Reviewed, UniProtKB/Swiss-Prot Q13740 (CD166_HUMAN)

Names and origin

Protein names

Recommended name:
    CD166 antigen
Alternative name(s):
    Activated leukocyte cell adhesion molecule
    CD_antigen=CD166

Gene names

Name:	ALCAM
Synonyms:	MEMD

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	583 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	Cell adhesion molecule that binds to CD6. Involved in neurite extension by neurons via heterophilic and homophilic interactions. May play a role in the binding of T- and B-cells to activated leukocytes, as well as in interactions between cells of the nervous system.
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	Spleen, placenta, liver, and weakly in liver. Expressed by activated T-cells, B-cells, monocytes and thymic epithelial cells. Expressed by neurons in the brain. Restricted expression in tumor cell lines. Preferentially expressed in highly metastasizing melanoma cell lines.
Domain	The CD6 binding site is located in the N-terminal Ig-like domain.
Sequence similarities	Contains 3 Ig-like C2-type (immunoglobulin-like) domains. Contains 2 Ig-like V-type (immunoglobulin-like) domains.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Immunoglobulin domain Repeat Signal Transmembrane
PTM	Glycoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	cell adhesion Ref.1 Traceable author statement. Source: ProtInc signal transduction Ref.1 Traceable author statement. Source: ProtInc
Molecular function	receptor binding Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q13740-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q13740-2)

The sequence of this isoform differs from the canonical sequence as follows:
     503-515: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Signal peptide

1 – 27

27

Potential

Chain

28 – 583

556

CD166 antigen

Regions

Topological domain

28 – 527

500

Extracellular Potential

Transmembrane

528 – 549

22

Potential

Topological domain

550 – 583

34

Cytoplasmic Potential

Domain

28 – 120

93

Ig-like V-type 1

Domain

125 – 234

110

Ig-like V-type 2

Domain

245 – 328

84

Ig-like C2-type 1

Domain

333 – 409

77

Ig-like C2-type 2

Domain

416 – 501

86

Ig-like C2-type 3

Amino acid modifications

Glycosylation

91

1

N-linked (GlcNAc...)

Glycosylation

95

1

N-linked (GlcNAc...)

Glycosylation

167

1

N-linked (GlcNAc...)

Glycosylation

265

1

N-linked (GlcNAc...)

Glycosylation

306

1

N-linked (GlcNAc...) Potential

Glycosylation

361

1

N-linked (GlcNAc...) Potential

Glycosylation

457

1

N-linked (GlcNAc...) Potential

Glycosylation

480

1

N-linked (GlcNAc...)

Glycosylation

499

1

N-linked (GlcNAc...)

Disulfide bond

43 ↔ 113

Potential

Disulfide bond

157 ↔ 220

Potential

Disulfide bond

270 ↔ 313

Potential

Disulfide bond

354 ↔ 392

Potential

Disulfide bond

435 ↔ 485

Potential

Natural variations

Alternative sequence

503 – 515

13

Missing in isoform 2.

Natural variant

229

1

G → D: dbSNP rs10933819.

Natural variant

258

1

N → S: dbSNP rs1044240.

Natural variant

301

1

T → M: dbSNP rs1044243.

Natural variant

315

1

L → M: dbSNP rs12629872.

Natural variant

352

1

V → M: dbSNP rs2291375.

Experimental info

Sequence conflict

516

1

D → N in ABF48405. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

583

Helix Strand Turn

Details...

Beta strand

39 – 44

6

Beta strand

51 – 59

9

Beta strand

65 – 71

7

Beta strand

76 – 80

5

Beta strand

86 – 90

5

Beta strand

92 – 102

11

Beta strand

105 – 107

3

Beta strand

109 – 117

9

Beta strand

120 – 123

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 28, 2006. Version 2. Checksum: 68FEFD67C14B0C57	FASTA	583	65,102
	10 20 30 40 50 60 MESKGASSCR LLFCLLISAT VFRPGLGWYT VNSAYGDTII IPCRLDVPQN LMFGKWKYEK 70 80 90 100 110 120 PDGSPVFIAF RSSTKKSVQY DDVPEYKDRL NLSENYTLSI SNARISDEKR FVCMLVTEDN 130 140 150 160 170 180 VFEAPTIVKV FKQPSKPEIV SKALFLETEQ LKKLGDCISE DSYPDGNITW YRNGKVLHPL 190 200 210 220 230 240 EGAVVIIFKK EMDPVTQLYT MTSTLEYKTT KADIQMPFTC SVTYYGPSGQ KTIHSEQAVF 250 260 270 280 290 300 DIYYPTEQVT IQVLPPKNAI KEGDNITLKC LGNGNPPPEE FLFYLPGQPE GIRSSNTYTL 310 320 330 340 350 360 TDVRRNATGD YKCSLIDKKS MIASTAITVH YLDLSLNPSG EVTRQIGDAL PVSCTISASR 370 380 390 400 410 420 NATVVWMKDN IRLRSSPSFS SLHYQDAGNY VCETALQEVE GLKKRESLTL IVEGKPQIKM 430 440 450 460 470 480 TKKTDPSGLS KTIICHVEGF PKPAIQWTIT GSGSVINQTE ESPYINGRYY SKIIISPEEN 490 500 510 520 530 540 VTLTCTAENQ LERTVNSLNV SAISIPEHDE ADEISDENRE KVNDQAKLIV GIVVGLLLAA 550 560 570 580 LVAGVVYWLY MKKSKTASKH VNKDLGNMEE NKKLEENNHK TEA
	Isoform 2 [UniParc]. Checksum: C961C5309281C422		570	63,666
	10 20 30 40 50 60 MESKGASSCR LLFCLLISAT VFRPGLGWYT VNSAYGDTII IPCRLDVPQN LMFGKWKYEK 70 80 90 100 110 120 PDGSPVFIAF RSSTKKSVQY DDVPEYKDRL NLSENYTLSI SNARISDEKR FVCMLVTEDN 130 140 150 160 170 180 VFEAPTIVKV FKQPSKPEIV SKALFLETEQ LKKLGDCISE DSYPDGNITW YRNGKVLHPL 190 200 210 220 230 240 EGAVVIIFKK EMDPVTQLYT MTSTLEYKTT KADIQMPFTC SVTYYGPSGQ KTIHSEQAVF 250 260 270 280 290 300 DIYYPTEQVT IQVLPPKNAI KEGDNITLKC LGNGNPPPEE FLFYLPGQPE GIRSSNTYTL 310 320 330 340 350 360 TDVRRNATGD YKCSLIDKKS MIASTAITVH YLDLSLNPSG EVTRQIGDAL PVSCTISASR 370 380 390 400 410 420 NATVVWMKDN IRLRSSPSFS SLHYQDAGNY VCETALQEVE GLKKRESLTL IVEGKPQIKM 430 440 450 460 470 480 TKKTDPSGLS KTIICHVEGF PKPAIQWTIT GSGSVINQTE ESPYINGRYY SKIIISPEEN 490 500 510 520 530 540 VTLTCTAENQ LERTVNSLNV SADENREKVN DQAKLIVGIV VGLLLAALVA GVVYWLYMKK 550 560 570 SKTASKHVNK DLGNMEENKK LEENNHKTEA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning, mapping, and characterization of activated leukocyte-cell adhesion molecule (ALCAM), a CD6 ligand." Bowen M.A., Patel D.D., Li X., Modrell B., Malacko A.R., Wang W.-C., Marquardt H., Neubauer M., Pesando J.M., Francke U., Haynes B.F., Aruffo A. J. Exp. Med. 181:2213-2220(1995) [PubMed: 7760007] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT MET-301, PARTIAL PROTEIN SEQUENCE.
[2]	"A novel alternatively spliced variant of activated leukocyte cell adhesion molecule (ALCAM/CD166) resulting from a deletion in the extracellular membrane proximal stem." Abe Y., Bui-Thanh N.-A., Smith C.W., Ballantyne C.M., Burns A.R. Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
[3]	"MEMD, a new cell adhesion molecule in metastasizing human melanoma cell lines, is identical to ALCAM (activated leukocyte cell adhesion molecule)." Degen W.G., van Kempen L.C., Gijzen E.G., van Groningen J.J., van Kooyk Y., Bloemers H.P.J., Swart G.W. Am. J. Pathol. 152:805-813(1998) [PubMed: 9502422] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 2-583 (ISOFORM 1), TISSUE SPECIFICITY.
[4]	"Recognition of diverse proteins by members of the immunoglobulin superfamily: delineation of the receptor binding site in the human CD6 ligand ALCAM." Skonier J.E., Bowen M.A., Emswiler J., Aruffo A., Bajorath J. Biochemistry 35:12287-12291(1996) [PubMed: 8823162] [Abstract] Cited for: DOMAIN CD6 BINDING.
[5]	"Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry." Zhang H., Li X.-J., Martin D.B., Aebersold R. Nat. Biotechnol. 21:660-666(2003) [PubMed: 12754519] [Abstract] Cited for: GLYCOSYLATION AT ASN-91; ASN-167; ASN-480 AND ASN-499.
[6]	"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-95; ASN-265 AND ASN-499, MASS SPECTROMETRY. Tissue: Plasma.
[7]	"Molecular model of the N-terminal receptor-binding domain of the human CD6 ligand ALCAM." Bajorath J., Bowen M.A., Aruffo A. Protein Sci. 4:1644-1647(1995) [PubMed: 8520490] [Abstract] Cited for: 3D-STRUCTURE MODELING OF 28-133.

Cross-references

Sequence databases

EMBLGenBankDDBJ

L38608 mRNA. Translation: AAB59499.1.
DQ486139 mRNA. Translation: ABF48405.1.
DQ486140 mRNA. Translation: ABF48406.1.
Y10183 mRNA. Translation: CAA71256.1.

PIR

I39428.

RefSeq

NP_001618.2.

UniGene

Hs.591293

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1KJC	model	-	A	28-133	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q13740.

PTM databases

PhosphoSite

Q13740.

Genome annotation databases

Ensembl

ENSG00000170017. Homo sapiens. [Contig view]

GeneID

214.

KEGG

hsa:214.

Organism-specific databases

H-InvDB

HIX0003517.

HGNC

HGNC:400. ALCAM.

HPA

CAB002148.
HPA010926.

MIM

601662. gene.

PharmGKB

PA24691.

GenAtlas

Search...

GeneCards

Search...

GeneLynx

Search...

Phylogenomic databases

HOGENOM

Q13740.

HOVERGEN

Q13740.

Gene expression databases

ArrayExpress

Q13740.

CleanEx

HS_ALCAM.

Family and domain databases

InterPro

IPR013162. CD80_C2-set.
IPR013151. Ig.
IPR007110. Ig-like.
IPR013783. Ig-like_fold.
IPR003006. Ig/MHC_CS.
IPR003599. Ig_sub.
[Graphical view]

Gene3D

G3DSA:2.60.40.10. Ig-like_fold. 3 hits.

Pfam

PF08205. C2-set_2. 1 hit.
PF00047. ig. 1 hit.
[Graphical view]

SMART

SM00409. IG. 3 hits.
[Graphical view]

PROSITE

PS50835. IG_LIKE. 4 hits.
[Graphical view]

ProDom

Q13740.
[Graphical view] [Entries sharing at least one domain]

BLOCKS

Search...

Other Resources

SOURCE

Search...

ProtoNet

Search...

Entry information

Entry name

CD166_HUMAN

Accession

Primary (citable) accession number: Q13740
Secondary accession number(s): O60892, Q1HGM8, Q1HGM9

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 28, 2006
Last modified:	July 22, 2008
This is version 80 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)