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Protein

Angiopoietin-4

Gene

ANGPT4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Binds to TEK/TIE2, modulating ANGPT1 signaling. Can induce tyrosine phosphorylation of TEK/TIE2. Promotes endothelial cell survival, migration and angiogenesis.1 Publication

GO - Molecular functioni

  1. receptor tyrosine kinase binding Source: UniProtKB
  2. transmembrane receptor protein tyrosine kinase activator activity Source: UniProtKB

GO - Biological processi

  1. activation of transmembrane receptor protein tyrosine kinase activity Source: GOC
  2. angiogenesis Source: UniProtKB-KW
  3. blood coagulation Source: Reactome
  4. cellular response to hypoxia Source: UniProtKB
  5. leukocyte migration Source: Reactome
  6. negative regulation of angiogenesis Source: UniProtKB
  7. negative regulation of apoptotic process Source: UniProtKB
  8. negative regulation of blood vessel endothelial cell migration Source: UniProtKB
  9. positive regulation of angiogenesis Source: UniProtKB
  10. positive regulation of blood vessel endothelial cell migration Source: UniProtKB
  11. positive regulation of endothelial cell migration Source: UniProtKB
  12. positive regulation of peptidyl-tyrosine phosphorylation Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Angiogenesis

Enzyme and pathway databases

ReactomeiREACT_12621. Tie2 Signaling.
SignaLinkiQ9Y264.

Names & Taxonomyi

Protein namesi
Recommended name:
Angiopoietin-4
Short name:
ANG-4
Alternative name(s):
Angiopoietin-3
Short name:
ANG-3
Gene namesi
Name:ANGPT4
Synonyms:ANG3, ANG4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 20

Organism-specific databases

HGNCiHGNC:487. ANGPT4.

Subcellular locationi

Secreted Curated

GO - Cellular componenti

  1. extracellular region Source: Reactome
  2. extracellular space Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA24793.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2424Sequence AnalysisAdd
BLAST
Chaini25 – 503479Angiopoietin-4PRO_0000009116Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi96 – 961N-linked (GlcNAc...)Sequence Analysis
Glycosylationi126 – 1261N-linked (GlcNAc...)Sequence Analysis
Glycosylationi140 – 1401N-linked (GlcNAc...)Sequence Analysis
Glycosylationi158 – 1581N-linked (GlcNAc...)Sequence Analysis
Glycosylationi247 – 2471N-linked (GlcNAc...)Sequence Analysis
Glycosylationi274 – 2741N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi291 ↔ 320PROSITE-ProRule annotation
Glycosylationi311 – 3111N-linked (GlcNAc...)Sequence Analysis
Glycosylationi337 – 3371N-linked (GlcNAc...)Sequence Analysis
Glycosylationi427 – 4271N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi444 ↔ 457PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ9Y264.
PRIDEiQ9Y264.

PTM databases

PhosphoSiteiQ9Y264.

Expressioni

Tissue specificityi

Highly expressed in the lung with much lower levels found in other tissues.

Gene expression databases

BgeeiQ9Y264.
CleanExiHS_ANGPT4.
GenevestigatoriQ9Y264.

Organism-specific databases

HPAiCAB013260.
CAB013305.

Interactioni

Subunit structurei

Homodimer; disulfide-linked. Interacts with TEK/TIE2.1 Publication

Protein-protein interaction databases

BioGridi119510. 2 interactions.
IntActiQ9Y264. 1 interaction.
STRINGi9606.ENSP00000371347.

Structurei

3D structure databases

ProteinModelPortaliQ9Y264.
SMRiQ9Y264. Positions 171-502.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini282 – 502221Fibrinogen C-terminalPROSITE-ProRule annotationAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili84 – 238155Sequence AnalysisAdd
BLAST

Sequence similaritiesi

Contains 1 fibrinogen C-terminal domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil, Signal

Phylogenomic databases

eggNOGiNOG273522.
GeneTreeiENSGT00760000118809.
HOGENOMiHOG000037128.
HOVERGENiHBG001644.
InParanoidiQ9Y264.
KOiK05467.
OMAiYYPARHH.
OrthoDBiEOG7X9G60.
PhylomeDBiQ9Y264.
TreeFamiTF336658.

Family and domain databases

Gene3Di3.90.215.10. 1 hit.
4.10.530.10. 1 hit.
InterProiIPR028845. Ang-4.
IPR014716. Fibrinogen_a/b/g_C_1.
IPR014715. Fibrinogen_a/b/g_C_2.
IPR002181. Fibrinogen_a/b/g_C_dom.
IPR020837. Fibrinogen_CS.
[Graphical view]
PANTHERiPTHR19143:SF31. PTHR19143:SF31. 1 hit.
PfamiPF00147. Fibrinogen_C. 1 hit.
[Graphical view]
SMARTiSM00186. FBG. 1 hit.
[Graphical view]
SUPFAMiSSF56496. SSF56496. 1 hit.
PROSITEiPS00514. FIBRINOGEN_C_1. 1 hit.
PS51406. FIBRINOGEN_C_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9Y264-1) [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
MLSQLAMLQG SLLLVVATMS VAQQTRQEAD RGCETLVVQH GHCSYTFLLP
60 70 80 90 100
KSEPCPPGPE VSRDSNTLQR ESLANPLHLG KLPTQQVKQL EQALQNNTQW
110 120 130 140 150
LKKLERAIKT ILRSKLEQVQ QQMAQNQTAP MLELGTSLLN QTTAQIRKLT
160 170 180 190 200
DMEAQLLNQT SRMDAQMPET FLSTNKLENQ LLLQRQKLQQ LQGQNSALEK
210 220 230 240 250
RLQALETKQQ EELASILSKK AKLLNTLSRQ SAALTNIERG LRGVRHNSSL
260 270 280 290 300
LQDQQHSLRQ LLVLLRHLVQ ERANASAPAF IMAGEQVFQD CAEIQRSGAS
310 320 330 340 350
ASGVYTIQVS NATKPRKVFC DLQSSGGRWT LIQRRENGTV NFQRNWKDYK
360 370 380 390 400
QGFGDPAGEH WLGNEVVHQL TRRAAYSLRV ELQDWEGHEA YAQYEHFHLG
410 420 430 440 450
SENQLYRLSV VGYSGSAGRQ SSLVLQNTSF STLDSDNDHC LCKCAQVMSG
460 470 480 490 500
GWWFDACGLS NLNGVYYHAP DNKYKMDGIR WHYFKGPSYS LRASRMMIRP

LDI
Length:503
Mass (Da):56,849
Last modified:November 1, 1999 - v1
Checksum:i79CE52F66B532340
GO
Isoform 2 (identifier: Q9Y264-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     408-503: LSVVGYSGSA...SRMMIRPLDI → VVV

Note: No experimental confirmation available.

Show »
Length:410
Mass (Da):46,416
Checksum:iD400123988B77BD8
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti395 – 3951E → K.
Corresponds to variant rs869171 [ dbSNP | Ensembl ].
VAR_049070

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei408 – 50396LSVVG…RPLDI → VVV in isoform 2. 1 PublicationVSP_055091Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF074332 mRNA. Translation: AAD31728.1.
AF113708 mRNA. Translation: AAD21587.1.
AK304756 mRNA. Translation: BAG65511.1.
AL161939, AL050325 Genomic DNA. Translation: CAC09933.2.
AL050325, AL161939 Genomic DNA. Translation: CAI22922.1.
BC111976 mRNA. Translation: AAI11977.1.
BC111978 mRNA. Translation: AAI11979.1.
CCDSiCCDS13009.1. [Q9Y264-1]
RefSeqiNP_057069.1. NM_015985.2. [Q9Y264-1]
XP_005260777.1. XM_005260720.1. [Q9Y264-2]
UniGeneiHs.278973.

Genome annotation databases

EnsembliENST00000381922; ENSP00000371347; ENSG00000101280. [Q9Y264-1]
GeneIDi51378.
KEGGihsa:51378.
UCSCiuc002wei.3. human. [Q9Y264-1]

Polymorphism databases

DMDMi17433288.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF074332 mRNA. Translation: AAD31728.1.
AF113708 mRNA. Translation: AAD21587.1.
AK304756 mRNA. Translation: BAG65511.1.
AL161939, AL050325 Genomic DNA. Translation: CAC09933.2.
AL050325, AL161939 Genomic DNA. Translation: CAI22922.1.
BC111976 mRNA. Translation: AAI11977.1.
BC111978 mRNA. Translation: AAI11979.1.
CCDSiCCDS13009.1. [Q9Y264-1]
RefSeqiNP_057069.1. NM_015985.2. [Q9Y264-1]
XP_005260777.1. XM_005260720.1. [Q9Y264-2]
UniGeneiHs.278973.

3D structure databases

ProteinModelPortaliQ9Y264.
SMRiQ9Y264. Positions 171-502.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119510. 2 interactions.
IntActiQ9Y264. 1 interaction.
STRINGi9606.ENSP00000371347.

PTM databases

PhosphoSiteiQ9Y264.

Polymorphism databases

DMDMi17433288.

Proteomic databases

PaxDbiQ9Y264.
PRIDEiQ9Y264.

Protocols and materials databases

DNASUi51378.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000381922; ENSP00000371347; ENSG00000101280. [Q9Y264-1]
GeneIDi51378.
KEGGihsa:51378.
UCSCiuc002wei.3. human. [Q9Y264-1]

Organism-specific databases

CTDi51378.
GeneCardsiGC20M000853.
HGNCiHGNC:487. ANGPT4.
HPAiCAB013260.
CAB013305.
MIMi603705. gene.
neXtProtiNX_Q9Y264.
PharmGKBiPA24793.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG273522.
GeneTreeiENSGT00760000118809.
HOGENOMiHOG000037128.
HOVERGENiHBG001644.
InParanoidiQ9Y264.
KOiK05467.
OMAiYYPARHH.
OrthoDBiEOG7X9G60.
PhylomeDBiQ9Y264.
TreeFamiTF336658.

Enzyme and pathway databases

ReactomeiREACT_12621. Tie2 Signaling.
SignaLinkiQ9Y264.

Miscellaneous databases

GeneWikiiANGPT4.
GenomeRNAii51378.
NextBioi35477558.
PROiQ9Y264.
SOURCEiSearch...

Gene expression databases

BgeeiQ9Y264.
CleanExiHS_ANGPT4.
GenevestigatoriQ9Y264.

Family and domain databases

Gene3Di3.90.215.10. 1 hit.
4.10.530.10. 1 hit.
InterProiIPR028845. Ang-4.
IPR014716. Fibrinogen_a/b/g_C_1.
IPR014715. Fibrinogen_a/b/g_C_2.
IPR002181. Fibrinogen_a/b/g_C_dom.
IPR020837. Fibrinogen_CS.
[Graphical view]
PANTHERiPTHR19143:SF31. PTHR19143:SF31. 1 hit.
PfamiPF00147. Fibrinogen_C. 1 hit.
[Graphical view]
SMARTiSM00186. FBG. 1 hit.
[Graphical view]
SUPFAMiSSF56496. SSF56496. 1 hit.
PROSITEiPS00514. FIBRINOGEN_C_1. 1 hit.
PS51406. FIBRINOGEN_C_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Angiopoietin-3, a novel member of the angiopoietin family."
    Nishimura M., Miki T., Yashima R., Yokoi N., Yano H., Sato Y., Seino S.
    FEBS Lett. 448:254-256(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Aorta.
  2. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Ovary.
  3. "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.
    , 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] (ISOFORM 2).
    Tissue: Uterus.
  4. "The DNA sequence and comparative analysis of human chromosome 20."
    Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E.
    , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
    Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "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] (ISOFORM 1).
  6. "Biological characterization of angiopoietin-3 and angiopoietin-4."
    Lee H.J., Cho C.H., Hwang S.J., Choi H.H., Kim K.T., Ahn S.Y., Kim J.H., Oh J.L., Lee G.M., Koh G.Y.
    FASEB J. 18:1200-1208(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN REGULATION OF ANGIOGENESIS; CELL SURVIVAL; CELL MIGRATION AND ACTIVATION OF AKT1, SUBUNIT, INTERACTION WITH TEK/TIE2.
  7. "Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system."
    Augustin H.G., Koh G.Y., Thurston G., Alitalo K.
    Nat. Rev. Mol. Cell Biol. 10:165-177(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.

Entry informationi

Entry nameiANGP4_HUMAN
AccessioniPrimary (citable) accession number: Q9Y264
Secondary accession number(s): B4E3J9, Q5TFF4, Q9H4Z4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 29, 2001
Last sequence update: November 1, 1999
Last modified: January 7, 2015
This is version 115 of the entry and version 1 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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 20
    Human chromosome 20: 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.