Q7RTS7 (K2C74_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Keratin, type II cytoskeletal 74

Alternative name(s):
Cytokeratin-74
Short name=CK-74
Keratin-5c
Short name=K5C
Keratin-74
Short name=K74
Type II inner root sheath-specific keratin-K6irs4
Type-II keratin Kb37

Gene names

Name:	KRT74
Synonyms:	K6IRS4, KB37, KRT5C, KRT6IRS4

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	529 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Has a role in hair formation. Specific component of keratin intermediate filaments in the inner root sheath (IRS) of the hair follicle Probable.
Subunit structure	Heterotetramer of two type I and two type II keratins.
Tissue specificity	Highly expressed in hair follicles from scalp. In hair, it is specifically present in the inner root sheath (IRS) of the hair follicle. Present in the IRS Huxley layer, but not in Henle layer or cuticle of the IRS. In the IRS Huxley layer, it is expressed in specialized Huxley cells, termed 'Fluegelzellen, along the area of differentiated Henle cells (at protein level). Ref.1 Ref.5
Involvement in disease	Woolly hair autosomal dominant (ADWH) [MIM:194300]: A hair shaft disorder characterized by fine and tightly curled hair. Compared to normal curly hair that is observed in some populations, woolly hair grows slowly and stops growing after a few inches. Under light microscopy, woolly hair shows some structural anomalies, including trichorrexis nodosa and tapered ends. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Hypotrichosis 3 (HYPT3) [MIM:613981]: A condition characterized by the presence of less than the normal amount of hair. Affected individuals have normal hair in early childhood but experience progressive hair loss limited to the scalp beginning in the middle of the first decade and almost complete baldness by the third decade. Body hair, beard, eyebrows, axillary hair, teeth, and nails develop normally. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8
Miscellaneous	There are two types of cytoskeletal and microfibrillar keratin, I (acidic) and II (neutral to basic) (40-55 and 56-70 kDa, respectively).
Sequence similarities	Belongs to the intermediate filament family.
Sequence caution	The sequence DAA00404.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Cellular component	Intermediate filament Keratin
Coding sequence diversity	Polymorphism
Disease	Disease mutation Hypotrichosis
Domain	Coiled coil
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Cellular_component	keratin filament Inferred from electronic annotation. Source: InterPro
Molecular_function	structural molecule activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 529	529	Keratin, type II cytoskeletal 74		PRO_0000314885
Regions
	Region	1 – 139	139	Head
	Region	140 – 449	310	Rod
	Region	140 – 175	36	Coil 1A
	Region	176 – 194	19	Linker 1
	Region	195 – 286	92	Coil 1B
	Region	287 – 310	24	Linker 12
	Region	311 – 449	139	Coil 2
	Region	450 – 529	80	Tail
	Compositional bias	10 – 111	102	Gly-rich
Sites
	Site	391	1	Stutter
Amino acid modifications
	Modified residue	513	1	Phosphothreonine Ref.6
Natural variations
	Natural variant	148	1	N → K in ADWH; results in disruption of keratin intermediate filament formation in cultured cells. Ref.7		VAR_063587
	Natural variant	165	1	N → K. Corresponds to variant rs11170177 [ dbSNP | Ensembl ].		VAR_038096
	Natural variant	178	1	L → Q. Corresponds to variant rs11170176 [ dbSNP | Ensembl ].		VAR_049806
	Natural variant	271	1	E → D. Ref.1 Ref.4 Corresponds to variant rs670741 [ dbSNP | Ensembl ].		VAR_038097
	Natural variant	392	1	R → Q. Corresponds to variant rs57387512 [ dbSNP | Ensembl ].		VAR_061299
	Natural variant	424	1	E → K. Corresponds to variant rs57711382 [ dbSNP | Ensembl ].		VAR_061300
	Natural variant	482	1	D → N in HYPT3. Ref.8		VAR_065951

Sequences

	Sequence		Length	Mass (Da)
	Q7RTS7 [UniParc]. Last modified January 15, 2008. Version 2. Checksum: CE81527DD4825CBF	FASTA	529	57,865
	10 20 30 40 50 60 MSRQLNIKSS GDKGNFSVHS AVVPRKAVGS LASYCAAGRG AGAGFGSRSL YSLGGNRRIS 70 80 90 100 110 120 FNVAGGGVRA GGYGFRPGSG YGGGRASGFA GSMFGSVALG PACLSVCPPG GIHQVTVNKS 130 140 150 160 170 180 LLAPLNVELD PEIQKVRAQE REQIKVLNDK FASFIDKVRF LEQQNQVLET KWELLQQLDL 190 200 210 220 230 240 NNCKKNLEPI LEGYISNLRK QLETLSGDRV RLDSELRSMR DLVEDYKKRY EVEINRRTTA 250 260 270 280 290 300 ENEFVVLKKD ADAAYAVKVE LQAKVDSLDK EIKFLKCLYD AEIAQIQTHA SETSVILSMD 310 320 330 340 350 360 NNRDLDLDSI IAEVRMHYEE IALKSKAEAE ALYQTKIQEL QLAASRHGDD LKHTRSEMVE 370 380 390 400 410 420 LNRLIQRIRC EIGNVKKQRA SLETAIADAE QRGDNALKDA QAKLDELEGA LHQAKEELAR 430 440 450 460 470 480 MLREYQELMS LKLALDMEIA TYRKLLEGEE CRMSGENPSS VSISVISSSS YSYHHPSSAG 490 500 510 520 VDLGASAVAG SSGSTQSGQT KTTEARGGDL KDTQGKSTPA SIPARKATR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"K6irs1, K6irs2, K6irs3, and K6irs4 represent the inner-root-sheath-specific type II epithelial keratins of the human hair follicle." Langbein L., Rogers M.A., Praetzel S., Winter H., Schweizer J. J. Invest. Dermatol. 120:512-522(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, VARIANT ASP-271. Tissue: Scalp.
[2]	"The finished DNA sequence of human chromosome 12." Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A. Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	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].
[4]	"Genes for intermediate filament proteins and the draft sequence of the human genome: novel keratin genes and a surprisingly high number of pseudogenes related to keratin genes 8 and 18." Hesse M., Magin T.M., Weber K. J. Cell Sci. 114:2569-2575(2001) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION, VARIANT ASP-271.
[5]	"K25 (K25irs1), K26 (K25irs2), K27 (K25irs3), and K28 (K25irs4) represent the type I inner root sheath keratins of the human hair follicle." Langbein L., Rogers M.A., Praetzel-Wunder S., Helmke B., Schirmacher P., Schweizer J. J. Invest. Dermatol. 126:2377-2386(2006) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[6]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-513, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[7]	"Autosomal-dominant woolly hair resulting from disruption of keratin 74 (KRT74), a potential determinant of human hair texture." Shimomura Y., Wajid M., Petukhova L., Kurban M., Christiano A.M. Am. J. Hum. Genet. 86:632-638(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ADWH LYS-148, CHARACTERIZATION OF VARIANT ADWH LYS-148.
[8]	"Novel mutations in the keratin-74 (KRT74) gene underlie autosomal dominant woolly hair/hypotrichosis in Pakistani families." Wasif N., Naqvi S.K., Basit S., Ali N., Ansar M., Ahmad W. Hum. Genet. 129:419-424(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HYPT3 ASN-482.
+	Additional computationally mapped references.

Web resources

Human Intermediate Filament Mutation Database

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ508777 mRNA. Translation: CAD48514.1. AC055715 Genomic DNA. No translation available. CH471054 Genomic DNA. Translation: EAW96637.1. BK000977 Genomic DNA. Translation: DAA00404.1. Sequence problems.
IPI	IPI00329306.
RefSeq	NP_778223.2. NM_175053.3.
UniGene	Hs.660125.
3D structure databases
HSSP	HSSP built from PDB template 1GK7 based on UniProtKB P08670.
ProteinModelPortal	Q7RTS7.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000307240.
PTM databases
PhosphoSite	Q7RTS7.
Polymorphism databases
DMDM	166218812.
Proteomic databases
PaxDb	Q7RTS7.
PRIDE	Q7RTS7.
Protocols and materials databases
DNASU	121391.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000305620; ENSP00000307240; ENSG00000170484.
GeneID	121391.
KEGG	hsa:121391.
UCSC	uc001sap.1. human.
Organism-specific databases
CTD	121391.
GeneCards	GC12M052959.
H-InvDB	HIX0036697.
HGNC	HGNC:28929. KRT74.
HPA	HPA048596.
MIM	194300. phenotype. 608248. gene. 613981. phenotype.
neXtProt	NX_Q7RTS7.
Orphanet	90368. Hypotrichosis simplex of the scalp. 170. Woolly hair.
PharmGKB	PA147357741.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG266742.
HOGENOM	HOG000230976.
HOVERGEN	HBG013015.
KO	K07605.
OrthoDB	EOG4SQWWS.
Gene expression databases
ArrayExpress	Q7RTS7.
Bgee	Q7RTS7.
CleanEx	HS_KRT74.
Genevestigator	Q7RTS7.
Family and domain databases
InterPro	IPR016044. F. IPR001664. IF. IPR018039. Intermediate_filament_CS. IPR003054. Keratin_II. [Graphical view]
PANTHER	PTHR23239. PTHR23239. 1 hit. PTHR23239:SF18. PTHR23239:SF18. 1 hit.
Pfam	PF00038. Filament. 1 hit. [Graphical view]
PRINTS	PR01276. TYPE2KERATIN.
PROSITE	PS00226. IF. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	121391.
NextBio	80732.
SOURCE	Search...

Entry information

Entry name

K2C74_HUMAN

Accession

Primary (citable) accession number: Q7RTS7
Secondary accession number(s): B5MD61, Q86Y45

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 15, 2008
Last sequence update:	January 15, 2008
Last modified:	May 1, 2013
This is version 75 of the entry and version 2 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.