LOCUS       NP_000553                584 aa            linear   PRI 09-JUN-2024
DEFINITION  complement component C8 alpha chain preproprotein [Homo sapiens].
ACCESSION   NP_000553
VERSION     NP_000553.1
DBSOURCE    REFSEQ: accession NM_000562.3
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 584)
  AUTHORS   Densen,P., Ackermann,L., Saucedo,L., Figueroa,J.E., Si,Z.H. and
            Stoltzfus,C.M.
  TITLE     A Point Mutation Creating a 3' Splice Site in C8A Is a Predominant
            Cause of C8alpha-gamma Deficiency in African Americans
  JOURNAL   J Immunol 205 (6), 1535-1539 (2020)
   PUBMED   32769119
  REMARK    GeneRIF: A Point Mutation Creating a 3' Splice Site in C8A Is a
            Predominant Cause of C8alpha-gamma Deficiency in African Americans.
REFERENCE   2  (residues 1 to 584)
  AUTHORS   Luck,K., Kim,D.K., Lambourne,L., Spirohn,K., Begg,B.E., Bian,W.,
            Brignall,R., Cafarelli,T., Campos-Laborie,F.J., Charloteaux,B.,
            Choi,D., Cote,A.G., Daley,M., Deimling,S., Desbuleux,A., Dricot,A.,
            Gebbia,M., Hardy,M.F., Kishore,N., Knapp,J.J., Kovacs,I.A.,
            Lemmens,I., Mee,M.W., Mellor,J.C., Pollis,C., Pons,C.,
            Richardson,A.D., Schlabach,S., Teeking,B., Yadav,A., Babor,M.,
            Balcha,D., Basha,O., Bowman-Colin,C., Chin,S.F., Choi,S.G.,
            Colabella,C., Coppin,G., D'Amata,C., De Ridder,D., De Rouck,S.,
            Duran-Frigola,M., Ennajdaoui,H., Goebels,F., Goehring,L., Gopal,A.,
            Haddad,G., Hatchi,E., Helmy,M., Jacob,Y., Kassa,Y., Landini,S.,
            Li,R., van Lieshout,N., MacWilliams,A., Markey,D., Paulson,J.N.,
            Rangarajan,S., Rasla,J., Rayhan,A., Rolland,T., San-Miguel,A.,
            Shen,Y., Sheykhkarimli,D., Sheynkman,G.M., Simonovsky,E., Tasan,M.,
            Tejeda,A., Tropepe,V., Twizere,J.C., Wang,Y., Weatheritt,R.J.,
            Weile,J., Xia,Y., Yang,X., Yeger-Lotem,E., Zhong,Q., Aloy,P.,
            Bader,G.D., De Las Rivas,J., Gaudet,S., Hao,T., Rak,J.,
            Tavernier,J., Hill,D.E., Vidal,M., Roth,F.P. and Calderwood,M.A.
  TITLE     A reference map of the human binary protein interactome
  JOURNAL   Nature 580 (7803), 402-408 (2020)
   PUBMED   32296183
REFERENCE   3  (residues 1 to 584)
  AUTHORS   Menny,A., Serna,M., Boyd,C.M., Gardner,S., Joseph,A.P.,
            Morgan,B.P., Topf,M., Brooks,N.J. and Bubeck,D.
  TITLE     CryoEM reveals how the complement membrane attack complex ruptures
            lipid bilayers
  JOURNAL   Nat Commun 9 (1), 5316 (2018)
   PUBMED   30552328
  REMARK    Publication Status: Online-Only
REFERENCE   4  (residues 1 to 584)
  AUTHORS   Franc,V., Zhu,J. and Heck,A.J.R.
  TITLE     Comprehensive Proteoform Characterization of Plasma Complement
            Component C8alphabetagamma by Hybrid Mass Spectrometry Approaches
  JOURNAL   J Am Soc Mass Spectrom 29 (6), 1099-1110 (2018)
   PUBMED   29532326
  REMARK    GeneRIF: These data provide a detailed specification of
            co-occurring C8 proteoforms, including experimental evidence on
            N-glycosylation, C-mannosylation, and O-glycosylation.
REFERENCE   5  (residues 1 to 584)
  AUTHORS   Weiland,M.H., Qian,Y. and Sodetz,J.M.
  TITLE     Membrane pore formation by human complement: functional importance
            of the transmembrane beta-hairpin (TMH) segments of C8alpha and C9
  JOURNAL   Mol Immunol 57 (2), 310-316 (2014)
   PUBMED   24239861
REFERENCE   6  (residues 1 to 584)
  AUTHORS   Theriault,A., Boyd,E., Whaley,K., Sodetz,J.M. and Connor,J.M.
  TITLE     Regional chromosomal assignment of genes encoding the alpha and
            beta subunits of human complement protein C8 to 1p32
  JOURNAL   Hum Genet 88 (6), 703-704 (1992)
   PUBMED   1551680
REFERENCE   7  (residues 1 to 584)
  AUTHORS   Kaufman,K.M., Snider,J.V., Spurr,N.K., Schwartz,C.E. and
            Sodetz,J.M.
  TITLE     Chromosomal assignment of genes encoding the alpha, beta, and gamma
            subunits of human complement protein C8: identification of a close
            physical linkage between the alpha and the beta loci
  JOURNAL   Genomics 5 (3), 475-480 (1989)
   PUBMED   2613233
REFERENCE   8  (residues 1 to 584)
  AUTHORS   Densen,P. and McRill,C.M.
  TITLE     Differential functional expression of the C8 subunits. Primary role
            of C8 beta in assembly of intact C8
  JOURNAL   J Immunol 141 (8), 2674-2679 (1988)
   PUBMED   3171181
REFERENCE   9  (residues 1 to 584)
  AUTHORS   Muller-Eberhard,H.J.
  TITLE     Molecular organization and function of the complement system
  JOURNAL   Annu Rev Biochem 57, 321-347 (1988)
   PUBMED   3052276
  REMARK    Review article
REFERENCE   10 (residues 1 to 584)
  AUTHORS   Rao,A.G., Howard,O.M., Ng,S.C., Whitehead,A.S., Colten,H.R. and
            Sodetz,J.M.
  TITLE     Complementary DNA and derived amino acid sequence of the alpha
            subunit of human complement protein C8: evidence for the existence
            of a separate alpha subunit messenger RNA
  JOURNAL   Biochemistry 26 (12), 3556-3564 (1987)
   PUBMED   2820471
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL121998.7 and M16974.1.
            
            Summary: C8 is a component of the complement system and contains
            three polypeptides, alpha, beta and gamma. This gene encodes the
            alpha subunit of C8. C8 participates in the formation of the
            membrane attack complex (MAC). The MAC assembles on bacterial
            membranes to form a pore, permitting disruption of bacterial
            membrane organization. Mutations in this gene cause complement C8
            alpha-gamma deficiency. [provided by RefSeq, Nov 2008].
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: M16974.1, BC132913.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA2145122, SAMEA2146982
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000361249.4/ ENSP00000354458.3
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..584
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="1"
                     /map="1p32.2"
     Protein         1..584
                     /product="complement component C8 alpha chain
                     preproprotein"
                     /note="complement component C8 alpha chain; complement
                     component 8 subunit alpha; complement component 8, alpha
                     polypeptide; complement component 8 alpha subunit"
                     /calculated_mol_wt=63006
     sig_peptide     1..20
                     /inference="COORDINATES: ab initio prediction:SignalP:6.0"
                     /calculated_mol_wt=2176
     mat_peptide     31..584
                     /product="Complement component C8 alpha chain.
                     /id=PRO_0000023586"
                     /note="propagated from UniProtKB/Swiss-Prot (P07357.2)"
                     /calculated_mol_wt=61711
     Region          39..>74
                     /region_name="TSP1_spondin"
                     /note="Spondin-like TSP1 domain; cl46269"
                     /db_xref="CDD:480609"
     Site            43
                     /site_type="other"
                     /note="Not glycosylated; propagated from
                     UniProtKB/Swiss-Prot (P07357.2)"
     Site            44
                     /site_type="glycosylation"
                     /note="C-linked (Man) tryptophan.
                     /evidence=ECO:0000269|PubMed:10551839; propagated from
                     UniProtKB/Swiss-Prot (P07357.2)"
     Region          96..130
                     /region_name="LDLa"
                     /note="Low Density Lipoprotein Receptor Class A domain, a
                     cysteine-rich repeat that plays a central role in
                     mammalian cholesterol metabolism; the receptor protein
                     binds LDL and transports it into cells by endocytosis; 7
                     successive cysteine-rich repeats of about...; cd00112"
                     /db_xref="CDD:238060"
     Site            order(100,109,120..121)
                     /site_type="active"
                     /note="putative binding surface [active]"
                     /db_xref="CDD:238060"
     Site            order(113,116,120,126..127)
                     /site_type="other"
                     /note="calcium-binding site [ion binding]"
                     /db_xref="CDD:238060"
     Site            123..127
                     /site_type="other"
                     /note="D-X-S-D-E motif"
                     /db_xref="CDD:238060"
     Region          289..492
                     /region_name="MACPF"
                     /note="membrane-attack complex / perforin; smart00457"
                     /db_xref="CDD:214671"
     Site            437
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:16335952,
                     ECO:0000269|PubMed:19159218; propagated from
                     UniProtKB/Swiss-Prot (P07357.2)"
     Site            542
                     /site_type="glycosylation"
                     /note="C-linked (Man) tryptophan.
                     /evidence=ECO:0000269|PubMed:10551839; propagated from
                     UniProtKB/Swiss-Prot (P07357.2)"
     Site            545
                     /site_type="glycosylation"
                     /note="C-linked (Man) tryptophan.
                     /evidence=ECO:0000269|PubMed:10551839; propagated from
                     UniProtKB/Swiss-Prot (P07357.2)"
     Site            548
                     /site_type="glycosylation"
                     /note="C-linked (Man) tryptophan.
                     /evidence=ECO:0000269|PubMed:10551839; propagated from
                     UniProtKB/Swiss-Prot (P07357.2)"
     Region          <551..584
                     /region_name="TSP1"
                     /note="Thrombospondin type 1 repeats; smart00209"
                     /db_xref="CDD:214559"
     Region          562..584
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (P07357.2)"
     CDS             1..584
                     /gene="C8A"
                     /coded_by="NM_000562.3:106..1860"
                     /db_xref="CCDS:CCDS606.1"
                     /db_xref="GeneID:731"
                     /db_xref="HGNC:HGNC:1352"
                     /db_xref="MIM:120950"
ORIGIN      
        1 mfavvffils lmtcqpgvta qekvnqrvrr aatpaavtcq lsnwsewtdc fpcqdkkyrh
       61 rsllqpnkfg gticsgdiwd qascsssttc vrqaqcgqdf qcketgrclk rhlvcngdqd
      121 cldgsdeddc edvraidedc sqyepipgsq kaalgynilt qedaqsvyda syyggqcetv
      181 yngewrelry dstcerlyyg ddekyfrkpy nflkyhfeal adtgissefy dnandllskv
      241 kkdksdsfgv tigigpagsp llvgvgvshs qdtsflneln kynekkfift riftkvqtah
      301 fkmrkddiml degmlqslme lpdqynygmy akfindygth yitsgsmggi yeyilvidka
      361 kmeslgitsr dittcfggsl giqyedkinv ggglsgdhck kfgggktera rkamavedii
      421 srvrggssgw sgglaqnrst ityrswgrsl kynpvvidfe mqpihevlrh tslgpleakr
      481 qnlrraldqy lmefnacrcg pcfnngvpil egtscrcqcr lgslgaaceq tqtegakadg
      541 swscwsswsv cragiqerrr ecdnpapqng gascpgrkvq tqac
//
