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Q01955

- CO4A3_HUMAN

UniProt

Q01955 - CO4A3_HUMAN

Protein

Collagen alpha-3(IV) chain

Gene

COL4A3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 171 (01 Oct 2014)
      Sequence version 3 (06 Mar 2007)
      Previous versions | rss
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    Functioni

    Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen.
    Tumstatin, a cleavage fragment corresponding to the collagen alpha 3(IV) NC1 domain, possesses both anti-angiogenic and anti-tumor cell activity; these two anti-tumor properties may be regulated via RGD-independent ITGB3-mediated mechanisms.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei1426 – 14272Cleavage; by collagenaseBy similarity

    GO - Molecular functioni

    1. extracellular matrix structural constituent Source: InterPro
    2. integrin binding Source: UniProtKB
    3. metalloendopeptidase inhibitor activity Source: UniProtKB
    4. protein binding Source: UniProtKB
    5. structural molecule activity Source: ProtInc

    GO - Biological processi

    1. activation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
    2. axon guidance Source: Reactome
    3. blood circulation Source: ProtInc
    4. cell adhesion Source: UniProtKB-KW
    5. cell proliferation Source: UniProtKB
    6. cell surface receptor signaling pathway Source: UniProtKB
    7. collagen catabolic process Source: Reactome
    8. endothelial cell apoptotic process Source: UniProtKB
    9. extracellular matrix disassembly Source: Reactome
    10. extracellular matrix organization Source: Reactome
    11. glomerular basement membrane development Source: UniProtKB
    12. negative regulation of angiogenesis Source: UniProtKB
    13. negative regulation of cell proliferation Source: ProtInc
    14. negative regulation of endopeptidase activity Source: GOC
    15. response to glucose Source: Ensembl
    16. sensory perception of sound Source: ProtInc

    Keywords - Biological processi

    Cell adhesion

    Enzyme and pathway databases

    ReactomeiREACT_118779. Extracellular matrix organization.
    REACT_121139. Collagen biosynthesis and modifying enzymes.
    REACT_13552. Integrin cell surface interactions.
    REACT_150180. Assembly of collagen fibrils and other multimeric structures.
    REACT_150268. Anchoring fibril formation.
    REACT_150401. Collagen degradation.
    REACT_163874. Non-integrin membrane-ECM interactions.
    REACT_163906. ECM proteoglycans.
    REACT_16888. Signaling by PDGF.
    REACT_169262. Laminin interactions.
    REACT_18312. NCAM1 interactions.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Collagen alpha-3(IV) chain
    Alternative name(s):
    Goodpasture antigen
    Cleaved into the following chain:
    Gene namesi
    Name:COL4A3
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:2204. COL4A3.

    Subcellular locationi

    Secretedextracellular spaceextracellular matrixbasement membrane
    Note: Colocalizes with COL4A4 and COL4A5 in GBM, tubular basement membrane (TBM) and synaptic basal lamina (BL).By similarity

    GO - Cellular componenti

    1. basement membrane Source: UniProtKB
    2. collagen type IV trimer Source: UniProtKB
    3. endoplasmic reticulum lumen Source: Reactome
    4. extracellular region Source: Reactome

    Keywords - Cellular componenti

    Basement membrane, Extracellular matrix, Secreted

    Pathology & Biotechi

    Involvement in diseasei

    Autoantibodies against the NC1 domain of alpha 3(IV) are found in Goodpasture syndrome, an autoimmune disease of lung and kidney.
    Alport syndrome, autosomal recessive (APSAR) [MIM:203780]: A syndrome characterized by progressive glomerulonephritis, glomerular basement membrane defects, renal failure, sensorineural deafness and specific eye abnormalities (lenticonous and macular flecks). The disorder shows considerable heterogeneity in that families differ in the age of end-stage renal disease and the occurrence of deafness.2 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti297 – 2971G → E in APSAR. 1 Publication
    VAR_011204
    Natural varianti407 – 4071G → R in APSAR. 1 Publication
    VAR_011206
    Natural varianti532 – 5321G → D in APSAR. 1 Publication
    VAR_030945
    Natural varianti640 – 6401G → R in APSAR. 1 Publication
    VAR_011210
    Natural varianti739 – 7391G → R in APSAR. 1 Publication
    VAR_030946
    Natural varianti853 – 8531G → R in APSAR. 1 Publication
    VAR_030947
    Natural varianti1207 – 12071G → E in APSAR; in isolated microhematuria at heterozygosity. 1 Publication
    VAR_011212
    Natural varianti1215 – 12151R → Q in APSAR; unknown pathological significance. 1 Publication
    VAR_011213
    Natural varianti1216 – 12161G → R in APSAR. 1 Publication
    VAR_030950
    Natural varianti1277 – 12771G → S in APSAR. 1 Publication
    Corresponds to variant rs190598500 [ dbSNP | Ensembl ].
    VAR_011215
    Natural varianti1330 – 13301I → T in APSAR; unknown pathological significance. 1 Publication
    VAR_011216
    Natural varianti1334 – 13341G → E in APSAR. 1 Publication
    VAR_011217
    Natural varianti1347 – 13471D → E in APSAR; unknown pathological significance. 1 Publication
    Corresponds to variant rs73996414 [ dbSNP | Ensembl ].
    VAR_011218
    Natural varianti1661 – 16611R → C in APSAR. 1 Publication
    VAR_011219
    Hematuria, benign familial (BFH) [MIM:141200]: An autosomal dominant condition characterized by non-progressive isolated microscopic hematuria that does not result in renal failure. It is characterized pathologically by thinning of the glomerular basement membrane.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti985 – 9851G → V in BFH. 1 Publication
    VAR_030948
    Natural varianti1015 – 10151G → E in BFH. 1 Publication
    VAR_030949
    Alport syndrome, autosomal dominant (APSAD) [MIM:104200]: A syndrome characterized by progressive glomerulonephritis, glomerular basement membrane defects, renal failure, sensorineural deafness and specific eye abnormalities (lenticonous and macular flecks). The disorder shows considerable heterogeneity in that families differ in the age of end-stage renal disease and the occurrence of deafness.2 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti1167 – 11671G → R in APSAD; in isolated microhematuria at heterozygosity. 1 Publication
    VAR_011211

    Keywords - Diseasei

    Alport syndrome, Deafness, Disease mutation

    Organism-specific databases

    MIMi104200. phenotype.
    141200. phenotype.
    203780. phenotype.
    Orphaneti88918. Autosomal dominant Alport syndrome.
    88919. Autosomal recessive Alport syndrome.
    97562. Benign familial hematuria.
    PharmGKBiPA26719.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2828Sequence AnalysisAdd
    BLAST
    Chaini29 – 16701642Collagen alpha-3(IV) chainPRO_0000005844Add
    BLAST
    Chaini1426 – 1670245TumstatinPRO_0000279684Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi253 – 2531N-linked (GlcNAc...)Sequence Analysis
    Cross-linki1414 – 1414Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
    Disulfide bondi1460 ↔ 1551Or C-1460 with C-1548PROSITE-ProRule annotation
    Disulfide bondi1493 ↔ 1548Or C-1493 with C-1551PROSITE-ProRule annotation
    Disulfide bondi1505 ↔ 1511PROSITE-ProRule annotation
    Cross-linki1533 – 1533S-Lysyl-methionine sulfilimine (Met-Lys) (interchain with K-1651)By similarity
    Disulfide bondi1570 ↔ 1665Or C-1570 with C-1662PROSITE-ProRule annotation
    Disulfide bondi1604 ↔ 1662Or C-1604 with C-1665PROSITE-ProRule annotation
    Disulfide bondi1616 ↔ 1622PROSITE-ProRule annotation
    Cross-linki1651 – 1651S-Lysyl-methionine sulfilimine (Lys-Met) (interchain with M-1533)By similarity

    Post-translational modificationi

    Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.
    Isoform 2 contains an additional N-linked glycosylation site.
    Type IV collagens contain numerous cysteine residues which are involved in inter- and intramolecular disulfide bonding. 12 of these, located in the NC1 domain, are conserved in all known type IV collagens.
    The trimeric structure of the NC1 domains is stabilized by covalent bonds between Lys and Met residues.By similarity
    Phosphorylated by the Goodpasture antigen-binding protein/COL4A3BP.1 Publication

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Hydroxylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiQ01955.
    PaxDbiQ01955.
    PRIDEiQ01955.

    PTM databases

    PhosphoSiteiQ01955.

    Expressioni

    Tissue specificityi

    Alpha 3 and alpha 4 type IV collagens are colocalized and present in kidney, eye, basement membranes of lens capsule, cochlea, lung, skeletal muscle, aorta, synaptic fibers, fetal kidney and fetal lung. PubMed:8083201 reports similar levels of expression of alpha 3 and alpha 4 type IV collagens in kidney, but PubMed:7523402 reports that in kidney levels of alpha 3 type IV collagen are significantly lower than those of alpha 4 type IV collagen. According to PubMed:8083201, alpha 3 type IV collagen is not detected in heart, brain, placenta, liver, pancreas, extrasynaptic muscle fibers, endoneurial and perineurial nerves, fetal brain, fetal heart and fetal liver. According to PubMed:7523402, alpha 3 type IV collagen is strongly expressed in pancreas, neuroretina and calvaria and not expressed in adrenal, ileum and skin. Isoform 1 and isoform 3 are strongly expressed in kidney, lung, suprarenal capsule, muscle and spleen, in each of these tissues isoform 1 is more abundant than isoform 3. Isoform 1 and isoform 3 are expressed at low levels in artery, fat, pericardium and peripherical nerve, but not in placenta, mesangium, skin, pleura and cultured umbilical endothelial cells.3 Publications

    Gene expression databases

    ArrayExpressiQ01955.
    BgeeiQ01955.
    CleanExiHS_COL4A3.
    GenevestigatoriQ01955.

    Organism-specific databases

    HPAiHPA042064.

    Interactioni

    Subunit structurei

    There are six type IV collagen isoforms, alpha 1(IV)-alpha 6(IV), each of which can form a triple helix structure with 2 other chains to generate type IV collagen network. The alpha 3(IV) chain forms a triple helical protomer with alpha 4(IV) and alpha 5(IV); this triple helical structure dimerizes through NC1-NC1 domain interactions such that the alpha 3(IV), alpha 4(IV) and alpha 5(IV) chains of one protomer connect with the alpha 5(IV), alpha 4(IV) and alpha 3(IV) chains of the opposite promoter, respectively. Interacts with COL4A3BP AND ITGB3. Associates with LAMB2 at the neuromuscular junction and in GBM By similarity.By similarity

    Protein-protein interaction databases

    BioGridi107682. 3 interactions.
    IntActiQ01955. 1 interaction.
    STRINGi9606.ENSP00000379823.

    Structurei

    3D structure databases

    ProteinModelPortaliQ01955.
    SMRiQ01955. Positions 1445-1668.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini1445 – 1669225Collagen IV NC1PROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni29 – 42147S domainAdd
    BLAST
    Regioni43 – 14381396Triple-helical regionAdd
    BLAST
    Regioni1427 – 144418Epitope recognized by Goodpasture antibodiesAdd
    BLAST
    Regioni1479 – 155779Required for the anti-angiogenic activity of tumstatinAdd
    BLAST
    Regioni1610 – 162819Required for the anti-tumor cell activity of tumstatinAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi791 – 7933Cell attachment siteSequence Analysis
    Motifi996 – 9983Cell attachment siteSequence Analysis
    Motifi1154 – 11563Cell attachment siteSequence Analysis
    Motifi1306 – 13083Cell attachment siteSequence Analysis
    Motifi1345 – 13473Cell attachment siteSequence Analysis
    Motifi1432 – 14343Cell attachment siteSequence Analysis

    Domaini

    Alpha chains of type IV collagen have a non-collagenous domain (NC1) at their C-terminus, frequent interruptions of the G-X-Y repeats in the long central triple-helical domain (which may cause flexibility in the triple helix), and a short N-terminal triple-helical 7S domain.

    Sequence similaritiesi

    Belongs to the type IV collagen family.PROSITE-ProRule annotation
    Contains 1 collagen IV NC1 (C-terminal non-collagenous) domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Collagen, Repeat, Signal

    Phylogenomic databases

    eggNOGiNOG12793.
    HOVERGENiHBG004933.
    KOiK06237.
    OMAiSPGCPGK.
    OrthoDBiEOG7RZ5P3.
    PhylomeDBiQ01955.
    TreeFamiTF344135.

    Family and domain databases

    Gene3Di2.170.240.10. 1 hit.
    InterProiIPR016187. C-type_lectin_fold.
    IPR008160. Collagen.
    IPR001442. Collagen_VI_NC.
    [Graphical view]
    PfamiPF01413. C4. 2 hits.
    PF01391. Collagen. 22 hits.
    [Graphical view]
    SMARTiSM00111. C4. 2 hits.
    [Graphical view]
    SUPFAMiSSF56436. SSF56436. 2 hits.
    PROSITEiPS51403. NC1_IV. 1 hit.
    [Graphical view]

    Sequences (5)i

    Sequence statusi: Complete.

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

    This entry describes 5 isoformsi produced by alternative splicing. Align

    Note: The majority of isoforms differ in the C-terminal part of the NC1 domain.

    Isoform 1 (identifier: Q01955-1) [UniParc]FASTAAdd to Basket

    Also known as: GP

    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

    MSARTAPRPQ VLLLPLLLVL LAAAPAASKG CVCKDKGQCF CDGAKGEKGE     50
    KGFPGPPGSP GQKGFTGPEG LPGPQGPKGF PGLPGLTGSK GVRGISGLPG 100
    FSGSPGLPGT PGNTGPYGLV GVPGCSGSKG EQGFPGLPGT LGYPGIPGAA 150
    GLKGQKGAPA KEEDIELDAK GDPGLPGAPG PQGLPGPPGF PGPVGPPGPP 200
    GFFGFPGAMG PRGPKGHMGE RVIGHKGERG VKGLTGPPGP PGTVIVTLTG 250
    PDNRTDLKGE KGDKGAMGEP GPPGPSGLPG ESYGSEKGAP GDPGLQGKPG 300
    KDGVPGFPGS EGVKGNRGFP GLMGEDGIKG QKGDIGPPGF RGPTEYYDTY 350
    QEKGDEGTPG PPGPRGARGP QGPSGPPGVP GSPGSSRPGL RGAPGWPGLK 400
    GSKGERGRPG KDAMGTPGSP GCAGSPGLPG SPGPPGPPGD IVFRKGPPGD 450
    HGLPGYLGSP GIPGVDGPKG EPGLLCTQCP YIPGPPGLPG LPGLHGVKGI 500
    PGRQGAAGLK GSPGSPGNTG LPGFPGFPGA QGDPGLKGEK GETLQPEGQV 550
    GVPGDPGLRG QPGRKGLDGI PGTPGVKGLP GPKGELALSG EKGDQGPPGD 600
    PGSPGSPGPA GPAGPPGYGP QGEPGLQGTQ GVPGAPGPPG EAGPRGELSV 650
    STPVPGPPGP PGPPGHPGPQ GPPGIPGSLG KCGDPGLPGP DGEPGIPGIG 700
    FPGPPGPKGD QGFPGTKGSL GCPGKMGEPG LPGKPGLPGA KGEPAVAMPG 750
    GPGTPGFPGE RGNSGEHGEI GLPGLPGLPG TPGNEGLDGP RGDPGQPGPP 800
    GEQGPPGRCI EGPRGAQGLP GLNGLKGQQG RRGKTGPKGD PGIPGLDRSG 850
    FPGETGSPGI PGHQGEMGPL GQRGYPGNPG ILGPPGEDGV IGMMGFPGAI 900
    GPPGPPGNPG TPGQRGSPGI PGVKGQRGTP GAKGEQGDKG NPGPSEISHV 950
    IGDKGEPGLK GFAGNPGEKG NRGVPGMPGL KGLKGLPGPA GPPGPRGDLG 1000
    STGNPGEPGL RGIPGSMGNM GMPGSKGKRG TLGFPGRAGR PGLPGIHGLQ 1050
    GDKGEPGYSE GTRPGPPGPT GDPGLPGDMG KKGEMGQPGP PGHLGPAGPE 1100
    GAPGSPGSPG LPGKPGPHGD LGFKGIKGLL GPPGIRGPPG LPGFPGSPGP 1150
    MGIRGDQGRD GIPGPAGEKG ETGLLRAPPG PRGNPGAQGA KGDRGAPGFP 1200
    GLPGRKGAMG DAGPRGPTGI EGFPGPPGLP GAIIPGQTGN RGPPGSRGSP 1250
    GAPGPPGPPG SHVIGIKGDK GSMGHPGPKG PPGTAGDMGP PGRLGAPGTP 1300
    GLPGPRGDPG FQGFPGVKGE KGNPGFLGSI GPPGPIGPKG PPGVRGDPGT 1350
    LKIISLPGSP GPPGTPGEPG MQGEPGPPGP PGNLGPCGPR GKPGKDGKPG 1400
    TPGPAGEKGN KGSKGEPGPA GSDGLPGLKG KRGDSGSPAT WTTRGFVFTR 1450
    HSQTTAIPSC PEGTVPLYSG FSFLFVQGNQ RAHGQDLGTL GSCLQRFTTM 1500
    PFLFCNVNDV CNFASRNDYS YWLSTPALMP MNMAPITGRA LEPYISRCTV 1550
    CEGPAIAIAV HSQTTDIPPC PHGWISLWKG FSFIMFTSAG SEGTGQALAS 1600
    PGSCLEEFRA SPFLECHGRG TCNYYSNSYS FWLASLNPER MFRKPIPSTV 1650
    KAGELEKIIS RCQVCMKKRH 1670
    Length:1,670
    Mass (Da):161,813
    Last modified:March 6, 2007 - v3
    Checksum:iAA65D50903D82B99
    GO
    Isoform 2 (identifier: Q01955-2) [UniParc]FASTAAdd to Basket

    Also known as: V, GP-V

    The sequence of this isoform differs from the canonical sequence as follows:
         1586-1670: FTSAGSEGTG...RCQVCMKKRH → KAYSINCESW...NKVMTEHAVI

    Show »
    Length:1,637
    Mass (Da):158,336
    Checksum:i92396B115CEA21DF
    GO
    Isoform 3 (identifier: Q01955-3) [UniParc]FASTAAdd to Basket

    Also known as: L5, GP-III, GP-III/V

    The sequence of this isoform differs from the canonical sequence as follows:
         1488-1670: GTLGSCLQRF...RCQVCMKKRH → DALFVKVLRSP

    Show »
    Length:1,498
    Mass (Da):142,741
    Checksum:i74CF6C2B17B98686
    GO
    Isoform 4 (identifier: Q01955-4) [UniParc]FASTAAdd to Basket

    Also known as: GP-III/IV/V

    The sequence of this isoform differs from the canonical sequence as follows:
         1488-1670: GTLGSCLQRF...RCQVCMKKRH → ESLFHQL

    Show »
    Length:1,494
    Mass (Da):142,369
    Checksum:iC24C75A6029B73C8
    GO
    Isoform 5 (identifier: Q01955-5) [UniParc]FASTAAdd to Basket

    Also known as: GP-II/III/IV/V

    The sequence of this isoform differs from the canonical sequence as follows:
         1418-1424: GPAGSDG → ESLFHQL
         1425-1670: Missing.

    Show »
    Length:1,424
    Mass (Da):135,079
    Checksum:i80BA77353C7013C6
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti911 – 9111T → R in CAC36101. (PubMed:11134255)Curated
    Sequence conflicti1539 – 15391R → I in AAA18942. (PubMed:8294492)Curated
    Sequence conflicti1594 – 15941T → A in AAB19637. (PubMed:1882840)Curated
    Sequence conflicti1663 – 16642QV → HL in AAA52044. 1 PublicationCurated
    Isoform 2 (identifier: Q01955-2)
    Sequence conflicti1539 – 15391R → I in AAA18942. (PubMed:8294492)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti43 – 431G → R.1 Publication
    Corresponds to variant rs13424243 [ dbSNP | Ensembl ].
    VAR_011202
    Natural varianti141 – 1411L → P.2 Publications
    Corresponds to variant rs10178458 [ dbSNP | Ensembl ].
    VAR_030944
    Natural varianti162 – 1621E → G.1 Publication
    Corresponds to variant rs6436669 [ dbSNP | Ensembl ].
    VAR_011203
    Natural varianti297 – 2971G → E in APSAR. 1 Publication
    VAR_011204
    Natural varianti326 – 3261D → Y.1 Publication
    Corresponds to variant rs55703767 [ dbSNP | Ensembl ].
    VAR_011205
    Natural varianti407 – 4071G → R in APSAR. 1 Publication
    VAR_011206
    Natural varianti408 – 4081R → H.1 Publication
    Corresponds to variant rs34505188 [ dbSNP | Ensembl ].
    VAR_011207
    Natural varianti451 – 4511H → R.1 Publication
    Corresponds to variant rs11677877 [ dbSNP | Ensembl ].
    VAR_011208
    Natural varianti532 – 5321G → D in APSAR. 1 Publication
    VAR_030945
    Natural varianti574 – 5741P → L.1 Publication
    Corresponds to variant rs28381984 [ dbSNP | Ensembl ].
    VAR_011209
    Natural varianti640 – 6401G → R in APSAR. 1 Publication
    VAR_011210
    Natural varianti739 – 7391G → R in APSAR. 1 Publication
    VAR_030946
    Natural varianti834 – 8341K → R.
    Corresponds to variant rs56226424 [ dbSNP | Ensembl ].
    VAR_061118
    Natural varianti853 – 8531G → R in APSAR. 1 Publication
    VAR_030947
    Natural varianti985 – 9851G → V in BFH. 1 Publication
    VAR_030948
    Natural varianti1015 – 10151G → E in BFH. 1 Publication
    VAR_030949
    Natural varianti1167 – 11671G → R in APSAD; in isolated microhematuria at heterozygosity. 1 Publication
    VAR_011211
    Natural varianti1207 – 12071G → E in APSAR; in isolated microhematuria at heterozygosity. 1 Publication
    VAR_011212
    Natural varianti1215 – 12151R → Q in APSAR; unknown pathological significance. 1 Publication
    VAR_011213
    Natural varianti1216 – 12161G → R in APSAR. 1 Publication
    VAR_030950
    Natural varianti1269 – 12691D → E.1 Publication
    Corresponds to variant rs57611801 [ dbSNP | Ensembl ].
    VAR_011214
    Natural varianti1277 – 12771G → S in APSAR. 1 Publication
    Corresponds to variant rs190598500 [ dbSNP | Ensembl ].
    VAR_011215
    Natural varianti1330 – 13301I → T in APSAR; unknown pathological significance. 1 Publication
    VAR_011216
    Natural varianti1334 – 13341G → E in APSAR. 1 Publication
    VAR_011217
    Natural varianti1347 – 13471D → E in APSAR; unknown pathological significance. 1 Publication
    Corresponds to variant rs73996414 [ dbSNP | Ensembl ].
    VAR_011218
    Natural varianti1474 – 14741L → P.2 Publications
    Corresponds to variant rs200302125 [ dbSNP | Ensembl ].
    VAR_001908
    Natural varianti1495 – 14951Q → R.
    Corresponds to variant rs77964815 [ dbSNP | Ensembl ].
    VAR_001909
    Natural varianti1661 – 16611R → C in APSAR. 1 Publication
    VAR_011219

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1418 – 14247GPAGSDG → ESLFHQL in isoform 5. 1 PublicationVSP_023498
    Alternative sequencei1425 – 1670246Missing in isoform 5. 1 PublicationVSP_023499Add
    BLAST
    Alternative sequencei1488 – 1670183GTLGS…MKKRH → DALFVKVLRSP in isoform 3. 2 PublicationsVSP_001171Add
    BLAST
    Alternative sequencei1488 – 1670183GTLGS…MKKRH → ESLFHQL in isoform 4. 1 PublicationVSP_023500Add
    BLAST
    Alternative sequencei1586 – 167085FTSAG…MKKRH → KAYSINCESWGIRKNNKSLS GVHEEKTLKLKKTAELVFFI LKNKVMTEHAVI in isoform 2. 2 PublicationsVSP_001170Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X80031 mRNA. Translation: CAA56335.1.
    AJ288487
    , AJ288488, AJ288489, AJ288490, AJ288491, AJ288492, AJ288493, AJ288494, AJ288495, AJ288496, AJ288497, AJ288498, AJ288499, AJ288500, AJ288501, AJ288502, AJ288503, AJ288504, AJ288505, AJ288506, AJ288507, AJ288508, AJ288509, AJ288510, AJ288511, AJ288512, AJ288513, AJ288514, AJ288515, AJ288516, AJ288517, AJ288518, AJ288519, AJ288520, AJ288521, AJ288522, AJ288523, AJ288524, AJ288525, AJ288526, AJ288527, AJ288528, AJ288529, AJ288530, AJ288531, AJ288532, AJ288533, AJ288534, AJ288535, AJ288536, AJ288537, AJ288538 Genomic DNA. Translation: CAC36101.1.
    AC079235 Genomic DNA. Translation: AAY14671.1.
    AC097662 Genomic DNA. Translation: AAY24251.1.
    AC107069 Genomic DNA. Translation: AAX93111.1.
    AB008496 Genomic DNA. Translation: BAA25064.1.
    M81379 mRNA. Translation: AAA51556.1.
    M92993 mRNA. Translation: AAA21610.1.
    AF258351 mRNA. Translation: AAF72632.1.
    U02519 mRNA. Translation: AAA18942.1.
    U02520 mRNA. Translation: AAA18943.1.
    S55790 mRNA. Translation: AAB19637.1.
    L08650 Genomic DNA. Translation: AAA52044.1.
    CCDSiCCDS42829.1. [Q01955-1]
    PIRiA49736.
    A54763. CGHU3B.
    B49736.
    S69113.
    RefSeqiNP_000082.2. NM_000091.4. [Q01955-1]
    UniGeneiHs.570065.

    Genome annotation databases

    EnsembliENST00000396578; ENSP00000379823; ENSG00000169031. [Q01955-1]
    GeneIDi1285.
    KEGGihsa:1285.
    UCSCiuc002vom.2. human. [Q01955-1]

    Polymorphism databases

    DMDMi134035067.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X80031 mRNA. Translation: CAA56335.1 .
    AJ288487
    , AJ288488 , AJ288489 , AJ288490 , AJ288491 , AJ288492 , AJ288493 , AJ288494 , AJ288495 , AJ288496 , AJ288497 , AJ288498 , AJ288499 , AJ288500 , AJ288501 , AJ288502 , AJ288503 , AJ288504 , AJ288505 , AJ288506 , AJ288507 , AJ288508 , AJ288509 , AJ288510 , AJ288511 , AJ288512 , AJ288513 , AJ288514 , AJ288515 , AJ288516 , AJ288517 , AJ288518 , AJ288519 , AJ288520 , AJ288521 , AJ288522 , AJ288523 , AJ288524 , AJ288525 , AJ288526 , AJ288527 , AJ288528 , AJ288529 , AJ288530 , AJ288531 , AJ288532 , AJ288533 , AJ288534 , AJ288535 , AJ288536 , AJ288537 , AJ288538 Genomic DNA. Translation: CAC36101.1 .
    AC079235 Genomic DNA. Translation: AAY14671.1 .
    AC097662 Genomic DNA. Translation: AAY24251.1 .
    AC107069 Genomic DNA. Translation: AAX93111.1 .
    AB008496 Genomic DNA. Translation: BAA25064.1 .
    M81379 mRNA. Translation: AAA51556.1 .
    M92993 mRNA. Translation: AAA21610.1 .
    AF258351 mRNA. Translation: AAF72632.1 .
    U02519 mRNA. Translation: AAA18942.1 .
    U02520 mRNA. Translation: AAA18943.1 .
    S55790 mRNA. Translation: AAB19637.1 .
    L08650 Genomic DNA. Translation: AAA52044.1 .
    CCDSi CCDS42829.1. [Q01955-1 ]
    PIRi A49736.
    A54763. CGHU3B.
    B49736.
    S69113.
    RefSeqi NP_000082.2. NM_000091.4. [Q01955-1 ]
    UniGenei Hs.570065.

    3D structure databases

    ProteinModelPortali Q01955.
    SMRi Q01955. Positions 1445-1668.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 107682. 3 interactions.
    IntActi Q01955. 1 interaction.
    STRINGi 9606.ENSP00000379823.

    Chemistry

    ChEMBLi CHEMBL2364188.

    PTM databases

    PhosphoSitei Q01955.

    Polymorphism databases

    DMDMi 134035067.

    Proteomic databases

    MaxQBi Q01955.
    PaxDbi Q01955.
    PRIDEi Q01955.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000396578 ; ENSP00000379823 ; ENSG00000169031 . [Q01955-1 ]
    GeneIDi 1285.
    KEGGi hsa:1285.
    UCSCi uc002vom.2. human. [Q01955-1 ]

    Organism-specific databases

    CTDi 1285.
    GeneCardsi GC02P227993.
    GeneReviewsi COL4A3.
    H-InvDB HIX0002893.
    HIX0029836.
    HGNCi HGNC:2204. COL4A3.
    HPAi HPA042064.
    MIMi 104200. phenotype.
    120070. gene.
    141200. phenotype.
    203780. phenotype.
    neXtProti NX_Q01955.
    Orphaneti 88918. Autosomal dominant Alport syndrome.
    88919. Autosomal recessive Alport syndrome.
    97562. Benign familial hematuria.
    PharmGKBi PA26719.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG12793.
    HOVERGENi HBG004933.
    KOi K06237.
    OMAi SPGCPGK.
    OrthoDBi EOG7RZ5P3.
    PhylomeDBi Q01955.
    TreeFami TF344135.

    Enzyme and pathway databases

    Reactomei REACT_118779. Extracellular matrix organization.
    REACT_121139. Collagen biosynthesis and modifying enzymes.
    REACT_13552. Integrin cell surface interactions.
    REACT_150180. Assembly of collagen fibrils and other multimeric structures.
    REACT_150268. Anchoring fibril formation.
    REACT_150401. Collagen degradation.
    REACT_163874. Non-integrin membrane-ECM interactions.
    REACT_163906. ECM proteoglycans.
    REACT_16888. Signaling by PDGF.
    REACT_169262. Laminin interactions.
    REACT_18312. NCAM1 interactions.

    Miscellaneous databases

    GeneWikii Collagen_alpha-3(IV)_chain.
    GenomeRNAii 1285.
    NextBioi 5191.
    PROi Q01955.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q01955.
    Bgeei Q01955.
    CleanExi HS_COL4A3.
    Genevestigatori Q01955.

    Family and domain databases

    Gene3Di 2.170.240.10. 1 hit.
    InterProi IPR016187. C-type_lectin_fold.
    IPR008160. Collagen.
    IPR001442. Collagen_VI_NC.
    [Graphical view ]
    Pfami PF01413. C4. 2 hits.
    PF01391. Collagen. 22 hits.
    [Graphical view ]
    SMARTi SM00111. C4. 2 hits.
    [Graphical view ]
    SUPFAMi SSF56436. SSF56436. 2 hits.
    PROSITEi PS51403. NC1_IV. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Complete primary structure of the human alpha 3(IV) collagen chain. Coexpression of the alpha 3(IV) and alpha 4(IV) collagen chains in human tissues."
      Mariyama M., Leinonen A., Mochizuki T., Tryggvason K., Reeders S.T.
      J. Biol. Chem. 269:23013-23017(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, VARIANTS PRO-141; GLY-162 AND LEU-574.
      Tissue: Kidney.
    2. Leinonen A.
      Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases
      Cited for: SEQUENCE REVISION.
    3. "Structure of the human type IV collagen gene COL4A3 and mutations in autosomal Alport syndrome."
      Heidet L., Arrondel C., Forestier L., Cohen-Solal L., Mollet G., Gutierrez B., Stavrou C., Gubler M.-C., Antignac C.
      J. Am. Soc. Nephrol. 12:97-106(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), VARIANTS APSAR GLU-297; ARG-407; ARG-640; GLU-1207; GLN-1215; SER-1277; THR-1330; GLU-1334; GLU-1347 AND CYS-1661, VARIANT APSAD ARG-1167, VARIANTS ARG-43; PRO-141; TYR-326; HIS-408; ARG-451; GLU-1269 AND PRO-1474.
    4. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
      Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
      , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
      Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "Two genes, COL4A3 and COL4A4 coding for the human alpha3(IV) and alpha4(IV) collagen chains are arranged head-to-head on chromosome 2q36."
      Momota R., Sugimoto M., Oohashi T., Kigasawa K., Yoshioka H., Ninomiya Y.
      FEBS Lett. 424:11-16(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-29.
    6. "Molecular cloning of the human Goodpasture antigen demonstrates it to be the alpha 3 chain of type IV collagen."
      Turner N., Mason P.J., Brown R., Fox M., Povey S., Rees A., Pusey C.D.
      J. Clin. Invest. 89:592-601(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 1331-1670 (ISOFORM 1).
      Tissue: Kidney.
    7. "Exon/intron structure of the human alpha 3(IV) gene encompassing the Goodpasture antigen (alpha 3(IV)NC1). Identification of a potentially antigenic region at the triple helix/NC1 domain junction."
      Quinones S., Bernal D., Garcia-Sogo M., Elena S.F., Saus J.
      J. Biol. Chem. 267:19780-19784(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1386-1670 (ISOFORM 1), PARTIAL PROTEIN SEQUENCE.
    8. Erratum
      Quinones S., Bernal D., Garcia-Sogo M., Elena S.F., Saus J.
      J. Biol. Chem. 269:17358-17358(1994) [PubMed] [Europe PMC] [Abstract]
    9. "Characterization and expression of multiple alternatively spliced transcripts of the Goodpasture antigen gene region. Goodpasture antibodies recognize recombinant proteins representing the autoantigen and one of its alternative forms."
      Penades J.R., Bernal D., Revert F., Johansson C., Fresquet V.J., Cervera J., Wieslander J., Quinones S., Saus J.
      Eur. J. Biochem. 229:754-760(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1386-1670 (ISOFORMS 1; 2; 3; 4 AND 5), ALTERNATIVE SPLICING.
      Tissue: Kidney.
    10. "Distinct antitumor properties of a type IV collagen domain derived from basement membrane."
      Maeshima Y., Colorado P.C., Torre A., Holthaus K.A., Grunkemeyer J.A., Ericksen M.B., Hopfer H., Xiao Y., Stillman I.E., Kalluri R.
      J. Biol. Chem. 275:21340-21348(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1426-1670 (ISOFORM 1), FUNCTION.
    11. "Alternative splicing of the NC1 domain of the human alpha 3(IV) collagen gene. Differential expression of mRNA transcripts that predict three protein variants with distinct carboxyl regions."
      Feng L., Xia Y., Wilson C.B.
      J. Biol. Chem. 269:2342-2348(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1439-1670 (ISOFORMS 2 AND 3), ALTERNATIVE SPLICING (ISOFORM 1).
      Tissue: Kidney.
    12. "Sequence and localization of a partial cDNA encoding the human alpha 3 chain of type IV collagen."
      Morrison K.E., Mariyama M., Yang-Feng T.L., Reeders S.T.
      Am. J. Hum. Genet. 49:545-554(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1453-1670 (ISOFORM 1).
    13. Ding J.
      Submitted (JAN-1993) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1644-1670 (ISOFORM 1).
      Tissue: Kidney.
    14. "The human mRNA encoding the Goodpasture antigen is alternatively spliced."
      Bernal D., Quinones S., Saus J.
      J. Biol. Chem. 268:12090-12094(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3), ALTERNATIVE SPLICING, TISSUE SPECIFICITY.
      Tissue: Kidney.
    15. "Complete primary structure of the human type IV collagen alpha 4(IV) chain. Comparison with structure and expression of the other alpha (IV) chains."
      Leinonen A., Mariyama M., Mochizuki T., Tryggvason K., Reeders S.T.
      J. Biol. Chem. 269:26172-26177(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    16. "Characterization of a novel type of serine/threonine kinase that specifically phosphorylates the human goodpasture antigen."
      Raya A., Revert F., Navarro S., Saus J.
      J. Biol. Chem. 274:12642-12649(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH COL4A3BP, PHOSPHORYLATION.
    17. "Two RGD-independent alpha vbeta 3 integrin binding sites on tumstatin regulate distinct anti-tumor properties."
      Maeshima Y., Colorado P.C., Kalluri R.
      J. Biol. Chem. 275:23745-23750(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    18. Cited for: INVOLVEMENT IN APSAD.
    19. "Quaternary organization of the goodpasture autoantigen, the alpha 3(IV) collagen chain. Sequestration of two cryptic autoepitopes by intrapromoter interactions with the alpha4 and alpha5 NC1 domains."
      Borza D.B., Bondar O., Todd P., Sundaramoorthy M., Sado Y., Ninomiya Y., Hudson B.G.
      J. Biol. Chem. 277:40075-40083(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: HEXAMERIZATION.
    20. "Human tumstatin and human endostatin exhibit distinct antiangiogenic activities mediated by alpha v beta 3 and alpha 5 beta 1 integrins."
      Sudhakar A., Sugimoto H., Yang C., Lively J., Zeisberg M., Kalluri R.
      Proc. Natl. Acad. Sci. U.S.A. 100:4766-4771(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH ITGB3.
    21. "Implication of tumstatin in tumor progression of human bronchopulmonary carcinomas."
      Caudroy S., Cucherousset J., Lorenzato M., Zahm J.-M., Martinella-Catusse C., Polette M., Birembaut P.
      Hum. Pathol. 35:1218-1222(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    22. "Tryptic digestion of ubiquitin standards reveals an improved strategy for identifying ubiquitinated proteins by mass spectrometry."
      Denis N.J., Vasilescu J., Lambert J.-P., Smith J.C., Figeys D.
      Proteomics 7:868-874(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-1414.
      Tissue: Mammary cancer.
    23. Cited for: VARIANT PRO-1474.
    24. "Mutations in the COL4A4 and COL4A3 genes cause familial benign hematuria."
      Badenas C., Praga M., Tazon B., Heidet L., Arrondel C., Armengol A., Andres A., Morales E., Camacho J.A., Lens X., Davila S., Mila M., Antignac C., Darnell A., Torra R.
      J. Am. Soc. Nephrol. 13:1248-1254(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS BFH VAL-985 AND GLU-1015.
    25. "Novel COL4A5, COL4A4, and COL4A3 mutations in Alport syndrome."
      Nagel M., Nagorka S., Gross O.
      Hum. Mutat. 26:60-60(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS APSAR ASP-532; ARG-739; ARG-853 AND ARG-1216.

    Entry informationi

    Entry nameiCO4A3_HUMAN
    AccessioniPrimary (citable) accession number: Q01955
    Secondary accession number(s): Q53QQ1
    , Q53R14, Q53RW8, Q9BQT2, Q9NYC4, Q9UDJ9, Q9UDK9, Q9UDL0, Q9UDL1
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1996
    Last sequence update: March 6, 2007
    Last modified: October 1, 2014
    This is version 171 of the entry and version 3 of the sequence. [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

    Miscellaneous

    The epitopes recognized by the Goodpasture autoantibodies are sequestered within the NC1 hexamer of the type IV collagen network.

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 2
      Human chromosome 2: 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
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3