P26010 (ITB7_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Integrin beta-7

Alternative name(s):
Gut homing receptor beta subunit

Gene names

Name:

ITGB7

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	798 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	Integrin alpha-4/beta-7 (Peyer patches-specific homing receptor LPAM-1) is an adhesion molecule that mediates lymphocyte migration and homing to gut-associated lymphoid tissue (GALT). Integrin alpha-4/beta-7 interacts with the cell surface adhesion molecules MADCAM1 which is normally expressed by the vascular endothelium of the gastrointestinal tract. Interacts also with VCAM1 and fibronectin, an extracellular matrix component. It recognizes one or more domains within the alternatively spliced CS-1 region of fibronectin. Interactions involves the tripeptide L-D-T in MADCAM1, and L-D-V in fibronectin. Binds to HIV-1 gp120, thereby allowing the virus to enter GALT, which is thought to be the major trigger of AIDS disease. Interaction would involve a tripeptide L-D-I in HIV-1 gp120. Integrin alpha-E/beta-7 (HML-1) is a receptor for E-cadherin.
Subunit structure	Heterodimer of an alpha and a beta subunit. Beta-7 associates with either alpha-4 or alpha-E. Integrin alpha-4/beta-7 interacts with MADCAM1, VCAM, fibronectin, and may also interact with HIV-1 gp120. Ref.6 Ref.10
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	Expressed in a variety of leukocyte lines.
Induction	Integrin alpha-E/beta-7 is induced by TGFB1. Ref.6
Domain	Domain I contains three cation-binding sites: the ligand-integrin-binding site (LIMBS), the metal ion-dependent adhesion site (MIDAS), and the adjacent to MIDAS site (ADMIDAS). In the absence of a ligand or in calcium-dependent binding, only ADMIDAS is occupied. In magnesium-dependent binding all three sites bind metal ions. LIMBS positively modify ligand binding whereas ADMIDAS negatively modify ligand binding.
Sequence similarities	Belongs to the integrin beta chain family. Contains 1 VWFA domain.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat Signal Transmembrane Transmembrane helix
Ligand	Magnesium Metal-binding
Molecular function	Host cell receptor for virus entry Integrin Receptor
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cell adhesion Traceable author statement Ref.3. Source: ProtInc cell-matrix adhesion Inferred from electronic annotation. Source: InterPro integrin-mediated signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW leukocyte migration Inferred from electronic annotation. Source: Compara multicellular organismal development Inferred from electronic annotation. Source: InterPro regulation of immune response Traceable author statement. Source: Reactome
Cellular_component	integrin complex Traceable author statement Ref.3. Source: ProtInc
Molecular_function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW receptor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Long (identifier: P26010-1)

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 Short (identifier: P26010-2)

The sequence of this isoform differs from the canonical sequence as follows:
     501-648: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 19

19

Ref.6 Ref.7

Chain

20 – 798

779

Integrin beta-7

PRO_0000016352

Regions

Topological domain

20 – 723

704

Extracellular Potential

Transmembrane

724 – 746

23

Helical; Potential

Topological domain

747 – 798

52

Cytoplasmic Potential

Domain

150 – 389

240

VWFA

Repeat

478 – 526

49

I

Repeat

527 – 565

39

II

Repeat

566 – 604

39

III

Repeat

605 – 640

36

IV

Region

478 – 640

163

Cysteine-rich tandem repeats

Sites

Metal binding

159

1

Magnesium; MIDAS motif By similarity

Metal binding

161

1

Magnesium; MIDAS motif By similarity

Metal binding

163

1

Magnesium; MIDAS motif By similarity

Metal binding

166

1

Magnesium or calcium; ADMIDAS motif By similarity

Metal binding

167

1

Magnesium or calcium; ADMIDAS motif By similarity

Metal binding

198

1

Magnesium; LIMBS motif By similarity

Metal binding

254

1

Magnesium; LIMBS motif By similarity

Metal binding

256

1

Magnesium; LIMBS motif By similarity

Metal binding

259

1

Magnesium; LIMBS motif By similarity

Metal binding

289

1

Magnesium; MIDAS motif By similarity

Amino acid modifications

Modified residue

778

1

Phosphotyrosine; by Tyr-kinases By similarity

Glycosylation

68

1

N-linked (GlcNAc...) Potential

Glycosylation

279

1

N-linked (GlcNAc...) Potential

Glycosylation

434

1

N-linked (GlcNAc...) Potential

Glycosylation

477

1

N-linked (GlcNAc...) Potential

Glycosylation

531

1

N-linked (GlcNAc...) Potential

Glycosylation

590

1

N-linked (GlcNAc...) Potential

Glycosylation

665

1

N-linked (GlcNAc...) Potential

Glycosylation

674

1

N-linked (GlcNAc...) Potential

Disulfide bond

45 ↔ 476

By similarity

Disulfide bond

51 ↔ 61

By similarity

Disulfide bond

54 ↔ 91

By similarity

Disulfide bond

64 ↔ 80

By similarity

Disulfide bond

216 ↔ 223

By similarity

Disulfide bond

271 ↔ 311

By similarity

Disulfide bond

412 ↔ 428

By similarity

Disulfide bond

448 ↔ 688

By similarity

Disulfide bond

474 ↔ 478

By similarity

Disulfide bond

488 ↔ 500

By similarity

Disulfide bond

497 ↔ 537

By similarity

Disulfide bond

502 ↔ 511

By similarity

Disulfide bond

513 ↔ 527

By similarity

Disulfide bond

543 ↔ 548

By similarity

Disulfide bond

545 ↔ 574

By similarity

Disulfide bond

550 ↔ 559

By similarity

Disulfide bond

561 ↔ 566

By similarity

Disulfide bond

580 ↔ 585

By similarity

Disulfide bond

582 ↔ 613

By similarity

Disulfide bond

587 ↔ 596

By similarity

Disulfide bond

598 ↔ 605

By similarity

Disulfide bond

619 ↔ 624

By similarity

Disulfide bond

621 ↔ 666

By similarity

Disulfide bond

626 ↔ 635

By similarity

Disulfide bond

638 ↔ 641

By similarity

Disulfide bond

645 ↔ 654

By similarity

Natural variations

Alternative sequence

501 – 648

148

Missing in isoform Short.

VSP_002753

Natural variant

672

1

H → Y.
Corresponds to variant rs11539433 [ dbSNP | Ensembl ].

VAR_049637

Experimental info

Mutagenesis

159

1

D → A: Loss of integrin alpha-E/beta-7 binding to E-cadherin and of integrin alpha-4/beta-7 binding to MADCAM1. Ref.8

Sequence conflict

34

1

W → A AA sequence Ref.7

Secondary structure

1

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798

Helix Strand Turn

Details...

Beta strand

102 – 105

4

Turn

114 – 116

3

Beta strand

117 – 119

3

Beta strand

127 – 131

5

Beta strand

138 – 145

8

Beta strand

152 – 159

8

Helix

162 – 164

3

Helix

165 – 173

9

Helix

176 – 182

7

Turn

183 – 185

3

Beta strand

189 – 196

8

Turn

202 – 204

3

Helix

209 – 213

5

Beta strand

219 – 221

3

Beta strand

228 – 237

10

Helix

240 – 246

7

Beta strand

255 – 259

5

Helix

261 – 270

10

Helix

272 – 275

4

Beta strand

279 – 290

12

Helix

297 – 299

3

Turn

300 – 302

3

Beta strand

317 – 319

3

Helix

320 – 324

5

Helix

330 – 339

10

Beta strand

342 – 348

7

Beta strand

350 – 352

3

Helix

353 – 360

8

Beta strand

367 – 370

4

Helix

378 – 390

13

Beta strand

393 – 396

4

Beta strand

404 – 408

5

Beta strand

413 – 415

3

Beta strand

423 – 428

6

Beta strand

436 – 445

10

Beta strand

454 – 460

7

Beta strand

465 – 469

5

Beta strand

777 – 786

10

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified May 1, 1992. Version 1. Checksum: CBE275E0E9992385	FASTA	798	86,903
	10 20 30 40 50 60 MVALPMVLVL LLVLSRGESE LDAKIPSTGD ATEWRNPHLS MLGSCQPAPS CQKCILSHPS 70 80 90 100 110 120 CAWCKQLNFT ASGEAEARRC ARREELLARG CPLEELEEPR GQQEVLQDQP LSQGARGEGA 130 140 150 160 170 180 TQLAPQRVRV TLRPGEPQQL QVRFLRAEGY PVDLYYLMDL SYSMKDDLER VRQLGHALLV 190 200 210 220 230 240 RLQEVTHSVR IGFGSFVDKT VLPFVSTVPS KLRHPCPTRL ERCQSPFSFH HVLSLTGDAQ 250 260 270 280 290 300 AFEREVGRQS VSGNLDSPEG GFDAILQAAL CQEQIGWRNV SRLLVFTSDD TFHTAGDGKL 310 320 330 340 350 360 GGIFMPSDGH CHLDSNGLYS RSTEFDYPSV GQVAQALSAA NIQPIFAVTS AALPVYQELS 370 380 390 400 410 420 KLIPKSAVGE LSEDSSNVVQ LIMDAYNSLS STVTLEHSSL PPGVHISYES QCEGPEKREG 430 440 450 460 470 480 KAEDRGQCNH VRINQTVTFW VSLQATHCLP EPHLLRLRAL GFSEELIVEL HTLCDCNCSD 490 500 510 520 530 540 TQPQAPHCSD GQGHLQCGVC SCAPGRLGRL CECSVAELSS PDLESGCRAP NGTGPLCSGK 550 560 570 580 590 600 GHCQCGRCSC SGQSSGHLCE CDDASCERHE GILCGGFGRC QCGVCHCHAN RTGRACECSG 610 620 630 640 650 660 DMDSCISPEG GLCSGHGRCK CNRCQCLDGY YGALCDQCPG CKTPCERHRD CAECGAFRTG 670 680 690 700 710 720 PLATNCSTAC AHTNVTLALA PILDDGWCKE RTLDNQLFFF LVEDDARGTV VLRVRPQEKG 730 740 750 760 770 780 ADHTQAIVLG CVGGIVAVGL GLVLAYRLSV EIYDRREYSR FEKEQQQLNW KQDSNPLYKS 790 AITTTINPRF QEADSPTL
	Isoform Short [UniParc]. Checksum: B247895C3772178D	FASTA	650	71,582
	10 20 30 40 50 60 MVALPMVLVL LLVLSRGESE LDAKIPSTGD ATEWRNPHLS MLGSCQPAPS CQKCILSHPS 70 80 90 100 110 120 CAWCKQLNFT ASGEAEARRC ARREELLARG CPLEELEEPR GQQEVLQDQP LSQGARGEGA 130 140 150 160 170 180 TQLAPQRVRV TLRPGEPQQL QVRFLRAEGY PVDLYYLMDL SYSMKDDLER VRQLGHALLV 190 200 210 220 230 240 RLQEVTHSVR IGFGSFVDKT VLPFVSTVPS KLRHPCPTRL ERCQSPFSFH HVLSLTGDAQ 250 260 270 280 290 300 AFEREVGRQS VSGNLDSPEG GFDAILQAAL CQEQIGWRNV SRLLVFTSDD TFHTAGDGKL 310 320 330 340 350 360 GGIFMPSDGH CHLDSNGLYS RSTEFDYPSV GQVAQALSAA NIQPIFAVTS AALPVYQELS 370 380 390 400 410 420 KLIPKSAVGE LSEDSSNVVQ LIMDAYNSLS STVTLEHSSL PPGVHISYES QCEGPEKREG 430 440 450 460 470 480 KAEDRGQCNH VRINQTVTFW VSLQATHCLP EPHLLRLRAL GFSEELIVEL HTLCDCNCSD 490 500 510 520 530 540 TQPQAPHCSD GQGHLQCGVC RDCAECGAFR TGPLATNCST ACAHTNVTLA LAPILDDGWC 550 560 570 580 590 600 KERTLDNQLF FFLVEDDARG TVVLRVRPQE KGADHTQAIV LGCVGGIVAV GLGLVLAYRL 610 620 630 640 650 SVEIYDRREY SRFEKEQQQL NWKQDSNPLY KSAITTTINP RFQEADSPTL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and sequence analysis of a novel beta 2-related integrin transcript from T lymphocytes: homology of integrin cysteine-rich repeats to domain III of laminin B chains." Yuan Q., Jiang W.-M., Krissansen G.W., Watson J.D. Int. Immunol. 2:1097-1108(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG). Tissue: T-cell.
[2]	"Cloning and sequence analysis of a novel beta 2-related integrin transcript from T lymphocytes: homology of integrin cysteine-rich repeats to domain III of laminin B chains." Yuan Q., Jiang W.-M., Krissansen G.W., Watson J.D. Int. Immunol. 3:1373-1374(1991) [PubMed] [Europe PMC] [Abstract] Cited for: SEQUENCE REVISION.
[3]	"Complete amino acid sequence of an integrin beta subunit (beta 7) identified in leukocytes." Erle D.J., Rueegg C., Sheppard D., Pytela R. J. Biol. Chem. 266:11009-11016(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT). Tissue: Leukocyte.
[4]	"The gene organization of the human beta 7 subunit, the common beta subunit of the leukocyte integrins HML-1 and LPAM-1." Jiang W.-M., Jenkins D., Yuan Q., Leung E., Choo K.H., Watson J.D., Krissansen G.W. Int. Immunol. 4:1031-1040(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"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 LONG). Tissue: Colon.
[6]	"A family of beta 7 integrins on human mucosal lymphocytes." Parker C.M., Cepek K.L., Russell G.J., Shaw S.K., Posnett D.N., Schwarting R., Brenner M.B. Proc. Natl. Acad. Sci. U.S.A. 89:1924-1928(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 20-36, INTERACTION WITH INTEGRIN ALPHA-4 AND INTEGRIN ALPHA-E, INDUCTION.
[7]	"HML-1 antigen on mucosa-associated T cells, activated cells, and hairy leukemic cells is a new integrin containing the beta 7 subunit." Micklem K.J., Dong Y., Willis A., Pulford K.A., Visser L., Duerkop H., Poppema S., Stein H., Mason D.Y. Am. J. Pathol. 139:1297-1301(1991) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 20-34. Tissue: Leukemia.
[8]	"The role of alpha and beta chains in ligand recognition by beta 7 integrins." Higgins J.M.G., Cernadas M., Tan K., Irie A., Wang J.-H., Takada Y., Brenner M.B. J. Biol. Chem. 275:25652-25664(2000) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF ASP-159.
[9]	"Integrins: bidirectional, allosteric signaling machines." Hynes R.O. Cell 110:673-687(2002) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[10]	"HIV-1 envelope protein binds to and signals through integrin alpha4beta7, the gut mucosal homing receptor for peripheral T cells." Arthos J., Cicala C., Martinelli E., Macleod K., Van Ryk D., Wei D., Xiao Z., Veenstra T.D., Conrad T.P., Lempicki R.A., McLaughlin S., Pascuccio M., Gopaul R., McNally J., Cruz C.C., Censoplano N., Chung E., Reitano K.N. , Kottilil S., Goode D.J., Fauci A.S. Nat. Immunol. 9:301-309(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HIV-1 GP120.
[11]	"The molecular basis of filamin binding to integrins and competition with talin." Kiema T., Lad Y., Jiang P., Oxley C.L., Baldassarre M., Wegener K.L., Campbell I.D., Ylanne J., Calderwood D.A. Mol. Cell 21:337-347(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 768-798.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M68892 mRNA. Translation: AAA59184.1.
S80335 mRNA. Translation: AAB21332.1.
M62880 mRNA. Translation: AAA59185.1.
L23823 , L23810, L23811, L23812, L23813, L23814, L23815, L23816, L23817, L23818, L23819, L23820, L23821, L23822 Genomic DNA. Translation: AAA36118.1.
S49378 , S49364, S49365, S49366, S49367, S49368, S49369, S49370, S49371, S49373, S49374, S49375, S49376, S49377 Genomic DNA. Translation: AAB23688.1.
BC015916 mRNA. Translation: AAH15916.1.

IPI

IPI00297880.
IPI00412656.

PIR

A40526.

RefSeq

NP_000880.1. NM_000889.1.

UniGene

Hs.654470.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2BRQ	X-ray	2.10	C/D	768-798	[»]
3V4P	X-ray	3.15	B/D	20-512	[»]
3V4V	X-ray	3.10	B/D	20-512	[»]

ProteinModelPortal

P26010.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-34970N.

IntAct

P26010. 2 interactions.

MINT

MINT-258650.

STRING

9606.ENSP00000267082.

PTM databases

PhosphoSite

P26010.

Polymorphism databases

DMDM

124973.

Proteomic databases

PaxDb

P26010.

PRIDE

P26010.

Protocols and materials databases

DNASU

3695.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000267082; ENSP00000267082; ENSG00000139626.
ENST00000338737; ENSP00000345501; ENSG00000139626.
ENST00000422257; ENSP00000408741; ENSG00000139626.
ENST00000550743; ENSP00000455374; ENSG00000139626.

GeneID

3695.

KEGG

hsa:3695.

UCSC

uc001scc.3. human.

Organism-specific databases

CTD

3695.

GeneCards

GC12M053585.

HGNC

HGNC:6162. ITGB7.

HPA

HPA042277.

MIM

147559. gene.

neXtProt

NX_P26010.

PharmGKB

PA29961.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG287997.

HOGENOM

HOG000252936.

HOVERGEN

HBG006190.

InParanoid

P26010.

KO

K06590.

OMA

DHTQAIV.

OrthoDB

EOG4640B9.

PhylomeDB

P26010.

Enzyme and pathway databases

Pathway_Interaction_DB

a4b1_a4b7_pathway. a4b1 and a4b7 Integrin signaling.
a4b1_paxdep_pathway. Paxillin-dependent events mediated by a4b1.
a4b1_paxindep_pathway. Paxillin-independent events mediated by a4b1 and a4b7.

Reactome

REACT_111102. Signal Transduction.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P26010.

Bgee

P26010.

CleanEx

HS_ITGB7.

Genevestigator

P26010.

GermOnline

ENSG00000139626. Homo sapiens.

Family and domain databases

InterPro

IPR013111. EGF_extracell.
IPR015812. Integrin_bsu.
IPR015437. Integrin_bsu-7.
IPR014836. Integrin_bsu_cyt_dom.
IPR002369. Integrin_bsu_N.
IPR012896. Integrin_bsu_tail.
IPR003659. Plexin-like.
IPR016201. Plexin-like_fold.
IPR002035. VWF_A.
[Graphical view]

PANTHER

PTHR10082. PTHR10082. 1 hit.
PTHR10082:SF27. PTHR10082:SF27. 1 hit.

Pfam

PF07974. EGF_2. 1 hit.
PF08725. Integrin_b_cyt. 1 hit.
PF00362. Integrin_beta. 1 hit.
[Graphical view]

PIRSF

PIRSF002512. Integrin_B. 1 hit.

PRINTS

PR01186. INTEGRINB.

SMART

SM00187. INB. 1 hit.
SM00423. PSI. 1 hit.
SM00327. VWA. 1 hit.
[Graphical view]

SUPFAM

SSF69687. Integrin_bsu_tail. 1 hit.
SSF103575. Plexin-like_fold. 1 hit.

PROSITE

PS00022. EGF_1. 4 hits. Uncertain.
PS01186. EGF_2. 1 hit. Uncertain.
PS00243. INTEGRIN_BETA. 3 hits.
PS50234. VWFA. False negative.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P26010.

ChEMBL

CHEMBL2979.

ChiTaRS

ITGB7. human.

EvolutionaryTrace

P26010.

GenomeRNAi

3695.

NextBio

14483.

SOURCE

Search...

Entry information

Entry name

ITB7_HUMAN

Accession

Primary (citable) accession number: P26010
Secondary accession number(s): Q9UCP7, Q9UCS7

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 1992
Last sequence update:	May 1, 1992
Last modified:	May 1, 2013
This is version 138 of the entry and version 1 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.