ID C4BPA_HUMAN Reviewed; 597 AA.
AC P04003; Q5VVQ8;
DT 23-OCT-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1993, sequence version 2.
DT 27-MAR-2024, entry version 213.
DE RecName: Full=C4b-binding protein alpha chain;
DE Short=C4bp;
DE AltName: Full=Proline-rich protein;
DE Short=PRP;
DE Flags: Precursor;
GN Name=C4BPA; Synonyms=C4BP;
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].
RC TISSUE=Liver;
RX PubMed=2590215; DOI=10.1016/0006-291x(89)91045-0;
RA Matsuguchi T., Okamura S., Aso T., Sata T., Niho Y.;
RT "Molecular cloning of the cDNA coding for proline-rich protein (PRP):
RT identity of PRP as C4b-binding protein.";
RL Biochem. Biophys. Res. Commun. 165:138-144(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX PubMed=1989602; DOI=10.1016/0006-291x(91)90509-6;
RA Aso T., Okamura S., Matsuguchi T., Sakamoto N., Sata T., Niho Y.;
RT "Genomic organization of the alpha chain of the human C4b-binding protein
RT gene.";
RL Biochem. Biophys. Res. Commun. 174:222-227(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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].
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 9-81.
RX PubMed=3378624; DOI=10.1016/0014-5793(88)80763-4;
RA Lintin S.J., Lewin A.R., Reid K.B.M.;
RT "Derivation of the sequence of the signal peptide in human C4b-binding
RT protein and interspecies cross-hybridisation of the C4bp cDNA sequence.";
RL FEBS Lett. 232:328-332(1988).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 203-288.
RX PubMed=3017751; DOI=10.1016/0014-5793(86)81390-4;
RA Lintin S.J., Reid K.B.M.;
RT "Studies on the structure of the human C4b-binding protein gene.";
RL FEBS Lett. 204:77-81(1986).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 80-597.
RX PubMed=3840370; DOI=10.1042/bj2300133;
RA Chung L.P., Bentley D.R., Reid K.B.M.;
RT "Molecular cloning and characterization of the cDNA coding for C4b-binding
RT protein, a regulatory protein of the classical pathway of the human
RT complement system.";
RL Biochem. J. 230:133-141(1985).
RN [9]
RP PROTEIN SEQUENCE OF 49-88.
RX PubMed=4033666; DOI=10.1016/0161-5890(85)90127-0;
RA Chung L.P., Gagnon J., Reid K.B.M.;
RT "Amino acid sequence studies of human C4b-binding protein: N-terminal
RT sequence analysis and alignment of the fragments produced by limited
RT proteolysis with chymotrypsin and the peptides produced by cyanogen bromide
RT treatment.";
RL Mol. Immunol. 22:427-435(1985).
RN [10]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-506 AND ASN-528.
RC TISSUE=Plasma;
RX PubMed=14760718; DOI=10.1002/pmic.200300556;
RA Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R.;
RT "Screening for N-glycosylated proteins by liquid chromatography mass
RT spectrometry.";
RL Proteomics 4:454-465(2004).
RN [11]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-221 AND ASN-506.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [12]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-221 AND ASN-506.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [14]
RP INTERACTION WITH STAPHYLOCOCCUS AUREUS PROTEIN SDRE (MICROBIAL INFECTION).
RX PubMed=24600566; DOI=10.1016/j.rinim.2013.10.004;
RA Hair P.S., Foley C.K., Krishna N.K., Nyalwidhe J.O., Geoghegan J.A.,
RA Foster T.J., Cunnion K.M.;
RT "Complement regulator C4BP binds to Staphylococcus aureus surface proteins
RT SdrE and Bbp inhibiting bacterial opsonization and killing.";
RL Results Immunol. 3:114-121(2013).
RN [15]
RP STRUCTURE BY ELECTRON MICROSCOPY, AND LIGAND-BINDING.
RX PubMed=6222381; DOI=10.1073/pnas.80.11.3461;
RA Dahlback B., Smith C.A., Mueller-Eberhard H.J.;
RT "Visualization of human C4b-binding protein and its complexes with vitamin
RT K-dependent protein S and complement protein C4b.";
RL Proc. Natl. Acad. Sci. U.S.A. 80:3461-3465(1983).
RN [16]
RP STRUCTURE BY NMR OF 49-172, AND DISULFIDE BONDS.
RX PubMed=16330538; DOI=10.1074/jbc.m511563200;
RA Jenkins H.T., Mark L., Ball G., Persson J., Lindahl G., Uhrin D.,
RA Blom A.M., Barlow P.N.;
RT "Human C4b-binding protein, structural basis for interaction with
RT streptococcal M protein, a major bacterial virulence factor.";
RL J. Biol. Chem. 281:3690-3697(2006).
CC -!- FUNCTION: Controls the classical pathway of complement activation. It
CC binds as a cofactor to C3b/C4b inactivator (C3bINA), which then
CC hydrolyzes the complement fragment C4b. It also accelerates the
CC degradation of the C4bC2a complex (C3 convertase) by dissociating the
CC complement fragment C2a. Alpha chain binds C4b. It interacts also with
CC anticoagulant protein S and with serum amyloid P component.
CC -!- SUBUNIT: Disulfide-linked complex of alpha and beta chains of 3
CC possible sorts: a 570 kDa complex of 7 alpha chains and 1 beta chain, a
CC 530 kDa homoheptamer of alpha chains or a 500 kDa complex of 6 alpha
CC chains and 1 beta chain. The central body of the alpha chain homomer
CC supports tentacles, each with the binding site for C4b at the end.
CC {ECO:0000269|PubMed:16330538}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Staphylococcus aureus
CC protein SdrE; this interaction inhibits complement-mediated bacterial
CC opsonization. {ECO:0000269|PubMed:24600566}.
CC -!- INTERACTION:
CC P04003; PRO_0000023526 [P02741]: CRP; NbExp=4; IntAct=EBI-978348, EBI-22033103;
CC P04003; P13050: arp4; Xeno; NbExp=5; IntAct=EBI-978348, EBI-978341;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Chylomicrons in the plasma.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-17 is the initiator.
CC {ECO:0000305}.
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DR EMBL; M31452; AAA36507.1; -; mRNA.
DR EMBL; M62486; AAA36506.1; -; Genomic_DNA.
DR EMBL; M62475; AAA36506.1; JOINED; Genomic_DNA.
DR EMBL; M62476; AAA36506.1; JOINED; Genomic_DNA.
DR EMBL; M62477; AAA36506.1; JOINED; Genomic_DNA.
DR EMBL; M62478; AAA36506.1; JOINED; Genomic_DNA.
DR EMBL; M62479; AAA36506.1; JOINED; Genomic_DNA.
DR EMBL; M62480; AAA36506.1; JOINED; Genomic_DNA.
DR EMBL; M62481; AAA36506.1; JOINED; Genomic_DNA.
DR EMBL; M62482; AAA36506.1; JOINED; Genomic_DNA.
DR EMBL; M62484; AAA36506.1; JOINED; Genomic_DNA.
DR EMBL; M62485; AAA36506.1; JOINED; Genomic_DNA.
DR EMBL; AK313164; BAG35982.1; -; mRNA.
DR EMBL; CH471100; EAW93502.1; -; Genomic_DNA.
DR EMBL; CH471100; EAW93503.1; -; Genomic_DNA.
DR EMBL; BC022312; AAH22312.1; -; mRNA.
DR EMBL; X07853; CAA30701.1; -; mRNA.
DR EMBL; X04284; CAB51244.1; -; Genomic_DNA.
DR EMBL; X04296; CAA27839.1; -; Genomic_DNA.
DR EMBL; X02865; CAA26617.1; -; mRNA.
DR CCDS; CCDS1477.1; -.
DR PIR; A33568; NBHUC4.
DR RefSeq; NP_000706.1; NM_000715.3.
DR RefSeq; XP_005273308.1; XM_005273251.1.
DR RefSeq; XP_005273309.1; XM_005273252.4.
DR PDB; 2A55; NMR; -; A=49-172.
DR PDB; 4B0F; X-ray; 2.80 A; A/B/C/D/E/F/G=540-597.
DR PDB; 5HYP; X-ray; 3.02 A; A=49-172.
DR PDB; 5HYT; X-ray; 2.54 A; B/D/F/H=49-172.
DR PDB; 5HYU; X-ray; 2.56 A; B=49-172.
DR PDB; 5HZP; X-ray; 2.74 A; B/D=49-172.
DR PDB; 5I0Q; X-ray; 2.29 A; B=49-172.
DR PDBsum; 2A55; -.
DR PDBsum; 4B0F; -.
DR PDBsum; 5HYP; -.
DR PDBsum; 5HYT; -.
DR PDBsum; 5HYU; -.
DR PDBsum; 5HZP; -.
DR PDBsum; 5I0Q; -.
DR AlphaFoldDB; P04003; -.
DR SMR; P04003; -.
DR BioGRID; 107183; 42.
DR IntAct; P04003; 26.
DR STRING; 9606.ENSP00000356037; -.
DR DrugBank; DB09130; Copper.
DR DrugBank; DB01593; Zinc.
DR DrugBank; DB14487; Zinc acetate.
DR DrugBank; DB14533; Zinc chloride.
DR DrugBank; DB14548; Zinc sulfate, unspecified form.
DR CarbonylDB; P04003; -.
DR GlyConnect; 1051; 9 N-Linked glycans (2 sites).
DR GlyCosmos; P04003; 8 sites, 17 glycans.
DR GlyGen; P04003; 9 sites, 19 N-linked glycans (2 sites), 2 O-linked glycans (5 sites).
DR iPTMnet; P04003; -.
DR PhosphoSitePlus; P04003; -.
DR SwissPalm; P04003; -.
DR BioMuta; C4BPA; -.
DR DMDM; 416733; -.
DR jPOST; P04003; -.
DR MassIVE; P04003; -.
DR PaxDb; 9606-ENSP00000356037; -.
DR PeptideAtlas; P04003; -.
DR ProteomicsDB; 51632; -.
DR Pumba; P04003; -.
DR Antibodypedia; 694; 323 antibodies from 29 providers.
DR DNASU; 722; -.
DR Ensembl; ENST00000367070.8; ENSP00000356037.3; ENSG00000123838.11.
DR GeneID; 722; -.
DR KEGG; hsa:722; -.
DR MANE-Select; ENST00000367070.8; ENSP00000356037.3; NM_000715.4; NP_000706.1.
DR UCSC; uc001hfo.3; human.
DR AGR; HGNC:1325; -.
DR CTD; 722; -.
DR DisGeNET; 722; -.
DR GeneCards; C4BPA; -.
DR HGNC; HGNC:1325; C4BPA.
DR HPA; ENSG00000123838; Tissue enriched (liver).
DR MIM; 120830; gene.
DR neXtProt; NX_P04003; -.
DR OpenTargets; ENSG00000123838; -.
DR PharmGKB; PA25905; -.
DR VEuPathDB; HostDB:ENSG00000123838; -.
DR eggNOG; ENOG502SHRK; Eukaryota.
DR GeneTree; ENSGT00940000154640; -.
DR HOGENOM; CLU_020107_5_2_1; -.
DR InParanoid; P04003; -.
DR OMA; VLRYRCH; -.
DR OrthoDB; 4551607at2759; -.
DR PhylomeDB; P04003; -.
DR TreeFam; TF334137; -.
DR PathwayCommons; P04003; -.
DR Reactome; R-HSA-977606; Regulation of Complement cascade.
DR SignaLink; P04003; -.
DR BioGRID-ORCS; 722; 10 hits in 1146 CRISPR screens.
DR ChiTaRS; C4BPA; human.
DR EvolutionaryTrace; P04003; -.
DR GenomeRNAi; 722; -.
DR Pharos; P04003; Tbio.
DR PRO; PR:P04003; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P04003; Protein.
DR Bgee; ENSG00000123838; Expressed in right lobe of liver and 115 other cell types or tissues.
DR ExpressionAtlas; P04003; baseline and differential.
DR Genevisible; P04003; HS.
DR GO; GO:0072562; C:blood microparticle; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; NAS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0006958; P:complement activation, classical pathway; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0045959; P:negative regulation of complement activation, classical pathway; IDA:BHF-UCL.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; IDA:BHF-UCL.
DR GO; GO:1903027; P:regulation of opsonization; IDA:BHF-UCL.
DR GO; GO:0009609; P:response to symbiotic bacterium; IDA:BHF-UCL.
DR GO; GO:0002456; P:T cell mediated immunity; IBA:GO_Central.
DR CDD; cd00033; CCP; 8.
DR Gene3D; 1.20.5.3730; -; 1.
DR Gene3D; 2.10.70.10; Complement Module, domain 1; 8.
DR InterPro; IPR040514; C4bp_oligo.
DR InterPro; IPR035976; Sushi/SCR/CCP_sf.
DR InterPro; IPR000436; Sushi_SCR_CCP_dom.
DR PANTHER; PTHR19325:SF564; C4B-BINDING PROTEIN ALPHA CHAIN; 1.
DR PANTHER; PTHR19325; COMPLEMENT COMPONENT-RELATED SUSHI DOMAIN-CONTAINING; 1.
DR Pfam; PF18453; C4bp_oligo; 1.
DR Pfam; PF00084; Sushi; 8.
DR SMART; SM00032; CCP; 8.
DR SUPFAM; SSF57535; Complement control module/SCR domain; 8.
DR PROSITE; PS50923; SUSHI; 8.
PE 1: Evidence at protein level;
KW 3D-structure; Complement pathway; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Immunity; Innate immunity;
KW Reference proteome; Repeat; Secreted; Signal; Sushi.
FT SIGNAL 1..48
FT /evidence="ECO:0000269|PubMed:4033666"
FT CHAIN 49..597
FT /note="C4b-binding protein alpha chain"
FT /id="PRO_0000005888"
FT DOMAIN 49..110
FT /note="Sushi 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 111..172
FT /note="Sushi 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 173..236
FT /note="Sushi 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 237..296
FT /note="Sushi 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 297..362
FT /note="Sushi 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 363..424
FT /note="Sushi 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 425..482
FT /note="Sushi 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 483..540
FT /note="Sushi 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT CARBOHYD 221
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:3840370"
FT CARBOHYD 506
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:14760718,
FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19159218,
FT ECO:0000269|PubMed:3840370"
FT CARBOHYD 528
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:14760718,
FT ECO:0000269|PubMed:3840370"
FT DISULFID 50..96
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:16330538"
FT DISULFID 81..108
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:16330538"
FT DISULFID 113..154
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:16330538"
FT DISULFID 140..170
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:16330538"
FT DISULFID 175..217
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 203..234
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 239..281
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 267..294
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 299..348
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 332..360
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 365..409
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 399..422
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 426..468
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 454..480
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 484..525
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 511..538
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 546
FT /note="Interchain (with beta chain)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 558
FT /note="Interchain (with beta chain)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT VARIANT 4
FT /note="P -> Q (in dbSNP:rs55867570)"
FT /id="VAR_061123"
FT VARIANT 60
FT /note="A -> V (in dbSNP:rs17020956)"
FT /id="VAR_048815"
FT VARIANT 240
FT /note="R -> H (in dbSNP:rs45574833)"
FT /id="VAR_061124"
FT VARIANT 300
FT /note="I -> T (in dbSNP:rs4844573)"
FT /id="VAR_024420"
FT VARIANT 357
FT /note="Y -> H"
FT /id="VAR_001978"
FT VARIANT 473
FT /note="W -> L (in dbSNP:rs1801341)"
FT /id="VAR_012038"
FT STRAND 57..63
FT /evidence="ECO:0007829|PDB:5I0Q"
FT STRAND 69..71
FT /evidence="ECO:0007829|PDB:5HYP"
FT STRAND 76..81
FT /evidence="ECO:0007829|PDB:5I0Q"
FT STRAND 85..87
FT /evidence="ECO:0007829|PDB:5I0Q"
FT STRAND 93..96
FT /evidence="ECO:0007829|PDB:5I0Q"
FT STRAND 98..100
FT /evidence="ECO:0007829|PDB:5HYP"
FT STRAND 108..110
FT /evidence="ECO:0007829|PDB:5I0Q"
FT STRAND 122..128
FT /evidence="ECO:0007829|PDB:5I0Q"
FT STRAND 130..133
FT /evidence="ECO:0007829|PDB:5HZP"
FT STRAND 135..140
FT /evidence="ECO:0007829|PDB:5I0Q"
FT STRAND 145..148
FT /evidence="ECO:0007829|PDB:5I0Q"
FT STRAND 150..157
FT /evidence="ECO:0007829|PDB:5I0Q"
FT STRAND 160..165
FT /evidence="ECO:0007829|PDB:5I0Q"
FT STRAND 169..171
FT /evidence="ECO:0007829|PDB:5I0Q"
FT HELIX 547..555
FT /evidence="ECO:0007829|PDB:4B0F"
FT STRAND 558..561
FT /evidence="ECO:0007829|PDB:4B0F"
FT HELIX 562..589
FT /evidence="ECO:0007829|PDB:4B0F"
FT HELIX 591..596
FT /evidence="ECO:0007829|PDB:4B0F"
SQ SEQUENCE 597 AA; 67033 MW; 67E03F2EA85A16DD CRC64;
MHPPKTPSGA LHRKRKMAAW PFSRLWKVSD PILFQMTLIA ALLPAVLGNC GPPPTLSFAA
PMDITLTETR FKTGTTLKYT CLPGYVRSHS TQTLTCNSDG EWVYNTFCIY KRCRHPGELR
NGQVEIKTDL SFGSQIEFSC SEGFFLIGST TSRCEVQDRG VGWSHPLPQC EIVKCKPPPD
IRNGRHSGEE NFYAYGFSVT YSCDPRFSLL GHASISCTVE NETIGVWRPS PPTCEKITCR
KPDVSHGEMV SGFGPIYNYK DTIVFKCQKG FVLRGSSVIH CDADSKWNPS PPACEPNSCI
NLPDIPHASW ETYPRPTKED VYVVGTVLRY RCHPGYKPTT DEPTTVICQK NLRWTPYQGC
EALCCPEPKL NNGEITQHRK SRPANHCVYF YGDEISFSCH ETSRFSAICQ GDGTWSPRTP
SCGDICNFPP KIAHGHYKQS SSYSFFKEEI IYECDKGYIL VGQAKLSCSY SHWSAPAPQC
KALCRKPELV NGRLSVDKDQ YVEPENVTIQ CDSGYGVVGP QSITCSGNRT WYPEVPKCEW
ETPEGCEQVL TGKRLMQCLP NPEDVKMALE VYKLSLEIEQ LELQRDSARQ STLDKEL
//
