Tclin ITGAL Integrin alpha-L

Protein Summary

Description

Integrin alpha-L/beta-2 is a receptor for ICAM1, ICAM2, ICAM3 and ICAM4. Integrin alpha-L/beta-2 is also a receptor for F11R (PubMed:11812992, PubMed:15528364). Involved in a variety of immune phenomena including leukocyte-endothelial cell interaction, cytotoxic T-cell mediated killing, and antibody dependent killing by granulocytes and monocytes. Contributes to natural killer cell cytotoxicity (PubMed:15356110). Involved in leukocyte adhesion and transmigration of leukocytes including T-cells and neutrophils (PubMed:11812992). Required for generation of common lymphoid progenitor cells in bone marrow, indicating a role in lymphopoiesis (By similarity). Integrin alpha-L/beta-2 in association with ICAM3, contributes to apoptotic neutrophil phagocytosis by macrophages (PubMed:23775590). ITGAL encodes the integrin alpha L chain. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. This I-domain containing alpha integrin combines with the beta 2 chain (ITGB2) to form the integrin lymphocyte function-associated antigen-1 (LFA-1), which is expressed on all leukocytes. LFA-1 plays a central role in leukocyte intercellular adhesion through interactions with its ligands, ICAMs 1-3 (intercellular adhesion molecules 1 through 3), and also functions in lymphocyte costimulatory signaling. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• P20701
• O43746
• Q45H73
• Q96HB1
• Q9UBC8

Gene Name

• ITGAL

Ensembl ID

• ENST00000356798
• ENSP00000349252
• ENSG00000005844
• ENST00000358164
• ENSP00000350886

Symbol

• CD11A
• CD11A
• LFA-1
• LFA1A

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
protein domain	0.85
biological process	0.8
cellular component	0.72
tissue sample	0.71
disease	0.67

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 905.01   (req: < 5)

Gene RIFs: 123   (req: <= 3)

Antibodies: 1879   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 905.01   (req: >= 5)

Gene RIFs: 123   (req: > 3)

Antibodies: 1879   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 20

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 72

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 2

Approved Drugs (2)

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1 – 2 of 2

lifitegrast

ITGALTclin

ANTAGONIST IC50: 8.04575729

efalizumab

ITGALTclin

ANTIBODY BINDING Kd: 11.4

Active Ligands (72)

Explore Active Ligands

1 – 10 of 72

CHEMBL1098726

ITGALTclin

IC50: 8.6

CHEMBL214529

ITGALTclin

IC50: 7.75

CHEMBL1098761

ITGALTclin

IC50: 7.92

CHEMBL1099103

ITGALTclin

IC50: 7.96

CHEMBL1096053

ITGALTclin

IC50: 7.89

CHEMBL1097733

ITGALTclin

IC50: 7.96

CHEMBL1096039

ITGALTclin

IC50: 7.96

CHEMBL1094753

ITGALTclin

IC50: 7.92

CHEMBL1097384

ITGALTclin

IC50: 7.96

CHEMBL1094127

ITGALTclin

IC50: 8.4

Protein Data Bank (39)

1 – 5 of 39

PDB Structure Id	Ligand	Method	Resolution (Å)	M.W. (kDa)	Pub Year	Title

PDB Structure Id	M.W.	Resolution	Pub Year

Pathways (42)

Reactome (14)

KEGG (11)

PathwayCommons (5)

WikiPathways (12)

Adaptive Immune System (R-HSA-1280218)

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Items per page:

5

1 – 5 of 14

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Adaptive Immune System	894 targets	R-HSA-1280218
Reactome	Cell surface interactions at the vascular wall	211 targets	R-HSA-202733
Reactome	Extracellular matrix organization	297 targets	R-HSA-1474244
Reactome	Gene expression (Transcription)	1452 targets	R-HSA-74160
Reactome	Generic Transcription Pathway	1195 targets	R-HSA-212436

Name	Explore in Pharos	Explore in Source
Adaptive Immune System	894 targets	R-HSA-1280218
Cell surface interactions at the vascular wall	211 targets	R-HSA-202733
Extracellular matrix organization	297 targets	R-HSA-1474244
Gene expression (Transcription)	1452 targets	R-HSA-74160
Generic Transcription Pathway	1195 targets	R-HSA-212436

Gene Ontology Terms (27)

Functions (5)

Components (7)

Processes (15)

Items per page:

10

1 – 5 of 5

GO Term	Evidence	Assigned by
cell adhesion molecule binding	Inferred from Mutant Phenotype (IMP)	UniProtKB
ICAM-3 receptor activity	Inferred from Mutant Phenotype (IMP)	UniProtKB
metal ion binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW
protein heterodimerization activity	Inferred from Electronic Annotation (IEA)	Ensembl
protein-containing complex binding	Inferred from Electronic Annotation (IEA)	Ensembl

Protein-Protein Interactions (297)

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1 – 10 of 297

• See Interactions on String-DB

ICAM1

Tchem

Novelty: 0.00011154

Score: 0.999

Data Source: STRINGDB

ITGB2

Tclin

Novelty: 0.00237551

Score: 0.999

Data Source: Reactome,STRINGDB

ICAM3

Tbio

Novelty: 0.00219774

Score: 0.997

Data Source: STRINGDB

ICAM5

Tbio

Novelty: 0.01644548

Score: 0.993

Data Source: STRINGDB

ITGB1

Tclin

Novelty: 0.00074903

Score: 0.98

Data Source: STRINGDB

ICAM2

Tbio

Novelty: 0.00637658

Score: 0.975

Data Source: STRINGDB

ITGB7

Tclin

Novelty: 0.02027194

Score: 0.969

Data Source: STRINGDB

CTLA4

Tclin

Novelty: 0.00017405

Score: 0.967

Data Source: STRINGDB

CD28

Tbio

Novelty: 0.00051946

Score: 0.967

Data Source: STRINGDB

ITGB3

Tclin

Novelty: 0.00086996

Score: 0.965

Data Source: STRINGDB

Publication Statistics

PubMed Score  905.01

PubMed score by year

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PubTator Score  1481.84

PubTator score by year

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Amino Acid Sequence

Residue Counts

Sequence

MKDSCITVMAMALLSGFFFFAPASSYNLDVRGARSFSPPRAGRHFGYRVLQVGNGVIVGAPGEGNSTGSL

1-70

YQCQSGTGHCLPVTLRGSNYTSKYLGMTLATDPTDGSILACDPGLSRTCDQNTYLSGLCYLFRQNLQGPM

70-140

LQGRPGFQECIKGNVDLVFLFDGSMSLQPDEFQKILDFMKDVMKKLSNTSYQFAAVQFSTSYKTEFDFSD

140-210

YVKRKDPDALLKHVKHMLLLTNTFGAINYVATEVFREELGARPDATKVLIIITDGEATDSGNIDAAKDII

210-280

RYIIGIGKHFQTKESQETLHKFASKPASEFVKILDTFEKLKDLFTELQKKIYVIEGTSKQDLTSFNMELS

280-350

SSGISADLSRGHAVVGAVGAKDWAGGFLDLKADLQDDTFIGNEPLTPEVRAGYLGYTVTWLPSRQKTSLL

350-420

ASGAPRYQHMGRVLLFQEPQGGGHWSQVQTIHGTQIGSYFGGELCGVDVDQDGETELLLIGAPLFYGEQR

420-490

GGRVFIYQRRQLGFEEVSELQGDPGYPLGRFGEAITALTDINGDGLVDVAVGAPLEEQGAVYIFNGRHGG

490-560

LSPQPSQRIEGTQVLSGIQWFGRSIHGVKDLEGDGLADVAVGAESQMIVLSSRPVVDMVTLMSFSPAEIP

560-630

VHEVECSYSTSNKMKEGVNITICFQIKSLIPQFQGRLVANLTYTLQLDGHRTRRRGLFPGGRHELRRNIA

630-700

VTTSMSCTDFSFHFPVCVQDLISPINVSLNFSLWEEEGTPRDQRAQGKDIPPILRPSLHSETWEIPFEKN

700-770

CGEDKKCEANLRVSFSPARSRALRLTAFASLSVELSLSNLEEDAYWVQLDLHFPPGLSFRKVEMLKPHSQ

770-840

IPVSCEELPEESRLLSRALSCNVSSPIFKAGHSVALQMMFNTLVNSSWGDSVELHANVTCNNEDSDLLED

840-910

NSATTIIPILYPINILIQDQEDSTLYVSFTPKGPKIHQVKHMYQVRIQPSIHDHNIPTLEAVVGVPQPPS

910-980

EGPITHQWSVQMEPPVPCHYEDLERLPDAAEPCLPGALFRCPVVFRQEILVQVIGTLELVGEIEASSMFS

980-1050

LCSSLSISFNSSKHFHLYGSNASLAQVVMKVDVVYEKQMLYLYVLSGIGGLLLLLLIFIVLYKVGFFKRN

1050-1120

LKEKMEAGRGVPNGIPAEDSEQLASGQEAGDPGCLKPLHEKDSESGGGKD

1120-1170

MKDSCITVMAMALLSGFFFFAPASSYNLDVRGARSFSPPRAGRHFGYRVLQVGNGVIVGAPGEGNSTGSLYQCQSGTGHCLPVTLRGSNYTSKYLGMTLATDPTDGSILACDPGLSRTCDQNTYLSGLCYLFRQNLQGPMLQGRPGFQECIKGNVDLVFLFDGSMSLQPDEFQKILDFMKDVMKKLSNTSYQFAAVQFSTSYKTEFDFSDYVKRKDPDALLKHVKHMLLLTNTFGAINYVATEVFREELGARPDATKVLIIITDGEATDSGNIDAAKDIIRYIIGIGKHFQTKESQETLHKFASKPASEFVKILDTFEKLKDLFTELQKKIYVIEGTSKQDLTSFNMELSSSGISADLSRGHAVVGAVGAKDWAGGFLDLKADLQDDTFIGNEPLTPEVRAGYLGYTVTWLPSRQKTSLLASGAPRYQHMGRVLLFQEPQGGGHWSQVQTIHGTQIGSYFGGELCGVDVDQDGETELLLIGAPLFYGEQRGGRVFIYQRRQLGFEEVSELQGDPGYPLGRFGEAITALTDINGDGLVDVAVGAPLEEQGAVYIFNGRHGGLSPQPSQRIEGTQVLSGIQWFGRSIHGVKDLEGDGLADVAVGAESQMIVLSSRPVVDMVTLMSFSPAEIPVHEVECSYSTSNKMKEGVNITICFQIKSLIPQFQGRLVANLTYTLQLDGHRTRRRGLFPGGRHELRRNIAVTTSMSCTDFSFHFPVCVQDLISPINVSLNFSLWEEEGTPRDQRAQGKDIPPILRPSLHSETWEIPFEKNCGEDKKCEANLRVSFSPARSRALRLTAFASLSVELSLSNLEEDAYWVQLDLHFPPGLSFRKVEMLKPHSQIPVSCEELPEESRLLSRALSCNVSSPIFKAGHSVALQMMFNTLVNSSWGDSVELHANVTCNNEDSDLLEDNSATTIIPILYPINILIQDQEDSTLYVSFTPKGPKIHQVKHMYQVRIQPSIHDHNIPTLEAVVGVPQPPSEGPITHQWSVQMEPPVPCHYEDLERLPDAAEPCLPGALFRCPVVFRQEILVQVIGTLELVGEIEASSMFSLCSSLSISFNSSKHFHLYGSNASLAQVVMKVDVVYEKQMLYLYVLSGIGGLLLLLLIFIVLYKVGFFKRNLKEKMEAGRGVPNGIPAEDSEQLASGQEAGDPGCLKPLHEKDSESGGGKD

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Uniprot Keyword

3D-structure
Alternative splicing
Calcium
Cell adhesion
Cell membrane
Complete proteome
Direct protein sequencing
Disulfide bond
Glycoprotein
Integrin