Q9UK73 (FEM1B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein fem-1 homolog B
Short name=FEM1b

Alternative name(s):
FEM1-beta
Fem-1-like death receptor-binding protein alpha
Fem-1-like in apoptotic pathway protein alpha
Short name=F1A-alpha

Gene names

Name:	FEM1B
Synonyms:	F1AA, KIAA0396

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	627 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Component of an E3 ubiquitin-protein ligase complex, in which it may act as a substrate recognition subunit. Involved in apoptosis by acting as a death receptor-associated protein that mediates apoptosis. Also involved in glucose homeostasis in pancreatic islet. Functions as an adapter/mediator in replication stress-induced signaling that leads to the activation of CHEK1. Ref.1 Ref.11
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Homooligomer. Component of a probable ECS E3 ubiquitin-protein ligase complex containing CUL2, RBX1, TCEB1, TCEB2 and FEM1B. Interacts with PPM1F and PHTF1. Interacts with the death domain of FAS/TNFRSF6 and TNFRSF1A. Interacts with CHEK1. Ref.1 Ref.9 Ref.10 Ref.11
Subcellular location	Cytoplasm. Nucleus. Note: In the nucleus, the protein level increased slightly after camptothecin (CPT) treatment. Associated with chromatin. Ref.11
Tissue specificity	Widely expressed. Highly expressed in testis. Weakly expressed in other tissues. Ref.1
Sequence similarities	Belongs to the fem-1 family. Contains 8 ANK repeats. Contains 1 TPR repeat.

Ontologies

Keywords
Biological process	Apoptosis Ubl conjugation pathway
Cellular component	Cytoplasm Nucleus
Domain	ANK repeat Repeat TPR repeat
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW branching involved in prostate gland morphogenesis Inferred from electronic annotation. Source: Compara epithelial cell maturation involved in prostate gland development Inferred from electronic annotation. Source: Compara induction of apoptosis Non-traceable author statement Ref.2. Source: UniProtKB regulation of DNA damage checkpoint Inferred from mutant phenotype Ref.11. Source: UniProtKB regulation of ubiquitin-protein ligase activity Inferred from mutant phenotype Ref.10. Source: UniProtKB
Cellular_component	cytoplasm Inferred from direct assay Ref.11. Source: UniProtKB nucleus Inferred from direct assay Ref.11. Source: UniProtKB
Molecular_function	death receptor binding Inferred from mutant phenotype Ref.1. Source: UniProtKB ubiquitin-protein ligase activity Inferred from mutant phenotype Ref.10. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 627	627	Protein fem-1 homolog B		PRO_0000324530
Regions
	Repeat	45 – 74	30	ANK 1
	Repeat	87 – 116	30	ANK 2
	Repeat	120 – 149	30	ANK 3
	Repeat	153 – 182	30	ANK 4
	Repeat	186 – 215	30	ANK 5
	Repeat	218 – 248	31	ANK 6
	Repeat	344 – 377	34	TPR
	Repeat	483 – 527	45	ANK 7
	Repeat	531 – 568	38	ANK 8
Sites
	Site	342 – 343	2	Cleavage; by a caspase-3-like protease
Experimental info
	Mutagenesis	342	1	D → A: Prevents cleavage by a caspase-3-like protease. Ref.1
	Mutagenesis	356	1	D → A: Does not affect cleavage by a caspase-3-like protease. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q9UK73 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 85DA943663A988C1	FASTA	627	70,264
	10 20 30 40 50 60 MEGLAGYVYK AASEGKVLTL AALLLNRSES DIRYLLGYVS QQGGQRSTPL IIAARNGHAK 70 80 90 100 110 120 VVRLLLEHYR VQTQQTGTVR FDGYVIDGAT ALWCAAGAGH FEVVKLLVSH GANVNHTTVT 130 140 150 160 170 180 NSTPLRAACF DGRLDIVKYL VENNANISIA NKYDNTCLMI AAYKGHTDVV RYLLEQRADP 190 200 210 220 230 240 NAKAHCGATA LHFAAEAGHI DIVKELIKWR AAIVVNGHGM TPLKVAAESC KADVVELLLS 250 260 270 280 290 300 HADCDRRSRI EALELLGASF ANDRENYDII KTYHYLYLAM LERFQDGDNI LEKEVLPPIH 310 320 330 340 350 360 AYGNRTECRN PQELESIRQD RDALHMEGLI VRERILGADN IDVSHPIIYR GAVYADNMEF 370 380 390 400 410 420 EQCIKLWLHA LHLRQKGNRN THKDLLRFAQ VFSQMIHLNE TVKAPDIECV LRCSVLEIEQ 430 440 450 460 470 480 SMNRVKNISD ADVHNAMDNY ECNLYTFLYL VCISTKTQCS EEDQCKINKQ IYNLIHLDPR 490 500 510 520 530 540 TREGFTLLHL AVNSNTPVDD FHTNDVCSFP NALVTKLLLD CGAEVNAVDN EGNSALHIIV 550 560 570 580 590 600 QYNRPISDFL TLHSIIISLV EAGAHTDMTN KQNKTPLDKS TTGVSEILLK TQMKMSLKCL 610 620 AARAVRANDI NYQDQIPRTL EEFVGFH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"F1Aalpha, a death receptor-binding protein homologous to the Caenorhabditis elegans sex-determining protein, FEM-1, is a caspase substrate that mediates apoptosis." Chan S.-L., Tan K.-O., Zhang L., Yee K.S.Y., Ronca F., Chan M.-Y., Yu V.C. J. Biol. Chem. 274:32461-32468(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CLEAVAGE, TISSUE SPECIFICITY, INTERACTION WITH FAS AND TNFRSF1A, MUTAGENESIS OF ASP-342 AND ASP-356.
[2]	"Sequence, organization, and expression of the human FEM1B gene." Ventura-Holman T., Maher J.F. Biochem. Biophys. Res. Commun. 267:317-320(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Prediction of the coding sequences of unidentified human genes. VIII. 78 new cDNA clones from brain which code for large proteins in vitro." Ishikawa K., Nagase T., Nakajima D., Seki N., Ohira M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 4:307-313(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[4]	"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones." Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T. DNA Res. 9:99-106(2002) [PubMed] [Europe PMC] [Abstract] Cited for: SEQUENCE REVISION.
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Thalamus.
[6]	"Analysis of the DNA sequence and duplication history of human chromosome 15." Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C. Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta.
[9]	"The Caenorhabditis elegans sex-determining protein fem-2 and its human homologue, hFEM-2, are Ca2+/calmodulin-dependent protein kinase phosphatases that promote apoptosis." Tan K.M.L., Chan S.-L., Tan K.O., Yu V.C. J. Biol. Chem. 276:44193-44202(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PPM1F.
[10]	"VHL-box and SOCS-box domains determine binding specificity for Cul2-Rbx1 and Cul5-Rbx2 modules of ubiquitin ligases." Kamura T., Maenaka K., Kotoshiba S., Matsumoto M., Kohda D., Conaway R.C., Conaway J.W., Nakayama K.I. Genes Dev. 18:3055-3065(2004) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN E3 UBIQUITIN-PROTEIN LIGASE COMPLEX WITH CUL2.
[11]	"Human FEM1B is required for Rad9 recruitment and CHK1 activation in response to replication stress." Sun T.P., Shieh S.Y. Oncogene 28:1971-1981(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CHEK1.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF178632 mRNA. Translation: AAF05314.1. AF204883 mRNA. Translation: AAF69303.1. AB007856 mRNA. Translation: BAA23692.2. AK290167 mRNA. Translation: BAF82856.1. AC021553 Genomic DNA. No translation available. AC107871 Genomic DNA. No translation available. CH471082 Genomic DNA. Translation: EAW77818.1. BC010122 mRNA. Translation: AAH10122.1. BC014558 mRNA. Translation: AAH14558.1.
IPI	IPI00033419.
RefSeq	NP_056137.1. NM_015322.3.
UniGene	Hs.362733.
3D structure databases
HSSP	HSSP built from PDB template 1AWC based on UniProtKB Q00420.
ProteinModelPortal	Q9UK73.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9UK73. 18 interactions.
STRING	9606.ENSP00000307298.
PTM databases
PhosphoSite	Q9UK73.
Polymorphism databases
DMDM	74753369.
Proteomic databases
PaxDb	Q9UK73.
PRIDE	Q9UK73.
Protocols and materials databases
DNASU	10116.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000306917; ENSP00000307298; ENSG00000169018.
GeneID	10116.
KEGG	hsa:10116.
UCSC	uc002arg.3. human.
Organism-specific databases
CTD	10116.
GeneCards	GC15P068570.
HGNC	HGNC:3649. FEM1B.
HPA	HPA041920. HPA042192.
MIM	613539. gene.
neXtProt	NX_Q9UK73.
PharmGKB	PA28089.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0666.
HOGENOM	HOG000008180.
HOVERGEN	HBG057774.
InParanoid	Q9UK73.
KO	K10349.
OMA	NIPDADV.
OrthoDB	EOG4RR6GX.
PhylomeDB	Q9UK73.
Enzyme and pathway databases
UniPathway	UPA00143.
Gene expression databases
ArrayExpress	Q9UK73.
Bgee	Q9UK73.
CleanEx	HS_FEM1B.
Genevestigator	Q9UK73.
Family and domain databases
Gene3D	1.25.40.20. 4 hits.
InterPro	IPR002110. Ankyrin_rpt. IPR020683. Ankyrin_rpt-contain_dom. [Graphical view]
Pfam	PF00023. Ank. 7 hits. [Graphical view]
PRINTS	PR01415. ANKYRIN.
SMART	SM00248. ANK. 8 hits. [Graphical view]
SUPFAM	SSF48403. ANK. 2 hits.
PROSITE	PS50297. ANK_REP_REGION. 2 hits. PS50088. ANK_REPEAT. 6 hits. PS50005. TPR. False negative. PS50293. TPR_REGION. False negative. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	10116.
NextBio	38269.
PMAP-CutDB	Q9UK73.
SOURCE	Search...

Entry information

Entry name

FEM1B_HUMAN

Accession

Primary (citable) accession number: Q9UK73
Secondary accession number(s): O43146

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 18, 2008
Last sequence update:	May 1, 2000
Last modified:	May 1, 2013
This is version 105 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.