Reviewed, UniProtKB/Swiss-Prot P05362 (ICAM1_HUMAN)

Names and origin

Protein names

Recommended name:
    Intercellular adhesion molecule 1
      Short name(s)=ICAM-1
Alternative name(s):
    Major group rhinovirus receptor
    CD_antigen=CD54

Gene names

Name:

ICAM1

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	532 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	ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical cups through SGEF and RHOG activation. In case of rhinovirus infection acts as a cellular receptor for the virus.
Subunit structure	Homodimer Probable. Interacts with human herpesvirus 8 MIR2 protein Probable. Interacts with MUC1 and promotes cell aggregation in epithelial cells. Interacts with SGEF. Binds to coxsackievirus A21 capsid proteins and acts as a receptor for this virus.
Subcellular location	Membrane; Single-pass type I membrane protein.
Post-translational modification	Monoubiquitinated, which is promoted by MARCH9 and leads to endocytosis.
Polymorphism	Homozygotes with ICAM1-Kalifi Met-56 seem to have an increased risk for cerebral malaria.
Sequence similarities	Belongs to the immunoglobulin superfamily. ICAM family. Contains 5 Ig-like C2-type (immunoglobulin-like) domains.

Ontologies

Keywords
Biological process	Cell adhesion Host-virus interaction
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Immunoglobulin domain Repeat Signal Transmembrane
PTM	Glycoprotein Ubl conjugation
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	leukocyte adhesion Inferred from expression pattern. Source: UniProtKB leukocyte migration Inferred from expression pattern. Source: UniProtKB membrane to membrane docking Inferred from expression pattern. Source: UniProtKB
Cellular component	extracellular space Inferred from direct assay. Source: UniProtKB integral to plasma membrane Ref.10 Traceable author statement. Source: ProtInc
Molecular function	transmembrane receptor activity Ref.10 Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Signal peptide

1 – 27

27

Chain

28 – 532

505

Intercellular adhesion molecule 1

Regions

Topological domain

28 – 480

453

Extracellular Potential

Transmembrane

481 – 503

23

Potential

Topological domain

504 – 532

29

Cytoplasmic Potential

Domain

41 – 103

63

Ig-like C2-type 1

Domain

128 – 193

66

Ig-like C2-type 2

Domain

230 – 297

68

Ig-like C2-type 3

Domain

325 – 378

54

Ig-like C2-type 4

Domain

412 – 464

53

Ig-like C2-type 5

Motif

152 – 154

3

Cell attachment site; atypical Potential

Amino acid modifications

Glycosylation

130

1

N-linked (GlcNAc...)

Glycosylation

145

1

N-linked (GlcNAc...)

Glycosylation

183

1

N-linked (GlcNAc...)

Glycosylation

202

1

N-linked (GlcNAc...)

Glycosylation

267

1

N-linked (GlcNAc...)

Glycosylation

296

1

N-linked (GlcNAc...)

Glycosylation

385

1

N-linked (GlcNAc...)

Glycosylation

406

1

N-linked (GlcNAc...) Potential

Disulfide bond

48 ↔ 92

Disulfide bond

52 ↔ 96

Disulfide bond

135 ↔ 186

Disulfide bond

237 ↔ 290

Disulfide bond

332 ↔ 371

Disulfide bond

403 ↔ 419

Disulfide bond

431 ↔ 457

Natural variations

Natural variant

56

1

K → M in Kilifi. dbSNP rs5491.

Natural variant

155

1

K → N: dbSNP rs5492.

Natural variant

241

1

G → R: dbSNP rs1799969.

Natural variant

315

1

V → M: dbSNP rs5495.

Natural variant

352

1

P → L: dbSNP rs1801714.

Natural variant

397

1

R → Q: dbSNP rs5497.

Natural variant

469

1

K → E: dbSNP rs5498.

Natural variant

478

1

R → W: dbSNP rs5030400.

Experimental info

Sequence conflict

9 – 10

2

AL → PV in CAA40441. Ref.8

Sequence conflict

17

1

L → F in AAQ14902. Ref.9

Sequence conflict

27

1

A → V in AAQ14902. Ref.9

Secondary structure

1

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532

Helix Strand Turn

Details...

Beta strand

220 – 222

3

Beta strand

225 – 228

4

Beta strand

231 – 241

11

Helix

245 – 247

3

Beta strand

249 – 254

6

Beta strand

262 – 266

5

Beta strand

269 – 277

9

Helix

280 – 282

3

Beta strand

284 – 294

11

Beta strand

297 – 308

12

Beta strand

314 – 318

5

Beta strand

320 – 323

4

Beta strand

327 – 333

7

Beta strand

353 – 359

7

Helix

362 – 364

3

Beta strand

368 – 377

10

Beta strand

380 – 389

10

Beta strand

391 – 397

7

Beta strand

405 – 410

6

Beta strand

422 – 425

4

Beta strand

428 – 433

6

Turn

434 – 436

3

Helix

449 – 451

3

Beta strand

453 – 461

9

Beta strand

464 – 475

12

Sequences

	Sequence		Length	Mass (Da)
	P05362-1 [UniParc]. Last modified June 21, 2005. Version 2. Checksum: 550089365A733AFB	FASTA	532	57,825
	10 20 30 40 50 60 MAPSSPRPAL PALLVLLGAL FPGPGNAQTS VSPSKVILPR GGSVLVTCST SCDQPKLLGI 70 80 90 100 110 120 ETPLPKKELL LPGNNRKVYE LSNVQEDSQP MCYSNCPDGQ STAKTFLTVY WTPERVELAP 130 140 150 160 170 180 LPSWQPVGKN LTLRCQVEGG APRANLTVVL LRGEKELKRE PAVGEPAEVT TTVLVRRDHH 190 200 210 220 230 240 GANFSCRTEL DLRPQGLELF ENTSAPYQLQ TFVLPATPPQ LVSPRVLEVD TQGTVVCSLD 250 260 270 280 290 300 GLFPVSEAQV HLALGDQRLN PTVTYGNDSF SAKASVSVTA EDEGTQRLTC AVILGNQSQE 310 320 330 340 350 360 TLQTVTIYSF PAPNVILTKP EVSEGTEVTV KCEAHPRAKV TLNGVPAQPL GPRAQLLLKA 370 380 390 400 410 420 TPEDNGRSFS CSATLEVAGQ LIHKNQTREL RVLYGPRLDE RDCPGNWTWP ENSQQTPMCQ 430 440 450 460 470 480 AWGNPLPELK CLKDGTFPLP IGESVTVTRD LEGTYLCRAR STQGEVTRKV TVNVLSPRYE 490 500 510 520 530 IVIITVVAAA VIMGTAGLST YLYNRQRKIK KYRLQQAQKG TPMKPNTQAT PP

References

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[1]	"ICAM, an adhesion ligand of LFA-1, is homologous to the neural cell adhesion molecule NCAM." Simmons D., Makgoba M.W., Seed B. Nature 331:624-627(1988) [PubMed: 3340213] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLU-469.
[2]	"Primary structure of ICAM-1 demonstrates interaction between members of the immunoglobulin and integrin supergene families." Staunton D.E., Marlin S.D., Stratowa C., Dustin M.L., Springer T.A. Cell 52:925-933(1988) [PubMed: 3349522] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLU-469.
[3]	"cDNA cloning reveals that the major group rhinovirus receptor on HeLa cells is intercellular adhesion molecule 1." Tomassini J.E., Graham D., Dewitt C.M., Lineberger D.W., Rodkey J.A., Colonno R.J. Proc. Natl. Acad. Sci. U.S.A. 86:4907-4911(1989) [PubMed: 2544880] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Cloning of the human gene for intercellular adhesion molecule 1 and analysis of its 5'-regulatory region. Induction by cytokines and phorbol ester." Voraberger G.F., Schaefer R., Stratowa C. J. Immunol. 147:2777-2786(1991) [PubMed: 1680919] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLU-469.
[5]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	SeattleSNPs program for genomic applications Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT KILIFI MET-56, VARIANTS ARG-241; LEU-352; GLN-397 AND TRP-478.
[7]	"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]. Tissue: Kidney.
[8]	"Structural characteristics of the 5' region of the human ICAM-1 gene." Stade B.G., Messer G., Riethmueller G., Johnson J.P. Immunobiology 182:79-87(1990) [PubMed: 1983003] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-22.
[9]	"The potential significance of adaptive evolution and dimerization in chimpanzee intercellular cell adhesion molecules (ICAMs)." Walter N.A.R., Stebbing J., Messier W. J. Theor. Biol. 232:339-346(2005) [PubMed: 15572059] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 5-532, VARIANT GLU-469. Tissue: Blood.
[10]	"The major human rhinovirus receptor is ICAM-1." Greve J.M., Davis G., Meyer A.M., Forte C.P., Yost S.C., Marlor C.W., Kamarck M.E., McClelland A. Cell 56:839-847(1989) [PubMed: 2538243] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, FUNCTION AS A RHINOVIRUS RECEPTOR.
[11]	"A soluble form of intercellular adhesion molecule-1 inhibits rhinovirus infection." Marlin S.D., Staunton D.E., Springer T.A., Stratowa C., Sommergruber W., Merluzzi V.J. Nature 344:70-72(1990) [PubMed: 1968231] [Abstract] Cited for: FUNCTION AS A RHINOVIRUS RECEPTOR.
[12]	"MUC1 mucin core protein binds to the domain 1 of ICAM-1." Hayashi T., Takahashi T., Motoya S., Ishida T., Itoh F., Adachi M., Hinoda Y., Imai K. Digestion 63 Suppl. 1:87-92(2001) [PubMed: 11173916] [Abstract] Cited for: INTERACTION WITH MUC1, FUNCTION.
[13]	"Interaction of coxsackievirus A21 with its cellular receptor, ICAM-1." Xiao C., Bator C.M., Bowman V.D., Rieder E., He Y., Hebert B., Bella J., Baker T.S., Wimmer E., Kuhn R.J., Rossmann M.G. J. Virol. 75:2444-2451(2001) [PubMed: 11160747] [Abstract] Cited for: INTERACTION WITH COXSACKIEVIRUS A21 CAPSID PROTEINS.
[14]	"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry." Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D. J. Proteome Res. 4:2070-2080(2005) [PubMed: 16335952] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-267, MASS SPECTROMETRY. Tissue: Plasma.
[15]	"MARCH-IX mediates ubiquitination and downregulation of ICAM-1." Hoer S., Smith L., Lehner P.J. FEBS Lett. 581:45-51(2007) [PubMed: 17174307] [Abstract] Cited for: UBIQUITINATION.
[16]	"RhoG regulates endothelial apical cup assembly downstream from ICAM1 engagement and is involved in leukocyte trans-endothelial migration." van Buul J.D., Allingham M.J., Samson T., Meller J., Boulter E., Garcia-Mata R., Burridge K. J. Cell Biol. 178:1279-1293(2007) [PubMed: 17875742] [Abstract] Cited for: INTERACTION WITH SGEF, FUNCTION.
[17]	"A dimeric crystal structure for the N-terminal two domains of intercellular adhesion molecule-1." Casasnovas J.M., Stehle T., Liu J.H., Wang J.H., Springer T.A. Proc. Natl. Acad. Sci. U.S.A. 95:4134-4139(1998) [PubMed: 9539702] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 28-217.
[18]	"The structure of the two amino-terminal domains of human ICAM-1 suggests how it functions as a rhinovirus receptor and as an LFA-1 integrin ligand." Bella J., Kolatkar P.R., Marlor C.W., Greve J.M., Rossmann M.G. Proc. Natl. Acad. Sci. U.S.A. 95:4140-4145(1998) [PubMed: 9539703] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.25 ANGSTROMS) OF 28-212 IN COMPLEX WITH HUMAN RHINOVIRUS 14.
[19]	"Structural studies of two rhinovirus serotypes complexed with fragments of their cellular receptor." Kolatkar P.R., Bella J., Olson N.H., Bator C.M., Baker T.S., Rossmann M.G. EMBO J. 18:6249-6259(1999) [PubMed: 10562537] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.25 ANGSTROMS) OF 28-212.
[20]	"Structures of the alpha L I domain and its complex with ICAM-1 reveal a shape-shifting pathway for integrin regulation." Shimaoka M., Xiao T., Liu J.H., Yang Y., Dong Y., Jun C.D., McCormack A., Zhang R., Joachimiak A., Takagi J., Wang J.H., Springer T.A. Cell 112:99-111(2003) [PubMed: 12526797] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) OF 28-318 IN COMPLEX WITH ITGAL VWFA DOMAIN, DISULFIDE BONDS, GLYCOSYLATION AT ASN-130; ASN-145; ASN-183 AND ASN-202.
[21]	"Structural basis for dimerization of ICAM-1 on the cell surface." Yang Y., Jun C.D., Liu J.H., Zha