KALM_HUMAN
ID KALM_HUMAN Reviewed; 680 AA.
AC P23352; B2RPF8;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2007, sequence version 3.
DT 03-AUG-2022, entry version 210.
DE RecName: Full=Anosmin-1 {ECO:0000303|PubMed:8832397, ECO:0000312|HGNC:HGNC:6211};
DE AltName: Full=Adhesion molecule-like X-linked;
DE AltName: Full=Kallmann syndrome protein {ECO:0000303|PubMed:1913827};
DE Flags: Precursor;
GN Name=ANOS1 {ECO:0000312|HGNC:HGNC:6211}; Synonyms=ADMLX, KAL, KAL1, KALIG1;
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], AND VARIANT ILE-534.
RX PubMed=1913827; DOI=10.1016/0092-8674(91)90193-3;
RA Legouis R., Hardelin J.-P., Levilliers J., Claverie J.-M., Compain S.,
RA Wunderle V., Millasseau P., le Paslier D., Cohen D., Caterina D.,
RA Bougueleret L., Delemarre-Van de Waal H., Lutfalla G., Weissenbach J.,
RA Petit C.;
RT "The candidate gene for the X-linked Kallmann syndrome encodes a protein
RT related to adhesion molecules.";
RL Cell 67:423-435(1991).
RN [2]
RP SEQUENCE REVISION.
RX PubMed=1303284; DOI=10.1038/ng1292-305;
RA del Castillo I., Cohen-Salmon M., Blanchard S., Lutfalla G., Petit C.;
RT "Structure of the X-linked Kallmann syndrome gene and its homologous
RT pseudogene on the Y chromosome.";
RL Nat. Genet. 2:305-310(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ILE-534.
RX PubMed=1922361; DOI=10.1038/353529a0;
RA Franco B., Guioli S., Pragliola A., Inceri B., Bardoni B., Tonlorenzi R.,
RA Carrozo R., Maestrini E., Pieretti M., Taillon-Miller P., Brown C.J.,
RA Willard H.F., Lawrence C., Persico N.G., Camerino G., Ballabio A.;
RT "A gene deleted in Kallmann's syndrome shares homology with neural cell
RT adhesion and axonal path-finding molecules.";
RL Nature 353:529-536(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ILE-534.
RA Mural R.J., Istrail S., Sutton G.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], AND VARIANT ILE-534.
RC TISSUE=Brain;
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 [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-71.
RX PubMed=7590336; DOI=10.1016/0378-1119(95)00481-k;
RA Cohen-Salmon M., Tronche F., del Castillo I., Petit C.;
RT "Characterization of the promoter of the human KAL gene, responsible for
RT the X-chromosome-linked Kallmann syndrome.";
RL Gene 164:235-242(1995).
RN [8]
RP SUBCELLULAR LOCATION, GLYCOSYLATION, AND PROTEOLYTIC CLEAVAGE.
RX PubMed=8842728; DOI=10.1093/hmg/5.8.1109;
RA Rugarli E.I., Ghezzi C., Valsecchi V., Ballabio A.;
RT "The Kallmann syndrome gene product expressed in COS cells is cleaved on
RT the cell surface to yield a diffusible component.";
RL Hum. Mol. Genet. 5:1109-1115(1996).
RN [9]
RP CHARACTERIZATION.
RX PubMed=8832397; DOI=10.1242/jcs.109.7.1749;
RA Soussi-Yanicostas N., Hardelin J.-P., del Mar Arroyo-Jimenez M.,
RA Ardouin O., Legouis R., Levilliers J., Traincard F., Betton J.-M.,
RA Cabanie L., Petit C.;
RT "Initial characterization of anosmin-1, a putative extracellular matrix
RT protein synthesized by definite neuronal cell populations in the central
RT nervous system.";
RL J. Cell Sci. 109:1749-1757(1996).
RN [10]
RP TISSUE SPECIFICITY.
RX PubMed=12007408; DOI=10.1016/s0092-8674(02)00713-4;
RA Soussi-Yanicostas N., de Castro F., Julliard A.K., Perfettini I.,
RA Chedotal A., Petit C.;
RT "Anosmin-1, defective in the X-linked form of Kallmann syndrome, promotes
RT axonal branch formation from olfactory bulb output neurons.";
RL Cell 109:217-228(2002).
RN [11]
RP FUNCTION, INTERACTION WITH FGFR1, CHARACTERIZATION OF VARIANTS HH1 LYS-267;
RP LYS-514 AND LEU-517, AND HEPARIN-BINDING.
RX PubMed=19696444; DOI=10.1074/jbc.m109.049155;
RA Hu Y., Guimond S.E., Travers P., Cadman S., Hohenester E., Turnbull J.E.,
RA Kim S.H., Bouloux P.M.;
RT "Novel mechanisms of fibroblast growth factor receptor 1 regulation by
RT extracellular matrix protein anosmin-1.";
RL J. Biol. Chem. 284:29905-29920(2009).
RN [12]
RP X-RAY SCATTERING SOLUTION STRUCTURE OF 24-680, AND DISULFIDE BONDS.
RX PubMed=15949815; DOI=10.1016/j.jmb.2005.04.031;
RA Hu Y., Sun Z., Eaton J.T., Bouloux P.M., Perkins S.J.;
RT "Extended and flexible domain solution structure of the extracellular
RT matrix protein anosmin-1 by X-ray scattering, analytical
RT ultracentrifugation and constrained modelling.";
RL J. Mol. Biol. 350:553-570(2005).
RN [13]
RP VARIANT HH1 LYS-267, AND VARIANT ILE-534.
RX PubMed=8504298; DOI=10.1093/hmg/2.4.373;
RA Hardelin J.-P., Levilliers J., Blanchard S., Carel J.-C., Leutenegger M.,
RA Pinard-Bertelletto J.-P., Bouloux P., Petit C.;
RT "Heterogeneity in the mutations responsible for X chromosome-linked
RT Kallmann syndrome.";
RL Hum. Mol. Genet. 2:373-377(1993).
RN [14]
RP VARIANT HH1 LEU-517, AND VARIANTS ILE-534 AND HIS-668.
RX PubMed=8989261; DOI=10.1210/jcem.82.1.3692;
RA Georgopoulos N.A., Pralong F.P., Seidman C.E., Seidman J.G.,
RA Crowley W.F. Jr., Vallejo M.;
RT "Genetic heterogeneity evidenced by low incidence of KAL-1 gene mutations
RT in sporadic cases of gonadotropin-releasing hormone deficiency.";
RL J. Clin. Endocrinol. Metab. 82:213-217(1997).
RN [15]
RP VARIANT HH1 LYS-514, AND VARIANT ILE-534.
RX PubMed=9589672; DOI=10.1210/jcem.83.5.4817;
RA Maya-Nunez G., Zenteno J.C., Ulloa-Aguirre A., Kofman-Alfaro S.,
RA Mendez J.P.;
RT "A recurrent missense mutation in the KAL gene in patients with X-linked
RT Kallmann's syndrome.";
RL J. Clin. Endocrinol. Metab. 83:1650-1653(1998).
RN [16]
RP VARIANT HH1 ARG-172, AND VARIANT ILE-534.
RX PubMed=11297579; DOI=10.1210/jcem.86.4.7420;
RA Oliveira L.M.B., Seminara S.B., Beranova M., Hayes F.J., Valkenburgh S.B.,
RA Schipani E., Costa E.M.F., Latronico A.C., Crowley W.F. Jr., Vallejo M.;
RT "The importance of autosomal genes in Kallmann syndrome: genotype-phenotype
RT correlations and neuroendocrine characteristics.";
RL J. Clin. Endocrinol. Metab. 86:1532-1538(2001).
RN [17]
RP CHARACTERIZATION OF VARIANTS HH1 LYS-267; LYS-514 AND LEU-517.
RX PubMed=15471890; DOI=10.1093/hmg/ddh309;
RA Cariboni A., Pimpinelli F., Colamarino S., Zaninetti R., Piccolella M.,
RA Rumio C., Piva F., Rugarli E.I., Maggi R.;
RT "The product of X-linked Kallmann's syndrome gene (KAL1) affects the
RT migratory activity of gonadotropin-releasing hormone (GnRH)-producing
RT neurons.";
RL Hum. Mol. Genet. 13:2781-2791(2004).
RN [18]
RP VARIANT HH1 TYR-163, AND VARIANT ILE-534.
RX PubMed=15001591; DOI=10.1210/jc.2003-030476;
RA Sato N., Katsumata N., Kagami M., Hasegawa T., Hori N., Kawakita S.,
RA Minowada S., Shimotsuka A., Shishiba Y., Yokozawa M., Yasuda T.,
RA Nagasaki K., Hasegawa D., Hasegawa Y., Tachibana K., Naiki Y., Horikawa R.,
RA Tanaka T., Ogata T.;
RT "Clinical assessment and mutation analysis of Kallmann syndrome 1 (KAL1)
RT and fibroblast growth factor receptor 1 (FGFR1, or KAL2) in five families
RT and 18 sporadic patients.";
RL J. Clin. Endocrinol. Metab. 89:1079-1088(2004).
RN [19]
RP VARIANTS HH1 PRO-262 AND ARG-571.
RX PubMed=15605412; DOI=10.1002/humu.9298;
RA Albuisson J., Pecheux C., Carel J.-C., Lacombe D., Leheup B., Lapuzina P.,
RA Bouchard P., Legius E., Matthijs G., Wasniewska M., Delpech M., Young J.,
RA Hardelin J.-P., Dode C.;
RT "Kallmann syndrome: 14 novel mutations in KAL1 and FGFR1 (KAL2).";
RL Hum. Mutat. 25:98-99(2005).
RN [20]
RP VARIANT HH1 LEU-396.
RX PubMed=17054399; DOI=10.1371/journal.pgen.0020175;
RA Dode C., Teixeira L., Levilliers J., Fouveaut C., Bouchard P.,
RA Kottler M.-L., Lespinasse J., Lienhardt-Roussie A., Mathieu M., Moerman A.,
RA Morgan G., Murat A., Toublanc J.-E., Wolczynski S., Delpech M., Petit C.,
RA Young J., Hardelin J.-P.;
RT "Kallmann syndrome: mutations in the genes encoding prokineticin-2 and
RT prokineticin receptor-2.";
RL PLoS Genet. 2:1648-1652(2006).
RN [21]
RP VARIANT HH1 SER-304, AND VARIANT ILE-534.
RX PubMed=17223984; DOI=10.1111/j.1365-2265.2006.02702.x;
RA Versiani B.R., Trarbach E., Koenigkam-Santos M., dos Santos A.C.,
RA Elias L.L.K., Moreira A.C., Latronico A.C., de Castro M.;
RT "Clinical assessment and molecular analysis of GnRHR and KAL1 genes in
RT males with idiopathic hypogonadotrophic hypogonadism.";
RL Clin. Endocrinol. (Oxf.) 66:173-179(2007).
RN [22]
RP VARIANT HH1 CYS-163 DEL, AND VARIANTS MET-666 AND HIS-668.
RX PubMed=17213338; DOI=10.1093/molehr/gal108;
RA Bhagavath B., Xu N., Ozata M., Rosenfield R.L., Bick D.P., Sherins R.J.,
RA Layman L.C.;
RT "KAL1 mutations are not a common cause of idiopathic hypogonadotrophic
RT hypogonadism in humans.";
RL Mol. Hum. Reprod. 13:165-170(2007).
RN [23]
RP VARIANTS HH1 LYS-514 AND LYS-539.
RX PubMed=21168128; DOI=10.1016/j.fertnstert.2010.11.045;
RA Zhang S., Wang T., Yang J., Liu Z., Wang S., Liu J.;
RT "A fertile male patient with Kallmann syndrome and two missense mutations
RT in the KAL1 gene.";
RL Fertil. Steril. 95:1789-1792(2011).
RN [24]
RP VARIANTS HH1 GLY-134 AND ARG-163.
RX PubMed=20530987; DOI=10.1007/bf03346695;
RA Jap T.S., Chiu C.Y., Lirng J.F., Won G.S.;
RT "Identification of two novel missense mutations in the KAL1 gene in Han
RT Chinese subjects with Kallmann Syndrome.";
RL J. Endocrinol. Invest. 34:53-59(2011).
RN [25]
RP VARIANT ASP-217.
RX PubMed=22927827; DOI=10.1371/journal.pgen.1002896;
RA Hanchate N.K., Giacobini P., Lhuillier P., Parkash J., Espy C.,
RA Fouveaut C., Leroy C., Baron S., Campagne C., Vanacker C., Collier F.,
RA Cruaud C., Meyer V., Garcia-Pinero A., Dewailly D., Cortet-Rudelli C.,
RA Gersak K., Metz C., Chabrier G., Pugeat M., Young J., Hardelin J.P.,
RA Prevot V., Dode C.;
RT "SEMA3A, a gene involved in axonal pathfinding, is mutated in patients with
RT Kallmann syndrome.";
RL PLoS Genet. 8:E1002896-E1002896(2012).
RN [26]
RP VARIANT HH1 LEU-587.
RX PubMed=23643382; DOI=10.1016/j.ajhg.2013.04.008;
RA Miraoui H., Dwyer A.A., Sykiotis G.P., Plummer L., Chung W., Feng B.,
RA Beenken A., Clarke J., Pers T.H., Dworzynski P., Keefe K., Niedziela M.,
RA Raivio T., Crowley W.F. Jr., Seminara S.B., Quinton R., Hughes V.A.,
RA Kumanov P., Young J., Yialamas M.A., Hall J.E., Van Vliet G.,
RA Chanoine J.P., Rubenstein J., Mohammadi M., Tsai P.S., Sidis Y., Lage K.,
RA Pitteloud N.;
RT "Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in
RT individuals with congenital hypogonadotropic hypogonadism.";
RL Am. J. Hum. Genet. 92:725-743(2013).
RN [27]
RP VARIANTS HH1 LEU-396 AND ARG-672.
RX PubMed=25077900; DOI=10.1210/jc.2014-2110;
RA Marcos S., Sarfati J., Leroy C., Fouveaut C., Parent P., Metz C.,
RA Wolczynski S., Gerard M., Bieth E., Kurtz F., Verier-Mine O., Perrin L.,
RA Archambeaud F., Cabrol S., Rodien P., Hove H., Prescott T., Lacombe D.,
RA Christin-Maitre S., Touraine P., Hieronimus S., Dewailly D., Young J.,
RA Pugeat M., Hardelin J.P., Dode C.;
RT "The prevalence of CHD7 missense versus truncating mutations is higher in
RT patients with Kallmann syndrome than in typical CHARGE patients.";
RL J. Clin. Endocrinol. Metab. 99:E2138-2143(2014).
CC -!- FUNCTION: Has a dual branch-promoting and guidance activity, which may
CC play an important role in the patterning of mitral and tufted cell
CC collaterals to the olfactory cortex (By similarity). Chemoattractant
CC for fetal olfactory epithelial cells. {ECO:0000250,
CC ECO:0000269|PubMed:19696444}.
CC -!- SUBUNIT: Interacts with FGFR1; this interaction does not interfere with
CC FGF2-binding to FGFR1. Binds heparin. Heparin may promote or interfere
CC with ANOS1-FGFR1-FGF2 complex formation depending on the sequential
CC order of its binding to the various constituents. For instance,
CC heparin-ANOS1 interaction favors subsequent binding to pre-existing
CC binary FGFR1-FGF2 complex, while heparin-FGF2 complex does not interact
CC with ANOS1-FGFR1. {ECO:0000269|PubMed:19696444}.
CC -!- INTERACTION:
CC P23352; P11362: FGFR1; NbExp=7; IntAct=EBI-5272188, EBI-1028277;
CC P23352; P61601: NCALD; NbExp=3; IntAct=EBI-5272188, EBI-749635;
CC P23352; Q9UMX0: UBQLN1; NbExp=3; IntAct=EBI-5272188, EBI-741480;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:8842728};
CC Peripheral membrane protein {ECO:0000269|PubMed:8842728}. Secreted
CC {ECO:0000269|PubMed:8842728}. Note=Proteolytic cleavage may release it
CC from the cell surface into the extracellular space.
CC -!- TISSUE SPECIFICITY: Expressed in the cerebellum (at protein level).
CC {ECO:0000269|PubMed:12007408}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:8842728}.
CC -!- PTM: May be proteolytically cleaved at the cell surface and released
CC from the cell surface. {ECO:0000269|PubMed:8842728}.
CC -!- DISEASE: Hypogonadotropic hypogonadism 1 with or without anosmia (HH1)
CC [MIM:308700]: A disorder characterized by absent or incomplete sexual
CC maturation by the age of 18 years, in conjunction with low levels of
CC circulating gonadotropins and testosterone and no other abnormalities
CC of the hypothalamic-pituitary axis. In some cases, it is associated
CC with non-reproductive phenotypes, such as anosmia, cleft palate, and
CC sensorineural hearing loss. Anosmia or hyposmia is related to the
CC absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism
CC is due to deficiency in gonadotropin-releasing hormone and probably
CC results from a failure of embryonic migration of gonadotropin-releasing
CC hormone-synthesizing neurons. In the presence of anosmia, idiopathic
CC hypogonadotropic hypogonadism is referred to as Kallmann syndrome,
CC whereas in the presence of a normal sense of smell, it has been termed
CC normosmic idiopathic hypogonadotropic hypogonadism (nIHH).
CC {ECO:0000269|PubMed:11297579, ECO:0000269|PubMed:15001591,
CC ECO:0000269|PubMed:15471890, ECO:0000269|PubMed:15605412,
CC ECO:0000269|PubMed:17054399, ECO:0000269|PubMed:17213338,
CC ECO:0000269|PubMed:17223984, ECO:0000269|PubMed:19696444,
CC ECO:0000269|PubMed:20530987, ECO:0000269|PubMed:21168128,
CC ECO:0000269|PubMed:23643382, ECO:0000269|PubMed:25077900,
CC ECO:0000269|PubMed:8504298, ECO:0000269|PubMed:8989261,
CC ECO:0000269|PubMed:9589672}. Note=The disease is caused by variants
CC affecting distinct genetic loci, including the gene represented in this
CC entry. The genetics of hypogonadotropic hypogonadism involves various
CC modes of transmission. Oligogenic inheritance has been reported in some
CC patients carrying mutations in ANOS1 as well as in other HH-associated
CC genes including FGFR1 and TACR3 (PubMed:23643382).
CC {ECO:0000269|PubMed:23643382}.
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DR EMBL; M97252; AAA59202.1; -; mRNA.
DR EMBL; S60085; AAB20108.1; ALT_SEQ; mRNA.
DR EMBL; X60299; CAA42841.1; -; mRNA.
DR EMBL; AC005184; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC006062; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC096511; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471074; EAW98759.1; -; Genomic_DNA.
DR EMBL; BC137426; AAI37427.1; -; mRNA.
DR EMBL; BC137427; AAI37428.1; -; mRNA.
DR EMBL; X82034; CAA57554.1; -; Genomic_DNA.
DR CCDS; CCDS14130.1; -.
DR PIR; A40351; A40351.
DR PIR; S17982; S17982.
DR RefSeq; NP_000207.2; NM_000216.3.
DR PDB; 1ZLG; X-ray; -; A=24-680.
DR PDBsum; 1ZLG; -.
DR AlphaFoldDB; P23352; -.
DR SMR; P23352; -.
DR BioGRID; 109933; 146.
DR CORUM; P23352; -.
DR IntAct; P23352; 7.
DR MINT; P23352; -.
DR STRING; 9606.ENSP00000262648; -.
DR MEROPS; I17.004; -.
DR GlyGen; P23352; 6 sites.
DR iPTMnet; P23352; -.
DR PhosphoSitePlus; P23352; -.
DR BioMuta; ANOS1; -.
DR DMDM; 134048661; -.
DR EPD; P23352; -.
DR jPOST; P23352; -.
DR MassIVE; P23352; -.
DR PaxDb; P23352; -.
DR PeptideAtlas; P23352; -.
DR PRIDE; P23352; -.
DR ProteomicsDB; 54081; -.
DR TopDownProteomics; P23352; -.
DR Antibodypedia; 23606; 217 antibodies from 30 providers.
DR DNASU; 3730; -.
DR Ensembl; ENST00000262648.8; ENSP00000262648.3; ENSG00000011201.12.
DR GeneID; 3730; -.
DR KEGG; hsa:3730; -.
DR MANE-Select; ENST00000262648.8; ENSP00000262648.3; NM_000216.4; NP_000207.2.
DR UCSC; uc004csf.3; human.
DR CTD; 3730; -.
DR DisGeNET; 3730; -.
DR GeneCards; ANOS1; -.
DR GeneReviews; ANOS1; -.
DR HGNC; HGNC:6211; ANOS1.
DR HPA; ENSG00000011201; Tissue enhanced (lung).
DR MalaCards; ANOS1; -.
DR MIM; 300836; gene.
DR MIM; 308700; phenotype.
DR neXtProt; NX_P23352; -.
DR OpenTargets; ENSG00000011201; -.
DR Orphanet; 478; Kallmann syndrome.
DR PharmGKB; PA30012; -.
DR VEuPathDB; HostDB:ENSG00000011201; -.
DR eggNOG; KOG4802; Eukaryota.
DR GeneTree; ENSGT00440000033720; -.
DR HOGENOM; CLU_030264_0_0_1; -.
DR InParanoid; P23352; -.
DR OMA; RPHLKHH; -.
DR OrthoDB; 979841at2759; -.
DR PhylomeDB; P23352; -.
DR TreeFam; TF318736; -.
DR PathwayCommons; P23352; -.
DR Reactome; R-HSA-190373; FGFR1c ligand binding and activation.
DR Reactome; R-HSA-5654726; Negative regulation of FGFR1 signaling.
DR SignaLink; P23352; -.
DR SIGNOR; P23352; -.
DR BioGRID-ORCS; 3730; 6 hits in 699 CRISPR screens.
DR ChiTaRS; ANOS1; human.
DR EvolutionaryTrace; P23352; -.
DR GenomeRNAi; 3730; -.
DR Pharos; P23352; Tbio.
DR PRO; PR:P23352; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; P23352; protein.
DR Bgee; ENSG00000011201; Expressed in visceral pleura and 183 other tissues.
DR Genevisible; P23352; HS.
DR GO; GO:0009986; C:cell surface; IBA:GO_Central.
DR GO; GO:0031012; C:extracellular matrix; TAS:ProtInc.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005201; F:extracellular matrix structural constituent; TAS:ProtInc.
DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0007411; P:axon guidance; TAS:ProtInc.
DR GO; GO:0007155; P:cell adhesion; TAS:ProtInc.
DR GO; GO:0006935; P:chemotaxis; TAS:ProtInc.
DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central.
DR CDD; cd00063; FN3; 3.
DR Gene3D; 2.60.40.10; -; 3.
DR Gene3D; 4.10.75.10; -; 1.
DR InterPro; IPR042447; Anosmin-1.
DR InterPro; IPR040957; Anosmin-1_Cys_box.
DR InterPro; IPR036645; Elafin-like_sf.
DR InterPro; IPR003961; FN3_dom.
DR InterPro; IPR036116; FN3_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR008197; WAP_dom.
DR PANTHER; PTHR14131; PTHR14131; 1.
DR Pfam; PF17869; Cys_box; 1.
DR Pfam; PF00041; fn3; 3.
DR Pfam; PF00095; WAP; 1.
DR PRINTS; PR00003; 4DISULPHCORE.
DR SMART; SM00060; FN3; 4.
DR SMART; SM00217; WAP; 1.
DR SUPFAM; SSF49265; SSF49265; 2.
DR SUPFAM; SSF57256; SSF57256; 1.
DR PROSITE; PS50853; FN3; 4.
DR PROSITE; PS51390; WAP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell adhesion; Cell membrane; Chemotaxis; Disease variant;
KW Disulfide bond; Glycoprotein; Heparin-binding;
KW Hypogonadotropic hypogonadism; Kallmann syndrome; Membrane;
KW Protease inhibitor; Reference proteome; Repeat; Secreted;
KW Serine protease inhibitor; Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..680
FT /note="Anosmin-1"
FT /id="PRO_0000041395"
FT DOMAIN 127..176
FT /note="WAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00722"
FT DOMAIN 186..287
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 292..400
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 425..523
FT /note="Fibronectin type-III 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 550..658
FT /note="Fibronectin type-III 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT REGION 642..680
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 71
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 209
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 300
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 470
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 553
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 564
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 49..83
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00722,
FT ECO:0000269|PubMed:15949815"
FT DISULFID 53..77
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00722,
FT ECO:0000269|PubMed:15949815"
FT DISULFID 86..105
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00722,
FT ECO:0000269|PubMed:15949815"
FT DISULFID 90..101
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00722,
FT ECO:0000269|PubMed:15949815"
FT DISULFID 116..120
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00722,
FT ECO:0000269|PubMed:15949815"
FT VARIANT 134
FT /note="C -> G (in HH1; phenotype consistent with Kallmann
FT syndrome)"
FT /evidence="ECO:0000269|PubMed:20530987"
FT /id="VAR_065362"
FT VARIANT 163
FT /note="C -> R (in HH1; phenotype consistent with Kallmann
FT syndrome)"
FT /evidence="ECO:0000269|PubMed:20530987"
FT /id="VAR_065363"
FT VARIANT 163
FT /note="C -> Y (in HH1; phenotype consistent with Kallmann
FT syndrome)"
FT /evidence="ECO:0000269|PubMed:15001591"
FT /id="VAR_031012"
FT VARIANT 163
FT /note="Missing (in HH1; phenotype consistent with Kallmann
FT syndrome)"
FT /evidence="ECO:0000269|PubMed:17213338"
FT /id="VAR_031011"
FT VARIANT 172
FT /note="C -> R (in HH1; phenotype consistent with Kallmann
FT syndrome; dbSNP:rs1394625082)"
FT /evidence="ECO:0000269|PubMed:11297579"
FT /id="VAR_031013"
FT VARIANT 217
FT /note="Y -> D (probable disease-associated variant found in
FT a patient with Kallmann syndrome; the patient also carries
FT mutation Ala-688 in SEMA3A)"
FT /evidence="ECO:0000269|PubMed:22927827"
FT /id="VAR_069207"
FT VARIANT 262
FT /note="R -> P (in HH1; phenotype consistent with Kallmann
FT syndrome)"
FT /evidence="ECO:0000269|PubMed:15605412"
FT /id="VAR_031014"
FT VARIANT 267
FT /note="N -> K (in HH1; phenotype consistent with Kallmann
FT syndrome; loss of effect on the migratory activity of GnRH
FT neurons; complete loss of FGFR1-binding)"
FT /evidence="ECO:0000269|PubMed:15471890,
FT ECO:0000269|PubMed:19696444, ECO:0000269|PubMed:8504298"
FT /id="VAR_007720"
FT VARIANT 304
FT /note="N -> S (in HH1; phenotype consistent with Kallmann
FT syndrome; dbSNP:rs140812865)"
FT /evidence="ECO:0000269|PubMed:17223984"
FT /id="VAR_031015"
FT VARIANT 396
FT /note="S -> L (in HH1; phenotype consistent with Kallmann
FT syndrome; dbSNP:rs137852517)"
FT /evidence="ECO:0000269|PubMed:17054399,
FT ECO:0000269|PubMed:25077900"
FT /id="VAR_031016"
FT VARIANT 514
FT /note="E -> K (in HH1; phenotype consistent with Kallmann
FT syndrome; loss of effect on the migratory activity of GnRH
FT neurons; reduced FGFR1-binding; dbSNP:rs137852515)"
FT /evidence="ECO:0000269|PubMed:15471890,
FT ECO:0000269|PubMed:19696444, ECO:0000269|PubMed:21168128,
FT ECO:0000269|PubMed:9589672"
FT /id="VAR_012742"
FT VARIANT 517
FT /note="F -> L (in HH1; phenotype consistent with Kallmann
FT syndrome; loss of effect on the migratory activity of GnRH
FT neurons; Reduced FGFR1-binding)"
FT /evidence="ECO:0000269|PubMed:15471890,
FT ECO:0000269|PubMed:19696444, ECO:0000269|PubMed:8989261"
FT /id="VAR_031017"
FT VARIANT 534
FT /note="V -> I (in dbSNP:rs808119)"
FT /evidence="ECO:0000269|PubMed:11297579,
FT ECO:0000269|PubMed:15001591, ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:17223984, ECO:0000269|PubMed:1913827,
FT ECO:0000269|PubMed:1922361, ECO:0000269|PubMed:8504298,
FT ECO:0000269|PubMed:8989261, ECO:0000269|PubMed:9589672,
FT ECO:0000269|Ref.5"
FT /id="VAR_007721"
FT VARIANT 539
FT /note="E -> K (in HH1; dbSNP:rs144586521)"
FT /evidence="ECO:0000269|PubMed:21168128"
FT /id="VAR_065364"
FT VARIANT 571
FT /note="W -> R (in HH1; phenotype consistent with Kallmann
FT syndrome; dbSNP:rs1170543613)"
FT /evidence="ECO:0000269|PubMed:15605412"
FT /id="VAR_031018"
FT VARIANT 587
FT /note="V -> L (in HH1; phenotype consistent with normosmic
FT idiopathic hypogonadotropic hypogonadism; the patient also
FT carries a mutation in FGFR1; dbSNP:rs137900287)"
FT /evidence="ECO:0000269|PubMed:23643382"
FT /id="VAR_069968"
FT VARIANT 666
FT /note="K -> M"
FT /evidence="ECO:0000269|PubMed:17213338"
FT /id="VAR_031019"
FT VARIANT 668
FT /note="R -> H (in dbSNP:rs775708192)"
FT /evidence="ECO:0000269|PubMed:17213338,
FT ECO:0000269|PubMed:8989261"
FT /id="VAR_031020"
FT VARIANT 672
FT /note="H -> R (in HH1; phenotype consistent with Kallmann
FT syndrome; dbSNP:rs199771303)"
FT /evidence="ECO:0000269|PubMed:25077900"
FT /id="VAR_072992"
FT CONFLICT 48
FT /note="R -> P (in Ref. 1; AAA59202, 3; CAA42841 and 7;
FT CAA57554)"
FT /evidence="ECO:0000305"
FT CONFLICT 70..71
FT /note="NN -> VR (in Ref. 7; CAA57554)"
FT /evidence="ECO:0000305"
FT CONFLICT 373
FT /note="E -> K (in Ref. 3; CAA42841)"
FT /evidence="ECO:0000305"
FT CONFLICT 540
FT /note="A -> R (in Ref. 3; CAA42841)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 680 AA; 76112 MW; F491FE94FFD9250E CRC64;
MVPGVPGAVL TLCLWLAASS GCLAAGPGAA AARRLDESLS AGSVQRARCA SRCLSLQITR
ISAFFQHFQN NGSLVWCQNH KQCSKCLEPC KESGDLRKHQ CQSFCEPLFP KKSYECLTSC
EFLKYILLVK QGDCPAPEKA SGFAAACVES CEVDNECSGV KKCCSNGCGH TCQVPKTLYK
GVPLKPRKEL RFTELQSGQL EVKWSSKFNI SIEPVIYVVQ RRWNYGIHPS EDDATHWQTV
AQTTDERVQL TDIRPSRWYQ FRVAAVNVHG TRGFTAPSKH FRSSKDPSAP PAPANLRLAN
STVNSDGSVT VTIVWDLPEE PDIPVHHYKV FWSWMVSSKS LVPTKKKRRK TTDGFQNSVI
LEKLQPDCDY VVELQAITYW GQTRLKSAKV SLHFTSTHAT NNKEQLVKTR KGGIQTQLPF
QRRRPTRPLE VGAPFYQDGQ LQVKVYWKKT EDPTVNRYHV RWFPEACAHN RTTGSEASSG
MTHENYIILQ DLSFSCKYKV TVQPIRPKSH SKAEAVFFTT PPCSALKGKS HKPVGCLGEA
GHVLSKVLAK PENLSASFIV QDVNITGHFS WKMAKANLYQ PMTGFQVTWA EVTTESRQNS
LPNSIISQSQ ILPSDHYVLT VPNLRPSTLY RLEVQVLTPG GEGPATIKTF RTPELPPSSA
HRSHLKHRHP HHYKPSPERY
