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   27-MAR-2024, entry version 176.
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, INTERACTION WITH TNFSF12, AND VARIANTS
RP   LYS-133 AND THR-698.
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   -!- 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; 60.
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; 9606-ENSP00000316109; -.
DR   PeptideAtlas; Q8N302; -.
DR   ProteomicsDB; 71746; -. [Q8N302-1]
DR   ProteomicsDB; 71747; -. [Q8N302-2]
DR   ProteomicsDB; 71748; -. [Q8N302-3]
DR   Pumba; Q8N302; -.
DR   Antibodypedia; 12482; 281 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   AGR; HGNC:24684; -.
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; 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; CGQEDHF; -.
DR   OrthoDB; 3086173at2759; -.
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; 13 hits in 1152 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 200 other cell types or tissues.
DR   ExpressionAtlas; Q8N302; baseline and differential.
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; cd22686; FHA_AGGF1; 1.
DR   CDD; cd16164; OCRE_VG5Q; 1.
DR   Gene3D; 2.60.200.20; -; 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   PANTHER; PTHR23106; ANGIOGENIC FACTOR WITH G PATCH AND FHA DOMAINS 1; 1.
DR   PANTHER; PTHR23106:SF24; ANGIOGENIC FACTOR WITH G PATCH AND FHA DOMAINS 1; 1.
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; SMAD/FHA domain; 1.
DR   PROSITE; PS50006; FHA_DOMAIN; 1.
DR   PROSITE; PS50174; G_PATCH; 1.
DR   Genevisible; Q8N302; HS.
PE   1: Evidence at protein level;
KW   Acetylation; Alternative splicing; Angiogenesis; Coiled coil; Cytoplasm;
KW   Developmental protein; Differentiation; Phosphoprotein; Reference proteome;
KW   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 (displays a stronger angiogenic activity;
FT                   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
//