Reviewed, UniProtKB/Swiss-Prot A2ARA8 (ITA8_MOUSE)

Names and origin

Protein names

Recommended name:
    Integrin alpha-8
Cleaved into the following 2 chains:
    1- Recommended name:
            Integrin alpha-8 heavy chain
    2- Recommended name:
            Integrin alpha-8 light chain

Gene names

Name:

Itga8

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	1062 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-8/beta-1 functions in the genesis of kidney and probably of other organs by regulating the recruitment of mesenchymal cells into epithelial structures. It recognizes the sequence R-G-D in a wide array of ligands including TNC, FN1, SPP1 TGFB1, TGFB3 and VTN. NPNT is probably its functional ligand in kidney genesis. Neuronal receptor for TNC it mediates cell-cell interactions and regulates neurite outgrowth of sensory and motor neurons. Ref.3 Ref.4 Ref.5 Ref.8 Ref.9 Ref.10 Ref.12 Ref.13
Subunit structure	Heterodimer of an alpha and a beta subunit. The alpha subunit is composed of an heavy and a light chain linked by a disulfide bond. Alpha-8 associates with beta-1.
Subcellular location	Membrane; Single-pass type I membrane protein. Ref.8
Tissue specificity	In brain, expressed in deep cortex, hippocampal CA1, basolateral amygdala and striatum. In kidney, expressed in glomerular mesengium (at protein level). Ref.6 Ref.7
Developmental stage	Expressed in mesenchymal cells of developping organs such as gut, lung, gonads and nephrogenic cord. Ref.3 Ref.11
Disruption phenotype	Mice display renal agenesis and dysgenesis. This is associated with a reduced expression of Gdnf that is similarly found in mice lacking Npnt. Adult mice also display increased susceptibility to glomerular capillary destruction upon mechanical stress. Mice lacking Itga8 also have difficulty balancing associated with structural defects in the inner ear where utricular hair cells lack stereocilia. Ref.3 Ref.8 Ref.10 Ref.13
Sequence similarities	Belongs to the integrin alpha chain family. Contains 7 FG-GAP repeats.

Ontologies

Keywords
Biological process	Cell adhesion Differentiation Neurogenesis
Cellular component	Membrane
Coding sequence diversity	Alternative splicing
Domain	Repeat Signal Transmembrane
Ligand	Calcium
Molecular function	Developmental protein Integrin Receptor
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein
Gene Ontology (GO)
Biological process	cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW cell projection organization Ref.8 Inferred from mutant phenotype. Source: MGI extracellular matrix organization Ref.8 Inferred from mutant phenotype. Source: MGI inner ear morphogenesis Ref.8 Inferred from mutant phenotype. Source: MGI integrin-mediated signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW memory Inferred from mutant phenotype. Source: MGI metanephros development Ref.13 Inferred from genetic interaction. Source: MGI nervous system development Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of transforming growth factor beta receptor signaling pathway Ref.13 Inferred from genetic interaction. Source: MGI
Cellular component	apical part of cell Ref.8 Inferred from direct assay. Source: MGI integrin complex Inferred from electronic annotation. Source: InterPro
Molecular function	calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from electronic annotation. Source: UniProtKB-KW receptor activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: A2ARA8-1)

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: A2ARA8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     282-286: ELVAG → GQRHP
     287-1062: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 35	35	Potential
	Chain	36 – 1062	1027	Integrin alpha-8		PRO_0000297709
	Chain	38 – 905	868	Integrin alpha-8 heavy chain Potential		PRO_0000297710
	Chain	906 – 1062	157	Integrin alpha-8 light chain Potential		PRO_0000297711
Regions
	Topological domain	36 – 1010	975	Extracellular Potential
	Transmembrane	1011 – 1031	21	Potential
	Topological domain	1032 – 1062	31	Cytoplasmic Potential
	Repeat	53 – 116	64	FG-GAP 1
	Repeat	132 – 197	66	FG-GAP 2
	Repeat	198 – 262	65	FG-GAP 3
	Repeat	263 – 316	54	FG-GAP 4
	Repeat	317 – 382	66	FG-GAP 5
	Repeat	383 – 442	60	FG-GAP 6
	Repeat	446 – 500	55	FG-GAP 7
	Calcium binding	328 – 336	9	Potential
	Calcium binding	394 – 402	9	Potential
	Calcium binding	458 – 466	9	Potential
	Motif	454 – 456	3	Cell attachment site Potential
Amino acid modifications
	Glycosylation	80	1	N-linked (GlcNAc...) Potential
	Glycosylation	121	1	N-linked (GlcNAc...) Potential
	Glycosylation	176	1	N-linked (GlcNAc...) Potential
	Glycosylation	238	1	N-linked (GlcNAc...) Potential
	Glycosylation	301	1	N-linked (GlcNAc...) Potential
	Glycosylation	310	1	N-linked (GlcNAc...) Potential
	Glycosylation	503	1	N-linked (GlcNAc...) Potential
	Glycosylation	600	1	N-linked (GlcNAc...) Potential
	Glycosylation	604	1	N-linked (GlcNAc...) Potential
	Glycosylation	718	1	N-linked (GlcNAc...) Potential
	Glycosylation	736	1	N-linked (GlcNAc...) Potential
	Glycosylation	752	1	N-linked (GlcNAc...) Potential
	Glycosylation	779	1	N-linked (GlcNAc...) Potential
	Glycosylation	895	1	N-linked (GlcNAc...) Potential
	Glycosylation	922	1	N-linked (GlcNAc...) Potential
	Glycosylation	1004	1	N-linked (GlcNAc...) Potential
	Disulfide bond	95 ↔ 105		By similarity
	Disulfide bond	149 ↔ 170		By similarity
	Disulfide bond	186 ↔ 199		By similarity
	Disulfide bond	506 ↔ 517		By similarity
	Disulfide bond	523 ↔ 579		By similarity
	Disulfide bond	640 ↔ 646		By similarity
	Disulfide bond	712 ↔ 725		By similarity
	Disulfide bond	866 ↔ 923		Interchain (between heavy and light chains) By similarity
	Disulfide bond	928 ↔ 933		By similarity
Natural variations
	Alternative sequence	282 – 286	5	ELVAG → GQRHP in isoform 2.		VSP_027364
	Alternative sequence	287 – 1062	776	Missing in isoform 2.		VSP_027365
Experimental info
	Sequence conflict	66	1	D → G in BAE22455. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 20, 2007. Version 1. Checksum: DB1ACA43FADD3AC0	FASTA	1,062	117,556
	10 20 30 40 50 60 MSAGTHCGPP GNRAPPFARL CCVSAALGML WSPACLAFNL DVDKLTVYSG PEGSYFGYSL 70 80 90 100 110 120 DFYIPDARTA SVLVGAPKAN TSQPDIVEGG AVYYCPWPSE RSAQCKQIPF DTTNNRKIRV 130 140 150 160 170 180 NGTKEPIEFK SNQWFGATVR AHKGKVVACA PLYHWRTLKP NPAKDPVGTC YVAIQNFSAY 190 200 210 220 230 240 AEHSPCRNSN ADPEGQGYCQ AGFSLDFYKN GDLIVGGPGS FYWQGQVITV SIADIIANYS 250 260 270 280 290 300 FKDILRKLAA EKQTDVAPAS YDDSYLGYSV AAGEFTGDSQ QELVAGIPRG AQNFGYVSII 310 320 330 340 350 360 NSTDMTFIQN FTGEQMASYF GYTVVVSDVN NDGMDDILVG APLFMEREFE SNPREVGQVY 370 380 390 400 410 420 LYLQASALLF QDPQVLTGTE TFGRFGSSVA HLGDLNQDGY NDIAIGVPFA GKDQRGKVLI 430 440 450 460 470 480 YNGNPRGLHS KPSQVLQGIW GSQTIPSGFG FSLRGDADID KNDYPDLLVG AFGKGKVAVY 490 500 510 520 530 540 RARPVVTVDA QLLLHPMIIN LENKTCQIPE FPTPVACFSV RVCASIAGQS ISNTIALLAE 550 560 570 580 590 600 VQLDFLKQKG AIKRTLFLHN HQSHFTFPFV MKQQKSLHCQ DFMVYLRDET EFRDKLSPIN 610 620 630 640 650 660 ISLNYSLDDS TFKDSLEVKP ILNHYRDNVV TEQAHILVDC GEDNLCVPDL KLSARPDKHQ 670 680 690 700 710 720 IIIGDENHLM LIINARNEGE GAYEAELFVI IPEEADYVGI ERNNKGLRPL SCEYKMENVT 730 740 750 760 770 780 RMVVCDLGNP MVTGTNFSLG LRFAVPRLEK TNMSINFDLQ IRSSNKDNPD SNFERVQINI 790 800 810 820 830 840 TAIAQVEIRG VSHPPQIVLP IHNWEPEKKP HKEEEVGPLV EHIYELHNIG PSTISDSILD 850 860 870 880 890 900 VGWPFSARDE FLLYIFHLQT LGPLQCQTNP EINPQDIKPA ASPEDTPELS AFLRNATIPH 910 920 930 940 950 960 LVRKRDVPVV QLHRQSPARI LNCTNIDCLQ ISCAVGRLGG GESAVLKVRS RLWAHTFLKR 970 980 990 1000 1010 1020 KNDHYALASL VSFEVKKMPY KEQPAKLPAG STAVKTSVIW ATPNVSFSIP LWVIILAILL 1030 1040 1050 1060 GLLVLAILTL ALWKCGFFDR ARPPQDEMTD REQLTSDKTP EA
	Isoform 2. Checksum: DB7BCE40C46F2921	FASTA	286	31,011
	10 20 30 40 50 60 MSAGTHCGPP GNRAPPFARL CCVSAALGML WSPACLAFNL DVDKLTVYSG PEGSYFGYSL 70 80 90 100 110 120 DFYIPDARTA SVLVGAPKAN TSQPDIVEGG AVYYCPWPSE RSAQCKQIPF DTTNNRKIRV 130 140 150 160 170 180 NGTKEPIEFK SNQWFGATVR AHKGKVVACA PLYHWRTLKP NPAKDPVGTC YVAIQNFSAY 190 200 210 220 230 240 AEHSPCRNSN ADPEGQGYCQ AGFSLDFYKN GDLIVGGPGS FYWQGQVITV SIADIIANYS 250 260 270 280 FKDILRKLAA EKQTDVAPAS YDDSYLGYSV AAGEFTGDSQ QGQRHP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Strain: C57BL/6J. Tissue: Embryo, Testis and Wolffian duct.
[2]	The mouse genome sequencing consortium Submitted (JAN-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[3]	"Integrin alpha8beta1 is critically important for epithelial-mesenchymal interactions during kidney morphogenesis." Mueller U., Wang D., Denda S., Meneses J.J., Pedersen R.A., Reichardt L.F. Cell 88:603-613(1997) [PubMed: 9054500] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 45-1056 (ISOFORM 1), FUNCTION, DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE. Tissue: Fibroblast.
[4]	"Utilization of a soluble integrin-alkaline phosphatase chimera to characterize integrin alpha 8 beta 1 receptor interactions with tenascin: murine alpha 8 beta 1 binds to the RGD site in tenascin-C fragments, but not to native tenascin-C." Denda S., Mueller U., Crossin K.L., Erickson H.P., Reichardt L.F. Biochemistry 37:5464-5474(1998) [PubMed: 9548928] [Abstract] Cited for: FUNCTION.
[5]	"Identification of osteopontin as a novel ligand for the integrin alpha8 beta1 and potential roles for this integrin-ligand interaction in kidney morphogenesis." Denda S., Reichardt L.F., Mueller U. Mol. Biol. Cell 9:1425-1435(1998) [PubMed: 9614184] [Abstract] Cited for: FUNCTION.
[6]	"Integrin subunit gene expression is regionally differentiated in adult brain." Pinkstaff J.K., Detterich J., Lynch G., Gall C. J. Neurosci. 19:1541-1556(1999) [PubMed: 10024342] [Abstract] Cited for: TISSUE SPECIFICITY.
[7]	"Alpha8 integrin in glomerular mesangial cells and in experimental glomerulonephritis." Hartner A., Schoecklmann H., Proels F., Mueller U., Sterzel R.B. Kidney Int. 56:1468-1480(1999) [PubMed: 10504498] [Abstract] Cited for: TISSUE SPECIFICITY.
[8]	"Stereocilia defects in the sensory hair cells of the inner ear in mice deficient in integrin alpha8beta1." Littlewood Evans A., Mueller U. Nat. Genet. 24:424-428(2000) [PubMed: 10742111] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION.
[9]	"Identification and characterization of a novel extracellular matrix protein nephronectin that is associated with integrin alpha8beta1 in the embryonic kidney." Brandenberger R., Schmidt A., Linton J., Wang D., Backus C., Denda S., Mueller U., Reichardt L.F. J. Cell Biol. 154:447-458(2001) [PubMed: 11470831] [Abstract] Cited for: FUNCTION.
[10]	"The alpha8 integrin chain affords mechanical stability to the glomerular capillary tuft in hypertensive glomerular disease." Hartner A., Cordasic N., Klanke B., Mueller U., Sterzel R.B., Hilgers K.F. Am. J. Pathol. 160:861-867(2002) [PubMed: 11891185] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[11]	"Expression of the integrin subunit alpha8 in murine lung development." Wagner T.E., Frevert C.W., Herzog E.L., Schnapp L.M. J. Histochem. Cytochem. 51:1307-1315(2003) [PubMed: 14500699] [Abstract] Cited for: DEVELOPMENTAL STAGE.
[12]	"Role of alpha8 integrin in mesangial cell adhesion, migration, and proliferation." Bieritz B., Spessotto P., Colombatti A., Jahn A., Prols F., Hartner A. Kidney Int. 64:119-127(2003) [PubMed: 12787402] [Abstract] Cited for: FUNCTION.
[13]	"The ECM protein nephronectin promotes kidney development via integrin alpha8beta1-mediated stimulation of Gdnf expression." Linton J.M., Martin G.R., Reichardt L.F. Development 134:2501-2509(2007) [PubMed: 17537792] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AK031326 mRNA. Translation: BAC27348.1. AK044910 mRNA. Translation: BAC32137.1. AK135193 mRNA. Translation: BAE22455.1. AL845313 Genomic DNA. Translation: CAM17354.1. AF041409 mRNA. Translation: AAC15665.1.
IPI	IPI00345112. IPI00857527.
RefSeq	NP_001001309.1.
UniGene	Mm.329997
3D structure databases
ModBase	Search...
PTM databases
PhosphoSite	A2ARA8.
Proteomic databases
PRIDE	A2ARA8.
Genome annotation databases
Ensembl	ENSMUSG00000026768. Mus musculus. [Contig view]
GeneID	241226.
KEGG	mmu:241226.
Organism-specific databases
MGI	MGI:109442. Itga8.
Phylogenomic databases
HOVERGEN	A2ARA8.
OMA	A2ARA8. GIPRGAQ.
Gene expression databases
Bgee	A2ARA8.
CleanEx	MM_ITGA8.
Family and domain databases
InterPro	IPR013517. FG-GAP. IPR013519. Int_alpha_beta-p. IPR000413. Integrin_alpha. IPR013649. Integrin_alpha-2. IPR013513. Integrin_alpha_C. IPR018184. Integrin_alpha_C_CS. [Graphical view]
Pfam	PF01839. FG-GAP. 2 hits. PF00357. Integrin_alpha. 1 hit. PF08441. Integrin_alpha2. 1 hit. [Graphical view]
PRINTS	PR01185. INTEGRINA.
SMART	SM00191. Int_alpha. 6 hits. [Graphical view]
PROSITE	PS00242. INTEGRIN_ALPHA. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	384935.
SOURCE	Search...

Entry information

Entry name

ITA8_MOUSE

Accession

Primary (citable) accession number: A2ARA8
Secondary accession number(s): O70304 , Q3UXV8, Q8BRG3, Q8C0H7

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 21, 2007
Last sequence update:	February 20, 2007
Last modified:	June 16, 2009
This is version 20 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)