LAMC2

Protein identityUniProt · HPA

UniProt accession

Q13753

Gene

LAMC2

Ensembl

ENSG00000058085

Chromosome

1

Canonical length

1193 aa

Protein class

Disease related genes, Human disease related genes, Plasma proteins, Predicted secreted proteins

Subcellular location

Endoplasmic reticulum,Golgi apparatus

Secretome location

Secreted to extracellular matrix

OverviewNCBI Gene

Laminins, a family of extracellular matrix glycoproteins, are the major noncollagenous constituent of basement membranes. They have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Laminins, composed of 3 non identical chains: laminin alpha, beta and gamma (formerly A, B1, and B2, respectively), have a cruciform structure consisting of 3 short arms, each formed by a different chain, and a long arm composed of all 3 chains. Each laminin chain is a multidomain protein encoded by a distinct gene. Several isoforms of each chain have been described. Different alpha, beta and gamma chain isomers combine to give rise to different heterotrimeric laminin isoforms which are designated by Arabic numerals in the order of their discovery, i.e. alpha1beta1gamma1 heterotrimer is laminin 1. The biological functions of the different chains and trimer molecules are largely unknown, but some of the chains have been shown to differ with respect to their tissue distribution, presumably reflecting diverse functions in vivo. This gene encodes the gamma chain isoform laminin, gamma 2. The gamma 2 chain, formerly thought to be a truncated version of beta chain (B2t), is highly homologous to the gamma 1 chain; however, it lacks domain VI, and domains V, IV and III are shorter. It is expressed in several fetal tissues but differently from gamma 1, and is specifically localized to epithelial cells in skin, lung and kidney. The gamma 2 chain together with alpha 3 and beta 3 chains constitute laminin 5 (earlier known as kalinin), which is an integral part of the anchoring filaments that connect epithelial cells to the underlying basement membrane. The epithelium-specific expression of the gamma 2 chain implied its role as an epithelium attachment molecule, and mutations in this gene have been associated with junctional epidermolysis bullosa, a skin disease characterized by blisters due to disruption of the epidermal-dermal junction. Two transcript variants resulting from alternative splicing of the 3' terminal exon, and encoding different isoforms of gamma 2 chain, have been described. The two variants are differentially expressed in embryonic tissues, however, the biological significance of the two forms is not known. Transcript variants utilizing alternative polyA_signal have also been noted in literature. [provided by RefSeq, Aug 2011]

Canonical amino-acid sequenceUniProt

1193 residues, UniProt reviewed canonical sequence.

>Q13753|LAMC2
     1  MPALWLGCCL CFSLLLPAAR ATSRREVCDC NGKSRQCIFD RELHRQTGNG FRCLNCNDNT
    61  DGIHCEKCKN GFYRHRERDR CLPCNCNSKG SLSARCDNSG RCSCKPGVTG ARCDRCLPGF
   121  HMLTDAGCTQ DQRLLDSKCD CDPAGIAGPC DAGRCVCKPA VTGERCDRCR SGYYNLDGGN
   181  PEGCTQCFCY GHSASCRSSA EYSVHKITST FHQDVDGWKA VQRNGSPAKL QWSQRHQDVF
   241  SSAQRLDPVY FVAPAKFLGN QQVSYGQSLS FDYRVDRGGR HPSAHDVILE GAGLRITAPL
   301  MPLGKTLPCG LTKTYTFRLN EHPSNNWSPQ LSYFEYRRLL RNLTALRIRA TYGEYSTGYI
   361  DNVTLISARP VSGAPAPWVE QCICPVGYKG QFCQDCASGY KRDSARLGPF GTCIPCNCQG
   421  GGACDPDTGD CYSGDENPDI ECADCPIGFY NDPHDPRSCK PCPCHNGFSC SVMPETEEVV
   481  CNNCPPGVTG ARCELCADGY FGDPFGEHGP VRPCQPCQCN NNVDPSASGN CDRLTGRCLK
   541  CIHNTAGIYC DQCKAGYFGD PLAPNPADKC RACNCNPMGS EPVGCRSDGT CVCKPGFGGP
   601  NCEHGAFSCP ACYNQVKIQM DQFMQQLQRM EALISKAQGG DGVVPDTELE GRMQQAEQAL
   661  QDILRDAQIS EGASRSLGLQ LAKVRSQENS YQSRLDDLKM TVERVRALGS QYQNRVRDTH
   721  RLITQMQLSL AESEASLGNT NIPASDHYVG PNGFKSLAQE ATRLAESHVE SASNMEQLTR
   781  ETEDYSKQAL SLVRKALHEG VGSGSGSPDG AVVQGLVEKL EKTKSLAQQL TREATQAEIE
   841  ADRSYQHSLR LLDSVSRLQG VSDQSFQVEE AKRIKQKADS LSSLVTRHMD EFKRTQKNLG
   901  NWKEEAQQLL QNGKSGREKS DQLLSRANLA KSRAQEALSM GNATFYEVES ILKNLREFDL
   961  QVDNRKAEAE EAMKRLSYIS QKVSDASDKT QQAERALGSA AADAQRAKNG AGEALEISSE
  1021  IEQEIGSLNL EANVTADGAL AMEKGLASLK SEMREVEGEL ERKELEFDTN MDAVQMVITE
  1081  AQKVDTRAKN AGVTIQDTLN TLDGLLHLMD QPLSVDEEGL VLLEQKLSRA KTQINSQLRP
  1141  MMSELEERAR QQRGHLHLLE TSIDGILADV KNLENIRDNL PPGCYNTQAL EQQ

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against LAMC2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.4

Highest tissue expression

37 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about LAMC2.

Disease | AllUniProt

Conditions LAMC2 is implicated in, by any mechanism.

• Epidermolysis bullosa, junctional 3A, intermediate (JEB3A) MIM:619785
• Epidermolysis bullosa, junctional 3B, severe (JEB3B) MIM:619786

Disease | GeneticClinVar

223 pathogenic / likely-pathogenic of 1,314 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Junctional epidermolysis bullosa gravis of Herlitz
• Epidermolysis bullosa, junctional 3B, severe
• Epidermolysis bullosa, junctional 3A, intermediate
• Junctional epidermolysis bullosa
• Junctional epidermolysis bullosa, non-Herlitz type

Disease | ImmuneIEDB

Conditions an epitope on LAMC2 was assayed in.

• pancreatic ductal adenocarcinoma T cell
• type 1 diabetes mellitus T cell
• colonic benign neoplasm T cell

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.65

gnomAD pLI

0

gnomAD missense Z

0.35

DepMap mean gene effect

-0.1

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cell adhesion
• epidermis development
• positive regulation of cell migration
• positive regulation of cell population proliferation

Molecular functions

• heparin binding

Cellular components

• cell cortex
• extracellular matrix
• extracellular region
• extracellular space
• laminin-2 complex
• perinuclear region of cytoplasm

Protein domainsUniProt · Pfam · InterPro

• Laminin IV
• EGF-like domain
• Laminin-type EGF domain
• Laminin/Netrin Extracellular Matrix
• Laminin B (Domain IV)
• Laminin EGF domain

KeywordsUniProt

• Basement membrane
• Cell adhesion
• Coiled coil
• Disulfide bond
• Epidermolysis bullosa
• Extracellular matrix
• Glycoprotein
• Heparin-binding
• Laminin EGF-like domain
• Proteoglycan
• Repeat
• Secreted
• Signal