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Protein

Regenerating islet-derived protein 3-alpha

Gene

REG3A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Bactericidal C-type lectin which acts exclusively against Gram-positive bacteria and mediates bacterial killing by binding to surface-exposed carbohydrate moieties of peptidoglycan. Regulates keratinocyte proliferation and differentiation after skin injury via activation of EXTL3-PI3K-AKT signaling pathway.1 Publication

GO - Molecular functioni

  • carbohydrate binding Source: ProtInc

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Antimicrobial

Keywords - Biological processi

Acute phase, Inflammatory response

Keywords - Ligandi

Lectin

Protein family/group databases

MEROPSiI63.002.
TCDBi1.C.111.1.2. the regiii (regiii) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Regenerating islet-derived protein 3-alpha
Short name:
REG-3-alpha
Alternative name(s):
Hepatointestinal pancreatic protein
Short name:
HIP/PAP
Human proislet peptide
Pancreatitis-associated protein 1
Regenerating islet-derived protein III-alpha
Short name:
Reg III-alpha
Cleaved into the following 2 chains:
Gene namesi
Name:REG3A
Synonyms:HIP, PAP, PAP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:8601. REG3A.

Subcellular locationi

  • Secreted

  • Note: Found in the apical region of pancreatic acinar cells.

GO - Cellular componenti

  • cytoplasm Source: ProtInc
  • extracellular space Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi114 – 1141E → Q: Reduces peptidoglycan binding and antibacterial activity. 1 Publication
Mutagenesisi118 – 1181E → Q: Reduces antibacterial activity but no effect on peptidoglycan binding. 1 Publication

Organism-specific databases

PharmGKBiPA32931.

Polymorphism and mutation databases

BioMutaiREG3A.
DMDMi464341.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2626By similarityAdd
BLAST
Chaini27 – 175149Regenerating islet-derived protein 3-alpha 16.5 kDa formPRO_0000017429Add
BLAST
Propeptidei27 – 37111 PublicationPRO_0000422741Add
BLAST
Chaini38 – 175138Regenerating islet-derived protein 3-alpha 15 kDa formPRO_0000422742Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi40 ↔ 51PROSITE-ProRule annotation
Disulfide bondi68 ↔ 171PROSITE-ProRule annotation
Disulfide bondi146 ↔ 163PROSITE-ProRule annotation

Post-translational modificationi

Proteolytic processing by trypsin removes an inhibitory N-terminal propeptide and is essential for peptidoglycan binding and antibacterial activity.1 Publication

Keywords - PTMi

Disulfide bond

Proteomic databases

EPDiQ06141.
PaxDbiQ06141.
PeptideAtlasiQ06141.
PRIDEiQ06141.

Miscellaneous databases

PMAP-CutDBQ06141.

Expressioni

Tissue specificityi

Highly expressed in epidermal keratinocytes of psoriasis patients (at protein level). Constitutively expressed in intestine. Low expression is found in healthy pancreas. Overexpressed during the acute phase of pancreatitis and in some patients with chronic pancreatitis.2 Publications

Inductioni

Appears in pancreatic juice after induction of pancreatic inflammation.

Gene expression databases

BgeeiQ06141.
CleanExiHS_REG3A.
ExpressionAtlasiQ06141. baseline and differential.
GenevisibleiQ06141. HS.

Organism-specific databases

HPAiHPA048334.

Interactioni

Subunit structurei

Interacts with EXTL3.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
MDFIQ997503EBI-10223932,EBI-724076

Protein-protein interaction databases

BioGridi111103. 6 interactions.
DIPiDIP-60688N.
IntActiQ06141. 1 interaction.
STRINGi9606.ENSP00000304311.

Structurei

Secondary structure

1
175
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi44 – 474Combined sources
Beta strandi50 – 5910Combined sources
Helixi61 – 688Combined sources
Helixi82 – 9211Combined sources
Beta strandi100 – 1078Combined sources
Turni109 – 1124Combined sources
Beta strandi114 – 1163Combined sources
Turni123 – 1253Combined sources
Beta strandi133 – 1353Combined sources
Helixi137 – 1393Combined sources
Beta strandi140 – 1423Combined sources
Beta strandi145 – 1506Combined sources
Helixi151 – 1533Combined sources
Beta strandi157 – 1615Combined sources
Beta strandi167 – 1737Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1UV0X-ray1.78A27-175[»]
2GO0NMR-A39-175[»]
4MTHX-ray1.47A38-175[»]
ProteinModelPortaliQ06141.
SMRiQ06141. Positions 38-175.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ06141.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini47 – 172126C-type lectinPROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi114 – 1163EPN

Domaini

The EPN motif is essential for recognition of the peptidoglycan carbohydrate backbone and for efficient bacterial killing with Glu-114 playing a key role in peptidoglycan binding and bactericidal activity.

Sequence similaritiesi

Contains 1 C-type lectin domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG4297. Eukaryota.
ENOG410XPJ1. LUCA.
HOGENOMiHOG000010281.
HOVERGENiHBG004151.
InParanoidiQ06141.
OMAiVKLPYVC.
OrthoDBiEOG738067.
PhylomeDBiQ06141.

Family and domain databases

Gene3Di3.10.100.10. 1 hit.
InterProiIPR001304. C-type_lectin.
IPR016186. C-type_lectin-like.
IPR018378. C-type_lectin_CS.
IPR016187. C-type_lectin_fold.
[Graphical view]
PfamiPF00059. Lectin_C. 1 hit.
[Graphical view]
SMARTiSM00034. CLECT. 1 hit.
[Graphical view]
SUPFAMiSSF56436. SSF56436. 1 hit.
PROSITEiPS00615. C_TYPE_LECTIN_1. 1 hit.
PS50041. C_TYPE_LECTIN_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q06141-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLPPMALPSV SWMLLSCLML LSQVQGEEPQ RELPSARIRC PKGSKAYGSH
60 70 80 90 100
CYALFLSPKS WTDADLACQK RPSGNLVSVL SGAEGSFVSS LVKSIGNSYS
110 120 130 140 150
YVWIGLHDPT QGTEPNGEGW EWSSSDVMNY FAWERNPSTI SSPGHCASLS
160 170
RSTAFLRWKD YNCNVRLPYV CKFTD
Length:175
Mass (Da):19,395
Last modified:February 1, 1994 - v1
Checksum:iC51149FAC22EB68C
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti173 – 1753FTD → VH in AAA36415 (PubMed:1469087).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D13510 mRNA. Translation: BAA02728.1.
M84337 mRNA. Translation: AAA36415.1.
S51768 mRNA. Translation: AAB24642.1.
X68641 mRNA. Translation: CAA48605.1.
L15533 Genomic DNA. Translation: AAA60020.1.
BC036776 mRNA. Translation: AAH36776.1.
CCDSiCCDS1965.1.
PIRiA49616.
RefSeqiNP_002571.1. NM_002580.2.
NP_620354.1. NM_138937.2.
NP_620355.1. NM_138938.2.
UniGeneiHs.567312.

Genome annotation databases

EnsembliENST00000305165; ENSP00000304311; ENSG00000172016.
ENST00000393878; ENSP00000377456; ENSG00000172016.
ENST00000409839; ENSP00000386630; ENSG00000172016.
GeneIDi5068.
KEGGihsa:5068.

Cross-referencesi

Web resourcesi

Functional Glycomics Gateway - Glycan Binding

Pancreatitis-associated protein 1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D13510 mRNA. Translation: BAA02728.1.
M84337 mRNA. Translation: AAA36415.1.
S51768 mRNA. Translation: AAB24642.1.
X68641 mRNA. Translation: CAA48605.1.
L15533 Genomic DNA. Translation: AAA60020.1.
BC036776 mRNA. Translation: AAH36776.1.
CCDSiCCDS1965.1.
PIRiA49616.
RefSeqiNP_002571.1. NM_002580.2.
NP_620354.1. NM_138937.2.
NP_620355.1. NM_138938.2.
UniGeneiHs.567312.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1UV0X-ray1.78A27-175[»]
2GO0NMR-A39-175[»]
4MTHX-ray1.47A38-175[»]
ProteinModelPortaliQ06141.
SMRiQ06141. Positions 38-175.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111103. 6 interactions.
DIPiDIP-60688N.
IntActiQ06141. 1 interaction.
STRINGi9606.ENSP00000304311.

Protein family/group databases

MEROPSiI63.002.
TCDBi1.C.111.1.2. the regiii (regiii) family.

Polymorphism and mutation databases

BioMutaiREG3A.
DMDMi464341.

Proteomic databases

EPDiQ06141.
PaxDbiQ06141.
PeptideAtlasiQ06141.
PRIDEiQ06141.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000305165; ENSP00000304311; ENSG00000172016.
ENST00000393878; ENSP00000377456; ENSG00000172016.
ENST00000409839; ENSP00000386630; ENSG00000172016.
GeneIDi5068.
KEGGihsa:5068.

Organism-specific databases

CTDi5068.
GeneCardsiREG3A.
HGNCiHGNC:8601. REG3A.
HPAiHPA048334.
MIMi167805. gene.
neXtProtiNX_Q06141.
PharmGKBiPA32931.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4297. Eukaryota.
ENOG410XPJ1. LUCA.
HOGENOMiHOG000010281.
HOVERGENiHBG004151.
InParanoidiQ06141.
OMAiVKLPYVC.
OrthoDBiEOG738067.
PhylomeDBiQ06141.

Miscellaneous databases

ChiTaRSiREG3A. human.
EvolutionaryTraceiQ06141.
GeneWikiiREG3A.
GenomeRNAii5068.
PMAP-CutDBQ06141.
PROiQ06141.
SOURCEiSearch...

Gene expression databases

BgeeiQ06141.
CleanExiHS_REG3A.
ExpressionAtlasiQ06141. baseline and differential.
GenevisibleiQ06141. HS.

Family and domain databases

Gene3Di3.10.100.10. 1 hit.
InterProiIPR001304. C-type_lectin.
IPR016186. C-type_lectin-like.
IPR018378. C-type_lectin_CS.
IPR016187. C-type_lectin_fold.
[Graphical view]
PfamiPF00059. Lectin_C. 1 hit.
[Graphical view]
SMARTiSM00034. CLECT. 1 hit.
[Graphical view]
SUPFAMiSSF56436. SSF56436. 1 hit.
PROSITEiPS00615. C_TYPE_LECTIN_1. 1 hit.
PS50041. C_TYPE_LECTIN_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and tissue-specific expression of cDNAs for the human and mouse homologues of rat pancreatitis-associated protein (PAP)."
    Itoh T., Teraoka H.
    Biochim. Biophys. Acta 1172:184-186(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Pancreas and Small intestine.
  2. "Human pancreatitis-associated protein. Messenger RNA cloning and expression in pancreatic diseases."
    Orelle B., Keim V., Masciotra L., Dagorn J.-C., Iovanna J.-L.
    J. Clin. Invest. 90:2284-2291(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
    Tissue: Pancreas.
  3. "A novel gene (HIP) activated in human primary liver cancer."
    Lasserre C., Christa L., Simon M.T., Vernier P., Brechot C.
    Cancer Res. 52:5089-5095(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Liver.
  4. "Molecular cloning, genomic organization, and chromosomal localization of the human pancreatitis-associated protein (PAP) gene."
    Dusetti N.J., Frigerio J.-M., Fox M.F., Swallow D.M., Dagorn J.-C., Iovanna J.L.
    Genomics 19:108-114(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Blood.
  5. "Structural organization and chromosomal localization of a human gene (HIP/PAP) encoding a C-type lectin overexpressed in primary liver cancer."
    Lasserre C., Simon M.T., Ishikawa H., Diriong S., Nguyen V.C., Christa L., Vernier P., Brechot C.
    Eur. J. Biochem. 224:29-38(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  6. "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: Pancreas.
  7. "Proteolytic activation of human pancreatitis-associated protein is required for peptidoglycan binding and bacterial aggregation."
    Medveczky P., Szmola R., Sahin-Toth M.
    Biochem. J. 420:335-343(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF N-TERMINUS, PROTEOLYTIC PROCESSING.
  8. "Symbiotic bacteria direct expression of an intestinal bactericidal lectin."
    Cash H.L., Whitham C.V., Behrendt C.L., Hooper L.V.
    Science 313:1126-1130(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, MANNAN- AND PEPTIDOGLYCAN-BINDING.
  9. "The antimicrobial protein REG3A regulates keratinocyte proliferation and differentiation after skin injury."
    Lai Y., Li D., Li C., Muehleisen B., Radek K.A., Park H.J., Jiang Z., Li Z., Lei H., Quan Y., Zhang T., Wu Y., Kotol P., Morizane S., Hata T.R., Iwatsuki K., Tang C., Gallo R.L.
    Immunity 37:74-84(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, INTERACTION WITH EXTL3.
  10. Cited for: STRUCTURE BY NMR, MOTIF EPN, MUTAGENESIS OF GLU-114 AND GLU-118.

Entry informationi

Entry nameiREG3A_HUMAN
AccessioniPrimary (citable) accession number: Q06141
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: February 1, 1994
Last modified: June 8, 2016
This is version 147 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.