Q13477 (MADCA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Mucosal addressin cell adhesion molecule 1
Short name=MAdCAM-1
Short name=hMAdCAM-1

Gene names

Name:

MADCAM1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	382 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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.
Subunit structure	Homodimer Probable.
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	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. Ref.1 Ref.2
Post-translational modification	The Ser/Thr-rich mucin-like domain may provide possible sites for O-glycosylation By similarity.
Polymorphism	The number of repeats in the mucin domain varies between 5 and 8 repeats.
Sequence similarities	Contains 2 Ig-like (immunoglobulin-like) domains.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Immunoglobulin domain Repeat Signal Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	aging Inferred from electronic annotation. Source: Compara cell adhesion Traceable author statement PubMed 8502297. Source: ProtInc embryo development Inferred from electronic annotation. Source: Compara immune response Traceable author statement PubMed 8502297. Source: ProtInc keratinocyte differentiation Inferred from electronic annotation. Source: Compara leukocyte migration Inferred from electronic annotation. Source: Compara positive regulation of leukocyte migration Inferred from electronic annotation. Source: Compara regulation of immune response Traceable author statement. Source: Reactome signal transduction Traceable author statement PubMed 8502297. Source: ProtInc
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: Reactome
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.

Isoform 1 (identifier: Q13477-1)

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.

Isoform 2 (identifier: Q13477-2)

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

Isoform 3 (identifier: Q13477-3)

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

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 18

18

Potential

Chain

19 – 382

364

Mucosal addressin cell adhesion molecule 1

PRO_0000014853

Regions

Topological domain

19 – 317

299

Extracellular Potential

Transmembrane

318 – 338

21

Helical; Potential

Topological domain

339 – 382

44

Cytoplasmic Potential

Domain

23 – 112

90

Ig-like 1

Domain

113 – 231

119

Ig-like 2

Repeat

228 – 231

4

1; truncated

Repeat

232 – 239

8

2

Repeat

240 – 247

8

3

Repeat

248 – 255

8

4

Repeat

256 – 263

8

5

Repeat

264 – 271

8

6

Region

226 – 317

92

Mucin-like

Region

228 – 271

44

5.5 X 8 AA tandem repeats of [PS]-P-D-T-T-S-[QP]-E

Amino acid modifications

Glycosylation

83

1

N-linked (GlcNAc...) Potential

Disulfide bond

47 ↔ 94

Disulfide bond

51 ↔ 98

Disulfide bond

134 ↔ 204

Natural variations

Alternative sequence

223 – 334

112

VLHSP…GLLLL → A in isoform 2.

VSP_050014

Alternative sequence

223 – 310

88

VLHSP…IPTGS → A in isoform 3.

VSP_043202

Natural variant

253

1

S → SPESPDTTSQEPPDTTSQEP PDTTS.

VAR_047901

Natural variant

300

1

P → H.
Corresponds to variant rs3745925 [ dbSNP | Ensembl ].

VAR_017580

Experimental info

Sequence conflict

240

1

S → P in AAB02194. Ref.2

Sequence conflict

240

1

S → P in AAC51354. Ref.3

Sequence conflict

242

1

D → N in AAB02194. Ref.2

Sequence conflict

242

1

D → N in AAC51354. Ref.3

Sequence conflict

254

1

Q → P in AAC13661. Ref.1

Secondary structure

1

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382

Helix Strand Turn

Details...

Beta strand

25 – 30

6

Beta strand

33 – 38

6

Beta strand

43 – 49

7

Beta strand

52 – 54

3

Beta strand

57 – 62

6

Turn

64 – 67

4

Beta strand

69 – 83

15

Helix

86 – 88

3

Beta strand

90 – 98

9

Beta strand

101 – 113

13

Beta strand

116 – 125

10

Beta strand

131 – 140

10

Turn

144 – 146

3

Beta strand

147 – 153

7

Beta strand

167 – 171

5

Beta strand

175 – 177

3

Beta strand

180 – 190

11

Beta strand

200 – 210

11

Beta strand

213 – 223

11

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 16, 2008. Version 2. Checksum: 9DCA60C30BA61E62	FASTA	382	40,155
	10 20 30 40 50 60 MDFGLALLLA GLLGLLLGQS LQVKPLQVEP PEPVVAVALG ASRQLTCRLA CADRGASVQW 70 80 90 100 110 120 RGLDTSLGAV QSDTGRSVLT VRNASLSAAG TRVCVGSCGG RTFQHTVQLL VYAFPDQLTV 130 140 150 160 170 180 SPAALVPGDP EVACTAHKVT PVDPNALSFS LLVGGQELEG AQALGPEVQE EEEEPQGDED 190 200 210 220 230 240 VLFRVTERWR LPPLGTPVPP ALYCQATMRL PGLELSHRQA IPVLHSPTSP EPPDTTSPES 250 260 270 280 290 300 PDTTSPESPD TTSQEPPDTT SPEPPDKTSP EPAPQQGSTH TPRSPGSTRT RRPEISQAGP 310 320 330 340 350 360 TQGEVIPTGS SKPAGDQLPA ALWTSSAVLG LLLLALPTYH LWKRCRHLAE DDTHPPASLR 370 380 LLPQVSAWAG LRGTGQVGIS PS
	Isoform 2 [UniParc]. Checksum: 3613F1F208F9F31D	FASTA	271	28,705
	10 20 30 40 50 60 MDFGLALLLA GLLGLLLGQS LQVKPLQVEP PEPVVAVALG ASRQLTCRLA CADRGASVQW 70 80 90 100 110 120 RGLDTSLGAV QSDTGRSVLT VRNASLSAAG TRVCVGSCGG RTFQHTVQLL VYAFPDQLTV 130 140 150 160 170 180 SPAALVPGDP EVACTAHKVT PVDPNALSFS LLVGGQELEG AQALGPEVQE EEEEPQGDED 190 200 210 220 230 240 VLFRVTERWR LPPLGTPVPP ALYCQATMRL PGLELSHRQA IPAALPTYHL WKRCRHLAED 250 260 270 DTHPPASLRL LPQVSAWAGL RGTGQVGISP S
	Isoform 3 [UniParc]. Checksum: F635D6F54504D68D	FASTA	295	31,109
	10 20 30 40 50 60 MDFGLALLLA GLLGLLLGQS LQVKPLQVEP PEPVVAVALG ASRQLTCRLA CADRGASVQW 70 80 90 100 110 120 RGLDTSLGAV QSDTGRSVLT VRNASLSAAG TRVCVGSCGG RTFQHTVQLL VYAFPDQLTV 130 140 150 160 170 180 SPAALVPGDP EVACTAHKVT PVDPNALSFS LLVGGQELEG AQALGPEVQE EEEEPQGDED 190 200 210 220 230 240 VLFRVTERWR LPPLGTPVPP ALYCQATMRL PGLELSHRQA IPASKPAGDQ LPAALWTSSA 250 260 270 280 290 VLGLLLLALP TYHLWKRCRH LAEDDTHPPA SLRLLPQVSA WAGLRGTGQV GISPS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of the mucosal addressin MAdCAM-1 from human brain: identification of novel alternatively spliced transcripts." Leung E., Greene J., Ni J., Raymond L.G., Lehnert K., Langley R., Krissansen G.W. Immunol. Cell Biol. 74:490-496(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ALTERNATIVE SPLICING, TISSUE SPECIFICITY. Tissue: Fetal brain.
[2]	"Human mucosal addressin cell adhesion molecule-1 (MAdCAM-1) demonstrates structural and functional similarities to the alpha 4 beta 7-integrin binding domains of murine MAdCAM-1, but extreme divergence of mucin-like sequences." Shyjan A.M., Bertagnolli M., Kenney C.J., Briskin M.J. J. Immunol. 156:2851-2857(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH ALPHA-4/BETA-7 INTEGRIN, TISSUE SPECIFICITY, VARIANT PRO-GLU-SER-PRO-ASP-THR-THR-SER-GLN-GLU-PRO-PRO-ASP-THR-THR-SER-GLN-GLU-PRO-PRO-ASP-THR-THR-SER-253 INS. Tissue: Lymph node.
[3]	"Genomic organization, chromosomal mapping, and analysis of the 5' promoter region of the human MAdCAM-1 gene." Leung E., Berg R.W., Langley R., Greene J., Raymond L.A., Augustus M., Ni J., Carter K.C., Spurr N., Choo K.H.A., Krissansen G.W. Immunogenetics 46:111-119(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2), VARIANT PRO-GLU-SER-PRO-ASP-THR-THR-SER-GLN-GLU-PRO-PRO-ASP-THR-THR-SER-GLN-GLU-PRO-PRO-ASP-THR-THR-SER-253 INS. Tissue: Placenta.
[4]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases 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] (ISOFORMS 1 AND 3), VARIANT PRO-GLU-SER-PRO-ASP-THR-THR-SER-GLN-GLU-PRO-PRO-ASP-THR-THR-SER-GLN-GLU-PRO-PRO-ASP-THR-THR-SER-253 INS. Tissue: Brain.
[7]	"The structure of immunoglobulin superfamily domains 1 and 2 of MAdCAM-1 reveals novel features important for integrin recognition." Tan K., Casasnovas J.M., Liu J.H., Briskin M.J., Springer T.A., Wang J.H. Structure 6:793-801(1998) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 23-231.
[8]	"A reassessment of the MAdCAM-1 structure and its role in integrin recognition." Dando J., Wilkinson K.W., Ortlepp S., King D.J., Brady R.L. Acta Crystallogr. D 58:233-241(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 23-224.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U43628 mRNA. Translation: AAB02194.1.
U80016 , U80012, U80013, U80014, U80015 Genomic DNA. Translation: AAC51354.1.
U82483 mRNA. Translation: AAC13661.1.
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.

IPI

IPI00289931.
IPI00289933.
IPI00915344.

RefSeq

NP_570116.2. NM_130760.2.
NP_570118.1. NM_130762.2.

UniGene

Hs.102598.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BQS	X-ray	2.20	A	23-231	[»]
1GSM	X-ray	1.90	A	19-224	[»]
4HBQ	X-ray	1.40	A/B	23-224	[»]
4HC1	X-ray	2.87	A/B	23-224	[»]
4HCR	X-ray	2.30	A/B	23-225	[»]
4HD9	X-ray	1.70	A	23-225	[»]

ProteinModelPortal

Q13477.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000215637.

Polymorphism databases

DMDM

218511712.

Proteomic databases

PaxDb

Q13477.

PRIDE

Q13477.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000215637; ENSP00000215637; ENSG00000099866.
ENST00000346144; ENSP00000304247; ENSG00000099866.

GeneID

8174.

KEGG

hsa:8174.

UCSC

uc002los.3. human.
uc002lot.3. human.

Organism-specific databases

CTD

8174.

GeneCards

GC19P000499.

H-InvDB

HIX0014553.

HGNC

HGNC:6765. MADCAM1.

MIM

102670. gene.

neXtProt

NX_Q13477.

PharmGKB

PA30522.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG26033.

HOGENOM

HOG000060103.

HOVERGEN

HBG108114.

InParanoid

Q13477.

KO

K06779.

Enzyme and pathway databases

Pathway_Interaction_DB

a4b1_paxindep_pathway. Paxillin-independent events mediated by a4b1 and a4b7.

Reactome

REACT_111102. Signal Transduction.
REACT_6900. Immune System.

SignaLink

Q13477.

Gene expression databases

ArrayExpress

Q13477.

Bgee

Q13477.

CleanEx

HS_MADCAM1.

Genevestigator

Q13477.

GermOnline

ENSG00000099866. Homo sapiens.

Family and domain databases

Gene3D

2.60.40.10. 2 hits.

InterPro

IPR015169. Adhes-Ig-like.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
[Graphical view]

Pfam

PF09085. Adhes-Ig_like. 1 hit.
[Graphical view]

ProDom

PD336606. Adhes-Ig-like. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00409. IG. 1 hit.
[Graphical view]

PROSITE

PS50835. IG_LIKE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q13477.

ChEMBL

CHEMBL4467.

EvolutionaryTrace

Q13477.

GenomeRNAi

8174.

NextBio

30850.

SOURCE

Search...

Entry information

Entry name

MADCA_HUMAN

Accession

Primary (citable) accession number: Q13477
Secondary accession number(s): A5PKV4 , B2RPL9, O60222, O75867

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 2, 2004
Last sequence update:	December 16, 2008
Last modified:	May 29, 2013
This is version 114 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.