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Protein

Regenerating islet-derived protein 4

Gene

REG4

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

Functioni

Calcium-independent lectin displaying mannose-binding specificity and able to maintain carbohydrate recognition activity in an acidic environment. May be involved in inflammatory and metaplastic responses of the gastrointestinal epithelium.2 Publications

GO - Molecular functioni

  • heparin binding Source: UniProtKB
  • mannan binding Source: UniProtKB
Complete GO annotation...

Keywords - Ligandi

Lectin

Protein family/group databases

MEROPSiI63.002.

Names & Taxonomyi

Protein namesi
Recommended name:
Regenerating islet-derived protein 4
Short name:
REG-4
Alternative name(s):
Gastrointestinal secretory protein
REG-like protein
Regenerating islet-derived protein IV
Short name:
Reg IV
Gene namesi
Name:REG4
Synonyms:GISP, RELP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:22977. REG4.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • extracellular region Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA134888932.

Polymorphism and mutation databases

BioMutaiREG4.
DMDMi68565834.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 22221 PublicationAdd
BLAST
Chaini23 – 158136Regenerating islet-derived protein 4PRO_0000017437Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi30 ↔ 41PROSITE-ProRule annotation1 Publication
Glycosylationi50 – 501N-linked (GlcNAc...)Sequence analysis
Disulfide bondi58 ↔ 154PROSITE-ProRule annotation1 Publication
Disulfide bondi129 ↔ 146PROSITE-ProRule annotation1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ9BYZ8.
PRIDEiQ9BYZ8.

PTM databases

PhosphoSiteiQ9BYZ8.

Expressioni

Tissue specificityi

Highly expressed in the gastrointestinal tract including the duodenum, jejunum, ileum, ileocecum, appendix, descending colon, pancreas and small intestine. Weakly expressed in normal colon and stomach. Strongly expressed in most colorectal tumors than in normal colon. Preferentially expressed in mucinous tumors and in some cases neuro-endocrine tumors. Expressed in mucus-secreting cells and enterocyte-like cells. In small intestine expressed at the basal perinuclear zone of goblet cells.3 Publications

Inductioni

Up-regulated by mucosal injury from active Crohn's disease or ulcerative colitis. Up-regulated in colorectal tumors. Up-regulated in epithelial cells at regenerating margins of peptic ulcers in the stomach and duodenum.3 Publications

Gene expression databases

BgeeiQ9BYZ8.
CleanExiHS_REG4.
ExpressionAtlasiQ9BYZ8. baseline and differential.
GenevisibleiQ9BYZ8. HS.

Organism-specific databases

HPAiCAB025867.
HPA046555.

Interactioni

Protein-protein interaction databases

BioGridi123843. 6 interactions.
STRINGi9606.ENSP00000256585.

Structurei

Secondary structure

1
158
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi40 – 4910Combined sources
Helixi51 – 599Combined sources
Beta strandi62 – 643Combined sources
Helixi73 – 8311Combined sources
Beta strandi95 – 973Combined sources
Beta strandi99 – 1035Combined sources
Beta strandi129 – 1324Combined sources
Beta strandi141 – 1444Combined sources
Beta strandi150 – 1567Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2KV3NMR-A29-158[»]
ProteinModelPortaliQ9BYZ8.
SMRiQ9BYZ8. Positions 29-158.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini37 – 155119C-type lectinPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni98 – 1036Carbohydrate-binding
Regioni135 – 1373Carbohydrate-binding

Sequence similaritiesi

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

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG4297. Eukaryota.
ENOG410XPJ1. LUCA.
GeneTreeiENSGT00700000104249.
HOGENOMiHOG000010281.
HOVERGENiHBG004151.
InParanoidiQ9BYZ8.
OMAiCNKRQHF.
OrthoDBiEOG7FFMQR.
PhylomeDBiQ9BYZ8.

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]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9BYZ8-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MASRSMRLLL LLSCLAKTGV LGDIIMRPSC APGWFYHKSN CYGYFRKLRN
60 70 80 90 100
WSDAELECQS YGNGAHLASI LSLKEASTIA EYISGYQRSQ PIWIGLHDPQ
110 120 130 140 150
KRQQWQWIDG AMYLYRSWSG KSMGGNKHCA EMSSNNNFLT WSSNECNKRQ

HFLCKYRP
Length:158
Mass (Da):18,230
Last modified:June 1, 2001 - v1
Checksum:i7308849CBBD6E93E
GO
Isoform 2 (identifier: Q9BYZ8-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     56-134: LECQSYGNGA...GNKHCAEMSS → VRNLLPAWPG...LDGLQAHTDT
     135-158: Missing.

Show »
Length:134
Mass (Da):14,993
Checksum:iE0E5AD9B96A53EB5
GO

Sequence cautioni

The sequence AAM95599.1 differs from that shown.Aberrant splicing.Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti135 – 1351N → H.
Corresponds to variant rs34996202 [ dbSNP | Ensembl ].
VAR_050122

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei56 – 13479LECQS…AEMSS → VRNLLPAWPGLSRAKDQPEP QISFDSGSSVLPGHYEEKPL WLVKWREEGCVFNSFNSVSI AEAGAVCQTLDGLQAHTDT in isoform 2. 1 PublicationVSP_014305Add
BLAST
Alternative sequencei135 – 15824Missing in isoform 2. 1 PublicationVSP_014308Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY007243 mRNA. Translation: AAG02562.1.
AY126670 mRNA. Translation: AAM95598.1.
AY126671 mRNA. Translation: AAM95599.1. Sequence problems.
AY126672 mRNA. Translation: AAM95600.1.
AF345934 mRNA. Translation: AAK59869.1.
AF254415 mRNA. Translation: AAK48435.1.
AL359752 Genomic DNA. Translation: CAI18972.1.
AL359752 Genomic DNA. Translation: CAI18973.1.
BC017089 mRNA. Translation: AAH17089.1.
CCDSiCCDS53354.1. [Q9BYZ8-2]
CCDS906.1. [Q9BYZ8-1]
RefSeqiNP_001152824.1. NM_001159352.1. [Q9BYZ8-1]
NP_001152825.1. NM_001159353.1. [Q9BYZ8-2]
NP_114433.1. NM_032044.3. [Q9BYZ8-1]
UniGeneiHs.660883.

Genome annotation databases

EnsembliENST00000256585; ENSP00000256585; ENSG00000134193. [Q9BYZ8-1]
ENST00000354219; ENSP00000346158; ENSG00000134193. [Q9BYZ8-1]
ENST00000369401; ENSP00000358409; ENSG00000134193. [Q9BYZ8-2]
GeneIDi83998.
KEGGihsa:83998.
UCSCiuc001eif.4. human. [Q9BYZ8-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
Functional Glycomics Gateway - Glycan Binding

Regenerating protein IV

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY007243 mRNA. Translation: AAG02562.1.
AY126670 mRNA. Translation: AAM95598.1.
AY126671 mRNA. Translation: AAM95599.1. Sequence problems.
AY126672 mRNA. Translation: AAM95600.1.
AF345934 mRNA. Translation: AAK59869.1.
AF254415 mRNA. Translation: AAK48435.1.
AL359752 Genomic DNA. Translation: CAI18972.1.
AL359752 Genomic DNA. Translation: CAI18973.1.
BC017089 mRNA. Translation: AAH17089.1.
CCDSiCCDS53354.1. [Q9BYZ8-2]
CCDS906.1. [Q9BYZ8-1]
RefSeqiNP_001152824.1. NM_001159352.1. [Q9BYZ8-1]
NP_001152825.1. NM_001159353.1. [Q9BYZ8-2]
NP_114433.1. NM_032044.3. [Q9BYZ8-1]
UniGeneiHs.660883.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2KV3NMR-A29-158[»]
ProteinModelPortaliQ9BYZ8.
SMRiQ9BYZ8. Positions 29-158.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi123843. 6 interactions.
STRINGi9606.ENSP00000256585.

Protein family/group databases

MEROPSiI63.002.

PTM databases

PhosphoSiteiQ9BYZ8.

Polymorphism and mutation databases

BioMutaiREG4.
DMDMi68565834.

Proteomic databases

PaxDbiQ9BYZ8.
PRIDEiQ9BYZ8.

Protocols and materials databases

DNASUi83998.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000256585; ENSP00000256585; ENSG00000134193. [Q9BYZ8-1]
ENST00000354219; ENSP00000346158; ENSG00000134193. [Q9BYZ8-1]
ENST00000369401; ENSP00000358409; ENSG00000134193. [Q9BYZ8-2]
GeneIDi83998.
KEGGihsa:83998.
UCSCiuc001eif.4. human. [Q9BYZ8-1]

Organism-specific databases

CTDi83998.
GeneCardsiREG4.
HGNCiHGNC:22977. REG4.
HPAiCAB025867.
HPA046555.
MIMi609846. gene.
neXtProtiNX_Q9BYZ8.
PharmGKBiPA134888932.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4297. Eukaryota.
ENOG410XPJ1. LUCA.
GeneTreeiENSGT00700000104249.
HOGENOMiHOG000010281.
HOVERGENiHBG004151.
InParanoidiQ9BYZ8.
OMAiCNKRQHF.
OrthoDBiEOG7FFMQR.
PhylomeDBiQ9BYZ8.

Miscellaneous databases

ChiTaRSiREG4. human.
GeneWikiiREG4.
GenomeRNAii83998.
NextBioi73156.
PROiQ9BYZ8.
SOURCEiSearch...

Gene expression databases

BgeeiQ9BYZ8.
CleanExiHS_REG4.
ExpressionAtlasiQ9BYZ8. baseline and differential.
GenevisibleiQ9BYZ8. 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. "Isolation and characterization of a cDNA encoding a novel member of the human regenerating protein family: Reg IV."
    Hartupee J.C., Zhang H., Bonaldo M.F., Soares M.B., Dieckgraefe B.K.
    Biochim. Biophys. Acta 1518:287-293(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, INDUCTION.
  2. "RELP, a novel human REG-like protein with up-regulated expression in inflammatory and metaplastic gastrointestinal mucosa."
    Kaemaeraeinen M., Heiskala K., Knuutila S., Heiskala M., Winqvist O., Andersson L.C.
    Am. J. Pathol. 163:11-20(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION.
  3. "Reg IV, a new member of the regenerating gene family, is overexpressed in colorectal carcinomas."
    Violette S., Festor E., Pandrea-Vasile I., Mitchell V., Adida C., Dussaulx E., Lacorte J.-M., Chambaz J., Lacasa M., Lesuffleur T.
    Int. J. Cancer 103:185-193(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, INDUCTION.
    Tissue: Colon cancer.
  4. "Identification of gastrointestinal secretory protein (GISP), a new member of lithostathine gene family."
    Lin W.-C.
    Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  5. "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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE 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] (ISOFORM 1).
    Tissue: Colon.
  7. "Signal peptide prediction based on analysis of experimentally verified cleavage sites."
    Zhang Z., Henzel W.J.
    Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 23-37.
  8. "Human RegIV protein adopts a typical C-type lectin fold but binds mannan with two calcium-independent sites."
    Ho M.R., Lou Y.C., Wei S.Y., Luo S.C., Lin W.C., Lyu P.C., Chen C.
    J. Mol. Biol. 402:682-695(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 29-158 OF MUTANT SER-91, FUNCTION, MANNAN-BINDING, HEPARIN-BINDING, DISULFIDE BONDS.

Entry informationi

Entry nameiREG4_HUMAN
AccessioniPrimary (citable) accession number: Q9BYZ8
Secondary accession number(s): Q8NER6, Q8NER7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 5, 2005
Last sequence update: June 1, 2001
Last modified: March 16, 2016
This is version 118 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 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.