Full text data of ITGA1
ITGA1
[Confidence: low (only semi-automatic identification from reviews)]
Integrin alpha-1 (CD49 antigen-like family member A; Laminin and collagen receptor; VLA-1; CD49a; Flags: Precursor)
Integrin alpha-1 (CD49 antigen-like family member A; Laminin and collagen receptor; VLA-1; CD49a; Flags: Precursor)
UniProt
P56199
ID ITA1_HUMAN Reviewed; 1179 AA.
AC P56199; B2RNU0;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 143.
DE RecName: Full=Integrin alpha-1;
DE AltName: Full=CD49 antigen-like family member A;
DE AltName: Full=Laminin and collagen receptor;
DE AltName: Full=VLA-1;
DE AltName: CD_antigen=CD49a;
DE Flags: Precursor;
GN Name=ITGA1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T.,
RA Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M.,
RA Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K.,
RA Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C.,
RA Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M.,
RA Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A.,
RA Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M.,
RA Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S.,
RA Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 29-1179.
RX PubMed=8428973;
RA Briesewitz R., Epstein M.R., Marcantonio E.E.;
RT "Expression of native and truncated forms of the human integrin alpha
RT 1 subunit.";
RL J. Biol. Chem. 268:2989-2996(1993).
RN [4]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-532, AND MASS
RP SPECTROMETRY.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E.,
RA Moore R.J., Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [5]
RP FUNCTION IN EGFR SIGNALING, AND INTERACTION WITH PTPN2.
RX PubMed=15592458; DOI=10.1038/ncb1209;
RA Mattila E., Pellinen T., Nevo J., Vuoriluoto K., Arjonen A.,
RA Ivaska J.;
RT "Negative regulation of EGFR signalling through integrin-alpha1beta1-
RT mediated activation of protein tyrosine phosphatase TCPTP.";
RL Nat. Cell Biol. 7:78-85(2005).
RN [6]
RP INTERACTION WITH RAB21.
RX PubMed=16754960; DOI=10.1083/jcb.200509019;
RA Pellinen T., Arjonen A., Vuoriluoto K., Kallio K., Fransen J.A.M.,
RA Ivaska J.;
RT "Small GTPase Rab21 regulates cell adhesion and controls endosomal
RT traffic of beta1-integrins.";
RL J. Cell Biol. 173:767-780(2006).
RN [7]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-100; ASN-105; ASN-217;
RP ASN-341; ASN-418; ASN-460; ASN-532; ASN-780; ASN-840; ASN-966; ASN-974
RP AND ASN-1008, AND MASS SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of
RT multiple enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 168-359.
RX PubMed=10455165; DOI=10.1074/jbc.274.35.24906;
RA Rich R.L., Deivanayagam C.C., Owens R.T., Carson M., Hook A.,
RA Moore D., Symersky J., Yang V.W., Narayana S.V., Hook M.;
RT "Trench-shaped binding sites promote multiple classes of interactions
RT between collagen and the adherence receptors, alpha(1)beta(1) integrin
RT and Staphylococcus aureus cna MSCRAMM.";
RL J. Biol. Chem. 274:24906-24913(1999).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.87 ANGSTROMS) OF 166-356.
RX PubMed=14660600; DOI=10.1074/jbc.M312912200;
RA Nymalm Y., Puranen J.S., Nyholm T.K., Kapyla J., Kidron H.,
RA Pentikainen O.T., Airenne T.T., Heino J., Slotte J.P., Johnson M.S.,
RA Salminen T.A.;
RT "Jararhagin-derived RKKH peptides induce structural changes in alpha1I
RT domain of human integrin alpha1beta1.";
RL J. Biol. Chem. 279:7962-7970(2004).
CC -!- FUNCTION: Integrin alpha-1/beta-1 is a receptor for laminin and
CC collagen. It recognizes the proline-hydroxylated sequence G-F-P-G-
CC E-R in collagen. Involved in anchorage-dependent, negative
CC regulation of EGF-stimulated cell growth.
CC -!- SUBUNIT: Heterodimer of an alpha and a beta subunit. Alpha-1
CC associates with beta-1. Interacts with RAB21. Interacts (via
CC cytoplasmic domain) with PTPN2; activates PTPN2 phosphatase
CC activity towards EGFR and negatively regulates EGF signaling.
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane
CC protein.
CC -!- DOMAIN: The integrin I-domain (insert) is a VWFA domain. Integrins
CC with I-domains do not undergo protease cleavage.
CC -!- SIMILARITY: Belongs to the integrin alpha chain family.
CC -!- SIMILARITY: Contains 7 FG-GAP repeats.
CC -!- SIMILARITY: Contains 1 VWFA domain.
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DR EMBL; AC027326; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC022133; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC025180; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC137121; AAI37122.1; -; mRNA.
DR EMBL; BC137122; AAI37123.1; -; mRNA.
DR EMBL; X68742; -; NOT_ANNOTATED_CDS; mRNA.
DR PIR; A45226; A45226.
DR RefSeq; NP_852478.1; NM_181501.1.
DR UniGene; Hs.644352; -.
DR PDB; 1PT6; X-ray; 1.87 A; A/B=166-366.
DR PDB; 1QC5; X-ray; 2.00 A; A/B=168-359.
DR PDB; 1QCY; X-ray; 2.30 A; A=169-361.
DR PDB; 2L8S; NMR; -; A=1135-1179.
DR PDB; 2M32; NMR; -; A=168-359.
DR PDB; 4A0Q; X-ray; 1.90 A; A/B=168-366.
DR PDBsum; 1PT6; -.
DR PDBsum; 1QC5; -.
DR PDBsum; 1QCY; -.
DR PDBsum; 2L8S; -.
DR PDBsum; 2M32; -.
DR PDBsum; 4A0Q; -.
DR ProteinModelPortal; P56199; -.
DR SMR; P56199; 29-167, 170-359, 371-1081, 1135-1179.
DR DIP; DIP-206N; -.
DR IntAct; P56199; 6.
DR MINT; MINT-7004837; -.
DR STRING; 9606.ENSP00000282588; -.
DR BindingDB; P56199; -.
DR ChEMBL; CHEMBL3682; -.
DR PhosphoSite; P56199; -.
DR DMDM; 124056463; -.
DR PaxDb; P56199; -.
DR PRIDE; P56199; -.
DR Ensembl; ENST00000282588; ENSP00000282588; ENSG00000213949.
DR GeneID; 3672; -.
DR KEGG; hsa:3672; -.
DR UCSC; uc003jou.3; human.
DR CTD; 3672; -.
DR GeneCards; GC05P052083; -.
DR HGNC; HGNC:6134; ITGA1.
DR HPA; HPA042555; -.
DR MIM; 192968; gene.
DR neXtProt; NX_P56199; -.
DR PharmGKB; PA29935; -.
DR eggNOG; NOG322251; -.
DR HOGENOM; HOG000059610; -.
DR HOVERGEN; HBG006185; -.
DR InParanoid; P56199; -.
DR KO; K06480; -.
DR OMA; QRFSIAI; -.
DR OrthoDB; EOG7GBFW6; -.
DR PhylomeDB; P56199; -.
DR Reactome; REACT_111045; Developmental Biology.
DR Reactome; REACT_118779; Extracellular matrix organization.
DR Reactome; REACT_17044; Muscle contraction.
DR Reactome; REACT_604; Hemostasis.
DR SignaLink; P56199; -.
DR EvolutionaryTrace; P56199; -.
DR GeneWiki; CD49a; -.
DR GenomeRNAi; 3672; -.
DR NextBio; 14373; -.
DR PRO; PR:P56199; -.
DR Bgee; P56199; -.
DR Genevestigator; P56199; -.
DR GO; GO:0001669; C:acrosomal vesicle; IEA:Ensembl.
DR GO; GO:0045178; C:basal part of cell; IEA:Ensembl.
DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl.
DR GO; GO:0008305; C:integrin complex; TAS:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IEA:Ensembl.
DR GO; GO:0043005; C:neuron projection; IEA:Ensembl.
DR GO; GO:0043204; C:perikaryon; IEA:Ensembl.
DR GO; GO:0005518; F:collagen binding; TAS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000187; P:activation of MAPK activity; IEA:Ensembl.
DR GO; GO:0007411; P:axon guidance; TAS:Reactome.
DR GO; GO:0007160; P:cell-matrix adhesion; NAS:UniProtKB.
DR GO; GO:0045123; P:cellular extravasation; IEA:Ensembl.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0006936; P:muscle contraction; TAS:Reactome.
DR GO; GO:0008285; P:negative regulation of cell proliferation; IMP:UniProtKB.
DR GO; GO:0042059; P:negative regulation of epidermal growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0030593; P:neutrophil chemotaxis; IEA:Ensembl.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0032516; P:positive regulation of phosphoprotein phosphatase activity; IDA:UniProtKB.
DR GO; GO:0042311; P:vasodilation; IEA:Ensembl.
DR InterPro; IPR013517; FG-GAP.
DR InterPro; IPR013519; Int_alpha_beta-p.
DR InterPro; IPR000413; Integrin_alpha.
DR InterPro; IPR013649; Integrin_alpha-2.
DR InterPro; IPR018184; Integrin_alpha_C_CS.
DR InterPro; IPR002035; VWF_A.
DR Pfam; PF01839; FG-GAP; 1.
DR Pfam; PF08441; Integrin_alpha2; 1.
DR Pfam; PF00092; VWA; 1.
DR PRINTS; PR01185; INTEGRINA.
DR SMART; SM00191; Int_alpha; 5.
DR SMART; SM00327; VWA; 1.
DR PROSITE; PS51470; FG_GAP; 7.
DR PROSITE; PS00242; INTEGRIN_ALPHA; 1.
DR PROSITE; PS50234; VWFA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Cell adhesion; Complete proteome;
KW Disulfide bond; Glycoprotein; Integrin; Magnesium; Membrane;
KW Metal-binding; Polymorphism; Receptor; Reference proteome; Repeat;
KW Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1 28 Potential.
FT CHAIN 29 1179 Integrin alpha-1.
FT /FTId=PRO_0000174215.
FT TOPO_DOM 29 1141 Extracellular (Potential).
FT TRANSMEM 1142 1164 Helical; (Potential).
FT TOPO_DOM 1165 1179 Cytoplasmic (Potential).
FT REPEAT 30 91 FG-GAP 1.
FT REPEAT 101 160 FG-GAP 2.
FT DOMAIN 161 360 VWFA.
FT REPEAT 365 417 FG-GAP 3.
FT REPEAT 422 475 FG-GAP 4.
FT REPEAT 476 538 FG-GAP 5.
FT REPEAT 557 615 FG-GAP 6.
FT REPEAT 619 679 FG-GAP 7.
FT CA_BIND 498 506 Potential.
FT CA_BIND 580 588 Potential.
FT CA_BIND 642 650 Potential.
FT MOTIF 1167 1171 GFFKR motif.
FT CARBOHYD 74 74 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 100 100 N-linked (GlcNAc...).
FT CARBOHYD 105 105 N-linked (GlcNAc...).
FT CARBOHYD 112 112 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 217 217 N-linked (GlcNAc...).
FT CARBOHYD 317 317 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 341 341 N-linked (GlcNAc...).
FT CARBOHYD 402 402 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 418 418 N-linked (GlcNAc...).
FT CARBOHYD 460 460 N-linked (GlcNAc...).
FT CARBOHYD 532 532 N-linked (GlcNAc...).
FT CARBOHYD 699 699 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 748 748 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 780 780 N-linked (GlcNAc...).
FT CARBOHYD 840 840 N-linked (GlcNAc...).
FT CARBOHYD 883 883 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 908 908 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 915 915 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 939 939 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 966 966 N-linked (GlcNAc...).
FT CARBOHYD 974 974 N-linked (GlcNAc...).
FT CARBOHYD 1008 1008 N-linked (GlcNAc...).
FT CARBOHYD 1073 1073 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1083 1083 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1102 1102 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1113 1113 N-linked (GlcNAc...) (Potential).
FT DISULFID 82 92 By similarity.
FT DISULFID 688 697 By similarity.
FT DISULFID 703 756 By similarity.
FT DISULFID 808 814 By similarity.
FT DISULFID 878 886 By similarity.
FT DISULFID 1030 1062 By similarity.
FT DISULFID 1065 1072 By similarity.
FT VARIANT 480 480 T -> M (in dbSNP:rs4145748).
FT /FTId=VAR_034022.
FT VARIANT 670 670 V -> I (in dbSNP:rs2279587).
FT /FTId=VAR_049630.
FT VARIANT 961 961 I -> M (in dbSNP:rs12520591).
FT /FTId=VAR_034023.
FT VARIANT 1108 1108 E -> G (in dbSNP:rs988574).
FT /FTId=VAR_034024.
FT CONFLICT 198 198 E -> K (in Ref. 3).
FT CONFLICT 254 254 I -> T (in Ref. 3).
FT CONFLICT 705 705 D -> E (in Ref. 3).
FT STRAND 171 178
FT HELIX 186 197
FT STRAND 206 222
FT TURN 224 226
FT HELIX 230 238
FT HELIX 250 259
FT TURN 260 262
FT HELIX 264 266
FT STRAND 273 282
FT HELIX 288 299
FT STRAND 302 309
FT HELIX 311 315
FT HELIX 321 330
FT HELIX 335 338
FT STRAND 339 344
FT HELIX 345 351
FT HELIX 352 359
FT HELIX 1143 1168
SQ SEQUENCE 1179 AA; 130848 MW; 1A86F30FD916C845 CRC64;
MAPRPRARPG VAVACCWLLT VVLRCCVSFN VDVKNSMTFS GPVEDMFGYT VQQYENEEGK
WVLIGSPLVG QPKNRTGDVY KCPVGRGESL PCVKLDLPVN TSIPNVTEVK ENMTFGSTLV
TNPNGGFLAC GPLYAYRCGH LHYTTGICSD VSPTFQVVNS IAPVQECSTQ LDIVIVLDGS
NSIYPWDSVT AFLNDLLERM DIGPKQTQVG IVQYGENVTH EFNLNKYSST EEVLVAAKKI
VQRGGRQTMT ALGIDTARKE AFTEARGARR GVKKVMVIVT DGESHDNHRL KKVIQDCEDE
NIQRFSIAIL GSYNRGNLST EKFVEEIKSI ASEPTEKHFF NVSDELALVT IVKTLGERIF
ALEATADQSA ASFEMEMSQT GFSAHYSQDW VMLGAVGAYD WNGTVVMQKA SQIIIPRNTT
FNVESTKKNE PLASYLGYTV NSATASSGDV LYIAGQPRYN HTGQVIIYRM EDGNIKILQT
LSGEQIGSYF GSILTTTDID KDSNTDILLV GAPMYMGTEK EEQGKVYVYA LNQTRFEYQM
SLEPIKQTCC SSRQHNSCTT ENKNEPCGAR FGTAIAAVKD LNLDGFNDIV IGAPLEDDHG
GAVYIYHGSG KTIRKEYAQR IPSGGDGKTL KFFGQSIHGE MDLNGDGLTD VTIGGLGGAA
LFWSRDVAVV KVTMNFEPNK VNIQKKNCHM EGKETVCINA TVCFDVKLKS KEDTIYEADL
QYRVTLDSLR QISRSFFSGT QERKVQRNIT VRKSECTKHS FYMLDKHDFQ DSVRITLDFN
LTDPENGPVL DDSLPNSVHE YIPFAKDCGN KEKCISDLSL HVATTEKDLL IVRSQNDKFN
VSLTVKNTKD SAYNTRTIVH YSPNLVFSGI EAIQKDSCES NHNITCKVGY PFLRRGEMVT
FKILFQFNTS YLMENVTIYL SATSDSEEPP ETLSDNVVNI SIPVKYEVGL QFYSSASEYH
ISIAANETVP EVINSTEDIG NEINIFYLIR KSGSFPMPEL KLSISFPNMT SNGYPVLYPT
GLSSSENANC RPHIFEDPFS INSGKKMTTS TDHLKRGTIL DCNTCKFATI TCNLTSSDIS
QVNVSLILWK PTFIKSYFSS LNLTIRGELR SENASLVLSS SNQKRELAIQ ISKDGLPGRV
PLWVILLSAF AGLLLLMLLI LALWKIGFFK RPLKKKMEK
//
ID ITA1_HUMAN Reviewed; 1179 AA.
AC P56199; B2RNU0;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 143.
DE RecName: Full=Integrin alpha-1;
DE AltName: Full=CD49 antigen-like family member A;
DE AltName: Full=Laminin and collagen receptor;
DE AltName: Full=VLA-1;
DE AltName: CD_antigen=CD49a;
DE Flags: Precursor;
GN Name=ITGA1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T.,
RA Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M.,
RA Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K.,
RA Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C.,
RA Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M.,
RA Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A.,
RA Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M.,
RA Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S.,
RA Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 29-1179.
RX PubMed=8428973;
RA Briesewitz R., Epstein M.R., Marcantonio E.E.;
RT "Expression of native and truncated forms of the human integrin alpha
RT 1 subunit.";
RL J. Biol. Chem. 268:2989-2996(1993).
RN [4]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-532, AND MASS
RP SPECTROMETRY.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E.,
RA Moore R.J., Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [5]
RP FUNCTION IN EGFR SIGNALING, AND INTERACTION WITH PTPN2.
RX PubMed=15592458; DOI=10.1038/ncb1209;
RA Mattila E., Pellinen T., Nevo J., Vuoriluoto K., Arjonen A.,
RA Ivaska J.;
RT "Negative regulation of EGFR signalling through integrin-alpha1beta1-
RT mediated activation of protein tyrosine phosphatase TCPTP.";
RL Nat. Cell Biol. 7:78-85(2005).
RN [6]
RP INTERACTION WITH RAB21.
RX PubMed=16754960; DOI=10.1083/jcb.200509019;
RA Pellinen T., Arjonen A., Vuoriluoto K., Kallio K., Fransen J.A.M.,
RA Ivaska J.;
RT "Small GTPase Rab21 regulates cell adhesion and controls endosomal
RT traffic of beta1-integrins.";
RL J. Cell Biol. 173:767-780(2006).
RN [7]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-100; ASN-105; ASN-217;
RP ASN-341; ASN-418; ASN-460; ASN-532; ASN-780; ASN-840; ASN-966; ASN-974
RP AND ASN-1008, AND MASS SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of
RT multiple enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 168-359.
RX PubMed=10455165; DOI=10.1074/jbc.274.35.24906;
RA Rich R.L., Deivanayagam C.C., Owens R.T., Carson M., Hook A.,
RA Moore D., Symersky J., Yang V.W., Narayana S.V., Hook M.;
RT "Trench-shaped binding sites promote multiple classes of interactions
RT between collagen and the adherence receptors, alpha(1)beta(1) integrin
RT and Staphylococcus aureus cna MSCRAMM.";
RL J. Biol. Chem. 274:24906-24913(1999).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.87 ANGSTROMS) OF 166-356.
RX PubMed=14660600; DOI=10.1074/jbc.M312912200;
RA Nymalm Y., Puranen J.S., Nyholm T.K., Kapyla J., Kidron H.,
RA Pentikainen O.T., Airenne T.T., Heino J., Slotte J.P., Johnson M.S.,
RA Salminen T.A.;
RT "Jararhagin-derived RKKH peptides induce structural changes in alpha1I
RT domain of human integrin alpha1beta1.";
RL J. Biol. Chem. 279:7962-7970(2004).
CC -!- FUNCTION: Integrin alpha-1/beta-1 is a receptor for laminin and
CC collagen. It recognizes the proline-hydroxylated sequence G-F-P-G-
CC E-R in collagen. Involved in anchorage-dependent, negative
CC regulation of EGF-stimulated cell growth.
CC -!- SUBUNIT: Heterodimer of an alpha and a beta subunit. Alpha-1
CC associates with beta-1. Interacts with RAB21. Interacts (via
CC cytoplasmic domain) with PTPN2; activates PTPN2 phosphatase
CC activity towards EGFR and negatively regulates EGF signaling.
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane
CC protein.
CC -!- DOMAIN: The integrin I-domain (insert) is a VWFA domain. Integrins
CC with I-domains do not undergo protease cleavage.
CC -!- SIMILARITY: Belongs to the integrin alpha chain family.
CC -!- SIMILARITY: Contains 7 FG-GAP repeats.
CC -!- SIMILARITY: Contains 1 VWFA domain.
CC -----------------------------------------------------------------------
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DR EMBL; AC027326; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC022133; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC025180; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC137121; AAI37122.1; -; mRNA.
DR EMBL; BC137122; AAI37123.1; -; mRNA.
DR EMBL; X68742; -; NOT_ANNOTATED_CDS; mRNA.
DR PIR; A45226; A45226.
DR RefSeq; NP_852478.1; NM_181501.1.
DR UniGene; Hs.644352; -.
DR PDB; 1PT6; X-ray; 1.87 A; A/B=166-366.
DR PDB; 1QC5; X-ray; 2.00 A; A/B=168-359.
DR PDB; 1QCY; X-ray; 2.30 A; A=169-361.
DR PDB; 2L8S; NMR; -; A=1135-1179.
DR PDB; 2M32; NMR; -; A=168-359.
DR PDB; 4A0Q; X-ray; 1.90 A; A/B=168-366.
DR PDBsum; 1PT6; -.
DR PDBsum; 1QC5; -.
DR PDBsum; 1QCY; -.
DR PDBsum; 2L8S; -.
DR PDBsum; 2M32; -.
DR PDBsum; 4A0Q; -.
DR ProteinModelPortal; P56199; -.
DR SMR; P56199; 29-167, 170-359, 371-1081, 1135-1179.
DR DIP; DIP-206N; -.
DR IntAct; P56199; 6.
DR MINT; MINT-7004837; -.
DR STRING; 9606.ENSP00000282588; -.
DR BindingDB; P56199; -.
DR ChEMBL; CHEMBL3682; -.
DR PhosphoSite; P56199; -.
DR DMDM; 124056463; -.
DR PaxDb; P56199; -.
DR PRIDE; P56199; -.
DR Ensembl; ENST00000282588; ENSP00000282588; ENSG00000213949.
DR GeneID; 3672; -.
DR KEGG; hsa:3672; -.
DR UCSC; uc003jou.3; human.
DR CTD; 3672; -.
DR GeneCards; GC05P052083; -.
DR HGNC; HGNC:6134; ITGA1.
DR HPA; HPA042555; -.
DR MIM; 192968; gene.
DR neXtProt; NX_P56199; -.
DR PharmGKB; PA29935; -.
DR eggNOG; NOG322251; -.
DR HOGENOM; HOG000059610; -.
DR HOVERGEN; HBG006185; -.
DR InParanoid; P56199; -.
DR KO; K06480; -.
DR OMA; QRFSIAI; -.
DR OrthoDB; EOG7GBFW6; -.
DR PhylomeDB; P56199; -.
DR Reactome; REACT_111045; Developmental Biology.
DR Reactome; REACT_118779; Extracellular matrix organization.
DR Reactome; REACT_17044; Muscle contraction.
DR Reactome; REACT_604; Hemostasis.
DR SignaLink; P56199; -.
DR EvolutionaryTrace; P56199; -.
DR GeneWiki; CD49a; -.
DR GenomeRNAi; 3672; -.
DR NextBio; 14373; -.
DR PRO; PR:P56199; -.
DR Bgee; P56199; -.
DR Genevestigator; P56199; -.
DR GO; GO:0001669; C:acrosomal vesicle; IEA:Ensembl.
DR GO; GO:0045178; C:basal part of cell; IEA:Ensembl.
DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl.
DR GO; GO:0008305; C:integrin complex; TAS:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IEA:Ensembl.
DR GO; GO:0043005; C:neuron projection; IEA:Ensembl.
DR GO; GO:0043204; C:perikaryon; IEA:Ensembl.
DR GO; GO:0005518; F:collagen binding; TAS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000187; P:activation of MAPK activity; IEA:Ensembl.
DR GO; GO:0007411; P:axon guidance; TAS:Reactome.
DR GO; GO:0007160; P:cell-matrix adhesion; NAS:UniProtKB.
DR GO; GO:0045123; P:cellular extravasation; IEA:Ensembl.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0006936; P:muscle contraction; TAS:Reactome.
DR GO; GO:0008285; P:negative regulation of cell proliferation; IMP:UniProtKB.
DR GO; GO:0042059; P:negative regulation of epidermal growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0030593; P:neutrophil chemotaxis; IEA:Ensembl.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0032516; P:positive regulation of phosphoprotein phosphatase activity; IDA:UniProtKB.
DR GO; GO:0042311; P:vasodilation; IEA:Ensembl.
DR InterPro; IPR013517; FG-GAP.
DR InterPro; IPR013519; Int_alpha_beta-p.
DR InterPro; IPR000413; Integrin_alpha.
DR InterPro; IPR013649; Integrin_alpha-2.
DR InterPro; IPR018184; Integrin_alpha_C_CS.
DR InterPro; IPR002035; VWF_A.
DR Pfam; PF01839; FG-GAP; 1.
DR Pfam; PF08441; Integrin_alpha2; 1.
DR Pfam; PF00092; VWA; 1.
DR PRINTS; PR01185; INTEGRINA.
DR SMART; SM00191; Int_alpha; 5.
DR SMART; SM00327; VWA; 1.
DR PROSITE; PS51470; FG_GAP; 7.
DR PROSITE; PS00242; INTEGRIN_ALPHA; 1.
DR PROSITE; PS50234; VWFA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Cell adhesion; Complete proteome;
KW Disulfide bond; Glycoprotein; Integrin; Magnesium; Membrane;
KW Metal-binding; Polymorphism; Receptor; Reference proteome; Repeat;
KW Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1 28 Potential.
FT CHAIN 29 1179 Integrin alpha-1.
FT /FTId=PRO_0000174215.
FT TOPO_DOM 29 1141 Extracellular (Potential).
FT TRANSMEM 1142 1164 Helical; (Potential).
FT TOPO_DOM 1165 1179 Cytoplasmic (Potential).
FT REPEAT 30 91 FG-GAP 1.
FT REPEAT 101 160 FG-GAP 2.
FT DOMAIN 161 360 VWFA.
FT REPEAT 365 417 FG-GAP 3.
FT REPEAT 422 475 FG-GAP 4.
FT REPEAT 476 538 FG-GAP 5.
FT REPEAT 557 615 FG-GAP 6.
FT REPEAT 619 679 FG-GAP 7.
FT CA_BIND 498 506 Potential.
FT CA_BIND 580 588 Potential.
FT CA_BIND 642 650 Potential.
FT MOTIF 1167 1171 GFFKR motif.
FT CARBOHYD 74 74 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 100 100 N-linked (GlcNAc...).
FT CARBOHYD 105 105 N-linked (GlcNAc...).
FT CARBOHYD 112 112 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 217 217 N-linked (GlcNAc...).
FT CARBOHYD 317 317 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 341 341 N-linked (GlcNAc...).
FT CARBOHYD 402 402 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 418 418 N-linked (GlcNAc...).
FT CARBOHYD 460 460 N-linked (GlcNAc...).
FT CARBOHYD 532 532 N-linked (GlcNAc...).
FT CARBOHYD 699 699 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 748 748 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 780 780 N-linked (GlcNAc...).
FT CARBOHYD 840 840 N-linked (GlcNAc...).
FT CARBOHYD 883 883 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 908 908 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 915 915 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 939 939 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 966 966 N-linked (GlcNAc...).
FT CARBOHYD 974 974 N-linked (GlcNAc...).
FT CARBOHYD 1008 1008 N-linked (GlcNAc...).
FT CARBOHYD 1073 1073 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1083 1083 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1102 1102 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1113 1113 N-linked (GlcNAc...) (Potential).
FT DISULFID 82 92 By similarity.
FT DISULFID 688 697 By similarity.
FT DISULFID 703 756 By similarity.
FT DISULFID 808 814 By similarity.
FT DISULFID 878 886 By similarity.
FT DISULFID 1030 1062 By similarity.
FT DISULFID 1065 1072 By similarity.
FT VARIANT 480 480 T -> M (in dbSNP:rs4145748).
FT /FTId=VAR_034022.
FT VARIANT 670 670 V -> I (in dbSNP:rs2279587).
FT /FTId=VAR_049630.
FT VARIANT 961 961 I -> M (in dbSNP:rs12520591).
FT /FTId=VAR_034023.
FT VARIANT 1108 1108 E -> G (in dbSNP:rs988574).
FT /FTId=VAR_034024.
FT CONFLICT 198 198 E -> K (in Ref. 3).
FT CONFLICT 254 254 I -> T (in Ref. 3).
FT CONFLICT 705 705 D -> E (in Ref. 3).
FT STRAND 171 178
FT HELIX 186 197
FT STRAND 206 222
FT TURN 224 226
FT HELIX 230 238
FT HELIX 250 259
FT TURN 260 262
FT HELIX 264 266
FT STRAND 273 282
FT HELIX 288 299
FT STRAND 302 309
FT HELIX 311 315
FT HELIX 321 330
FT HELIX 335 338
FT STRAND 339 344
FT HELIX 345 351
FT HELIX 352 359
FT HELIX 1143 1168
SQ SEQUENCE 1179 AA; 130848 MW; 1A86F30FD916C845 CRC64;
MAPRPRARPG VAVACCWLLT VVLRCCVSFN VDVKNSMTFS GPVEDMFGYT VQQYENEEGK
WVLIGSPLVG QPKNRTGDVY KCPVGRGESL PCVKLDLPVN TSIPNVTEVK ENMTFGSTLV
TNPNGGFLAC GPLYAYRCGH LHYTTGICSD VSPTFQVVNS IAPVQECSTQ LDIVIVLDGS
NSIYPWDSVT AFLNDLLERM DIGPKQTQVG IVQYGENVTH EFNLNKYSST EEVLVAAKKI
VQRGGRQTMT ALGIDTARKE AFTEARGARR GVKKVMVIVT DGESHDNHRL KKVIQDCEDE
NIQRFSIAIL GSYNRGNLST EKFVEEIKSI ASEPTEKHFF NVSDELALVT IVKTLGERIF
ALEATADQSA ASFEMEMSQT GFSAHYSQDW VMLGAVGAYD WNGTVVMQKA SQIIIPRNTT
FNVESTKKNE PLASYLGYTV NSATASSGDV LYIAGQPRYN HTGQVIIYRM EDGNIKILQT
LSGEQIGSYF GSILTTTDID KDSNTDILLV GAPMYMGTEK EEQGKVYVYA LNQTRFEYQM
SLEPIKQTCC SSRQHNSCTT ENKNEPCGAR FGTAIAAVKD LNLDGFNDIV IGAPLEDDHG
GAVYIYHGSG KTIRKEYAQR IPSGGDGKTL KFFGQSIHGE MDLNGDGLTD VTIGGLGGAA
LFWSRDVAVV KVTMNFEPNK VNIQKKNCHM EGKETVCINA TVCFDVKLKS KEDTIYEADL
QYRVTLDSLR QISRSFFSGT QERKVQRNIT VRKSECTKHS FYMLDKHDFQ DSVRITLDFN
LTDPENGPVL DDSLPNSVHE YIPFAKDCGN KEKCISDLSL HVATTEKDLL IVRSQNDKFN
VSLTVKNTKD SAYNTRTIVH YSPNLVFSGI EAIQKDSCES NHNITCKVGY PFLRRGEMVT
FKILFQFNTS YLMENVTIYL SATSDSEEPP ETLSDNVVNI SIPVKYEVGL QFYSSASEYH
ISIAANETVP EVINSTEDIG NEINIFYLIR KSGSFPMPEL KLSISFPNMT SNGYPVLYPT
GLSSSENANC RPHIFEDPFS INSGKKMTTS TDHLKRGTIL DCNTCKFATI TCNLTSSDIS
QVNVSLILWK PTFIKSYFSS LNLTIRGELR SENASLVLSS SNQKRELAIQ ISKDGLPGRV
PLWVILLSAF AGLLLLMLLI LALWKIGFFK RPLKKKMEK
//
MIM
192968
*RECORD*
*FIELD* NO
192968
*FIELD* TI
*192968 INTEGRIN, ALPHA-1; ITGA1
;;VERY LATE ACTIVATION PROTEIN 1; VLA1
*FIELD* TX
read more
DESCRIPTION
The integrin alpha-1 chain associates with the beta-1 chain (ITGB1;
135630) to form a heterodimer that functions as a dual laminin/collagen
receptor in neural cells and hematopoietic cells. It has a role in cell
attachment and neurite outgrowth on laminin (see 150325) and collagen as
well as in peripheral nerve regeneration (Douville et al., 1992).
CLONING
By screening a human hepatoblastoma cell line cDNA library with a rat
Itga1 probe, followed by 5-prime RACE, Briesewitz et al. (1993) cloned
an ITGA1 cDNA encoding all of the ITGA1 protein except for the complete
N-terminal signal sequence. The deduced protein contains 1,152 amino
acids, including the expected 28-amino acid N-terminal signal sequence.
ITGA1 has a 206-amino acid I domain in its N-terminal half, followed by
3 divalent cation-binding sites and a C-terminal transmembrane domain
with a short cytoplasmic tail. It also has 28 potential N-glycosylation
sites. Human ITGA1 was expressed in a mouse fibroblast cell line as a
180-kD protein.
GENE FUNCTION
Briesewitz et al. (1993) demonstrated that a truncated, soluble form of
human ITGA1 assembled with truncated soluble forms of chicken or human
ITGB1 (135630) in heterodimeric complexes following cotransfection into
a mouse fibroblast cell line. Secretion of truncated ITGA1 into the
medium was dependent upon heterodimerization with soluble ITGB1. The
soluble heterodimer bound immobilized collagen IV (see COL4A1; 120130)
in an in vitro binding assay, and binding required Mg(2+). Biosynthetic
studies using stably expressing cell lines demonstrated that the soluble
heterodimers and the native heterodimers were formed independently,
suggesting that the transmembrane or cytoplasmic domains of the alpha
and beta subunits are involved in the assembly of native heterodimers.
Suzuki et al. (2007) demonstrated that semaphorin 7A (SRMA7A; 607961),
which is expressed on activated T cells, stimulates cytokine production
in monocytes and macrophages through alpha-1-beta-1 integrin (also known
as very late antigen-1) as a component of the immunologic synapse, and
is critical for the effector phase of the inflammatory immune response.
Sema7A-null mice are defective in cell-mediated immune responses such as
contact hypersensitivity and experimental autoimmune encephalomyelitis.
Although antigen-specific and cytokine-producing effector T cells could
develop and migrate into antigen-challenged sites in Sema7a-null mice,
Sema7a-null T cells failed to induce contact hypersensitivity even when
directly injected into the antigen-challenged sites. Thus, Suzuki et al.
(2007) concluded that the interaction between SEMA7A and alpha-1-beta-1
integrin is crucial at the site of inflammation.
Conrad et al. (2007) showed that blocking the interaction of
alpha-1-beta-1 integrin (VLA-1) with collagen prevented accumulation of
epidermal T cells and immunopathology of psoriasis (177900).
Alpha-1-beta-1 integrin, a major collagen-binding surface receptor, was
exclusively expressed by epidermal but not dermal T cells.
Alpha-1-beta-1-positive T cells showed characteristic surface markers of
effector memory cells and contained high levels of interferon-gamma
(147570) but not interleukin-4 (147780). Blockade of alpha-1-beta-1
inhibited migration of T cells into the epidermis in a clinically
relevant xenotransplantation model. This was paralleled by a complete
inhibition of psoriasis development, comparable to that caused by tumor
necrosis factor-alpha (TNFA; 191160) blockers. Conrad et al. (2007)
concluded that their results defined a crucial role for alpha-1-beta-1
in controlling the accumulation of epidermal type 1 polarized effector
memory T cells in a common human immunopathology and provided the basis
for new strategies in psoriasis treatment focusing on T
cell-extracellular matrix interactions.
MAPPING
Douville et al. (1992) used an interspecies backcross gene-mapping
strategy to locate the Vla1 gene to mouse chromosome 13, 3.5 cM distal
to Ctla3 (140050). The mapping to chromosome 13 was confirmed in
recombinant inbred (RI) mice. Since the CTLA3 gene is on human
chromosome 5, it is likely that the human VLA1 gene is likewise on
chromosome 5.
ANIMAL MODEL
Ekholm et al. (2002) studied the regeneration of a fractured long bone
in alpha-1-null mice. The null mice developed significantly less callus
tissue than the wildtype mice and displayed a defect in cartilage
formation. During the first 9 days of healing, the mRNA levels of
cartilage-related genes, including several collagen genes, were lower in
alpha-1-null mice than in wildtype mice, consistent with the reduced
synthesis of cartilaginous matrix seen in tissue sections. There were
fewer chondrocytes in the alpha-1-null callus as well as a reduction of
mesenchymal progenitors at the callus site. Ekholm et al. (2002)
concluded that proper collagen-integrin interaction is important in
fracture healing and suggested that alpha-1 integrin plays an essential
role in the regulation of mesenchymal stem cell proliferation and
cartilage production.
Zemmyo et al. (2003) developed alpha-1 integrin-null mice and compared
their knee joints to those of wildtype mice at ages 4 to 15 months. In
wildtype mice, the alpha-1 integrin subunit was detected in hypertrophic
chondrocytes in the growth plate and in a subpopulation of cells in the
deep zone of articular cartilage. There was a marked increase in
alpha-1-positive chondrocytes in the superficial and upper mid-zones in
osteoarthritis-affected areas in joints from old wildtype mice. The
alpha-1-null mice showed more severe cartilage degradation, glycosamine
depletion, and synovial hyperplasia as compared with the wildtype mice.
In cartilage from alpha-1-null mice, the cellularity was reduced and the
frequency of apoptotic cells was increased. Zemmyo et al. (2003)
suggested that the alpha-1 integrin subunit is involved in the early
remodeling process in osteoarthritic cartilage.
*FIELD* RF
1. Briesewitz, R.; Epstein, M. R.; Marcantonio, E. E.: Expression
of native and truncated forms of the human integrin alpha-1 subunit. J.
Biol. Chem. 268: 2989-2996, 1993.
2. Conrad, C.; Boyman, O.; Tonel, G.; Tun-Kyi, A.; Laggner, U.; de
Fougerolles, A.; Kotelianski, V.; Gardner, H.; Nestle, F. O.: Alpha-1-beta-1
integrin is crucial for accumulation of epidermal T cells and the
development of psoriasis. Nature Med. 13: 836-841, 2007.
3. Douville, P.; Seldin, M. F.; Carbonetto, S.: Genetic mapping of
the integrin alpha-1 gene (Vla1) to mouse chromosome 13. Genomics 14:
503-505, 1992.
4. Ekholm, E.; Hankenson, K. D.; Uusitalo, H.; Hiltunen, A.; Gardner,
H.; Heino, J.; Penttinen, R.: Diminished callus size and cartilage
synthesis in alpha-1 beta-1 integrin-deficient mice during bone fracture
healing. Am. J. Path. 160: 1779-1785, 2002.
5. Suzuki, K.; Okuno, T.; Yamamoto, M.; Pasterkamp, R. J.; Takegahara,
N.; Takamatsu, H.; Kitao, T.; Takagi, J.; Rennert, P. D.; Kolodkin,
A. L.; Kumanogoh, A.; Kikutani, H.: Semaphorin 7A initiates T-cell-mediated
inflammatory responses through alpha-1-beta-1 integrin. Nature 446:
680-684, 2007.
6. Zemmyo, M.; Meharra, E. J.; Kuhn, K.; Creighton-Achermann, L.;
Lotz, M.: Accelerated, aging-dependent development of osteoarthritis
in alpha-1 integrin-deficient mice. Arthritis Rheum. 48: 2873-2880,
2003.
*FIELD* CN
Ada Hamosh - updated: 2/25/2008
Ada Hamosh - updated: 4/27/2007
Patricia A. Hartz - updated: 10/26/2004
Marla J. F. O'Neill - updated: 9/8/2004
Marla J. F. O'Neill - updated: 9/1/2004
*FIELD* CD
Victor A. McKusick: 10/15/1992
*FIELD* ED
alopez: 03/03/2008
alopez: 3/3/2008
terry: 2/25/2008
alopez: 5/10/2007
terry: 4/27/2007
terry: 4/4/2005
mgross: 10/26/2004
carol: 9/8/2004
carol: 9/2/2004
terry: 9/1/2004
dkim: 9/9/1998
mark: 6/12/1997
carol: 10/15/1992
*RECORD*
*FIELD* NO
192968
*FIELD* TI
*192968 INTEGRIN, ALPHA-1; ITGA1
;;VERY LATE ACTIVATION PROTEIN 1; VLA1
*FIELD* TX
read more
DESCRIPTION
The integrin alpha-1 chain associates with the beta-1 chain (ITGB1;
135630) to form a heterodimer that functions as a dual laminin/collagen
receptor in neural cells and hematopoietic cells. It has a role in cell
attachment and neurite outgrowth on laminin (see 150325) and collagen as
well as in peripheral nerve regeneration (Douville et al., 1992).
CLONING
By screening a human hepatoblastoma cell line cDNA library with a rat
Itga1 probe, followed by 5-prime RACE, Briesewitz et al. (1993) cloned
an ITGA1 cDNA encoding all of the ITGA1 protein except for the complete
N-terminal signal sequence. The deduced protein contains 1,152 amino
acids, including the expected 28-amino acid N-terminal signal sequence.
ITGA1 has a 206-amino acid I domain in its N-terminal half, followed by
3 divalent cation-binding sites and a C-terminal transmembrane domain
with a short cytoplasmic tail. It also has 28 potential N-glycosylation
sites. Human ITGA1 was expressed in a mouse fibroblast cell line as a
180-kD protein.
GENE FUNCTION
Briesewitz et al. (1993) demonstrated that a truncated, soluble form of
human ITGA1 assembled with truncated soluble forms of chicken or human
ITGB1 (135630) in heterodimeric complexes following cotransfection into
a mouse fibroblast cell line. Secretion of truncated ITGA1 into the
medium was dependent upon heterodimerization with soluble ITGB1. The
soluble heterodimer bound immobilized collagen IV (see COL4A1; 120130)
in an in vitro binding assay, and binding required Mg(2+). Biosynthetic
studies using stably expressing cell lines demonstrated that the soluble
heterodimers and the native heterodimers were formed independently,
suggesting that the transmembrane or cytoplasmic domains of the alpha
and beta subunits are involved in the assembly of native heterodimers.
Suzuki et al. (2007) demonstrated that semaphorin 7A (SRMA7A; 607961),
which is expressed on activated T cells, stimulates cytokine production
in monocytes and macrophages through alpha-1-beta-1 integrin (also known
as very late antigen-1) as a component of the immunologic synapse, and
is critical for the effector phase of the inflammatory immune response.
Sema7A-null mice are defective in cell-mediated immune responses such as
contact hypersensitivity and experimental autoimmune encephalomyelitis.
Although antigen-specific and cytokine-producing effector T cells could
develop and migrate into antigen-challenged sites in Sema7a-null mice,
Sema7a-null T cells failed to induce contact hypersensitivity even when
directly injected into the antigen-challenged sites. Thus, Suzuki et al.
(2007) concluded that the interaction between SEMA7A and alpha-1-beta-1
integrin is crucial at the site of inflammation.
Conrad et al. (2007) showed that blocking the interaction of
alpha-1-beta-1 integrin (VLA-1) with collagen prevented accumulation of
epidermal T cells and immunopathology of psoriasis (177900).
Alpha-1-beta-1 integrin, a major collagen-binding surface receptor, was
exclusively expressed by epidermal but not dermal T cells.
Alpha-1-beta-1-positive T cells showed characteristic surface markers of
effector memory cells and contained high levels of interferon-gamma
(147570) but not interleukin-4 (147780). Blockade of alpha-1-beta-1
inhibited migration of T cells into the epidermis in a clinically
relevant xenotransplantation model. This was paralleled by a complete
inhibition of psoriasis development, comparable to that caused by tumor
necrosis factor-alpha (TNFA; 191160) blockers. Conrad et al. (2007)
concluded that their results defined a crucial role for alpha-1-beta-1
in controlling the accumulation of epidermal type 1 polarized effector
memory T cells in a common human immunopathology and provided the basis
for new strategies in psoriasis treatment focusing on T
cell-extracellular matrix interactions.
MAPPING
Douville et al. (1992) used an interspecies backcross gene-mapping
strategy to locate the Vla1 gene to mouse chromosome 13, 3.5 cM distal
to Ctla3 (140050). The mapping to chromosome 13 was confirmed in
recombinant inbred (RI) mice. Since the CTLA3 gene is on human
chromosome 5, it is likely that the human VLA1 gene is likewise on
chromosome 5.
ANIMAL MODEL
Ekholm et al. (2002) studied the regeneration of a fractured long bone
in alpha-1-null mice. The null mice developed significantly less callus
tissue than the wildtype mice and displayed a defect in cartilage
formation. During the first 9 days of healing, the mRNA levels of
cartilage-related genes, including several collagen genes, were lower in
alpha-1-null mice than in wildtype mice, consistent with the reduced
synthesis of cartilaginous matrix seen in tissue sections. There were
fewer chondrocytes in the alpha-1-null callus as well as a reduction of
mesenchymal progenitors at the callus site. Ekholm et al. (2002)
concluded that proper collagen-integrin interaction is important in
fracture healing and suggested that alpha-1 integrin plays an essential
role in the regulation of mesenchymal stem cell proliferation and
cartilage production.
Zemmyo et al. (2003) developed alpha-1 integrin-null mice and compared
their knee joints to those of wildtype mice at ages 4 to 15 months. In
wildtype mice, the alpha-1 integrin subunit was detected in hypertrophic
chondrocytes in the growth plate and in a subpopulation of cells in the
deep zone of articular cartilage. There was a marked increase in
alpha-1-positive chondrocytes in the superficial and upper mid-zones in
osteoarthritis-affected areas in joints from old wildtype mice. The
alpha-1-null mice showed more severe cartilage degradation, glycosamine
depletion, and synovial hyperplasia as compared with the wildtype mice.
In cartilage from alpha-1-null mice, the cellularity was reduced and the
frequency of apoptotic cells was increased. Zemmyo et al. (2003)
suggested that the alpha-1 integrin subunit is involved in the early
remodeling process in osteoarthritic cartilage.
*FIELD* RF
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2. Conrad, C.; Boyman, O.; Tonel, G.; Tun-Kyi, A.; Laggner, U.; de
Fougerolles, A.; Kotelianski, V.; Gardner, H.; Nestle, F. O.: Alpha-1-beta-1
integrin is crucial for accumulation of epidermal T cells and the
development of psoriasis. Nature Med. 13: 836-841, 2007.
3. Douville, P.; Seldin, M. F.; Carbonetto, S.: Genetic mapping of
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503-505, 1992.
4. Ekholm, E.; Hankenson, K. D.; Uusitalo, H.; Hiltunen, A.; Gardner,
H.; Heino, J.; Penttinen, R.: Diminished callus size and cartilage
synthesis in alpha-1 beta-1 integrin-deficient mice during bone fracture
healing. Am. J. Path. 160: 1779-1785, 2002.
5. Suzuki, K.; Okuno, T.; Yamamoto, M.; Pasterkamp, R. J.; Takegahara,
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6. Zemmyo, M.; Meharra, E. J.; Kuhn, K.; Creighton-Achermann, L.;
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*FIELD* CN
Ada Hamosh - updated: 2/25/2008
Ada Hamosh - updated: 4/27/2007
Patricia A. Hartz - updated: 10/26/2004
Marla J. F. O'Neill - updated: 9/8/2004
Marla J. F. O'Neill - updated: 9/1/2004
*FIELD* CD
Victor A. McKusick: 10/15/1992
*FIELD* ED
alopez: 03/03/2008
alopez: 3/3/2008
terry: 2/25/2008
alopez: 5/10/2007
terry: 4/27/2007
terry: 4/4/2005
mgross: 10/26/2004
carol: 9/8/2004
carol: 9/2/2004
terry: 9/1/2004
dkim: 9/9/1998
mark: 6/12/1997
carol: 10/15/1992