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 24-JAN-2024, entry version 217. 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}; GN 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 GlyCosmos; P23352; 6 sites, No reported glycans. 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; 9606-ENSP00000262648; -. DR PeptideAtlas; P23352; -. DR ProteomicsDB; 54081; -. DR Pumba; P23352; -. DR TopDownProteomics; P23352; -. DR Antibodypedia; 23606; 239 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 AGR; HGNC:6211; -. 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; 2995832at2759; -. 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; 7 hits in 772 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 185 other cell types or tissues. 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 CDD; cd00199; WAP; 1. DR Gene3D; 4.10.75.10; Elafin-like; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 3. 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; ANOSMIN; 1. DR PANTHER; PTHR14131:SF5; ANOSMIN-1; 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; SSF57256; Elafin-like; 1. DR SUPFAM; SSF49265; Fibronectin type III; 2. DR PROSITE; PS50853; FN3; 4. DR PROSITE; PS51390; WAP; 1. DR Genevisible; P23352; HS. 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 (found in a patient with Kallmann syndrome; FT likely pathogenic; the patient also carries mutation FT 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 //