ANGL2_HUMAN
ID ANGL2_HUMAN Reviewed; 493 AA.
AC Q9UKU9; Q5JT58; Q8NCH7;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Angiopoietin-related protein 2;
DE AltName: Full=Angiopoietin-like protein 2;
DE Flags: Precursor;
GN Name=ANGPTL2; Synonyms=ARP2; ORFNames=UNQ170/PRO196;
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 [MRNA] (ISOFORM 1).
RC TISSUE=Heart;
RX PubMed=10473614; DOI=10.1074/jbc.274.37.26523;
RA Kim I., Moon S.-O., Koh K.N., Kim H., Uhm C.-S., Kwak H.J., Kim N.-G.,
RA Koh G.Y.;
RT "Molecular cloning, expression, and characterization of angiopoietin-
RT related protein. angiopoietin-related protein induces endothelial cell
RT sprouting.";
RL J. Biol. Chem. 274:26523-26528(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Ovary;
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).
CC -!- FUNCTION: Induces sprouting in endothelial cells through an autocrine
CC and paracrine action.
CC -!- INTERACTION:
CC Q9UKU9; Q8N423: LILRB2; NbExp=5; IntAct=EBI-15485893, EBI-2816428;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9UKU9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UKU9-2; Sequence=VSP_056934;
CC -!- TISSUE SPECIFICITY: Widely expressed in heart, small intestine, spleen
CC and stomach. Also found in lower levels in colon, ovary, adrenal gland,
CC skeletal muscle and in prostate.
CC -!- PTM: N-glycosylated.
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DR EMBL; AF125175; AAD55357.1; -; mRNA.
DR EMBL; AY358274; AAQ88641.1; -; mRNA.
DR EMBL; AK074726; BAC11164.1; -; mRNA.
DR EMBL; AL356862; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471090; EAW87651.1; -; Genomic_DNA.
DR EMBL; BC012368; AAH12368.1; -; mRNA.
DR CCDS; CCDS6868.1; -. [Q9UKU9-1]
DR RefSeq; NP_036230.1; NM_012098.2. [Q9UKU9-1]
DR PDB; 6Y41; X-ray; 1.79 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P=269-493.
DR PDBsum; 6Y41; -.
DR AlphaFoldDB; Q9UKU9; -.
DR SMR; Q9UKU9; -.
DR BioGRID; 117018; 7.
DR DIP; DIP-59886N; -.
DR IntAct; Q9UKU9; 4.
DR STRING; 9606.ENSP00000362524; -.
DR GlyConnect; 1009; 9 N-Linked glycans (2 sites).
DR GlyGen; Q9UKU9; 3 sites, 8 N-linked glycans (2 sites), 2 O-linked glycans (1 site).
DR iPTMnet; Q9UKU9; -.
DR PhosphoSitePlus; Q9UKU9; -.
DR BioMuta; ANGPTL2; -.
DR DMDM; 13626119; -.
DR jPOST; Q9UKU9; -.
DR MassIVE; Q9UKU9; -.
DR PaxDb; Q9UKU9; -.
DR PeptideAtlas; Q9UKU9; -.
DR PRIDE; Q9UKU9; -.
DR ProteomicsDB; 72896; -.
DR ProteomicsDB; 84880; -. [Q9UKU9-1]
DR Antibodypedia; 30639; 306 antibodies from 31 providers.
DR DNASU; 23452; -.
DR Ensembl; ENST00000373417.1; ENSP00000362516.1; ENSG00000136859.10. [Q9UKU9-2]
DR Ensembl; ENST00000373425.8; ENSP00000362524.3; ENSG00000136859.10. [Q9UKU9-1]
DR GeneID; 23452; -.
DR KEGG; hsa:23452; -.
DR MANE-Select; ENST00000373425.8; ENSP00000362524.3; NM_012098.3; NP_036230.1.
DR UCSC; uc004bqr.2; human. [Q9UKU9-1]
DR CTD; 23452; -.
DR DisGeNET; 23452; -.
DR GeneCards; ANGPTL2; -.
DR HGNC; HGNC:490; ANGPTL2.
DR HPA; ENSG00000136859; Low tissue specificity.
DR MIM; 605001; gene.
DR neXtProt; NX_Q9UKU9; -.
DR OpenTargets; ENSG00000136859; -.
DR PharmGKB; PA24795; -.
DR VEuPathDB; HostDB:ENSG00000136859; -.
DR eggNOG; KOG2579; Eukaryota.
DR GeneTree; ENSGT00940000155946; -.
DR HOGENOM; CLU_038628_0_0_1; -.
DR InParanoid; Q9UKU9; -.
DR OMA; CVTYWWL; -.
DR PhylomeDB; Q9UKU9; -.
DR TreeFam; TF336658; -.
DR PathwayCommons; Q9UKU9; -.
DR SignaLink; Q9UKU9; -.
DR BioGRID-ORCS; 23452; 11 hits in 1064 CRISPR screens.
DR GeneWiki; ANGPTL2; -.
DR GenomeRNAi; 23452; -.
DR Pharos; Q9UKU9; Tbio.
DR PRO; PR:Q9UKU9; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q9UKU9; protein.
DR Bgee; ENSG00000136859; Expressed in tendon of biceps brachii and 176 other tissues.
DR ExpressionAtlas; Q9UKU9; baseline and differential.
DR Genevisible; Q9UKU9; HS.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR CDD; cd00087; FReD; 1.
DR Gene3D; 3.90.215.10; -; 1.
DR InterPro; IPR036056; Fibrinogen-like_C.
DR InterPro; IPR014716; Fibrinogen_a/b/g_C_1.
DR InterPro; IPR002181; Fibrinogen_a/b/g_C_dom.
DR InterPro; IPR020837; Fibrinogen_CS.
DR Pfam; PF00147; Fibrinogen_C; 1.
DR SMART; SM00186; FBG; 1.
DR SUPFAM; SSF56496; SSF56496; 1.
DR PROSITE; PS00514; FIBRINOGEN_C_1; 1.
DR PROSITE; PS51406; FIBRINOGEN_C_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Coiled coil; Disulfide bond;
KW Glycoprotein; Reference proteome; Secreted; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..493
FT /note="Angiopoietin-related protein 2"
FT /id="PRO_0000009120"
FT DOMAIN 269..489
FT /note="Fibrinogen C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00739"
FT COILED 76..115
FT /evidence="ECO:0000255"
FT COILED 152..206
FT /evidence="ECO:0000255"
FT CARBOHYD 164
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 192
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 278..307
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00739"
FT DISULFID 430..443
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00739"
FT VAR_SEQ 1..302
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056934"
FT STRAND 275..277
FT /evidence="ECO:0007829|PDB:6Y41"
FT HELIX 278..283
FT /evidence="ECO:0007829|PDB:6Y41"
FT STRAND 290..294
FT /evidence="ECO:0007829|PDB:6Y41"
FT STRAND 303..308
FT /evidence="ECO:0007829|PDB:6Y41"
FT STRAND 316..325
FT /evidence="ECO:0007829|PDB:6Y41"
FT HELIX 333..338
FT /evidence="ECO:0007829|PDB:6Y41"
FT STRAND 345..348
FT /evidence="ECO:0007829|PDB:6Y41"
FT HELIX 351..358
FT /evidence="ECO:0007829|PDB:6Y41"
FT STRAND 363..370
FT /evidence="ECO:0007829|PDB:6Y41"
FT STRAND 376..382
FT /evidence="ECO:0007829|PDB:6Y41"
FT STRAND 384..386
FT /evidence="ECO:0007829|PDB:6Y41"
FT HELIX 389..391
FT /evidence="ECO:0007829|PDB:6Y41"
FT STRAND 395..397
FT /evidence="ECO:0007829|PDB:6Y41"
FT STRAND 400..404
FT /evidence="ECO:0007829|PDB:6Y41"
FT HELIX 409..411
FT /evidence="ECO:0007829|PDB:6Y41"
FT STRAND 424..428
FT /evidence="ECO:0007829|PDB:6Y41"
FT HELIX 431..434
FT /evidence="ECO:0007829|PDB:6Y41"
FT STRAND 441..443
FT /evidence="ECO:0007829|PDB:6Y41"
FT HELIX 469..472
FT /evidence="ECO:0007829|PDB:6Y41"
FT STRAND 479..487
FT /evidence="ECO:0007829|PDB:6Y41"
SQ SEQUENCE 493 AA; 57104 MW; 0F2ADECE53D185CA CRC64;
MRPLCVTCWW LGLLAAMGAV AGQEDGFEGT EEGSPREFIY LNRYKRAGES QDKCTYTFIV
PQQRVTGAIC VNSKEPEVLL ENRVHKQELE LLNNELLKQK RQIETLQQLV EVDGGIVSEV
KLLRKESRNM NSRVTQLYMQ LLHEIIRKRD NALELSQLEN RILNQTADML QLASKYKDLE
HKYQHLATLA HNQSEIIAQL EEHCQRVPSA RPVPQPPPAA PPRVYQPPTY NRIINQISTN
EIQSDQNLKV LPPPLPTMPT LTSLPSSTDK PSGPWRDCLQ ALEDGHDTSS IYLVKPENTN
RLMQVWCDQR HDPGGWTVIQ RRLDGSVNFF RNWETYKQGF GNIDGEYWLG LENIYWLTNQ
GNYKLLVTME DWSGRKVFAE YASFRLEPES EYYKLRLGRY HGNAGDSFTW HNGKQFTTLD
RDHDVYTGNC AHYQKGGWWY NACAHSNLNG VWYRGGHYRS RYQDGVYWAE FRGGSYSLKK
VVMMIRPNPN TFH
