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Protein

Mucosal addressin cell adhesion molecule 1

Gene

MADCAM1

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

Functioni

Cell adhesion leukocyte receptor expressed by mucosal venules, helps to direct lymphocyte traffic into mucosal tissues including the Peyer patches and the intestinal lamina propria. It can bind both integrin alpha-4/beta-7 and L-selectin, regulating both the passage and retention of leukocytes. Isoform 2, lacking the mucin-like domain, may be specialized in supporting integrin alpha-4/beta-7-dependent adhesion strengthening, independent of L-selectin binding.

Caution

GO - Molecular functioni

  • integrin binding involved in cell-matrix adhesion Source: UniProtKB

GO - Biological processi

  • cell adhesion Source: ProtInc
  • cell-matrix adhesion Source: UniProtKB
  • extracellular matrix organization Source: Reactome
  • heterotypic cell-cell adhesion Source: UniProtKB
  • immune response Source: ProtInc
  • integrin-mediated signaling pathway Source: UniProtKB
  • leukocyte tethering or rolling Source: UniProtKB
  • positive regulation of leukocyte migration Source: GO_Central
  • positive regulation of lymphocyte migration Source: InterPro
  • receptor clustering Source: UniProtKB
  • regulation of immune response Source: Reactome
  • signal transduction Source: ProtInc

Keywordsi

Biological processCell adhesion

Enzyme and pathway databases

ReactomeiR-HSA-198933 Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-216083 Integrin cell surface interactions
SignaLinkiQ13477
SIGNORiQ13477

Names & Taxonomyi

Protein namesi
Recommended name:
Mucosal addressin cell adhesion molecule 1
Short name:
MAdCAM-1
Short name:
hMAdCAM-1
Gene namesi
Name:MADCAM1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000099866.14
HGNCiHGNC:6765 MADCAM1
MIMi102670 gene
neXtProtiNX_Q13477

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini19 – 317ExtracellularSequence analysisAdd BLAST299
Transmembranei318 – 338HelicalSequence analysisAdd BLAST21
Topological domaini339 – 382CytoplasmicSequence analysisAdd BLAST44

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi8174
OpenTargetsiENSG00000099866
PharmGKBiPA30522

Chemistry databases

ChEMBLiCHEMBL4467

Polymorphism and mutation databases

BioMutaiMADCAM1
DMDMi218511712

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 18Sequence analysisAdd BLAST18
ChainiPRO_000001485319 – 382Mucosal addressin cell adhesion molecule 1Add BLAST364

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi47 ↔ 94Combined sources3 Publications
Disulfide bondi51 ↔ 98Combined sources3 Publications
Glycosylationi83N-linked (GlcNAc...) asparagineSequence analysis1 Publication1
Disulfide bondi134 ↔ 204Combined sources3 Publications

Post-translational modificationi

The Ser/Thr-rich mucin-like domain may provide possible sites for O-glycosylation.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ13477
PeptideAtlasiQ13477
PRIDEiQ13477

PTM databases

iPTMnetiQ13477
PhosphoSitePlusiQ13477

Expressioni

Tissue specificityi

Highly expressed on high endothelial venules (HEV) and lamina propia venules found in the small intestine, and to a lesser extent in the colon and spleen. Very low levels of expression found in pancreas and brain. Not expressed in the thymus, prostate, ovaries, testis, heart, placenta, lung, liver, skeletal muscle, kidney or peripheral blood leukocytes.2 Publications

Gene expression databases

BgeeiENSG00000099866
CleanExiHS_MADCAM1
ExpressionAtlasiQ13477 baseline and differential
GenevisibleiQ13477 HS

Interactioni

Subunit structurei

Homodimer.Curated

GO - Molecular functioni

  • integrin binding involved in cell-matrix adhesion Source: UniProtKB

Protein-protein interaction databases

BioGridi1138254 interactors.
IntActiQ13477 1 interactor.
STRINGi9606.ENSP00000215637

Chemistry databases

BindingDBiQ13477

Structurei

Secondary structure

1382
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi25 – 30Combined sources6
Beta strandi33 – 38Combined sources6
Beta strandi43 – 49Combined sources7
Beta strandi52 – 54Combined sources3
Beta strandi57 – 62Combined sources6
Turni64 – 67Combined sources4
Beta strandi69 – 83Combined sources15
Helixi86 – 88Combined sources3
Beta strandi90 – 98Combined sources9
Beta strandi101 – 113Combined sources13
Beta strandi116 – 125Combined sources10
Beta strandi131 – 140Combined sources10
Turni144 – 146Combined sources3
Beta strandi147 – 153Combined sources7
Beta strandi167 – 171Combined sources5
Beta strandi175 – 177Combined sources3
Beta strandi180 – 190Combined sources11
Beta strandi200 – 210Combined sources11
Beta strandi213 – 223Combined sources11

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1BQSX-ray2.20A23-231[»]
1GSMX-ray1.90A19-224[»]
4HBQX-ray1.40A/B23-171[»]
A/B180-224[»]
4HC1X-ray2.87A/B23-171[»]
A/B180-224[»]
4HCRX-ray2.30A/B23-225[»]
4HD9X-ray1.70A23-225[»]
ProteinModelPortaliQ13477
SMRiQ13477
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ13477

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini23 – 112Ig-like 1Add BLAST90
Domaini113 – 231Ig-like 2Add BLAST119
Repeati228 – 2311; truncated4
Repeati232 – 23928
Repeati240 – 24738
Repeati248 – 25548
Repeati256 – 26358
Repeati264 – 27168

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni226 – 317Mucin-likeAdd BLAST92
Regioni228 – 2715.5 X 8 AA tandem repeats of [PS]-P-D-T-T-S-[QP]-EAdd BLAST44

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410J133 Eukaryota
ENOG411140D LUCA
GeneTreeiENSGT00510000049549
HOGENOMiHOG000060103
HOVERGENiHBG108114
InParanoidiQ13477
KOiK06779
TreeFamiTF337571

Family and domain databases

Gene3Di2.60.40.102 hits
InterProiView protein in InterPro
IPR015169 Adhes-Ig-like
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR003599 Ig_sub
IPR037413 MADCAM1
PANTHERiPTHR14162 PTHR14162, 1 hit
PfamiView protein in Pfam
PF09085 Adhes-Ig_like, 1 hit
ProDomiView protein in ProDom or Entries sharing at least one domain
PD336606 Adhes-Ig-like, 1 hit
SMARTiView protein in SMART
SM00409 IG, 1 hit
SUPFAMiSSF48726 SSF48726, 2 hits
PROSITEiView protein in PROSITE
PS50835 IG_LIKE, 1 hit

Sequences (4)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: Q13477-1) [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
MDFGLALLLA GLLGLLLGQS LQVKPLQVEP PEPVVAVALG ASRQLTCRLA
60 70 80 90 100
CADRGASVQW RGLDTSLGAV QSDTGRSVLT VRNASLSAAG TRVCVGSCGG
110 120 130 140 150
RTFQHTVQLL VYAFPDQLTV SPAALVPGDP EVACTAHKVT PVDPNALSFS
160 170 180 190 200
LLVGGQELEG AQALGPEVQE EEEEPQGDED VLFRVTERWR LPPLGTPVPP
210 220 230 240 250
ALYCQATMRL PGLELSHRQA IPVLHSPTSP EPPDTTSPES PDTTSPESPD
260 270 280 290 300
TTSQEPPDTT SPEPPDKTSP EPAPQQGSTH TPRSPGSTRT RRPEISQAGP
310 320 330 340 350
TQGEVIPTGS SKPAGDQLPA ALWTSSAVLG LLLLALPTYH LWKRCRHLAE
360 370 380
DDTHPPASLR LLPQVSAWAG LRGTGQVGIS PS
Length:382
Mass (Da):40,155
Last modified:December 16, 2008 - v2
Checksum:i9DCA60C30BA61E62
GO
Isoform 2 (identifier: Q13477-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     223-334: VLHSPTSPEP...SSAVLGLLLL → A

Show »
Length:271
Mass (Da):28,705
Checksum:i3613F1F208F9F31D
GO
Isoform 3 (identifier: Q13477-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     223-310: VLHSPTSPEP...TQGEVIPTGS → A

Note: No experimental confirmation available.
Show »
Length:295
Mass (Da):31,109
Checksum:iF635D6F54504D68D
GO
Isoform 4 (identifier: Q13477-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     18-112: Missing.
     223-310: VLHSPTSPEP...TQGEVIPTGS → A

Show »
Length:200
Mass (Da):21,247
Checksum:i84204D98FC1FC7C7
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti240S → P in AAB02194 (PubMed:8609404).Curated1
Sequence conflicti240S → P in AAC51354 (PubMed:9162097).Curated1
Sequence conflicti242D → N in AAB02194 (PubMed:8609404).Curated1
Sequence conflicti242D → N in AAC51354 (PubMed:9162097).Curated1
Sequence conflicti254Q → P in AAC13661 (PubMed:8989586).Curated1

Polymorphismi

The number of repeats in the mucin domain varies between 5 and 8 repeats.2 Publications

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_047901253S → SPESPDTTSQEPPDTTSQEP PDTTS3 Publications1
Natural variantiVAR_017580300P → H. Corresponds to variant dbSNP:rs3745925Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04769418 – 112Missing in isoform 4. 1 PublicationAdd BLAST95
Alternative sequenceiVSP_050014223 – 334VLHSP…GLLLL → A in isoform 2. CuratedAdd BLAST112
Alternative sequenceiVSP_043202223 – 310VLHSP…IPTGS → A in isoform 3 and isoform 4. 2 PublicationsAdd BLAST88

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U43628 mRNA Translation: AAB02194.1
U80016
, U80012, U80013, U80014, U80015 Genomic DNA Translation: AAC51354.1
U82483 mRNA Translation: AAC13661.1
AY732484 mRNA Translation: AAV33123.1
AC005775 Genomic DNA Translation: AAC62844.1
CH471242 Genomic DNA Translation: EAW61195.1
BC137506 mRNA Translation: AAI37507.1
BC137507 mRNA Translation: AAI37508.1
BC144065 mRNA Translation: AAI44066.1
BC142629 mRNA Translation: AAI42630.1
CCDSiCCDS12028.1 [Q13477-1]
CCDS12029.1 [Q13477-3]
RefSeqiNP_570116.2, NM_130760.2 [Q13477-1]
NP_570118.1, NM_130762.2 [Q13477-3]
UniGeneiHs.102598

Genome annotation databases

EnsembliENST00000215637; ENSP00000215637; ENSG00000099866 [Q13477-1]
ENST00000346144; ENSP00000304247; ENSG00000099866 [Q13477-3]
ENST00000382683; ENSP00000372130; ENSG00000099866 [Q13477-4]
GeneIDi8174
KEGGihsa:8174
UCSCiuc002los.4 human [Q13477-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiMADCA_HUMAN
AccessioniPrimary (citable) accession number: Q13477
Secondary accession number(s): A5PKV4
, B2RPL9, O60222, O75867, Q5UGI7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 2, 2004
Last sequence update: December 16, 2008
Last modified: February 28, 2018
This is version 152 of the entry and version 2 of the sequence. See 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, Reference proteome