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Q14CZ8 (HECAM_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 72. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Hepatocyte cell adhesion molecule

Short name=Protein hepaCAM
Gene names
Name:HEPACAM
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length416 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Involved in regulating cell motility and cell-matrix interactions. May inhibit cell growth through suppression of cell proliferation. Ref.1 Ref.5

Subunit structure

Homodimer. Dimer formation occurs predominantly through cis interactions on the cell surface. Part of a complex containing MLC1, TRPV4, AQP4 and ATP1B1. Ref.5 Ref.6

Subcellular location

Cytoplasm. Membrane; Single-pass type I membrane protein; Cytoplasmic side. Note: In MCF-7 breast carcinoma and hepatic Hep 3B2.1-7 and Hep-G2 cell lines, localization of HEPACAM is cell density-dependent. In well spread cells, localized to punctate structures in the perinuclear membrane, cytoplasm, and at cell surface of protusions. In confluent cells, localized predominantly to the cytoplasmic membrane, particularly in areas of cell-cell contacts. Colocalizes with CDH1. Ref.1 Ref.5

Induction

Down-regulated in 20 out of 23 of hepatocellular carcinoma (HCC) samples and is undetectable in 5 HCC cell lines tested. Ref.1

Domain

The cytoplasmic domain plays an important role in regulation of cell-matrix adhesion and cell motility. Ref.5

Post-translational modification

N-glycosylated. Ref.1 Ref.5

Involvement in disease

Leukoencephalopathy, megalencephalic, with subcortical cysts, 2A (MLC2A) [MIM:613925]: A neurodegenerative disorder characterized by infantile-onset macrocephaly and later onset of motor deterioration, with ataxia and spasticity, seizures, and cognitive decline of variable severity. The brain appears swollen on magnetic resonance imaging with white-matter abnormalities and subcortical cysts, in all stages of the disease.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7

Leukoencephalopathy, megalencephalic, with subcortical cysts, 2B (MLC2B) [MIM:613926]: A neurodegenerative disorder characterized by infantile-onset of macrocephaly and mildly delayed motor development associated with white-matter abnormalities on brain magnetic resonance imaging. The phenotype is milder that MLC2A, with better preserved cerebellar white matter and no subcortical cysts outside the temporal region. On follow-up, patients show normal or almost normal motor function. Some patients have normal intelligence, whereas others have a significant cognitive deficiency.
Note: The disease is caused by mutations affecting the gene represented in this entry.

Sequence similarities

Contains 1 Ig-like C2-type (immunoglobulin-like) domain.

Contains 1 Ig-like V-type (immunoglobulin-like) domain.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 Ref.1 (identifier: Q14CZ8-1)

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 Ref.2 (identifier: Q14CZ8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     293-367: ADTLPRSGEQ...ARRYPRSPAR → GELPATQSPI...PSTLSVSVHE
     368-416: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3333 Potential
Chain34 – 416383Hepatocyte cell adhesion molecule
PRO_0000298777

Regions

Topological domain34 – 240207Extracellular Potential
Transmembrane241 – 26121Helical; Potential
Topological domain262 – 416155Cytoplasmic Potential
Domain34 – 142109Ig-like V-type
Domain148 – 23487Ig-like C2-type

Amino acid modifications

Glycosylation351N-linked (GlcNAc...) Potential
Glycosylation1381N-linked (GlcNAc...) Potential
Glycosylation1671N-linked (GlcNAc...) Potential
Glycosylation1891N-linked (GlcNAc...) Potential
Disulfide bond168 ↔ 217 By similarity

Natural variations

Alternative sequence293 – 36775ADTLP…RSPAR → GELPATQSPIPSTIRSVGCW EKAELGDKENSSAGTLPSDL GASKGKEPEPASLASSHSLP RRHAMPSTLSVSVHE in isoform 2. Ref.2
VSP_052497
Alternative sequence368 – 41649Missing in isoform 2. Ref.2
VSP_052498
Natural variant231L → H in MLC2A. Ref.7
VAR_065849
Natural variant891G → D in MLC2B. Ref.7
VAR_065850
Natural variant891G → S in MLC2B. Ref.7
VAR_065851
Natural variant921R → Q in MLC2A. Ref.7
VAR_065852
Natural variant921R → W in MLC2B. Ref.7
VAR_065853
Natural variant981R → C in MLC2A. Ref.7
VAR_065854
Natural variant1281D → N in MLC2B. Ref.7
VAR_065855
Natural variant1351Missing in MLC2B. Ref.7
VAR_065856
Natural variant1481P → S in MLC2A. Ref.7
VAR_065857
Natural variant1961S → Y in MLC2A. Ref.7
VAR_065858
Natural variant2111D → N in MLC2A. Ref.7
VAR_065859
Natural variant2181M → V. Ref.2 Ref.3
Corresponds to variant rs10790715 [ dbSNP | Ensembl ].
VAR_034731
Natural variant2881R → C in MLC2B. Ref.7
VAR_065860

Experimental info

Sequence conflict21K → E in AAQ93018. Ref.1
Sequence conflict951Y → S in BAC85486. Ref.2
Sequence conflict2841Q → R in AAQ93018. Ref.1
Sequence conflict2931Missing in CAD39081. Ref.4

Sequences

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

Last modified August 22, 2006. Version 1.
Checksum: 3CB5111207135F3C

FASTA41646,026
        10         20         30         40         50         60 
MKRERGALSR ASRALRLAPF VYLLLIQTDP LEGVNITSPV RLIHGTVGKS ALLSVQYSST 

        70         80         90        100        110        120 
SSDRPVVKWQ LKRDKPVTVV QSIGTEVIGT LRPDYRDRIR LFENGSLLLS DLQLADEGTY 

       130        140        150        160        170        180 
EVEISITDDT FTGEKTINLT VDVPISRPQV LVASTTVLEL SEAFTLNCSH ENGTKPSYTW 

       190        200        210        220        230        240 
LKDGKPLLND SRMLLSPDQK VLTITRVLME DDDLYSCMVE NPISQGRSLP VKITVYRRSS 

       250        260        270        280        290        300 
LYIILSTGGI FLLVTLVTVC ACWKPSKRKQ KKLEKQNSLE YMDQNDDRLK PEADTLPRSG 

       310        320        330        340        350        360 
EQERKNPMAL YILKDKDSPE TEENPAPEPR SATEPGPPGY SVSPAVPGRS PGLPIRSARR 

       370        380        390        400        410 
YPRSPARSPA TGRTHSSPPR APSSPGRSRS ASRTLRTAGV HIIREQDEAG PVEISA 

« Hide

Isoform 2 [UniParc].

Checksum: 375DEF58F3C9725A
Show »

FASTA36740,564

References

« Hide 'large scale' references
[1]"Cloning and characterization of hepaCAM, a novel Ig-like cell adhesion molecule suppressed in human hepatocellular carcinoma."
Moh M.C., Lee L.H., Shen S.
J. Hepatol. 42:833-841(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, INDUCTION, GLYCOSYLATION.
Tissue: Liver.
[2]"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] (ISOFORMS 1 AND 2), VARIANT VAL-218.
Tissue: Brain.
[3]"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), VARIANT VAL-218.
Tissue: Brain.
[4]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 251-416 (ISOFORM 1).
Tissue: Fetal brain.
[5]"Structural and functional analyses of a novel Ig-like cell adhesion molecule, hepaCAM, in the human breast carcinoma MCF7 cells."
Moh M.C., Zhang C., Luo C., Lee L.H., Shen S.
J. Biol. Chem. 280:27366-27374(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, TOPOLOGY, DOMAIN, GLYCOSYLATION, PHOSPHORYLATION.
[6]"Megalencephalic leukoencephalopathy with subcortical cysts protein 1 functionally cooperates with the TRPV4 cation channel to activate the response of astrocytes to osmotic stress: dysregulation by pathological mutations."
Lanciotti A., Brignone M.S., Molinari P., Visentin S., De Nuccio C., Macchia G., Aiello C., Bertini E., Aloisi F., Petrucci T.C., Ambrosini E.
Hum. Mol. Genet. 21:2166-2180(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT.
[7]"Mutant GlialCAM causes megalencephalic leukoencephalopathy with subcortical cysts, benign familial macrocephaly, and macrocephaly with retardation and autism."
Lopez-Hernandez T., Ridder M.C., Montolio M., Capdevila-Nortes X., Polder E., Sirisi S., Duarri A., Schulte U., Fakler B., Nunes V., Scheper G.C., Martinez A., Estevez R., van der Knaap M.S.
Am. J. Hum. Genet. 88:422-432(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MLC2A HIS-23; GLN-92; CYS-98; SER-148; TYR-196 AND ASN-211, VARIANTS MLC2B ASP-89; SER-89; TRP-92; ASN-128; LYS-135 DEL AND CYS-288.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY047587 mRNA. Translation: AAQ93018.1.
AK098396 mRNA. Translation: BAC05297.1.
AK122595 mRNA. Translation: BAC85486.1.
BC104831 mRNA. Translation: AAI04832.1.
BC113562 mRNA. Translation: AAI13563.1.
AL834419 mRNA. Translation: CAD39081.1.
RefSeqNP_689935.2. NM_152722.4.
UniGeneHs.745294.

3D structure databases

ProteinModelPortalQ14CZ8.
SMRQ14CZ8. Positions 36-239.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000298251.

Protein family/group databases

MEROPSI43.001.

PTM databases

PhosphoSiteQ14CZ8.

Polymorphism databases

DMDM121945515.

Proteomic databases

PaxDbQ14CZ8.
PRIDEQ14CZ8.

Protocols and materials databases

DNASU220296.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000298251; ENSP00000298251; ENSG00000165478. [Q14CZ8-1]
GeneID220296.
KEGGhsa:220296.
UCSCuc001qbk.3. human. [Q14CZ8-1]
uc001qbl.1. human. [Q14CZ8-2]

Organism-specific databases

CTD220296.
GeneCardsGC11M124789.
H-InvDBHIX0010231.
HGNCHGNC:26361. HEPACAM.
HPACAB025486.
MIM611642. gene.
613925. phenotype.
613926. phenotype.
neXtProtNX_Q14CZ8.
Orphanet2478. Megalencephalic leukoencephalopathy with subcortical cysts.
PharmGKBPA162390830.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG80335.
HOGENOMHOG000060194.
HOVERGENHBG107974.
InParanoidQ14CZ8.
OMAWKPSKKS.
OrthoDBEOG71P2B5.
PhylomeDBQ14CZ8.
TreeFamTF331199.

Gene expression databases

BgeeQ14CZ8.
CleanExHS_HEPACAM.
GenevestigatorQ14CZ8.

Family and domain databases

Gene3D2.60.40.10. 2 hits.
InterProIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR013106. Ig_V-set.
[Graphical view]
PfamPF07686. V-set. 1 hit.
[Graphical view]
SMARTSM00409. IG. 1 hit.
SM00408. IGc2. 1 hit.
[Graphical view]
PROSITEPS50835. IG_LIKE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi220296.
NextBio91036.
PROQ14CZ8.
SOURCESearch...

Entry information

Entry nameHECAM_HUMAN
AccessionPrimary (citable) accession number: Q14CZ8
Secondary accession number(s): Q67IP8 expand/collapse secondary AC list , Q6ZWL4, Q8N7I3, Q8ND35
Entry history
Integrated into UniProtKB/Swiss-Prot: August 21, 2007
Last sequence update: August 22, 2006
Last modified: April 16, 2014
This is version 72 of the entry and version 1 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