Reviewed, UniProtKB/Swiss-Prot P17301 (ITA2_HUMAN)

Names and origin

Protein names

Recommended name:
    Integrin alpha-2
Alternative name(s):
    Platelet membrane glycoprotein Ia
      Short name=GPIa
    Collagen receptor
    VLA-2 alpha chain
    CD49 antigen-like family member B
    CD_antigen=CD49b

Gene names

Name:	ITGA2
Synonyms:	CD49B

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1181 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-2/beta-1 is a receptor for laminin, collagen, collagen C-propeptides, fibronectin and E-cadherin. It recognizes the proline-hydroxylated sequence G-F-P-G-E-R in collagen. It is responsible for adhesion of platelets and other cells to collagens, modulation of collagen and collagenase gene expression, force generation and organization of newly synthesized extracellular matrix.
Subunit structure	Heterodimer of an alpha and a beta subunit. Alpha-2 associates with beta-1. Interacts with HPS5 and RAB21. Binds to human echoviruses 1 and 8 capsid proteins and acts as a receptor for these viruses. Interacts (via ITAG2 I-domain) with rotavirus A VP4; this interaction only occurs in rotavirus integrin-dependent strains, for which ITGA2 acts as a receptor. Ref.5 Ref.6 Ref.7
Subcellular location	Membrane; Single-pass type I membrane protein.
Domain	The integrin I-domain (insert) is a VWFA domain. Integrins with I-domains do not undergo protease cleavage.
Polymorphism	Position 534 is associated with platelet-specific alloantigen HPA-5 (Br). HPA-5A/Br(a) has Lys-534 and HPA-5B/Br(b) has Glu-534. HPA-5B is involved in neonatal alloimmune thrombocytopenia (NAIT or NATP). The Lys-534-Glu polymorphism may play a role in coronary artery disease (CAD).
Sequence similarities	Belongs to the integrin alpha chain family. Contains 7 FG-GAP repeats. Contains 1 VWFA domain.

Ontologies

Keywords
Biological process	Cell adhesion Host-virus interaction
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Repeat Signal Transmembrane
Ligand	Calcium Magnesium
Molecular function	Integrin Receptor
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	blood coagulation Traceable author statement. Source: ProtInc cell-matrix adhesion Ref.1 Traceable author statement. Source: ProtInc integrin-mediated signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW organ morphogenesis Traceable author statement. Source: ProtInc
Cellular component	integrin complex Ref.1 Traceable author statement. Source: ProtInc
Molecular function	calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW collagen binding Traceable author statement. Source: ProtInc identical protein binding Inferred from physical interaction. Source: IntAct magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW receptor activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		2	EBI-702960,EBI-702960

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 29

29

Ref.1

Chain

30 – 1181

1152

Integrin alpha-2

PRO_0000016233

Regions

Topological domain

30 – 1132

1103

Extracellular Potential

Transmembrane

1133 – 1154

22

Potential

Topological domain

1155 – 1181

27

Cytoplasmic Potential

Repeat

45 – 103

59

FG-GAP 1

Repeat

104 – ?

FG-GAP 2

Domain

188 – 378

191

VWFA

Repeat

379 – 433

55

FG-GAP 3

Repeat

434 – 486

53

FG-GAP 4

Repeat

488 – 549

62

FG-GAP 5

Repeat

551 – 610

60

FG-GAP 6

Repeat

615 – 667

53

FG-GAP 7

Calcium binding

499 – 507

9

Potential

Calcium binding

563 – 571

9

Potential

Calcium binding

627 – 635

9

Potential

Region

1155 – 1161

7

Interaction with HPS5

Motif

1157 – 1161

5

GFFKR motif

Amino acid modifications

Modified residue

1177

1

Phosphothreonine Ref.10

Glycosylation

105

1

N-linked (GlcNAc...) Potential

Glycosylation

112

1

N-linked (GlcNAc...) Potential

Glycosylation

343

1

N-linked (GlcNAc...) Ref.8 Ref.11 Ref.12

Glycosylation

432

1

N-linked (GlcNAc...) Potential

Glycosylation

460

1

N-linked (GlcNAc...) Potential

Glycosylation

475

1

N-linked (GlcNAc...) Potential

Glycosylation

699

1

N-linked (GlcNAc...) Potential

Glycosylation

1057

1

N-linked (GlcNAc...) Potential

Glycosylation

1074

1

N-linked (GlcNAc...) Potential

Glycosylation

1081

1

N-linked (GlcNAc...) Potential

Disulfide bond

83 ↔ 92

By similarity

Disulfide bond

680 ↔ 737

By similarity

Disulfide bond

789 ↔ 795

By similarity

Disulfide bond

865 ↔ 876

By similarity

Disulfide bond

1019 ↔ 1050

By similarity

Disulfide bond

1055 ↔ 1060

By similarity

Natural variations

Natural variant

534

1

K → E in alloantigen HPA-5B. dbSNP rs1801106. Ref.14 Ref.15

VAR_003977

Natural variant

691

1

N → K: dbSNP rs3212557. Ref.2

VAR_029146

Natural variant

927

1

N → S: dbSNP rs2287870.

VAR_021855

Natural variant

1127

1

K → Q: dbSNP rs3212645. Ref.2

VAR_020036

Experimental info

Mutagenesis

1159

1

F → A: No significant reduction of RAB21-binding by co-immunoprecipitation assay; when associated with A-1160 and A-1162. Ref.7

Mutagenesis

1160

1

K → A: No effect on RAB21-binding. Significant reduction of RAB21-binding; when associated with A-1161. Shows defective cytokinesis on collagen, but not on fibronectin; when associated with A-1161. Ref.7 Ref.9

Mutagenesis

1161

1

R → A: Significant reduction of RAB21-binding; when associated with A-1160. Shows defective cytokinesis on collagen, but not on fibronectin; when associated with A-1160. Ref.7 Ref.9

Mutagenesis

1162

1

K → A: No significant reduction of RAB21-binding by co-immunoprecipitation assay; when associated with A-1159 and A-1160. Ref.7 Ref.9

Mutagenesis

1162

1

K → P: Markedly weakens RAB21-binding. Shows defective cytokinesis on collagen, but not on fibronectin. Ref.7 Ref.9

Mutagenesis

1164

1

E → A: Significant reduction of RAB21-binding; when associated with A-1160; A-1161 and A-1165. Ref.7 Ref.9

Mutagenesis

1165

1

K → A: Significant reduction of RAB21-binding; when associated with A-1160; A-1161 and A-1164. Ref.7 Ref.9

Sequence conflict

17

1

L → V in AAA16619. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

1181

Helix Strand Turn

Details...

Beta strand

173 – 180

8

Helix

188 – 199

12

Beta strand

208 – 224

17

Turn

226 – 228

3

Helix

232 – 240

9

Helix

252 – 262

11

Helix

266 – 268

3

Beta strand

272 – 284

13

Helix

289 – 291

3

Helix

292 – 301

10

Beta strand

304 – 311

8

Helix

313 – 317

5

Helix

323 – 330

8

Helix

337 – 340

4

Beta strand

341 – 346

6

Helix

347 – 353

7

Helix

354 – 362

9

Sequences

	Sequence		Length	Mass (Da)
	P17301-1 [UniParc]. Last modified August 1, 1990. Version 1. Checksum: 7E1B7ED968A94070	FASTA	1,181	129,295
	10 20 30 40 50 60 MGPERTGAAP LPLLLVLALS QGILNCCLAY NVGLPEAKIF SGPSSEQFGY AVQQFINPKG 70 80 90 100 110 120 NWLLVGSPWS GFPENRMGDV YKCPVDLSTA TCEKLNLQTS TSIPNVTEMK TNMSLGLILT 130 140 150 160 170 180 RNMGTGGFLT CGPLWAQQCG NQYYTTGVCS DISPDFQLSA SFSPATQPCP SLIDVVVVCD 190 200 210 220 230 240 ESNSIYPWDA VKNFLEKFVQ GLDIGPTKTQ VGLIQYANNP RVVFNLNTYK TKEEMIVATS 250 260 270 280 290 300 QTSQYGGDLT NTFGAIQYAR KYAYSAASGG RRSATKVMVV VTDGESHDGS MLKAVIDQCN 310 320 330 340 350 360 HDNILRFGIA VLGYLNRNAL DTKNLIKEIK AIASIPTERY FFNVSDEAAL LEKAGTLGEQ 370 380 390 400 410 420 IFSIEGTVQG GDNFQMEMSQ VGFSADYSSQ NDILMLGAVG AFGWSGTIVQ KTSHGHLIFP 430 440 450 460 470 480 KQAFDQILQD RNHSSYLGYS VAAISTGEST HFVAGAPRAN YTGQIVLYSV NENGNITVIQ 490 500 510 520 530 540 AHRGDQIGSY FGSVLCSVDV DKDTITDVLL VGAPMYMSDL KKEEGRVYLF TIKKGILGQH 550 560 570 580 590 600 QFLEGPEGIE NTRFGSAIAA LSDINMDGFN DVIVGSPLEN QNSGAVYIYN GHQGTIRTKY 610 620 630 640 650 660 SQKILGSDGA FRSHLQYFGR SLDGYGDLNG DSITDVSIGA FGQVVQLWSQ SIADVAIEAS 670 680 690 700 710 720 FTPEKITLVN KNAQIILKLC FSAKFRPTKQ NNQVAIVYNI TLDADGFSSR VTSRGLFKEN 730 740 750 760 770 780 NERCLQKNMV VNQAQSCPEH IIYIQEPSDV VNSLDLRVDI SLENPGTSPA LEAYSETAKV 790 800 810 820 830 840 FSIPFHKDCG EDGLCISDLV LDVRQIPAAQ EQPFIVSNQN KRLTFSVTLK NKRESAYNTG 850 860 870 880 890 900 IVVDFSENLF FASFSLPVDG TEVTCQVAAS QKSVACDVGY PALKREQQVT FTINFDFNLQ 910 920 930 940 950 960 NLQNQASLSF QALSESQEEN KADNLVNLKI PLLYDAEIHL TRSTNINFYE ISSDGNVPSI 970 980 990 1000 1010 1020 VHSFEDVGPK FIFSLKVTTG SVPVSMATVI IHIPQYTKEK NPLMYLTGVQ TDKAGDISCN 1030 1040 1050 1060 1070 1080 ADINPLKIGQ TSSSVSFKSE NFRHTKELNC RTASCSNVTC WLKDVHMKGE YFVNVTTRIW 1090 1100 1110 1120 1130 1140 NGTFASSTFQ TVQLTAAAEI NTYNPEIYVI EDNTVTIPLM IMKPDEKAEV PTGVIIGSII 1150 1160 1170 1180 AGILLLLALV AILWKLGFFK RKYEKMTKNP DEIDETTELS S

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The primary structure of the VLA-2/collagen receptor alpha 2 subunit (platelet GPIa): homology to other integrins and the presence of a possible collagen-binding domain." Takada Y., Hemler M.E. J. Cell Biol. 109:397-407(1989) [PubMed: 2545729] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 30-44. Tissue: Endothelial cell.
[2]	SeattleSNPs variation discovery resource Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LYS-691 AND GLN-1127.
[3]	"The DNA sequence and comparative analysis of human chromosome 5." Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M. Nature 431:268-274(2004) [PubMed: 15372022] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT GLU-534.
[4]	"The human alpha 2 integrin gene promoter. Identification of positive and negative regulatory elements important for cell-type and developmentally restricted gene expression." Zutter M.M., Santoro S.A., Painter A.S., Tsung Y.L., Gafford A. J. Biol. Chem. 269:463-469(1994) [PubMed: 8276836] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-21.
[5]	"Infection by echoviruses 1 and 8 depends on the alpha 2 subunit of human VLA-2." Bergelson J.M., St John N., Kawaguchi S., Chan M., Stubdal H., Modlin J., Finberg R.W. J. Virol. 67:6847-6852(1993) [PubMed: 8411387] [Abstract] Cited for: INTERACTION WITH HUMAN ECHOVIRUS 1 AND HUMAN ECHOVIRUS 8 CAPSID PROTEINS.
[6]	"Integrin-using rotaviruses bind alpha2beta1 integrin alpha2 I domain via VP4 DGE sequence and recognize alphaXbeta2 and alphaVbeta3 by using VP7 during cell entry." Graham K.L., Halasz P., Tan Y., Hewish M.J., Takada Y., Mackow E.R., Robinson M.K., Coulson B.S. J. Virol. 77:9969-9978(2003) [PubMed: 12941907] [Abstract] Cited for: INTERACTION WITH ROTAVIRUS A VP4.
[7]	"Small GTPase Rab21 regulates cell adhesion and controls endosomal traffic of beta1-integrins." Pellinen T., Arjonen A., Vuoriluoto K., Kallio K., Fransen J.A.M., Ivaska J. J. Cell Biol. 173:767-780(2006) [PubMed: 16754960] [Abstract] Cited for: INTERACTION WITH RAB21, MUTAGENESIS OF PHE-1159; LYS-1160; ARG-1161; LYS-1162; GLU-1164 AND LYS-1165.
[8]	"Elucidation of N-glycosylation sites on human platelet proteins: a glycoproteomic approach." Lewandrowski U., Moebius J., Walter U., Sickmann A. Mol. Cell. Proteomics 5:226-233(2006) [PubMed: 16263699] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-343, MASS SPECTROMETRY. Tissue: Platelet.
[9]	"Integrin trafficking regulated by Rab21 is necessary for cytokinesis." Pellinen T., Tuomi S., Arjonen A., Wolf M., Edgren H., Meyer H., Grosse R., Kitzing T., Rantala J.K., Kallioniemi O., Faessler R., Kallio M., Ivaska J. Dev. Cell 15:371-385(2008) [PubMed: 18804435] [Abstract] Cited for: MUTAGENESIS OF LYS-1160; ARG-1161 AND LYS-1162.
[10]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed: 18088087] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-1177, MASS SPECTROMETRY. Tissue: Platelet.
[11]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-343, MASS SPECTROMETRY. Tissue: Liver.
[12]	"Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins." Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D. Nat. Biotechnol. 27:378-386(2009) [PubMed: 19349973] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-343, MASS SPECTROMETRY.
[13]	"Crystal structure of the I domain from integrin alpha2beta1." Emsley J., King S.L., Bergelson J.M., Liddington R.C. J. Biol. Chem. 272:28512-28517(1997) [PubMed: 9353312] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 168-368.
[14]	"The human platelet alloantigens Br(a) and Brb are associated with a single amino acid polymorphism on glycoprotein Ia (integrin subunit alpha 2)." Santoso S., Kalb R., Walka M., Kiefel V., Mueller-Eckhardt C., Newman P.J. J. Clin. Invest. 92:2427-2432(1993) [PubMed: 7901236] [Abstract] Cited for: VARIANT GLU-534.
[15]	"The impact of the glycoprotein Ia collagen receptor subunit A1648G gene polymorphism on coronary artery disease and acute myocardial infarction." Kroll H., Gardemann A., Fechter A., Haberbosch W., Santoso S. Thromb. Haemost. 83:392-396(2000) [PubMed: 10744142] [Abstract] Cited for: VARIANT GLU-534.
+	Additional computationally mapped references.

Web resources

GeneReviews

SeattleSNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

X17033 mRNA. Translation: CAA34894.1.
AF512556 Genomic DNA. Translation: AAM34795.1.
L24121 Genomic DNA. Translation: AAA16619.2.

IPI

IPI00013744.

PIR

A33998.

RefSeq

NP_002194.2.

UniGene

Hs.482077

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AOX	X-ray	2.10	A/B	169-366	[»]
1DZI	X-ray	2.10	A	172-355	[»]
1PQB	model	-	A/B	169-366	[»]
1V7P	X-ray	1.90	C	170-366	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:67N.

IntAct

P17301. 3 interactions.

STRING

P17301.

PTM databases

PhosphoSite

P17301.

Proteomic databases

PRIDE

P17301.

Genome annotation databases

Ensembl

ENST00000296585; ENSP00000296585; ENSG00000164171; Homo sapiens. [Genome view]

GeneID

3673.

KEGG

hsa:3673.

UCSC

uc003joy.1. human.

Organism-specific databases

CTD

3673.

GeneCards

GC05P052321.

H-InvDB

HIX0032121.

HGNC

HGNC:6137. ITGA2.

HPA

CAB017690.

MIM

192974. gene+phenotype.

Orphanet

853. Fetal and neonatal alloimmune thrombocytopenia.

PharmGKB

PA204.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P17301.

HOVERGEN

P17301.

Enzyme and pathway databases

Pathway_Interaction_DB

arf6_traffickingpathway. Arf6 trafficking events.
syndecan_2_pathway. Syndecan-2-mediated signaling events.
lymphangiogenesis_pathway. VEGFR3 signaling in lymphatic endothelium.

Reactome

REACT_13552. Integrin cell surface interactions.
REACT_604. Hemostasis.

Gene expression databases

ArrayExpress

P17301.

Bgee

P17301.

CleanEx

HS_ITGA2.

Genevestigator

P17301.

GermOnline

ENSG00000164171. Homo sapiens.

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.
IPR002035. VWF_A.
[Graphical view]

Pfam

PF01839. FG-GAP. 2 hits.
PF00357. Integrin_alpha. 1 hit.
PF08441. Integrin_alpha2. 1 hit.
PF00092. VWA. 1 hit.
[Graphical view]

PRINTS

PR01185. INTEGRINA.

SMART

SM00191. Int_alpha. 5 hits.
SM00327. VWA. 1 hit.
[Graphical view]

PROSITE

PS00242. INTEGRIN_ALPHA. 1 hit.
PS50234. VWFA. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

14377.

SOURCE

Search...

Entry information

Entry name

ITA2_HUMAN

Accession

Primary (citable) accession number: P17301
Secondary accession number(s): Q14595

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	August 1, 1990
Last modified:	November 24, 2009
This is version 123 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.