Reviewed, UniProtKB/Swiss-Prot P26006 (ITA3_HUMAN)

Names and origin

Protein names

Recommended name:
    Integrin alpha-3
Alternative name(s):
    Galactoprotein B3
      Short name=GAPB3
    VLA-3 alpha chain
    FRP-2
    CD49 antigen-like family member C
    CD_antigen=CD49c
Cleaved into the following 2 chains:
    1- Recommended name:
            Integrin alpha-3 heavy chain
    2- Recommended name:
            Integrin alpha-3 light chain

Gene names

Name:	ITGA3
Synonyms:	MSK18

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	1066 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-3/beta-1 is a receptor for fibronectin, laminin, collagen, epiligrin, thrombospondin and CSPG4. Alpha-3/beta-1 may mediate with LGALS3 the stimulation by CSPG4 of endothelial cells migration.
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-3 associates with beta-1. Interacts with HPS5.
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	Isoform alpha-3A is widely expressed. Isoform alpha-3B is expressed in brain and heart. In brain, both isoforms are exclusively expressed on vascular smooth muscle cells, whereas in heart isoform alpha-3A is strongly expressed on vascular smooth muscle cells, isoform alpha-3B is detected only on endothelial vein cells.
Post-translational modification	Isoform alpha-3A, but not isoform alpha-3B, is phosphorylated on serine residues. Phosphorylation increases after phorbol 12-myristate 13-acetate stimulation. Isoform alpha-3A is phosphorylated on Tyr-1051.
Sequence similarities	Belongs to the integrin alpha chain family. Contains 7 FG-GAP repeats.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Membrane
Coding sequence diversity	Alternative splicing
Domain	Repeat Signal Transmembrane
Ligand	Calcium
Molecular function	Integrin Receptor
PTM	Cleavage on pair of basic residues Glycoprotein Phosphoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	cell-matrix adhesion Ref.1 Traceable author statement. Source: ProtInc
Cellular component	integrin complex Ref.1 Traceable author statement. Source: ProtInc
Molecular function	protein binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Alternative products

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

Isoform Alpha-3B (identifier: P26006-1)

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 Alpha-3A (identifier: P26006-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1022-1066: TRYYQIMPKYHAVRIREEERYPPPGSTLPTKKHWVTSWQTRDQYY → ARTRALYEAKRQKAEMKSQPSETERLTDDY

Notes: Phosphorylated on Tyr-1051.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Signal peptide	1 – 32	32
	Chain	33 – 1066	1034	Integrin alpha-3
	Chain	33 – 872	840	Integrin alpha-3 heavy chain Potential
	Chain	876 – 1066	191	Integrin alpha-3 light chain Potential
Regions
	Topological domain	33 – 991	959	Extracellular Potential
	Transmembrane	992 – 1014	23	Potential
	Topological domain	1015 – 1066	52	Cytoplasmic Potential
	Repeat	49 – 94	46	FG-GAP 1
	Repeat	120 – 165	46	FG-GAP 2
	Repeat	195 – 227	33	FG-GAP 3
	Repeat	246 – 279	34	FG-GAP 4
	Repeat	304 – 345	42	FG-GAP 5
	Repeat	366 – 402	37	FG-GAP 6
	Repeat	426 – 461	36	FG-GAP 7
	Calcium binding	315 – 323	9	Potential
	Calcium binding	378 – 386	9	Potential
	Calcium binding	439 – 447	9	Potential
	Region	1015 – 1021	7	Interaction with HPS5
	Motif	1017 – 1021	5	GFFKR motif
Amino acid modifications
	Glycosylation	86	1	N-linked (GlcNAc...) Potential
	Glycosylation	107	1	N-linked (GlcNAc...) Potential
	Glycosylation	265	1	N-linked (GlcNAc...) Potential
	Glycosylation	500	1	N-linked (GlcNAc...) Potential
	Glycosylation	511	1	N-linked (GlcNAc...) Potential
	Glycosylation	573	1	N-linked (GlcNAc...) Potential
	Glycosylation	605	1	N-linked (GlcNAc...) Potential
	Glycosylation	656	1	N-linked (GlcNAc...) Potential
	Glycosylation	697	1	N-linked (GlcNAc...) Potential
	Glycosylation	841	1	N-linked (GlcNAc...) Potential
	Glycosylation	857	1	N-linked (GlcNAc...) Potential
	Glycosylation	926	1	N-linked (GlcNAc...) Potential
	Glycosylation	935	1	N-linked (GlcNAc...) Potential
	Glycosylation	969	1	N-linked (GlcNAc...) Potential
	Disulfide bond	94 ↔ 103
	Disulfide bond	140 ↔ 162
	Disulfide bond	185 ↔ 197
	Disulfide bond	485 ↔ 490		By similarity
	Disulfide bond	496 ↔ 550		By similarity
	Disulfide bond	615 ↔ 621
	Disulfide bond	694 ↔ 702
	Disulfide bond	846 ↔ 904		Interchain (between heavy and light chains)
	Disulfide bond	911 ↔ 916
Natural variations
	Alternative sequence	1022 – 1066	45	TRYYQ…RDQYY → ARTRALYEAKRQKAEMKSQP SETERLTDDY in isoform Alpha-3A.

Sequences

	Sequence		Length	Mass (Da)
	Isoform Alpha-3B [UniParc]. Last modified December 1, 2000. Version 3. Checksum: 18F008E5CDF6B8CE	FASTA	1,066	118,698
	10 20 30 40 50 60 MGPGPSRAPR APRLMLCALA LMVAAGGCVV SAFNLDTRFL VVKEAGNPGS LFGYSVALHR 70 80 90 100 110 120 QTERQQRYLL LAGAPRELAV PDGYTNRTGA VYLCPLTAHK DDCERMNITV KNDPGHHIIE 130 140 150 160 170 180 DMWLGVTVAS QGPAGRVLVC AHRYTQVLWS GSEDQRRMVG KCYVRGNDLE LDSSDDWQTY 190 200 210 220 230 240 HNEMCNSNTD YLETGMCQLG TSGGFTQNTV YFGAPGAYNW KGNSYMIQRK EWDLSEYSYK 250 260 270 280 290 300 DPEDQGNLYI GYTMQVGSFI LHPKNITIVT GAPRHRHMGA VFLLSQEAGG DLRRRQVLEG 310 320 330 340 350 360 SQVGAYFGSA IALADLNNDG WQDLLVGAPY YFERKEEVGG AIYVFMNQAG TSFPAHPSLL 370 380 390 400 410 420 LHGPSGSAFG LSVASIGDIN QDGFQDIAVG APFEGLGKVY IYHSSSKGLL RQPQQVIHGE 430 440 450 460 470 480 KLGLPGLATF GYSLSGQMDV DENFYPDLLV GSLSDHIVLL RARPVINIVH KTLVPRPAVL 490 500 510 520 530 540 DPALCTATSC VQVELCFAYN QSAGNPNYRR NITLAYTLEA DRDRRPPRLR FAGSESAVFH 550 560 570 580 590 600 GFFSMPEMRC QKLELLLMDN LRDKLRPIII SMNYSLPLRM PDRPRLGLRS LDAYPILNQA 610 620 630 640 650 660 QALENHTEVQ FQKECGPDNK CESNLQMRAA FVSEQQQKLS RLQYSRDVRK LLLSINVTNT 670 680 690 700 710 720 RTSERSGEDA HEALLTLVVP PALLLSSVRP PGACQANETI FCELGNPFKR NQRMELLIAF 730 740 750 760 770 780 EVIGVTLHTR DLQVQLQLST SSHQDNLWPM ILTLLVDYTL QTSLSMVNHR LQSFFGGTVM 790 800 810 820 830 840 GESGMKTVED VGSPLKYEFQ VGPMGEGLVG LGTLVLGLEW PYEVSNGKWL LYPTEITVHG 850 860 870 880 890 900 NGSWPCRPPG DLINPLNLTL SDPGDRPSSP QRRRRQLDPG GGQGPPPVTL AAAKKAKSET 910 920 930 940 950 960 VLTCATGRAH CVWLECPIPD APVVTNVTVK ARVWNSTFIE DYRDFDRVRV NGWATLFLRT 970 980 990 1000 1010 1020 SIPTINMENK TTWFSVDIDS ELVEELPAEI ELWLVLVAVG AGLLLLGLII LLLWKCGFFK 1030 1040 1050 1060 RTRYYQIMPK YHAVRIREEE RYPPPGSTLP TKKHWVTSWQ TRDQYY
	Isoform Alpha-3A [UniParc]. Checksum: EEAFA7778EF17B21		1,051	116,612
	10 20 30 40 50 60 MGPGPSRAPR APRLMLCALA LMVAAGGCVV SAFNLDTRFL VVKEAGNPGS LFGYSVALHR 70 80 90 100 110 120 QTERQQRYLL LAGAPRELAV PDGYTNRTGA VYLCPLTAHK DDCERMNITV KNDPGHHIIE 130 140 150 160 170 180 DMWLGVTVAS QGPAGRVLVC AHRYTQVLWS GSEDQRRMVG KCYVRGNDLE LDSSDDWQTY 190 200 210 220 230 240 HNEMCNSNTD YLETGMCQLG TSGGFTQNTV YFGAPGAYNW KGNSYMIQRK EWDLSEYSYK 250 260 270 280 290 300 DPEDQGNLYI GYTMQVGSFI LHPKNITIVT GAPRHRHMGA VFLLSQEAGG DLRRRQVLEG 310 320 330 340 350 360 SQVGAYFGSA IALADLNNDG WQDLLVGAPY YFERKEEVGG AIYVFMNQAG TSFPAHPSLL 370 380 390 400 410 420 LHGPSGSAFG LSVASIGDIN QDGFQDIAVG APFEGLGKVY IYHSSSKGLL RQPQQVIHGE 430 440 450 460 470 480 KLGLPGLATF GYSLSGQMDV DENFYPDLLV GSLSDHIVLL RARPVINIVH KTLVPRPAVL 490 500 510 520 530 540 DPALCTATSC VQVELCFAYN QSAGNPNYRR NITLAYTLEA DRDRRPPRLR FAGSESAVFH 550 560 570 580 590 600 GFFSMPEMRC QKLELLLMDN LRDKLRPIII SMNYSLPLRM PDRPRLGLRS LDAYPILNQA 610 620 630 640 650 660 QALENHTEVQ FQKECGPDNK CESNLQMRAA FVSEQQQKLS RLQYSRDVRK LLLSINVTNT 670 680 690 700 710 720 RTSERSGEDA HEALLTLVVP PALLLSSVRP PGACQANETI FCELGNPFKR NQRMELLIAF 730 740 750 760 770 780 EVIGVTLHTR DLQVQLQLST SSHQDNLWPM ILTLLVDYTL QTSLSMVNHR LQSFFGGTVM 790 800 810 820 830 840 GESGMKTVED VGSPLKYEFQ VGPMGEGLVG LGTLVLGLEW PYEVSNGKWL LYPTEITVHG 850 860 870 880 890 900 NGSWPCRPPG DLINPLNLTL SDPGDRPSSP QRRRRQLDPG GGQGPPPVTL AAAKKAKSET 910 920 930 940 950 960 VLTCATGRAH CVWLECPIPD APVVTNVTVK ARVWNSTFIE DYRDFDRVRV NGWATLFLRT 970 980 990 1000 1010 1020 SIPTINMENK TTWFSVDIDS ELVEELPAEI ELWLVLVAVG AGLLLLGLII LLLWKCGFFK 1030 1040 1050 RARTRALYEA KRQKAEMKSQ PSETERLTDD Y

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and expression of the cDNA for alpha 3 subunit of human alpha 3 beta 1 (VLA-3), an integrin receptor for fibronectin, laminin, and collagen." Takada Y., Murphy E., Pil P., Chen C., Ginsberg M.H., Hemler M.E. J. Cell Biol. 115:257-266(1991) [PubMed: 1655803] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA-3A AND ALPHA-3B).
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA-3A). Tissue: Hippocampus.
[3]	Mural R.J., Istrail S., Sutton G.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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA-3A).
[5]	"Identification of human galactoprotein b3, an oncogenic transformation-induced membrane glycoprotein, as VLA-3 alpha subunit: the primary structure of human integrin alpha 3." Tsuji T., Hakomori S., Osawa T. J. Biochem. 109:659-665(1991) [PubMed: 1714443] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 33-1066 (ISOFORM ALPHA-3A). Tissue: Fibroblast.
[6]	"Molecular and biological characterization of fusion regulatory proteins (FRPs): anti-FRP mAbs induced HIV-mediated cell fusion via an integrin system." Ohta H., Tsurudome M., Matsumura H., Koga Y., Morikawa S., Kawano M., Kusugawa S., Komada H., Nishio M., Ito Y. EMBO J. 13:2044-2055(1994) [PubMed: 8187758] [Abstract] Cited for: PROTEIN SEQUENCE OF 33-49.
[7]	"The very late antigen family of heterodimers is part of a superfamily of molecules involved in adhesion and embryogenesis." Takada Y., Strominger J.L., Hemler M.E. Proc. Natl. Acad. Sci. U.S.A. 84:3239-3243(1987) [PubMed: 3033641] [Abstract] Cited for: PROTEIN SEQUENCE OF 33-46.
[8]	"The A and B variants of the alpha 3 integrin subunit: tissue distribution and functional characterization." de Melker A.A., Sterk L.M., Delwel G.O., Fles D.L., Daams H., Weening J.J., Sonnenberg A. Lab. Invest. 76:547-563(1997) [PubMed: 9111516] [Abstract] Cited for: ALTERNATIVE SPLICING, PHOSPHORYLATION, TISSUE SPECIFICITY.
[9]	"Mass spectrometric based mapping of the disulfide bonding patterns of integrin alpha chains." Krokhin O.V., Cheng K., Sousa S.L., Ens W., Standing K.G., Wilkins J.A. Biochemistry 42:12950-12959(2003) [PubMed: 14596610] [Abstract] Cited for: DISULFIDE BONDS.
[10]	"NG2 proteoglycan promotes endothelial cell motility and angiogenesis via engagement of galectin-3 and alpha3beta1 integrin." Fukushi J., Makagiansar I.T., Stallcup W.B. Mol. Biol. Cell 15:3580-3590(2004) [PubMed: 15181153] [Abstract] Cited for: INTERACTION WITH ITGB1; LGALS3 AND CSPG4, FUNCTION.
[11]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1051 (ISOFORM ALPHA-3A), MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	M59911 mRNA. Translation: AAA36120.1. AK289961 mRNA. Translation: BAF82650.1. CH471109 Genomic DNA. Translation: EAW94645.1. BC150190 mRNA. Translation: AAI50191.1. D01038 mRNA. Translation: BAA00845.1.
PIR	A40021.
UniGene	Hs.265829
3D structure databases
HSSP	HSSP built from PDB template 1A8X based on UniProtKB P11215.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP:140N.
Genome annotation databases
Ensembl	ENSG00000005884. Homo sapiens. [Contig view]
Organism-specific databases
H-InvDB	HIX0017318.
HGNC	HGNC:6139. ITGA3.
MIM	605025. gene.
PharmGKB	PA29939.
GenAtlas	Search...