LAMA4

Protein identityUniProt · HPA

UniProt accession

Q16363

Gene

LAMA4

Ensembl

ENSG00000112769

Chromosome

6

Canonical length

1823 aa

Protein class

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

Subcellular location

Plasma membrane,Cytosol

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 are composed of 3 non identical chains: laminin alpha, beta and gamma (formerly A, B1, and B2, respectively) and they form 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 alpha chain isoform laminin, alpha 4. The domain structure of alpha 4 is similar to that of alpha 3, both of which resemble truncated versions of alpha 1 and alpha 2, in that approximately 1,200 residues at the N-terminus (domains IV, V and VI) have been lost. Laminin, alpha 4 contains the C-terminal G domain which distinguishes all alpha chains from the beta and gamma chains. The RNA analysis from adult and fetal tissues revealed developmental regulation of expression, however, the exact function of laminin, alpha 4 is not known. Tissue-specific utilization of alternative polyA-signal has been described in literature. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Aug 2011]

Canonical amino-acid sequenceUniProt

1823 residues, UniProt reviewed canonical sequence.

>Q16363|LAMA4
     1  MALSSAWRSV LPLWLLWSAA CSRAASGDDN AFPFDIEGSS AVGRQDPPET SEPRVALGRL
    61  PPAAEKCNAG FFHTLSGECV PCDCNGNSNE CLDGSGYCVH CQRNTTGEHC EKCLDGYIGD
   121  SIRGAPQFCQ PCPCPLPHLA NFAESCYRKN GAVRCICNEN YAGPNCERCA PGYYGNPLLI
   181  GSTCKKCDCS GNSDPNLIFE DCDEVTGQCR NCLRNTTGFK CERCAPGYYG DARIAKNCAV
   241  CNCGGGPCDS VTGECLEEGF EPPTGMDCPT ISCDKCVWDL TDDLRLAALS IEEGKSGVLS
   301  VSSGAAAHRH VNEINATIYL LKTKLSEREN QYALRKIQIN NAENTMKSLL SDVEELVEKE
   361  NQASRKGQLV QKESMDTINH ASQLVEQAHD MRDKIQEINN KMLYYGEEHE LSPKEISEKL
   421  VLAQKMLEEI RSRQPFFTQR ELVDEEADEA YELLSQAESW QRLHNETRTL FPVVLEQLDD
   481  YNAKLSDLQE ALDQALNYVR DAEDMNRATA ARQRDHEKQQ ERVREQMEVV NMSLSTSADS
   541  LTTPRLTLSE LDDIIKNASG IYAEIDGAKS ELQVKLSNLS NLSHDLVQEA IDHAQDLQQE
   601  ANELSRKLHS SDMNGLVQKA LDASNVYENI VNYVSEANET AEFALNTTDR IYDAVSGIDT
   661  QIIYHKDESE NLLNQARELQ AKAESSSDEA VADTSRRVGG ALARKSALKT RLSDAVKQLQ
   721  AAERGDAQQR LGQSRLITEE ANRTTMEVQQ ATAPMANNLT NWSQNLQHFD SSAYNTAVNS
   781  ARDAVRNLTE VVPQLLDQLR TVEQKRPASN VSASIQRIRE LIAQTRSVAS KIQVSMMFDG
   841  QSAVEVHSRT SMDDLKAFTS LSLYMKPPVK RPELTETADQ FILYLGSKNA KKEYMGLAIK
   901  NDNLVYVYNL GTKDVEIPLD SKPVSSWPAY FSIVKIERVG KHGKVFLTVP SLSSTAEEKF
   961  IKKGEFSGDD SLLDLDPEDT VFYVGGVPSN FKLPTSLNLP GFVGCLELAT LNNDVISLYN
  1021  FKHIYNMDPS TSVPCARDKL AFTQSRAASY FFDGSGYAVV RDITRRGKFG QVTRFDIEVR
  1081  TPADNGLILL MVNGSMFFRL EMRNGYLHVF YDFGFSGGPV HLEDTLKKAQ INDAKYHEIS
  1141  IIYHNDKKMI LVVDRRHVKS MDNEKMKIPF TDIYIGGAPP EILQSRALRA HLPLDINFRG
  1201  CMKGFQFQKK DFNLLEQTET LGVGYGCPED SLISRRAYFN GQSFIASIQK ISFFDGFEGG
  1261  FNFRTLQPNG LLFYYASGSD VFSISLDNGT VIMDVKGIKV QSVDKQYNDG LSHFVISSVS
  1321  PTRYELIVDK SRVGSKNPTK GKIEQTQASE KKFYFGGSPI SAQYANFTGC ISNAYFTRVD
  1381  RDVEVEDFQR YTEKVHTSLY ECPIESSPLF LLHKKGKNLS KPKASQNKKG GKSKDAPSWD
  1441  PVALKLPERN TPRNSHCHLS NSPRAIEHAY QYGGTANSRQ EFEHLKGDFG AKSQFSIRLR
  1501  TRSSHGMIFY VSDQEENDFM TLFLAHGRLV YMFNVGHKKL KIRSQEKYND GLWHDVIFIR
  1561  ERSSGRLVID GLRVLEESLP PTEATWKIKG PIYLGGVAPG KAVKNVQINS IYSFSGCLSN
  1621  LQLNGASITS ASQTFSVTPC FEGPMETGTY FSTEGGYVVL DESFNIGLKF EIAFEVRPRS
  1681  SSGTLVHGHS VNGEYLNVHM KNGQVIVKVN NGIRDFSTSV TPKQSLCDGR WHRITVIRDS
  1741  NVVQLDVDSE VNHVVGPLNP KPIDHREPVF VGGVPESLLT PRLAPSKPFT GCIRHFVIDG
  1801  HPVSFSKAAL VSGAVSINSC PAA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against LAMA4 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)

0.35

Highest tissue expression

163 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about LAMA4.

Disease | AllUniProt

Conditions LAMA4 is implicated in, by any mechanism.

• Cardiomyopathy, dilated, 1JJ (CMD1JJ) MIM:615235

Disease | GeneticClinVar

3 pathogenic / likely-pathogenic of 2,270 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Dilated cardiomyopathy 1JJ

Disease | ImmuneIEDB

Conditions an epitope on LAMA4 was assayed in.

• brain glioblastoma multiforme 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)

0.73

gnomAD pLI

0

gnomAD missense Z

0.15

DepMap mean gene effect

0.05

DepMap dependency class

none

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
• negative regulation of cold-induced thermogenesis
• regulation of cell adhesion
• regulation of cell migration
• regulation of embryonic development

Molecular functions

• extracellular matrix structural constituent
• signaling receptor binding

Cellular components

• basement membrane
• extracellular exosome
• extracellular matrix
• extracellular region

Protein domainsUniProt · Pfam · InterPro

• EGF-like domain
• Laminin G domain
• Laminin-type EGF domain
• Laminin alpha, domain I
• Laminin domain II
• Concanavalin A-like lectin/glucanase domain superfamily
• Neurexin-related cell adhesion and synaptic protein
• Laminin/attractin/netrin-like, EGF domain
• Laminin EGF domain
• Laminin G domain
• Laminin Domain I
• Laminin Domain II
• Laminin/attractin EGF domain

KeywordsUniProt

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

InteractionsUniProt · HPA

Protein binding partners of LAMA4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• TP53