REG4_HUMAN
ID REG4_HUMAN Reviewed; 158 AA.
AC Q9BYZ8; Q8NER6; Q8NER7;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Regenerating islet-derived protein 4;
DE Short=REG-4;
DE AltName: Full=Gastrointestinal secretory protein;
DE AltName: Full=REG-like protein;
DE AltName: Full=Regenerating islet-derived protein IV;
DE Short=Reg IV;
DE Flags: Precursor;
GN Name=REG4; Synonyms=GISP, RELP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=11311942; DOI=10.1016/s0167-4781(00)00284-0;
RA Hartupee J.C., Zhang H., Bonaldo M.F., Soares M.B., Dieckgraefe B.K.;
RT "Isolation and characterization of a cDNA encoding a novel member of the
RT human regenerating protein family: Reg IV.";
RL Biochim. Biophys. Acta 1518:287-293(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=12819006; DOI=10.1016/s0002-9440(10)63625-5;
RA Kaemaeraeinen M., Heiskala K., Knuutila S., Heiskala M., Winqvist O.,
RA Andersson L.C.;
RT "RELP, a novel human REG-like protein with up-regulated expression in
RT inflammatory and metaplastic gastrointestinal mucosa.";
RL Am. J. Pathol. 163:11-20(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND INDUCTION.
RC TISSUE=Colon cancer;
RX PubMed=12455032; DOI=10.1002/ijc.10788;
RA Violette S., Festor E., Pandrea-Vasile I., Mitchell V., Adida C.,
RA Dussaulx E., Lacorte J.-M., Chambaz J., Lacasa M., Lesuffleur T.;
RT "Reg IV, a new member of the regenerating gene family, is overexpressed in
RT colorectal carcinomas.";
RL Int. J. Cancer 103:185-193(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Lin W.-C.;
RT "Identification of gastrointestinal secretory protein (GISP), a new member
RT of lithostathine gene family.";
RL Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 23-37.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [8]
RP STRUCTURE BY NMR OF 29-158 OF MUTANT SER-91, FUNCTION, MANNAN-BINDING,
RP HEPARIN-BINDING, AND DISULFIDE BONDS.
RX PubMed=20692269; DOI=10.1016/j.jmb.2010.07.061;
RA Ho M.R., Lou Y.C., Wei S.Y., Luo S.C., Lin W.C., Lyu P.C., Chen C.;
RT "Human RegIV protein adopts a typical C-type lectin fold but binds mannan
RT with two calcium-independent sites.";
RL J. Mol. Biol. 402:682-695(2010).
CC -!- FUNCTION: Calcium-independent lectin displaying mannose-binding
CC specificity and able to maintain carbohydrate recognition activity in
CC an acidic environment. May be involved in inflammatory and metaplastic
CC responses of the gastrointestinal epithelium.
CC {ECO:0000269|PubMed:12819006, ECO:0000269|PubMed:20692269}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12819006}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9BYZ8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BYZ8-2; Sequence=VSP_014305, VSP_014308;
CC -!- TISSUE SPECIFICITY: Highly expressed in the gastrointestinal tract
CC including the duodenum, jejunum, ileum, ileocecum, appendix, descending
CC colon, pancreas and small intestine. Weakly expressed in normal colon
CC and stomach. Strongly expressed in most colorectal tumors than in
CC normal colon. Preferentially expressed in mucinous tumors and in some
CC cases neuro-endocrine tumors. Expressed in mucus-secreting cells and
CC enterocyte-like cells. In small intestine expressed at the basal
CC perinuclear zone of goblet cells. {ECO:0000269|PubMed:11311942,
CC ECO:0000269|PubMed:12455032, ECO:0000269|PubMed:12819006}.
CC -!- INDUCTION: Up-regulated by mucosal injury from active Crohn's disease
CC or ulcerative colitis. Up-regulated in colorectal tumors. Up-regulated
CC in epithelial cells at regenerating margins of peptic ulcers in the
CC stomach and duodenum. {ECO:0000269|PubMed:11311942,
CC ECO:0000269|PubMed:12455032, ECO:0000269|PubMed:12819006}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAM95599.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/REGIVID485.html";
CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - Glycan Binding;
CC Note=Regenerating protein IV;
CC URL="http://www.functionalglycomics.org/glycomics/GBPServlet?&operationType=view&cbpId=cbp_hum_Ctlect_257";
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DR EMBL; AY007243; AAG02562.1; -; mRNA.
DR EMBL; AY126670; AAM95598.1; -; mRNA.
DR EMBL; AY126671; AAM95599.1; ALT_SEQ; mRNA.
DR EMBL; AY126672; AAM95600.1; -; mRNA.
DR EMBL; AF345934; AAK59869.1; -; mRNA.
DR EMBL; AF254415; AAK48435.1; -; mRNA.
DR EMBL; AL359752; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC017089; AAH17089.1; -; mRNA.
DR CCDS; CCDS53354.1; -. [Q9BYZ8-2]
DR CCDS; CCDS906.1; -. [Q9BYZ8-1]
DR RefSeq; NP_001152824.1; NM_001159352.1. [Q9BYZ8-1]
DR RefSeq; NP_001152825.1; NM_001159353.1. [Q9BYZ8-2]
DR RefSeq; NP_114433.1; NM_032044.3. [Q9BYZ8-1]
DR PDB; 2KV3; NMR; -; A=29-158.
DR PDBsum; 2KV3; -.
DR AlphaFoldDB; Q9BYZ8; -.
DR BMRB; Q9BYZ8; -.
DR SMR; Q9BYZ8; -.
DR BioGRID; 123843; 8.
DR IntAct; Q9BYZ8; 6.
DR STRING; 9606.ENSP00000346158; -.
DR MEROPS; I63.002; -.
DR GlyGen; Q9BYZ8; 1 site.
DR iPTMnet; Q9BYZ8; -.
DR PhosphoSitePlus; Q9BYZ8; -.
DR BioMuta; REG4; -.
DR DMDM; 68565834; -.
DR jPOST; Q9BYZ8; -.
DR MassIVE; Q9BYZ8; -.
DR PaxDb; Q9BYZ8; -.
DR PeptideAtlas; Q9BYZ8; -.
DR PRIDE; Q9BYZ8; -.
DR ProteomicsDB; 79745; -. [Q9BYZ8-1]
DR ProteomicsDB; 79746; -. [Q9BYZ8-2]
DR Antibodypedia; 46951; 208 antibodies from 27 providers.
DR DNASU; 83998; -.
DR Ensembl; ENST00000256585.10; ENSP00000256585.5; ENSG00000134193.15. [Q9BYZ8-1]
DR Ensembl; ENST00000354219.5; ENSP00000346158.1; ENSG00000134193.15. [Q9BYZ8-1]
DR Ensembl; ENST00000369401.4; ENSP00000358409.4; ENSG00000134193.15. [Q9BYZ8-2]
DR GeneID; 83998; -.
DR KEGG; hsa:83998; -.
DR MANE-Select; ENST00000256585.10; ENSP00000256585.5; NM_032044.4; NP_114433.1.
DR UCSC; uc001eif.4; human. [Q9BYZ8-1]
DR CTD; 83998; -.
DR DisGeNET; 83998; -.
DR GeneCards; REG4; -.
DR HGNC; HGNC:22977; REG4.
DR HPA; ENSG00000134193; Tissue enriched (intestine).
DR MIM; 609846; gene.
DR neXtProt; NX_Q9BYZ8; -.
DR OpenTargets; ENSG00000134193; -.
DR PharmGKB; PA134888932; -.
DR VEuPathDB; HostDB:ENSG00000134193; -.
DR eggNOG; KOG4297; Eukaryota.
DR GeneTree; ENSGT00940000161011; -.
DR HOGENOM; CLU_049894_10_1_1; -.
DR InParanoid; Q9BYZ8; -.
DR OMA; WNSNECN; -.
DR PhylomeDB; Q9BYZ8; -.
DR PathwayCommons; Q9BYZ8; -.
DR SignaLink; Q9BYZ8; -.
DR BioGRID-ORCS; 83998; 17 hits in 1073 CRISPR screens.
DR ChiTaRS; REG4; human.
DR GeneWiki; REG4; -.
DR GenomeRNAi; 83998; -.
DR Pharos; Q9BYZ8; Tbio.
DR PRO; PR:Q9BYZ8; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9BYZ8; protein.
DR Bgee; ENSG00000134193; Expressed in ileal mucosa and 88 other tissues.
DR ExpressionAtlas; Q9BYZ8; baseline and differential.
DR Genevisible; Q9BYZ8; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0008201; F:heparin binding; IDA:UniProtKB.
DR GO; GO:2001065; F:mannan binding; IDA:UniProtKB.
DR GO; GO:0038023; F:signaling receptor activity; IBA:GO_Central.
DR GO; GO:0009617; P:response to bacterium; IEA:Ensembl.
DR Gene3D; 3.10.100.10; -; 1.
DR InterPro; IPR001304; C-type_lectin-like.
DR InterPro; IPR016186; C-type_lectin-like/link_sf.
DR InterPro; IPR018378; C-type_lectin_CS.
DR InterPro; IPR016187; CTDL_fold.
DR Pfam; PF00059; Lectin_C; 1.
DR SMART; SM00034; CLECT; 1.
DR SUPFAM; SSF56436; SSF56436; 1.
DR PROSITE; PS00615; C_TYPE_LECTIN_1; 1.
DR PROSITE; PS50041; C_TYPE_LECTIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Lectin; Reference proteome; Secreted; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 23..158
FT /note="Regenerating islet-derived protein 4"
FT /id="PRO_0000017437"
FT DOMAIN 37..155
FT /note="C-type lectin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT BINDING 98..103
FT /ligand="a carbohydrate"
FT /ligand_id="ChEBI:CHEBI:16646"
FT BINDING 135..137
FT /ligand="a carbohydrate"
FT /ligand_id="ChEBI:CHEBI:16646"
FT CARBOHYD 50
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 30..41
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040,
FT ECO:0000269|PubMed:20692269"
FT DISULFID 58..154
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040,
FT ECO:0000269|PubMed:20692269"
FT DISULFID 129..146
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040,
FT ECO:0000269|PubMed:20692269"
FT VAR_SEQ 56..134
FT /note="LECQSYGNGAHLASILSLKEASTIAEYISGYQRSQPIWIGLHDPQKRQQWQW
FT IDGAMYLYRSWSGKSMGGNKHCAEMSS -> VRNLLPAWPGLSRAKDQPEPQISFDSGS
FT SVLPGHYEEKPLWLVKWREEGCVFNSFNSVSIAEAGAVCQTLDGLQAHTDT (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:12819006"
FT /id="VSP_014305"
FT VAR_SEQ 135..158
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12819006"
FT /id="VSP_014308"
FT VARIANT 135
FT /note="N -> H (in dbSNP:rs34996202)"
FT /id="VAR_050122"
FT STRAND 40..49
FT /evidence="ECO:0007829|PDB:2KV3"
FT HELIX 51..59
FT /evidence="ECO:0007829|PDB:2KV3"
FT STRAND 62..64
FT /evidence="ECO:0007829|PDB:2KV3"
FT HELIX 73..83
FT /evidence="ECO:0007829|PDB:2KV3"
FT STRAND 95..97
FT /evidence="ECO:0007829|PDB:2KV3"
FT STRAND 99..103
FT /evidence="ECO:0007829|PDB:2KV3"
FT STRAND 129..132
FT /evidence="ECO:0007829|PDB:2KV3"
FT STRAND 141..144
FT /evidence="ECO:0007829|PDB:2KV3"
FT STRAND 150..156
FT /evidence="ECO:0007829|PDB:2KV3"
SQ SEQUENCE 158 AA; 18230 MW; 7308849CBBD6E93E CRC64;
MASRSMRLLL LLSCLAKTGV LGDIIMRPSC APGWFYHKSN CYGYFRKLRN WSDAELECQS
YGNGAHLASI LSLKEASTIA EYISGYQRSQ PIWIGLHDPQ KRQQWQWIDG AMYLYRSWSG
KSMGGNKHCA EMSSNNNFLT WSSNECNKRQ HFLCKYRP
