HFM1_HUMAN
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 03-AUG-2022, entry version 130.
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}.
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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 iPTMnet; A2PYH4; -.
DR PhosphoSitePlus; A2PYH4; -.
DR BioMuta; HFM1; -.
DR EPD; A2PYH4; -.
DR MassIVE; A2PYH4; -.
DR PaxDb; A2PYH4; -.
DR PeptideAtlas; A2PYH4; -.
DR PRIDE; A2PYH4; -.
DR ProteomicsDB; 456; -. [A2PYH4-1]
DR ProteomicsDB; 457; -. [A2PYH4-2]
DR Antibodypedia; 51797; 118 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 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; CLKMDER; -.
DR OrthoDB; 154891at2759; -.
DR PhylomeDB; A2PYH4; -.
DR TreeFam; TF328936; -.
DR PathwayCommons; A2PYH4; -.
DR BioGRID-ORCS; 164045; 7 hits in 1063 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 pituitary gland and 99 other tissues.
DR ExpressionAtlas; A2PYH4; baseline and differential.
DR Genevisible; A2PYH4; HS.
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 Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 3.40.50.300; -; 2.
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 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; SSF46785; SSF46785; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1.
DR PROSITE; PS51194; HELICASE_CTER; 1.
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
