Q13740 (CD166_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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. Ref.6
Domain	The CD6 binding site is located in the N-terminal Ig-like domain. Ref.7
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 Transmembrane helix
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	axon guidance Traceable author statement. Source: Reactome cell adhesion Traceable author statement Ref.1. Source: ProtInc motor neuron axon guidance Inferred from electronic annotation. Source: Compara signal transduction Traceable author statement Ref.1. Source: ProtInc
Cellular_component	axon Inferred from electronic annotation. Source: Compara external side of plasma membrane Inferred from electronic annotation. Source: Compara integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW neuronal cell body Inferred from electronic annotation. Source: Compara
Molecular_function	receptor binding Traceable author statement Ref.1. 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:
     503-516: ISIPEHDEADEISD → N

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 27

27

Potential

Chain

28 – 583

556

CD166 antigen

PRO_0000014659

Regions

Topological domain

28 – 527

500

Extracellular Potential

Transmembrane

528 – 549

22

Helical; 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...) Ref.8 Ref.10

Glycosylation

95

1

N-linked (GlcNAc...) Ref.9 Ref.10

Glycosylation

167

1

N-linked (GlcNAc...) Ref.8

Glycosylation

265

1

N-linked (GlcNAc...) Ref.9

Glycosylation

306

1

N-linked (GlcNAc...) Potential

Glycosylation

361

1

N-linked (GlcNAc...) Potential

Glycosylation

457

1

N-linked (GlcNAc...) Ref.10 Ref.11

Glycosylation

466

1

N-linked (GlcNAc...) Ref.11

Glycosylation

480

1

N-linked (GlcNAc...) Ref.8 Ref.10

Glycosylation

499

1

N-linked (GlcNAc...) Ref.8 Ref.9

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 – 516

14

ISIPE…DEISD → N in isoform 2.

VSP_021797

Natural variant

229

1

G → D.
Corresponds to variant rs10933819 [ dbSNP | Ensembl ].

VAR_029514

Natural variant

258

1

N → S.
Corresponds to variant rs1044240 [ dbSNP | Ensembl ].

VAR_003907

Natural variant

301

1

T → M. Ref.1
Corresponds to variant rs1044243 [ dbSNP | Ensembl ].

VAR_003908

Natural variant

315

1

L → M.
Corresponds to variant rs12629872 [ dbSNP | Ensembl ].

VAR_029515

Natural variant

352

1

V → M.
Corresponds to variant rs2291375 [ dbSNP | Ensembl ].

VAR_029516

Natural variant

367

1

M → I.
Corresponds to variant rs34926152 [ dbSNP | Ensembl ].

VAR_049856

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: 4B61C53E7C61CACC	FASTA	570	63,665
	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 SANENREKVN 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] [Europe PMC] [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]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Placenta.
[5]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Lung.
[6]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 2-583 (ISOFORM 1), TISSUE SPECIFICITY.
[7]	"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] [Europe PMC] [Abstract] Cited for: DOMAIN CD6 BINDING.
[8]	"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] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT ASN-91; ASN-167; ASN-480 AND ASN-499.
[9]	"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] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-95; ASN-265 AND ASN-499, MASS SPECTROMETRY. Tissue: Plasma.
[10]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-91; ASN-95; ASN-457 AND ASN-480, MASS SPECTROMETRY. Tissue: Liver.
[11]	"Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins." Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D. Nat. Biotechnol. 27:378-386(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-457 AND ASN-466, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[12]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]	"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] [Europe PMC] [Abstract] Cited for: 3D-STRUCTURE MODELING OF 28-133.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L38608 mRNA. Translation: AAB59499.1.
DQ486139 mRNA. Translation: ABF48405.1.
DQ486140 mRNA. Translation: ABF48406.1.
AK300362 mRNA. Translation: BAG62102.1.
AK316113 mRNA. Translation: BAH14484.1.
AC023602 Genomic DNA. No translation available.
AC078806 Genomic DNA. No translation available.
AC133476 Genomic DNA. No translation available.
BC137096 mRNA. Translation: AAI37097.1.
BC137097 mRNA. Translation: AAI37098.1.
Y10183 mRNA. Translation: CAA71256.1.

IPI

IPI00015102.
IPI00807403.
IPI00944977.

PIR

I39428.

RefSeq

NP_001230209.1. NM_001243280.1.
NP_001618.2. NM_001627.3.

UniGene

Hs.591293.
Hs.740441.

3D structure databases

PDBe
RCSB PDB
PDBj

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

ProteinModelPortal

Q13740.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q13740. 2 interactions.

STRING

9606.ENSP00000305988.

Protein family/group databases

MEROPS

I43.001.

PTM databases

PhosphoSite

Q13740.

Polymorphism databases

DMDM

118572629.

Proteomic databases

PaxDb

Q13740.

PRIDE

Q13740.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000306107; ENSP00000305988; ENSG00000170017.
ENST00000472644; ENSP00000419236; ENSG00000170017.

GeneID

214.

KEGG

hsa:214.

UCSC

uc003dvw.2. human.
uc003dvy.3. human.

Organism-specific databases

CTD

214.

GeneCards

GC03P105085.

HGNC

HGNC:400. ALCAM.

HPA

CAB002148.
HPA010926.

MIM

601662. gene.

neXtProt

NX_Q13740.

PharmGKB

PA24691.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG148902.

HOGENOM

HOG000070101.

HOVERGEN

HBG050847.

InParanoid

Q13740.

KO

K06547.

OMA

GNITWYR.

OrthoDB

EOG4933J2.

Enzyme and pathway databases

Reactome

REACT_111045. Developmental Biology.

Gene expression databases

ArrayExpress

Q13740.

Bgee

Q13740.

CleanEx

HS_ALCAM.

Genevestigator

Q13740.

Family and domain databases

Gene3D

2.60.40.10. 5 hits.

InterPro

IPR013162. CD80_C2-set.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR013106. Ig_V-set.
[Graphical view]

Pfam

PF08205. C2-set_2. 1 hit.
PF07686. V-set. 1 hit.
[Graphical view]

SMART

SM00409. IG. 3 hits.
[Graphical view]

PROSITE

PS50835. IG_LIKE. 4 hits.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

ALCAM. human.

GenomeRNAi

214.

NextBio

866.

PMAP-CutDB

Q13740.

SOURCE

Search...

Entry information

Entry name

CD166_HUMAN

Accession

Primary (citable) accession number: Q13740
Secondary accession number(s): B2RNS3 , B4DTU0, O60892, Q1HGM8, Q1HGM9

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 28, 2006
Last modified:	May 29, 2013
This is version 127 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.