ID INS_HUMAN      STANDARD;      PRT;   110 AA.
AC   P01308;
DT   21-JUL-1986 (REL. 01, CREATED)
DT   21-JUL-1986 (REL. 01, LAST SEQUENCE UPDATE)
DT   01-FEB-1995 (REL. 31, LAST ANNOTATION UPDATE)
DE   INSULIN PRECURSOR.
GN   INS.
OS   HOMO SAPIENS (HUMAN).
OC   EUKARYOTA; METAZOA; CHORDATA; VERTEBRATA; TETRAPODA; MAMMALIA;
OC   EUTHERIA; PRIMATES.
RN   [1]
RP   SEQUENCE FROM N.A.
RX   MEDLINE; 80120725. 
RA   BELL G.I., PICTET R.L., RUTTER W.J., CORDELL B., TISCHER E.,
RA   GOODMAN H.M.;
RL   NATURE 284:26-32(1980).
RN   [2]
RP   SEQUENCE FROM N.A.
RX   MEDLINE; 80236313. 
RA   ULLRICH A., DULL T.J., GRAY A., BROSIUS J., SURES I.;
RL   SCIENCE 209:612-615(1980).
RN   [3]
RP   SEQUENCE FROM N.A.
RX   MEDLINE; 80054779. 
RA   BELL G.I., SWAIN W.F., PICTET R.L., CORDELL B., GOODMAN H.M.,
RA   RUTTER W.J.;
RL   NATURE 282:525-527(1979).
RN   [4]
RP   SEQUENCE FROM N.A.
RX   MEDLINE; 80147417. 
RA   SURES I., GOEDDEL D.V., GRAY A., ULLRICH A.;
RL   SCIENCE 208:57-59(1980).
RN   [5]
RP   SEQUENCE OF 25-54 AND 90-110.
RA   NICOL D.S.H.W., SMITH L.F.;
RL   NATURE 187:483-485(1960).
RN   [6]
RP   SEQUENCE OF 57-87.
RX   MEDLINE; 71116410. 
RA   OYER P.E., CHO S., PETERSON J.D., STEINER D.F.;
RL   J. BIOL. CHEM. 246:1375-1386(1971).
RN   [7]
RP   SEQUENCE OF 57-87.
RX   MEDLINE; 71257722. 
RA   KO A., SMYTH D.G., MARKUSSEN J., SUNDBY F.;
RL   EUR. J. BIOCHEM. 20:190-199(1971).
RN   [8]
RP   SYNTHESIS.
RX   MEDLINE; 75077277. 
RA   SIEBER P., KAMBER B., HARTMANN A., JOEHL A., RINIKER B., RITTEL W.;
RL   HELV. CHIM. ACTA 57:2617-2621(1974).
RN   [9]
RP   SYNTHESIS OF 57-87.
RX   MEDLINE; 75040007. 
RA   NAITHANI V.K.;
RL   HOPPE-SEYLER'S Z. PHYSIOL. CHEM. 354:659-672(1973).
RN   [10]
RP   SYNTHESIS OF 57-87.
RA   GEIGER R., JAEGER G., KOENIG W.;
RL   CHEM. BER. 106:2347-2352(1973).
RN   [11]
RP   VARIANT LOS ANGELES.
RX   MEDLINE; 84016053. 
RA   HANEDA M., CHAN S.J., KWOK S.C.M., RUBENSTEIN A.H., STEINER D.F.;
RL   PROC. NATL. ACAD. SCI. U.S.A. 80:6366-6370(1983).
RN   [12]
RP   VARIANTS LOS ANGELES AND CHICAGO.
RX   MEDLINE; 84170233. 
RA   SHOELSON S., FICKOVA M., HANEDA M., NAHUM A., MUSSO G., KAISER E.T.,
RA   RUBENSTEIN A.H., TAGER H.;
RL   PROC. NATL. ACAD. SCI. U.S.A. 80:7390-7394(1983).
RN   [13]
RP   VARIANT PROVIDENCE.
RX   MEDLINE; 87175640. 
RA   CHAN S.J., SEINO S., GRUPPUSO P.A., SCHWARTZ R., STEINER D.F.;
RL   PROC. NATL. ACAD. SCI. U.S.A. 84:2194-2197(1987).
RN   [14]
RP   VARIANT WAKAKYAMA.
RX   MEDLINE; 87058122. 
RA   SAKURA H., IWAMOTO Y., SAKAMOTO Y., KUZUYA T., HIRATA H.;
RL   J. CLIN. INVEST. 78:1666-1672(1986).
RN   [15]
RP   VARIANT HIS-89.
RX   MEDLINE; 90317021. 
RA   BARBETTI F., RABEN N., KADOWAKI T., CAMA A., ACCILI D., GABBAY K.H.,
RA   MERENICH J.A., TAYLOR S.I., ROTH J.;
RL   J. CLIN. ENDOCRINOL. METAB. 71:164-169(1990).
RN   [16]
RP   VARIANT HIS-89.
RX   MEDLINE; 85261996. 
RA   SHIBASAKI Y., KAWAKAMI T., KANAZAWA Y., AKANUMA Y., TAKAKU F.;
RL   J. CLIN. INVEST. 76:378-380(1985).
RN   [17]
RP   VARIANT KYOTO.
RX   MEDLINE; 92291307. 
RA   YANO H., KITANO N., MORIMOTO M., POLONSKY K.S., IMURA H., SEINO Y.;
RL   J. CLIN. INVEST. 89:1902-1907(1992).
RN   [18]
RP   STRUCTURE BY NMR.
RX   MEDLINE; 91104966. 
RA   HUA Q.-X., WEISS M.A.;
RL   BIOCHEMISTRY 29:10545-10555(1990).
RN   [19]
RP   STRUCTURE BY NMR.
RX   MEDLINE; 91242467. 
RA   HUA Q.-X., WEISS M.A.;
RL   BIOCHEMISTRY 30:5505-5515(1991).
RN   [20]
RP   STRUCTURE BY NMR.
RX   MEDLINE; 91265527. 
RA   HUA Q.-X., WEISS M.A.;
RL   BIOCHIM. BIOPHYS. ACTA 1078:101-110(1991).
RN   [21]
RP   STRUCTURE BY NMR OF VARIANT LOS-ANGELES.
RX   MEDLINE; 93133832. 
RA   HUA Q.-X., SHOELSON S.E., INOUYE K., WEISS M.A.;
RL   PROC. NATL. ACAD. SCI. U.S.A. 90:582-586(1993).
CC   -!- FUNCTION: INSULIN DECREASES BLOOD GLUCOSE CONCENTRATION. IT
CC       INCREASES CELL PERMEABILITY TO MONOSACCHARIDES, AMINO ACIDS AND
CC       FATTY ACIDS. IT ACCELERATES GLYCOLYSIS, THE PENTOSE PHOSPHATE
CC       CYCLE, AND GLYCOGEN SYNTHESIS IN LIVER.
CC   -!- SUBUNIT: HETERODIMER OF A B CHAIN AND AN A CHAIN LINKED BY TWO
CC       DISULFIDE BONDS.
CC   -!- SUBCELLULAR LOCATION: SECRETED.
CC   -!- DISEASE: DEFECTS OF INSULIN ARE THE CAUSE OF HYPERPROINSULINEMIA
CC       AND OF TYPE-II DIABETES MELLITUS.
CC   -!- SIMILARITY: BELONGS TO THE INSULIN/IGF/RELAXIN FAMILY.
DR   EMBL; V00565; G758088; -. 
DR   EMBL; M10039; G386829; -.
DR   EMBL; J00265; G386828; -.
DR   EMBL; X70508; G394766; -.
DR   PIR; A01579; IPHU.
DR   PDB; 1HIQ; 31-JAN-94.
DR   PDB; 1HIS; 31-JAN-94.
DR   PDB; 1HIT; 31-JAN-94.
DR   PDB; 1HIU; 31-JAN-94.
DR   PDB; 1TYL; 30-SEP-94.
DR   PDB; 1TYM; 30-SEP-94.
DR   PDB; 1TRZ; 31-JAN-94.
DR   SWISS-3DIMAGE; INS_HUMAN.
DR   MIM; 176730; 11TH EDITION.
DR   PROSITE; PS00262; INSULIN.
DR   PRODOM [Domain structure / List of seq. sharing at least 1 domain]
DR   SWISS-2DPAGE; GET REGION ON 2D PAGE.
KW   HORMONE; GLUCOSE METABOLISM; SIGNAL; DISEASE MUTATION; DIABETES;
KW   3D-STRUCTURE.
FT   SIGNAL        1     24
FT   CHAIN        25     54       B CHAIN.
FT   PROPEP       57     87       C PEPTIDE.
FT   CHAIN        90    110       A CHAIN.
FT   DISULFID     31     96       INTERCHAIN.
FT   DISULFID     43    109       INTERCHAIN.
FT   DISULFID     95    100
FT   VARIANT      34     34       H -> D (IN PROVIDENCE; FAMILIAL HYPERPROINSULINEMIA).
FT   VARIANT      48     48       F -> S (IN LOS-ANGELES; TYPE-II DIABETES MELLITUS).
FT   VARIANT      49     49       F -> L (IN CHICAGO).
FT   VARIANT      89     89       R -> H (IN FAMILIAL HYPERPROINSULINEMIA; IMPAIRS POSTTRANSLATIONAL CLEAVAGE).
FT   VARIANT      89     89       R -> L (IN KYOTO; FAMILIAL HYPERPROINSULINEMIA).
FT   VARIANT      92     92       V -> L (IN WAKAYAMA).
FT   TURN         32     32
FT   HELIX        33     46
FT   STRAND       48     50
FT   HELIX        91     95
FT   TURN         96     97
FT   HELIX       102    108
FT   STRAND      109    109
SQ   SEQUENCE   110 AA;  11981 MW;  C30056AD CRC32;
     MALWMRLLPL LALLALWGPD PAAAFVNQHL CGSHLVEALY LVCGERGFFY TPKTRREAED
     LQVGQVELGG GPGAGSLQPL ALEGSLQKRG IVEQCCTSIC SLYQLENYCN
//
IRIS sequences %