LAMA4 (laminin subunit alpha 4)

Gene

• Entrez ID: 3910
• Gene name: Laminin subunit alpha 4
• Gene symbol: LAMA4
• Synonyms: CMD1JJ, LAMA3, LAMA4*-1
• Chromosome: 6
• Chromosome location: 6q21
• Summary: 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]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs3752579	A>T	Conflicting-interpretations-of-pathogenicity, benign	Genic downstream transcript variant, coding sequence variant, non coding transcript variant, missense variant
rs145897390	G>A,C	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Genic downstream transcript variant, coding sequence variant, non coding transcript variant, missense variant
rs150084275	G>A,C	Likely-benign, conflicting-interpretations-of-pathogenicity	Genic downstream transcript variant, coding sequence variant, non coding transcript variant, missense variant
rs200112094	A>G	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Coding sequence variant, non coding transcript variant, missense variant, genic downstream transcript variant
rs201209516	G>A	Conflicting-interpretations-of-pathogenicity	Intron variant, genic downstream transcript variant
rs371906362	C>A,G,T	Conflicting-interpretations-of-pathogenicity	Genic downstream transcript variant, intron variant
rs782010849	C>T	Conflicting-interpretations-of-pathogenicity	Non coding transcript variant, genic downstream transcript variant, missense variant, coding sequence variant
rs863223690	C>T	Likely-pathogenic	Genic downstream transcript variant, coding sequence variant, missense variant, non coding transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT022144	hsa-miR-124-3p	Microarray	18668037
MIRT038757	hsa-miR-93-3p	CLASH	23622248
MIRT462251	hsa-miR-4291	PAR-CLIP	23592263
MIRT462252	hsa-miR-657	PAR-CLIP	23592263
MIRT462253	hsa-miR-3665	PAR-CLIP	23592263
MIRT462254	hsa-miR-103b	PAR-CLIP	23592263
MIRT462255	hsa-miR-761	PAR-CLIP	23592263
MIRT462256	hsa-miR-3619-5p	PAR-CLIP	23592263
MIRT462257	hsa-miR-214-3p	PAR-CLIP	23592263
MIRT462258	hsa-miR-922	PAR-CLIP	23592263
MIRT462259	hsa-miR-7705	PAR-CLIP	23592263
MIRT462260	hsa-miR-6854-5p	PAR-CLIP	23592263
MIRT462261	hsa-miR-4274	PAR-CLIP	23592263

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005102	Function	Signaling receptor binding	IEA
GO:0005201	Function	Extracellular matrix structural constituent	ISS
GO:0005201	Function	Extracellular matrix structural constituent	RCA	25037231, 27068509, 27559042, 28675934
GO:0005515	Function	Protein binding	IPI	16169070, 25241761
GO:0005576	Component	Extracellular region	TAS
GO:0005604	Component	Basement membrane	IDA	14557481
GO:0007155	Process	Cell adhesion	IEA
GO:0030155	Process	Regulation of cell adhesion	IEA
GO:0030198	Process	Extracellular matrix organization	TAS
GO:0030334	Process	Regulation of cell migration	IEA
GO:0045995	Process	Regulation of embryonic development	IEA
GO:0062023	Component	Collagen-containing extracellular matrix	HDA	25037231, 27068509, 27559042, 28675934
GO:0062023	Component	Collagen-containing extracellular matrix	ISS	22261194
GO:0070062	Component	Extracellular exosome	HDA	19199708, 21362503
GO:0120163	Process	Negative regulation of cold-induced thermogenesis	ISS	28973559

Other IDs

• MIM: 600133
• HGNC: 6484
• e!Ensembl: ENSG00000112769

Protein

• UniProt ID: Q16363
• Protein name: Laminin subunit alpha-4 (Laminin-14 subunit alpha) (Laminin-8 subunit alpha) (Laminin-9 subunit alpha)
• Protein function: Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00053	Laminin_EGF	82 → 129	Laminin EGF domain	Domain
  PF00053	Laminin_EGF	132 → 184	Laminin EGF domain	Domain
  PF00053	Laminin_EGF	187 → 241	Laminin EGF domain	Domain
  PF06008	Laminin_I	298 → 555	Laminin Domain I	Coiled-coil
  PF06009	Laminin_II	734 → 861	Laminin Domain II	Coiled-coil
  PF02210	Laminin_G_2	874 → 1014	Laminin G domain	Domain
  PF02210	Laminin_G_2	1079 → 1210	Laminin G domain	Domain
  PF02210	Laminin_G_2	1263 → 1379	Laminin G domain	Domain
  PF02210	Laminin_G_2	1499 → 1626	Laminin G domain	Domain
  PF02210	Laminin_G_2	1676 → 1801	Laminin G domain	Domain

• Sequence:

  MALSSAWRSVLPLWLLWSAACSRAASGDDNAFPFDIEGSSAVGRQDPPETSEPRVALGRL
  PPAAEKCNAGFFHTLSGECVPCDCNGNSNECLDGSGYCVHCQRNTTGEHCEKCLDGYIGD
  SIRGAPQFCQPCPCPLPHLANFAESCYRKNGAVRCICNENYAGPNCERCAPGYYGNPLLI
  GSTCKKCDCSGNSDPNLIFEDCDEVTGQCRNCLRNTTGFKCERCAPGYYGDARIAKNCAV
  CNCGGGPCDSVTGECLEEGFEPPTGMDCPTISCDKCVWDLTDALRLAALSIEEGKSGVLS
  VSSGAAAHRHVNEINATIYLLKTKLSERENQYALRKIQINNAENTMKSLLSDVEELVEKE
  NQASRKGQLVQKESMDTINHASQLVEQAHDMRDKIQEINNKMLYYGEEHELSPKEISEKL
  VLAQKMLEEIRSRQPFFTQRELVDEEADEAYELLSQAESWQRLHNETRTLFPVVLEQLDD
  YNAKLSDLQEALDQALNYVRDAEDMNRATAARQRDHEKQQERVREQMEVVNMSLSTSADS
  LTTPRLTLSELDDIIKNASGIYAEIDGAKSELQVKLSNLSNLSHDLVQEAIDHAQDLQQE
  ANELSRKLHSSDMNGLVQKALDASNVYENIVNYVSEANETAEFALNTTDRIYDAVSGIDT
  QIIYHKDESENLLNQARELQAKAESSSDEAVADTSRRVGGALARKSALKTRLSDAVKQLQ
  AAERGDAQQRLGQSRLITEEANRTTMEVQQATAPMANNLTNWSQNLQHFDSSAYNTAVNS
  ARDAVRNLTEVVPQLLDQLRTVEQKRPASNVSASIQRIRELIAQTRSVASKIQVSMMFDG
  QSAVEVHSRTSMDDLKAFTSLSLYMKPPVKRPELTETADQFILYLGSKNAKKEYMGLAIK
  NDNLVYVYNLGTKDVEIPLDSKPVSSWPAYFSIVKIERVGKHGKVFLTVPSLSSTAEEKF
  IKKGEFSGDDSLLDLDPEDTVFYVGGVPSNFKLPTSLNLPGFVGCLELATLNNDVISLYN
  FKHIYNMDPSTSVPCARDKLAFTQSRAASYFFDGSGYAVVRDITRRGKFGQVTRFDIEVR
  TPADNGLILLMVNGSMFFRLEMRNGYLHVFYDFGFSGGPVHLEDTLKKAQINDAKYHEIS
  IIYHNDKKMILVVDRRHVKSMDNEKMKIPFTDIYIGGAPPEILQSRALRAHLPLDINFRG
  CMKGFQFQKKDFNLLEQTETLGVGYGCPEDSLISRRAYFNGQSFIASIQKISFFDGFEGG
  FNFRTLQPNGLLFYYASGSDVFSISLDNGTVIMDVKGIKVQSVDKQYNDGLSHFVISSVS
  PTRYELIVDKSRVGSKNPTKGKIEQTQASEKKFYFGGSPISAQYANFTGCISNAYFTRVD
  RDVEVEDFQRYTEKVHTSLYECPIESSPLFLLHKKGKNLSKPKASQNKKGGKSKDAPSWD
  PVALKLPERNTPRNSHCHLSNSPRAIEHAYQYGGTANSRQEFEHLKGDFGAKSQFSIRLR
  TRSSHGMIFYVSDQEENDFMTLFLAHGRLVYMFNVGHKKLKIRSQEKYNDGLWHDVIFIR
  ERSSGRLVIDGLRVLEESLPPTEATWKIKGPIYLGGVAPGKAVKNVQINSIYSFSGCLSN
  LQLNGASITSASQTFSVTPCFEGPMETGTYFSTEGGYVVLDESFNIGLKFEIAFEVRPRS
  SSGTLVHGHSVNGEYLNVHMKNGQVIVKVNNGIRDFSTSVTPKQSLCDGRWHRITVIRDS
  NVVQLDVDSEVNHVVGPLNPKPIDHREPVFVGGVPESLLTPRLAPSKPFTGCIRHFVIDG
  HPVSFSKAALVSGAVSINSCPAA

• Sequence length: 1823