P81172 (HEPC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Hepcidin

Alternative name(s):
Liver-expressed antimicrobial peptide 1
Short name=LEAP-1
Putative liver tumor regressor
Short name=PLTR

Cleaved into the following 2 chains:

1. Hepcidin-25
   Short name=Hepc25
2. Hepcidin-20
   Short name=Hepc20

Gene names

Name:	HAMP
Synonyms:	HEPC, LEAP1
ORF Names:	UNQ487/PRO1003

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	84 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	Seems to act as a signaling molecule involved in the maintenance of iron homeostasis. Seems to be required in conjunction with HFE to regulate both intestinal iron absorption and iron storage in macrophages By similarity. Ref.2 Has strong antimicrobial activity against E.coli ML35P N.cinerea and weaker against S.epidermidis, S.aureus and group b streptococcus bacteria. Active against the fungus C.albicans. No activity against P.aeruginosa. Ref.2
Subcellular location	Secreted.
Tissue specificity	Highest expression in liver and to a lesser extent in heart and brain. Low levels in lung, tonsils, salivary gland, trachea, prostate gland, adrenal gland and thyroid gland. Secreted into the urine. Ref.2
Involvement in disease	Defects in HAMP are the cause of hemochromatosis type 2B (HFE2B) [MIM:613313]; also known as juvenile hemochromatosis (JH). HFE2B is a disorder of iron metabolism with excess deposition of iron in the tissues, bronze skin pigmentation, hepatic cirrhosis, arthropathy and diabetes. The most common symptoms of hemochromatosis type 2 at presentation are hypogonadism and cardiomyopathy. Ref.11 Ref.12 Ref.13 Ref.14 Ref.15
Sequence similarities	Belongs to the hepcidin family.
Mass spectrometry	Molecular mass is 2789.8 Da from positions 60 - 84. Determined by MALDI. Ref.2

Ontologies

Keywords
Cellular component	Secreted
Disease	Disease mutation
Domain	Signal
Molecular function	Antibiotic Antimicrobial Fungicide Hormone
PTM	Cleavage on pair of basic residues Disulfide bond
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 electronic annotation. Source: UniProtKB-KW immune response Traceable author statement Ref.1. Source: UniProtKB killing of cells of other organism Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	extracellular region Non-traceable author statement Ref.2. Source: UniProtKB
Molecular function	hormone activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 24

24

Potential

Propeptide

25 – 54

30

PRO_0000013378

Peptide

60 – 84

25

Hepcidin-25 Ref.1 Ref.2

PRO_0000013379

Peptide

65 – 84

20

Hepcidin-20

PRO_0000013380

Amino acid modifications

Disulfide bond

66 ↔ 82

Ref.9 Ref.10

Disulfide bond

69 ↔ 72

Ref.9 Ref.10

Disulfide bond

70 ↔ 78

Ref.9 Ref.10

Disulfide bond

73 ↔ 81

Ref.9 Ref.10

Natural variations

Natural variant

59

1

R → G in HFE2B. Ref.14

VAR_042512

Natural variant

70

1

C → R in HFE2B. Ref.13

VAR_042513

Natural variant

71

1

G → D in HFE2B. Ref.11 Ref.12 Ref.14

VAR_026648

Natural variant

78

1

C → Y in HFE2B. Ref.15

VAR_042514

Experimental info

Sequence conflict

31

1

T → M in AAK14912. Ref.3

Secondary structure

1

.

.

.

.

.

84

Helix Strand Turn

Details...

Beta strand

67 – 74

8

Beta strand

76 – 81

6

Sequences

	Sequence		Length	Mass (Da)
	P81172 [UniParc]. Last modified December 1, 2000. Version 2. Checksum: 5F8DCA23D19D29F7	FASTA	84	9,408
	10 20 30 40 50 60 MALSSQIWAA CLLLLLLLAS LTSGSVFPQQ TGQLAELQPQ DRAGARASWM PMFQRRRRRD 70 80 THFPICIFCC GCCHRSKCGM CCKT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Hepcidin: a urinary antimicrobial peptide synthesized in the liver." Park C.H., Valore E.V., Waring A.J., Ganz T. J. Biol. Chem. 276:7806-7810(2001) [PubMed: 11113131] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 60-84. Tissue: Liver and Urine.
[2]	"LEAP-1, a novel highly disulfide-bonded human peptide exhibits antimicrobial activity." Krause A., Neitz S., Maegert H.-J., Schulz A., Forssmann W.-G., Schulz-Knappe P., Adermann K. FEBS Lett. 480:147-150(2000) [PubMed: 11034317] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 60-84, FUNCTION, TISSUE SPECIFICITY, MASS SPECTROMETRY. Tissue: Blood and Liver.
[3]	Jung J.-W., Shin W.-S., Yoon Y., Lee S.-T. Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	NHLBI resequencing and genotyping service (RS&G) Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"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].
[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]. Tissue: Liver.
[8]	"Chemical synthesis of beta-defensins and LEAP-1/hepcidin." Kluever E., Schulz A., Forssmann W.-G., Adermann K. J. Pept. Res. 59:241-248(2002) [PubMed: 12010514] [Abstract] Cited for: SYNTHESIS OF 60-84.
[9]	"The solution structure of human hepcidin, a peptide hormone with antimicrobial activity that is involved in iron uptake and hereditary hemochromatosis." Hunter H.N., Fulton D.B., Ganz T., Vogel H.J. J. Biol. Chem. 277:37597-37603(2002) [PubMed: 12138110] [Abstract] Cited for: STRUCTURE BY NMR OF 60-84, PRELIMINARY DISULFIDE BONDS.
[10]	"Hepcidin revisited, disulfide connectivity, dynamics, and structure." Jordan J.B., Poppe L., Haniu M., Arvedson T., Syed R., Li V., Kohno H., Kim H., Schnier P.D., Harvey T.S., Miranda L.P., Cheetham J., Sasu B.J. J. Biol. Chem. 284:24155-24167(2009) [PubMed: 19553669] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.89 ANGSTROMS) OF 60-84, DISULFIDE BONDS.
[11]	"Identification of new mutations of the HFE, hepcidin, and transferrin receptor 2 genes by denaturing HPLC analysis of individuals with biochemical indications of iron overload." Biasiotto G., Belloli S., Ruggeri G., Zanella I., Gerardi G., Corrado M., Gobbi E., Albertini A., Arosio P. Clin. Chem. 49:1981-1988(2003) [PubMed: 14633868] [Abstract] Cited for: VARIANT HFE2B ASP-71.
[12]	"Digenic inheritance of mutations in HAMP and HFE results in different types of haemochromatosis." Merryweather-Clarke A.T., Cadet E., Bomford A., Capron D., Viprakasit V., Miller A., McHugh P.J., Chapman R.W., Pointon J.J., Wimhurst V.L., Livesey K.J., Tanphaichitr V., Rochette J., Robson K.J. Hum. Mol. Genet. 12:2241-2247(2003) [PubMed: 12915468] [Abstract] Cited for: VARIANT HFE2B ASP-71.
[13]	"Screening hepcidin for mutations in juvenile hemochromatosis: identification of a new mutation (C70R)." Roetto A., Daraio F., Porporato P., Caruso R., Cox T.M., Cazzola M., Gasparini P., Piperno A., Camaschella C. Blood 103:2407-2409(2004) [PubMed: 14630809] [Abstract] Cited for: VARIANT HFE2B ARG-70.
[14]	"HAMP as a modifier gene that increases the phenotypic expression of the HFE pC282Y homozygous genotype." Jacolot S., Le Gac G., Scotet V., Quere I., Mura C., Ferec C. Blood 103:2835-2840(2004) [PubMed: 14670915] [Abstract] Cited for: VARIANTS HFE2B GLY-59 AND ASP-71.
[15]	"A homozygous HAMP mutation in a multiply consanguineous family with pseudo-dominant juvenile hemochromatosis." Delatycki M.B., Allen K.J., Gow P., MacFarlane J., Radomski C., Thompson J., Hayden M.R., Goldberg Y.P., Samuels M.E. Clin. Genet. 65:378-383(2004) [PubMed: 15099344] [Abstract] Cited for: VARIANT HFE2B TYR-78.
+	Additional computationally mapped references.

Web resources

GeneReviews

Wikipedia

Hepcidin entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF309489 mRNA. Translation: AAG23966.1.
AJ277280 mRNA. Translation: CAC09419.1.
AF131292 mRNA. Translation: AAK14912.1.
AY358669 mRNA. Translation: AAQ89032.1.
DQ496109 Genomic DNA. Translation: ABF47098.1.
AD000684 Genomic DNA. No translation available.
BC020612 mRNA. Translation: AAH20612.1.

IPI

IPI00025992.

RefSeq

NP_066998.1. NM_021175.2.

UniGene

Hs.8821.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1M4E	NMR	-	A	65-84	[»]
1M4F	NMR	-	A	60-84	[»]
2KEF	NMR	-	A	60-84	[»]
3H0T	X-ray	1.89	C	60-84	[»]

ProteinModelPortal

P81172.

ModBase

Search...

Protein-protein interaction databases

IntAct

P81172. 1 interaction.

STRING

P81172.

Polymorphism databases

DMDM

10720397.

Proteomic databases

PRIDE

P81172.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000222304; ENSP00000222304; ENSG00000105697.

GeneID

57817.

KEGG

hsa:57817.

UCSC

uc002nyw.1. human.

Organism-specific databases

CTD

57817.

GeneCards

GC19P035773.

H-InvDB

HIX0019408.

HGNC

HGNC:15598. HAMP.

MIM

606464. gene.
613313. phenotype.

neXtProt

NX_P81172.

Orphanet

79230. Hemochromatosis type 2.

PharmGKB

PA29182.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG21194.

GeneTree

ENSGT00390000003154.

HOGENOM

HBG126894.

HOVERGEN

HBG003716.

InParanoid

P81172.

OMA

QPQDRAG.

OrthoDB

EOG4V9TS9.

PhylomeDB

P81172.

Gene expression databases

ArrayExpress

P81172.

Bgee

P81172.

CleanEx

HS_HAMP.

Genevestigator

P81172.

GermOnline

ENSG00000105697. Homo sapiens.

Family and domain databases

InterPro

IPR010500. Hepcidin.
[Graphical view]

Pfam

PF06446. Hepcidin. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

64762.

SOURCE

Search...

Entry information

Entry name

HEPC_HUMAN

Accession

Primary (citable) accession number: P81172
Secondary accession number(s): Q1HE14, Q9BY68

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 15, 1998
Last sequence update:	December 1, 2000
Last modified:	January 25, 2012
This is version 113 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.