P43121 (MUC18_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	646 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	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.

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 Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cell adhesion Traceable author statement Ref.2. Source: ProtInc glomerular filtration Inferred from expression pattern PubMed 20354148. Source: UniProtKB vascular wound healing Inferred from expression pattern PubMed 20354148. Source: UniProtKB
Cellular_component	external side of plasma membrane Inferred from direct assay PubMed 20354148. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 23	23	Ref.7
	Chain	24 – 646	623	Cell surface glycoprotein MUC18		PRO_0000014891
Regions
	Topological domain	24 – 559	536	Extracellular Potential
	Transmembrane	560 – 583	24	Helical; Potential
	Topological domain	584 – 646	63	Cytoplasmic Potential
	Domain	24 – 129	106	Ig-like V-type 1
	Domain	139 – 242	104	Ig-like V-type 2
	Domain	244 – 330	87	Ig-like C2-type 1
	Domain	335 – 424	90	Ig-like C2-type 2
	Domain	430 – 510	81	Ig-like C2-type 3
Amino acid modifications
	Modified residue	614	1	Phosphoserine Ref.11 Ref.13
	Modified residue	628	1	Phosphoserine Ref.13
	Glycosylation	56	1	N-linked (GlcNAc...) Potential
	Glycosylation	418	1	N-linked (GlcNAc...) Potential
	Glycosylation	449	1	N-linked (GlcNAc...) Potential
	Glycosylation	467	1	N-linked (GlcNAc...) Ref.12
	Glycosylation	508	1	N-linked (GlcNAc...) Potential
	Glycosylation	518	1	N-linked (GlcNAc...) Potential
	Glycosylation	527	1	N-linked (GlcNAc...) Potential
	Glycosylation	544	1	N-linked (GlcNAc...) Potential
	Disulfide bond	48 ↔ 116		Probable
	Disulfide bond	161 ↔ 223		Probable
	Disulfide bond	272 ↔ 320		Probable
	Disulfide bond	365 ↔ 407		Probable
	Disulfide bond	452 ↔ 499		Probable
Natural variations
	Alternative sequence	1 – 187	187	MGLPR…EEKNR → MVYIVRQFLLYNVSGSVYLD QLIVLLTAKFSILRIAGSRV HHSPFSGHLDGCSFLSLQHS LHTSLDMSRHENVFLGLTLS SKSAGLKGFQLAFVPGLLQG TGGYLDGPLPTPVDNPRVGL EVGLRLSLPPLPPCPG in isoform 2.		VSP_016938
	Alternative sequence	549 – 646	98	ERKLP…IDLRH → GKPGLAREQGCARASFLPCP SPESPVQKGE in isoform 2.		VSP_016939
	Natural variant	89	1	E → G. Ref.5 Corresponds to variant rs34587557 [ dbSNP | Ensembl ].		VAR_049915
Experimental info
	Sequence conflict	322 – 324	3	GLD → AWN Ref.1
	Sequence conflict	322 – 324	3	GLD → AWN Ref.2
	Sequence conflict	383	1	G → D Ref.1
	Sequence conflict	383	1	G → D Ref.2
	Sequence conflict	383	1	G → D Ref.3
	Sequence conflict	424 – 425	2	NV → KL Ref.1
	Sequence conflict	424 – 425	2	NV → KL Ref.2
	Sequence conflict	606	1	S → T Ref.1
	Sequence conflict	606	1	S → T Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 10, 2006. Version 2. Checksum: E46CB8AC7BA0738E	FASTA	646	71,607
	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
	Isoform 2 [UniParc]. Checksum: 68F5C36C5FFD36D6	FASTA	527	57,605
	10 20 30 40 50 60 MVYIVRQFLL YNVSGSVYLD QLIVLLTAKF SILRIAGSRV HHSPFSGHLD GCSFLSLQHS 70 80 90 100 110 120 LHTSLDMSRH ENVFLGLTLS SKSAGLKGFQ LAFVPGLLQG TGGYLDGPLP TPVDNPRVGL 130 140 150 160 170 180 EVGLRLSLPP LPPCPGVHIQ SSQTVESSGL YTLQSILKAQ LVKEDKDAQF YCELNYRLPS 190 200 210 220 230 240 GNHMKESREV TVPVFYPTEK VWLEVEPVGM LKEGDRVEIR CLADGNPPPH FSISKQNPST 250 260 270 280 290 300 REAEEETTND NGVLVLEPAR KEHSGRYECQ GLDLDTMISL LSEPQELLVN YVSDVRVSPA 310 320 330 340 350 360 APERQEGSSL TLTCEAESSQ DLEFQWLREE TGQVLERGPV LQLHDLKREA GGGYRCVASV 370 380 390 400 410 420 PSIPGLNRTQ LVNVAIFGPP WMAFKERKVW VKENMVLNLS CEASGHPRPT ISWNVNGTAS 430 440 450 460 470 480 EQDQDPQRVL STLNVLVTPE LLETGVECTA SNDLGKNTSI LFLELVNLTT LTPDSNTTTG 490 500 510 520 LSTSTASPHT RANSTSTGKP GLAREQGCAR ASFLPCPSPE SPVQKGE

References

	« Hide 'large scale' referencesShow '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. , 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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 , 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.
IPI	IPI00016334. IPI00445227.
PIR	I38049.
RefSeq	NP_006491.2. NM_006500.2.
UniGene	Hs.599039.
3D structure databases
ProteinModelPortal	P43121.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-52791N.
IntAct	P43121. 1 interaction.
MINT	MINT-1184800.
STRING	9606.ENSP00000264036.
PTM databases
PhosphoSite	P43121.
Polymorphism databases
DMDM	85681878.
Proteomic databases
PaxDb	P43121.
PeptideAtlas	P43121.
PRIDE	P43121.
Protocols and materials databases
DNASU	4162.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000264036; ENSP00000264036; ENSG00000076706. ENST00000392814; ENSP00000376561; ENSG00000076706.
GeneID	4162.
KEGG	hsa:4162.
UCSC	uc001pwf.3. human.
Organism-specific databases
CTD	4162.
GeneCards	GC11M119179.
HGNC	HGNC:6934. MCAM.
HPA	CAB002147. HPA008848.
MIM	155735. gene.
neXtProt	NX_P43121.
PharmGKB	PA30678.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG116686.
HOGENOM	HOG000015427.
HOVERGEN	HBG002808.
InParanoid	P43121.
KO	K06534.
OMA	IFLCQGK.
OrthoDB	EOG4ZGPBZ.
PhylomeDB	P43121.
Gene expression databases
Bgee	P43121.
CleanEx	HS_MCAM.
Genevestigator	P43121.
GermOnline	ENSG00000076706. Homo sapiens.
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. IPR003598. Ig_sub2. IPR013106. Ig_V-set. IPR013151. Immunoglobulin. [Graphical view]
Pfam	PF08205. C2-set_2. 1 hit. PF00047. ig. 2 hits. PF07686. V-set. 1 hit. [Graphical view]
SMART	SM00409. IG. 1 hit. SM00408. IGc2. 2 hits. [Graphical view]
PROSITE	PS50835. IG_LIKE. 5 hits. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	MCAM. human.
GenomeRNAi	4162.
NextBio	16398.
SOURCE	Search...

Entry information

Entry name

MUC18_HUMAN

Accession

Primary (citable) accession number: P43121
Secondary accession number(s): O95812 , Q59E86, Q6PHR3, Q6ZTR2

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	January 10, 2006
Last modified:	May 1, 2013
This is version 122 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.