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O95967 (FBLN4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 149. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
EGF-containing fibulin-like extracellular matrix protein 2
Alternative name(s):
Fibulin-4
Short name=FIBL-4
Protein UPH1
Gene names
Name:EFEMP2
Synonyms:FBLN4
ORF Names:UNQ200/PRO226
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length443 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Subcellular location

Secreted.

Involvement in disease

Cutis laxa, autosomal recessive, 1B (ARCL1B) [MIM:614437]: A connective tissue disorder characterized by loose, hyperextensible skin with decreased resilience and elasticity leading to a premature aged appearance. Face, hands, feet, joints, and torso may be differentially affected. The clinical spectrum of autosomal recessive cutis laxa is highly heterogeneous with respect to organ involvement and severity. ARCL1B features include emphysema, lethal pulmonary artery occlusion, aortic aneurysm, cardiopulmonary insufficiency, birth fractures, arachnodactyly, and fragility of blood vessels.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10 Ref.11 Ref.12

Sequence similarities

Belongs to the fibulin family.

Contains 6 EGF-like domains.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2525 Potential
Chain26 – 443418EGF-containing fibulin-like extracellular matrix protein 2
PRO_0000007575

Regions

Domain36 – 8146EGF-like 1; atypical
Domain123 – 16341EGF-like 2; calcium-binding Potential
Domain164 – 20239EGF-like 3; calcium-binding Potential
Domain203 – 24240EGF-like 4; calcium-binding Potential
Domain243 – 28240EGF-like 5; calcium-binding Potential
Domain283 – 32846EGF-like 6; calcium-binding Potential

Amino acid modifications

Glycosylation1981N-linked (GlcNAc...) Potential
Glycosylation3941N-linked (GlcNAc...) Potential
Disulfide bond58 ↔ 121 Ref.9
Disulfide bond65 ↔ 80 Ref.9
Disulfide bond71 ↔ 109 Ref.9
Disulfide bond127 ↔ 140 By similarity
Disulfide bond134 ↔ 149 By similarity
Disulfide bond151 ↔ 162 By similarity
Disulfide bond168 ↔ 177 By similarity
Disulfide bond173 ↔ 186 By similarity
Disulfide bond188 ↔ 201 By similarity
Disulfide bond207 ↔ 217 By similarity
Disulfide bond213 ↔ 226 By similarity
Disulfide bond228 ↔ 241 By similarity
Disulfide bond247 ↔ 258 By similarity
Disulfide bond254 ↔ 267 By similarity
Disulfide bond269 ↔ 281 By similarity
Disulfide bond287 ↔ 300 By similarity
Disulfide bond294 ↔ 309 By similarity
Disulfide bond315 ↔ 327 By similarity

Natural variations

Natural variant571E → K in ARCL1B. Ref.10
VAR_027019
Natural variant2591I → V. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5 Ref.6 Ref.8
Corresponds to variant rs601314 [ dbSNP | Ensembl ].
VAR_027020
Natural variant2671C → Y in ARCL1B. Ref.12
VAR_067069
Natural variant2791R → C in ARCL1B. Ref.11
VAR_067070

Experimental info

Sequence conflict51A → T in CAA10791. Ref.1
Sequence conflict44 – 518EWDPDSQH → TQTAN in AAC62108. Ref.2
Sequence conflict461D → G in BAF84768. Ref.4
Sequence conflict961P → L in BAG50843. Ref.4
Sequence conflict103 – 1119AQHPNPCPP → VNTQPLPT in AAC62108. Ref.2
Sequence conflict2941C → W in AAC62108. Ref.2
Sequence conflict354 – 3563RSV → AER in AAC62108. Ref.2
Sequence conflict3551S → R in AAF65188. Ref.3

Secondary structure

....... 443
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O95967 [UniParc].

Last modified March 20, 2007. Version 3.
Checksum: 9315CFBBAA0FD3A7

FASTA44349,405
        10         20         30         40         50         60 
MLPCASCLPG SLLLWALLLL LLGSASPQDS EEPDSYTECT DGYEWDPDSQ HCRDVNECLT 

        70         80         90        100        110        120 
IPEACKGEMK CINHYGGYLC LPRSAAVIND LHGEGPPPPV PPAQHPNPCP PGYEPDDQDS 

       130        140        150        160        170        180 
CVDVDECAQA LHDCRPSQDC HNLPGSYQCT CPDGYRKIGP ECVDIDECRY RYCQHRCVNL 

       190        200        210        220        230        240 
PGSFRCQCEP GFQLGPNNRS CVDVNECDMG APCEQRCFNS YGTFLCRCHQ GYELHRDGFS 

       250        260        270        280        290        300 
CSDIDECSYS SYLCQYRCIN EPGRFSCHCP QGYQLLATRL CQDIDECESG AHQCSEAQTC 

       310        320        330        340        350        360 
VNFHGGYRCV DTNRCVEPYI QVSENRCLCP ASNPLCREQP SSIVHRYMTI TSERSVPADV 

       370        380        390        400        410        420 
FQIQATSVYP GAYNAFQIRA GNSQGDFYIR QINNVSAMLV LARPVTGPRE YVLDLEMVTM 

       430        440 
NSLMSYRASS VLRLTVFVGA YTF 

« Hide

References

« Hide 'large scale' references
[1]"Sequence, recombinant expression and tissue localization of two novel extracellular matrix proteins, fibulin-3 and fibulin-4."
Giltay R., Timpl R., Kostka G.
Matrix Biol. 18:469-480(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT VAL-259.
Tissue: Melanoma.
[2]Zemel R., Shaul Y.
Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT VAL-259.
[3]"Isolation of a paralog of the Doyne honeycomb retinal dystrophy gene from the multiple retinopathy critical region on 11q13."
Katsanis N., Venable S., Smith J.R., Lupski J.R.
Hum. Genet. 106:66-72(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT VAL-259.
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT VAL-259.
Tissue: Embryo and Synovium.
[5]"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. expand/collapse author list , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.
Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT VAL-259.
[6]"Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries."
Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J., Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S., Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y. expand/collapse author list , Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S., Isogai T.
DNA Res. 12:117-126(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT VAL-259.
Tissue: Placenta.
[7]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT VAL-259.
Tissue: Brain.
[9]"Solution NMR structure of the EGF-like 1 domain of human fibulin-4."
Northeast structural genomics consortium (NESG)
Submitted (JUL-2009) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 54-123, DISULFIDE BONDS.
[10]"Fibulin-4: a novel gene for an autosomal recessive cutis laxa syndrome."
Hucthagowder V., Sausgruber N., Kim K.H., Angle B., Marmorstein L.Y., Urban Z.
Am. J. Hum. Genet. 78:1075-1080(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ARCL1B LYS-57.
[11]"Compound heterozygous mutations in fibulin-4 causing neonatal lethal pulmonary artery occlusion, aortic aneurysm, arachnodactyly, and mild cutis laxa."
Dasouki M., Markova D., Garola R., Sasaki T., Charbonneau N.L., Sakai L.Y., Chu M.L.
Am. J. Med. Genet. A 143:2635-2641(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ARCL1B CYS-279.
[12]"Lethal cutis laxa with contractural arachnodactyly, overgrowth and soft tissue bleeding due to a novel homozygous fibulin-4 gene mutation."
Hoyer J., Kraus C., Hammersen G., Geppert J.P., Rauch A.
Clin. Genet. 76:276-281(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ARCL1B TYR-267.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ132819 mRNA. Translation: CAA10791.2.
AF093119 mRNA. Translation: AAC62108.1.
AF109121 mRNA. Translation: AAF65188.1.
AK000980 mRNA. Translation: BAG50843.1.
AK292079 mRNA. Translation: BAF84768.1.
AY358899 mRNA. Translation: AAQ89258.1.
AK075453 mRNA. Translation: BAG52143.1.
AP001201 Genomic DNA. No translation available.
BC010456 mRNA. Translation: AAH10456.1.
CCDSCCDS8116.1.
RefSeqNP_058634.4. NM_016938.4.
UniGeneHs.731454.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2KL7NMR-A54-123[»]
ProteinModelPortalO95967.
SMRO95967. Positions 54-309.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid119026. 38 interactions.
DIPDIP-34518N.
IntActO95967. 44 interactions.
MINTMINT-1439082.
STRING9606.ENSP00000309953.

PTM databases

PhosphoSiteO95967.

Proteomic databases

PaxDbO95967.
PRIDEO95967.

Protocols and materials databases

DNASU30008.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000307998; ENSP00000309953; ENSG00000172638.
ENST00000531972; ENSP00000435295; ENSG00000172638.
GeneID30008.
KEGGhsa:30008.
UCSCuc001ofy.4. human.

Organism-specific databases

CTD30008.
GeneCardsGC11M065633.
GeneReviewsEFEMP2.
HGNCHGNC:3219. EFEMP2.
HPAHPA023270.
MIM604633. gene.
614437. phenotype.
neXtProtNX_O95967.
Orphanet90349. Autosomal recessive cutis laxa type 1.
314718. Lethal arteriopathy syndrome due to Fibulin-4 deficiency.
PharmGKBPA27653.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG254862.
HOGENOMHOG000234337.
HOVERGENHBG051560.
InParanoidO95967.
OMAQECHNLP.
PhylomeDBO95967.
TreeFamTF317514.

Enzyme and pathway databases

ReactomeREACT_118779. Extracellular matrix organization.

Gene expression databases

ArrayExpressO95967.
BgeeO95967.
CleanExHS_EFEMP2.
GenevestigatorO95967.

Family and domain databases

InterProIPR026823. cEGF.
IPR026824. Efemp2.
IPR000742. EG-like_dom.
IPR001881. EGF-like_Ca-bd_dom.
IPR013032. EGF-like_CS.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
IPR009030. Growth_fac_rcpt_N_dom.
IPR001491. Thrombomodulin.
[Graphical view]
PANTHERPTHR24048:SF2. PTHR24048:SF2. 1 hit.
PfamPF12662. cEGF. 2 hits.
PF07645. EGF_CA. 3 hits.
[Graphical view]
PRINTSPR00907. THRMBOMODULN.
SMARTSM00181. EGF. 1 hit.
SM00179. EGF_CA. 4 hits.
[Graphical view]
SUPFAMSSF57184. SSF57184. 2 hits.
PROSITEPS00010. ASX_HYDROXYL. 4 hits.
PS01186. EGF_2. 4 hits.
PS50026. EGF_3. 4 hits.
PS01187. EGF_CA. 6 hits.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO95967.
GeneWikiEFEMP2.
GenomeRNAi30008.
NextBio52820.
PROO95967.
SOURCESearch...

Entry information

Entry nameFBLN4_HUMAN
AccessionPrimary (citable) accession number: O95967
Secondary accession number(s): A8K7R4 expand/collapse secondary AC list , B3KM31, B3KQT1, O75967
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: March 20, 2007
Last modified: July 9, 2014
This is version 149 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM