Details of the Target

General Information of Target

Target ID LDTP02669
Target Name Integrin alpha-4 (ITGA4)
Gene Name ITGA4
Gene ID 3676
Synonyms
CD49D; Integrin alpha-4; CD49 antigen-like family member D; Integrin alpha-IV; VLA-4 subunit alpha; CD antigen CD49d
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MAWEARREPGPRRAAVRETVMLLLCLGVPTGRPYNVDTESALLYQGPHNTLFGYSVVLHS
HGANRWLLVGAPTANWLANASVINPGAIYRCRIGKNPGQTCEQLQLGSPNGEPCGKTCLE
ERDNQWLGVTLSRQPGENGSIVTCGHRWKNIFYIKNENKLPTGGCYGVPPDLRTELSKRI
APCYQDYVKKFGENFASCQAGISSFYTKDLIVMGAPGSSYWTGSLFVYNITTNKYKAFLD
KQNQVKFGSYLGYSVGAGHFRSQHTTEVVGGAPQHEQIGKAYIFSIDEKELNILHEMKGK
KLGSYFGASVCAVDLNADGFSDLLVGAPMQSTIREEGRVFVYINSGSGAVMNAMETNLVG
SDKYAARFGESIVNLGDIDNDGFEDVAIGAPQEDDLQGAIYIYNGRADGISSTFSQRIEG
LQISKSLSMFGQSISGQIDADNNGYVDVAVGAFRSDSAVLLRTRPVVIVDASLSHPESVN
RTKFDCVENGWPSVCIDLTLCFSYKGKEVPGYIVLFYNMSLDVNRKAESPPRFYFSSNGT
SDVITGSIQVSSREANCRTHQAFMRKDVRDILTPIQIEAAYHLGPHVISKRSTEEFPPLQ
PILQQKKEKDIMKKTINFARFCAHENCSADLQVSAKIGFLKPHENKTYLAVGSMKTLMLN
VSLFNAGDDAYETTLHVKLPVGLYFIKILELEEKQINCEVTDNSGVVQLDCSIGYIYVDH
LSRIDISFLLDVSSLSRAEEDLSITVHATCENEEEMDNLKHSRVTVAIPLKYEVKLTVHG
FVNPTSFVYGSNDENEPETCMVEKMNLTFHVINTGNSMAPNVSVEIMVPNSFSPQTDKLF
NILDVQTTTGECHFENYQRVCALEQQKSAMQTLKGIVRFLSKTDKRLLYCIKADPHCLNF
LCNFGKMESGKEASVHIQLEGRPSILEMDETSALKFEIRATGFPEPNPRVIELNKDENVA
HVLLEGLHHQRPKRYFTIVIISSSLLLGLIVLLLISYVMWKAGFFKRQYKSILQEENRRD
SWSYINSKSNDD
Target Type
Successful
Target Bioclass
Other
Family
Integrin alpha chain family
Subcellular location
Membrane
Function
Integrins alpha-4/beta-1 (VLA-4) and alpha-4/beta-7 are receptors for fibronectin. They recognize one or more domains within the alternatively spliced CS-1 and CS-5 regions of fibronectin. They are also receptors for VCAM1. Integrin alpha-4/beta-1 recognizes the sequence Q-I-D-S in VCAM1. Integrin alpha-4/beta-7 is also a receptor for MADCAM1. It recognizes the sequence L-D-T in MADCAM1. On activated endothelial cells integrin VLA-4 triggers homotypic aggregation for most VLA-4-positive leukocyte cell lines. It may also participate in cytolytic T-cell interactions with target cells. ITGA4:ITGB1 binds to fractalkine (CX3CL1) and may act as its coreceptor in CX3CR1-dependent fractalkine signaling. ITGA4:ITGB1 binds to PLA2G2A via a site (site 2) which is distinct from the classical ligand-binding site (site 1) and this induces integrin conformational changes and enhanced ligand binding to site 1. Integrin ITGA4:ITGB1 represses PRKCA-mediated L-type voltage-gated channel Ca(2+) influx and ROCK-mediated calcium sensitivity in vascular smooth muscle cells via its interaction with SVEP1, thereby inhibiting vasocontraction.
TTD ID
T97587
Uniprot ID
P13612
DrugMap ID
TT4BT06
Ensemble ID
ENST00000339307.8
HGNC ID
HGNC:6140
ChEMBL ID
CHEMBL278

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
FUOV1 Insertion: p.T615NfsTer11 .
HCT116 SNV: p.T50M .
HS936T SNV: p.S426L .
ICC9 SNV: p.G10S .
MDAMB453 SNV: p.L375F .
MEWO SNV: p.D456N DBIA    Probe Info 
MFE319 Deletion: p.P170LfsTer7 .
MOLT4 SNV: p.S552N IA-alkyne    Probe Info 
NCIH2286 SNV: p.C800Ter .
NCIH23 SNV: p.A738E .
PF382 SNV: p.S371A .
SW403 SNV: p.G31S .
THP1 SNV: p.Q708K .
YSCCC SNV: p.D669N .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 8 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
OPA-S-S-alkyne
 Probe Info  		K526(1.76)  LDD3494  [1]
DBIA
 Probe Info  		C183(2.87)  LDD3333  [2]
4-Iodoacetamidophenylacetylene
 Probe Info  		C198(0.00); C852(0.00); C165(0.00); C861(0.00)  LDD0038  [3]
IA-alkyne
 Probe Info  		C198(0.00); C852(0.00); C165(0.00); C861(0.00)  LDD0036  [3]
Lodoacetamide azide
 Probe Info  		C198(0.00); C183(0.00); C852(0.00); C165(0.00)  LDD0037  [3]
Compound 10
 Probe Info  		C183(0.00); C198(0.00)  LDD2216  [4]
Compound 11
 Probe Info  		C183(0.00); C198(0.00)  LDD2213  [4]
IPM
 Probe Info  		N.A.  LDD0147  [5]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0022  KB02 A101D C861(3.23)  LDD2250  [2]
 LDCM0023  KB03 A101D C861(4.06)  LDD2667  [2]
 LDCM0024  KB05 MOLM-13 C183(2.87)  LDD3333  [2]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Transporter and channel
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Integrin beta-1 (ITGB1) Integrin beta chain family P05556
Other
Click To Hide/Show 3 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Integrin beta-7 (ITGB7) Integrin beta chain family P26010
Paxillin (PXN) Paxillin family P49023
Transforming growth factor beta-1-induced transcript 1 protein (TGFB1I1) Paxillin family O43294

The Drug(s) Related To This Target

Approved
Click To Hide/Show 5 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Antegren Antibody D09EBL
Natalizumab BiotechDrug DB00108
Vedolizumab BiotechDrug DB09033
Vedolizmab Monoclonal antibody D0N5ZS
Tinzaparin Small molecular drug DB06822
Phase 2
Click To Hide/Show 4 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Amg-181 Antibody D04WQJ
Bio-1211 Small molecular drug D0Q5LF
Gsk683699 Small molecular drug D0C9XA
Senktide Small molecular drug D05ZWG
Phase 1
Click To Hide/Show 3 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Elnd-002 . D01CYT
Elnd-004 . D05JPJ
Ptg-100 . D0FU1J
Investigative
Click To Hide/Show 6 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Cdp323 Small molecular drug DB05092
R1295 Small molecular drug DB05122
R411 Small molecular drug DB05468
Asp-2002 . D05SHQ
Atl1102 . DB04997
Ct301 . D00GWR

References

1 A chemical proteomics approach for global mapping of functional lysines on cell surface of living cell. Nat Commun. 2024 Apr 8;15(1):2997. doi: 10.1038/s41467-024-47033-w.
Mass spectrometry data entry: PXD042888
2 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840
3 Enhancing Cysteine Chemoproteomic Coverage through Systematic Assessment of Click Chemistry Product Fragmentation. Anal Chem. 2022 Mar 8;94(9):3800-3810. doi: 10.1021/acs.analchem.1c04402. Epub 2022 Feb 23.
Mass spectrometry data entry: PXD028853
4 Multiplexed CuAAC Suzuki-Miyaura Labeling for Tandem Activity-Based Chemoproteomic Profiling. Anal Chem. 2021 Feb 2;93(4):2610-2618. doi: 10.1021/acs.analchem.0c04726. Epub 2021 Jan 20.
Mass spectrometry data entry: PXD022279
5 Chemoproteomic Profiling by Cysteine Fluoroalkylation Reveals Myrocin G as an Inhibitor of the Nonhomologous End Joining DNA Repair Pathway. J Am Chem Soc. 2021 Dec 8;143(48):20332-20342. doi: 10.1021/jacs.1c09724. Epub 2021 Nov 24.
Mass spectrometry data entry: PXD029255