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Protein

CD166 antigen

Gene

ALCAM

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

  • receptor binding Source: ProtInc

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Adaptive immunity, Cell adhesion, Immunity

Enzyme and pathway databases

BioCyciZFISH:ENSG00000170017-MONOMER.
ReactomeiR-HSA-373760. L1CAM interactions.

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

HGNCiHGNC:400. ALCAM.

Subcellular locationi

Isoform 3 :
  • Secreted 1 Publication

Topology

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

GO - Cellular componenti

  • axon Source: UniProtKB
  • dendrite Source: UniProtKB-SubCell
  • external side of plasma membrane Source: Ensembl
  • extracellular exosome Source: UniProtKB
  • focal adhesion Source: UniProtKB
  • immunological synapse Source: UniProtKB
  • integral component of plasma membrane Source: UniProtKB
  • intrinsic component of plasma membrane Source: UniProtKB
  • neuronal cell body Source: Ensembl
Complete GO annotation...

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...)2 Publications1
Glycosylationi95N-linked (GlcNAc...)2 Publications1
Disulfide bondi157 ↔ 220PROSITE-ProRule annotationCombined sources
Glycosylationi167N-linked (GlcNAc...)1 Publication1
Glycosylationi265N-linked (GlcNAc...)1 Publication1
Disulfide bondi270 ↔ 313PROSITE-ProRule annotation
Glycosylationi306N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi354 ↔ 392PROSITE-ProRule annotation
Glycosylationi361N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi435 ↔ 485PROSITE-ProRule annotation
Glycosylationi457N-linked (GlcNAc...)2 Publications1
Glycosylationi466N-linked (GlcNAc...); atypical1 Publication1
Glycosylationi480N-linked (GlcNAc...)2 Publications1
Glycosylationi499N-linked (GlcNAc...)2 Publications1

Post-translational modificationi

Glycosylated.1 Publication1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiQ13740.
MaxQBiQ13740.
PaxDbiQ13740.
PeptideAtlasiQ13740.
PRIDEiQ13740.

PTM databases

iPTMnetiQ13740.
PhosphoSitePlusiQ13740.
SwissPalmiQ13740.

Miscellaneous databases

PMAP-CutDBQ13740.

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

WithEntry#Exp.IntActNotes
CD6P302032EBI-1188108,EBI-2873748
LGALS1P093823EBI-1188108,EBI-1048875
LGALS3P179313EBI-1188108,EBI-1170392

GO - Molecular functioni

  • receptor binding Source: ProtInc

Protein-protein interaction databases

BioGridi106716. 11 interactors.
DIPiDIP-39093N.
IntActiQ13740. 5 interactors.
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

Sequence similaritiesi

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

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

Family and domain databases

Gene3Di2.60.40.10. 5 hits.
InterProiIPR013162. CD80_C2-set.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR013106. Ig_V-set.
[Graphical view]
PfamiPF08205. C2-set_2. 1 hit.
[Graphical view]
SMARTiSM00409. IG. 3 hits.
SM00408. IGc2. 3 hits.
SM00406. IGv. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 6 hits.
PROSITEiPS50835. IG_LIKE. 4 hits.
[Graphical view]

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 rs10933819dbSNPEnsembl.1
Natural variantiVAR_003907258N → S.Corresponds to variant rs1044240dbSNPEnsembl.1
Natural variantiVAR_003908301T → M.1 PublicationCorresponds to variant rs1044243dbSNPEnsembl.1
Natural variantiVAR_029515315L → M.Corresponds to variant rs12629872dbSNPEnsembl.1
Natural variantiVAR_029516352V → M.Corresponds to variant rs2291375dbSNPEnsembl.1
Natural variantiVAR_049856367M → I.Corresponds to variant rs34926152dbSNPEnsembl.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

Cross-referencesi

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.

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...

Protein-protein interaction databases

BioGridi106716. 11 interactors.
DIPiDIP-39093N.
IntActiQ13740. 5 interactors.
STRINGi9606.ENSP00000305988.

PTM databases

iPTMnetiQ13740.
PhosphoSitePlusiQ13740.
SwissPalmiQ13740.

Polymorphism and mutation databases

BioMutaiALCAM.
DMDMi118572629.

Proteomic databases

EPDiQ13740.
MaxQBiQ13740.
PaxDbiQ13740.
PeptideAtlasiQ13740.
PRIDEiQ13740.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi214.
DisGeNETi214.
GeneCardsiALCAM.
HGNCiHGNC:400. ALCAM.
HPAiCAB002148.
HPA010926.
MIMi601662. gene.
neXtProtiNX_Q13740.
OpenTargetsiENSG00000170017.
PharmGKBiPA24691.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000170017-MONOMER.
ReactomeiR-HSA-373760. L1CAM interactions.

Miscellaneous databases

ChiTaRSiALCAM. human.
GeneWikiiALCAM.
GenomeRNAii214.
PMAP-CutDBQ13740.
PROiQ13740.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000170017.
CleanExiHS_ALCAM.
ExpressionAtlasiQ13740. baseline and differential.
GenevisibleiQ13740. HS.

Family and domain databases

Gene3Di2.60.40.10. 5 hits.
InterProiIPR013162. CD80_C2-set.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR013106. Ig_V-set.
[Graphical view]
PfamiPF08205. C2-set_2. 1 hit.
[Graphical view]
SMARTiSM00409. IG. 3 hits.
SM00408. IGc2. 3 hits.
SM00406. IGv. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 6 hits.
PROSITEiPS50835. IG_LIKE. 4 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCD166_HUMAN
AccessioniPrimary (citable) accession number: Q13740
Secondary accession number(s): B2RNS3
, B4DTU0, O60892, Q1HGM8, Q1HGM9, Q6PEY4, Q6ZS95
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 28, 2006
Last modified: November 2, 2016
This is version 162 of the entry and version 2 of the sequence. [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
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.