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Protein

Laminin subunit alpha-4

Gene

LAMA4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.

Caution

Gene LAMA4 was formerly called LAMA3.Curated

GO - Molecular functioni

  • extracellular matrix structural constituent Source: ProtInc
  • signaling receptor binding Source: InterPro

GO - Biological processi

Keywordsi

Biological processCell adhesion

Enzyme and pathway databases

ReactomeiR-HSA-3000157 Laminin interactions
R-HSA-3000171 Non-integrin membrane-ECM interactions
R-HSA-3000178 ECM proteoglycans
R-HSA-8874081 MET activates PTK2 signaling
SIGNORiQ16363

Names & Taxonomyi

Protein namesi
Recommended name:
Laminin subunit alpha-4
Alternative name(s):
Laminin-14 subunit alpha
Laminin-8 subunit alpha
Laminin-9 subunit alpha
Gene namesi
Name:LAMA4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000112769.18
HGNCiHGNC:6484 LAMA4
MIMi600133 gene
neXtProtiNX_Q16363

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Basement membrane, Extracellular matrix, Secreted

Pathology & Biotechi

Involvement in diseasei

Cardiomyopathy, dilated 1JJ (CMD1JJ)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.
See also OMIM:615235
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_069708950P → L in CMD1JJ; loss of integrin-binding capacity. 1 Publication1

Keywords - Diseasei

Cardiomyopathy, Disease mutation

Organism-specific databases

DisGeNETi3910
MalaCardsiLAMA4
MIMi615235 phenotype
OpenTargetsiENSG00000112769
Orphaneti154 Familial isolated dilated cardiomyopathy
PharmGKBiPA30273

Chemistry databases

ChEMBLiCHEMBL2364187

Polymorphism and mutation databases

BioMutaiLAMA4
DMDMi292495093

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24Sequence analysisAdd BLAST24
ChainiPRO_000001706025 – 1823Laminin subunit alpha-4Add BLAST1799

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi82 ↔ 91By similarity
Disulfide bondi84 ↔ 98By similarity
Disulfide bondi101 ↔ 110By similarity
Glycosylationi104N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi113 ↔ 129By similarity
Disulfide bondi132 ↔ 146By similarity
Disulfide bondi134 ↔ 155By similarity
Disulfide bondi157 ↔ 166By similarity
Disulfide bondi169 ↔ 184By similarity
Disulfide bondi187 ↔ 202By similarity
Disulfide bondi189 ↔ 209By similarity
Disulfide bondi212 ↔ 221By similarity
Glycosylationi215N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi224 ↔ 238By similarity
Disulfide bondi273InterchainCurated
Disulfide bondi276InterchainCurated
Glycosylationi315N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi465N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi531N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi557N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi578N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi581N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi638N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi646N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi742N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi758N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi761N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi787N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi810N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi1005 ↔ 1035By similarity
Glycosylationi1093N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi1201 ↔ 1227By similarity
Glycosylationi1288N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1366N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi1370 ↔ 1402By similarity
Glycosylationi1418N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi1617 ↔ 1640By similarity
Disulfide bondi1792 ↔ 1820By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiQ16363
MaxQBiQ16363
PaxDbiQ16363
PeptideAtlasiQ16363
PRIDEiQ16363

PTM databases

iPTMnetiQ16363
PhosphoSitePlusiQ16363
SwissPalmiQ16363

Expressioni

Tissue specificityi

In adult, strong expression in heart, lung, ovary small and large intestines, placenta, liver; weak or no expression in skeletal muscle, kidney, pancreas, testis, prostate, brain. High expression in fetal lung and kidney. Expression in fetal and newborn tissues is observed in certain mesenchymal cells in tissues such as smooth muscle and dermis.

Gene expression databases

BgeeiENSG00000112769
CleanExiHS_LAMA4
ExpressionAtlasiQ16363 baseline and differential
GenevisibleiQ16363 HS

Organism-specific databases

HPAiCAB078156
HPA015693

Interactioni

Subunit structurei

Laminin is a complex glycoprotein, consisting of three different polypeptide chains (alpha, beta, gamma), which are bound to each other by disulfide bonds into a cross-shaped molecule comprising one long and three short arms with globules at each end. Alpha-4 is a subunit of laminin-8 (laminin-411), laminin-9 (laminin-421) and laminin-14 (laminin-423).

Binary interactionsi

WithEntry#Exp.IntActNotes
TP53P046372EBI-711505,EBI-366083

GO - Molecular functioni

Protein-protein interaction databases

BioGridi110104, 22 interactors
CORUMiQ16363
IntActiQ16363, 18 interactors
MINTiQ16363
STRINGi9606.ENSP00000230538

Structurei

3D structure databases

ProteinModelPortaliQ16363
SMRiQ16363
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini82 – 131Laminin EGF-like 1PROSITE-ProRule annotationAdd BLAST50
Domaini132 – 186Laminin EGF-like 2PROSITE-ProRule annotationAdd BLAST55
Domaini187 – 240Laminin EGF-like 3PROSITE-ProRule annotationAdd BLAST54
Domaini241 – 255Laminin EGF-like 4; truncatedPROSITE-ProRule annotationAdd BLAST15
Domaini833 – 1035Laminin G-like 1PROSITE-ProRule annotationAdd BLAST203
Domaini1047 – 1227Laminin G-like 2PROSITE-ProRule annotationAdd BLAST181
Domaini1234 – 1402Laminin G-like 3PROSITE-ProRule annotationAdd BLAST169
Domaini1469 – 1640Laminin G-like 4PROSITE-ProRule annotationAdd BLAST172
Domaini1647 – 1820Laminin G-like 5PROSITE-ProRule annotationAdd BLAST174

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni256 – 832Domain II and IAdd BLAST577

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili320 – 403Sequence analysisAdd BLAST84
Coiled coili473 – 528Sequence analysisAdd BLAST56
Coiled coili581 – 614Sequence analysisAdd BLAST34
Coiled coili662 – 724Sequence analysisAdd BLAST63
Coiled coili777 – 806Sequence analysisAdd BLAST30

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi724 – 726Cell attachment siteSequence analysis3

Domaini

The alpha-helical domains I and II are thought to interact with other laminin chains to form a coiled coil structure.
Domain G is globular.

Keywords - Domaini

Coiled coil, Laminin EGF-like domain, Repeat, Signal

Phylogenomic databases

eggNOGiENOG410IP6G Eukaryota
ENOG410Z3D5 LUCA
GeneTreeiENSGT00780000121851
HOVERGENiHBG052299
InParanoidiQ16363
KOiK06241
PhylomeDBiQ16363
TreeFamiTF335359

Family and domain databases

InterProiView protein in InterPro
IPR013320 ConA-like_dom_sf
IPR000742 EGF-like_dom
IPR009254 Laminin_aI
IPR010307 Laminin_dom_II
IPR002049 Laminin_EGF
IPR001791 Laminin_G
PfamiView protein in Pfam
PF00053 Laminin_EGF, 3 hits
PF02210 Laminin_G_2, 5 hits
PF06008 Laminin_I, 1 hit
PF06009 Laminin_II, 1 hit
SMARTiView protein in SMART
SM00181 EGF, 3 hits
SM00180 EGF_Lam, 3 hits
SM00282 LamG, 5 hits
SUPFAMiSSF49899 SSF49899, 5 hits
PROSITEiView protein in PROSITE
PS00022 EGF_1, 1 hit
PS01248 EGF_LAM_1, 3 hits
PS50027 EGF_LAM_2, 3 hits
PS50025 LAM_G_DOMAIN, 5 hits

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q16363-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MALSSAWRSV LPLWLLWSAA CSRAASGDDN AFPFDIEGSS AVGRQDPPET
60 70 80 90 100
SEPRVALGRL PPAAEKCNAG FFHTLSGECV PCDCNGNSNE CLDGSGYCVH
110 120 130 140 150
CQRNTTGEHC EKCLDGYIGD SIRGAPQFCQ PCPCPLPHLA NFAESCYRKN
160 170 180 190 200
GAVRCICNEN YAGPNCERCA PGYYGNPLLI GSTCKKCDCS GNSDPNLIFE
210 220 230 240 250
DCDEVTGQCR NCLRNTTGFK CERCAPGYYG DARIAKNCAV CNCGGGPCDS
260 270 280 290 300
VTGECLEEGF EPPTGMDCPT ISCDKCVWDL TDALRLAALS IEEGKSGVLS
310 320 330 340 350
VSSGAAAHRH VNEINATIYL LKTKLSEREN QYALRKIQIN NAENTMKSLL
360 370 380 390 400
SDVEELVEKE NQASRKGQLV QKESMDTINH ASQLVEQAHD MRDKIQEINN
410 420 430 440 450
KMLYYGEEHE LSPKEISEKL VLAQKMLEEI RSRQPFFTQR ELVDEEADEA
460 470 480 490 500
YELLSQAESW QRLHNETRTL FPVVLEQLDD YNAKLSDLQE ALDQALNYVR
510 520 530 540 550
DAEDMNRATA ARQRDHEKQQ ERVREQMEVV NMSLSTSADS LTTPRLTLSE
560 570 580 590 600
LDDIIKNASG IYAEIDGAKS ELQVKLSNLS NLSHDLVQEA IDHAQDLQQE
610 620 630 640 650
ANELSRKLHS SDMNGLVQKA LDASNVYENI VNYVSEANET AEFALNTTDR
660 670 680 690 700
IYDAVSGIDT QIIYHKDESE NLLNQARELQ AKAESSSDEA VADTSRRVGG
710 720 730 740 750
ALARKSALKT RLSDAVKQLQ AAERGDAQQR LGQSRLITEE ANRTTMEVQQ
760 770 780 790 800
ATAPMANNLT NWSQNLQHFD SSAYNTAVNS ARDAVRNLTE VVPQLLDQLR
810 820 830 840 850
TVEQKRPASN VSASIQRIRE LIAQTRSVAS KIQVSMMFDG QSAVEVHSRT
860 870 880 890 900
SMDDLKAFTS LSLYMKPPVK RPELTETADQ FILYLGSKNA KKEYMGLAIK
910 920 930 940 950
NDNLVYVYNL GTKDVEIPLD SKPVSSWPAY FSIVKIERVG KHGKVFLTVP
960 970 980 990 1000
SLSSTAEEKF IKKGEFSGDD SLLDLDPEDT VFYVGGVPSN FKLPTSLNLP
1010 1020 1030 1040 1050
GFVGCLELAT LNNDVISLYN FKHIYNMDPS TSVPCARDKL AFTQSRAASY
1060 1070 1080 1090 1100
FFDGSGYAVV RDITRRGKFG QVTRFDIEVR TPADNGLILL MVNGSMFFRL
1110 1120 1130 1140 1150
EMRNGYLHVF YDFGFSGGPV HLEDTLKKAQ INDAKYHEIS IIYHNDKKMI
1160 1170 1180 1190 1200
LVVDRRHVKS MDNEKMKIPF TDIYIGGAPP EILQSRALRA HLPLDINFRG
1210 1220 1230 1240 1250
CMKGFQFQKK DFNLLEQTET LGVGYGCPED SLISRRAYFN GQSFIASIQK
1260 1270 1280 1290 1300
ISFFDGFEGG FNFRTLQPNG LLFYYASGSD VFSISLDNGT VIMDVKGIKV
1310 1320 1330 1340 1350
QSVDKQYNDG LSHFVISSVS PTRYELIVDK SRVGSKNPTK GKIEQTQASE
1360 1370 1380 1390 1400
KKFYFGGSPI SAQYANFTGC ISNAYFTRVD RDVEVEDFQR YTEKVHTSLY
1410 1420 1430 1440 1450
ECPIESSPLF LLHKKGKNLS KPKASQNKKG GKSKDAPSWD PVALKLPERN
1460 1470 1480 1490 1500
TPRNSHCHLS NSPRAIEHAY QYGGTANSRQ EFEHLKGDFG AKSQFSIRLR
1510 1520 1530 1540 1550
TRSSHGMIFY VSDQEENDFM TLFLAHGRLV YMFNVGHKKL KIRSQEKYND
1560 1570 1580 1590 1600
GLWHDVIFIR ERSSGRLVID GLRVLEESLP PTEATWKIKG PIYLGGVAPG
1610 1620 1630 1640 1650
KAVKNVQINS IYSFSGCLSN LQLNGASITS ASQTFSVTPC FEGPMETGTY
1660 1670 1680 1690 1700
FSTEGGYVVL DESFNIGLKF EIAFEVRPRS SSGTLVHGHS VNGEYLNVHM
1710 1720 1730 1740 1750
KNGQVIVKVN NGIRDFSTSV TPKQSLCDGR WHRITVIRDS NVVQLDVDSE
1760 1770 1780 1790 1800
VNHVVGPLNP KPIDHREPVF VGGVPESLLT PRLAPSKPFT GCIRHFVIDG
1810 1820
HPVSFSKAAL VSGAVSINSC PAA
Length:1,823
Mass (Da):202,524
Last modified:March 23, 2010 - v4
Checksum:i25BFB6120C2A86F1
GO
Isoform 2 (identifier: Q16363-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     266-272: Missing.

Show »
Length:1,816
Mass (Da):201,776
Checksum:iAEC1A024B5A180ED
GO
Isoform 3 (identifier: Q16363-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     66-120: KCNAGFFHTL...EKCLDGYIGD → VQCPCHCHPA...RKLEIKSFPL
     121-1823: Missing.

Show »
Length:120
Mass (Da):12,819
Checksum:i6ABF63CBA663BF3F
GO

Sequence cautioni

The sequence BAE06109 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti143A → P in AAB34635 (PubMed:7781776).Curated1
Sequence conflicti178L → F in AAB34635 (PubMed:7781776).Curated1
Sequence conflicti283A → D in AAB34635 (PubMed:7781776).Curated1
Sequence conflicti283A → D in CAA62596 (PubMed:8706685).Curated1
Sequence conflicti283A → D in BAE06109 (Ref. 3) Curated1
Sequence conflicti283A → D in CAA54258 (PubMed:7959779).Curated1
Sequence conflicti1064T → P in AAB34635 (PubMed:7781776).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05614094G → S. Corresponds to variant dbSNP:rs35349917EnsemblClinVar.1
Natural variantiVAR_056141154R → W. Corresponds to variant dbSNP:rs11757455EnsemblClinVar.1
Natural variantiVAR_061348283A → E. Corresponds to variant dbSNP:rs9400522Ensembl.1
Natural variantiVAR_056142492L → H. Corresponds to variant dbSNP:rs3752579Ensembl.1
Natural variantiVAR_025550498Y → H2 PublicationsCorresponds to variant dbSNP:rs1050348Ensembl.1
Natural variantiVAR_069708950P → L in CMD1JJ; loss of integrin-binding capacity. 1 Publication1
Natural variantiVAR_0255511117G → S3 PublicationsCorresponds to variant dbSNP:rs2032567Ensembl.1
Natural variantiVAR_0255521119P → R3 PublicationsCorresponds to variant dbSNP:rs1050349Ensembl.1
Natural variantiVAR_0561431549N → S1 PublicationCorresponds to variant dbSNP:rs12110554Ensembl.1
Natural variantiVAR_0561441815V → I. Corresponds to variant dbSNP:rs3734292Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_03885366 – 120KCNAG…GYIGD → VQCPCHCHPAGAPAPPRAVP HSSFSLSPPLSSPQCLESFT WARSVRKLEIKSFPL in isoform 3. 2 PublicationsAdd BLAST55
Alternative sequenceiVSP_038854121 – 1823Missing in isoform 3. 2 PublicationsAdd BLAST1703
Alternative sequenceiVSP_017542266 – 272Missing in isoform 2. 3 Publications7

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S78569 mRNA Translation: AAB34635.1
X91171 mRNA Translation: CAA62596.1
X70904 mRNA Translation: CAA50261.1
AB210027 mRNA Translation: BAE06109.1 Different initiation.
BT006690 mRNA Translation: AAP35336.1
AL590106 Genomic DNA No translation available.
Z99289 Genomic DNA No translation available.
BC004241 mRNA Translation: AAH04241.1
Y14240 Genomic DNA Translation: CAA74636.1
X76939 mRNA Translation: CAA54258.1
CCDSiCCDS34514.1 [Q16363-2]
CCDS43491.1 [Q16363-1]
CCDS43492.1 [Q16363-3]
PIRiS68960
RefSeqiNP_001098676.2, NM_001105206.2
NP_001098677.2, NM_001105207.2
NP_001098678.1, NM_001105208.2 [Q16363-3]
NP_001098679.1, NM_001105209.2 [Q16363-3]
NP_002281.3, NM_002290.4
XP_005267040.2, XM_005266983.3
XP_005267041.2, XM_005266984.3
UniGeneiHs.654572

Genome annotation databases

EnsembliENST00000368638; ENSP00000357627; ENSG00000112769 [Q16363-3]
ENST00000453937; ENSP00000398226; ENSG00000112769 [Q16363-3]
ENST00000455073; ENSP00000408604; ENSG00000112769 [Q16363-3]
GeneIDi3910
KEGGihsa:3910
UCSCiuc010kdz.3 human [Q16363-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiLAMA4_HUMAN
AccessioniPrimary (citable) accession number: Q16363
Secondary accession number(s): Q14731
, Q14735, Q15335, Q4LE44, Q5SZG8, Q9BTB8, Q9UE18, Q9UJN9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: March 23, 2010
Last modified: May 23, 2018
This is version 183 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

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