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P43121 (MUC18_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 133. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cell surface glycoprotein MUC18
Alternative name(s):
Cell surface glycoprotein P1H12
Melanoma cell adhesion molecule
Melanoma-associated antigen A32
Melanoma-associated antigen MUC18
S-endo 1 endothelial-associated antigen
CD_antigen=CD146
Gene names
Name:MCAM
Synonyms:MUC18
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length646 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Plays a role in cell adhesion, and in cohesion of the endothelial monolayer at intercellular junctions in vascular tissue. Its expression may allow melanoma cells to interact with cellular elements of the vascular system, thereby enhancing hematogeneous tumor spread. Could be an adhesion molecule active in neural crest cells during embryonic development. Acts as surface receptor that triggers tyrosine phosphorylation of FYN and PTK2/FAK1, and a transient increase in the intracellular calcium concentration. Ref.9 Ref.10

Subcellular location

Membrane; Single-pass type I membrane protein.

Tissue specificity

Detected in endothelial cells in vascular tissue throughout the body. May appear at the surface of neural crest cells during their embryonic migration. Appears to be limited to vascular smooth muscle in normal adult tissues. Associated with tumor progression and the development of metastasis in human malignant melanoma. Expressed most strongly on metastatic lesions and advanced primary tumors and is only rarely detected in benign melanocytic nevi and thin primary melanomas with a low probability of metastasis.

Sequence similarities

Contains 3 Ig-like C2-type (immunoglobulin-like) domains.

Contains 2 Ig-like V-type (immunoglobulin-like) domains.

Sequence caution

The sequence BAD93162.1 differs from that shown. Reason: Erroneous initiation.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P43121-1)

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: P43121-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-187: MGLPRLVCAF...GRPLKEEKNR → MVYIVRQFLL...SLPPLPPCPG
     549-646: ERKLPEPESR...QGEKYIDLRH → GKPGLAREQGCARASFLPCPSPESPVQKGE
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323 Ref.7
Chain24 – 646623Cell surface glycoprotein MUC18
PRO_0000014891

Regions

Topological domain24 – 559536Extracellular Potential
Transmembrane560 – 58324Helical; Potential
Topological domain584 – 64663Cytoplasmic Potential
Domain24 – 129106Ig-like V-type 1
Domain139 – 242104Ig-like V-type 2
Domain244 – 33087Ig-like C2-type 1
Domain335 – 42490Ig-like C2-type 2
Domain430 – 51081Ig-like C2-type 3

Amino acid modifications

Modified residue6141Phosphoserine Ref.11 Ref.13
Modified residue6281Phosphoserine Ref.13
Glycosylation561N-linked (GlcNAc...) Potential
Glycosylation4181N-linked (GlcNAc...) Potential
Glycosylation4491N-linked (GlcNAc...) Potential
Glycosylation4671N-linked (GlcNAc...) Ref.12
Glycosylation5081N-linked (GlcNAc...) Potential
Glycosylation5181N-linked (GlcNAc...) Potential
Glycosylation5271N-linked (GlcNAc...) Potential
Glycosylation5441N-linked (GlcNAc...) Potential
Disulfide bond48 ↔ 116 Probable
Disulfide bond161 ↔ 223 Probable
Disulfide bond272 ↔ 320 Probable
Disulfide bond365 ↔ 407 Probable
Disulfide bond452 ↔ 499 Probable

Natural variations

Alternative sequence1 – 187187MGLPR…EEKNR → MVYIVRQFLLYNVSGSVYLD QLIVLLTAKFSILRIAGSRV HHSPFSGHLDGCSFLSLQHS LHTSLDMSRHENVFLGLTLS SKSAGLKGFQLAFVPGLLQG TGGYLDGPLPTPVDNPRVGL EVGLRLSLPPLPPCPG in isoform 2.
VSP_016938
Alternative sequence549 – 64698ERKLP…IDLRH → GKPGLAREQGCARASFLPCP SPESPVQKGE in isoform 2.
VSP_016939
Natural variant891E → G. Ref.5
Corresponds to variant rs34587557 [ dbSNP | Ensembl ].
VAR_049915

Experimental info

Sequence conflict322 – 3243GLD → AWN Ref.1
Sequence conflict322 – 3243GLD → AWN Ref.2
Sequence conflict3831G → D Ref.1
Sequence conflict3831G → D Ref.2
Sequence conflict3831G → D Ref.3
Sequence conflict424 – 4252NV → KL Ref.1
Sequence conflict424 – 4252NV → KL Ref.2
Sequence conflict6061S → T Ref.1
Sequence conflict6061S → T Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 10, 2006. Version 2.
Checksum: E46CB8AC7BA0738E

FASTA64671,607
        10         20         30         40         50         60 
MGLPRLVCAF LLAACCCCPR VAGVPGEAEQ PAPELVEVEV GSTALLKCGL SQSQGNLSHV 

        70         80         90        100        110        120 
DWFSVHKEKR TLIFRVRQGQ GQSEPGEYEQ RLSLQDRGAT LALTQVTPQD ERIFLCQGKR 

       130        140        150        160        170        180 
PRSQEYRIQL RVYKAPEEPN IQVNPLGIPV NSKEPEEVAT CVGRNGYPIP QVIWYKNGRP 

       190        200        210        220        230        240 
LKEEKNRVHI QSSQTVESSG LYTLQSILKA QLVKEDKDAQ FYCELNYRLP SGNHMKESRE 

       250        260        270        280        290        300 
VTVPVFYPTE KVWLEVEPVG MLKEGDRVEI RCLADGNPPP HFSISKQNPS TREAEEETTN 

       310        320        330        340        350        360 
DNGVLVLEPA RKEHSGRYEC QGLDLDTMIS LLSEPQELLV NYVSDVRVSP AAPERQEGSS 

       370        380        390        400        410        420 
LTLTCEAESS QDLEFQWLRE ETGQVLERGP VLQLHDLKRE AGGGYRCVAS VPSIPGLNRT 

       430        440        450        460        470        480 
QLVNVAIFGP PWMAFKERKV WVKENMVLNL SCEASGHPRP TISWNVNGTA SEQDQDPQRV 

       490        500        510        520        530        540 
LSTLNVLVTP ELLETGVECT ASNDLGKNTS ILFLELVNLT TLTPDSNTTT GLSTSTASPH 

       550        560        570        580        590        600 
TRANSTSTER KLPEPESRGV VIVAVIVCIL VLAVLGAVLY FLYKKGKLPC RRSGKQEITL 

       610        620        630        640 
PPSRKSELVV EVKSDKLPEE MGLLQGSSGD KRAPGDQGEK YIDLRH 

« Hide

Isoform 2 [UniParc].

Checksum: 68F5C36C5FFD36D6
Show »

FASTA52757,605

References

« Hide 'large scale' references
[1]"MUC18, a marker of tumor progression in human melanoma, shows sequence similarity to the neural cell adhesion molecules of the immunoglobulin superfamily."
Lehmann J.M., Riethmueller G., Johnson J.P.
Proc. Natl. Acad. Sci. U.S.A. 86:9891-9895(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Melanoma.
[2]"Genomic organization of the melanoma-associated glycoprotein MUC18: implications for the evolution of the immunoglobulin domains."
Sers C., Kirsch K., Rothbaecher U., Riethmueller G., Johnson J.P.
Proc. Natl. Acad. Sci. U.S.A. 90:8514-8518(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), SEQUENCE REVISION.
Tissue: Melanoma.
[3]"Identification and functional assessment of endothelial P1H12."
Solovey A.N., Gui L., Chang L., Enenstein J., Browne P.V., Hebbel R.P.
J. Lab. Clin. Med. 138:322-331(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[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. expand/collapse author list , 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: Trachea.
[5]Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F.
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT GLY-89.
Tissue: Aortic endothelium.
[6]"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: PNS.
[7]"Isolation and functional characterization of the A32 melanoma-associated antigen."
Shih I.-M., Eleder D.E., Speicher D., Johnson J.P., Herlyn M.
Cancer Res. 54:2514-2520(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 24-44; 98-112; 135-153; 240-260; 379-389 AND 460-478.
[8]"Identification of the S-endo 1 endothelial-associated antigen."
Bardin N., Frances V., Lesaule G., Horschowski N., George F., Sampol J.
Biochem. Biophys. Res. Commun. 218:210-216(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 27-40; 98-112 AND 236-260.
[9]"The progression associated antigen MUC18: a unique member of the immunoglobulin supergene family."
Johnson J.P., Rothbacher U., Sers C.
Melanoma Res. 3:337-340(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"Outside-in signaling pathway linked to CD146 engagement in human endothelial cells."
Anfosso F., Bardin N., Vivier E., Sabatier F., Sampol J., Dignat-George F.
J. Biol. Chem. 276:1564-1569(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[11]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-614, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[12]"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-467.
Tissue: Liver.
[13]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-614 AND SER-628, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[14]"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].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M29277 mRNA. Translation: AAA20824.1.
M28882 mRNA. Translation: AAA20922.1.
X68264 expand/collapse EMBL AC list , X68265, X68266, X68267, X68268, X68270, X68271 Genomic DNA. Translation: CAA48332.1.
AF089868 mRNA. Translation: AAD17799.1.
AK126303 mRNA. Translation: BAC86520.1.
AB209925 mRNA. Translation: BAD93162.1. Different initiation.
BC056418 mRNA. Translation: AAH56418.1.
CCDSCCDS31690.1. [P43121-1]
PIRI38049.
RefSeqNP_006491.2. NM_006500.2. [P43121-1]
UniGeneHs.599039.

3D structure databases

ProteinModelPortalP43121.
SMRP43121. Positions 27-510.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110332. 4 interactions.
DIPDIP-52791N.
IntActP43121. 3 interactions.
MINTMINT-1184800.
STRING9606.ENSP00000264036.

PTM databases

PhosphoSiteP43121.

Polymorphism databases

DMDM85681878.

Proteomic databases

MaxQBP43121.
PaxDbP43121.
PeptideAtlasP43121.
PRIDEP43121.

Protocols and materials databases

DNASU4162.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000264036; ENSP00000264036; ENSG00000076706. [P43121-1]
ENST00000392814; ENSP00000376561; ENSG00000076706. [P43121-2]
GeneID4162.
KEGGhsa:4162.
UCSCuc001pwf.3. human. [P43121-1]

Organism-specific databases

CTD4162.
GeneCardsGC11M119179.
HGNCHGNC:6934. MCAM.
HPACAB002147.
HPA008848.
MIM155735. gene.
neXtProtNX_P43121.
PharmGKBPA30678.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG116686.
HOGENOMHOG000015427.
HOVERGENHBG002808.
InParanoidP43121.
KOK06534.
OMADQGEKYI.
OrthoDBEOG7RFTH4.
PhylomeDBP43121.
TreeFamTF330534.

Gene expression databases

BgeeP43121.
CleanExHS_MCAM.
GenevestigatorP43121.

Family and domain databases

Gene3D2.60.40.10. 5 hits.
InterProIPR013162. CD80_C2-set.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR013106. Ig_V-set.
IPR013151. Immunoglobulin.
[Graphical view]
PfamPF08205. C2-set_2. 1 hit.
PF00047. ig. 1 hit.
PF07686. V-set. 1 hit.
[Graphical view]
SMARTSM00409. IG. 1 hit.
SM00408. IGc2. 2 hits.
[Graphical view]
PROSITEPS50835. IG_LIKE. 5 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSMCAM. human.
GeneWikiCD146.
GenomeRNAi4162.
NextBio16398.
PROP43121.
SOURCESearch...

Entry information

Entry nameMUC18_HUMAN
AccessionPrimary (citable) accession number: P43121
Secondary accession number(s): O95812 expand/collapse secondary AC list , Q59E86, Q6PHR3, Q6ZTR2
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: January 10, 2006
Last modified: July 9, 2014
This is version 133 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries