MADCA_MOUSE
ID MADCA_MOUSE Reviewed; 405 AA.
AC Q61826; O35530; Q61278; Q64275; Q8R1M6;
DT 02-FEB-2004, integrated into UniProtKB/Swiss-Prot.
DT 02-FEB-2004, sequence version 2.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Mucosal addressin cell adhesion molecule 1;
DE Short=MAdCAM-1;
DE Short=mMAdCAM-1;
DE Flags: Precursor;
GN Name=Madcam1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE (ISOFORM 1), INTERACTION WITH ALPHA-4/BETA-7 INTEGRIN,
RP AND TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ; TISSUE=Brain;
RX PubMed=8502297; DOI=10.1038/363461a0;
RA Briskin M.J., McEvoy L.M., Butcher E.C.;
RT "MAdCAM-1 has homology to immunoglobulin and mucin-like adhesion receptors
RT and to IgA1.";
RL Nature 363:461-464(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2).
RC STRAIN=SRB; TISSUE=Liver;
RX PubMed=7650378;
RA Sampaio S.O., Li X., Takeuchi M., Mei C., Francke U., Butcher E.C.,
RA Briskin M.J.;
RT "Organization, regulatory sequences, and alternatively spliced transcripts
RT of the mucosal addressin cell adhesion molecule-1 (MAdCAM-1) gene.";
RL J. Immunol. 155:2477-2486(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), ALTERNATIVE SPLICING, AND
RP FUNCTION.
RC STRAIN=BALB/cJ; TISSUE=Lymph node;
RX PubMed=7488084; DOI=10.1006/bbrc.1995.2606;
RA Schiffer S.G., Day E., Latanision S.M., Tizard R., Osborn L.;
RT "An alternately spliced mRNA encoding functional domains of murine MAdCAM-
RT 1.";
RL Biochem. Biophys. Res. Commun. 216:170-176(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), AND DISEASE.
RC STRAIN=BALB/cJ;
RX PubMed=9316640; DOI=10.1006/cimm.1997.1177;
RA Koike R., Watanabe T., Satoh H., Hee C.S., Kitada K., Kuramoto T.,
RA Serikawa T., Miyawaki S., Miyasaka M.;
RT "Analysis of expression of lymphocyte homing-related adhesion molecules in
RT ALY mice deficient in lymph nodes and Peyer's patches.";
RL Cell. Immunol. 180:62-69(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [6]
RP INTERACTION WITH ALPHA-4/BETA-7 INTEGRIN.
RC TISSUE=Lymph node;
RX PubMed=7687523; DOI=10.1016/0092-8674(93)90305-a;
RA Berlin C., Berg E.L., Briskin M.J., Andrew D.P., Kilshaw P.J., Holzmann B.,
RA Weissman I.L., Hamann A., Butcher E.C.;
RT "Alpha 4 beta 7 integrin mediates lymphocyte binding to the mucosal
RT vascular addressin MAdCAM-1.";
RL Cell 74:185-195(1993).
RN [7]
RP TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=3340147; DOI=10.1038/331041a0;
RA Streeter P.R., Berg E.L., Rouse B.T.N., Bargatze R.F., Butcher E.C.;
RT "A tissue-specific endothelial cell molecule involved in lymphocyte
RT homing.";
RL Nature 331:41-46(1988).
RN [8]
RP TISSUE SPECIFICITY, AND INDUCTION.
RC STRAIN=NOD;
RX PubMed=7693764; DOI=10.1172/jci116859;
RA Hanninen A., Taylor C., Streeter P.R., Stark L.S., Sarte J.M.,
RA Shizuru J.A., Simell O., Michie S.A.;
RT "Vascular addressins are induced on islet vessels during insulitis in
RT nonobese diabetic mice and are involved in lymphoid cell binding to islet
RT endothelium.";
RL J. Clin. Invest. 92:2509-2515(1993).
RN [9]
RP INTERACTION WITH L-SELECTIN, AND GLYCOSYLATION.
RX PubMed=7505053; DOI=10.1038/366695a0;
RA Berg E.L., McEvoy L.M., Berlin C., Bargatze R.F., Butcher E.C.;
RT "L-selectin-mediated lymphocyte rolling on MAdCAM-1.";
RL Nature 366:695-698(1993).
RN [10]
RP INDUCTION BY TNF-ALPHA.
RX PubMed=7724598; DOI=10.1073/pnas.92.8.3561;
RA Takeuchi M., Baichwal V.R.;
RT "Induction of the gene encoding mucosal vascular addressin cell adhesion
RT molecule 1 by tumor necrosis factor alpha is mediated by NF-kappa B
RT proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:3561-3565(1995).
CC -!- FUNCTION: Cell adhesion leukocyte receptor expressed by mucosal
CC venules, helps to direct lymphocyte traffic into mucosal tissues
CC including the Peyer patches and the intestinal lamina propria. It can
CC bind both the integrin alpha-4/beta-7 and L-selectin, regulating both
CC the passage and retention of leukocytes. Both isoform 1 and isoform 2
CC can adhere to integrin alpha-4/beta-7. Isoform 2, lacking the mucin-
CC like domain, may be specialized in supporting integrin alpha-4/beta-7-
CC dependent adhesion strengthening, independent of L-selectin binding.
CC {ECO:0000269|PubMed:3340147, ECO:0000269|PubMed:7488084}.
CC -!- SUBUNIT: Homodimer. {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Long, MadCAM-384;
CC IsoId=Q61826-1; Sequence=Displayed;
CC Name=2; Synonyms=Short, MadCAM-240;
CC IsoId=Q61826-2; Sequence=VSP_050423;
CC -!- TISSUE SPECIFICITY: Highly expressed on high endothelial venules (HEV)
CC of organized intestinal lymphoid tissues like the Peyer patches and
CC mesenteric lymph nodes, and in the lamina propria of the intestine.
CC Some expression found in the spleen, and low levels of expression in
CC the peripheral lymph nodes and the lactating mammary gland. No
CC expression was detected in the liver, kidneys, lungs or in normal
CC brain. Expressed as well in brain endothelioma cells, and mucosal
CC tissues which are in a chronic state of inflammation, such as inflamed
CC pancreas. {ECO:0000269|PubMed:3340147, ECO:0000269|PubMed:7693764,
CC ECO:0000269|PubMed:8502297}.
CC -!- INDUCTION: By TNF-alpha, and chronic inflammation.
CC {ECO:0000269|PubMed:7693764, ECO:0000269|PubMed:7724598}.
CC -!- PTM: O-glycosylated; contains syalic acid. The Ser/Thr-rich mucin-like
CC domain may provide possible sites for O-glycosylation.
CC {ECO:0000269|PubMed:7505053}.
CC -!- DISEASE: Note=Absence of Madcam1 in the spleen has been found in
CC aly/aly mice, but normal expression is found in intestinal venules.
CC This aberrant expression is a secondary defect and not the direct cause
CC of aly alymphoplasia, an autosomal recessive mutation which induces
CC total aplasia of lymph nodes and Peyer patches.
CC {ECO:0000269|PubMed:9316640}.
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DR EMBL; L21203; AAA39485.1; -; mRNA.
DR EMBL; U14729; AAA81639.1; -; Genomic_DNA.
DR EMBL; U14552; AAA81639.1; JOINED; Genomic_DNA.
DR EMBL; U14729; AAA81638.1; -; Genomic_DNA.
DR EMBL; U14552; AAA81638.1; JOINED; Genomic_DNA.
DR EMBL; S80258; AAB35609.1; -; mRNA.
DR EMBL; D50434; BAA23364.1; -; Genomic_DNA.
DR EMBL; BC024372; AAH24372.1; -; mRNA.
DR CCDS; CCDS23981.1; -. [Q61826-1]
DR CCDS; CCDS88048.1; -. [Q61826-2]
DR PIR; I48645; I48645.
DR PIR; S33601; S33601.
DR RefSeq; XP_006513356.1; XM_006513293.3.
DR AlphaFoldDB; Q61826; -.
DR SMR; Q61826; -.
DR STRING; 10090.ENSMUSP00000020554; -.
DR BindingDB; Q61826; -.
DR GlyGen; Q61826; 3 sites.
DR PhosphoSitePlus; Q61826; -.
DR PaxDb; Q61826; -.
DR PRIDE; Q61826; -.
DR ProteomicsDB; 292145; -. [Q61826-1]
DR ProteomicsDB; 292146; -. [Q61826-2]
DR Antibodypedia; 9993; 738 antibodies from 34 providers.
DR Ensembl; ENSMUST00000217748; ENSMUSP00000151928; ENSMUSG00000020310. [Q61826-2]
DR MGI; MGI:103579; Madcam1.
DR VEuPathDB; HostDB:ENSMUSG00000020310; -.
DR eggNOG; ENOG502SR0W; Eukaryota.
DR GeneTree; ENSGT00510000049549; -.
DR InParanoid; Q61826; -.
DR PhylomeDB; Q61826; -.
DR Reactome; R-MMU-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR Reactome; R-MMU-216083; Integrin cell surface interactions.
DR BioGRID-ORCS; 17123; 6 hits in 73 CRISPR screens.
DR PRO; PR:Q61826; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q61826; protein.
DR Bgee; ENSMUSG00000020310; Expressed in mesenteric lymph node and 68 other tissues.
DR ExpressionAtlas; Q61826; baseline and differential.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:GOC.
DR GO; GO:0098640; F:integrin binding involved in cell-matrix adhesion; ISO:MGI.
DR GO; GO:0007155; P:cell adhesion; ISO:MGI.
DR GO; GO:0007160; P:cell-matrix adhesion; ISO:MGI.
DR GO; GO:0034113; P:heterotypic cell-cell adhesion; ISO:MGI.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; ISO:MGI.
DR GO; GO:0030216; P:keratinocyte differentiation; IMP:MGI.
DR GO; GO:0050900; P:leukocyte migration; IMP:MGI.
DR GO; GO:0050901; P:leukocyte tethering or rolling; ISO:MGI.
DR GO; GO:0002687; P:positive regulation of leukocyte migration; ISO:MGI.
DR GO; GO:2000403; P:positive regulation of lymphocyte migration; IEA:InterPro.
DR GO; GO:0043113; P:receptor clustering; ISO:MGI.
DR Gene3D; 2.60.40.10; -; 2.
DR InterPro; IPR015169; Adhes-Ig-like.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR037413; MADCAM1.
DR PANTHER; PTHR14162; PTHR14162; 1.
DR Pfam; PF09085; Adhes-Ig_like; 1.
DR SUPFAM; SSF48726; SSF48726; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell adhesion; Disulfide bond; Glycoprotein;
KW Immunoglobulin domain; Membrane; Reference proteome; Repeat; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..405
FT /note="Mucosal addressin cell adhesion molecule 1"
FT /id="PRO_0000014854"
FT TOPO_DOM 22..364
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 365..385
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 386..405
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 22..109
FT /note="Ig-like 1"
FT DOMAIN 110..227
FT /note="Ig-like 2"
FT DOMAIN 258..357
FT /note="Ig-like 3"
FT REGION 221..257
FT /note="Mucin-like"
FT REGION 255..275
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 230
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 253
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 361
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 45..91
FT /evidence="ECO:0000250|UniProtKB:Q13477"
FT DISULFID 49..95
FT /evidence="ECO:0000250|UniProtKB:Q13477"
FT DISULFID 132..200
FT /evidence="ECO:0000250|UniProtKB:Q13477"
FT DISULFID 293..341
FT /evidence="ECO:0000255"
FT VAR_SEQ 219..363
FT /note="VLQSQTSPKPPNTTSAEPYILTSSSTAEAVSTGLNITTLPSAPPYPKLSPRT
FT LSSEGPCRPKIHQDLEAGWELLCEASCGPGVTVRWTLAPGDLATYHKREAGAQAWLSVL
FT PPGPMVEGWFQCRQDPGGEVTNLYVPGQVTPNSS -> A (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:7488084"
FT /id="VSP_050423"
FT CONFLICT 6
FT /note="A -> S (in Ref. 4; BAA23364)"
FT /evidence="ECO:0000305"
FT CONFLICT 10
FT /note="A -> S (in Ref. 4)"
FT /evidence="ECO:0000305"
FT CONFLICT 12
FT /note="A -> S (in Ref. 4)"
FT /evidence="ECO:0000305"
FT CONFLICT 61
FT /note="L -> R (in Ref. 1 and 4)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 405 AA; 43652 MW; 4F2D08418EA51980 CRC64;
MESILALLLA LALVPYQLSR GQSFQVNPPE SEVAVAMGTS LQITCSMSCD EGVARVHWRG
LDTSLGSVQT LPGSSILSVR GMLSDTGTPV CVGSCGSRSF QHSVKILVYA FPDQLVVSPE
FLVPGQDQVV SCTAHNIWPA DPNSLSFALL LGEQRLEGAQ ALEPEQEEEI QEAEGTPLFR
MTQRWRLPSL GTPAPPALHC QVTMQLPKLV LTHRKEIPVL QSQTSPKPPN TTSAEPYILT
SSSTAEAVST GLNITTLPSA PPYPKLSPRT LSSEGPCRPK IHQDLEAGWE LLCEASCGPG
VTVRWTLAPG DLATYHKREA GAQAWLSVLP PGPMVEGWFQ CRQDPGGEVT NLYVPGQVTP
NSSSTVVLWI GSLVLGLLAL VFLAYRLWKC YRPGPRPDTS SCTHL
