Reviewed,
UniProtKB/Swiss-Prot Q9BY76 (ANGL4_HUMAN)
Last modified
January 19, 2010.
Version 82.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Angiopoietin-related protein 4 Alternative name(s): Angiopoietin-like protein 4 Hepatic fibrinogen/angiopoietin-related protein Short name=HFARP | ||||||
| Gene names |
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| Organism | Homo sapiens (Human) [Complete proteome] | ||||||
| Taxonomic identifier | 9606 [NCBI] | ||||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 406 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Protein with hypoxia-induced expression in endothelial cells. May act as a regulator of angiogenesis and modulate tumorgenesis. Inhibits proliferation, migration, and tubule formation of endothelial cells and reduces vascular leakage. May exert a protective function on endothelial cells through an endocrine action. It is directly involved in regulating glucose homeostasis, lipid metabolism, and insulin sensitivity. In response to hypoxia, the unprocessed form of the protein accumulates in the subendothelial extracellular matrix (ECM). The matrix-associated and immobilized unprocessed form limits the formation of actin stress fibers and focal contacts in the adhering endothelial cells and inhibits their adhesion. It also decreases motility of endothelial cells and inhibits the sprouting and tube formation By similarity. Ref.2 Ref.4 Ref.9 |
| Subunit structure | Homooligomer. The homooligomer undergoes proteolytic processing to release its carboxyl fibrinogen-like domain, which circulates as a monomer. The homooligomer unprocessed form is able to interact with the extracellular matrix By similarity. |
| Subcellular location | Secreted. Secreted › extracellular space › extracellular matrix By similarity. Note: The unprocessed form interacts with the extracellular matrix. This may constitute a dynamic reservoir, a regulatory mechanism of the bioavailability of ANGPTL4 By similarity. Ref.1 |
| Tissue specificity | Expressed at high levels in the placenta, heart, liver, muscle, pancreas and lung but expressed poorly in the brain and kidney. Ref.9 Ref.1 |
| Post-translational modification | N-glycosylated. Ref.1 |
| Sequence similarities | Contains 1 fibrinogen C-terminal domain. |
Ontologies
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||
Molecule processing | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Signal peptide | 1 – 25 | 25 | Potential | ||||||||
| Chain | 26 – 406 | 381 | Angiopoietin-related protein 4 | PRO_0000009124 | |||||||
Regions | |||||||||||
| Domain | 179 – 401 | 223 | Fibrinogen C-terminal | ||||||||
| Coiled coil | 100 – 143 | 44 | Potential | ||||||||
Amino acid modifications | |||||||||||
| Glycosylation | 177 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Disulfide bond | 188 ↔ 216 | By similarity | |||||||||
| Disulfide bond | 341 ↔ 354 | By similarity | |||||||||
Natural variations | |||||||||||
| Natural variant | 5 | 1 | P → L | VAR_032642 | |||||||
| Natural variant | 40 | 1 | E → K Associated with lower plasma levels of triglyceride and higher levels of HDL cholesterol. Ref.10 | VAR_032643 | |||||||
| Natural variant | 41 | 1 | M → I | VAR_032644 | |||||||
| Natural variant | 67 | 1 | S → R | VAR_032645 | |||||||
| Natural variant | 72 | 1 | R → L | VAR_032646 | |||||||
| Natural variant | 77 | 1 | G → R | VAR_032647 | |||||||
| Natural variant | 167 | 1 | E → K | VAR_032648 | |||||||
| Natural variant | 174 | 1 | P → S | VAR_032649 | |||||||
| Natural variant | 190 | 1 | E → Q | VAR_032650 | |||||||
| Natural variant | 196 | 1 | E → K | VAR_032651 | |||||||
| Natural variant | 230 | 1 | R → C | VAR_032652 | |||||||
| Natural variant | 233 | 1 | G → R | VAR_032653 | |||||||
| Natural variant | 237 | 1 | F → V | VAR_032654 | |||||||
| Natural variant | 251 | 1 | P → T | VAR_032655 | |||||||
| Natural variant | 266 | 1 | T → M: dbSNP rs1044250. Ref.1 Ref.10 Ref.7 | VAR_020428 | |||||||
| Natural variant | 278 | 1 | R → Q: dbSNP rs35061979. Ref.10 | VAR_032656 | |||||||
| Natural variant | 291 | 1 | V → M | VAR_032657 | |||||||
| Natural variant | 293 | 1 | L → M | VAR_032658 | |||||||
| Natural variant | 296 | 1 | E → V | VAR_032659 | |||||||
| Natural variant | 307 | 1 | P → S | VAR_032660 | |||||||
| Natural variant | 308 | 1 | V → M | VAR_032661 | |||||||
| Natural variant | 336 | 1 | R → C | VAR_032662 | |||||||
| Natural variant | 338 | 1 | D → E | VAR_032663 | |||||||
| Natural variant | 349 | 1 | W → C | VAR_032664 | |||||||
| Natural variant | 361 | 1 | G → R | VAR_032665 | |||||||
| Natural variant | 361 | 1 | G → S | VAR_032666 | |||||||
| Natural variant | 371 | 1 | R → Q | VAR_032667 | |||||||
| Natural variant | 384 | 1 | R → W | VAR_032668 | |||||||
Experimental info | |||||||||||
| Sequence conflict | 55 – 71 | 17 | LREHA…SALER → CANTGAHPQSAERAGA in AAD41088. Ref.5 | ||||||||
| Sequence conflict | 60 | 1 | E → G in BAB40692. Ref.4 | ||||||||
| Sequence conflict | 175 | 1 | A → P in AAF62868. Ref.1 | ||||||||
| Sequence conflict | 251 | 1 | P → S in BAD96209. Ref.7 | ||||||||
| Sequence conflict | 270 | 1 | N → D in BAD96209. Ref.7 | ||||||||
| Sequence conflict | 277 | 1 | L → R in BAD96244. Ref.7 | ||||||||
| Sequence conflict | 304 | 1 | L → F in AAF62868. Ref.1 | ||||||||
| Sequence conflict | 363 | 1 | Y → H in BAD96209. Ref.7 | ||||||||
| Sequence conflict | 389 | 1 | P → S in AAF62868. Ref.1 | ||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Hepatic expression, synthesis and secretion of a novel fibrinogen/angiopoietin-related protein that prevents endothelial-cell apoptosis." Kim I., Kim H.-G., Kim H., Kim H.-H., Park S.K., Uhm C.-S., Lee Z.H., Koh G.Y. Biochem. J. 346:603-610(2000) [PubMed: 10698685] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, SUBCELLULAR LOCATION, GLYCOSYLATION, VARIANT MET-266. |
| [2] | "Peroxisome proliferator-activated receptor gamma target gene encoding a novel angiopoietin-related protein associated with adipose differentiation." Yoon J.C., Chickering T.W., Rosen E.D., Dussault B., Qin Y., Soukas A., Friedman J.M., Holmes W.E., Spiegelman B.M. Mol. Cell. Biol. 20:5343-5349(2000) [PubMed: 10866690] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], POSSIBLE FUNCTION. Tissue: Aortic endothelium. |
| [3] | "Cloning of a novel gene, ANGPTL4 and the functional study in angiogenesis." Zhu H., Li J., Qin W., Yang Y., He X., Wan D., Gu J. Zhonghua Yi Xue Za Zhi 82:94-99(2002) [PubMed: 11953136] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta. |
| [4] | "Inhibition of angiogenesis and vascular leakiness by angiopoietin-related protein 4." Ito Y., Oike Y., Yasunaga K., Hamada K., Miyata K., Matsumoto S., Sugano S., Tanihara H., Masuho Y., Suda T. Cancer Res. 63:6651-6657(2003) [PubMed: 14583458] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION. Tissue: Placenta. |
| [5] | "A catalogue of genes in the human dermal papilla cells as identified by expressed sequence tags." Kim M.K., Kim Y.H., Seo J.M., Lee H.M., Chung H.J., Sohn M.Y., Hwang S.Y., Im S.U., Jung E.J., Lee J.H., Kim J.C. Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Hair follicle dermal papilla. |
| [6] | "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. Gray A.M.Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. |
| [7] | Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT MET-266. Tissue: Adipose tissue. |
| [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Pancreas. |
| [9] | "Expression and function of hepatocellular carcinoma-related gene pp1158." Zhu H., Li J., Wan D., Yang Y., Qin W., Ge C., Yao M., Gu J. Zhonghua Zhong Liu Za Zhi 24:123-125(2002) [PubMed: 12015030] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY. |
| [10] | "Population-based resequencing of ANGPTL4 uncovers variations that reduce triglycerides and increase HDL." Romeo S., Pennacchio L.A., Fu Y., Boerwinkle E., Tybjaerg-Hansen A., Hobbs H.H., Cohen J.C. Nat. Genet. 39:513-516(2007) [PubMed: 17322881] [Abstract] Cited for: VARIANTS LEU-5; LYS-40; ILE-41; ARG-67; LEU-72; ARG-77; LYS-167; SER-174; GLN-190; LYS-196; CYS-230; ARG-233; VAL-237; THR-251; MET-266; GLN-278; MET-291; MET-293; VAL-296; SER-307; MET-308; CYS-336; GLU-338; CYS-349; SER-361; ARG-361; GLN-371 AND TRP-384. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | AF169312 mRNA. Translation: AAF62868.1. AF202636 mRNA. Translation: AAG22490.1. AB056477 mRNA. Translation: BAB40692.1. AF153606 mRNA. Translation: AAD41088.1. AY358275 mRNA. Translation: AAQ88642.1. Different initiation. AK222489 mRNA. Translation: BAD96209.1. AK222524 mRNA. Translation: BAD96244.1. BC023647 mRNA. Translation: AAH23647.1. |
| IPI | IPI00153060. |
| RefSeq | NP_001034756.1. NP_647475.1. |
| UniGene | Hs.9613 |
3D structure databases | |
| SMR | Q9BY76. Positions 186-400. |
| ModBase | Search... |
Protein-protein interaction databases | |
| STRING | Q9BY76. |
Proteomic databases | |
| PRIDE | Q9BY76. |
Genome annotation databases | |
| Ensembl | ENST00000301455; ENSP00000301455; ENSG00000167772; Homo sapiens. [Genome view] |
| GeneID | 51129. |
| KEGG | hsa:51129. |
| UCSC | uc002mjq.1. human. |
Organism-specific databases | |
| CTD | 51129. |
| GeneCards | GC19P008335. |
| H-InvDB | HIX0027444. |
| HGNC | HGNC:16039. ANGPTL4. |
| HPA | HPA007879. |
| MIM | 605910. gene. |
| PharmGKB | PA24797. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | prNOG09521. |
| HOVERGEN | Q9BY76. |
| InParanoid | Q9BY76. |
| OMA | MRCAPTA. |
| OrthoDB | EOG9QJV6X. |
| PhylomeDB | Q9BY76. |
Enzyme and pathway databases | |
| Reactome | REACT_602. Metabolism of lipids and lipoproteins. |
Gene expression databases | |
| ArrayExpress | Q9BY76. |
| Bgee | Q9BY76. |
| CleanEx | HS_ANGPTL4. |
| Genevestigator | Q9BY76. |
| GermOnline | ENSG00000167772. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR002181. Fibrinogen_a/b/g_C. IPR014716. Fibrinogen_a/b/g_C_1. IPR014715. Fibrinogen_a/b/g_C_2. IPR020837. Fibrinogen_CS. [Graphical view] |
| Gene3D | G3DSA:3.90.215.10. Fibrinogen_a/b/g_C_1. 1 hit. G3DSA:4.10.530.10. Fibrinogen_a/b/g_C_2. 1 hit. |
| Pfam | PF00147. Fibrinogen_C. 1 hit. [Graphical view] |
| SMART | SM00186. FBG. 1 hit. [Graphical view] |
| PROSITE | PS00514. FIBRINOGEN_C_1. 1 hit. PS51406. FIBRINOGEN_C_2. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 53949. |
| SOURCE | Search... |
Entry information
| Entry name | ANGL4_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q9BY76 Secondary accession number(s): Q53HQ6 Q9Y5B3 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| Disclaimer | Any 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
| Human chromosome 19 Human chromosome 19: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with


