ID   HFM1_HUMAN              Reviewed;        1435 AA.
AC   A2PYH4; B1B0B6; Q8N9Q0;
DT   18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT   23-SEP-2008, sequence version 2.
DT   24-JAN-2024, entry version 138.
DE   RecName: Full=Probable ATP-dependent DNA helicase HFM1;
DE            EC=3.6.4.12;
DE   AltName: Full=SEC63 domain-containing protein 1;
GN   Name=HFM1; Synonyms=SEC3D1;
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] (ISOFORM 1), TISSUE SPECIFICITY, AND VARIANTS
RP   PRO-115 AND VAL-117.
RX   PubMed=17286053; DOI=10.1080/10425170600805433;
RA   Tanaka K., Miyamoto N., Shouguchi-Miyata J., Ikeda J.E.;
RT   "HFM1, the human homologue of yeast Mer3, encodes a putative DNA helicase
RT   expressed specifically in germ-line cells.";
RL   DNA Seq. 17:242-246(2006).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Uterus;
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16710414; DOI=10.1038/nature04727;
RA   Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA   Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA   Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA   Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA   Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA   Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA   Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA   Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA   Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA   Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA   Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA   Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA   Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA   Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA   Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA   Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA   Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA   Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA   McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA   Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA   Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA   Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA   Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA   Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA   White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA   Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA   Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA   Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT   "The DNA sequence and biological annotation of human chromosome 1.";
RL   Nature 441:315-321(2006).
RN   [4]
RP   POSSIBLE INVOLVEMENT IN POF9, AND VARIANTS POF9 SER-736 AND SER-884.
RX   PubMed=24597873; DOI=10.1056/nejmc1310150;
RA   Wang J., Zhang W., Jiang H., Wu B.L., Wu B.L., An Y., Wu B., Yu L.,
RA   Zhou W., Jiang H., Zhang W., Song X., Zhang W., Jiang H., Wu J., Pu D.,
RA   Zhang M., Wu B.L., Shen Y., Wu B.L., Wang J., Zhang W., Shen Y., Lin C.,
RA   Grimmett L., Liao E., Shao H., Shen X., Platt O.;
RT   "Mutations in HFM1 in recessive primary ovarian insufficiency.";
RL   N. Engl. J. Med. 370:972-974(2014).
CC   -!- FUNCTION: Required for crossover formation and complete synapsis of
CC       homologous chromosomes during meiosis. {ECO:0000250|UniProtKB:D3Z4R1}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.12;
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=A2PYH4-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=A2PYH4-2; Sequence=VSP_032249, VSP_032250, VSP_032251;
CC   -!- TISSUE SPECIFICITY: Preferentially expressed in testis and ovary.
CC       {ECO:0000269|PubMed:17286053}.
CC   -!- DISEASE: Premature ovarian failure 9 (POF9) [MIM:615724]: An ovarian
CC       disorder defined as the cessation of ovarian function under the age of
CC       40 years. It is characterized by oligomenorrhea or amenorrhea, in the
CC       presence of elevated levels of serum gonadotropins and low estradiol.
CC       {ECO:0000303|PubMed:24597873}. Note=The disease may be caused by
CC       variants affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the helicase family. SKI2 subfamily.
CC       {ECO:0000305}.
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; AB204867; BAF45466.1; -; mRNA.
DR   EMBL; AK094079; BAC04281.1; -; mRNA.
DR   EMBL; AC098691; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BX323048; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS30769.2; -. [A2PYH4-1]
DR   RefSeq; NP_001017975.4; NM_001017975.4. [A2PYH4-1]
DR   RefSeq; XP_011539151.1; XM_011540849.1. [A2PYH4-1]
DR   RefSeq; XP_011539152.1; XM_011540850.2. [A2PYH4-1]
DR   RefSeq; XP_011539153.1; XM_011540851.1. [A2PYH4-1]
DR   RefSeq; XP_011539154.1; XM_011540852.2. [A2PYH4-1]
DR   AlphaFoldDB; A2PYH4; -.
DR   SMR; A2PYH4; -.
DR   BioGRID; 127886; 125.
DR   STRING; 9606.ENSP00000359454; -.
DR   GlyGen; A2PYH4; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; A2PYH4; -.
DR   PhosphoSitePlus; A2PYH4; -.
DR   BioMuta; HFM1; -.
DR   EPD; A2PYH4; -.
DR   MassIVE; A2PYH4; -.
DR   PaxDb; 9606-ENSP00000359454; -.
DR   PeptideAtlas; A2PYH4; -.
DR   ProteomicsDB; 456; -. [A2PYH4-1]
DR   ProteomicsDB; 457; -. [A2PYH4-2]
DR   Antibodypedia; 51797; 141 antibodies from 19 providers.
DR   DNASU; 164045; -.
DR   Ensembl; ENST00000370425.8; ENSP00000359454.3; ENSG00000162669.16. [A2PYH4-1]
DR   GeneID; 164045; -.
DR   KEGG; hsa:164045; -.
DR   MANE-Select; ENST00000370425.8; ENSP00000359454.3; NM_001017975.6; NP_001017975.5.
DR   UCSC; uc001doa.4; human. [A2PYH4-1]
DR   AGR; HGNC:20193; -.
DR   CTD; 164045; -.
DR   DisGeNET; 164045; -.
DR   GeneCards; HFM1; -.
DR   HGNC; HGNC:20193; HFM1.
DR   HPA; ENSG00000162669; Tissue enhanced (pituitary gland, testis).
DR   MalaCards; HFM1; -.
DR   MIM; 615684; gene.
DR   MIM; 615724; phenotype.
DR   neXtProt; NX_A2PYH4; -.
DR   OpenTargets; ENSG00000162669; -.
DR   Orphanet; 619; NON RARE IN EUROPE: Primary ovarian failure.
DR   PharmGKB; PA142671690; -.
DR   VEuPathDB; HostDB:ENSG00000162669; -.
DR   eggNOG; KOG0952; Eukaryota.
DR   GeneTree; ENSGT00550000074822; -.
DR   HOGENOM; CLU_000335_0_0_1; -.
DR   InParanoid; A2PYH4; -.
DR   OMA; HCKNKHT; -.
DR   OrthoDB; 57056at2759; -.
DR   PhylomeDB; A2PYH4; -.
DR   TreeFam; TF328936; -.
DR   PathwayCommons; A2PYH4; -.
DR   BioGRID-ORCS; 164045; 9 hits in 1141 CRISPR screens.
DR   ChiTaRS; HFM1; human.
DR   GenomeRNAi; 164045; -.
DR   Pharos; A2PYH4; Tbio.
DR   PRO; PR:A2PYH4; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   RNAct; A2PYH4; Protein.
DR   Bgee; ENSG00000162669; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 101 other cell types or tissues.
DR   ExpressionAtlas; A2PYH4; baseline and differential.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR   GO; GO:0003678; F:DNA helicase activity; IBA:GO_Central.
DR   GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
DR   GO; GO:0000712; P:resolution of meiotic recombination intermediates; IBA:GO_Central.
DR   CDD; cd18023; DEXHc_HFM1; 1.
DR   CDD; cd18795; SF2_C_Ski2; 1.
DR   Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 2.
DR   Gene3D; 1.10.3380.10; Sec63 N-terminal domain-like domain; 1.
DR   Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 1.
DR   InterPro; IPR011545; DEAD/DEAH_box_helicase_dom.
DR   InterPro; IPR014001; Helicase_ATP-bd.
DR   InterPro; IPR001650; Helicase_C.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   InterPro; IPR004179; Sec63-dom.
DR   InterPro; IPR036388; WH-like_DNA-bd_sf.
DR   InterPro; IPR036390; WH_DNA-bd_sf.
DR   PANTHER; PTHR47835; HFM1, ATP DEPENDENT DNA HELICASE HOMOLOG; 1.
DR   PANTHER; PTHR47835:SF2; SEC63 DOMAIN-CONTAINING PROTEIN; 1.
DR   Pfam; PF00270; DEAD; 1.
DR   Pfam; PF00271; Helicase_C; 1.
DR   Pfam; PF02889; Sec63; 1.
DR   SMART; SM00487; DEXDc; 1.
DR   SMART; SM00490; HELICc; 1.
DR   SMART; SM00973; Sec63; 1.
DR   SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
DR   SUPFAM; SSF158702; Sec63 N-terminal domain-like; 1.
DR   SUPFAM; SSF46785; Winged helix' DNA-binding domain; 1.
DR   PROSITE; PS51192; HELICASE_ATP_BIND_1; 1.
DR   PROSITE; PS51194; HELICASE_CTER; 1.
DR   Genevisible; A2PYH4; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; ATP-binding; Disease variant; Helicase; Hydrolase;
KW   Meiosis; Nucleotide-binding; Premature ovarian failure; Reference proteome.
FT   CHAIN           1..1435
FT                   /note="Probable ATP-dependent DNA helicase HFM1"
FT                   /id="PRO_0000324393"
FT   DOMAIN          290..478
FT                   /note="Helicase ATP-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT   DOMAIN          519..720
FT                   /note="Helicase C-terminal"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00542"
FT   DOMAIN          777..1092
FT                   /note="SEC63"
FT   REGION          1109..1139
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1295..1315
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           411..414
FT                   /note="DEAH box"
FT   BINDING         303..310
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT   VAR_SEQ         1..768
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_032249"
FT   VAR_SEQ         1295..1418
FT                   /note="GFGNTLSSSTRGSKLPLQESKSKFQREMSNSFVSSHEMSDISLSNSAMPKFS
FT                   ASSMTKLPQQAGNAVIVHFQERKPQNLSPEIEKQCFTFSEKNPNSSNYKKVDFFIRNSE
FT                   CKKEVDFSMYHPD -> VLFHHMRCRIFLYQILLCPSSVHPP (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_032250"
FT   VAR_SEQ         1419..1435
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_032251"
FT   VARIANT         115
FT                   /note="S -> P (in dbSNP:rs11165778)"
FT                   /evidence="ECO:0000269|PubMed:17286053"
FT                   /id="VAR_039799"
FT   VARIANT         117
FT                   /note="I -> V (in dbSNP:rs282009)"
FT                   /evidence="ECO:0000269|PubMed:17286053"
FT                   /id="VAR_039800"
FT   VARIANT         736
FT                   /note="G -> S (in POF9; dbSNP:rs587777269)"
FT                   /evidence="ECO:0000269|PubMed:24597873"
FT                   /id="VAR_071262"
FT   VARIANT         884
FT                   /note="I -> S (in POF9; dbSNP:rs587777268)"
FT                   /evidence="ECO:0000269|PubMed:24597873"
FT                   /id="VAR_071263"
FT   VARIANT         939
FT                   /note="I -> V (in dbSNP:rs11584478)"
FT                   /id="VAR_049338"
FT   CONFLICT        408
FT                   /note="F -> L (in Ref. 1; BAF45466)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        684
FT                   /note="C -> Y (in Ref. 1; BAF45466)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1435 AA;  162610 MW;  9FEFDF74FB990741 CRC64;
     MLKSNDCLFS LENLFFEKPD EVENHPDNEK SLDWFLPPAP LISEIPDTQE LEEELESHKL
     LGQEKRPKML TSNLKITNED TNYISLTQKF QFAFPSDKYE QDDLNLEGVG NNDLSHIAGK
     LTYASQKYKN HIGTEIAPEK SVPDDTKLVN FAEDKGESTS VFRKRLFKIS DNIHGSAYSN
     DNELDSHIGS VKIVQTEMNK GKSRNYSNSK QKFQYSANVF TANNAFSASE IGEGMFKAPS
     FSVAFQPHDI QEVTENGLGS LKAVTEIPAK FRSIFKEFPY FNYIQSKAFD DLLYTDRNFV
     ICAPTGSGKT VVFELAITRL LMEVPLPWLN IKIVYMAPIK ALCSQRFDDW KEKFGPIGLN
     CKELTGDTVM DDLFEIQHAH IIMTTPEKWD SMTRKWRDNS LVQLVRLFLI DEVHIVKDEN
     RGPTLEVVVS RMKTVQSVSQ TLKNTSTAIP MRFVAVSATI PNAEDIAEWL SDGERPAVCL
     KMDESHRPVK LQKVVLGFPC SSNQTEFKFD LTLNYKIASV IQMYSDQKPT LVFCATRKGV
     QQAASVLVKD AKFIMTVEQK QRLQKYAYSV RDSKLRDILK DGAAYHHAGM ELSDRKVVEG
     AFTVGDLPVL FTTSTLAMGV NLPAHLVVIK STMHYAGGLF EEYSETDILQ MIGRAGRPQF
     DTTATAVIMT RLSTRDKYIQ MLACRDTVES SLHRHLIEHL NAEIVLHTIT DVNIAVEWIR
     STLLYIRALK NPSHYGFASG LNKDGIEAKL QELCLKNLND LSSLDLIKMD EGVNFKPTEA
     GRLMAWYYIT FETVKKFYTI SGKETLSDLV TLIAGCKEFL DIQLRINEKK TLNTLNKDPN
     RITIRFPMEG RIKTREMKVN CLIQAQLGCI PIQDFALTQD TAKIFRHGSR ITRWLSDFVA
     AQEKKFAVLL NSLILAKCFR CKLWENSLHV SKQLEKIGIT LSNAIVNAGL TSFKKIEETD
     ARELELILNR HPPFGTQIKE TVMYLPKYEL KVEQITRYSD TTAEILVTVI LRNFEQLQTK
     RTASDSHYVT LIIGDADNQV VYLHKITDSV LLKAGSWAKK IAVKRALKSE DLSINLISSE
     FVGLDIQQKL TVFYLEPKRF GNQITMQRKS ETQISHSKHS DISTIAGPNK GTTASKKPGN
     RECNHLCKSK HTCGHDCCKI GVAQKSEIKE STISSYLSDL RNRNAVSSVP PVKRLKIQMN
     KSQSVDLKEF GFTPKPSLPS ISRSEYLNIS ELPIMEQWDQ PEIYGKVRQE PSEYQDKEVL
     NVNFELGNEV WDDFDDENLE VTSFSTDTEK TKISGFGNTL SSSTRGSKLP LQESKSKFQR
     EMSNSFVSSH EMSDISLSNS AMPKFSASSM TKLPQQAGNA VIVHFQERKP QNLSPEIEKQ
     CFTFSEKNPN SSNYKKVDFF IRNSECKKEV DFSMYHPDDE ADEMKSLLGI FDGIF
//