding

19 – 32

14

1; low affinity By similarity

Calcium binding

62 – 73

12

2; high affinity By similarity

Experimental info

Sequence conflict

7

1

H → V AA sequence Ref.8

Sequence conflict

12 – 13

2

VN → YS AA sequence Ref.8

Sequence conflict

16

1

H → F AA sequence Ref.8

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

92

Helix Strand Turn

Details...

Helix

3 – 19

17

Beta strand

21 – 24

4

Helix

30 – 40

11

Turn

42 – 44

3

Turn

46 – 49

4

Helix

51 – 61

11

Helix

71 – 87

17

Sequences

	Sequence		Length	Mass (Da)
	P80511 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 52AF75A31BDC222A	FASTA	92	10,575
	10 20 30 40 50 60 MTKLEEHLEG IVNIFHQYSV RKGHFDTLSK GELKQLLTKE LANTIKNIKD KAVIDEIFQG 70 80 90 LDANQDEQVD FQEFISLVAI ALKAAHYHTH KE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human CAAF1 gene -- molecular cloning, gene structure, and chromosome mapping." Yamamura T., Hitomi J., Nagasaki K., Suzuki M., Takahashi E., Saito S., Tsukada T., Yamaguchi K. Biochem. Biophys. Res. Commun. 221:356-360(1996) [PubMed: 8619860] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[2]	"Characterization of the human S100A12 (calgranulin C, p6, CAAF1, CGRP) gene, a new member of the S100 gene cluster on chromosome 1q21." Wicki R., Marenholz I., Mischke D., Schaefer B.W., Heizmann C.W. Cell Calcium 20:459-464(1996) [PubMed: 8985590] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[3]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [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]. Tissue: Blood.
[5]	"Host-parasite interaction in human onchocerciasis: identification and sequence analysis of a novel human calgranulin." Marti T., Erttmann K.D., Gallin M.Y. Biochem. Biophys. Res. Commun. 221:454-458(1996) [PubMed: 8619876] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-92.
[6]	"Amino acid sequence determination of human S100A12 (P6, calgranulin C, CGRP, CAAF1) by tandem mass spectrometry." Ilg E.C., Troxler H., Buergisser D.M., Kuster T., Markert M., Guignard F., Hunziker P., Birchler N., Heizmann C.W. Biochem. Biophys. Res. Commun. 225:146-150(1996) [PubMed: 8769108] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-92. Tissue: Neutrophil.
[7]	"Identification and characterization of a novel human neutrophil protein related to the S100 family." Guignard F., Mauel J., Markert M. Biochem. J. 309:395-401(1995) [PubMed: 7626002] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-21.
[8]	"Identification, isolation, and partial characterization of a 7.5-kDa surfactant-associated protein." Singh G., Katyal S.L., Brown W.E., Kennedy A.L., Wong-Chong M.-L., Gottron S.A. Exp. Lung Res. 17:559-567(1991) [PubMed: 1860454] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-16.
[9]	"Calcitermin, a novel antimicrobial peptide isolated from human airway secretions." Cole A.M., Kim Y.-H., Tahk S., Hong T., Weis P., Waring A.J., Ganz T. FEBS Lett. 504:5-10(2001) [PubMed: 11522286] [Abstract] Cited for: PROTEIN SEQUENCE OF 78-92, FUNCTION AS AN ANTIMICROBIAL PROTEIN, MASS SPECTROMETRY. Tissue: Nasal mucus.
[10]	"Both Ca2+ and Zn2+ are essential for S100A12 protein oligomerization and function." Moroz O.V., Burkitt W., Wittkowski H., He W., Ianoul A., Novitskaya V., Xie J., Polyakova O., Lednev I.K., Shekhtman A., Derrick P.J., Bjoerk P., Foell D., Bronstein I.B. BMC Biochem. 10:11-11(2009) [PubMed: 19386136] [Abstract] Cited for: FUNCTION, SUBUNIT, INTERACTION WITH AGER.
[11]	"The three-dimensional structure of human S100A12." Moroz O.V., Antson A.A., Murshudov G.N., Maitland N.J., Dodson G.G., Wilson K.S., Skibshoj I., Lukanidin E.M., Bronstein I.B. Acta Crystallogr. D 57:20-29(2001) [PubMed: 11134923] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D49549 mRNA. Translation: BAA08497.1.
D83657 Genomic DNA. Translation: BAA12030.1.
D83664 mRNA. Translation: BAA12036.1.
X97859 mRNA. Translation: CAA66453.1.
X98289, X98290 Genomic DNA. Translation: CAB94792.1.
AL591704 Genomic DNA. Translation: CAI19495.1.
BC070294 mRNA. Translation: AAH70294.1.

IPI

IPI00218131.

PIR

A61522.
JC4712.

RefSeq

NP_005612.1. NM_005621.1.

UniGene

Hs.19413.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1E8A	X-ray	1.95	A/B	2-92	[»]
1GQM	X-ray	2.70	A/B/C/D/E/F/G/H/I/J/K/L	2-92	[»]
1ODB	X-ray	2.19	A/B/C/D/E/F	2-92	[»]
2WC8	X-ray	1.88	A/B/C/D	2-92	[»]
2WCB	X-ray	1.73	A/B	2-92	[»]
2WCE	X-ray	1.77	A/B	2-92	[»]
2WCF	X-ray	2.78	A/B/C/D/E/F	2-92	[»]

ProteinModelPortal

P80511.

SMR

P80511. Positions 2-92.

ModBase

Search...

Protein-protein interaction databases

IntAct

P80511. 1 interaction.

STRING

P80511.

Polymorphism databases

DMDM

2507565.

Proteomic databases

PRIDE

P80511.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000368737; ENSP00000357726; ENSG00000163221.

GeneID

6283.

KEGG

hsa:6283.

UCSC

uc001fbr.1. human.

Organism-specific databases

CTD

6283.

GeneCards

GC01M153346.

H-InvDB

HIX0028791.

HGNC

HGNC:10489. S100A12.

HPA

CAB025872.
HPA002881.

MIM

603112. gene.

neXtProt

NX_P80511.

PharmGKB

PA34901.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG21559.

GeneTree

ENSGT00600000084283.

HOGENOM

HBG716817.

HOVERGEN

HBG001479.

InParanoid

P80511.

OMA

QDLDADK.

OrthoDB

EOG4FFD3C.

PhylomeDB

P80511.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P80511.

Bgee

P80511.

CleanEx

HS_S100A12.

Genevestigator

P80511.

GermOnline

ENSG00000163221. Homo sapiens.

Family and domain databases

InterPro

IPR011992. EF-hand-like_dom.
IPR018249. EF_HAND_2.
IPR001751. S100/CaBP-9k_CS.
IPR013787. S100_Ca-bd_sub.
[Graphical view]

Gene3D

G3DSA:1.10.238.10. EF-Hand_type. 1 hit.

Pfam

PF01023. S_100. 1 hit.
[Graphical view]

PROSITE

PS00018. EF_HAND_1. False negative.
PS50222. EF_HAND_2. 1 hit.
PS00303. S100_CABP. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB01025. Amlexanox.

NextBio

24389.

SOURCE

Search...

Entry information

Entry name

S10AC_HUMAN

Accession

Primary (citable) accession number: P80511
Secondary accession number(s): P83219, Q5SY66, Q7M4R1

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	January 23, 2007
Last modified:	January 25, 2012
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.