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Protein

CD166 antigen

Gene

ALCAM

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Cell adhesion molecule that mediates both heterotypic cell-cell contacts via its interaction with CD6, as well as homotypic cell-cell contacts (PubMed:7760007, PubMed:15496415, PubMed:15048703, PubMed:16352806, PubMed:23169771, PubMed:24945728). Promotes T-cell activation and proliferation via its interactions with CD6 (PubMed:15048703, PubMed:16352806, PubMed:24945728). Contributes to the formation and maturation of the immunological synapse via its interactions with CD6 (PubMed:15294938, PubMed:16352806). Mediates homotypic interactions with cells that express ALCAM (PubMed:15496415, PubMed:16352806). Required for normal hematopoietic stem cell engraftment in the bone marrow (PubMed:24740813). Mediates attachment of dendritic cells onto endothelial cells via homotypic interaction (PubMed:23169771). Inhibits endothelial cell migration and promotes endothelial tube formation via homotypic interactions (PubMed:15496415, PubMed:23169771). Required for normal organization of the lymph vessel network. Required for normal hematopoietic stem cell engraftment in the bone marrow. Plays a role in hematopoiesis; required for normal numbers of hematopoietic stem cells in bone marrow. Promotes in vitro osteoblast proliferation and differentiation (By similarity). Promotes neurite extension, axon growth and axon guidance; axons grow preferentially on surfaces that contain ALCAM. Mediates outgrowth and pathfinding for retinal ganglion cell axons (By similarity).By similarity6 Publications
Isoform 3: Inhibits activities of membrane-bound isoforms by competing for the same interaction partners. Inhibits cell attachment via homotypic interactions. Promotes endothelial cell migration. Inhibits endothelial cell tube formation.1 Publication

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • signaling receptor binding Source: ProtInc

GO - Biological processi

Keywordsi

Biological processAdaptive immunity, Cell adhesion, Immunity

Enzyme and pathway databases

ReactomeiR-HSA-373760 L1CAM interactions
SIGNORiQ13740

Protein family/group databases

TCDBi8.A.23.1.10 the basigin (basigin) family

Names & Taxonomyi

Protein namesi
Recommended name:
CD166 antigen
Alternative name(s):
Activated leukocyte cell adhesion molecule
CD_antigen: CD166
Gene namesi
Name:ALCAM
Synonyms:MEMD1 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000170017.12
HGNCiHGNC:400 ALCAM
MIMi601662 gene
neXtProtiNX_Q13740

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini28 – 527ExtracellularSequence analysisAdd BLAST500
Transmembranei528 – 549HelicalSequence analysisAdd BLAST22
Topological domaini550 – 583CytoplasmicSequence analysisAdd BLAST34

Keywords - Cellular componenti

Cell membrane, Cell projection, Membrane, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi214
OpenTargetsiENSG00000170017
PharmGKBiPA24691

Polymorphism and mutation databases

BioMutaiALCAM
DMDMi118572629

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 27Sequence analysisAdd BLAST27
ChainiPRO_000001465928 – 583CD166 antigenAdd BLAST556

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi43 ↔ 113PROSITE-ProRule annotationCombined sources
Glycosylationi91N-linked (GlcNAc...) asparagine2 Publications1
Glycosylationi95N-linked (GlcNAc...) asparagine2 Publications1
Disulfide bondi157 ↔ 220PROSITE-ProRule annotationCombined sources
Glycosylationi167N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi265N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi270 ↔ 313PROSITE-ProRule annotation
Glycosylationi306N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi354 ↔ 392PROSITE-ProRule annotation
Glycosylationi361N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi435 ↔ 485PROSITE-ProRule annotation
Glycosylationi457N-linked (GlcNAc...) asparagine2 Publications1
Glycosylationi466N-linked (GlcNAc...) asparagine; atypical1 Publication1
Glycosylationi480N-linked (GlcNAc...) asparagine2 Publications1
Glycosylationi499N-linked (GlcNAc...) asparagine2 Publications1

Post-translational modificationi

Glycosylated.1 Publication1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiQ13740
MaxQBiQ13740
PaxDbiQ13740
PeptideAtlasiQ13740
PRIDEiQ13740
ProteomicsDBi59670
59671 [Q13740-2]

PTM databases

iPTMnetiQ13740
PhosphoSitePlusiQ13740
SwissPalmiQ13740

Miscellaneous databases

PMAP-CutDBiQ13740

Expressioni

Tissue specificityi

Detected on hematopoietic stem cells derived from umbilical cord blood (PubMed:24740813). Detected on lymph vessel endothelial cells, skin and tonsil (PubMed:23169771). Detected on peripheral blood monocytes (PubMed:15048703). Detected on monocyte-derived dendritic cells (at protein level) (PubMed:16352806). Detected at low levels in spleen, placenta, liver (PubMed:9502422). Expressed by activated T-cells, B-cells, monocytes and thymic epithelial cells (PubMed:7760007). Isoform 1 and isoform 3 are detected in vein and artery endothelial cells, astrocytes, keratinocytes and artery smooth muscle cells (PubMed:15496415). Expressed by neurons in the brain. Restricted expression in tumor cell lines. Detected in highly metastasizing melanoma cell lines (PubMed:9502422).4 Publications

Inductioni

Up-regulated by TNF and IFNG (at protein level).1 Publication

Gene expression databases

BgeeiENSG00000170017
CleanExiHS_ALCAM
ExpressionAtlasiQ13740 baseline and differential
GenevisibleiQ13740 HS

Organism-specific databases

HPAiCAB002148
HPA010926

Interactioni

Subunit structurei

Homodimer (PubMed:7760007, PubMed:16352806, PubMed:15048703, PubMed:26146185). Interacts (via extracellular domain) with CD6 (via extracellular domain) (PubMed:7760007, PubMed:8823162, PubMed:15048703, PubMed:16914752, PubMed:24945728, PubMed:26146185). Homodimerization and interaction with CD6 involve the same region and cannot occur simultaneously. The affinity for CD6 is much higher than the affinity for self-association (PubMed:15048703). Interacts (via glycosylated extracellular domain) with LGALS1 and LGALS3 (PubMed:24945728). Interaction with LGALS1 or LGALS3 inhibits interaction with CD6 (PubMed:24945728).7 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • signaling receptor binding Source: ProtInc

Protein-protein interaction databases

BioGridi106716, 15 interactors
DIPiDIP-39093N
IntActiQ13740, 5 interactors
MINTiQ13740
STRINGi9606.ENSP00000305988

Structurei

Secondary structure

1583
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi30 – 34Combined sources5
Beta strandi39 – 41Combined sources3
Beta strandi51 – 59Combined sources9
Beta strandi65 – 72Combined sources8
Turni73 – 75Combined sources3
Beta strandi78 – 80Combined sources3
Helixi84 – 86Combined sources3
Turni87 – 89Combined sources3
Beta strandi90 – 92Combined sources3
Beta strandi98 – 102Combined sources5
Helixi105 – 107Combined sources3
Beta strandi109 – 117Combined sources9
Beta strandi120 – 132Combined sources13
Beta strandi138 – 141Combined sources4
Beta strandi144 – 148Combined sources5
Beta strandi152 – 164Combined sources13
Beta strandi167 – 172Combined sources6
Turni181 – 183Combined sources3
Beta strandi184 – 192Combined sources9
Turni194 – 196Combined sources3
Beta strandi199 – 207Combined sources9
Helixi211 – 213Combined sources3
Beta strandi218 – 226Combined sources9
Beta strandi229 – 234Combined sources6
Beta strandi241 – 243Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1KJCmodel-A28-133[»]
5A2FX-ray1.86A1-583[»]
ProteinModelPortaliQ13740
SMRiQ13740
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini28 – 120Ig-like V-type 1Add BLAST93
Domaini125 – 234Ig-like V-type 2Add BLAST110
Domaini245 – 328Ig-like C2-type 1Add BLAST84
Domaini333 – 409Ig-like C2-type 2Add BLAST77
Domaini416 – 501Ig-like C2-type 3Add BLAST86

Domaini

The CD6 binding site is located in the N-terminal Ig-like domain.1 Publication

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IFQ2 Eukaryota
ENOG410ZWU9 LUCA
GeneTreeiENSGT00530000063457
HOGENOMiHOG000070101
HOVERGENiHBG050847
InParanoidiQ13740
KOiK06547
OMAiCTAENQL
OrthoDBiEOG091G04XY
PhylomeDBiQ13740
TreeFamiTF321859

Family and domain databases

Gene3Di2.60.40.10, 5 hits
InterProiView protein in InterPro
IPR013162 CD80_C2-set
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR003599 Ig_sub
IPR003598 Ig_sub2
IPR013106 Ig_V-set
PfamiView protein in Pfam
PF08205 C2-set_2, 1 hit
SMARTiView protein in SMART
SM00409 IG, 3 hits
SM00408 IGc2, 3 hits
SM00406 IGv, 1 hit
SUPFAMiSSF48726 SSF48726, 6 hits
PROSITEiView protein in PROSITE
PS50835 IG_LIKE, 4 hits

Sequences (4)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q13740-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MESKGASSCR LLFCLLISAT VFRPGLGWYT VNSAYGDTII IPCRLDVPQN
60 70 80 90 100
LMFGKWKYEK PDGSPVFIAF RSSTKKSVQY DDVPEYKDRL NLSENYTLSI
110 120 130 140 150
SNARISDEKR FVCMLVTEDN VFEAPTIVKV FKQPSKPEIV SKALFLETEQ
160 170 180 190 200
LKKLGDCISE DSYPDGNITW YRNGKVLHPL EGAVVIIFKK EMDPVTQLYT
210 220 230 240 250
MTSTLEYKTT KADIQMPFTC SVTYYGPSGQ KTIHSEQAVF DIYYPTEQVT
260 270 280 290 300
IQVLPPKNAI KEGDNITLKC LGNGNPPPEE FLFYLPGQPE GIRSSNTYTL
310 320 330 340 350
TDVRRNATGD YKCSLIDKKS MIASTAITVH YLDLSLNPSG EVTRQIGDAL
360 370 380 390 400
PVSCTISASR NATVVWMKDN IRLRSSPSFS SLHYQDAGNY VCETALQEVE
410 420 430 440 450
GLKKRESLTL IVEGKPQIKM TKKTDPSGLS KTIICHVEGF PKPAIQWTIT
460 470 480 490 500
GSGSVINQTE ESPYINGRYY SKIIISPEEN VTLTCTAENQ LERTVNSLNV
510 520 530 540 550
SAISIPEHDE ADEISDENRE KVNDQAKLIV GIVVGLLLAA LVAGVVYWLY
560 570 580
MKKSKTASKH VNKDLGNMEE NKKLEENNHK TEA
Length:583
Mass (Da):65,102
Last modified:November 28, 2006 - v2
Checksum:i68FEFD67C14B0C57
GO
Isoform 2 (identifier: Q13740-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     503-516: ISIPEHDEADEISD → N

Show »
Length:570
Mass (Da):63,665
Checksum:i4B61C53E7C61CACC
GO
Isoform 3 (identifier: Q13740-3) [UniParc]FASTAAdd to basket
Also known as: sALCAM

The sequence of this isoform differs from the canonical sequence as follows:
     132-133: KQ → SK
     134-583: Missing.

Note: Secreted form, inhibits isoform 1 homophilic interaction.
Show »
Length:133
Mass (Da):15,109
Checksum:iC7B35209EA8BFC35
GO
Isoform 4 (identifier: Q13740-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-191: Missing.
     244-330: Missing.

Note: No experimental confirmation available.
Show »
Length:305
Mass (Da):33,878
Checksum:iFB5F5FBB6D4E6DCC
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_029514229G → D. Corresponds to variant dbSNP:rs10933819Ensembl.1
Natural variantiVAR_003907258N → S. Corresponds to variant dbSNP:rs1044240Ensembl.1
Natural variantiVAR_003908301T → M1 PublicationCorresponds to variant dbSNP:rs1044243Ensembl.1
Natural variantiVAR_029515315L → M. Corresponds to variant dbSNP:rs12629872Ensembl.1
Natural variantiVAR_029516352V → M. Corresponds to variant dbSNP:rs2291375Ensembl.1
Natural variantiVAR_049856367M → I. Corresponds to variant dbSNP:rs34926152Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0535291 – 191Missing in isoform 4. 1 PublicationAdd BLAST191
Alternative sequenceiVSP_053530132 – 133KQ → SK in isoform 3. 2 Publications2
Alternative sequenceiVSP_053531134 – 583Missing in isoform 3. 2 PublicationsAdd BLAST450
Alternative sequenceiVSP_053532244 – 330Missing in isoform 4. 1 PublicationAdd BLAST87
Alternative sequenceiVSP_021797503 – 516ISIPE…DEISD → N in isoform 2. 2 PublicationsAdd BLAST14

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L38608 mRNA Translation: AAB59499.1
AY644765 mRNA Translation: AAV28819.1
DQ486139 mRNA Translation: ABF48405.1
DQ486140 mRNA Translation: ABF48406.1
AK127617 mRNA Translation: BAC87059.1
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.
BC057809 mRNA Translation: AAH57809.1
BC137096 mRNA Translation: AAI37097.1
BC137097 mRNA Translation: AAI37098.1
Y10183 mRNA Translation: CAA71256.1
CCDSiCCDS33810.1 [Q13740-1]
CCDS58841.1 [Q13740-2]
PIRiI39428
RefSeqiNP_001230209.1, NM_001243280.1 [Q13740-2]
NP_001230212.1, NM_001243283.1 [Q13740-3]
NP_001618.2, NM_001627.3 [Q13740-1]
UniGeneiHs.591293
Hs.740441

Genome annotation databases

EnsembliENST00000306107; ENSP00000305988; ENSG00000170017 [Q13740-1]
ENST00000472644; ENSP00000419236; ENSG00000170017 [Q13740-2]
GeneIDi214
KEGGihsa:214
UCSCiuc003dvx.4 human [Q13740-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiCD166_HUMAN
AccessioniPrimary (citable) accession number: Q13740
Secondary accession number(s): B2RNS3
, B4DTU0, O60892, Q1HGM8, Q1HGM9, Q6PEY4, Q6ZS95
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 28, 2006
Last modified: June 20, 2018
This is version 173 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

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