Tumor Endothelial Marker Report: TEM30 (Integrin alpha-1)

TEM domain structure

	TEM domain structure

TEM Sequence Analysis

name from to source/E description

FG-GAP 16 75 Pfam, E= 3.8e-06 FG-GAP repeats fold into a beta propeller structure. Integrin ligands and a putative Mg2+ ion are predicted to bind to the upper face of the propeller.

VWA 144 327 Pfam, E= 4.3e-65 The domain adopts a classic alpha/beta Rossmann fold and contains an unusual metal ion coordination site at its surface. It is conserved in alpha1, -2, -L, -X, -D, -M and -E, and serves in ligand binding. VWA is predominantly present at extracellular matrix (in non-fibrillar collagens and non-collagenous proteins) with a number of modules ranging from one to twelve.

FG-GAP 405 457 Pfam, E= 3.1e-07 The alpha-integrin FG-GAP repeat has been predicted to fold into a beta propeller structure. The repeat is called the FG-GAP repeat after two conserved motifs in the repeat. Integrin ligands and a putative Mg2+ ion are predicted to bind to the upper face of the propeller, in a manner analogous to the way in which the trimeric G-protein beta subunit (G beta) binds the G protein alpha subunit.

FG-GAP 459 505 Pfam, E= 4.5e-14

FG-GAP 540 599 Pfam, E= 1.5e-16

FG-GAP 602 654 Pfam, E= 1.9e-07

-- 655 1115 -- --

TM 1116 1136 TOPPREDM, 2.490, LCR(L)

integrin_A 1137 1151 Pfam, E= 0.091 The conserved integrin alpha cytoplasmic region does not affect adhesion, but influences stress fiber formation via the conserved GFFKR motif.

1151

	TEM Sequence Analysis

name	from	to	source/E	description
FG-GAP	16	75	Pfam, E= 3.8e-06	FG-GAP repeats fold into a beta propeller structure. Integrin ligands and a putative Mg2+ ion are predicted to bind to the upper face of the propeller.
VWA	144	327	Pfam, E= 4.3e-65	The domain adopts a classic alpha/beta Rossmann fold and contains an unusual metal ion coordination site at its surface. It is conserved in alpha1, -2, -L, -X, -D, -M and -E, and serves in ligand binding. VWA is predominantly present at extracellular matrix (in non-fibrillar collagens and non-collagenous proteins) with a number of modules ranging from one to twelve.
FG-GAP	405	457	Pfam, E= 3.1e-07	The alpha-integrin FG-GAP repeat has been predicted to fold into a beta propeller structure. The repeat is called the FG-GAP repeat after two conserved motifs in the repeat. Integrin ligands and a putative Mg2+ ion are predicted to bind to the upper face of the propeller, in a manner analogous to the way in which the trimeric G-protein beta subunit (G beta) binds the G protein alpha subunit.
FG-GAP	459	505	Pfam, E= 4.5e-14
FG-GAP	540	599	Pfam, E= 1.5e-16
FG-GAP	602	654	Pfam, E= 1.9e-07
--	655	1115	--	--
TM	1116	1136	TOPPREDM, 2.490,	LCR(L)
integrin_A	1137	1151	Pfam, E= 0.091	The conserved integrin alpha cytoplasmic region does not affect adhesion, but influences stress fiber formation via the conserved GFFKR motif.
1151

Remarks

	Remarks

CLASSIFICATION: The family of integrins containing the beta1 subunit contains high affinity receptors for ECM proteins including fibronectin, laminin, and the collagens. From this family alpha1beta1, alpha2beta1, and alpha3beta1 are known to be the major receptors for collagens (Gardner et al,1996).
INTERACTIONS:
- Associates with the beta-subunit.
- The VWA domains from alpha1 and alpha2 integrin can bind collagens I, collagen IV, laminin and the collagen IV fragment CB3 in a divalent cation-dependent manner. It is proposed that cation, ligand and VWA domain form a ternary complex (Calderwood etal, 1997).
FUNCTION:
- Alpha1beta1 and alpha2beta1 integrins are important for VEGF-driven angiogenesis in vivo (Senger et al, 1997). In vitro, they have been shown to function in cell migration and in reorganization and contraction of collagen. They confer invasive behavior by regulating stromelysin-1 expression. Antibodies against alpha1 and alpha2 integrin subunits inhibited both transcription and protein expression of the matrix metalloproteinase stromelysin-1 (Lochter et al, 1999).
- Integrin alpha1 regulates collagen synthesis. Alpha1-null animals lack negative feedback regulation of collagen synthesis and synthesize excess dermal collagen in vivo. This is not apparent morphologically as the animals also show increased synthesis of collagenases and, thus, compensate excess synthesis with increased breakdown (Gardner et al, 1999).
- Out of the three major integrin receptors for collagens, alpha1 uniquely confers on fibroblasts the ability to adhere and migrate on collagen IV.
- Functions in control of cell growth and proliferation via the Ras-MAPK. Out of alpha1beta1, alpha2beta1, and alpha3beta1, alpha1beta1 is the only one of these that is able mediate a collagen-induced signal to the Ras-MAPK pathway via the adaptor protein Shc (Pozzi et al, 1998).
PROTEASE BALANCE: Integrin alpha1 is proposed to signal through the Ras/Shc/MAPK pathway to inhibit MMP synthesis. Integrins a2b1, a4b1 and a5b1, on the other hand, are able to up-regulate expression of different MMPs. It has been hypothesized that in alpha1 null mice angiogenesis is reduced due to secretion of excess MMPs. These lead to auto-inhibition of angiogenesis by generating angiostatin from circulating plasminogen (Pozzi et al, 2000).

Sequence Information

TEM TEM30 integrin, alpha 1

Reliability of Gen2Tag mapping

Cid->tag (Hs.116774) frequency :
tem30: CATG-CATTATCCAA=3/5 (3 oriented ESTs)

Analysis
BlastP against nr

Output Created by a Suite of Single Sequence Analysis Techniques

Protein Description

SEQ.SOURCE: gi|2829468|sp|P56199|ITA1_HUMAN INTEGRIN ALPHA-1
(LAMININ AND COLLAGEN RECEPTOR) (VLA-1) (CD49A)

Protein Sequence

FNVDVKNSMTFSGPVEDMFGYTVQQYENEEGKWVLIGSPLVGQPKNRTGDVYKCPVGRGESLPCVKLDLP VNTSIPNVTEVKENMTFGSTLVTNPNGGFLACGPLYAYRCGHLHYTTGICSDVSPTFQVVNSIAPVQECS TQLDIVIVLDGSNSIYPWDSVTAFLNDLLKRMDIGPKQTQVGIVQYGENVTHEFNLNKYSSTEEVLVAAK KIVQRGGRQTMTALGTDTARKEAFTEARGARRGVKKVMVIVTDGESHDNHRLKKVIQDCEDENIQRFSIA ILGSYNRGNLSTEKFVEEIKSIASEPTEKHFFNVSDELALVTIVKTLGERIFALEATADQSAASFEMEMS QTGFSAHYSQDWVMLGAVGAYDWNGTVVMQKASQIIIPRNTTFNVESTKKNEPLASYLGYTVNSATASSG DVLYIAGQPRYNHTGQVIIYRMEDGNIKILQTLSGEQIGSYFGSILTTTDIDKDSNTDILLVGAPMYMGT EKEEQGKVYVYALNQTRFEYQMSLEPIKQTCCSSRQHNSCTTENKNEPCGARFGTAIAAVKDLNLDGFND IVIGAPLEDDHGGAVYIYHGSGKTIRKEYAQRIPSGGDGKTLKFFGQSIHGEMDLNGDGLTDVTIGGLGG AALFWSRDVAVVKVTMNFEPNKVNIQKKNCHMEGKETVCINATVCFEVKLKSKEDTIYEADLQYRVTLDS LRQISRSFFSGTQERKVQRNITVRKSECTKHSFYMLDKHDFQDSVRITLDFNLTDPENGPVLDDSLPNSV HEYIPFAKDCGNKEKCISDLSLHVATTEKDLLIVRSQNDKFNVSLTVKNTKDSAYNTRTIVHYSPNLVFS GIEAIQKDSCESNHNITCKVGYPFLRRGEMVTFKILFQFNTSYLMENVTIYLSATSDSEEPPETLSDNVV NISIPVKYEVGLQFYSSASEYHISIAANETVPEVINSTEDIGNEINIFYLIRKSGSFPMPELKLSISFPN MTSNGYPVLYPTGLSSSENANCRPHIFEDPFSINSGKKMTTSTDHLKRGTILDCNTCKFATITCNLTSSD ISQVNVSLILWKPTFIKSYFSSLNLTIRGELRSENASLVLSSSNQKRELAIQISKDGLPGRVPLWVILLS AFAGLLLLMLLILALWKIGFFKRPLKKKMEK

SAGE-Tag CATG-CATTATCCAAA

EST/cluster Description

UNIGEN CLUSTER: UniGene Cluster Hs.116774 ITGA1

MARKINGS: tem30 Tag in red

EST/cluster Sequence

TTCAATGTTGATGTGAAAAACTCAATGACTTTCAGCGGCCCGGTGGAAGACATGTTTGGATATACTGTTCAACAATATGA AAATGAAGAAGGAAAATGGGTGCTTATTGGTTCTCCGTTAGTTGGCCAACCCAAAAACAGAACTGGAGATGTCTATAAGT GTCCAGTTGGGAGAGGTGAATCATTACCTTGCGTAAAGTTGGATCTACCAGTTAATACATCAATTCCCAATGTCACAGAA GTAAAGGAGAACATGACATTTGGATCAACTTTAGTCACCAACCCAAATGGAGGATTTCTGGCTTGTGGGCCCTTATATGC CTATAGATGTGGACATTTGCATTACACAACTGGAATCTGTTCTGACGTCAGCCCCACATTTCAAGTCGTGAATTCCATTG CCCCTGTACAAGAATGCAGCACTCAACTGGACATAGTCATAGTGCTGGATGGTTCCAACAGTATTTACCCATGGGACAGT GTTACAGCTTTTTTAAATGACCTCTTGAAAAGAATGGATATTGGTCCTAAACAGACACAGGTTGGAATTGTACAGTATGG AGAAAACGTGACCCATGAGTTCAACCTCAATAAGTATTCTTCCACCGAAGAGGTACTTGTTGCAGCAAAGAAAATAGTCC AGAGAGGTGGCCGCCAGACTATGACAGCTCTTGGAACAGACACAGCAAGAAAGGAGGCATTCACGGAAGCCCGGGGTGCC CGAAGAGGAGTTAAAAAAGTCATGGTTATTGTGACAGATGGAGAGTCTCATGACAATCATCGACTGAAGAAGGTCATCCA AGACTGTGAAGATGAAAACATTCAACGGTTTTCCATAGCTATTCTTGGCAGCTATAACCGAGGAAATTTAAGCACTGAAA AATTTGTGGAGGAAATAAAATCAATTGCAAGTGAACCCACTGAAAAGCATTTCTTCAATGTCTCTGATGAATTGGCTCTA GTCACCATTGTTAAAACTCTGGGAGAAAGAATATTTGCCCTGGAAGCCACAGCTGACCAGTCAGCAGCTTCATTTGAAAT GGAAATGTCTCAGACTGGCTTCAGTGCTCATTATTCACAGGACTGGGTCATGCTTGGAGCAGTAGGAGCCTATGATTGGA ATGGAACAGTTGTCATGCAGAAGGCTAGTCAAATCATAATCCCTCGAAACACAACCTTTAATGTTGAGTCTACCAAAAAG AATGAACCGCTTGCTTCTTATTTAGGTTACACTGTAAACTCTGCTACTGCTTCTTCTGGAGATGTGCTCTATATTGCTGG ACAGCCTCGGTACAATCATACAGGCCAGGTCATTATCTACAGGATGGAAGATGGAAACATCAAAATTCTCCAGACGCTCA GTGGAGAACAGATTGGTTCCTACTTTGGCAGTATTTTAACAACAACTGACATTGACAAGGATTCTAATACTGACATTCTT CTAGTCGGAGCCCCTATGTACATGGGAACAGAGAAGGAGGAGCAAGGAAAAGTGTATGTGTATGCTCTCAATCAGACAAG GTTTGAATATCAAATGAGCCTGGAACCTATTAAGCAGACGTGCTGTTCATCTCGGCAGCACAATTCATGCACAACAGAAA ACAAAAATGAGCCATGCGGGGCTCGTTTTGGAACTGCAATTGCTGCTGTAAAAGACCTCAATCTTGATGGATTTAATGAC ATCGTGATAGGAGCTCCGCTGGAAGATGATCACGGGGGAGCTGTGTACATTTATCATGGAAGTGGCAAGACTATAAGGAA AGAGTATGCACAACGTATTCCATCAGGTGGGGATGGTAAGACACTGAAATTTTTTGGCCAGTCTATCCACGGAGAAATGG ATTTAAATGGTGACGGTCTGACAGATGTGACTATTGGGGGCCTTGGTGGTGCTGCCCTCTTCTGGTCCCGAGATGTGGCC GTAGTTAAAGTGACCATGAATTTTGAGCCAAATAAAGTGAATATTCAAAAGAAAAACTGCCATATGGAGGGAAAGGAAAC AGTATGCATAAATGCTACAGTGTGTTTTGAGGTTAAATTAAAGTCTAAAGAAGACACGATTTATGAAGCTGATTTGCAGT ACCGTGTCACCCTAGATTCACTAAGACAAATATCACGAAGTTTTTTCTCTGGAACTCAAGAGAGAAAGGTTCAAAGGAAC ATCACAGTTCGAAAATCAGAATGCACTAAGCACTCCTTCTACATGTTGGACAAGCATGACTTTCAGGACTCTGTGAGAAT AACGTTGGACTTTAATCTTACCGATCCAGAAAATGGGCCTGTTCTTGATGATTCTCTACCAAACTCAGTACATGAATATA TTCCCTTTGCCAAAGATTGTGGAAATAAGGAAAAATGTATCTCAGACCTCAGCCTGCATGTCGCCACCACTGAAAAGGAC CTGCTGATTGTCCGATCCCAGAATGATAAGTTCAACGTTAGCCTCACAGTCAAAAATACAAAGGACAGTGCCTATAACAC CAGGACAATAGTGCATTATTCTCCAAATCTAGTTTTTTCAGGAATTGAGGCTATCCAAAAAGACAGTTGTGAATCTAATC ATAATATCACATGTAAAGTTGGATATCCCTTCCTGAGAAGAGGAGAGATGGTAACTTTCAAAATATTGTTTCAGTTTAAC ACATCCTATCTCATGGAAAATGTGACCATTTATTTAAGTGCAACAAGTGACAGCGAAGAACCTCCTGAAACCCTTTCTGA TAATGTAGTAAACATTTCTATCCCGGTAAAATATGAAGTTGGACTACAGTTTTACAGCTCTGCAAGTGAATACCACATTT CAATTGCTGCCAATGAGACAGTCCCTGAAGTTATTAATTCTACTGAGGACATTGGAAATGAAATTAATATCTTCTACTTG ATTAGAAAAAGTGGATCTTTTCCAATGCCAGAGCTTAAGCTGTCAATTTCATTCCCCAATATGACATCAAATGGTTACCC TGTGCTGTACCCAACTGGATTGTCATCTTCTGAGAATGCAAACTGCAGACCCCATATCTTTGAGGATCCTTTCAGTATCA ACTCTGGAAAGAAAATGACTACATCAACTGACCATCTCAAACGAGGCACAATTCTGGACTGCAATACATGTAAATTTGCT ACCATCACATGTAATCTCACTTCTTCTGACATCAGCCAAGTCAATGTTTCGCTTATCTTGTGGAAACCAACTTTTATAAA ATCATATTTTTCCAGCTTAAATCTTACTATAAGGGGAGAACTTCGGAGTGAAAATGCATCTCTGGTTTTAAGTAGCAGCA ATCAAAAAAGAGAGCTTGCTATTCAAATATCCAAAGATGGGCTACCGGGCAGAGTGCCATTATGGGTCATCCTGCTGAGT GCTTTTGCCGGATTGTTGCTGTTAATGCTGCTCATTTTAGCACTGTGGAAGATTGGATTCTTCAAAAGACCACTGAAAAA GAAAATGGAGAAATGAAATATTTTACGAAAGAAAATAATAACAATTATTCAATAATCTATCCTCAGGTTTGCCTCAAATA TGTGACAAGAAATGTATAATTCATGACATAGTCATGTAACTATGTAATCCATCAGGGATTCATTACTTGGAAAATGACAG GTCATGCATTATCCAAAAACAATACCAAAAAGACATATTTTATAAAATGACAAAAAATATTTTACATAATTACTCATTTT TGTTGAGTAAGCAAAATTACAAAGTGTTTTTAAAAAAACCTGTACAAATATGTTTATGTATTAAATCACCATCCAAAATA TTTAAGGAATATATAAAAAGATTTTTATGATCAT

Genomic Sequence Description

Genomic Sequence

	Sequence Information

Literature

	Literature

PubMed:10681423
PCNA:97/5/2202 Elevated matrix metalloprotease and angiostatin levels in integrin alpha 1 knockout mice cause reduced tumor vascularization.
Pozzi A, Moberg PE, Miles LA, Wagner S, Soloway P, Gardner HA.
Proc Natl Acad Sci U S A. 2000 Feb 29;97(5):2202-7.

Pubmed: 9950676 alpha1 and alpha2 integrins mediate invasive activity of mouse mammary carcinoma cells through regulation of stromelysin-1 expression.
Lochter A, Navre M, Werb Z, Bissell MJ.
Mol Biol Cell. 1999 Feb;10(2):271-82.

Pubmed: 9885280 Absence of integrin alpha1beta1 in the mouse causes loss of feedback regulation of collagen synthesis in normal and wounded dermis.
Gardner H, Broberg A, Pozzi A, Laato M, Heino J.
J Cell Sci 1999 Feb;112 ( Pt 3):263-72

Pubmed: 9679154
JBC:142/2/587 Integrin alpha1beta1 mediates a unique collagen-dependent proliferation pathway in vivo.
Pozzi A, Wary KK, Giancotti FG, Gardner HA.
J Cell Biol. 1998 Jul 27;142(2):587-94.

Pubmed: 9391074
PCNA:94/25/13612 Angiogenesis promoted by vascular endothelial growth factor: regulation through alpha1beta1 and alpha2beta1 integrins.
Senger DR, Claffey KP, Benes JE, Perruzzi CA, Sergiou AP, Detmar M.
Proc Natl Acad Sci U S A 1997 Dec 9;94(25):13612-7

Pubmed: 9139675
The integrin alpha1 A-domain is a ligand binding site for collagens and laminin.
Calderwood DA, Tuckwell DS, Eble J, Kuhn K, Humphries MJ.
J Biol Chem. 1997 May 9;272(19):12311-7.

PubMed: 8428973 Expression of native and truncated forms of the human integrin alpha 1 subunit.
Briesewitz R, Epstein MR, Marcantonio EE
J Biol Chem 1993 Feb 5;268(4):2989-96

FAQ

PubMed:10681423 PCNA:97/5/2202	Elevated matrix metalloprotease and angiostatin levels in integrin alpha 1 knockout mice cause reduced tumor vascularization. Pozzi A, Moberg PE, Miles LA, Wagner S, Soloway P, Gardner HA. Proc Natl Acad Sci U S A. 2000 Feb 29;97(5):2202-7.
Pubmed: 9950676	alpha1 and alpha2 integrins mediate invasive activity of mouse mammary carcinoma cells through regulation of stromelysin-1 expression. Lochter A, Navre M, Werb Z, Bissell MJ. Mol Biol Cell. 1999 Feb;10(2):271-82.
Pubmed: 9885280	Absence of integrin alpha1beta1 in the mouse causes loss of feedback regulation of collagen synthesis in normal and wounded dermis. Gardner H, Broberg A, Pozzi A, Laato M, Heino J. J Cell Sci 1999 Feb;112 ( Pt 3):263-72
Pubmed: 9679154 JBC:142/2/587	Integrin alpha1beta1 mediates a unique collagen-dependent proliferation pathway in vivo. Pozzi A, Wary KK, Giancotti FG, Gardner HA. J Cell Biol. 1998 Jul 27;142(2):587-94.
Pubmed: 9391074 PCNA:94/25/13612	Angiogenesis promoted by vascular endothelial growth factor: regulation through alpha1beta1 and alpha2beta1 integrins. Senger DR, Claffey KP, Benes JE, Perruzzi CA, Sergiou AP, Detmar M. Proc Natl Acad Sci U S A 1997 Dec 9;94(25):13612-7
Pubmed: 9139675	The integrin alpha1 A-domain is a ligand binding site for collagens and laminin. Calderwood DA, Tuckwell DS, Eble J, Kuhn K, Humphries MJ. J Biol Chem. 1997 May 9;272(19):12311-7.
PubMed: 8428973	Expression of native and truncated forms of the human integrin alpha 1 subunit. Briesewitz R, Epstein MR, Marcantonio EE J Biol Chem 1993 Feb 5;268(4):2989-96