AGGF1_HUMAN
ID AGGF1_HUMAN Reviewed; 714 AA.
AC Q8N302; O00581; Q53YS3; Q9BU84; Q9NW66;
DT 15-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2004, sequence version 2.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Angiogenic factor with G patch and FHA domains 1;
DE AltName: Full=Angiogenic factor VG5Q;
DE Short=hVG5Q;
DE AltName: Full=G patch domain-containing protein 7;
DE AltName: Full=Vasculogenesis gene on 5q protein;
GN Name=AGGF1; Synonyms=GPATC7, GPATCH7, VG5Q;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, DISEASE, INTERACTION WITH TNFSF12, VARIANT
RP THR-698, AND VARIANT KTS LYS-133.
RX PubMed=14961121; DOI=10.1038/nature02320.;
RA Tian X.-L., Kadaba R., You S.-A., Liu M., Timur A.A., Yang L., Chen Q.,
RA Szafranski P., Rao S., Wu L., Housman D.E., DiCorleto P.E., Driscoll D.J.,
RA Borrow J., Wang Q.;
RT "Identification of an angiogenic factor that when mutated causes
RT susceptibility to Klippel-Trenaunay syndrome.";
RL Nature 427:640-645(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RC TISSUE=Fetus;
RA Dickson M.C., Heather L.J., Lyle L., Clark L.N.C., Deutekom J.C.T.,
RA Wright T.J., Flint J., Frants R.R., Hewitt J.E.;
RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 438-714 (ISOFORM 1), AND VARIANT PRO-471.
RC TISSUE=Melanoma;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 370-714 (ISOFORM 1).
RC TISSUE=Embryo, and Uterus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-664, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-7; SER-11 AND SER-344, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
CC -!- FUNCTION: Promotes angiogenesis and the proliferation of endothelial
CC cells. Able to bind to endothelial cells and promote cell
CC proliferation, suggesting that it may act in an autocrine fashion.
CC {ECO:0000269|PubMed:14961121}.
CC -!- SUBUNIT: Interacts with the secreted angiogenic factor TNFSF12.
CC {ECO:0000269|PubMed:14961121}.
CC -!- INTERACTION:
CC Q8N302; O43143: DHX15; NbExp=3; IntAct=EBI-747899, EBI-1237044;
CC Q8N302; Q9NVF7: FBXO28; NbExp=3; IntAct=EBI-747899, EBI-740282;
CC Q8N302; Q8N8X9: MAB21L3; NbExp=4; IntAct=EBI-747899, EBI-10268010;
CC Q8N302; Q96EZ8: MCRS1; NbExp=3; IntAct=EBI-747899, EBI-348259;
CC Q8N302-2; P28329-3: CHAT; NbExp=3; IntAct=EBI-25838028, EBI-25837549;
CC Q8N302-2; P22607: FGFR3; NbExp=3; IntAct=EBI-25838028, EBI-348399;
CC Q8N302-2; P06396: GSN; NbExp=3; IntAct=EBI-25838028, EBI-351506;
CC Q8N302-2; Q96CV9: OPTN; NbExp=3; IntAct=EBI-25838028, EBI-748974;
CC Q8N302-2; P16284: PECAM1; NbExp=3; IntAct=EBI-25838028, EBI-716404;
CC Q8N302-2; Q5JTV8: TOR1AIP1; NbExp=3; IntAct=EBI-25838028, EBI-2559665;
CC Q8N302-2; P08670: VIM; NbExp=3; IntAct=EBI-25838028, EBI-353844;
CC Q8N302-2; Q9Y649; NbExp=3; IntAct=EBI-25838028, EBI-25900580;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14961121}. Secreted
CC {ECO:0000269|PubMed:14961121}. Note=Cytoplasmic in microvascular
CC endothelial cells. Upon angiogenesis, when endothelial cell tube
CC formation is initiated, it is secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8N302-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8N302-2; Sequence=VSP_009631, VSP_009632;
CC Name=3;
CC IsoId=Q8N302-3; Sequence=VSP_009633, VSP_009634;
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed in endothelial cells,
CC vascular smooth muscle cells and osteoblasts. Expressed in umbilical
CC vein endothelial cells and microvascular endothelial cells.
CC {ECO:0000269|PubMed:14961121}.
CC -!- DISEASE: Klippel-Trenaunay syndrome (KTS) [MIM:149000]: Congenital
CC disease characterized by malformations of capillary (98% of KTS
CC patients), venous (72%) and lymphatic (11%) vessels, and bony and soft
CC tissue hypertrophy that leads to large cutaneous hemangiomata with
CC hypertrophy of the related bones and soft tissues.
CC {ECO:0000269|PubMed:14961121}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH29382.2; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA91519.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AY500994; AAR97615.1; -; mRNA.
DR EMBL; AY500996; AAR97617.1; -; Genomic_DNA.
DR EMBL; U84971; AAB60856.1; -; mRNA.
DR EMBL; BC002828; AAH02828.1; -; mRNA.
DR EMBL; BC029382; AAH29382.2; ALT_SEQ; mRNA.
DR EMBL; AK001145; BAA91519.1; ALT_INIT; mRNA.
DR CCDS; CCDS4035.1; -. [Q8N302-1]
DR RefSeq; NP_060516.2; NM_018046.4. [Q8N302-1]
DR AlphaFoldDB; Q8N302; -.
DR SMR; Q8N302; -.
DR BioGRID; 120419; 57.
DR IntAct; Q8N302; 43.
DR MINT; Q8N302; -.
DR STRING; 9606.ENSP00000316109; -.
DR iPTMnet; Q8N302; -.
DR PhosphoSitePlus; Q8N302; -.
DR BioMuta; AGGF1; -.
DR DMDM; 45477317; -.
DR EPD; Q8N302; -.
DR jPOST; Q8N302; -.
DR MassIVE; Q8N302; -.
DR MaxQB; Q8N302; -.
DR PaxDb; Q8N302; -.
DR PeptideAtlas; Q8N302; -.
DR PRIDE; Q8N302; -.
DR ProteomicsDB; 71746; -. [Q8N302-1]
DR ProteomicsDB; 71747; -. [Q8N302-2]
DR ProteomicsDB; 71748; -. [Q8N302-3]
DR Antibodypedia; 12482; 264 antibodies from 29 providers.
DR DNASU; 55109; -.
DR Ensembl; ENST00000312916.12; ENSP00000316109.7; ENSG00000164252.13. [Q8N302-1]
DR Ensembl; ENST00000506806.1; ENSP00000424733.1; ENSG00000164252.13. [Q8N302-3]
DR GeneID; 55109; -.
DR KEGG; hsa:55109; -.
DR MANE-Select; ENST00000312916.12; ENSP00000316109.7; NM_018046.5; NP_060516.2.
DR UCSC; uc003kes.4; human. [Q8N302-1]
DR CTD; 55109; -.
DR DisGeNET; 55109; -.
DR GeneCards; AGGF1; -.
DR HGNC; HGNC:24684; AGGF1.
DR HPA; ENSG00000164252; Low tissue specificity.
DR MalaCards; AGGF1; -.
DR MIM; 149000; phenotype.
DR MIM; 608464; gene.
DR neXtProt; NX_Q8N302; -.
DR OpenTargets; ENSG00000164252; -.
DR Orphanet; 90308; Klippel-Trenaunay syndrome.
DR PharmGKB; PA134951291; -.
DR VEuPathDB; HostDB:ENSG00000164252; -.
DR eggNOG; KOG0154; Eukaryota.
DR GeneTree; ENSGT00730000111121; -.
DR HOGENOM; CLU_023817_1_0_1; -.
DR InParanoid; Q8N302; -.
DR OMA; FAENFQD; -.
DR OrthoDB; 683607at2759; -.
DR PhylomeDB; Q8N302; -.
DR TreeFam; TF315789; -.
DR PathwayCommons; Q8N302; -.
DR Reactome; R-HSA-6802952; Signaling by BRAF and RAF1 fusions.
DR SignaLink; Q8N302; -.
DR SIGNOR; Q8N302; -.
DR BioGRID-ORCS; 55109; 11 hits in 1074 CRISPR screens.
DR ChiTaRS; AGGF1; human.
DR GeneWiki; AGGF1; -.
DR GenomeRNAi; 55109; -.
DR Pharos; Q8N302; Tbio.
DR PRO; PR:Q8N302; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q8N302; protein.
DR Bgee; ENSG00000164252; Expressed in choroid plexus epithelium and 198 other tissues.
DR ExpressionAtlas; Q8N302; baseline and differential.
DR Genevisible; Q8N302; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0007155; P:cell adhesion; IDA:UniProtKB.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IDA:UniProtKB.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IDA:UniProtKB.
DR GO; GO:0001570; P:vasculogenesis; TAS:UniProtKB.
DR CDD; cd00060; FHA; 1.
DR CDD; cd16164; OCRE_VG5Q; 1.
DR InterPro; IPR035624; AGGF1_OCRE.
DR InterPro; IPR000253; FHA_dom.
DR InterPro; IPR000467; G_patch_dom.
DR InterPro; IPR041591; OCRE.
DR InterPro; IPR008984; SMAD_FHA_dom_sf.
DR Pfam; PF00498; FHA; 1.
DR Pfam; PF01585; G-patch; 1.
DR Pfam; PF17780; OCRE; 1.
DR SMART; SM00240; FHA; 1.
DR SMART; SM00443; G_patch; 1.
DR SUPFAM; SSF49879; SSF49879; 1.
DR PROSITE; PS50006; FHA_DOMAIN; 1.
DR PROSITE; PS50174; G_PATCH; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Angiogenesis; Coiled coil; Cytoplasm;
KW Developmental protein; Differentiation; Disease variant; Phosphoprotein;
KW Reference proteome; Secreted.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330"
FT CHAIN 2..714
FT /note="Angiogenic factor with G patch and FHA domains 1"
FT /id="PRO_0000064495"
FT DOMAIN 434..487
FT /note="FHA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00086"
FT DOMAIN 619..665
FT /note="G-patch"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00092"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 259..307
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 322..384
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 586..617
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 655..714
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 18..88
FT /evidence="ECO:0000255"
FT COMPBIAS 1..20
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 275..307
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 331..357
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 365..379
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 586..602
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 673..698
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT MOD_RES 7
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 11
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 344
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 664
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT VAR_SEQ 72..109
FT /note="EELSKILQRGRNEDNKKSDVEVQTENHAPWSISDYFYQ -> RGPPQPRAPS
FT SPGEAFEARDSLGRGPWQGLRTTVEYLK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_009631"
FT VAR_SEQ 110..714
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_009632"
FT VAR_SEQ 173..176
FT /note="EPAS -> VIKC (in isoform 3)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_009633"
FT VAR_SEQ 177..714
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_009634"
FT VARIANT 133
FT /note="E -> K (in KTS; in 5 patients; displays a stronger
FT angiogenic activity; dbSNP:rs34203073)"
FT /evidence="ECO:0000269|PubMed:14961121"
FT /id="VAR_017901"
FT VARIANT 180
FT /note="T -> A (in dbSNP:rs9715897)"
FT /id="VAR_037446"
FT VARIANT 471
FT /note="L -> P (in dbSNP:rs17856835)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_037447"
FT VARIANT 698
FT /note="P -> T (in dbSNP:rs34400049)"
FT /evidence="ECO:0000269|PubMed:14961121"
FT /id="VAR_017902"
FT CONFLICT 370
FT /note="E -> G (in Ref. 4)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 714 AA; 80977 MW; 3CC88FBDA9853EF1 CRC64;
MASEAPSPPR SPPPPTSPEP ELAQLRRKVE KLERELRSCK RQVREIEKLL HHTERLYQNA
ESNNQELRTQ VEELSKILQR GRNEDNKKSD VEVQTENHAP WSISDYFYQT YYNDVSLPNK
VTELSDQQDQ AIETSILNSK DHLQVENDAY PGTDRTENVK YRQVDHFASN SQEPASALAT
EDTSLEGSSL AESLRAAAEA AVSQTGFSYD ENTGLYFDHS TGFYYDSENQ LYYDPSTGIY
YYCDVESGRY QFHSRVDLQP YPTSSTKQSK DKKLKKKRKD PDSSATNEEK DLNSEDQKAF
SVEHTSCNEE ENFANMKKKA KIGIHHKNSP PKVTVPTSGN TIESPLHENI SNSTSFKDEK
IMETDSEPEE GEITDSQTED SYDEAITSEG NVTAEDSEDE DEDKIWPPCI RVIVIRSPVL
QIGSLFIITA VNPATIGREK DMEHTLRIPE VGVSKFHAEI YFDHDLQSYV LVDQGSQNGT
IVNGKQILQP KTKCDPYVLE HGDEVKIGET VLSFHIHPGS DTCDGCEPGQ VRAHLRLDKK
DESFVGPTLS KEEKELERRK ELKKIRVKYG LQNTEYEDEK TLKNPKYKDR AGKRREQVGS
EGTFQRDDAP ASVHSEITDS NKGRKMLEKM GWKKGEGLGK DGGGMKTPIQ LQLRRTHAGL
GTGKPSSFED VHLLQNKNKK NWDKARERFT ENFPETKPQK DDPGTMPWVK GTLE
